Landmark Papers in Plastic Surgery-1stkhajuria2024

Landmark
Papers in
Plastic Surgery
Commented Guide by Authors
and Experts
Ankur Khajuria
Joon Pio Hong
Peter Neligan
Editors
Foreword by Rod J. Rohrich
123
Landmark Papers in Plastic Surgery
Ankur Khajuria • Joon Pio Hong
Peter Neligan
Editors
Landmark Papers in
Plastic Surgery
Commented Guide by Authors
and Experts
Foreword by Rod J. Rohrich

Editors
Ankur Khajuria Joon Pio Hong
Kellogg College Department of Plastic Surgery
University of Oxford Asan Medical Center
Oxford, UK Seoul, Korea (Republic of)
Department of Surgery and Cancer

Imperial College London
London, UK
Peter Neligan
Department of Surgery
University of Washington
Seattle, WA, USA
ISBN 978-3-031-57131-2 ISBN 978-3-031-57132-9 (eBook)

https://doi.org/10.1007/978-3-031-57132-9
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature
Switzerland AG 2024
This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher,
whether the whole or part of the material is concerned, specifically the rights of translation,
reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any
other physical way, and transmission or information storage and retrieval, electronic adaptation,
computer software, or by similar or dissimilar methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publication does not imply, even in the absence of a specific statement, that such names are
exempt from the relevant protective laws and regulations and therefore free for general use.
The publisher, the authors and the editors are safe to assume that the advice and information in
this book are believed to be true and accurate at the date of publication. Neither the publisher nor
the authors or the editors give a warranty, expressed or implied, with respect to the material
contained herein or for any errors or omissions that may have been made. The publisher remains
neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This Springer imprint is published by the registered company Springer Nature Switzerland AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
If disposing of this product, please recycle the paper.

Foreword
In the ever-evolving realm of medicine, a few disciplines have seen as much

innovation and transformation as plastic surgery. This field, which encom-
passes a wide range of surgical procedures aimed at restoring, enhancing, or
reconstructing the human form, has a rich history of ground-breaking discov-
eries and transformative moments. The book you hold in your hands,
Landmark Papers in Plastic Surgery, is a testament to the enduring impact of
these pivotal moments and their influence on the course of plastic surgery.
Defining Landmark Papers
Before delving into the significance of this unique book, it is crucial to clarify
what we mean by “landmark papers” in the context of plastic surgery. In the
vast sea of scientific literature, landmark papers stand out as beacons of prog-
ress. They are not merely publications that garnered attention or citations;
they are the true catalysts of change, the sparks that ignited innovation, and
the drivers of paradigm shifts within the field. In essence, landmark papers
are the cornerstone upon which the edifice of modern plastic surgery stands.
Such papers are characterized by their ability to challenge the status quo.
They question existing practices, methodologies, or beliefs, often daring to
swim against the prevailing currents of thought. They are the bold statements
that say, “We can do better, we can improve, and we can change lives.” The
studies featured in this book are not content with the ordinary; they push the
boundaries of what was previously deemed possible, urging us to rethink our
approaches and strive for excellence. The list of these landmark papers
includes a diverse group of global plastic surgery innovators.
Importantly, these landmark papers have a profound and lasting impact.
They serve as the genesis of innovation and evolution within the field of
plastic surgery. They inspire future generations of surgeons, researchers,
and healthcare professionals to build upon the foundation they provide. In
this book, the authors have meticulously curated and presented a selection
of original studies that have met these stringent criteria. These are the
papers that have shaped, and continue to shape, the landscape of plastic
surgery.
v
vi Foreword
The Journey Through Landmark Papers
As you embark on this journey through Landmark Papers in Plastic Surgery,

you will traverse the annals of our discipline, guided by the wisdom and
vision of the pioneers who blazed the trail. Each chapter is a portal into a dif-
ferent era, a different challenge, and a different triumph. You will witness the
transformation of techniques, the refinement of approaches, and the enhance-
ment of patient outcomes.
From the pioneering work of Sir Harold Gillies in reconstructive surgery
during World War I to the modern era of microsurgery and tissue engineering,
the chapters in this book span a wide range of topics and areas. Whether it be
the ground-breaking innovations in cleft lip and palate repair, the revolution-
ary developments in breast reconstruction, or the transformative techniques
in craniofacial surgery and aesthetic surgery, these landmark papers have left
an indelible mark on our field.
In the pages of this book, a diverse audience awaits—medical students,
trainees, seasoned surgeons, scholars, and those seeking inspiration from the
fascinating journey of innovations in our field. Through an exploration of
pioneering works in our specialty, readers embark on a profound odyssey,
gaining insights into the field’s transformative evolution. Unraveling the
threads of ground-breaking papers, this book not only illuminates the past but
also imparts invaluable lessons on innovation. For trainees on the cusp of
pivotal board exams, this volume stands as an indispensable guide to excel.
Expert Commentary: Navigating the Future
In addition to presenting these seminal studies, Landmark Papers in Plastic

Surgery also includes a closing expert commentary in each chapter. This
commentary serves as a compass, guiding us forward as we reflect on the
past. It provides a comprehensive summary of the field, weaving together the
threads of knowledge and insight gained from the featured papers. More
importantly, it offers direction for the future, illuminating the path ahead in
light of the landmark studies and the evolving landscape of plastic surgery.
This expert commentary is a testament to the dynamic nature of our field.
It recognizes that while we honor the achievements of the past, we must
remain vigilant in our pursuit of progress. As plastic surgery continues to
evolve and transform, this commentary serves as a beacon of wisdom, help-
ing us navigate the challenges and opportunities that lie ahead.
Expert Concluding Commentary
In conclusion, Landmark Papers in Plastic Surgery is more than just a collec-

tion of historical documents; it is a tribute to the relentless pursuit of excel-
lence that defines our field. It is a celebration of the surgeons, researchers, and
innovators who have dedicated their lives to advancing the art and science of
plastic surgery. It is a reminder that our journey is far from over, that there are
Foreword vii
still uncharted territories to explore, and that the potential for discovery and
improvement is limitless.
As you read the pages of this book and immerse yourself in the world of
landmark papers, I invite you to reflect on the transformative power of knowl-
edge and innovation. Let these papers inspire you to question, to innovate,
and to challenge the status quo in your own pursuits. For it is through the
collective efforts of individuals like you that the field of plastic surgery will
continue to evolve and transform, ensuring a brighter and more promising
future for patients around the world.
May Landmark Papers in Plastic Surgery serve as a source of inspiration,
knowledge, and guidance for all who seek to make a meaningful impact in the
field of plastic surgery. As we honor the past and embrace the future, we may
continue to push the boundaries of what is possible, one landmark paper at a
time. I personally congratulate the co-authors of this amazing book, Ankur
Khajuria, JP Hong, and Peter Neligan, for having the foresight to organize
and bring us this valuable text.
Sincerely,
Rod
Department of Plastic Surgery, UTSW J. Rohrich
Dallas, TX, USA
Baylor College of Medicine
Houston, TX, USA
Preface
Why do we need another book in Plastic Surgery highlighting papers that are
already in the literature? There is a tendency for people in their professional
reading to look only at the most recent papers. Of course, it is extremely
important to keep abreast of the latest developments in one’s specialty and
reading the latest literature is important. However, it is also important to be
familiar with how current practice evolved. The phrase “Those who do not
learn history are destined to repeat it” was most likely uttered by the Spanish
Philosopher George Santayana though it has been attributed to several famous
figures. We didn’t want this to be a book on history though. We felt that it
would be useful to compile a list of the papers that changed and continue to
change the practice of Plastic Surgery. We wondered how best to do this. The
obvious solution was to base it on some sort of citation or bibliometric analy-
sis. This would make sense. Then we thought that such a method could also
capture papers that were widely read but were not landmark papers. So what
is a landmark paper? According to WikiJournalClub, Landmark papers are
highly influential papers that have substantially changed the practice of medi-
cine or provided the missing evidence to support current practices. We dis-
covered that some of the most influential papers were case reports, not
extensive research works. An example is the report of the first free flap. Case
reports are generally not widely cited so that relying on a citation index would
not necessarily capture what we needed. What we were looking for, then, was
the paper that sparked a significant change in practice and led to the evolution
of that area of practice. We therefore decided to ask the experts; recognized
authorities in the different areas of practice (and often those who contributed
to the landmark papers themselves) in order to get their consensus on what
papers should be included but also to provide a commentary on where they
saw the future. We also asked the contributors not only to choose five land-
mark chapters for each topic, but also to include a more extensive bibliogra-
phy in order to put the subject in context. We initially drew up a table of
contents (TOC) and invited contributors. As chapters came in, we realized
that we needed to expand the TOC in many areas. As an example, we realized
that a chapter on the evolution of microsurgery was too broad to include an
in-depth look at the evolution of reconstruction of the jaws. Several of the
chapters in the book fall into that category. We tried to maintain the same
format for each chapter, highlighting the chosen landmark papers, explaining
why they were considered the most important papers, but also putting them in
context with the rest of the relevant literature on that topic. Most importantly,
ix
x Preface
we asked the contributors to provide an analysis of where they saw the future
of each subject.
Our book is intended for a diverse audience, including medical students,
trainees, senior surgeons, academics, and anyone looking to be inspired by
how innovations happened in our specialty. By exploring the ground-breaking
papers in Plastic Surgery, readers can gain insights into the evolution of the
field and learn valuable lessons on how to innovate. For trainees preparing for
board or exit exams, such as the FRCS (Plast), this book serves as an invalu-
able reference source, providing access to key landmark studies. The unique
aspect of our comprehensive text is its coverage of all aspects of Plastic
Surgery, ensuring that readers have a holistic understanding of the field’s
development. We aim to bridge the gap between historical knowledge and
contemporary practice. Landmark papers are not just a part of history; they
continue to shape our present and future practices in Plastic Surgery.
In the forthcoming editions of this book, we endeavour to chart the unfold-
ing horizons of Plastic Surgery. As the evidence base expands and technology
propels our field into new realms, there will be greater focus on the cutting-
edge innovations that define the future of Plastic Surgery. Emerging technolo-
gies such as robotics, artificial intelligence, and tissue engineering will take
centre stage, guiding the next generation of surgeons and academics toward a
transformative era in our specialty. With each edition, we aim to capture not
only the historical foundations but also the dynamic evolution that continues
to shape the very essence of our specialty, ensuring our readers are prepared
for the challenges and opportunities of tomorrow.
It has been an enjoyable exercise to put this book together and we hope
that you not only enjoy it but find it useful.
Oxford, UK Ankur Khajuria

Seattle, WA, USA Peter Neligan
Seoul, Republic of Korea Joon Pio Hong
Contents
Part I Basic Science
1
The Evolution of Microsurgery�� 3
Peter Neligan and Ankur Khajuria
2 Emerging Flaps�� 9
Joon Pio Hong
3 Evolution of Vascularized Composite Allotransplantation�� 15
Lioba Huelsboemer and Bohdan Pomahac
4 Evolution of Wound Healing �� 29
Ryoko Hamaguchi and Dennis P. Orgill
5
Evolution of Lymphedema Management�� 39
Peter Neligan and Isao Koshima
6
Emergence of Nerve Interfaces with Robotic Applications�� 45
Katherine L. Burke, Gregory A. Dumanian,
and Paul S. Cederna
7
Evolution of Breast Imaging in Plastic Surgery�� 55
Dominick J. Falcon, Valeria P. Bustos, and Bernard T. Lee
8
Evolution of Imaging in Flap Reconstruction �� 63
Jeremy M. Sun and Takumi Yamamoto
9
Evolution of Imaging in Cranio-Maxillo-Facial Surgery �� 77
Jong-Woo (JW) Choi and Young Chul Kim
Part II Head and Neck
10
Evolution of Craniofacial Trauma Management�� 87
11
Evolution of Cleft Care�� 97
Benjamin B. Massenburg and Raymond W. Tse
12
Evolution of Orthognathic Surgery�� 111
Srinivas M. Susarla and R. Bruce Donoff
xi
xii Contents
13 Evolution
of Head and Neck Cancer Management�� 119
Sydney Ch’Ng and Yu Jin Jeong
14 Evolution
of Bony Microsurgical Reconstruction
of the Jaws�� 133
Rushil R. Dang, Shao-Yu Hung, and Fu-Chan Wei
15 Evolution
of Reconstruction in Facial Paralysis �� 139
Alan Tom, Gerald J. Wu, Ronald M. Zuker,
and Gregory H. Borschel
Part III Breast Surgery
16 Evolution
of Reconstructive Implant Breast Surgery�� 149
Danielle H. Rochlin and Joseph J. Disa
17 Evolution
of Reconstructive Autologous Breast Surgery �� 161
Nakul Gamanlal Patel and Venkat Ramakrishnan
18 Evolution
of Aesthetic Breast Surgery �� 169
Maurizio Bruno Nava, Alberto Rancati, Patrick Mallucci,
and Nicola Rocco
19 Science
of Breast Implants�� 181
Jose Foppiani, Angelica Hernandez Alvarez, Lacey Foster,
Mark Clemens, and Samuel J. Lin
Part IV Hand and Upper Extremity
20 Evolution
of Upper Extremity Trauma Management�� 195
Ronald D. Brown, Stefan Czerniecki, and Amy Moore
21 Innovations
in Care for Congenital Hand Differences �� 205
Shimpei Ono and Kevin C. Chung
22 Inflammatory
and Degenerative Disease of the
Hand and Upper Extremity�� 215
Krystle R. Tuaño, Jonathan Lans, Ophelie Lavoie-Gagne,
Justin J. Koh, and Kyle R. Eberlin
Part V Nerve Surgery
23 Landmark
Studies in Nerve Surgery �� 229
Jenna-Lynn Senger, Kitty Y Wu, Amy Moore,
and Susan E. Mackinnon
Part VI Skin Cancer Management
24 Evolution
of Melanoma and Non-Melanoma
Skin Cancer Management�� 243
Contents xiii
Part VII Burn Surgery
25
Evolution of Burn Surgery�� 263
August Schaeffer, Laxmi Dongur, and Steven E. Wolf
Part VIII Trunk Reconstruction
26 Evolution of Trunk Reconstruction�� 273

Geoffrey G. Hallock
Part IX Abdominal Wall Reconstruction
27 Evolution of Abdominal Wall Reconstruction�� 285

Rami Elmorsi, Abbas Hassan, Jeffrey E. Janis,
and Charles E. Butler
Part X Lower Extremity
28
Evolution of Lower Limb Orthoplastic Management�� 297
Dominik Kaiser, Stephen Kovach, and L. Scott Levin
29
Evolution of Diabetic Foot Reconstruction�� 303
Joon Pio Hong
Part XI Genitourinary Reconstruction
30
Evolution of Genitourinary Reconstruction�� 309
Brooke L. Moore, Alan Yang, and Curtis Cetrulo
Part XII Perineal and Pelvic Reconstruction
31
Evolution of Perineal and Pelvic Reconstruction�� 323
Raymund E. Horch, Andreas Arkudas,
and Alexander Geierlehner
Part XIII Aesthetic Surgery
32
Evolution of Facelift Surgery�� 331
Katherine B. Santosa and Foad Nahai
33
Evolution of Rhinoplasty Surgery�� 341
Bahman Guyuron and Anthony DeLeonibus
34
Evolution of Post Massive Weight Loss Surgery �� 353
Francesco M. Egro, Mario Alessandri Bonetti,
and J. Peter Rubin
xiv Contents
35 Evolution
of Fat Grafting�� 363
Shawn J. Loder, Roy Kazan, Francesco M. Egro,
and J. Peter Rubin
36 Evolution
of Body Contouring Surgery �� 373
Alfredo Hoyos and Mauricio Perez
37 Evolution of Hair Transplantation �� 387
Jae Hyun Park
38 Evolution
of Non-surgical/Minimally Invasive Treatments �� 397
Neil M. Vranis, Erez Dyan, and Spero Theodorou
Part XIV Evolution of Patient-Reported Outcomes (PROs)
39 The
Evolution of Patient-Reported Outcome
Measures (PROMs) in Plastic Surgery�� 411
Colby J. Hyland, Anne F. Klassen, and Andrea L. Pusic
Contributors
Angelica Hernandez Alvarez Division of Plastic and Reconstructive

Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School,
Boston, MA, USA
Andreas Arkudas Department of Plastic and Hand Surgery, University
Hospital Erlangen, Friedrich Alexander University Erlangen Nuernberg FAU,
Erlangen, Germany
Mario Alessandri Bonetti Department of Plastic Surgery, University of
Pittsburgh, Pittsburgh, PA, USA
Gregory H. Borschel Division of Plastic Surgery, Indiana University School
of Medicine, Indianapolis, IN, USA
Riley Hospital for Children, Indianapolis, IN, USA
Ronald D. Brown Department of Plastic and Reconstructive Surgery, The
Ohio State University, Columbus, OH, USA
Katherine L. Burke Section of Plastic Surgery, University of Michigan,
Ann Arbor, MI, USA
Valeria P. Bustos Division of Plastic and Reconstructive Surgery, Beth Israel
Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Charles E. Butler Department of Plastic Surgery, The University of Texas
MD Anderson Cancer Center, Houston, TX, USA
Paul S. Cederna Department of Biomedical Engineering, University of
Michigan, Ann Arbor, MI, USA
Curtis Cetrulo Division of Plastic and Reconstructive Surgery,
Massachusetts General Hospital, Boston, MA, USA
Sydney Ch’Ng The University of Sydney, Camperdown, NSW, Australia
The University of Sydney, Sydney, NSW, Australia
Jong-Woo (JW) Choi Department of Plastic and Reconstructive Surgery,
University of Ulsan College of Medicine, Asan Medical Center, Seoul, South
Korea
Kevin C. Chung Department of Surgery, The University of Michigan Health
System, Ann Arbor, MI, USA
xv
xvi Contributors
Mark Clemens MD Anderson Cancer Center, The University of Texas,

Austin, TX, USA
Stefan Czerniecki Department of Plastic and Reconstructive Surgery, The
Ohio State University, Columbus, OH, USA
Rushil R. Dang Department of Plastic and Reconstruction Surgery, Chang
Gung Memorial Hospital, Linkou, Taiwan
Anthony DeLeonibus Department of Plastic and Reconstructive Surgery,
Cleveland Clinic Foundation, Cleveland, OH, USA
Joseph J. Disa Plastic and Reconstructive, Surgery Service, Department of
Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Laxmi Dongur Department of Surgery, University of Texas Medical Branch,
Galveston, TX, USA
R. Bruce Donoff Harvard School of Dental Medicine, Boston, MA, USA
Gregory A. Dumanian Division of Plastic and Reconstructive Surgery,
Northwestern Memorial Hospital, Chicago, IL, USA
Erez Dyan Avance Plastic Surgery, Reno, NV, USA
Kyle R. Eberlin Hand and Upper Extremity Service, Department of
Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA, USA
Division of Plastic and Reconstructive Surgery, Department of Surgery,
Francesco M. Egro Department of Plastic Surgery, University of Pittsburgh,
Pittsburgh, PA, USA
Rami Elmorsi Department of Plastic Surgery, The University of Texas MD
Anderson Cancer Center, Houston, TX, USA
Dominick J. Falcon Division of Plastic and Reconstructive Surgery, Beth
Israel Deaconess Medical Center, Harvard Medical School, Boston, MA,
USA
Jose Foppiani Division of Plastic and Reconstructive Surgery, Beth Israel
Lacey Foster Keck School of Medicine, University of Southern California,
Los Angeles, CA, USA
Alexander Geierlehner Department of Plastic and Hand Surgery, University
Erlangen, Germany
Bahman Guyuron Zeeba Clinic, Lyndhurst, OH, USA
Case Western Reserve University, Cleveland, OH, USA
Geoffrey G. Hallock Division of Plastic Surgery, St. Luke’s Hospital,
Sacred Heart Division, Allentown, PA, USA
Contributors xvii
Ryoko Hamaguchi Division of Plastic and Reconstructive Surgery, Brigham

and Women’s Hospital, Boston, MA, USA
Abbas Hassan Division of Plastic Surgery, Department of Surgery, Indiana
University School of Medicine, Indianapolis, IN, USA
Joon Pio Hong Department of Plastic Surgery, Asan Medical Center, Seoul,
Korea (Republic of)
Raymund E. Horch Department of Plastic and Hand Surgery, University
Erlangen, Germany
Alfredo Hoyos Dhara Clinic, Bogota, Colombia
Lioba Huelsboemer Division of Plastic and Reconstructive Surgery, Yale
School of Medicine, New Haven, CT, USA
Shao-Yu Hung Department of Plastic and Reconstructive Surgery, Chang
Gung Memorial Hospital and Chang Gung University Medical College,
Linkou, Taiwan
Colby J. Hyland Division of Plastic and Reconstructive Surgery, Brigham
Patient-Reported Outcomes, Value & Experience (PROVE) Center, Boston,
MA, USA
Jeffrey E. Janis Department of Plastic and Reconstructive Surgery, The
Ohio State University Wexner Medical Center, Columbus, OH, USA
Yu Jin Jeong Royal Prince Alfred Hospital, Camperdown, NSW, Australia
Dominik Kaiser Department of Orthopaedic Surgery, Penn Medicine
University City, Philadelphia, PA, USA
Roy Kazan Department of Plastic Surgery, University of Pittsburgh,
Pittsburgh, PA, USA
Ankur Khajuria Kellogg College, University of Oxford, Oxford, UK
Department of Surgery and Cancer, Imperial College London, London, UK
Young Chul Kim Department of Plastic and Reconstructive Surgery,
University of Ulsan College of Medicine, Asan Medical Center, Seoul, South
Korea
Anne F. Klassen McMaster University, Hamilton, ON, Canada
Justin J. Koh Department of Orthopaedic Surgery, Cedars-Sinai Medical
Center, Los Angeles, CA, USA
Isao Koshima International Center for Lymphedema, Hiroshima University
Hospital, Hiroshima, Japan
Stephen Kovach Division of Plastic Surgery, Perelman Center for Advanced
Medicine, Philadelphia, PA, USA
xviii Contributors
Jonathan Lans Hand and Upper Extremity Service, Department of

Ophelie Lavoie-Gagne Hand and Upper Extremity Service, Department of
Bernard T. Lee Division of Plastic and Reconstructive Surgery, Beth Israel
L. Scott Levin Department of Orthopaedic Surgery, Penn Medicine
Samuel J. Lin Division of Plastic and Reconstructive Surgery, Beth Israel
Shawn J. Loder Department of Plastic Surgery, University of Pittsburgh,
Pittsburgh, PA, USA
Susan E. Mackinnon Division of Plastic and Reconstructive Surgery, St.
Louis, MO, USA
Patrick Mallucci Mallucci London, London, UK
Benjamin B. Massenburg Division of Plastic Surgery, Department of
Surgery, University of Washington, Seattle, WA, USA
Amy Moore Department of Plastic and Reconstructive Surgery, The Ohio
State University, Columbus, OH, USA
Brooke L. Moore Department of Urology, Massachusetts General Hospital,
Boston, MA, USA
Foad Nahai Center for Plastic Surgery at MetroDerm, Atlanta, GA, USA
Emory University, Atlanta, GA, USA
Maurizio Bruno Nava G.RE.T.A. Group for Reconstructive and Therapeutic
Advancements, Milan, Naples, Catania, Italy
Plastic and Reconstructive Surgery Department, University of Buenos Aires,
Buenos Aires, Argentina
Peter Neligan Department of Surgery, University of Washington, Seattle,
WA, USA
Shimpei Ono Department of Plastic, Reconstructive and Aesthetic Surgery,
Nippon Medical School, Tokyo, Japan
Dennis P. Orgill Division of Plastic and Reconstructive Surgery, Brigham
Jae Hyun Park Dana Plastic Surgery Clinic, Seoul, South Korea
Nakul Gamanlal Patel Department of Plastic Surgery and Burns, The Royal
Infirmary Hospital, University Hospitals of Leicester, Leicester, UK
St. Andrew’s Centre for Plastic Surgery and Burns, Broomfield Hospital,
Chelmsford, Essex, UK
Contributors xix
Mauricio Perez Total Definer, Rochester, MN, USA

Bohdan Pomahac Division of Plastic and Reconstructive Surgery, Yale
School of Medicine, New Haven, CT, USA
Andrea L. Pusic Division of Plastic and Reconstructive Surgery, Brigham
Patient-Reported Outcomes, Value & Experience (PROVE) Center, Boston,
MA, USA
Venkat Ramakrishnan Department of Plastic Surgery and Burns, The
Royal Infirmary Hospital, University Hospitals of Leicester, Leicester, UK
St. Andrew’s Centre for Plastic Surgery and Burns, Broomfield Hospital,
Chelmsford, Essex, UK
Alberto Rancati Plastic and Reconstructive Surgery Department, University
of Buenos Aires, Buenos Aires, Argentina
Nicola Rocco G.RE.T.A. Group for Reconstructive and Therapeutic
Department of Advanced Biomedical Sciences, University of Naples
“Federico II”, Naples, Italy
Danielle H. Rochlin Plastic and Reconstructive, Surgery Service,
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York,
NY, USA
J. Peter Rubin Department of Plastic Surgery, University of Pittsburgh,
Pittsburgh, PA, USA
Katherine B. Santosa Center for Plastic Surgery at MetroDerm, Atlanta,
GA, USA
Artisan Plastic Surgery, Atlanta, GA, USA
August Schaeffer Department of Surgery, University of Texas Medical
Branch, Galveston, TX, USA
Jenna-Lynn Senger Division of Plastic Surgery, Vancouver General
Hospital, Vancouver, BC, Canada
Jeremy M. Sun Changi General Hospital, Singapore, Singapore
Srinivas M. Susarla Craniofacial Center, Seattle Children’s Hospital,
Seattle, WA, USA
Spero Theodorou BodySculpt, New York, NY, USA
Alan Tom Division of Plastic Surgery, Indiana University School of
Medicine, Indianapolis, IN, USA
Raymond W. Tse Division of Craniofacial and Plastic Surgery, Department
of Surgery, Seattle Children’s Hospital, Seattle, WA, USA
xx Contributors
Krystle R. Tuaño Hand and Upper Extremity Service, Department of

Division of Plastic and Reconstructive Surgery, Department of Surgery,
Neil M. Vranis Ghavami Plastic Surgery, Beverly Hills, CA, USA
Fu-Chan Wei Department of Plastic and Reconstructive Surgery, Chang
Gung Memorial Hospital and Chang Gung University Medical College,
Linkou, Taiwan
Steven E. Wolf Department of Surgery, University of Texas Medical Branch,
Galveston, TX, USA
Gerald J. Wu Division of Plastic Surgery, Indiana University School of
Medicine, Indianapolis, IN, USA
Kitty Y Wu Division of Plastic Surgery, Mayo Clinic, Rochester, MN, USA
Takumi Yamamoto National Centre for Global Health and Medicine,
Tokyo, Japan
Alan Yang Division of Plastic and Reconstructive Surgery, Massachusetts
General Hospital, Boston, MA, USA
Ronald M. Zuker The Hospital for Sick Children and University of Toronto,
Toronto, ON, Canada
Part I
Basic Science
The Evolution of Microsurgery
1
Peter Neligan and Ankur Khajuria
Abstract The Five Most Impactful Papers

This chapter highlights five key landmark 1. Komatsu S, Tamai S. Successful replantation
papers that sparked innovation, challenged the of a completely cut off thumb. Plastic
status quo, and helped shape the evolution of Reconstr Surg. 1968;42(4):374–7.
microsurgery. From the first successful thumb 2. Taylor GI, Daniel RK. The free flap: com-
replantation and free flap cases to the intro- posite tissue transfer by vascular anastomo-
duction of supermicrosurgery, this chapter sis. Aust N Z J Surg. 1973;43(1):1–3.
provides a comprehensive overview of the 3. Acland RD. Microvascular anastomosis: a
transformative journey of microsurgery and its device for holding stay sutures and a new
potential for shaping the future of reconstruc- vascular clamp. Surgery. 1974;75(2):185–7.
tive practice. Finally, other references are 4. Godina M. Early microsurgical reconstruc-
cited to provide perspective and to put the five tion of complex trauma of the extremities.
landmark papers into context, and future Plast Reconstr Surg. 1986;78(3):285–92.
directions are discussed. 5. Koshima I, et al. Supermicrosurgical lym-
phaticovenular anastomosis for the treatment
of lymphedema in the upper extremities. J
Keywords Reconstr Microsurg. 2000;16(6):437–42.
Microsurgery · Supermicrosurgery · Free flap ·
Alexis Carrell is the father of vascular surgery
Anastomosis · Replantation
and received the Nobel Prize for physiology or
medicine in 1912 for pioneering vascular sutur-
ing techniques [1]. This, of course, was a land-
mark and changed the practice of surgery as
well as giving birth to vascular surgery. We have
P. Neligan (*) not chosen it as a landmark paper in the evolu-
Department of Surgery, University of Washington, tion of microsurgery though. Use of the micro-
Seattle, WA, USA scope in surgery was first pioneered by
A. Khajuria otolaryngologists. In 1921, Carl-Olof Nylén
Kellogg College, University of Oxford, Oxford, UK used a microscope built at the University of
Department of Surgery and Cancer, Imperial College Stockholm to operate on a patient with chronic
London, London, UK
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024 3

A. Khajuria et al. (eds.), Landmark Papers in Plastic Surgery,
https://doi.org/10.1007/978-3-031-57132-9_1
4 P. Neligan and A. Khajuria
otitis who had a labyrinthine fistula [2]. This scope, he performed coupling of vessels as
original monocular microscope was soon super- small as 1.4 mm and coined the term microsur-
seded by a binocular model. In 1953, Dr. Hans gery [3, 4]. Jacobson is widely regarded as one
Littmann (1908–1991), head of Med-Lab at of the fathers of Microsurgery. Buncke was
Zeiss-Opton Oberkochen, West Germany (now another giant in the field and did extensive
Carl Zeiss A.G.), and his team of technicians research into microsurgical techniques in the
designed their first ophthalmic operating micro- 1960s [5, 6]. Drs. Harold Kleinert and Mort
scope. Plastic surgery didn’t adopt the micro- Kasdan, performed the first revascularization of
scope until the 1960s. The first microvascular a partial digital amputation in 1963 [7]. The first
surgery, using a microscope to aid in the repair reported case of successful reimplantation of an
of blood vessels, was described by a vascular amputated thumb was by Susumu Tamai in 1968
surgeon, Julius H. Jacobson II of the University [8]. We have chosen this as the first landmark
of Vermont in 1960. Using an operating micro- paper.
Komatsu S, Tamai S. Successful replantation of a completely cut off thumb. Plastic Reconstr Surg.
1968;42(4):374–7
Strengths • This paper was the first to report a successful clinical case of digital replantation
Limitations • This was a single case report
Impact Though many centers were preparing to do such a case, this first case proved the feasibility of such
surgery and the field subsequently developed exponentially
While digital replantation dominated early micro- large scalp defect [9]. This was likely the first pub-
surgical reconstruction, the possibility of transfer- lished free tissue transfer. However, a year later,
ring tissue from distant sites to reconstruct a given Taylor and Daniel published the first report and
defect was an elusive goal. In 1972 Buncke pub- coined the phrase free flap [10] and they have been
lished a paper on transferring omentum to cover a credited with this accolade.
Taylor GI, Daniel RK. The free flap: composite tissue transfer by vascular anastomosis. Aust N Z J Surg.
1973;43(1):1–3
Strengths • The first reported case of a “Free Flap”
Limitations • Single case report
Impact This case report changed the course of microsurgery and led not only to the refinement of the
technique but indirectly to the subsequent explosive development of flaps
Much of the evolution of microsurgery is linked the perforator flap [15]. While all of these are
to the evolution of flaps. This probably started landmark papers in their own right, because of
with McGregor and Jackson’s recognition of the fact that they changed practice, this chapter
the axiality of the blood supply of the groin flap is about the evolution of microsurgery so we
[11] though at that time the groin flap was not have endeavored to confine our landmark paper
used as a microsurgical free flap. Mathes and discussion to those which impacted the evolu-
Nahai elucidated the blood supply of the myo- tion of microsurgery, rather than the former
cutaneous flap [12] as did Cormack and which evolved because of the introduction of
Lamberty for fasciocutaneous flaps [13]. Taylor microsurgery.
and Palmer, through a series of elegant lead- Apart from introducing magnification to sur-
oxide injections described the vascular territo- gery, microsurgery demanded the development
ries of the body which they called angiosomes of certain instruments to facilitate its practice.
[14]. And more recently, Koshima introduced One of these is the micro clamp and probably the
1 The Evolution of Microsurgery 5
most ubiquitous of these is the Acland Clamp. Acland, and others, working with industry, devel-
Robert Acland introduced this in 1974 [16] and oped many instruments which are still in com-
we have chosen this as our third landmark paper. mon use today [17–19].
Acland RD. Microvascular anastomosis: a device for holding stay sutures and a new vascular clamp. Surgery.
1974;75(2):185–7
Strengths • Introduction of a clamp which could be used to gently hold vessels and at the same time, hold
stay sutures to aid in a microvascular anastomosis
Limitations • A single surgeon’s perspective on how best to perform a microvascular anastomosis
Impact This was one of the first clamps introduced to aid in a microvascular anastomosis and while there
are many such clamps available, this was one of the first and widely adopted
As well as instruments, microvascular sutures ments led to a change in practice in many areas
had to be developed and refined [20]. Another including hand [22], head and neck [23], breast
such device that proved to be a game-changer [24], peripheral nerve [25], but one of the most
was the microvascular coupler. The concept was impactful papers that led to a change in practice
first introduced as far back as 1986 [21] and was as well as an expanded indication for microsur-
ultimately developed into the venous coupler that gery is that by Godina in the treatment of com-
is in common use today. All of these develop- plex extremity trauma [26].
Godina M. Early microsurgical reconstruction of complex trauma of the extremities. Plast Reconstr Surg.
1986;78(3):285–92
Strength • This was one of the first papers that espoused the concept of early reconstruction of complex
extremity trauma
Limitations • This was a retrospective single institution study
Impact This paper essentially changed people’s thinking of how to deal with complex trauma and spawned
not just a change in practice, but numerous other studies that looked at the results of this concept
This chapter concentrates on the evolution of tackle new horizons. However, apart from
microsurgery as it applies to plastic surgery. changes in things such as the optics of micro-
There were, naturally, similar advances in other scopes, the advancement of suture technology
areas, such as gynecology, ophthalmology, lar- and the improvement in instrumentation, the
yngology [27], and of course, neurosurgery technique of microsurgery itself had to change.
[28]. All of the references cited so far in this That change was brought about by Isao Koshima
chapter are old and that is because these cita- who introduced the concept of supermicrosur-
tions relate to the initial development of micro- gery [29].
surgery and related subjects. Many of them will Supermicrosurgery, defined as anastomosis of
appear in other chapters, such as those on the vessels less than 0.8 mm, has greatly expanded
evolution of flaps, hand surgery, etc. What is the armamentarium of the reconstructive sur-
unique about microsurgery itself is that there geon. Current applications include the use of
was very little change in the technology and perforator-to-perforator free-
styled flaps, lym-
optics of microscopes until relatively recently phovenous anastomoses (LVAs), and vascular-
and it was really evolution in practice that ized lymph node transfer (VLNT) in lymphedema,
demanded that change eventually. The optics fingertip replantation, microneural repair, and
have improved so that the surgeon is now able to diabetic foot management.
6 P. Neligan and A. Khajuria
Koshima I, et al. Supermicrosurgical lymphaticovenular anastomosis for the treatment of lymphedema in the upper
extremities. J Reconstr Microsurg. 2000;16(6):437–42
Strengths • This paper describes the technique of supermicrosurgery, an evolution of microsurgery that allows
for the repair of smaller structures
Limitations • Single institution technical study
Impact The impact of this has been significant and has led to the adoption of supermicrosurgery techniques.
This has enabled surgeons to develop lymphatic surgery and to refine free flap surgery
1.1 Expert Concluding high-definition 3D cameras provides the oppor-

Commentary tunity to replace conventional operating micro-
scopes. One of the factors driving this is the
Microsurgery has been around now for over ergonomic problem presented by operating with
50 years. For the first several decades of its exis- loupes as well as operating under the scope. This
tence, there was a lot of work done on the devel- demands long periods of unnatural positioning
opment of different applications for microsurgery that has resulted in significant health problems
in all specialties. Despite this, there was very lit- for many surgeons [36, 37]. Other specialties
tle development in the technology of the operat- have already started to adopt this technology
ing microscope; there were many advances in the [38]. With the development of supermicrosurgi-
accessories of microsurgery; improvements in cal techniques we are working with smaller and
the physical manipulation of the microscope, smaller structures. This leaves the human hand as
introduction of better sutures, couplers, etc. a limiting factor in microsurgery. Everyone has a
However, there was little change in the optics of tremor and this becomes a problem the greater
the standard operating microscope for many the magnification. A dedicated robot for micro-
years. Advances in techniques not only expanded surgery has been developed by two companies,
the indications for microsurgery but ultimately one Italian and one Dutch. A robot can help to
led to the development of more sophisticated overcome tremor by enhancing the precision and
microscopes, high definition scopes with greater stability of the surgeons’ hands. This has culmi-
magnification and this has led to even further nated in a first-in-human robotic supermicrosur-
advances in microsurgery such as supermicrosurgery case for breast cancer-related lymphedema
gery and nanomicrosurgery. The use of imaging [39], and more recently in the first robot-assisted
has also changed the landscape. The handheld microsurgical free flap reconstruction using a
doppler has been around for a long time and is perforator-to-perforator flap technique [40].
used universally [30]. The use of CT angiogra- Using a dedicated microsurgical robot in combi-
phy [31] was another great advance that took a nation with a 4 K-3D exoscope is just beginning
lot of the guesswork out of dissecting flaps. to be used clinically [41]. This is the future of
Fluorescence imaging has advanced the reliabil- microsurgery.
ity of both flap and lymphedema surgery [32].
The smartphone has seen the affordable introduc-
tion of thermography to flap planning [33] and References
ultrasound, particularly ultra-high frequency
ultrasound (UHFUS) has been a game changer 1. Carre A. La technique operatoire des anastomoses
vasculaires et la transplantation des visceres. Lyon
not only in planning flaps [34], but in expanding Med. 1902;98:859–63.
the indications for lymphatic surgery [35]. So, 2. Nylen CO. The microscope in aural surgery, its first
microsurgery has evolved because of all of these use and later development. Acta Otolaryngol Suppl.
factors. We are now about to enter a new phase; 1954;116:226–40.
3. Jacobson JH, Suarez EL. Microvascular surgery. Dis
the days of the operating microscope as we know Chest. 1962;41:220–4.
it are on the way out. Evolving technology of
1 The Evolution of Microsurgery 7
4. Jacobson J, Suarez E. Microsurgery in anastomosis of 25. Smith JW. Microsurgery of peripheral nerves. Plast
small vessels. Surg Forum. 1960;9:245. Reconstr Surg. 1964;33:317–29.
5. Buncke HJ, Schulz WP. Total ear reimplantation in 26. Godina M. Early microsurgical reconstruction of
the rabbit utilising microminiature vascular anasto- complex trauma of the extremities. Plast Reconstr
moses. Br J Plast Surg. 1966;19(1):15–22. Surg. 1986;78(3):285–92.
6. Buncke HJ, Schulz WP. Experimental digital ampu- 27. Smith JW. Microsurgery: review of the literature and
tation and reimplantation. Plast Reconstr Surg. discussion of microtechniques. Plast Reconstr Surg.
1965;36:62–70. 1966;37(3):227–45.
7. Kleinert HE, Kasdan ML. Restoration of blood flow 28. Samson DS, Boone S. Extracranial-intracranial (EC-
in upper extremity injuries. J Trauma. 1963;3:461–76. IC) arterial bypass: past performance and current con-
8. Komatsu S, Tamai S. Successful replantation of a cepts. Neurosurgery. 1978;3(1):79–86.
completely cut off thumb. Plastic Reconstr Surg. 29. Koshima I, et al. Supermicrosurgical lymphaticoven-
1968;42(4):374–7. ular anastomosis for the treatment of lymphedema
9. McLean DH, Buncke HJ. Autotransplant of omentum in the upper extremities. J Reconstr Microsurg.
to a large scalp defect, with microsurgical revascular- 2000;16(6):437–42.
ization. Plast Reconstr Surg. 1972;49(3):268–74. 30. Solomon GA, Yaremchuk MJ, Manson PN. Doppler
10. Taylor GI, Daniel RK. The free flap: composite tis- ultrasound surface monitoring of both arterial and
sue transfer by vascular anastomosis. Aust N Z J Surg. venous flow in clinical free tissue transfers. J Reconstr
1973;43(1):1–3. Microsurg. 1986;3(1):39–41.
11. McGregor IA, Jackson IT. The groin flap. Br J Plast 31. Masia J, et al. Preoperative computed tomographic
Surg. 1972;25(1):3–16. angiogram for deep inferior epigastric artery perfora-
12. Mathes SJ, Nahai F. Classification of the vascular tor flap breast reconstruction. J Reconstr Microsurg.
anatomy of muscles: experimental and clinical corre- 2010;26(1):21–8.
lation. Plast Reconstr Surg. 1981;67(2):177–87. 32. Dip F, et al. Intraoperative fluorescence imaging in
13. Cormack GC, Lamberty BG. A classification of different surgical fields: consensus among 140 inter-
fascio-cutaneous flaps according to their patterns of continental experts. Surgery. 2022;172(6S):S54–9.
vascularisation. Br J Plast Surg. 1984;37(1):80–7. 33. Pereira N, Hallock GG. Smartphone thermography
14. Taylor GI, Palmer JH. The vascular territories (angio- for lower extremity local flap perforator mapping. J
somes) of the body: experimental study and clinical Reconstr Microsurg. 2021;37(1):59–66.
applications. Br J Plast Surg. 1987;40(2):113–41. 34. Tashiro K, et al. Locating recipient perforators for
15. Koshima I, Soeda S. Inferior epigastric artery skin perforator-to-perforator anastomosis using color dop-
flaps without rectus abdominis muscle. Br J Plast pler ultrasonography. J Plast Reconstr Aesthet Surg.
Surg. 1989;42(6):645–8. 2014;67(12):1680–3.
16. Acland RD. Microvascular anastomosis: a device 35. Hayashi A, et al. Ultrasound visualization of the
for holding stay sutures and a new vascular clamp. lymphatic vessels in the lower leg. Microsurgery.
Surgery. 1974;75(2):185–7. 2016;36(5):397–401.
17. Acland R. New instruments for microvascular sur- 36. Fisher SM, Teven CM, Song DH. Ergonomics in the
gery. Br J Surg. 1972;59(3):181–4. operating room: the cervicospinal health of today’s
18. Acland R. A new needle for microvascular surgery. surgeons. Plast Reconstr Surg. 2018;142(5):1380–7.
Surgery. 1972;71(1):130–1. 37. Lakhiani C, et al. Ergonomics in microsurgery. J Surg
19. Acland RD. Modified needleholder for microsurgery. Oncol. 2018;118(5):840–4.
Br Med J. 1969;1(5644):635. 38. Siller S, et al. A high-definition 3D exoscope
20. Roberts WN. Development of needles and as an alternative to the operating microscope
sutures for microsurgery. J Biomed Mater Res. in spinal microsurgery. J Neurosurg Spine.
1975;9(5):399–405. 2020;33(5):705–14.
21. Ostrup LT, Berggren A. The UNILINK instrument 39. van Mulken TJM, et al. First-in-human robotic
system for fast and safe microvascular anastomosis. supermicrosurgery using a dedicated microsurgi-
Ann Plast Surg. 1986;17(6):521–5. cal robot for treating breast cancer-related lymph-
22. Kleinert HE, Serafin D, Daniel RK. The place of edema: a randomized pilot trial. Nat Commun.
microsurgery in hand surgery. Orthop Clin North Am. 2020;11(1):757.
1973;4(4):929–44. 40. Innocenti M, Malzone G, Menichini G. First-in-
23. Serafin D, Georgiade NG, Peters CR. Microsurgical human free flap tissue reconstruction using a dedi-
composite tissue transplantation: a method of imme- cated microsurgical robotic platform. Plast Reconstr
diate reconstruction of the head and neck. Clin Plast Surg. 2023;151(5):1078–82.
Surg. 1976;3(3):447–57. 41. van Mulken TJM, et al. First-in-human integrated
24. Harashina T, et al. Breast reconstruction with micro- use of a dedicated microsurgical robot with a 4K 3D
surgical free composite tissue transplantation. Br J exoscope: the future of microsurgery. Life (Basel).
Plast Surg. 1980;33(1):30–7. 2023;13(3):692.
Emerging Flaps
2
Joon Pio Hong
Abstract 3. Behan FC. The keystone design perforator

In this chapter, relatively recent concept of island flap in reconstructive surgery. Anz J
“perforator-based flap” along with flaps Sug. 2003;73(3):112–20.
emerging from this concept is reviewed by 4. Koshima I, et al. The anterolateral thigh flap;
presenting the five landmark publication that variations in its vascular pedicle. Br J Plast
have contributed to the evolution of modern Surg. 1989;42(3):260–2.
flaps. Details are not given on individual tech- 5. Allen RJ, Treece P. Deep inferior epigastric
niques but rather discuss how these papers perforator flap for breast reconstruction. Ann
have shaped the direction of modern recon- Plast Sug. 1994;32(1):32–8.
struction with regard to flap utilization. Other
references are cited to provide some perspec-
tive as it is impossible to cover such a large 2.1 Introduction
topic with just five references.
The concept of perforator flap is a natural evolu-
tion of efficiently utilizing the vascular anatomy.
Keywords Since the depiction of axial pattern arteries
Perforator flap · Propeller flap · Keystone flap · within the skin and subcutaneous fat, we have
DIEP flap · ALT free flap evolved from random pattern flaps to now using
a small perforator as the sole source of blood
supply to the flap. Where the classical free flaps
The Five Most Impactful Papers using muscle and its relevant pedicle in conjunc-
1. Koshima I, Soeda S. Inferior epigastric artery tion with skin have faced numerous issues such
skin flaps without rectus abdominis muscle. as excess bulk, loss of muscle function, limited
Br J Plast Surg. 1989;42(6):645–8. donor sites, and unfavorable aesthetic outcome.
2. Hyakusoku H, et al. The propeller flap method. As part of a natural evolution, with the increased
Br J Plast Surg. 1991;44(1):53–4. knowledge on end vessels, linking vessels, and
the territory of these small vessels, the introduc-
tion of perforator flaps revolutionized the way
reconstruction is performed. It provided the ideal
coverage for skin defects, better function, less
J. P. Hong (*)
Department of Plastic Surgery, Asan Medical Center, donor site morbidity, and enhanced aesthetic
Seoul, Korea (Republic of) outcome.

https://doi.org/10.1007/978-3-031-57132-9_2
10 J. P. Hong
2.2 Perforator Flaps vive on a single muscle perforator [3]. This piv-
otal study opened the possibilities of using
As plastic surgery 101 mandates like with like, it perforator flaps as a free flap which brought new
is a natural evolution that surface defects were advantages over the already existing free flaps
tried to be covered with skin flaps. This effort such as reduced donor-site morbidity, able to har-
began with random pattern flap evolving into vest lengthy pedicle, possibility to customize the
axial pattern, musculocutaneous, fasciocutane- flaps accordingly with multiple flaps/tissues, and
ous, and ultimately perforator flaps. It was the controlled thickness.
work of Taylor and Palmer in 1987 defining the As the use of perforator flaps started to grow,
vascular territories of source vessels which they the controversy in defining what is a perforator
termed angiosomes that provided the anatomical flap emerged that led to an attempt to introduce
basis for perforator flaps [1]. standardized nomenclature [4]. However, a variety
In 1988, Kroll and Rosenfield reported on a of terms are still used widely based on location,
new type of flap based on an unnamed perforator arterial supply, or muscle origin. Nevertheless, a
as an island flap validating the idea of perforator simplified concept of a skin flap based on any per-
flap “Perforator-based flaps for low posterior forator is gaining acceptance. The use of these
midline defects” [2]. In 1989, Koshima and perforator-based free flaps ultimately led to the
Soeda described an inferior epigastric artery skin concept of “freestyle flaps” where any flap can be
flap without rectus abdominis muscle for recon- elevated based on a single perforator and eventu-
struction of floor-of-the-mouth and groin defects, ally to using perforator as a recipient “perforator-
noting that a large flap without muscle could sur- to-perforator style reconstruction” [5–7].
Koshima I, Soeda S. Inferior epigastric artery skin flaps without rectus abdominis muscle. Br J Plast Surg.
1989;42(6):645–8
Strengths • Described a perforator-based skin flap without taking the muscular portion
• Described that a large skin portion was able to survive on a single perforator
Limitations • Small study group
Impact This was the study that delivered the concept of perforator-based skin flaps as a free flap. Describing
the muscle portion of the flap is not needed and a single perforator is able to provide adequate
circulation to the distal skin organ was a paradigm shift. This paper opened the era of perforator flaps
2.3 Propeller Flap ment flap and avoids a midline scar prone for
dehiscence [8].
A propeller flap is defined as an island flap Hyakusoku et al. published a pivotal paper in
based on a perforator that reaches the recipient 1991 “The propeller flap method” which demon-
site through an axial rotation. The preopera- strated that the skin flap based on a subcutaneous
tive design and vascular assessment can be pedicle rotated 90 degrees to cover the defect
easily made by a handheld Doppler. As the avoiding a complex free flap application [9].
pedicle is often dissected and identified visu- Further refinement was made by Hallock by com-
ally, it allows having a more reliable vascular bining the concepts of propeller and perforator flap
pedicle leading to more mobility, versatile to achieve 180 degrees rotations based on a pivot-
design while having minimal donor-site mor- ing perforator pedicle ultimately leading to the cur-
bidity. One example of the advantage of the rent concept of propeller flaps [10]. Teo popularized
propeller flap can be seen when reconstructing this concept especially in lower extremity chal-
a large sacral pressure sore. The use of propel- lenging the classic paradigm for free flap recon-
ler flap prevents using a bilateral V-Y advance- struction of the lower 1/3 of the leg [11].
2 Emerging Flaps 11
Hyakusoku H, et al. The propeller flap method. Br J Plast Surg. 1991;44(1):53–4

Strengths • The first report on a new flap based on a perforator with a propeller style rotation
• Efficient utilization of the surrounding tissue
Limitations • Crude description of pedicle and technical aspect of the propeller flap
Impact This was the first study to show that the perforator-based skin flap can be rotated in a propeller style.
This is a very simple approach with high reliability often eliminating the need for a complex free flap
reconstruction. Now with the presence of any perforator, one can first think of designing a propeller
flap as a first line option for reconstruction. This approach has simplified the reconstruction for the
trunk and extremity
2.4 Keystone Flaps cent to the long axis of the defect. The wound is
closed directly; the mid-line area is the line of
The keystone island flap was first described by maximum tension and by V-Y advancement of
Behan in 2003 [12]. This approach allowed to each end of the flap, the “islanded” flap fills the
overcome the limitations of the regional or local defect. This allows the secondary defect on the
flaps where the arc of rotation or the movement is opposite side to be closed, exploiting the mobil-
often limited by the underlying tissue attached to ity of the adjacent surrounding tissue [12]. The
the base. By combining the concepts fasciocuta- beauty of this technique is that it allows simple
neous perforators and local flaps, the keystone and reliable solutions in regions where recon-
island flap offers both the robust vascularity and struction was unreliable such as the posterior
relative ease and speed of local tissue rearrange- trunk and thigh regions. It provides a superior
ment. The keystone flap derives its name from its aesthetic result as it allocates regional tissues.
similarity to the architectural keystone piece that From the initial presentation many variations and
marks the central portion of the arch. It is essen- modifications have been made to maximize the
tially elliptical in shape with its long axis adja- reconstructive benefit from this approach.
Behan FC. The keystone design perforator island flap in reconstructive surgery. Anz J Sug. 2003;73(3):112–20
Strengths • A strong study utilizing the concept of perforators on local flaps
• Extensive research on identifying randomly located perforators to maximize the benefits of
keystone flap based on over 300 flap experience
• Identified variations of this approach
Limitations • Low impact journal and took a lot of time till it reached the major audience
Impact This is the first paper introducing the concept of keystone flaps. It is a natural evolution of flap surgery
in identifying the perforators that supplies the skin tissue. The remarkable yet simple design allows to
close even extensive defects by utilizing one or more keystone. As long as the donor site is able to
provide adequate size, the application allows to avoid complex free flaps
2.5 ALT (Anterolateral eral thigh flap: variations in this vascular pedicle”
Thigh) Flap that displayed clear concepts, anatomy, and the
benefits of using the ALT flap [15]. In this paper, it
On the contrary to the common citing that Song depicts not only the main perforator as the source
et al. was the first to describe the ALT flap in 1984 vessel but describes the benefits of using the ALT
“The free thigh flap: a new free flap concept based such as thin and pliable skin, long and large pedi-
on the septocutaneous artery,” the actual first report cle, good donor scar, and the technical possibility
was made by S.M. Baek in 1983 “Two new cutane- of combining with fascia, sensory nerve, and iliac
ous free flaps: the medial and lateral thigh flaps” bone. Consequently, Wei et al. publication in 2002
[13, 14]. He describes that the lateral thigh flap has on describing the ALT as the ideal flap for recon-
its vascular pedicle from the third perforating struction, “Have we found an ideal soft-tissue flap?
artery of the profunda femoris artery and its accom- An experience with 672 anterolateral thigh flaps,”
panying vein. However, it was not until Koshima started the true era of ALT as one of the workhorse
et al. published the paper in 1989 “The anterolat- flaps around the world [16].
12 J. P. Hong
Koshima I, et al. The anterolateral thigh flap; variations in its vascular pedicle. Br J Plast Surg. 1989;42(3):260–2
Strengths • Comprehensive description of the flap
• Depiction of the characters and the attributes of the ALT flap
• Description of alternative options when source pedicle is not reliable
Limitations • Small study group
• Early and crude description of anatomy
Impact This was one of the first studies that showed a clear picture of anatomy of the anterolateral thigh flaps
and the clear benefits of using a skin perforator flap. This paper provided the groundwork to become
one of the most widely used flaps of today
DIEP flap provided the bulk of tissue while spar-

2.6 DIEP (Deep Inferior ing the muscle function by preserving the rectus
Epigastric Perforator) Flap muscles and fascia. This was a significant benefit
over the TRAM (transverse rectus abdominis
The DIEP (deep inferior epigastric perforator) muscle) flap reconstruction in that it was able to
flap was first described in 1989 by Koshima and decrease ventral hernia or muscle weakness.
Soeda where an inferior epigastric artery skin flap The DIEP flap depicts the typical evolution of
without rectus abdominis muscle was harvested a perforator flap where it evolved from TRAM
for reconstruction noting that a large flap without musculocutaneous flap, then to partial muscle
muscle could survive on a single muscle perfora- sparing, and ultimately to DIEP flap where the
tor [3]. The true value of DIEP flap was not perforator is skeletonized demonstrating that the
revealed until 1994 when Robert Allen reported skin/fat tissue can survive completely without the
application for breast reconstruction [17]. The addition of deep fascia and muscle.
Allen RJ, Treece P. Deep inferior epigastric perforator flap for breast reconstruction. Ann Plast Sug.
1994;32(1):32–8
Strengths • Well conducted study with both experimental and clinical evidence
• Demonstrated clear surgical approach
• Results with significant benefits over the TRAM flap
Limitations Recent innovations such as perfusion imaging is not covered
Impact This study opened the new era for microsurgical breast reconstruction as to popularize the concept of
perforator flaps. It clearly demonstrated the benefits of the perforator flap approach over conventional
flaps
2.7 Expert Concluding I am excited to be part of the rapid evolution

Commentary witnessing and utilizing this technique to improve
functional and aesthetic outcome for reconstruc-
With the better knowledge of angiosomes, perfo- tive surgery. Stemming from this idea, under-
rasomes, and perforators opened a new era for standing the anatomical structures and functions
perforator flaps. This is a natural evolution from of perforators, we now are able to customize not
classical flaps gradually understanding the capa- only the composition of the flaps but the thick-
bilities of a single perforator as well as the terri- ness of the flap (safely elevating from different
tory that it supplies. The use of these small layers of the fat and even a pure skin perforator
vessels paved the door to the concept of supermi- flap) customizing to the need of the recipient site
crosurgery, perforator to perforator surgery, and a stepping closer to the true reconstructive elevator
new set of imaging to support the realization of concept [18, 19]. This evolution allows the sur-
the technique. geons to have the tools not only to cover the
2 Emerging Flaps 13
defects but now achieve the best possible results 8. Oh TS, Hallock G, Hong JP. Freestyle propeller flaps
to reconstruct defects of the posterior trunk: a sim-
while minimizing the morbidity of donor sites as ple approach to a difficult problem. Ann Plast Surg.
well as to design the best possible efficient 2012;68(1):79–82.
surgery. 9. Hyakusoku H, Yamamoto T, Fumiiri M. The propeller
I believe that the evolution will not stop with flap method. Br J Plast Surg. 1991;44(1):53–4.
10. Hallock GG. The propeller flap version of the adduc-
perforator. The father of supermicrosurgery, Dr. tor muscle perforator flap for coverage of ischial
Isao Koshima has been saying the dimension of or trochanteric pressure sores. Ann Plast Surg.
microsurgery will further become smaller into 2006;56(5):540–2.
“nano” level. I am excited to see where this eval- 11. Teo TC. The propeller flap concept. Clin Plast Surg.
2010;37(4):615–26. vi
uation will take us. 12. Behan FC. The keystone design perforator Island
flap in reconstructive surgery. ANZ J Surg.
2003;73(3):112–20.
13. Song YG, Chen GZ, Song YL. The free thigh flap: a
References new free flap concept based on the septocutaneous
artery. Br J Plast Surg. 1984;37(2):149–59.
1. Taylor GI, Palmer JH. The vascular territories (angio- 14. Baek SM. Two new cutaneous free flaps: the
somes) of the body: experimental study and clinical medial and lateral thigh flaps. Plast Reconstr Surg.
applications. Br J Plast Surg. 1987;40(2):113–41. 1983;71(3):354–65.
2. Kroll SS, Rosenfield L. Perforator-based flaps for 15. Koshima I, Fukuda H, Utunomiya R, Soeda S. The
low posterior midline defects. Plast Reconstr Surg. anterolateral thigh flap; variations in its vascular ped-
1988;81(4):561–6. icle. Br J Plast Surg. 1989;42(3):260–2.
3. Koshima I, Soeda S. Inferior epigastric artery skin 16. Wei FC, Jain V, Celik N, Chen HC, Chuang DC,
flaps without rectus abdominis muscle. Br J Plast Lin CH. Have we found an ideal soft-tissue flap? An
Surg. 1989;42(6):645–8. experience with 672 anterolateral thigh flaps. Plast
4. Saint-Cyr M, Schaverien MV, Rohrich RJ. Perforator Reconstr Surg. 2002;109(7):2219–26; discussion
flaps: history, controversies, physiology, anatomy, 27–30
and use in reconstruction. Plast Reconstr Surg. 17. Allen RJ, Treece P. Deep inferior epigastric perfo-
2009;123(4):132e–45e. rator flap for breast reconstruction. Ann Plast Surg.
5. Asko-Seljavaara S. Abstracts of the seventh con- 1994;32(1):32–8.
gress of the International Society of Reconstructive 18. Gottlieb LJ, Krieger LM. From the reconstructive lad-
Microsurgery 1983. New York; 1983. der to the reconstructive elevator. Plast Reconstr Surg.
6. Hong JP, Koshima I. Using perforators as recipient ves- 1994;93(7):1503–4.
sels (supermicrosurgery) for free flap reconstruction 19. Kwon JG, Brown E, Suh HP, Pak CJ, Hong JP. Planes
of the knee region. Ann Plast Surg. 2010;64(3):291–3. for perforator/skin flap elevation-definition, clas-
7. Wei FC, Mardini S. Free-style free flaps. Plast sification, and techniques. J Reconstr Microsurg.
Reconstr Surg. 2004;114(4):910–6. 2023;39(3):179–86.
Evolution of Vascularized
Composite Allotransplantation
3
Lioba Huelsboemer and Bohdan Pomahac
Abstract and presenting hereon the highlights as well as

Vascularized composite allotransplantation the history, challenges, and achievements to
(VCA) is a relatively new and broad field give an all-encompassing overview.
allowing for reconstruction of complex tissue
defects with allotransplantation of equivalent Keywords
human parts. Major medical developments Vascularized composite allotransplantation ·
occurred over the past several decades result- Face transplantation · Hand transplantation ·
ing in satisfying aesthetic and functional out- Reconstruction · Tolerance induction ·
comes of, for example, face, hand, abdominal Perfusion · Immunosuppressive therapy ·
wall, larynx, knee, scalp, penis, or uterus trans- Ischemia reperfusion injury · Acute and
plants. The composite nature of multiple tis- chronic rejection · Reconstructive surgery
sues as well as significant immunogenicity of
skin makes VCA unique as compared to solid
organ transplantation (SOT). Given a small Key Landmark Papers
number of cases worldwide, major challenges 1. Dubernard JM, et al. First human hand
still need to be addressed including agreement transplantation. Case report. Transpl Int.
on indication and patient selection, prolonga- 2000;13:S521–7.
tion of ischemia time, management of acute 2. Devauchelle B, et al. First human face allograft
and chronic rejection, reduction of long-term early report. Lancet; 2006; 368:203–9.
toxicity of immunosuppressive medications, 3. Pomahac B, et al. Novel surgical tech-
and potentially tolerance induction. A long- nique for full face transplantation. PRS;
term goal facilitating mainstream adoption of 2012;130:549–55.
VCA is the development of non-toxic, patient- 4. Pomahac B, et al. Three patients with
specific immunosuppressive and/or tolero- full face transplantation. N Engl J Med.
genic strategies. In this chapter, we will discuss 2012;366:715–22.
four key landmark papers on hand and face
transplantation in context of VCA in general
3.1 Introduction
Vascularized composite allotransplantation (VCA)

L. Huelsboemer · B. Pomahac (*) is the latest tool to reconstruct complex and severe
Division of Plastic and Reconstructive Surgery, defects of the human body. Potential defects usu-
Yale School of Medicine, New Haven, CT, USA

https://doi.org/10.1007/978-3-031-57132-9_3
16 L. Huelsboemer and B. Pomahac
ally result from trauma (e.g., car accident, the fact that the difficulty was no longer the tech-
attempted suicide, amputation, animal bites, burn) nical implementation but the patient’s aftercare
or as a consequence of tumor, infectious diseases, in terms of rejection and side effects of immuno-
or congenital malformation. For the last decades, suppression, which was still a limiting factor for
milestones along the way of inventing the novel long-term graft and patient’s survival. In 1979,
field of VCA have been usually based on findings another immunosuppressive drug called cyclo-
and results from solid organ transplantation. Back sporine A (CsA), a calcineurin inhibitor, has been
in the early 1950s, allograft transplantation of clinically applied for the first time and showed
solid organs was impossible given the subsequent improved results in terms of less toxicity and
immune response. The absence of therapeutic improved graft function compared to azathio-
options and a lack of understanding of the mecha- prine, especially in combination with predniso-
nisms of acute rejection resulted in the effort of lone [7]. Later, azathioprine could be replaced
initially proving the technical feasibility of kidney with mycophenolate mofetil (MMF), a mycophe-
transplantation rather than focusing on acute rejec- nolic acid prodrug that inhibits B- and T-cell pro-
tion. It was assumed that solid organs might be liferation and hereby suppresses the immune
tolerated between identical twins as it was well system, that showed reduced rejection episodes
studied that skin transplantation didn’t lead to and improved graft function as well as patients’
acute or chronic rejection in identical twins. Joseph survival in combination with CsA and steroids
Edward Murray and his team performed the first [9]. The invention of tacrolimus, another calci-
successfully transplanted human kidney that func- neurin inhibitor, allowed a withdrawal from pred-
tioned immediately in identical twins in 1954 nisolone in selective cases when combined with
(Boston, USA) [5]. The next few years were char- MMF [10]. While the short-term outcome of kid-
acterized by intensive research into the invention ney allotransplantation was improved through
of therapeutics that enabled solid organ transplan- novel therapeutics such as calcineurin inhibitors
tation (SOT) in genetically different individuals by and MMF, the long-term graft function as well as
suppressing the human immune system without patient’s long-term survival was still a major con-
disabling it completely. First approaches were cern due to toxic side effects (e.g., nephrotoxic-
made with total body irradiation but didn’t lead to ity, neurotoxicity, hypertension, hyperglycemia,
success. The invention of the immunosuppressant gastrointestinal disturbances, infections, and
(IS) azathioprine, a prodrug that reduces the syn- malignancy) [11]. In 2011, a fusion protein called
thesis of white blood cells, showed promising belatacept inhibiting T-cell activation by binding
results following kidney allotransplantation in to CD80 and CD86 (important costimulatory
dogs in 1957 and raised hope for SOT in geneti- molecules expressed on T-cells) demonstrated
cally diverse human individuals [6, 7]. increased patient’s and graft survival with less
Hereupon, the first successful human kidney nephrotoxicity compared to calcineurin inhibi-
allotransplantation was performed by Joseph tors and could serve as a substitute in special
Edward Murray and his team from a deceased cases when tacrolimus lead to reduced kidney
donor (Boston, USA) in 1962. In the beginning function [12].
of kidney allotransplantation, protocols included However, first-line treatment was invented
azathioprine, azaserine, actinomycin C, and/or with the introduction of calcineurin inhibitors as
prednisone. After lethality caused by drug over- the results demonstrated a substantial increase in
dosages occurred, the regimen was changed to not just short-term but also long-term survival of
minimal drug dosage with treatment of rejection kidney transplantation and proving immunosup-
instead. Azathioprine was the most important pressants following solid organ transplantation
immunosuppressive drug at that time and showed as safe and feasible concept [13–15]. Research
even better results when combined with predni- in the field of SOT and immunosuppression (IS)
sone, but strong side effects were also reported has entered a new era in medicine as well as
[8]. The following years were characterized by pushed the field of VCA further as adequate
3 Evolution of Vascularized Composite Allotransplantation 17
knowledge was collected to make another 148 upper extremity, 80 uterus, 48 face, 46
attempt with VCA in humans [16]. The first ever abdominal wall, 5 penis, and 2 lower extremity
reported VCA in humans, a hand transplantation, transplantations have been performed on patients
was performed in Ecuador in 1964 but failed due worldwide [19–23]. Approximately 40 VCA
to rejection, 21 days posttransplant as the immu- programs across five continents are established
nosuppressive regimen only consisted of predni- and more will likely follow [24, 25]. The surgi-
sone, a single dose of radiation and azathioprine cal reconstruction of severe defects of the human
[17]. Due to concerns about skin immunogenic- body has been proven feasible and is showing
ity, lack of potent IS in the 1960s as well as per- satisfying results in aesthetics, motor and sen-
sisting ethical questions related to this sory function, and organ-specific function by
life-enhancing rather than life-saving therapy, means of VCA. Face transplantation, upper arm
progress in this field stalled for the next several (hand) transplantation, abdominal wall trans-
decades [18]. In 1998, the first human hand plantation, larynx, scalp, knee, flexor tendon
transplantation was successfully performed by apparatus, trachea, peripheral nerve, uterus, and
Jean-Michel Dubernard and his team in Lyon, penis transplantation have been performed suc-
France [1]. To date, over 300 VCAs including cessfully in humans worldwide [1, 26–31].
Dubernard JM, et al. First human hand transplantation. Case report. Transpl Int. 2000;13:S521–7
Strengths • First successfully allotransplanted hand worldwide
• Detailed description of procedure, immunosuppressive regimen, challenges, and functional
outcome
Limitations • This case is only described for 210 days postoperatively in the follow-up care
Impact This is a landmark paper in VCA as it proved the feasibility of allohand transplantation as safe
concept. This paper served as catalysator for further improvement and over 100 hand transplantations
have been performed since then
3.2 Milestones in VCA Through occurred, and wound healing was uneventful.
Face and Hand Today, due to increased experience of surgical
Transplantation teams and recovery logistics, the total ischemia
time can be in most cases reduced to under 4 h
The first successful hand transplantation is truly a depending on the procedure [33]. To address cell-
milestone in the history of VCA and was per- based damage that occurs through ischemia and
formed by Jean-Michael Dubernard and his team reperfusion in general and prolong ischemia time
in Lyon, France, in September 1998 [1]. The to expand the donor circle, an ex vivo machine
recipient, a 48-year-old male New Zealander, perfusion (EVMP) was invented. EVMP of SOT
underwent a traumatic circular saw amputation and extremities has demonstrated decreased graft
of his right forearm in 1984. Treatment and han- immunogenicity and reduced ischemia reperfu-
dling of graft and patient at that time was mostly sion injury (IRI) in preclinical trials and animal
based on the experience and research gained studies already [34, 35]. Tools such as EVMP
through SOT. The gold standard for organ preser- will most likely improve the implementation and
vation was and still is the University of Wisconsin outcomes of VCA including extension of donor
(UW) solution and static cold storage (SCS) [32]. recovery radius and facilitate global organ shar-
Therefore, the donor’s extremity was irrigated ing. The immunosuppressive therapy regimen
with the UW solution (500 mL, 4 °C) and stored also followed the principles of the treatment of
on ice slurry. The graft’s ischemia time was SOT. As the acute rejection of composite skin
750 min in total, no surgical complications containing tissues was expected to happen more
likely and viciously than in SOT, the most potent is measured by scores such as Action Research
immunosuppressive regimen at that time was Arm Test (ARAT), Carroll Upper Extremity
administered. The regimen consisted of induction Function Test (UEFT), Hand Transplantation
therapy with Thymoglobulin 75 mg/day for Score System (HTSS), Southampton Hand
10 days and anti-CD25 monoclonal antibody Assessment Procedure (SHAP), Disabilities of
therapy (mAb) on day 26 and day 100 posttrans- the Arm, Shoulder, and Hand measure (DASH),
plant. Thymoglobulin served as lympho-ablative and many more [36, 37]. The functional outcome
agent to prevent early acute rejection. The nowadays shows protective sensation in all
anti-CD25 mAb therapy was additionally applied patients, 90% have tactile sensation and 84%
when levels of circulating antilymphocyte anti- have discriminative sensation. Most patients
bodies decreased following the induction. As ini- regain function of extrinsic and intrinsic muscle
tial maintenance therapy, tacrolimus in levels of function after 9 up to 15 months posttransplant.
10–15 ng/mL was applied for the first month Altogether, the functional outcome enables
along with MMF 2 g/day and steroids 250 mg on patients most daily activities (eating, writing,
day one gradually tapered to 20 mg/day. The dressing, diving) and sensory return along with
long-term maintenance therapy was subsequently regained body image [36].
reduced to tacrolimus levels of 5–10 ng/mL, After less than 12 months, the first hand
mycophenolate mofetil (2 g/day), and prednisone transplant patient became non-adherent to his
20 mg for 3 months. At the time, acute rejection immunosuppressive medications and no longer
was neither classified nor defined as it is today by participated in physical therapy which resulted
means of the Banff Classification (2007). in severe signs of rejection. At 29 months post-
Therefore, the obtained skin biopsies on weekly transplant, the hand graft was amputated on the
basis could only be analyzed in context of the patient’s own request [38]. This case demon-
clinical symptoms and serum levels of C reactive strated both the surgical triumph as well as
protein to look for signs of acute allograft importance of proper patient selection. Some
rejection. patients may benefit from a well fitted prosthe-
The biopsies did show inflammatory infil- sis rather than dealing with consequences of
trates on days 57, 63, and 77 posttransplant long-term immunosuppressive therapy that
which was treated as acute rejection in context includes medical complications and frequent
with the clinical symptoms. Rejection treatment medical office visits. A multicenter study by
consisted of increase in doses of tacrolimus and Salminger et al. couldn’t show any significant
prednisone as well as application of topical difference between hand transplantation and
immunosuppression containing tacrolimus and prosthetics in terms of functional outcome [37].
clobetasol. The rejection was successfully con- Nevertheless, it should not remain unmentioned
trolled and follow- up biopsies were negative. that the human hand is not just a functional
The physical and mental health of the patient instrument but rather a sensory and social tool.
was satisfactory after the surgery. He started Therefore, hand transplantation can certainly
with physical therapy only 10 h posttransplant bring many advantages for well-selected
and received psychological support daily during patients. This first successful transplanted hand
the first weeks. After the first months he was by Dubernard and his team still proved hand
already able to undergo daily activities such as transplantation as feasible and safe option for
writing or grasping a glass, which was consid- patients who suffer from complex composite
ered a very good result. Today, the functional tissue deficits and paved the way for further
outcome of hand transplantation (or prosthetics) clinical application of VCA [39].
Devauchelle B, et al. First human face allograft early report. Lancet; 2006; 368:203–9
Strengths • First successfully allotransplanted partial face worldwide
• Detailed description of procedure, immunosuppressive regimen, challenges, and outcome
Limitations • A short period of 4 months was followed up in this early report and it was a partial face
transplantation only
Impact This is a landmark paper in VCA as it proved the feasibility of allo-partial face transplantation as
safe concept. This paper served as catalysator for further improvement and over 40 face
transplantations have been performed since then
This groundbreaking event was followed by the below this time is desirable [42]. The induction
first successful partial face transplantation, per- therapy regimen included Thymoglobulin, tacro-
formed by Bernard Devauchelle and his team in limus (target level of 10–15 ng/mL), mycopheno-
Amiens, France, in November 2005 [2]. The late mofetil (2 g/d), and prednisone (250 mg/d
recipient, a 38-year-old female, was mauled by and tapered to 5 mg/d). Because of a decrease in
her dog, an injury that resulted in a complete renal function, tacrolimus was replaced with
amputation of her distal nose, upper and lower sirolimus later, another immunosuppressive drug
lips, the chin, and parts of the right and left cheek. from the class of mTOR-inhibitors that is not
The face allograft contained corresponding skin, nephrotoxic. Additionally, the patient received a
subcutaneous tissue, all perioral muscles includ- bone marrow infusion of the donor on days 4 and
ing innervation from the zygomatic, buccal, and 11 posttransplant. Preceding results with bone
mandibular branches of the facial nerve as well marrow infusion in SOT did show reduced epi-
as oral mucosa. The entire distal nose and right sodes of chronic rejection in humans and the
and left infraorbital and mental sensory nerves induction of tolerance in animal studies which
were included. Additionally, a radial forearm flap raised the hope, that infusing donor bone marrow
was taken as sentinel flap and connected to the cells simultaneously to face transplantation
recipient’s left axillary vessels. The sentinel flap would show similar effects. Till the present day,
served as a surrogate tissue with intent to perform research exploring potential tolerogenic effects
biopsies away from transplanted facial skin. of transfused bone marrow cells is actively ongo-
Biopsies were still taken from the facial skin for ing [37, 38]. Patient’s biopsies on postoperative
proper correlation as well as from oral mucosa. day 24 revealed a perivascular infiltration of
Skin biopsies of sentinel flap and face showed mononuclear cells in the skin and mucosa, apop-
similar results while oral mucosa biopsies totic keratinocytes, vacuolization of basal cells
showed signs of rejection earlier than in facial or which was considered a rejection episode.
sentinel samples. A rejection description was extrapolated from
Today, mucosal biopsies are the focus of prior hand transplantation experience as Banff
ongoing research to gain a deeper understanding Classification was not established yet. Hereupon,
of rejection and to detect signs of acute and the immunosuppressive regimen was increased,
chronic rejection earlier and more accurately which treated signs of rejection successfully. The
[40]. Both grafts were irrigated with Institute patient started with physical therapy 48 h after
Georges Lopez (ILG-1) solution (500 mL, 4 °C) the transplantation and received psychological
and stored on ice. ILG-1 is an alternative to UW support continuously. The physical and mental
solution with lower potassium and viscosity lev- health of the patient was satisfactory after the
els, demonstrating good results in kidney preser- transplantation. After 18 months, light touch and
vation too [41]. Ischemia time was 230 min, no cold/warm sensitivity returned to normal, com-
surgical complications were reported, and wound plete mouth closure was achieved (after
healing was uneventful. Due to ischemic toler- 10 months), and psychological acceptance of the
ance of muscle (maximum of 240 min), staying new face improved along with the graft function
[29]. Outcome of subsequent partial or full-face with a higher risk for antibody-mediated rejec-
transplantations in general showed a motor tion. She developed terminal chronic rejection
recovery after 6–8 months posttransplant, which (necrosis) several months later. The rejection did
is average for motor recovery outcomes. Usually, not respond to intensive treatment with plasma-
sensory recovery is faster than motor recovery pheresis, immunoglobulins, or bortezomib which
and is expected after 3 months with good results inevitably resulted in surgical removal of the
8–12 months posttransplant. The recovery of lower lip, labial commissures, and a part of the
breathing, eating, taste, smell, speech, facial right cheek in May 2015. Because of her young
expression, and sensation is what the outcome of age she was considered for re-transplantation.
face transplantation is measured by [43]. Five Unfortunately, the patient developed a small-cell
years posttransplant, the aesthetical, motor/func- lung cancer at that time, most likely secondary to
tional, and sensory outcome was still satisfying, her lifetime smoking as this type of cancer does
and she could talk, eat, and breathe normally, not appear to be strongly associated with immu-
without further episodes of rejections [44]. nosuppression. The patient passed away in April
Unfortunately, about seven and a half years post- 2016 [45]. The first successful partial face trans-
transplant, the patient developed de novo class plantation is still a major milestone in VCA’s
II-donor specific antibodies, which are associated history.
Pomahac B, et al. Novel surgical technique for full face transplantation. PRS; 2012;130:549–55
Strengths • Novel technique for full face transplantation
• Detailed description of procedure
Limitations • Cadaver study
Impact This is a landmark paper in VCA as it proved the technical feasibility of full face transplantation with
a new approach. This paper provided the foundation to plan and perform full face transplantation in
humans
However, it has been assumed that it’s almost Encouraged by the promising results of partial
impossible to reconstruct completely deformed face transplantations, attempts have been made to
and damaged faces to near-normal appearance enable full face transplantation since 2005. The
and function by reconstruction with conventional Boston team hypothesized that anastomosing just
surgical techniques. the bilateral facial artery without superficial tem-
Human faces consist of numerous different poral vessels would be sufficient to carry a full
and sophisticated anatomical structures that have face allograft. This approach allowed for exclu-
unique color and texture incompatible with virtu- sion of the parotid gland allowing more space for
ally any autologous donor tissue. Additionally, nerve coaptation and better esthetic outcome
faces are ubiquitous in human’s life, critical for (Fig. 3.1). This technique was tested on cadavers
social function, and integration which raises ethi- as described by Pomahac et al. in 2010 [3, 48].
cal questions about the transplantation of a face The cadaver study demonstrated a novel, simple,
and hereby the potential transfer of identity of a and reproducible surgical recovery technique that
human being [47]. What previously also had pre- could be performed within 4 h and allows critical
vented teams of carrying out face transplantation principles of sensory motor and nerve
(fVCA) were the unknowns of graft’s sufficient coaptation.
blood supply. While facial vessels were consid- The cadaver grafts included the fronto-
ered essential for successful facial transplanta- temporo-parietal regions of the scalp to the coro-
tion, it was unknown whether superficial temporal nal level, eyelids, nose and/or maxilla, muscles
vessels are needed for a full face transplant. of facial animation, lips, motor and sensory
nerves, skin of the neck to the level of the hyoid fully long-term immunosuppressive management
bone, and the facial artery and corresponding following VCA, these were all foundations to ful-
veins [3]. Demonstration of feasibility in cadav- fill face transplantation in humans. In March
ers, long-term experience with the management 2010, the worldwide first full face transplantation
of acute and chronic rejection over decades of was performed by Joan Pere Barret and his team
SOT, and seeing patients that underwent success- in Barcelona, Spain.
Pomahac B, et al. Three patients with full face transplantation. N Engl J Med. 2012;366:715–22
Strengths • Detailed description of procedure and follow up with immunosuppressive regimen and
complications in all three patients
Limitations • Short follow up of 6 months postoperative
Impact This is a landmark paper in VCA as it demonstrated the technical feasibility of full allo-face
transplantation in three patients. This work encouraged other centers to start their own face
transplant program
This event was closely followed by the first full full face transplantation as safe and feasible con-
face transplantation in the US that was conducted cept. The pretransplant appearance, immediate
by a team of over 30 physicians, nurses, anesthe- posttransplant outcome, and follow- up several
siologists, and residents at the Brigham and months after the transplantation of the first three
Women’s Hospital (Boston, USA) in March 2011 full-face transplantation recipients operated by
[4]. Facial vessels-based allograft technique was the Brigham’s Team in Boston since 2011 are
for the first time confirmed in human and proved shown in Fig. 3.2.
Multiple surgical procedures, for example,
face, hand, or sentinel flap transplantation were
performed simultaneously in several patients
requiring organization of teams into smaller units
of surgeons, nurses, and residents, each assigned
to separate procedure, body part for both the
donor and the recipient. Detailed planning and
coordination of the different teams, the anatomi-
cal planning (Figs. 3.3 and 3.4), and patient prep-
aration was conducted.
All allografts were irrigated with UW solu-
tion and transported in ice-water slurry. Surgical
complications were reported as substantial intra-
operative bleeding in two patients. The immuno-
suppressive regimen included an induction with
rabbit antithymocyte globulin (1.5 mg/kg/day) at
the time of allograft face reperfusion, myco-phe-
nolate mofetil (1 g), and prednisone (500 mg).
Postoperatively, the patients received physical
therapy, social worker, and psychiatry support.
Fig. 3.1 The photo shows a dissected mock cadaver with The five-year follow-up of the four full-face and
branches of facial nerves (black arrow), buccal neurovas- two partial-face transplant patients operated by the
cular bundle (green arrow), and vessel loops are around
Brigham and Women´s Hospital (BWH) team
facial artery and vein, a retractor holds buccal fat pad.
Republication with permission of [46] showed a significant improvement in sensory return
Pre-Transplant 18 months post-Transplant Five years post-Transplant
Pat 1
Pat 2
Pat 3
Fig. 3.2 The left column shows the preoperative appearance, the middle column shows the postoperative outcome after
18 months, and the right column shows the outcome after 5 years
(2-point discrimination, hot/cold and pressure test- score (Center for Epidemiologic Studies Depression
ing), an improvement in self-reported quality of life Scale) compared to pretransplant. The maintenance
(EuroQol Group-5 Dimension Visual Analogue immunosuppressive regimen included typically tacro-
Scale), as well as a trend for a decreased depression limus (day level of 6–10 ng/mL after the first year),
Fig. 3.3 To map the

detailed recipient’s
vessels, volume-
rendered CT scans of
head and neck were
taken for preoperative
planning of
fVCA. Republication
with permission of [47]
a b e f
c d g h
Sensory nerve (infraorbital, supraorbital, buccal, mental) Sensory nerve (infraorbital, supraorbital, buccal, mental)
Motor nerve (facial nerve and branches) Motor nerve (facial nerve and branches)
Artery (common, internal and external carotid and branches) Artery (common, internal and external carotid and branches)
Vein (internal and external jugular with facial tributaries) Vein (internal and external jugular with facial tributaries)
Fig. 3.4 Left (a) shows normal facial anatomy; left (b–d) soft-tissue anatomy; (f–h) show all three donor full-face
show actual preoperative anatomy of the recipients with allografts of three patients with the required structures to
their structural deficits; right (e) shows full-face VCA reconstruct their faces individually. Republication with
containing all structures needed to be transplanted for a permission of [3]
hypothetical patient without any nervous, vascular, or
MMF, and prednisone. Episodes of acute rejection, estimated glomerular filtration rate (GFR) was
diagnosed according to the Banff Classification, seen but never fell below 60 mL/min.
occurred with a median of 5.5 (range 2–7) and resulted Fortunately, no cancer has been reported [49].
in additional immunosuppressive treatment. Until In summary, the results of the Brigham’s team
then, no long-term side effects such as new-onset dia- and those of other groups proved fVCA as a
betes mellitus or lipid disorders were reported. safe and feasible technique for sophisticated
One patient was diagnosed with arterial facial reconstruction. Face transplantation is
hypertension two and a half years posttrans- arguably the most challenging procedure in the
plant. An average decrease of 25 mL/min in the field of surgery.
3.3 Evolution of Indication, patients with severe facial defects and exclude
Acute and Chronic Rejection, those that have an increased risk for failure, com-
Monitoring (Banff plications, and side effects. Acute rejections are
Classification), usually mediated through T-cells and occur in
and Immunosuppressive 80% of the cases. The signs for acute rejection are
Therapy Regimen well described on physical examination, still not
very specific. Skin biopsies are evaluated based
As standard prosthetics and conventional free tis- on Banff pathological classification developed in
sue transfer have failed to achieve satisfactory 2007 that is listed in Table 3.1 [52]. Contrary to
results in severely damaged human faces, full- the follow-up of SOT, complications such as acute
face transplantation seems to be an option that and chronic rejection can be typically diagnosed
can be offered to suitable patients. Over 48 face on physical examination (graft inspection) due to
transplantations have been performed worldwide easy access of the graft itself. Episodes of acute
(e.g., France, Spain, Turkey, Belgium, Poland, rejections will usually be treated by a steroid
Finland, Russia, China, and the US) but the bolus application. If the rejection is steroid-
results vary from center to center with a mortality resistant, the maintenance of immunosuppressive
rate of currently 25% as death of ten patients has therapy is increased and the steroid resistant rejec-
been reported [20, 50]. This high mortality rate tions may require alemtuzumab, basiliximab, or
reflects the steep learning curve of various inter- the IS antithymocyte globulin [53]. Topical
national teams. immunosuppression has been utilized as well
As face transplantation is accompanied by sig- without clear evidence of its utility.
nificant risks such as graft loss, unsatisfactory Chronic rejection is an ill-defined process that
results, long-term side effects of immunosuppres- is still not fully understood. Rejection targets
sants such as kidney failure or cancer, episodes of appear to be stem cells of the bulge area of hair
acute and chronic rejection, and multiple follow- follicles, basal membrane stem cells, and endo-
up operations, indications and patients selection thelium. Chronic rejection is typically a result of
must be considered carefully [47]. The general multiple episodes of acute rejection and the ter-
specifications for fVCA are large defects such as minal phase is antibody mediated. Due to the
25% or more of the facial surface area and the loss limited number of patients and data in VCA,
of one or more central facial parts that cannot be chronic rejection classification is not included in
remedied by conventional reconstructive opera- the Banff classification yet [54–56]. Signs of
tions [51]. Ideally, selected patients are in good chronic rejection are either clinical (e.g., scaly
physical and mental health and integrated socially psoriasiform cutaneous plaques, purpuric cutane-
with a well-established support network. They ous lesions, necrotic skin ulcerations, skin sclero-
must agree on taking life-long immunosuppres- sis, dyschromia, finger thinning nail loss or pain),
sive medications. Furthermore, potential candi- or pathological (e.g., vasculopathy, epidermal
dates must be approved by their surgical/medical and adnexal atrophy, dermal sclerosis, capillary
team that includes psychiatrist(s) [47]. The aim vessel thrombosis, tertiary lymphoid organ-like
during the process of patient selection is to include follicles) in nature and can lead to graft loss. As
Table 3.1 The Banff VCA working classification for acute rejection (invented 2007)
Grade Inflammatory rate Involvement of epithelium
0 (no rejection) None/rare None
I (mild rejection) Mild perivascular None
II (moderate rejection) Moderate to severe perivascular Mild (limited to spongiosis or lymphocytic exocytosis)
III (severe rejection) Dense Apoptosis, dyskeratosis and/or keratinolysis
IV (acute necrotizing Frank necrosis of the epidermis
rejection) or its structures
no sufficient treatment is available, preventing same techniques as described in the landmark

chronic rejection by close IS therapy monitoring, papers are still used and the courage of the sur-
early acute rejection treatment, patient geons and their teams of the time to perform pro-
compliance, and proper patient selection are all cedures in humans that have never been performed,
critical [56]. let alone turned out to be successful, is remark-
As reperfusion following allograft transplan- able. Since the first successful hand allotransplan-
tation triggers pathophysiological mechanisms tation was performed, the status of VCA has been
such as an intense activation of the recipient’s transformed over the past 25 years from an exper-
immune system targeting donor tissue and cells, imental to a well-established stage today.
an induction therapy is necessary at the onset of Technical feasibility of the procedure and long-
transplantation. This induction therapy includes term survival of graft and the patients have been
usually antithymocyte globulin, the most com- proven by multiple centers worldwide. Current
monly used T-cell depleting drug, or alternatives hurdles include toxic side effects of immunosup-
such as the monoclonal antibodies basiliximab or pressive therapy regimen as well as chronic rejec-
alemtuzumab. The maintenance therapy is based tion that can lead to graft loss and death potentially.
on the therapy of SOT and usually contains a tri- The future application of VCA is depending on
ple therapy of tacrolimus, MMF, and steroids changing the risk/benefit ratio in a positive way to
[53]. To address the toxic long-term side effects enable more patients access with less or even
of IS, novel approaches are necessary and further without toxic side effects by long-term therapy
research is conducted here as this is still the most regimen. Further research is still necessary.
limiting factor that prevents VCA from becoming However, tolerance induction protocols in pre-
a standard procedure worldwide [57]. Novel clinical models were recently published that suc-
approaches are based on the concept of tolerance cessfully induced tolerance and will hopefully
induction, defined as a long-term pave the way for VCA to become a standard pro-
immunosuppression-free graft acceptance that is cedure similar to what SOT is today.
free from clinical or histological evidence of
acute or chronic rejection and reduces hereby the
risks that are still associated with VCA [58]. References
Tolerance induction, using either cellular or
pharmaceutical- based strategies, has been 1. Dubernard J-M, Owen E, Lefrançois N, et al. First
achieved successfully in small and large preclini- human hand transplantation case report. Transpl Int.
cal animal models so far and some protocols 2000;13:S521–7.
2. Devauchelle B, Badet L, Lengelé B, et al. First human
were applied in human studies with promising face allograft: early report. Lancet. 2006;368:203–9.
preliminary results [59]. 3. Pomahac B, Pribaz JJ, Bueno EM, et al. Novel sur-
gical technique for full face transplantation. Plast
Reconstr Surg. 2012b;130:549–55.
4. Pomahac B, Pribaz J, Eriksson E, et al. Three patients
3.4 Expert Concluding with full facial transplantation. N Engl J Med.
Commentary 2012a;366:715–22.
5. Merrill JP. Successful homotransplantation of the
VCA is still a new and evolving field that provides human kidney between identical twins. JAMA J Am
Med Assoc. 1956;160:277.
sophisticated solutions for severe damages in the 6. Murray JE, Merrill JP, Dammin GJ, et al. Kidney
physical composition of humans. VCA is also an transplantation in modified recipients. Ann Surg.
important new field in reconstructive surgery. 1962;156:337–55.
This powerful technique can improve outcomes 7. Toledo-Pereyra LH, Toledo AH. 1954. J Investig
Surg. 2005;18:285–90.
of severe facial defects and improve patient’s 8. Murray JE, Merrill JP, Harrison JH, et al. Prolonged
quality of life. The four landmark papers pre- survival of human-kidney homografts by immu-
sented here have made an enormous and essential nosuppressive drug therapy. N Engl J Med.
contribution to the development of VCA. The 1963;268:1315–23.
9. Sollinger HW. Mycophenolates in transplantation. 28. de la Garza M, Sauerbier M, Günter G, et al.

Clin Transpl. 2004;18:485–92. Microsurgical reconstruction of the burned hand and
10. Kahl A, Bechstein WO, Platz K, et al. First results upper extremity. Hand Clin. 2017;33:347–61.
with a quadruple therapy regimen including tacroli- 29. Dubernard J-M, Lengelé B, Morelon E, et al.
mus and mycophenolate mofetil in patients after com- Outcomes 18 months after the first human partial face
bined pancreas and kidney transplantation. Transplant transplantation. N Engl J Med. 2007;357:2451–60.
Proc. 1998;30:505–6. 30. Gordon CR, Nazzal J, Lozano-Calderan SA, et al.
11. Mihatsch MJ, Kyo M, Morozumi K, et al. The side- From experimental rat hindlimb to clinical face com-
effects of ciclosporine-a and tacrolimus. Clin Nephrol. posite tissue allotransplantation: historical background
1998;49:356–63. and current status. Microsurgery. 2006;26:566–72.
12. Vincenti F, Dritselis A, Kirkpatrick P. Belatacept. Nat 31. Levi DM, Tzakis AG, Kato T, et al. Transplantation of
Rev Drug Discov. 2011;10:655–6. the abdominal wall. Lancet. 2003;361:2173–6.
13. Hariharan S, Johnson CP, Bresnahan BA, et al. 32. Stewart ZA. UW solution: still the “gold standard”
Improved graft survival after renal transplantation for liver transplantation. Am J Transplant. 2015;15:
in the United States, 1988 to 1996. N Engl J Med. 295–6.
2000;342:605–12. 33. Jones JW, Gruber SA, Barker JH, Breidenbach
14. Jordan ML, Shapiro R, Fung J, et al. Initial studies WC. Successful hand transplantation—one-year fol-
with FK506 in renal transplantation. Cleve Clin J low-up. N Engl J Med. 2000;343:468–73.
Med. 1991;58:444–6. 34. Kueckelhaus M, Puscz F, Dermietzel A, et al.
15. Stähelin HF. The history of cyclosporin a Extracorporeal perfusion in vascularized composite
(Sandimmune®) revisited: another point of view. allotransplantation. Ann Plast Surg. 2018;80:669–78.
Experientia. 1996;52:5–13. 35. Zulpaite R, Miknevicius P, Leber B, et al. Ex-vivo
16. Morris P. Joseph E. Murray (1919–2012). Nature. kidney machine perfusion: therapeutic potential.
2013;493:164. Front Med (Lausanne). 2021;8:808719.
17. Gilbert Fernandez J, Febres-Cordero R, Simpson 36. Ninkovic M, Weissenbacher A, Gabl M, et al.
R. The untold story of the first hand transplant: dedi- Functional outcome after hand and forearm trans-
cated to the memory of one of the great minds of plantation: what can be achieved? Hand Clin.
the ecuadorian medical community and the world. J 2011;27:455–65.
Reconstr Microsurg. 2019;35:163–7. 37. Salminger S, Sturma A, Roche AD, et al. Functional
18. Moseley RV, Sheil AGR, Mitchell RM, Murray and psychosocial outcomes of hand transplantation
JE. Immunologic relationships between skin and compared with prosthetic fitting in below-elbow
kidney homografts in dogs on immunosuppressive amputees: a multicenter cohort study. PLoS One.
therapy. Transplantation. 1966;4:678–87. 2016;11:e0162507.
19. Brännström M, Belfort MA, Ayoubi JM. Uterus 38. Petruzzo P, Dubernard JM. World experience after
transplantation worldwide: clinical activities and out- more than a decade of clinical hand transplanta-
comes. Curr Opin Organ Transplant. 2021;26:616–26. tion: update on the French program. Hand Clin.
20. Diep GK, Berman ZP, Alfonso AR, et al. The 2020 2011;27:411–6.
facial transplantation update: a 15-year compendium. 39. Dubernard J-M, Owen E, Herzberg G, et al. Human
Plast Reconstr Surg Glob Open. 2021;9:e3586. hand allograft: report on first 6 months. Lancet.
21. Honeyman C, Dolan R, Stark H, et al. Abdominal 1999;353:1315–20.
wall transplantation: indications and outcomes. Curr 40. Kauke-Navarro M, Tchiloemba B, Haug V, et al.
Transplant Rep. 2020;7:279–90. Pathologies of oral and sinonasal mucosa following
22. Lopez CD, Girard AO, Lake IV, et al. Lessons learned facial vascularized composite allotransplantation. J
from the first 15 years of penile transplantation and Plast Reconstr Aesthet Surg. 2021;74:1562–71.
updates to the Baltimore criteria. Nat Rev Urol. 41. Igreja MR, Wiederkehr JC, Wiederkehr BA, et al.
2023;20:294. Use of Georges Lopez Institute preservation solu-
23. Wells MW, Rampazzo A, Papay F, Gharb BB. Two tion IGL-1 in pancreas transplantation: a series of 47
decades of hand transplantation. Ann Plast Surg. cases. Transplant Proc. 2018;50:702–4.
2022;88:335–44. 42. Kueckelhaus M, Lehnhardt M, Fischer S, et al.
24. Tchiloemba B, Kauke M, Haug V, et al. Long-term Fortschritte in der Gesichtstransplantation.
outcomes after facial allotransplantation: sys- HandchirurgieMikrochirurgie Plastische. Chirurgie.
tematic review of the literature. Transplantation. 2014;46:206–13.
2021;105:1869–80. 43. Tasigiorgos S, Kollar B, Krezdorn N, et al. Face
25. Thuong M, Petruzzo P, Landin L, et al. Vascularized transplantation- current status and future develop-
composite allotransplantation—a Council of Europe ments. Transpl Int. 2018;31:677–88.
position paper. Transpl Int. 2019;32:233–40. 44. Petruzzo P, Testelin S, Kanitakis J, et al. First
26. Bateman C. World’s first successful penis transplant human face transplantation. Transplantation.
at Tygerberg hospital. S Afr Med J. 2015;105:251. 2012;93:236–40.
27. Brännström M, Johannesson L, Bokström H, et al. 45. Morelon E, Petruzzo P, Kanitakis J, et al. Face trans-
Livebirth after uterus transplantation. Lancet. plantation: partial graft loss of the first case 10 years
2015;385:607–16. later. Am J Transplant. 2017;17:1935–40.
46. Pomahac B, Lengele B, Ridgway EB, et al. Vascular composite allotransplantation—The American
considerations in composite midfacial allotransplan- Society of Reconstructive Transplantation and
tation. Plast Reconstr Surg. 2010;125:517–22. International Society of Vascularized Composite
47. Pomahac B, Nowinski D, Diaz-Siso JR, et al. Face Allotransplantation chronic rejection working
transplantation. Curr Probl Surg. 2011;48:293–357. group: 2018 American Society of Reconstructive
48. Siemionow M, Agaoglu G, Unal S. A cadaver study Transplantation meeting report and white paper
in preparation for facial allograft transplantation in Research goals in defining chronic rejection in vas-
humans: part II. Mock facial transplantation. Plast cularized composite allotransplantation. SAGE Open
Reconstr Surg. 2006;117:876–85. Med. 2020;8:205031212094042.
49. Tasigiorgos S, Kollar B, Turk M, et al. Five-year 55. Lian CG, Bueno EM, Granter SR, et al. Biomarker
follow-up after face transplantation. N Engl J Med. evaluation of face transplant rejection: association
2019;380:2579–81. of donor T cells with target cell injury. Mod Pathol.
50. Siemionow M. The past the present and the future 2014;27:788–99.
of face transplantation. Curr Opin Organ Transplant. 56. Morelon E, Petruzzo P, Kanitakis J. Chronic rejection
2020;25:568–75. in vascularized composite allotransplantation. Curr
51. González-Ulloa M. Restoration of the face covering Opin Organ Transplant. 2018;23:582–91.
by means of selected skin in regional aesthetics units. 57. Yang JH, Johnson AC, Colakoglu S, et al. Clinical
Br J Plast Surg. 1956;9:212–21. and preclinical tolerance protocols for vascularized
52. Schneider M, Cardones ARG, Selim MA, Cendales composite allograft transplantation. Arch Plast Surg.
LC. Vascularized composite allotransplantation: 2021;48:703–13.
a closer look at the Banff working classification. 58. Leonard DA, Cetrulo CL, McGrouther DA, Sachs
Transpl Int. 2016;29:663–71. DH. Induction of tolerance of vascularized composite
53. Kueckelhaus M, Fischer S, Seyda M, et al. allografts. Transplantation. 2013;95:403–9.
Vascularized composite allotransplantation: current 59. Kauke M, Safi A-F, Panayi AC, et al. A systematic
standards and novel approaches to prevent acute review of immunomodulatory strategies used in
rejection and chronic allograft deterioration. Transpl skin-containing preclinical vascularized composite
Int. 2016;29:655–62. allotransplant models. J Plast Reconstr Aesthet Surg.
54. Kaufman CL, Kanitakis J, Weissenbacher A, 2022;75:586–604.
et al. Defining chronic rejection in vascularized
Evolution of Wound Healing
4
Ryoko Hamaguchi and Dennis P. Orgill

We review five pivotal conceptual advances in 1. Winter GD. Formation of the scab and the
wound healing over the last 60 years, spotlight- rate of epithelization of superficial wounds in
ing one landmark publication in each of these the skin of the young domestic pig. Nature.
areas and its impact in guiding clinical care and 1962;193:293–4.
catalyzing further research and innovation. In 2. Argenta LC, Morykwas MJ. Vacuum assisted
addition, we selected other references that pro- closure: a new method for wound control and
vide further context on more recent develop- treatment: clinical experience. Ann Plast
ments in these areas along with our own clinical Surg. 1997;38(6):563–76. discussion 577.
experience and provide our opinions on these 3. Heimbach D, Luterman A, Burke J, Cram A,
treatment modalities’ strengths and shortcom- Herndon D, Hunt J, Jordan M, McManus W,
ings in achieving widespread penetrance in Solem L, Warden G. Artificial dermis for
today’s clinical setting, discussing potential major burns. A multi-center randomized
parameters that may be used to guide future clinical trial. Ann Surg. 1988;208(3):313–20.
innovations in wound care. 4. Gallico GG, O’Connor NE, Compton CC,
Kehinde O, Green H. Permanent coverage of
large burn wounds with autologous cultured
human epithelium. N Engl J Med.
Keywords 1984;311(7):448–51.
5. Steed DL. Clinical evaluation of recombi-
Landmark · Wound healing · Negative
nant human platelet-derived growth factor
pressure wound therapy · Acellular dermal
for the treatment of lower extremity ulcers.
matrix · Integra · Autologous cultured human
Plast Reconstr Surg. 2006;117(7
epithelium · Platelet-derived growth factor
Suppl):143S–9S. discussion 150S–151S.
R. Hamaguchi · D. P. Orgill (*)

Division of Plastic and Reconstructive Surgery,
Brigham and Women’s Hospital, Boston, MA, USA

https://doi.org/10.1007/978-3-031-57132-9_4
30 R. Hamaguchi and D. P. Orgill
4.1 Introduction of wound care, but to guide future efforts to max-

imize the clinical utility and overall impact of
We believe that five major discoveries over the future tools and interventions in this field.
last 60 years catalyzed many advances in clinical
wound healing. These include the importance of
moisture at the wound surface, the strategic 4.1.1 Moist Wound Healing
application of mechanical forces, the application
of dermal matrices, the use of cells, and the use of The earliest innovations in wound healing
topical growth factors. Each discovery has added involved understanding and exploiting the body’s
new therapeutics to our armamentarium to treat natural mechanisms to facilitate wound re-
complex wounds. Yet, due to the complexities of epithelialization. In 1962, Winter et al. published
actually applying these technologies in clinical a porcine model study that demonstrated improved
settings many have been limited by regulatory wound healing in full-thickness wounds that were
hurdles, cost, and complexity of application. We simply kept moist with an overlying polythene
discuss one seminal article in each of these areas dressing, when compared to control wounds left
that is widely quoted. open to air [1]. Specifically, they demonstrated
Factors that may play a role in driving the more rapid re-epithelialization of the wound bed
relative applicability in the clinical setting can be in the former treatment group, corroborated by
categorized into three main areas: (1) Patient- histological findings showing significantly thicker
specific factors (i.e. impact on pain and other new epidermis seen under the normal dry scab in
quality-of-life elements), (2) Physician-specific the treatment group. In this original paper, the
factors (i.e. simplicity of concept and ease of use authors theorize that moist wound healing allows
across a variety of specialties and adjunct health- for an altered histology and path of neo-epithelial-
care professions), and finally, (3) Logistical/gov- ization following an injury—while in exposed
ernmental hurdles (i.e. FDA approval) and cost. wounds new keratinocytes must migrate through
Using the five landmark papers as a foundation, the fibrous tissue (the “scab”) forming within 24 h
we critically analyze each of these noteworthy of the original injury. Moist wound healing allows
wound healing innovations in each of these fea- for the moving sheet of epidermal cells to migrate
tures, drawing informed conclusions to not only through the serous exudate on the wound surface
better understand the current evolving landscape above the fibrous tissue of the dermis.
Winter GD. Formation of the scab and the rate of epithelization of superficial wounds in the skin of the young
domestic pig. Nature. 1962;193:293–4
Strengths • Elegant and simple creation of a moist wound environment by covering wound bed with polythene
film
• Quantitatively captures histological changes in wound healing through measurement of percentage
epidermis regeneration
Limitations • Animal study that may not be generalizable to human wounds
• Results in artificially created full-thickness defects may not be recapitulated in other wound
contexts, such as burn wound, irradiated tissue, or infected areas
• Limited number of animals (2 pigs, 12 wounds each)
Impact This was the first study to qualitatively demonstrate histological changes in wound healing through
the simple intervention of maintaining wound bed moisture, paving the way for countless topical
wound care products based on this principle that are on the market today
A simple yet powerful observation, this work has market, including but not limited to Vaseline-
become the underlying principle of standard impregnated gauze, alginate-based, hydrocol-
wound care practices such as daily normal saline loid, and hydrogel products that are utilized by a
wet-to-dry dressings as well as the vast arma- wide variety of providers across a variety of clin-
mentarium of wound dressings available on the ical settings.
4 Evolution of Wound Healing 31
4.1.2 Negative Pressure Wound medical-grade reticulated polyurethane ether

Therapy (Vacuum-Assisted foam with pore sizes ranging between
Closure) 400–600 μm to maximize tissue ingrowth and
ensure equal pressure distribution to where the
The development of negative pressure wound wound contacts the foam, (2) a noncollapsible
therapy (NPWT), alongside its numerous product evacuation tube that connects the foam to the suc-
iterations, is arguably one of the most impactful tion source, (3) an adhesive sealing dressing that
clinical innovations in wound healing of the past transforms an open wound into a functionally
three decades, fundamentally altering not only closed wound, and (4) a proximal collection can-
patient care but also driving new research trajec- ister and adjustable vacuum pump with the abil-
tories investigating the effect of mechanical force ity to sense leaks in the system as well as
on the biological processes of wound remodel- abnormally rapid fluid/blood egress. The authors
ing. Whereas prior approaches to wound closure document their initial clinical experience using
were limited to healing by secondary intention, NPWT in 175 chronic wounds (i.e. pressure inju-
primary closure or more extensive reconstructive ries, chronic dehisced wounds, venous stasis
interventions such as skin grafts and local and ulcers, radiation-associated injuries, vascular and
free flaps, NPWT introduced a powerful modal- diabetic ulcers), 94 subacute wounds that have
ity that could flexibly be applied as an alternative been open for less than 7 days (i.e. dehisced
to operative intervention in a poor surgical candi- wounds, open wound with exposed hardware
date or an adjunctive “bridging” treatment and/or bone), and 31 acute wounds (i.e. acute tis-
between the rungs of the reconstructive ladder. sue avulsions, evacuated hematomas, gunshot
In their landmark paper, Argenta and wounds, and eviscerations). In this original work,
Morykwas documented the use of the NPWT the authors postulate the underlying mechanism
system on a total of 300 wounds of varying chro- of NPWT to be multifactorial, including the
nicity and etiology, demonstrating an enhanced removal of excess interstitial fluid, increased vas-
rate of granulation tissue formation with treat- cularity of the wound bed and associated reduc-
ment [2]. The original NPWT system compro- tion of bacterial load, and local biological
mised of four simple components: (1) responses of the tissue to the mechanical forces.
Argenta LC, Morykwas MJ. Vacuum assisted closure: a new method for wound control and treatment: clinical
experience. Ann Plast Surg. 1997;38(6):563–76. discussion 577
Strengths • Captures experience with a large number of wounds (n = 300) of varying chronicity, ranging from
chronic to acute
• Demonstrates, albeit anecdotally without quantitative evidence, the safe use of NPWT by non-MD
providers such as outpatient nurses, family members, and patients themselves
• Provides practical advice on troubleshooting as well as customizing NPWT treatments to their
specific indications (i.e. use of intervening nonadherent dressing and reduced suction pressure for
split-thickness skin grafts)
Limitations • Publication is limited to description of authors’ experience with wounds treated with NPWT with
no true control or experimental group
• Results limited to authors’ qualitative assessments of wound progression, with little to no
quantitative endpoints
Impact Though not an experimental study and purely a narrative of the authors’ initial experience with
NPWT, this landmark publication was the first to not only describe the safe use of NPWT in a variety
of wound contexts (across chronicity as well as anatomical sites), but provide practical considerations
for early adoptees of the technique as well as hypothesize the underlying biophysical mechanisms that
lay the groundwork for a large body of literature investigating the role of mechanical forces in wound
healing
Since this pioneering work, numerous studies here. As described in a recent article by Climov
have further explored the biophysical mecha- et al. applying the previously established
nisms underlying the effects of NPWT, which are Technology Innovation Maturation Evaluation
summarized in great detail elsewhere and are (TIME) framework to this niche of wound heal-
described as both macrodeformational (quantita- ing innovation, skin replacement therapies (SRT)
tive wound shrinkage induced by pore collapse may be further divided into three sub-categories:
when suction applied to foam) and microdefor- processed biologics technologies (PBTs), extra-
mational (microscopic undulations created at the cellular matrix technologies (EMT), and cell-
wound-dressing interface), which is thought to based therapies (CBT) [6]. PBTs, the oldest of
modulate the cytoskeleton of resident cells these categories, broadly encompass technolo-
through shear forces and optimize the wound gies for harvesting, processing, sterilizing, and
environment by activating wound healing signal- storing skin grafts. EMTs aim to provide a scaf-
ing cascades, facilitating granulation tissue for- fold to regenerate or replace the native human
mation, and inducing angiogenesis in response to dermis through processes such as engraftment
local hypoxia [3, 4]. Recently, NPWT was dem- and angiogenesis, which has been shown in prod-
onstrated to enhance lymphangiogenesis in full- ucts such as Integra® Dermal Regeneration
thickness wounds in a diabetic murine model, as Template (IDRT, Integra LifeSciences
demonstrated by quantitative increases in lym- Corporation, Plainsboro, NJ), discussed in fur-
phatic density as well as upregulation of ther detail below, and decellularized dermal
lymphatic-specific protein markers and increased matrices such as AlloDerm™ (LifeCell
local B-cell infiltration—thus suggesting possi- Corporation, Branchburg, NJ). Finally CBTs uti-
ble utility of NPWT wound healing through lize living cells of different origins, either as cul-
enhanced lymphatic drainage [5]. tured cells or incorporated into layered constructs,
Perhaps the most powerful aspect of NPWT is for skin substitution or regeneration.
its applicability across a variety of wound con- Initially developed for application in the acute
texts, including but not limited to nonhealing phase of burn injuries, IDRT is a bilayered dermal
open wounds, skin graft, and dermal scaffold substitute comprised of a first layer of bovine col-
recipient sites, burn wounds, deep sternal wound lagen and chondroitin-6-sulfate, cross-linked with
infections, large soft tissue mass resection sites. glutaraldehyde, and a superficial second layer of
Furthermore, the past few decades have also seen silicone membrane functioning as a temporary
the birth of various iterations of the traditional epidermis. Recipient fibroblasts and blood vessels
NPWT system, including incisional NPWT (top- from the wound infiltrate the dermal matrix to
ical application of NPWT over a closed wound) create a neodermis, after which the silicone layer
and several combinatorial treatment systems may be removed for definitive placement of a skin
such as instillation NPWT (featuring a secondary graft over a healthy, revascularized wound bed [7,
port for the injection of fluids such as normal 8]. In 1988, Heimbach et al. published an 11-cen-
saline, dilute sodium hypochlorite, or antibiotic ter prospective randomized control comparing the
solution) and the use of silver-impregnated application of Integra vs. standard skin grafting
foams. material on patients with life-threatening burns
who underwent primary excision and grafting
within 7 days of injury [9]. Epidermal grafts were
4.1.3 Acellular Dermal Matrices applied to the study site during a second opera-
(Skin Replacement Therapies) tion, with a follow-up time of 1 year for surviving
patients. Compared to initial grafting of autograft,
Dermal scaffolds have had a major impact in allograft, xenograft, or synthetic dressing as con-
treating a variety of wounds. Some have been trol materials, wounds treated with the artificial
referred to as “skin substitute” materials, two of dermis were seen to require significantly thinner
which will be featured and critically analyzed donor site thickness, with less hypertrophic scar-
ring and patients ultimately preferring the artifi- ulcers present for greater than 6 weeks without
cial dermis to the control graft. This pivotal paper, exposure of the joint capsule, tendon, or bone.
studying 139 sites on a total of 109 patients, Today, the clinical applications far exceed these
established the utility of Integra in not only tem- initial indications and have shown clinical appli-
porizing acute burns in critically ill patients but cations across various areas of the body, includ-
ultimately improving functional and aesthetic ing but not limited to broader wounds of the
outcomes, forming a foundation for the expanded extremities with exposed tendon with no
use of Integra like products in a variety of clinical paratenon, trunk wounds such as those following
contexts over the past three decades. the excision of keloids and giant congenital mela-
Since this work, these collagen-glycosamino- tocytic nevi, and head and neck defects including
glycan (GAG) scaffolds, and derivative products, oncological scalp reconstruction and lining resto-
received FDA approval for use in burns (1996), ration following orbital exenteration or excisions
burn scars (2002), and chronic diabetic foot of invasive intraoral malignancies [10].
Heimbach D, Luterman A, Burke J, Cram A, Herndon D, Hunt J, Jordan M, McManus W, Solem L, Warden G.
Artificial dermis for major burns. A multi-center randomized clinical trial. Ann Surg. 1988;208(3):313–20
Strengths • Multi-centered randomized clinical trial with relatively large number of patients (n = 106) and
wound sites (n = 139)
• One-year follow-up with assessment of multiple patient-reported parameters (i.e. pruritus,
scaliness, dryness, sensation) and patient/surgeon preference of donor sites where artificial dermis
was used or not used
Limitations • Limited discussion of long-term outcomes such as rate of wound healing complications, infections,
revision surgeries
• Challenging to accurately compare sites using artificial dermis and secondary skin grafting vs.
primary skin grafting, as the former was inevitably less mature at the time of patient discharge
Impact This publication represents one of the largest multi-site randomized trials to date on the clinical use
of Integra-like products, and is unique in its quantitative assessment of donor site thickness required
for wound coverage as well as patient and surgeon perspectives and preferences between standard
grafting procedures and the use of artificial dermis prior to final grafting
4.1.4 Cell-Based Therapies: sheets that can be clipped onto petroleum-

Autologous Cultured Human impregnated gauze, then sutured onto the wound
Epithelium (Skin Replacement bed. Histological studies demonstrated that the
Therapies) cultured epithelium thickened over the course of
2–3 weeks to stratify into a granular and a horny
The advent of cell-based therapies (CBTs) was layer, with a periodic acid-Schiff stain demon-
powered by an improved method of culturing strating the formation of a basement membrane
human keratinocytes. In a case report published with dispersed melanocytes, though unclear
in 1984, Gallico et al. discussed a method of from this data whether these cells arose via mul-
culturing autologous sheets of human keratino- tiplication of resident cells in the cultured graft
cytes, or cultured epithelial autografts (CEA), or through upward migration from deeper tis-
which were subsequently applied in two chil- sues. While limited in its generalizable evidence
dren who had suffered extensive burns to over as a case report of two patients, nevertheless this
95% of their bodies, successfully covering half was a critical study that demonstrated the clini-
or more of the total burned surface with cultured cal use of this innovative skin expansion method,
autograft [11]. Here, full-thickness skin biop- circumventing the devastating lack of healthy
sies were obtained from each patient, minced donor skin area in these severely burned
into single cell suspensions, then cultured into children.
Gallico GG, O’Connor NE, Compton CC, Kehinde O, Green H. Permanent coverage of large burn wounds with
autologous cultured human epithelium. N Engl J Med. 1984;311(7):448–51
Strengths • First application of CEA technique in massive burn (TBSA >95%) with successful coverage of
more than half of body surface
• Histological analysis of epidermis following grafting, demonstrating auto-stratification, presence
of a basal layer and melanocytes, presence of maturing Type I collagen in subepithelial connective
tissue
Limitations • Highly limited case report comprised of two pediatric patients
Impact Despite the limited sample size, this work was the first to demonstrate the utility of CEAs beyond
animal models and small human burns, suggesting that it can be a viable option in severe, massive
burns where there is a poor chance of survival and severely limited donor site availability
Despite the great promise of this technique, CEAs only one approved growth factor on the market
have had a more limited penetrance in the real- today in the US. Platelet-derived growth factor
world clinical setting than the aforementioned (PDGF), or becaplermin, showed a statistically
three wound healing innovations, perhaps due to significant effect in phase II, III, and IV clinical
the limited applicability outside of massive burns trials. The FDA-approved the topical application
as well as barriers of cost, long-term fragility, and more than two decades ago. PDGF is normally
inability to apply them onto infected or otherwise produced by platelets, macrophages, and endothe-
compromised wound beds. A retrospective review lial cells with a multitude of effects on wound
of 32 pediatric patients with devastating burns healing, including synthesis of extracellular matrix
(TBSA >90%) between 1988 and 1998 demon- components, facilitation of cell mitogenesis and
strated that while those treated with CEA achieved migration, and activation of inflammatory cells. A
better quality of burn scars (as quantified by sur- landmark publication by Steed et al. investigated
face regularity, border height, thickness, and pig- the safety and efficacy of PDGF in chronic (pres-
mentation) but incurred higher hospital costs as ent >8 weeks) full-thickness diabetic neurotrophic
well as longer lengths of stay [12]. foot ulcers by entering 922 patients meeting inclu-
sion criteria into one of five randomized, prospec-
tive, blinded clinical trials comparing PDGF to a
4.1.5 Growth Factors: Platelet- placebo gel treatment [13]. Combined analysis
Derived Growth Factor (PDGF) demonstrated that, among ulcers with a baseline
area of 10 cm2 or smaller, those treated with
The discovery of growth factors in cell culture rap- 100 μg/g PDGF not only achieved significantly
idly gave rise to the idea of applying these to higher rates of complete healing compared to pla-
chronic wounds. There have been extensive efforts cebo, but also decreased time to complete healing
by many investigators to look at many of these without significant differences in complications or
growth factors in wound healing but there is now rate of ulcer recurrence.
Steed DL. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower
extremity ulcers. Plast Reconstr Surg. 2006;117(7 Suppl):143S–9S. discussion 150S–151S
Strengths • A report of five randomized control trials, encompassing a total of 922 patients and including phase
II, III, and post-marketing IV clinical trials
• Combined analysis performed
Limitations • Patients included in the study were required to have adequate perfusion of the extremity, devoid of
infections, completed extensive debridement, and adhered to pressure off-loading interventions—
Which, combined, are likely not representative of a large population of patients suffering chronic
diabetic ulcers and results may not be generalizable to less optimal wounds
• Difficult to ascertain effect of modalities on diabetic foot ulcer recurrence given possible
confounding factors such patient adherence to orthotic use and other pressure off-loading practices
Impact This publication performs a combined analysis of multiple randomized control studies to demonstrate
improved wound healing with the use of PDGF compared to placebo without increase in ulcer
recurrence or other adverse outcomes
4.1.6 Barriers and Hurdles (i.e. FDA approval, cost, and insurance coverage)
in Wound Care (Table 4.1). Clearly, these are not mutually exclu-
sive but closely intertwined realms, with cost as a
These five discoveries not only exemplify inno- key overlapping factor that affects all three cate-
vations in various parameters that drive wound gories. Innovations that successfully optimize as
healing mechanisms ranging from the micro- many of the three key categories of success have
scopic to macroscopic, but also demonstrates key the highest likelihood of achieving penetrance
determinants of success for bench-to-bedside into the healthcare market and utility in the mod-
translational research. Such determinants, while ern clinical landscape. Figure 4.1 draws upon our
not comprehensive, may be conceptualized as experience in both the active development, criti-
three overlapping categories: (1) patient-specific cal review, and versatile application of various
factors (i.e. impact on pain and other quality-of- wound healing methods to assess the five fea-
life determinants); (2) physician-specific factors tured landmark innovations across these core
(i.e. simplicity of concept and ease of use across parameters, providing a visual comparison
a variety of specialties and adjunct healthcare between their respective potential strengths and
professions); and finally, (3) bureaucratic hurdles weaknesses.
Table 4.1 Determinants of success for wound healing innovations

Category of determinants Examples
1. Patient-specific factors • What is the cost of the intervention?
• How much does it impact patient’s quality of life? (pain control, ease of wound
care, etc.)
2. Provider-specific factors • How cumbersome are the preparatory and application steps?
• Is it operator-dependent?
• Can it be used in both the inpatient and outpatient settings?
• Can it be used in a wide spectrum of clinical settings? (community hospitals,
urgent care clinics, academic tertiary medical centers, etc.)
3. Bureaucratic hurdles • How difficult is it to prove efficacy through a large, randomized control trial?
• How readily can it be FDA-approved?
• Is it covered by insurance?
Cost Patient Provider Bureaucratic
• Can be used by providers

Moist wound
• Simple dressing change of all levels (MD, RN, APPs)

healing
$ regimens that can be performed

by patient and family
• Multiple dressing options
available Low regulatory hurdles
• Daily changes may be • Applicable across diverse

painful and distressing practice settings (inpatient/
outpatient, urban/rural)
• Decreased pain • Can be used by providers

of all levels (MD, RN, APPs)
• Decreased frequency of
NPWT
• Does require visiting nursing

$ $ dressing changes compared to
standard wound care
care for home changes Challenges remain with
• Applicable across diverse insurance coverage
• Faster wound healing practice settings (inpatient/
outpatient, urban/rural)
Dermal scaffolds
• Decreased pain • Requires operating room

and MD for safe and sterile
• Decreased frequency of Variability of regulatory
placement
$ $ $ dressing changes compared to
standard wound care
pathways depending on
particular ADM product
• Requires vigilant outpatient
• Potential for dermal monitoring by provider
regeneration
• Largely limited to • Requires operating room

specialized cases such as and MD for safe and sterile
• Complex production and
large TBSA burns placement
shipping/handling
CEA
$ $ $ $ $ • Provides large quantity of • Requires specialized

autologous tissue in cases of harvesting and culturing • Variable insurance
highly limited donor site method coverage
availability • Requires 2-3 weeks for
completion of autograft
• Topical ointment that patient or

family can apply
• Data limited to pressure-off- • Topical ointment that can easily
PDGF
$ $ $ $ loaded, non-infected diabetic

ulcers and with unclear
be applied in clinic setting Complex approval process
generalizable applicability
across other types of
wounds
Fig. 4.1 Moist wound healing, NPWT (negative pressure unique strengths and weaknesses from the patient, pro-
wound therapy), dermal scaffolds, CEA (cultured epithe- vider and bureaucratic perspective that must be consid-
lial autografts), and PDGF (platelet derived growth factor) ered in designing the optimal approach for each case
are five landmark innovations in wound healing with
4.2 Expert Concluding (2) biophysical effects of mechanical forces, (3)

Commentary dermal regeneration and the presence of a dermal
matrix for ingrowth of tissue, (4) recruitment of
Five key discoveries over the last 60 years in cells to facilitate re-epithelialization and other crit-
wound healing emphasize methods to clinically ical aspects of wound healing, (5) growth factors,
alter the underlying biology of wound healing and cytokines and other elements of the wound micro-
include: (1) a moist wound macro-environment, environment (Fig. 4.2). A critical analysis of these
Effective wound healing
Endogenous growth factor

production by resident cells +
exogenous addition of growth factors
facilitate wound healing
5 Growth factors
4 Cells
Cells infiltrate and populate Mechanical forces induce
infrastructure provided by cytoskeleton and other cellular
acellular dermal matrix changes
Enhanced epidermal
3 Scaffolds cell migration
2 Mechanical forces
1 Moist Wound Healing
Fig. 4.2 Five interconnected innovations in wound heal- that serve as the drivers of re-epithelialization and other
ing include (1) a moist wound macro-environment that critical aspects of wound healing, and (5) both endoge-
encourages cell migration, (2) mechanical forces and their nous and exogenous growth factors that facilitate the heal-
biophysical effects on cell behavior, (3) dermal matrices ing and remodeling process
that undergo cell infiltration and tissue ingrowth, (4) cells
landmark papers, combined with clinical experi- The future of wound healing may lie in the
ence evidence, also provides insight into the chal- customized combination of these modalities for
lenges in translating an idea into an actual product patient- and wound-specific treatment. This has
used in patients. While none of these technologies already been foreshadowed by work such as
solve all issues in wound healing, they have invari- that studies showing enhanced take of Integra
ably transformed the our thinking and have served and decreased time to definitive skin graft with
as the foundation for iterative innovation, which the combined used of Integra and NPWT and
we currently see both in the number of new dress- other adjunct topical treatments [20, 21], as
ing materials produced each year as well as a large well as studies exploring the combined use of
number of advanced wound care products that CEAs over IDRT to circumvent the challenges
have been developed or are currently being stud- of CEA take over full-thickness defects of
ied. Some exciting developments include alterna- chronically infected burn wounds [22]. It is our
tive autologous cell-based therapies such as hope that this chapter not only serves as a
sprayable non-cultured, autologous skin cell sus- focused historical review of wound healing
pensions (“spray-on skin”) demonstrating promise innovations over the past several decades, but
in burn care [14, 15], and recent exciting advances also a roadmap for innovators and providers
investigating the roles of alternative growth factors alike in better understanding the current barri-
such as fibroblast growth factor (FGF) [16], epi- ers to effective wound management and miti-
dermal growth factor (EGF) [17], and hepatocyte gating them through cost-effective novel
growth factor [18, 19] in wound healing. treatment modalities.
References ment of lower extremity ulcers. Plast Reconstr Surg.

2006;117(7 Suppl):143S–9S; discussion 150S–151S.
14. Bairagi A, Griffin B, Banani T, McPhail SM, Kimble
1. Winter GD. Formation of the scab and the rate of
R, Tyack Z. A systematic review and meta-analysis of
epithelization of superficial wounds in the skin of the
randomized trials evaluating the efficacy of autologous
young domestic pig. Nature. 1962;193:293–4.
skin cell suspensions for re-epithelialization of acute
2. Argenta LC, Morykwas MJ. Vacuum-assisted closure:
partial thickness burn injuries and split-thickness skin
a new method for wound control and treatment: clini-
graft donor sites. Burns. 2021;47(6):1225–40.
cal experience. Ann Plast Surg. 1997;38(6):563–76;
15. Magnusson M, Papini RP, Rea SM, Reed CC, Wood
discussion 577
FM. Cultured autologous keratinocytes in suspension
3. Orgill DP, Bayer LR. Negative pressure wound
accelerate epithelial maturation in an in vivo wound
therapy: past, present and future. Int Wound J.
model as measured by surface electrical capacitance.
2013;10(s1):15–9.
Plast Reconstr Surg. 2007;119(2):495–9.
4. Panayi AC, Leavitt T, Orgill DP. Evidence based
16. Akita S, Akino K, Hirano A. Basic fibroblast growth
review of negative pressure wound therapy. World J
factor in scarless wound healing. Adv Wound Care
Dermatol. 2017;6(1):1–16.
(New Rochelle). 2013;2(2):44–9.
5. Wu M, Matar DY, Yu Z, Chen Z, Knoedler S, Ng B,
17. Berlanga-Acosta J, Camacho-Rodríguez H, Mendoza-
Darwish O, Haug V, Friedman L, Orgill DP, Panayi
Marí Y, Falcón-Cama V, García-Ojalvo A, Herrera-
AC. Modulation of lymphangiogenesis in inci-
Martínez L, Guillén-Nieto G. Epidermal growth factor
sional murine diabetic wound healing using nega-
in healing diabetic foot ulcers: from gene expression
tive pressure wound therapy. Adv Wound Care (New
to tissue healing and systemic biomarker circulation.
Rochelle). 2023;12:483–97.
MEDICC Rev. 2020;22(3):24–31.
6. Climov M, Panayi AC, Borah G, Orgill DP. The life-
18. Li J-F, Duan H-F, Wu C-T, Zhang D-J, Deng Y, Yin
cycles of skin replacement technologies. PLoS One.
H-L, Han B, Gong H-C, Wang H-W, Wang Y-L. HGF
2020;15(3):e0229455.
accelerates wound healing by promoting the dediffer-
7. Burke JF, Yannas IV, Quinby WC, Bondoc CC, Jung
entiation of epidermal cells through β1-integrin/ILK
WK. Successful use of a physiologically acceptable
pathway. Biomed Res Int. 2013;2013:470418.
artificial skin in the treatment of extensive burn injury.
19. Morishita R, Shimamura M, Takeya Y, Nakagami
Ann Surg. 1981;194(4):413–28.
H, Chujo M, Ishihama T, Yamada E, Rakugi
8. Yannas IV, Lee E, Orgill DP, Skrabut EM, Murphy
H. Combined analysis of clinical data on HGF gene
GF. Synthesis and characterization of a model extra-
therapy to treat critical limb ischemia in Japan. Curr
cellular matrix that induces partial regeneration of
Gene Ther. 2020;20(1):25–35.
adult mammalian skin. Proc Natl Acad Sci USA.
20. Jeschke MG, Rose C, Angele P, Füchtmeier B, Nerlich
1989;86(3):933–7.
MN, Bolder U. Development of new reconstructive
9. Heimbach D, Luterman A, Burke J, Cram A,
techniques: use of Integra in combination with fibrin
Herndon D, Hunt J, Jordan M, McManus W, Solem
glue and negative-pressure therapy for reconstruction
L, Warden G. Artificial dermis for major burns. A
of acute and chronic wounds. Plast Reconstr Surg.
multi-center randomized clinical trial. Ann Surg.
2004;113(2):525–30.
1988;208(3):313–20.
21. Molnar JA, DeFranzo AJ, Hadaegh A, Morykwas MJ,
10. Chang DK, Louis MR, Gimenez A, Reece EM. The
Shen P, Argenta LC. Acceleration of integra incorpo-
basics of integra dermal regeneration template and
ration in complex tissue defects with subatmospheric
its expanding clinical applications. Semin Plast Surg.
pressure. Plast Reconstr Surg. 2004;113(5):1339–46.
2019;33(3):185–9.
22. Akita S, Hayashida K, Yoshimoto H, Fujioka M, Senju
11. Gallico GG, O’Connor NE, Compton CC, Kehinde O,
C, Morooka S, Nishimura G, Mukae N, Kobayashi K,
Green H. Permanent coverage of large burn wounds
Anraku K, Murakami R, Hirano A, Oishi M, Ikenoya
with autologous cultured human epithelium. N Engl J
S, Amano N, Nakagawa H, Nagasaki University
Med. 1984;311(7):448–51.
Plastic Surgeons Group. Novel application of cultured
12. Barret JP, Wolf SE, Desai MH, Herndon DN. Cost-
epithelial autografts (CEA) with expanded mesh skin
efficacy of cultured epidermal autografts in massive
grafting over an artificial dermis or dermal wound bed
pediatric burns. Ann Surg. 2000;231(6):869–76.
preparation. Int J Mol Sci. 2018;19(1):57.
13. Steed DL. Clinical evaluation of recombinant
human platelet-derived growth factor for the treat-
Evolution of Lymphedema
Management
5
Peter Neligan and Isao Koshima

In this chapter the evolution of lymphedema 1. Brorson H, et al. Liposuction reduces arm
management is discussed in the context of five lymphedema without significantly altering
landmark publications that have guided that the already impaired lymph transport.
evolution. Details are not given on individual Lymphology. 1998;31(4):156–72.
techniques unless specifically indicated. Other 2. Koshima I, et al. Supermicrosurgical lym-
references are cited to provide some perspec- phaticovenular anastomosis for the treatment
tive as it is impossible to cover such a large of lymphedema in the upper extremities. J
topic with just five references. However only Reconstr Microsurg. 2000;16(6):437–42.
those five that have had a major influence on 3. Narushima M, et al. Indocyanine green lym-
the direction of lymphedema management are phography findings in limb lymphedema. J
discussed in detail and the reasons why they Reconstr Microsurg. 2016;32(1):72–9.
are so important are examined. 4. Dayan JH, Dayan E, Smith ML. Reverse
lymphatic mapping: a new technique for
maximizing safety in vascularized lymph
Keywords node transfer. Plast Reconstr Surg.
2015;135(1):277–85.
Lymphedema · Swelling · Landmark · LVB ·
5. Hayashi A, et al. Effective and efficient lym-
VLNT · Liposuction
phaticovenular anastomosis using preopera-
tive ultrasound detection technique of
lymphatic vessels in lower extremity lymph-
edema. J Surg Oncol. 2018;117(2):290–8.
5.1 Introduction
Lymphedema management has been a challenge

P. Neligan (*) that has been addressed in various ways as sur-
Department of Surgery, University of Washington, gery itself has evolved. In this chapter, we will
Seattle, WA, USA concentrate on the recent evolution of lymph-
I. Koshima edema management and particularly on the devel-
International Center for Lymphedema, Hiroshima opment of microsurgical techniques to treat this
University Hospital, Hiroshima, Japan

https://doi.org/10.1007/978-3-031-57132-9_5
40 P. Neligan and I. Koshima
condition. However some of the older approaches, with liposuction combined with controlled com-
such as excisional procedures [1], still have a role pression therapy (CCD), the other group with CCD
to play. As an excisional approach, liposuction is alone. Thorough measurement with water displace-
the most widely used and has been shown to be ment showed significant reduction in the liposuc-
very effective. It is discussed in more detail below. tion group compared with the CCD only group.
Also, conventional treatment with manual lym- Furthermore, using indirect lymphoscintigraphy
phatic drainage (MLD) and complete decompres- (ILS) he showed that the abnormality of lymphatic
sion therapy (CDT) continue to be important flow persisted in both groups. The reason this study
components of lymphedema treatment [2]. is important is that, until the early 2000s, fat accu-
mulation was not recognized as being part of the
pathology of lymphedema. In fact, when Dr.
5.2 Liposuction Brorson first presented this fact at an international
and Lymphedema meeting of the Society of Lymphology (ISL), his
finding was greeted with disbelief. His very amus-
Hakan Bròrson was the first to recognize the impor- ing and methodical retort to this reception was sub-
tance of accumulated fibrofatty tissue in peripheral sequently published in Lymphology in 2004 [4].
lymphedema. Among the many papers he has writ- Currently liposuction is widely used in the
ten on the subject, the one we feel has had the most treatment of lymphedema. Some use it as the pri-
impact is the 1998 paper in “Lymphology” in which mary treatment, like Brorson, realizing that it
he shows that lymphedema in the arm of post-mas- treats the bulk, not the lymphedema and that
tectomy patients can be significantly reduced by patients require 24/7 compression to maintain the
liposuction without altering the already impaired achieved reduction. Others use it as an adjunct to
lymphatic transport [3]. This study is important the physiological lymphatic reconstruction pro-
because it describes the accumulated fibrofatty tis- cedures. There is controversy as to whether lipo-
sue in lymphedema. Following his usually meticu- suction should be done before or after physiologic
lous approach, Dr. Brorson compared two groups of treatment. Both approaches have been shown to
post-mastectomy patients; one group was treated work [5].
Brorson H, et al. Liposuction reduces arm lymphedema without significantly altering the already impaired lymph
transport. Lymphology. 1998;31(4):156–72
Strength • Well conducted study
• Careful selection of study groups
• Standardized measurements
• Prospective study
Limitations • Small study groups
• Low impact specialized journal so likely not widely read
Impact This was the first scientific study to show that liposuction successfully reduced arm lymphedema
without altering the abnormal lymphatic circulation. Brorson had already shown that lymphedema
works to reduce volume [6] but in this study showed that it did so without altering lymphatic flow
and therefore rationalized the need for 24/7 compression following liposuction
5.3 Physiologic Procedures formed lymphaticovenous anastomosis or

bypass in the 1970s and experimented with
Physicians have been trying to come up with an lymph node transfer [8]. However, Koshima
effective treatment for lymphedema for over a rightly identified the shortcoming in O’Brien’s
century. Julius Jacobson, a pioneer of microsur- work through his studies on lymphatic vessels
gery [7], was the first American surgeon to tackle [9]. He recognized that the pressure differential
lymphedema microsurgically. O’Brien per- between the lymphatic and venous systems
5 Evolution of Lymphedema Management 41
demanded anastomosis of the lymphatics to venules, obviating the pressure differential that
venules, precursors of veins with a lower pres- plagued previous attempts at lymphatico-venous
sure. This required finer techniques and Koshima bypass. This was the breakthrough that was
introduced us to the concept of supermicrosur- required and is the second landmark paper we
gery [10] to anastomose lymphatic channels to have chosen.
Koshima I, et al. Supermicrosurgical lymphaticovenular anastomosis for the treatment of lymphedema in the upper
extremities. J Reconstr Microsurg. 2000;16(6):437–42
Strengths • Controlled study comparing surgery with non-surgery patients
• Reasoned approach to the development of technique
• New technique
Limitations • Small study (12 patients in each arm)
• Retrospective study
Impact This paper introduces supermicrosurgery for the treatment of lymphedema for the first time allowing
anastomosis between lymphatic channels and venules. This approach has now been generally adopted
Koshima used indigo carmine to stain the lym- in our opinion, the third landmark paper in the
phatics and acknowledged that this method was development of lymphedema treatment [12]. In
not satisfactory. The biggest problem was how this paper Narushima et al. describe the four
to identify the lymphatic channels and it wasn’t main patterns of indocyanine green mapping
until Unno et al. introduced the use of indocya- that we see in lymphedema. These patterns, lin-
nine green (ICG) [11] that this problem was ear, splash, stardust, and diffuse, correspond
solved. However, though this was a significant with the clinical appearances of the lymphatic
advance, the interpretation of the various pat- channels that we see, as well as the clinical
terns that we saw with indocyanine green, by stages that had previously been described by
Koshima’s group, was more significant and is, Mihara [13].
Narushima M, et al. Indocyanine green lymphography findings in limb lymphedema. J Reconstr Microsurg.
2016;32(1):72–9
Strengths • Detailed description of technique of ICG injection
• Listing of near infra-red camera manufacturers
• Description of ICG patterns in upper and lower limbs
• Correlation of ICG pattern with clinical stage
Limitations • No mention of how many patient examinations were studied
Impact Though the use of ICG had already been reported [11], this paper was the first to present a
classification of ICG patterns as well as to correlate these to clinical lymphedema stages. This allowed
better interpretation of ICG results
Lymphaticovenular anastomosis or bypass abnormal in the limb drained by those nodes

(LVB) is only one of the physiologic procedures [17]. Because of reports of iatrogenic-induced
offered to lymphedema patients. Vascularized lymphedema at the donor site of some lymph
lymph node transplant (VLNT) also has a place node transfers [18] many surgeons stayed away
in lymphedema treatment. As already men- from VLNT initially. Dayan et al. introduced
tioned, O’Brien experimented on VLNT in a the technique of reverse lymphatic mapping
canine model in the 1980s [14] as did Corinne which allowed identification of nodes planned
Becker from Paris [15] who has one of the larg- for harvest and whether they played a role in
est experiences of lymph node transfer in the drainage of the adjacent limb, harvest of which
world and was one of the first to report it [16]. might result in lymphedema [19]. This paper
Saaristo and her group showed that lymphatic proved to be a game-changer for many who had
function following lymph node harvest was previously avoided VLNT because of fear of
inducing lymphedema. Pons et al. used ICG for abdomen or chest to identify the nodes (thoracic
reverse lymphatic mapping [20] but the concept or lateral inguinal) that he wanted to harvest. In
is the same. Dayan did a prospective study in this way it was possible to ascertain that the
which he looked at both axillary and groin nodes to be harvested played no part in draining
lymph node harvest. He injected technetium-99 the limb making it possible to mitigate the pre-
into the hand or foot to identify the sentinel viously reported complication of iatrogenic
node of the limb and used ICG injected into the lymphedema with VLNT.
Dayan JH, Dayan E, Smith ML. Reverse lymphatic mapping: a new technique for maximizing safety in vascularized
lymph node transfer. Plast Reconstr Surg. 2015;135(1):277–85
Strengths • Prospective study
• Well documented
• Detailed description of technique with good video
Limitations • Small number of patients
Impact This paper provided a technique to help avoid the most feared complication of VLNT, iatrogenic
lymphedema at the donor site. This stimulated wider application of VLNT
With evidence that both LVG and VLNT play a machine, veins and lymphatics can be distin-
role in successfully treating lymphedema [21] guished. Using ultrasound then, we can now
the question of patient selection, which patient to identify channels within these areas and target
choose for which operation, arises. One of the them for LVB, something that was not possible
factors that has helped with the understanding of before. This has expanded the indications for
lymphedema and with advances in its manage- LVB and has further expanded the way we can
ment is imaging. ICG has already been discussed treat lymphedema. Now we can not only identify
and is an invaluable tool in the management of lymphatic channels but we can also image veins
lymphedema. Magnetic resonance lymphangiog- that may be used to achieve the connection. More
raphy (MRL) is also extremely helpful and is recently, ultra-high frequency ultrasound has
widely used [22]. Hayashi et al. published the been introduced, providing greater definition.
results of a series of 55 patients in whom the lym- Because of the high resolution, it is not only pos-
phatic channels were identified with ultrasound, sible to visualize lymphatic channels, but to iden-
even within areas of dermal backflow. This again tify functioning ones with functioning valves.
has changed the way lymphedema can be treated The introduction of ultra-high frequency (UHF)
because we can now identify lymphatic channels ultrasound to the field of lymphedema has proved
within areas of dermal backflow. Using ICG, to be another significant advance in the under-
areas of dermal backflow appear as an undiffer- standing and management of lymphedema [24].
entiated white blot with no way to identify lym- UHF ultrasound was shown to be superior to con-
phatic channels within it [23]. Furthermore, ventional ultrasound in detecting lymphatic
using the duplex color mode on the ultrasound channels [25].
Hayashi A, et al. Effective and efficient lymphaticovenular anastomosis using preoperative ultrasound detection
technique of lymphatic vessels in lower extremity lymphedema. J Surg Oncol. 2018;117(2):290–8
Strengths • Significant number of patients in whom lymphatic channel identification was possible
• Veins and lymphatics visualized
Limitations • Retrospective study
Impact This study introduces ultrasound to the options for imaging lymphatics enabling identification of
both lymphatics and veins. Identifying lymphatic channels within areas of dermal backflow expands
the indications for LVB and further advances the possibilities for treating lymphedema
5 Evolution of Lymphedema Management 43
5.4 Expert Concluding 6. Brorson H, Svensson H. Complete reduction of

lymphoedema of the arm by liposuction after breast
Commentary cancer. Scand J Plast Reconstr Surg Hand Surg.
1997;31(2):137–43.
There have been many publications that have 7. Jacobson JH, Suarez EL. Microvascular surgery. Dis
moved this science along. We have endeavored to Chest. 1962;41:220–4.
8. O’Brien BM, Chait LA, Hurwitz PJ. Microlymphatic
highlight the five papers that, in our estimation, surgery. Orthop Clin North Am. 1977;8(2):405–24.
have had the most impact in advancing the under- 9. Koshima I, et al. Ultrastructural observations of lym-
standing and treatment of lymphedema. We have phatic vessels in lymphedema in human extremities.
cited other papers in order to help put these cho- Plast Reconstr Surg. 1996;97(2):397–405. discussion
406–7
sen five in perspective. One of the shortcomings 10. Koshima I, et al. Supermicrosurgical lymphaticoven-
we have discovered in the lymphedema literature ular anastomosis for the treatment of lymphedema
is the sparsity of good quality papers and a small in the upper extremities. J Reconstr Microsurg.
number of patients that are presented in each 2000;16(6):437–42.
11. Unno N, et al. Preliminary experience with a novel
study. This was also the finding of the meta- fluorescence lymphography using indocyanine green
analysis we did several years ago [21]. However, in patients with secondary lymphedema. J Vasc Surg.
another realization is the difference between 2007;45(5):1016–21.
impact factor and impactfulness. The former is a 12. Narushima M, et al. Indocyanine green Lymphography
findings in limb lymphedema. J Reconstr Microsurg.
measure of a journal and an indication of the 2016;32(1):72–9.
quality of the papers in that journal. The latter is 13. Mihara M, et al. Pathological steps of cancer-related
a more meaningful measure of how a particular lymphedema: histological changes in the collecting
paper has affected practice. This is what we have lymphatic vessels after lymphadenectomy. PLoS One.
2012;7(7):e41126.
tried to achieve in this chapter. The treatment of 14. Chen HC, et al. Lymph node transfer for the treatment
lymphedema is a moving target and we have no of obstructive lymphoedema in the canine model. Br J
doubt that we will see other impactful papers Plast Surg. 1990;43(5):578–86.
appear on the topic. 15. Becker C, Hidden G. Transfer of free lymphatic flaps.
Microsurgery and anatomical study. J Mal Vasc.
1988;13(2):119–22.
16. Becker C, et al. Postmastectomy lymphedema: long-
References term results following microsurgical lymph node
transplantation. Ann Surg. 2006;243(3):313–5.
1. Viviano SL, Neligan PC. Updates on excisional pro- 17. Viitanen TP, et al. Donor-site lymphatic function after
cedures for lymphedema. Adv Wound Care (New microvascular lymph node transfer. Plast Reconstr
Rochelle). 2021;11:419. Surg. 2012;130(6):1246–53.
2. Consensus document of the International Society of 18. Vignes S, et al. Complications of autologous lymph-
Lymphology Executive Committee. The diagnosis and node transplantation for limb lymphoedema. Eur J
treatment of peripheral lymphedema. Lymphology. Vasc Endovasc Surg. 2013;45(5):516–20.
1995;28(3):113–7. 19. Dayan JH, Dayan E, Smith ML. Reverse lymphatic
3. Brorson H, et al. Liposuction reduces arm mapping: a new technique for maximizing safety in
lymphedema without significantly altering the vascularized lymph node transfer. Plast Reconstr
already impaired lymph transport. Lymphology. Surg. 2015;135(1):277–85.
1998;31(4):156–72. 20. Pons G, et al. Reverse lymph node mapping using
4. Brorson H. Adipose tissue in lymphedema: the igno- Indocyanine green lymphography: a step forward
rance of adipose tissue in lymphedema. Lymphology. in minimizing donor-site morbidity in vascular-
2004;37(4):175–7. ized lymph node transfer. Plast Reconstr Surg.
5. Brazio PS, Nguyen DH. Combined liposuction and 2021;147(2):207e–12e.
physiologic treatment achieves durable limb volume 21. Chang DW, et al. Surgical treatment of lymphedema: a
normalization in class II–III lymphedema: a treatment systematic review and meta-analysis of controlled tri-
algorithm to optimize outcomes. Ann Plast Surg. als. Results of a consensus conference. Plast Reconstr
2021;86(5S Suppl 3):S384–9. Surg. 2021;147(4):975–93.
22. Mitsumori LM, et al. Mr Lymphangiography: how I their histological features: a step forward in lym-
do it. J Magn Reson Imaging. 2015;42(6):1465–77. phatic surgery. J Plast Reconstr Aesthet Surg.
23. Hayashi A, et al. Effective and efficient lymphati- 2020;73(9):1622–9.
covenular anastomosis using preoperative ultra- 25. Hayashi A, et al. Ultra high-frequency ultrasono-
sound detection technique of lymphatic vessels graphic imaging with 70 MHz scanner for visualiza-
in lower extremity lymphedema. J Surg Oncol. tion of the lymphatic vessels. Plast Reconstr Surg
2018;117(2):290–8. Glob Open. 2019;7(1):e2086.
24. Bianchi A, et al. Ultra-high frequency ultrasound
imaging of lymphatic channels correlates with

Emergence of Nerve Interfaces
with Robotic Applications
6
Katherine L. Burke, Gregory A. Dumanian,
and Paul S. Cederna
Abstract such control strategies are now capable of

Innovations in the fields of prosthetic devices facilitating intuitive, real-time, and naturalis-
and neuroprosthetic control strategies have tic prosthetic experiences for patients with
opened new frontiers for optimizing func- amputations. This article describes regenera-
tional restoration for people suffering from tive peripheral nerve interfaces (RPNI) and
limb loss. Commercial prosthetic devices are targeted muscle reinnervation (TMR), the
now available with sophisticated electrical two most promising surgical procedures to
and mechanical components that can closely enhance prosthetic rehabilitation with the
replicate the functions of the human muscu- goal of providing a prosthetic device that
loskeletal system. However, to truly recog- looks, moves, and feels like a normal hand.
nize the potential of such prosthetic devices In this manuscript, we will also discuss how
and develop the next generation of bionic both of these surgical approaches have been
limbs, a highly reliable prosthetic device shown to effectively prevent and treat neu-
control strategy is required. In the past few roma pain and phantom limb pain in patients
years, refined surgical techniques have with limb loss. Two landmark papers have
enabled neuroprosthetic control strategies to been selected to highlight the management of
record efferent motor and stimulate afferent neuroma pain and phantom limb pain in
sensory action potentials from a residual patients with limb loss. Three landmark
limb with extraordinary specificity, signal papers have been selected to demonstrate the
quality, and long-term stability. As a result, newest peripheral nerve interface strategies
to optimize prosthetic function following
amputation.
K. L. Burke
Keywords
Section of Plastic Surgery, University of Michigan, Regenerative peripheral nerve interface
Ann Arbor, MI, USA
(RPNI) · Targeted muscle reinnervation
G. A. Dumanian (TMR) · Neuroma pain · Prosthesis · Phantom
limb pain
Northwestern Memorial Hospital, Chicago, IL, USA
P. S. Cederna (*)
Department of Biomedical Engineering, University of
Michigan, Ann Arbor, MI, USA

https://doi.org/10.1007/978-3-031-57132-9_6
46 K. L. Burke et al.
The Five Most Impactful Papers niques that have been developed to enhance pros-
1. Dumanian GA, Potter BK, Mioton LM, et thetic control, the regenerative peripheral nerve
al. Targeted muscle reinnervation treats neu- interface (RPNI) and targeted muscle reinnerva-
roma and phantom pain in major limb ampu- tion (TMR).
tees: a randomized clinical trial. Ann Surg. Residual limb pain remains a severe conse-
2019;270(2):238–46. quence of amputation and can adversely impact
2. Kubiak CA, Kemp SWP, Cederna PS, a person’s ability to wear their socket and utilize
Kung TA. Prophylactic regenerative their prosthetic device. Developing a technique
peripheral nerve interfaces to prevent post- to reduce or eliminate phantom limb pain and
amputation pain. Plast Reconstr Surg. neuroma pain would be a significant advance for
2019;144(3):421e–30e. patients with limb loss and would help to opti-
3. Simon AM, Turner KL, Miller LA, et al. mize prosthetic rehabilitation. Unfortunately,
Myoelectric prosthesis hand grasp control there currently is no gold standard for the pre-
following targeted muscle reinnervation vention or treatment of postamputation pain,
in individuals with transradial amputation. including symptomatic neuromas [5]. In this
PLoS One. 2023;18(1):e0280210. chapter, we will discuss the effectiveness of
4. Vu PP, Vaskov AK, Irwin ZT, et al. A regen- RPNI and TMR for both the treatment and pre-
erative peripheral nerve interface allows vention of postamputation pain in patients with
real time control of an artificial hand in limb loss.
upper limb amputees. Sci Transl Med.
2020;12(533):eaay2857.
5. Vu PP, Lu CW, Vaskov AK, et al. Restoration 6.2 Nerve Interfaces
of proprioceptive and cutaneous sensation for Postamputation Pain
using regenerative peripheral nerve interfaces
in humans with upper limb amputations. Plast People experience severe, debilitating chronic
Reconstr Surg. 2022;149(6):1149e–54e. neuroma and phantom limb pain (PLP) following
major limb amputations. This residual limb pain
(RLP) is associated with severe functional conse-
6.1 Introduction quences, including prosthetic abandonment,
impairments in the ability to perform simple
People with limb loss not only experience devas- activities of daily living, and worsened quality of
tating functional consequences that adversely life [6, 7]. Unfortunately, there currently remains
impact their lives, but also experience negative no gold standard for the treatment of symptom-
psychosocial sequelae that impact their quality of atic neuromas, RLP, or PLP.
life and emotional well-being [1]. Recently, inno- A novel strategy for treatment of symptomatic
vations in robotic technology have resulted in terminal neuromas was first performed by Greg
upper limb prosthetic devices that have the capa- Dumanian who discovered that TMR, initially
bility to emulate precise movements of the wrist, developed for advanced myoelectric prosthetic
hand, and fingers [2]. Despite these advances, control, also successfully treated symptomatic
people with upper extremity limb loss continue to neuromas. TMR promotes newly divided nerves
reject these devices at high rates, preferring con- to regenerate and reinnervate a denervated target
ventional body-powered or myoelectric prosthet- end organ, preventing the process of erratic axo-
ics. The reason for this high rate of abandonment nal sprouting and therefore, neuroma formation.
is that these devices only partially restore lost This creative and thoughtful approach to manag-
function, due to a lack of an intuitive, functional ing neuromas was an active intervention to pro-
interface that can provide high-fidelity motor vide the end of a divided nerve “somewhere to go
control signals [3, 4]. In this chapter, we discuss and something to do.” This approach was dra-
the two most significant emerging surgical tech- matically different than the traditional passive
6 Emergence of Nerve Interfaces with Robotic Applications 47
approaches used for managing neuromas includ- blinded, randomized clinical trial that compared
ing ligating, cauterizing, injecting, capping, the effectiveness of TMR to the traditional, stan-
burying it in innervated muscle, or burying it in dard neuroma treatment involving neuroma
bone. TMR tried to heal the end of the nerve excision followed by burying the transected
while standard neuroma treatments up until that nerve end in innervated muscle. Results of this
point tried to hide the nerve ending. study provided evidence that patients who
The landmark paper chosen to highlight the underwent TMR surgery had decreased PLP and
impact of TMR on this field is the 2019 paper trended toward decreased RLP compared to
published in Annals of Surgery. This paper patients who underwent standard symptomatic
details the prospective, multicenter, single- neuroma treatment [8].
Dumanian GA, Potter BK, Mioton LM, et al. Targeted muscle reinnervation treats neuroma and phantom pain in
major limb amputees: a randomized clinical trial. Ann Surg. 2019;270(2):238–46
Strengths • Prospective, single-blinded, multicenter, randomized controlled trial (RCT)
• First surgical RCT for treatment of neuromas
• Participant adherence to protocol, reasonable-follow up for all participants, and crossover patients
demonstrating the successful treatment of pain even after initial management failure
Limitations • Potential for the size mismatch between donor and recipient nerves to create symptomatic
neuromas-in-continuity
• No improvement in functional outcomes
• Patient bias associated with patient-reported outcome instruments
• Study did not include comparison to other surgical approaches (such as RPNI) and only compared
the experimental treatment to 1 standard neuroma surgery
Impact This study showed that TMR is an effective and superior treatment for improving PLP and RLP in
patients with major limb amputations compared with conventional surgical neuroma treatment
RPNIs are a creative and novel surgical proce- underwent limb amputation and RPNIs were per-
dure which has been designed to prevent and formed on their divided peripheral nerves. Forty-
treat neuroma formation and PLP by providing five patients underwent limb amputation and had
targets for nerve regeneration and muscle rein- the traditional approaches for management of the
nervation. This active approach for the manage- nerves performed including burying the nerves in
ment of the end of a divided nerve provides innervated muscle, ligating, or capping the
physiologic targets for the sprouting and elongat- nerves. The two groups were followed for a mini-
ing axons, decreasing the number of aberrant mum of 12 months postoperatively and were
axons responsible for the formation of painful well-matched for sex and level of amputation.
neuromas. RPNIs were originally designed as a Postoperatively, zero patients in the RPNI group
peripheral nerve interface capable of amplifying developed symptomatic neuromas during the
efferent motor action potentials for intuitive pros- entire study period compared to 13.3% in the
thetic control. However, in rodent and non-human control group. In addition, only 51.5% of RPNI
primates’ studies, no neuromas were identified patients had any PLP postoperatively compared
within the RPNI construct, prompting further to 91.1% of patients in the control group. This
investigation into its use as a potential treatment study demonstrated that prophylactic perfor-
for symptomatic neuromas or prophylactic pro- mance of RPNIs at the time of amputation
cedure to prevent neuroma formation [9–11]. In reduced the formation of symptomatic neuromas
the 2019 Plastic and Reconstructive Surgery in addition to the development of PLP. This sim-
study by Kubiak et al., the postoperative out- ple and straightforward surgical technique has
comes of 90 patients who underwent limb ampu- significantly impacted the postoperative course
tation with and without prophylactic RPNI for individuals with amputations improving both
implantation was evaluated. Forty-five patients functional outcomes and quality of life.
Kubiak CA, Kemp SWP, Cederna PS, Kung TA. Prophylactic regenerative peripheral nerve interfaces to prevent
postamputation pain. Plast Reconstr Surg. 2019;144(3):421e–30e
Strengths • Detailed description of surgical technique for RPNI creation
• Simple surgical technique that does not require microsurgical expertise
• Compared rates of both symptomatic neuromas and phantom limb pain in patients undergoing
prophylactic RPNI at the time of primary amputation to traditional amputation techniques
• Control patients were matched to experimental patients by age, sex, level of amputation, and mean
duration of follow-up
• Direct comparison to other surgical approaches (ligation, capping, burying nerve in muscle or bone)
Limitations • Retrospective review
• Patient-reported pain outcomes
• Patient cohort differences in baseline comorbidities
• Cohorts not matched for indication or mechanism of amputation
Impact This study demonstrated that the use of prophylactic RPNIs is an effective technique for the prevention
of postamputation symptomatic neuroma formation and the development of PLP
6.3 Neural Interfaces extend the fingers [14]. Even more advanced
for Prosthetic Control control systems allow numerous electrodes to be
placed on the skin surface of the residual limb
Remarkable advances in the field of myoelectric and muscle contraction patterns can be recorded
prosthetics have resulted in devices that are capa- and interpreted to provide more naturalistic func-
ble of controlling multiple degrees of freedom tion without having to co-contract muscle groups
(DoFs), allowing for simultaneous control of to select the desired prosthetic hand preset grip.
elbow, wrist, and even individual fingers [12, 13]. Control paradigm that requires the same muscle
Current myoelectric prosthetic devices are con- group to sequentially signal different prosthetic
trolled by the contraction of available agonist- joints by definition is slow and non-intuitive.
antagonist muscle pairs, using one muscle group In addition, this mode of operation is not only
(e.g. biceps) to control one function (e.g. close cumbersome but also may require contraction of
hand) and the antagonist muscle group (e.g. tri- residual muscles which do not correspond to the
ceps) to control the antagonistic function (e.g. appropriate hand function. These cumbersome
open hand). Control of the prosthetic is achieved control paradigms increase the users’ cognitive
by recording electromyographic (EMG) signals burden, increase the overall frustration with the
from skin surface electrodes placed over the device, and ultimately may lead to prosthesis aban-
residual innervated muscles in the limb [14]. The donment [16]. Advanced prosthetic devices with
residual muscle’s EMG signals control the direc- pattern recognition systems can only provide func-
tion of movement of the prosthetic joint, while tion by recording EMG signals from residual
the amplitude of the signal proportionally con- innervated muscles. Unfortunately, in a person
trols the speed of movement [15]. with an above-elbow amputation, there are no
Advanced myoelectric devices can provide residual innervated muscles to control the finger
even more functions by allowing not only a sin- function, so this control paradigm becomes sub-
gle, paired agonist/antagonist function to open stantially less effective. In addition, the systems
and close the hand, but allow “mode selection” require recalibration because the skin surface elec-
where co-contraction of the same agonist/antago- trodes shift position over the underlying muscles
nist muscle group allows the user to select spe- and begin recording different, unrecognized mus-
cific preset grip patterns to provide the function cle-firing patterns. Although the control strategies
they want. For example, by co-contracting the used by myoelectric prostheses have demonstrated
triceps and biceps, the user can shift modes to reliable performance over the course of decades,
finger flexion/extension and once they select the the capabilities of these devices are far from achiev-
desired mode, they can then contract their biceps ing the goal of restoring normal hand function to a
to flex the fingers and contract the triceps to person following an upper limb amputation.
Directly interfacing to the peripheral nervous from the peripheral nerve itself [21]. This novel
system is a promising option to achieve the intu- and creative strategy allowed the motor control
itive control that is lacking in the clinically signals to be recorded from a peripheral nerve
available myoelectric prosthetic devices. In fact, without implants, electrodes, cuffs, or wires. The
several myoelectric prosthetics using peripheral muscle acted as a biologic amplifier of the nerve
nerve interfaces have been developed with the signal to overcome the poor signal-to-noise ratio
goal of producing volitional, real-time, and in peripheral nerve recordings. It also created a
coordinated movements [17]. The majority of stable connection to the peripheral nerve to allow
these experimental devices utilize epineural and long-term recording of peripheral nerve signals.
intraneural electrodes which have several disad- TMR was first performed on a patient with a
vantages including: (1) Iatrogenic nerve injury shoulder disarticulation by transferring residual
from insertion of the intraneural electrode; (2) nerves from the brachial plexus to motor
long-term compression neuropathies from epi- branches of residual innervated muscles of the
neural electrodes; (3) insufficient signal selec- chest. Surface EMG electrodes were then placed
tivity due to unfavorable signal-to-noise ratios; on the chest, over each of the corresponding
(4) lack of long-term stability of signal due to newly innervated muscle targets, to record
biofouling of the electrode; and (5) inability to peripheral nerve signals corresponding to the
record reproducible signals [12, 18, 19]. associated brachial plexus nerves [22]. Following
Although there is enormous potential with these the development and successful implementation
approaches, clinically available devices have of TMR for advanced myoelectric prosthetic
not been created to date. Patients continue to use control in proximal upper limb amputations,
devices with suboptimal control strategies TMR was then refined to allow control of pros-
resulting in poor prosthetic performance despite thetics in patients with distal limb amputations.
significant training time [20]. These limitations Thus, the first landmark paper we have chosen is
have inspired a surge of research focused on the the 2023 paper in PLOS ONE in which the
development of improved control systems and authors discuss the use of TMR for hand grasp
neural interfaces. control in individuals with transradial amputa-
Todd Kuiken and Greg Dumanian were the tions. This study was important because it dem-
first to explore the potential to record control sig- onstrated the benefits of TMR surgery in patients
nals from amputated peripheral nerves. Dr. with distal upper extremity amputations.
Dumanian performed a nerve transfer from a Importantly, this paper highlighted the improve-
peripheral nerve in the residual limb to a motor ments in control strategies and decrease in clas-
branch of a nearby otherwise functionless mus- sification errors of EMG signals, when post-TMR
cle. The muscle has no function, as the distal scores were compared to pre-TMR scores on
joint that it had previously moved was removed functional outcome measures. In addition, this
by the amputation. By doing this nerve transfer, study showed that the denervation of target
the efferent motor control signals from the resid- residual forearm muscles did not negatively
ual peripheral nerve could then be recorded from affect residual muscle function nor lead to worse
the newly innervated muscle rather than directly prosthetic control.
Simon AM, Turner KL, Miller LA, et al. Myoelectric prosthesis hand grasp control following targeted muscle
reinnervation in individuals with transradial amputation. PLoS One. 2023;18(1):e0280210
Strengths • Assessments performed in real life setting (home trials)
• Multiple functional outcome measures performed
Limitations • Non-randomized study
• Finite number of available EMG signal sites which precludes simultaneous activation of multiple
joints
• Signal fidelity issues due to the use of surface electrodes
Impact This paper showed functional control benefits of a multi-articulating hand prosthesis following TMR
surgery in transradial amputations. This was the first study to evaluate the use of TMR in distal upper
extremity amputations
TMR was the first peripheral nerve interface rather than surface EMG, has been shown to
strategy designed to control a prosthetic device, improve control accuracy and reduce movement
where an efferent motor action potential was not variability, independent of changes to the control
recorded directly from a peripheral nerve but strategy utilized [25, 26]. Also, contrary to TMR,
instead was recorded from a corresponding mus- the RPNI approach is not restricted to the utiliza-
cle reinnervated by that nerve. With this approach, tion of vascularized muscle within the residual
the motor intent could be recorded from the rein- limb or the nearby chest wall, thereby permitting
nervated muscle to provide control signals to physiologically relevant connections to individu-
actuate the prosthesis. The major benefits of this ally functioning fascicles within the peripheral
approach were that it allowed all of the adverse nerve [24]. Furthermore, RPNIs directly extract
sequelae of direct nerve interfacing to be avoided efferent motor action potentials from an already
including micro shear forces in the nerve or for- transected peripheral nerve, opposed to methods
eign body reactions to the electrode. In addition, which require dividing nerve branches to residual
TMR facilitated amplification of the peripheral innervated muscles, resulting in denervation of
nerve signals by transcutaneous recording EMG any remaining muscle in an amputated limb.
signals from muscle rather than small efferent Initial experimentation using animal models
motor action potentials from nerves. However, confirmed the biologic stability of the construct
there remained shortcomings of this interface, and interface as well as provided histologic evi-
including the reliance on surface EMG for signal dence of axonal regeneration and synaptogene-
acquisition and the resultant signal instability and sis within the construct [27–31]. Of the many
daily calibration required for pattern recognition papers published by Dr. Cederna and his
[23]. Additionally, this technique requires dener- research team, the paper we have determined to
vation of a normally innervated muscle and can have had the greatest impact is the 2020 paper in
require implantation of multiple nerves into the Science Translational Medicine. This pilot clin-
same target muscle if the number of nearby motor ical study demonstrated that the RPNI is a bio-
nerves is less than the number of recipients logically stable bioamplifier of efferent motor
required. This surgery requires a specific knowl- action potentials with long-term stability in four
edge of anatomy of the motor nerves of the chest, participants with varying levels of upper limb
upper arm, forearm, thigh, and calf, and therefore amputations including transradial, wrist disar-
may not be generally within the armamentarium ticulation, and shoulder disarticulation [18].
of most surgeons. Finally, reliance on surface Each participant underwent the creation of
electrodes may create difficulties with recording RPNIs on upper extremity peripheral nerves.
independent control signals from each individual The number of RPNIs created per nerve and per
nerve or fascicle, limiting the number of indepen- patient varied. Participants completed continu-
dent movements patients can achieve. ous and discrete tasks to measure motor perfor-
To overcome these limitations, while also mance and the ability to control multiple degrees
expanding on the concept of leveraging the phys- of freedom (DoF). These tests were performed
iologic processes of nerve and muscle regenera- over the course of months and years to deter-
tion and reinnervation, Paul Cederna developed mine the stability of the RPNI, the quality of the
the RPNI [24]. The RPNI consists of a free autol- signal-to-noise ratio (SNR), and the need for
ogous skeletal muscle graft that has been neuro- recalibration over time. All participants were
tized by the end of a residual transected peripheral able to control their p rosthetic with high accu-
nerve. The muscle becomes reinnervated by the racy throughout the study period, there was no
nerve and provides amplification of efferent decrease in the signal-to-noise ratio indicated
motor action potentials, which can be detected by healthy and stable RPNI’s, and there was no
biocompatible electrodes inserted into the free need for recalibration. This study also compared
muscle of each RPNI. The use of surgically the signal quality recorded from RPNIs with
implanted intramuscular or epimysial electrodes, percutaneous fine wires and surgically implanted
bipolar electrodes. The SNR of the recorded different volitional movements. This finding
EMG from indwelling electrodes was found to was strong evidence that RPNIs have different
be substantially larger than the percutaneous motor units reinnervating distinct portions of
fine wire electrodes. In addition, the SNR the muscle graft and are therefore functionally
recorded from RPNI were substantially larger selective.
than any SNR that has been recorded from any This paper is significant because it was the
direct nerve interfacing approach [32, 33]. first clinical trial to demonstrate that RPNIs are
Furthermore, these SNR values remained stable capable of amplifying nerve signals to provide
over time, including over 4 years in one partici- high SNRs needed for high-fidelity control of
pant [15]. Importantly, the utilization of dynamic hand and finger functions. This study also dem-
ultrasound to evaluate the health and function onstrated the ability of RPNIs to enable motor
(i.e. contraction) of RPNIs over time demon- selectivity, allow smooth continuous control of
strated that all RPNIs were healthy and that dif- multiple DOF movements, and remain a stable
ferent subregions of each RPNI contracted for peripheral nerve interface over time.
Vu PP, Vaskov AK, Irwin ZT, et al. A regenerative peripheral nerve interface allows real time control of an artificial
hand in upper limb amputees. Sci Transl Med. 2020;12(533):eaay2857
Strengths • Experiments designed to demonstrate RPNI’s viability in human subjects, determine the long-term
stability of one DOF motor performance, and improve volitional control of a virtual and physical
hand prosthesis for functional tasks
• Detailed descriptions of data collection methods, analysis, and functional tasks with associated
videos
• Well-documented results of individual participants
• High impact journal
Limitations • Study did not include direct comparison to other surgical approaches (such as TMR)
• Limited number of intramuscular electrodes that could be implanted due to safety reasons (not all
relevant residual muscles were implanted)
Impact This study showed that RPNIs effectively amplify motor nerve signals, enable motor selectivity, allow
smooth continuous control of one or more DOF thumb movements, and produce signals that remain
stable over time
The RPNI technique has the potential to revolutionize clinical prosthetic technology and significantly
improve the quality of life for patients with amputations
6.4 Neural Interfaces for Sensory embodiment. Peripheral nerve interfaces provide
Feedback the opportunity to restore a certain level of tactile
feedback by providing referred sensations to the
Despite the advances that have been made in the prosthetic limb. Studies have shown that the
motor control of advanced neuroprosthetic stimulation of peripheral nerves can improve
devices, users of these devices still rely heavily functional task accuracy and object identification
on visual feedback for control. Without meaning- [34–36]. Some existing neural interfaces have
ful and intuitive sensory feedback, it is extremely shown promising results suggesting their ability
difficult to restore naturalistic prosthetic function to evoke meaningful sensory feedback to enhance
to a person with limb loss. The restoration of tac- prosthetic use. Unfortunately, none of these inter-
tile sensation and proprioception would relieve faces are able to reliably provide both motor con-
the high cognitive burden associated with relying trol and sensory feedback through one interface
solely on visual cues to monitor motor com- [37–39].
mands. In addition, restoring the sense of touch The RPNI has enormous potential to serve
would provide tremendous psychological benefits as a novel bidirectional motor and sensory neu-
and enhance an individual’s sense of prosthetic roprosthetic interface. For this reason, we have
chosen the 2022 Plastic and Reconstructive period of 271 days and 437 days for partici-
Surgery paper which describes a clinical study pants 1 and 2, respectively. Of great signifi-
demonstrating use of RPNIs for the restoration cance, participant 2 had two ulnar nerve RPNIs
of proprioceptive and cutaneous sensory feed- which each demonstrated unique and somato-
back in two participants with distal upper limb topically distinct proprioceptive and cutaneous
amputations. In this study, RPNIs were stimu- sensory distributions: (1) Ulnar Nerve RPNI 1
lated evoking anatomically appropriate pro- provided sensory feedback to the small finger
prioceptive and cutaneous sensations. and ulnar border of the hand; and (2) Ulnar
Importantly, perception thresholds did not Nerve RPNI 2 provided sensory feedback to the
either change or improve throughout the study ring finger.
Vu PP, Lu CW, Vaskov AK, et al. Restoration of proprioceptive and cutaneous sensation using regenerative
peripheral nerve interfaces in humans with upper limb amputations. Plast Reconstr Surg. 2022;149(6):1149e–54e
Strengths • Experiments designed to characterize potential sensory afferent feedback capabilities of the RPNI
• Patients blinded to the location and type of sensory afferent feedback being provided in each trial
through long-term implanted bipolar electrodes
• Inclusion of videos demonstrating the methods of stimulation and reporting of sensations performed
Limitations • Study did not include direct comparison of afferent percepts shown with other neural interfaces
Impact The results of this study demonstrate the potential of RPNIs to restore both proprioceptive and
cutaneous sensory feedback that could result in the control of an ideal, intuitive prosthetic device
6.5 Expert Concluding creative approaches are changing the paradigm

Commentary regarding how we view the prevention and treat-
ment of neuromas, but also how we can poten-
Patients undergoing major limb amputation are tially provide people with limb loss more
severely compromised functionally and psycho- naturalistic function with their prosthesis. RPNI
logically. Any approach that can be used to and TMR have helped to bridge the critical sig-
reduce the amount of pain they experience fol- naling gap between a residual peripheral nerve
lowing their amputation would make a dramatic and a mechanical device, offering tremendous
improvement in their quality of life. Any tech- potential to facilitate intuitive motor function and
nique which would improve their prosthetic reha- sensory feedback from advanced prostheses.
bilitation will also enhance their functional Clinically, both TMR and RPNI strategies should
restoration following limb loss and would simi- be considered, and the appropriate method should
larly improve their quality of life. The goal of all be tailored to the individual patient to maximize
interventions should be to enhance recovery fol- patient outcomes and functional restoration. In
lowing major limb loss. There have been a great addition, the use of these techniques can be
deal of basic science and clinical work that were highly effective adjuncts to standard amputation
performed in the past to improve function and treatment by reducing or eliminating neuroma
reduce pain following amputation. However, pain and PLP. These innovative interfacing tech-
none of them have completely accomplished the niques have revolutionized the potential of neu-
stated goals of reduced pain and improved pros- roprosthetic control and at the same time reduced
thetic function. RPNI and TMR have shown great residual limb pain in patients experiencing limb
promise in not only preventing and treating neu- loss, bringing us closer to providing patients with
roma pain and PLP, but also provided more natu- a pain-free residual limb and naturalistic pros-
ralistic prosthetic function. These two novel and thetic function.
References faces and implanted EMG electrodes. J Neural Eng.

2023;20(2):026039.
16. Biddiss E, Chau T. Upper-limb prosthetics: criti-
1. Armstrong TW, Williamson MLC, Elliott TR,
cal factors in device abandonment. Am J Phys Med
Jackson WT, Kearns NT, Ryan T. Psychological dis-
Rehabil. 2007;86(12):977–87.
tress among persons with upper extremity limb loss.
17. Ganesh Kumar N, Kung TA, Cederna PS. Regenerative
Br J Health Psychol. 2019;24(4):746–63.
peripheral nerve interfaces for advanced control
2. Trent L, Intintoli M, Prigge P, Bollinger C, Walters
of upper extremity prosthetic devices. Hand Clin.
LS, Conyers D, et al. A narrative review: cur-
2021;37(3):425–33.
rent upper limb prosthetic options and design.
18. Vu PP, Vaskov AK, Irwin ZT, Henning PT, Lueders
Disabil Rehabil Assist Technol. 2020;15(6):
DR, Laidlaw AT, et al. A regenerative peripheral
604–13.
nerve interface allows real-time control of an artifi-
3. Yildiz KA, Shin AY, Kaufman KR. Interfaces with
cial hand in upper limb amputees. Sci Transl Med.
the peripheral nervous system for the control of a
2020;12(533):eaay2857.
neuroprosthetic limb: a review. J Neuroeng Rehabil.
19. Schultz AE, Kuiken TA. Neural interfaces for control
2020;17(1):43.
of upper limb prostheses: the state of the art and future
4. Uellendahl J. Myoelectric versus body-powered
possibilities. PM R. 2011;3(1):55–67.
upper-limb prostheses: a clinical perspective. J
20. Vu PP, Irwin ZT, Bullard AJ, Ambani SW, Sando IC,
Prosthetics Orthotics. 2017;29(4):25–9.
Urbanchek MG, et al. Closed-loop continuous hand
5. Ives GC, Kung TA, Nghiem BT, Ursu DC, Brown
control via chronic recording of regenerative periph-
DL, Cederna PS, et al. Current state of the surgi-
eral nerve interfaces. IEEE Trans Neural Syst Rehabil
cal treatment of terminal neuromas. Neurosurgery.
Eng. 2018;26(2):515–26.
2018;83(3):354–64.
21. Kuiken TA, Stoykov NS, Popovic M, Lowery M,
6. Hanley MA, Ehde DM, Jensen M, Czerniecki J,
Taflove A. Finite element modeling of electromag-
Smith DG, Robinson LR. Chronic pain associ-
netic signal propagation in a phantom arm. IEEE
ated with upper-limb loss. Am J Phys Med Rehabil.
Trans Neural Syst Rehabil Eng. 2001;9(4):346–54.
2009;88(9):742–51; quiz 52, 79
22. Kuiken TA, Dumanian GA, Lipschutz RD, Miller LA,
7. Sinha R, van den Heuvel WJ, Arokiasamy P. Factors
Stubblefield KA. The use of targeted muscle rein-
affecting quality of life in lower limb amputees.
nervation for improved myoelectric prosthesis con-
Prosthetics Orthot Int. 2011;35(1):90–6.
trol in a bilateral shoulder disarticulation amputee.
8. Dumanian GA, Potter BK, Mioton LM, Ko JH,
Prosthetics Orthot Int. 2004;28(3):245–53.
Cheesborough JE, Souza JM, et al. Targeted muscle
23. Langhals NB, Woo SL, Moon JD, Larson JV, Leach
reinnervation treats neuroma and phantom pain in
MK, Cederna PS, et al. Electrically stimulated sig-
major limb amputees: a randomized clinical trial. Ann
nals from a long-term regenerative peripheral nerve
Surg. 2019;270(2):238–46.
interface. Annu Int Conf IEEE Eng Med Biol Soc.
9. Woo S, Kung TA, Brown DL, Leonard JA, Kelly BM,
2014;2014:1989–92.
Cederna PS. Regenerative peripheral nerve inter-
24. Woo SL, Urbanchek MG, Leach MK, Moon JD,
faces for the treatment of postamputation neuroma
Cederna P, Langhals NB. Quantification of muscle-
pain: a pilot study. Plastic Surgery Global Open.
derived signal interference during monopolar needle
2016;4(12):e1038–44.
electromyography of a peripheral nerve interface in
10. Kubiak CA, SWP K, Cederna PS. The regenerative
the rat hind limb. Annu Int Conf IEEE Eng Med Biol
peripheral nerve interface for neuroma management.
Soc. 2014;2014:4382–5.
JAMA Surg. 2018;153(7):681–2.
25. Pasquina PF, Evangelista M, Carvalho AJ, Lockhart
11. Santosa KB, Oliver JD, Cederna PS, Kung
J, Griffin S, Nanos G, et al. First-in-man demonstra-
TA. Regenerative peripheral nerve interfaces for pre-
tion of a fully implanted myoelectric sensors system
vention and management of neuromas. Clin Plastic
to control an advanced electromechanical prosthetic
Surg. 2020;47(2):311–23.
hand. J Neurosci Methods. 2015;244:85–93.
12. Kung TA, Bueno RA, Alkhalefah GK, Langhals
26. Dewald HA, Lukyanenko P, Lambrecht JM, Anderson
NB, Urbanchek MG, Cederna PS. Innovations in
JR, Tyler DJ, Kirsch RF, et al. Stable, three degree-
prosthetic interfaces for the upper extremity. Plast
of-freedom myoelectric prosthetic control via chronic
Reconstr Surg. 2013;132(6):1515–23.
bipolar intramuscular electrodes: a case study. J
13. Belter JT, Segil JL, Dollar AM, Weir RF. Mechanical
Neuroeng Rehabil. 2019;16(1):147.
design and performance specifications of anthropo-
27. Frost CM, Ursu DC, Flattery SM, Nedic A, Hassett
morphic prosthetic hands: a review. J Rehabil Res
CA, Moon JD, et al. Regenerative peripheral
Dev. 2013;50(5):599–618.
nerve interfaces for real-time, proportional con-
14. Roche AD, Rehbaum H, Farina D, Aszmann
trol of a neuroprosthetic hand. J Neuroeng Rehabil.
OC. Prosthetic myoelectric control strategies: a clini-
2018;15(1):108.
cal perspective. Curr Surg Rep. 2014;2(44)
28. Ursu DC, Urbanchek MG, Nedic A, Cederna PS,
15. Vu PP, Vaskov AK, Lee C, Jillala RR, Wallace DM,
Gillespie RB. In vivo characterization of regenera-
Davis AJ, et al. Long-term upper-extremity prosthetic
tive peripheral nerve interface function. J Neural Eng.
control using regenerative peripheral nerve inter-
2016;13(2):026012.
29. Irwin ZT, Schroeder KE, Vu PP, Tat DM, Bullard stimulation of peripheral tactile and proprioceptive
AJ, Woo SL, et al. Chronic recording of hand pros- pathways with intrafascicular electrodes. IEEE Trans
thesis control signals via a regenerative peripheral Neural Syst Rehabil Eng. 2011;19(5):483–9.
nerve interface in a rhesus macaque. J Neural Eng. 35. Schiefer MA, Graczyk EL, Sidik SM, Tan DW, Tyler
2016;13(4):046007. DJ. Artificial tactile and proprioceptive feedback
30. Ursu D, Nedic A, Urbanchek M, Cederna P, Gillespie improves performance and confidence on object iden-
RB. Adjacent regenerative peripheral nerve inter- tification tasks. PLoS One. 2018;13(12):e0207659.
faces produce phase-antagonist signals during 36. George JA, Kluger DT, Davis TS, Wendelken SM,
voluntary walking in rats. J Neuroeng Rehabil. Okorokova EV, He Q, et al. Biomimetic sensory
2017;14(1):33. feedback through peripheral nerve stimulation
31. Hu Y, Ursu DC, Sohasky RA, Sando IC, Ambani improves dexterous use of a bionic hand. Sci Robot.
SLW, French ZP, et al. Regenerative peripheral nerve 2019;4(32):eaax2352.
interface free muscle graft mass and function. Muscle 37. Tan DW, Schiefer MA, Keith MW, Anderson JR,
Nerve. 2021;63(3):421–9. Tyler J, Tyler DJ. A neural interface provides long-
32. Davis TS, Wark HA, Hutchinson DT, Warren DJ, term stable natural touch perception. Sci Transl Med.
O’Neill K, Scheinblum T, et al. Restoring motor 2014;6(257):257ra138.
control and sensory feedback in people with upper 38. Raspopovic S, Capogrosso M, Petrini FM, Bonizzato
extremity amputations using arrays of 96 microelec- M, Rigosa J, Di Pino G, et al. Restoring natural sen-
trodes implanted in the median and ulnar nerves. J sory feedback in real-time bidirectional hand prosthe-
Neural Eng. 2016;13(3):036001. ses. Sci Transl Med. 2014;6(222):222ra19.
33. Struijk JJ, Thomsen M, Larsen JO, Sinkjaer T. Cuff 39. D’Anna E, Valle G, Mazzoni A, Strauss I, Iberite F,
electrodes for long-term recording of natural sen- Patton J, et al. A closed-loop hand prosthesis with
sory information. IEEE Eng Med Biol Mag. simultaneous intraneural tactile and position feed-
1999;18(3):91–8. back. Sci Robot. 2019;4(27):eaau8892.
34. Horch K, Meek S, Taylor TG, Hutchinson DT. Object
discrimination with an artificial hand using electrical
Evolution of Breast Imaging
in Plastic Surgery
7
Dominick J. Falcon, Valeria P. Bustos,
and Bernard T. Lee

We discuss five landmark advances in breast 1. Ahn CY, Shaw WW, Narayanan K, et al.
imaging within plastic and reconstructive sur- Definitive diagnosis of breast implant rup-
gery from the last several decades, focusing ture using magnetic resonance imaging. Plast
on their contributions in guiding surgical care. Reconstr Surg. 1993;92(4):681–91.
We also discuss in depth the context of each 2. Fiaschetti V, Pistolese CA, Fornari M, et al.
landmark paper, delving further into the prac- Magnetic resonance imaging and ultrasound
tices before the innovation, its relevance to evaluation after breast autologous fat graft-
clinical care and research, and the more recent ing combined with platelet-rich plasma. Plast
developments in breast imaging following its Reconstr Surg. 2013;132(4):498e–509e.
publication. We also highlight the strengths 3. Rha EY, Choi IK, Yoo G. Accuracy of the
and weaknesses of the innovations in breast method for estimating breast volume on
imaging, commenting on the future of each three-dimensional simulated magnetic reso-
imaging modality as surgical care continues to nance imaging scans in breast reconstruc-
advance. tion. Plast Reconstr Surg. 2014;133(1):14.
4. Losken A, Seify H, Denson DD, Paredes AA,
Carlson GW. Validating three-dimensional
Keywords imaging of the breast. Ann Plast Surg.
2005;54(5):471–6. discussion 477–478.
Imaging · Plastic surgery · Trends · Breast
5. Holm C, Mayr M, Höfter E, Becker A,
Pfeiffer UJ, Mühlbauer W. Intraoperative
evaluation of skin-flap viability using laser
induced fluorescence of indocyanine green.
Br J Plast Surg. 2002;55(8):635–44.
D. J. Falcon · V. P. Bustos · B. T. Lee (*)
Beth Israel Deaconess Medical Center,
Harvard Medical School, Boston, MA, USA

https://doi.org/10.1007/978-3-031-57132-9_7
56 D. J. Falcon et al.
7.1 Introduction safety of breast implants was controversial [1].

With an increasing number of implant ruptures,
Imaging has become an integral component of there was a high need to find a reliable and accu-
plastic and reconstructive surgery in the preoper- rate imaging technique for diagnosis. Surgeons
ative planning, diagnosis, management, and often turned to mammography, computed tomog-
monitoring of patients. The expansive utility of raphy (CT), and ultrasound to determine if a
imaging in breast surgery includes making breast implant was ruptured. However, these
volumetric measurements, ensuring adequate
methods were unreliable with many ruptured
perfusion of flaps, developing 3D images for sur- implants going undetected. While MRI was also
gical planning, and assessing lymphatic vessels. utilized by radiologists, Ahn et al. was among the
Over the decades, technology has advanced to first to evaluate it as a tool for the definitive diag-
bring high-resolution images to the field. With nosis of breast implant rupture in 1992, which
the increasing portability of imaging techniques, ultimately shaped the diagnostic workup for
plastic surgeons can obtain real-time informa- implant ruptures henceforth [1].
tion, which is particularly applicable intraopera- In this landmark investigation, Ahn and col-
tively. Thus, imaging is a core tool for the leagues retrospectively evaluated 100 consecu-
planning and monitoring of breast surgery. tive symptomatic patients with suspected breast
With continuing innovation, a multitude of implant rupture who underwent MRI scans for
imaging modalities have gained attention and diagnosis. Of those patients, 80 underwent
popularity in plastic and reconstructive surgery. removal of the breast implant, and the MRI
This chapter aims to assess five landmark papers results were compared to the operative findings at
in plastic and reconstructive surgery describing explantation. The study found that MRI had a
breast imaging techniques over the recent sensitivity of 76% and a specificity of 97%, with
decades. The goal is to summarize five key a 4% false positive and false negative rate [1].
imaging-related technologies that helped propel They also described how they optimized the use
the field of breast reconstruction forward. These of coils and suppression to better visualize rup-
papers cover the role of magnetic resonance tures with MRI, characterizing common pitfalls
imaging (MRI) in surgical complications, screen- and techniques. In a later study, Ahn and col-
ing, and monitoring, the use of 3D laser scan- leagues compared MRI with mammography and
ning, and the utility of indocyanine green (ICG) sonography, finding that MRI had the highest
perfusion mapping. With these five landmark sensitivity (82%) and specificity (92%) when
papers, we analyze the innovations in breast compared to sonography (sensitivity 70%, speci-
imaging that have propelled the field of plastic ficity 92%) and mammography (sensitivity 11%,
surgery forward and reflect on their relevance. specificity 89%) [2]. These results were con-
The analysis aims to not only highlight the impor- firmed in several other studies, all showing MRI
tant contributions of imaging within breast recon- to be the most accurate in assessing breast implant
struction, but to also understand the future rupture.
applications and evolution of imaging. While MRI continues to be the gold standard
for implant rupture diagnosis, there are several
drawbacks to the approach. Compared with ultra-
7.2 Diagnosis of Breast Implant sound, MRI is costly, making it an undesirable
Rupture with MRI screening tool. As such, MRI is recommended as
a confirmatory test for symptomatic patients,
Implant rupture is a common complication that with ultrasound being a better first test for sus-
often requires surgical removal. Prior to removal, pected implant rupture [3–5]. Nonetheless, the
implant rupture should be definitively diagnosed utility of MRI in breast imaging became apparent
with imaging. In the 1980s and early 1990s, the with the introduction of breast implant evalua-
7 Evolution of Breast Imaging in Plastic Surgery 57
tion. Given its ability to characterize soft tissues duction of MRI into breast imaging ultimately
and abnormalities, MRI pushed the frontier of opened the door for its use in the screening, diag-
breast imaging by giving surgeons and oncolo- nosis, and monitoring of breast pathology in the
gists a clear view of breast implants. This intro- field.
Ahn CY, Shaw WW, Narayanan K, et al. Definitive diagnosis of breast implant rupture using magnetic resonance
imaging. Plast Reconstr Surg. 1993;92(4):681–91
Strengths • Performed consecutively to limit selection bias
• Characterized the techniques of suppression to better visualize rupture
Limitations • No comparison group
• Can be more costly and time-consuming
Impact This work was among the earliest to evaluate breast implants with MRI, introducing it as an effective
method for diagnosing a rupture. Currently, MRI continues to be used for the definitive diagnosis of
implant rupture. The application of MRI in implant rupture also allowed for the imaging modality to
become more commonly utilized within plastic surgery, ultimately leading to volumetric assessment
and monitoring
7.3 Assessing Fat-Grafting imaged the patients with mammography before

and Complications with MRI and 12 months following the last lipofilling ses-
sion. They found that ultrasound was the best at
Aside from breast implants, fat grafting became a detecting small oily cysts and evaluating dense
popularized method of breast reconstruction, but breasts, whereas MRI was better at differentiat-
complications such as microcalcifications and ing normal cysts from abnormal findings. The
oily cysts challenged its use in the 1990s. During study also found that while mammograms
this time, the safety of fat grafting was contested, detected microcalcifications, consistent follow-
with many arguing that its complications can up easily classified these findings as benign [9].
mimic breast cancer and challenge screening [6]. Furthermore, the aid of MRI and ultrasound
As a result, clear guidelines and imaging was adequately characterized cysts and potential
needed to differentiate benign complications of masses to rule out malignancy. This study dem-
fat grafting from breast cancer. Prior to the turn onstrated that MRI is a useful tool to evaluate
of the century, MRI became a complementary breast complications and quantitatively study
tool not only for the detection of implant rupture, volume retention over time.
but also for breast cancer detection [7, 8]. Given By describing the significance of MRI in post-
the early challenges with fat grafting, MRI fat graft monitoring, Fiaschetti and colleagues
showed promise as a tool for distinguishing post- pushed for the establishment of a clear protocol
surgical changes from cancer. for breast evaluation. While the study had a lim-
Fiaschetti et al. demonstrated the utility of ited sample size and follow-up time, further stud-
MRI in conjunction with ultrasound and mam- ies showed that MRI is the most sensitive at
mography to evaluate post-lipofilling breast detecting and following the progression of micro-
changes [9]. They used ultrasound and MRI to calcifications. It also is the modality of choice to
evaluate 24 breasts pre-lipofilling, 3 months detect breast cancer, making it a useful tool in
after the first session, and at 3, 6, and 12 months monitoring patients with fat-grafting changes to
after the last lipofilling session. They also the breast.
Fiaschetti V, Pistolese CA, Fornari M, et al. Magnetic resonance imaging and ultrasound evaluation after breast
autologous fat grafting combined with platelet-rich plasma. Plast Reconstr Surg. 2013;132(4):498e–509e
Strengths • Compares the benefits and challenges of MRI with ultrasound and mammography
• Applied 3D MRI principles for volumetric assessment
Limitations • Small sample size
• Limited follow-up time
Impact The study characterized common complications of fat grafting to the breast and compared the ability
of various imaging modalities to detect these changes. The paper described the safety of fat grafting
as well, delineating methods to distinguish surgical changes from oncological changes. The study
also demonstrates the utility of MRI in volumetric assessment, which pushed for its use in volume
monitoring and cancer screening
7.4 Volumetric Assessment mean error of 54.63 ± 46.30 and a correlation

of the Breast Using MRI coefficient of 0.945, compared to the plaster
method that had a mean error 137.4 ± 97.66 and
Along with monitoring for complications such as a correlation coefficient of 0.629 [10]. The study
implant rupture or oily cysts, an accurate and demonstrated the higher accuracy and predict-
reliable volumetric assessment of breasts can be ability of MRI volumetry measurements and
useful for breast reconstruction and augmenta- established it as a reliable tool.
tion. Early methods to determine breast volume While MRI is not the most cost-effective
include anthropometric measurements, method, the authors argue that many patients
Archimedean methods, plaster, and two- already require MRI for breast cancer evalua-
dimensional imaging, but these methods failed to tion, making this method easily accessible.
produce reliable measurements [10]. The earliest Other studies consistently show that MRI is a
use of MRI for a volumetric study was in 1983 by superior method for volumetric measurements
Fisher and Knight, followed by Fowler and col- when compared to CT and other early methods
leagues in 1990 to make relative comparisons of [12]. Beyond building on the utility of MRI as
breast volumes in the same patient [11]. As MRI a tool for volumetric assessment, the study
became increasingly utilized in breast cancer and takes MRI images and converts them into 3D
reconstruction, it also gained traction as a tool for reconstructions. As a result, the study opens the
volumetric measurements. In 2013, this was vali- door to visualize pathologies, vessels, and
dated by Rha, Choi, and Yoo who constructed breast anatomy in 3D, allowing for more pre-
three-dimensional images from MRI to measure cise preoperative planning. In more recent
breast volumes in their landmark study [10]. studies, MRI scans were used to create 3D
In this study, they retrospectively evaluated 18 images for virtual surgery. The recent literature
mastectomy patients (20 breasts) who underwent utilizes 3D-VR to plan surgical sites for fat
the plaster cast maneuver and MRI. They con- grafting and lumpectomy planning, making it
verted MRI images to 3D simulations using the an innovative approach for more exact surgical
1.5 T Signa Excite MRI device and measured the excision and reconstruction [13, 14]. Ultimately,
volumes using the Volume Viewer Plus. The mas- 3D MRI has the potential to not only measure
tectomy volume was used to compare the 3D breast volumes, but it can also aid in modeling
MRI volumes and the plaster cast maneuver vol- surgical planning and predicting the outcomes
umes. They found that 3D MRI estimations had a of breast reconstruction.
Rha EY, Choi IK, Yoo G. Accuracy of the method for estimating breast volume on three-dimensional simulated
magnetic resonance imaging scans in breast reconstruction. Plast Reconstr Surg. 2014;133(1):14
Strengths • Comparison study between mastectomy, MRI, and plaster casting volumetric methods
• Assesses MRI volumetry across various breast sizes
Limitations • Time-consuming to convert MRI images to 3D simulations
• Small sample size
• Method to establish boundaries can lead to higher error
Impact While 3D MRI volumetry had been introduced prior to this paper, it clearly demonstrates the utility
and accuracy of 3D MRI modeling for breast volumetric measurements. This early work to
demonstrate the ability to model the breast architecture in a 3D model for volumetric assessment
pushed the possibilities of surgical planning, ultimately leading to virtual surgery and 3D modelling
7.5 Three-Dimensional Breast plan for surgeries and assess post-operative out-
Imaging comes. As a planning tool, 3D-SI can predict
what can be achieved with augmentation by pre-
Alongside the use of MRI, 3D laser scanners dicting the estimated breast implant volume
showed promise for volumetric measurements of (EBIV) [16]. This can help patients and surgeons
the breast. Losken et al. provided an early evalua- predict the ideal size and shape of an implant. It
tion of 3D surface imaging (3D-SI) of the breast to can also help surgeons achieve better symmetry
determine its utility and reliability in mammomet- in breast reductions. More recently, the PICTURE
rics and volume calculations [15]. While 3D-SI project has used 3D imaging to predict breast
was primarily used for facial anthropometrics, it appearance after a breast-conserving surgery to
began to be used as a tool for breast s urgery in the help educate patients and tailor expectations
early 2000s [16]. Following the early assessments [16]. Also, 3D-SI can assess outcomes of surgery
of 3D imaging in breast surgery, hundreds of stud- by evaluating symmetry in breast augmentation
ies were later conducted to assess its reliability and and reduction, monitor breast changes over time,
superiority over other breast measurement meth- and determine the retention of fat grafting. In
ods. As investigated in this landmark paper, and research, 3D-SI can also objectively compare the
validated in other studies, 3D-SI has shown a high aesthetic outcome of one procedure with another,
level of precision and reliability in determining such as comparing different breast reduction
breast volumes and anthropomorphic measure- techniques [16].
ments. In the study, 19 breasts were measured Losken et al. opened the door to many other
using 3dMD Torso technology with 12 cameras to studies investigating 3D-SI in breast surgery;
image the breast, which was compared with however, the tool has yet to become a standard in
anthropometric measurements and the water dis- clinical practice. While it offers a fast and accu-
placement technique. Their findings showed high rate measurement of breast shape, volume, and
interrater agreement along with accurate and anthropometrics, it remains expensive and bulky.
reproducible breast measurements. While limited Furthermore, 3D-SI requires training, frequent
by its ability to predict the boundary of the chest calibration, and consistent lighting to give accu-
wall, 3D-SI has shown consistent, and often supe- rate measurements. Nonetheless, through studies
rior, results when compared to other methods. such as Losken et al., 3D-SI has proven to be a
Further studies elucidated 3D-SI’s ability to calcu- promising tool in research and clinical practice
late breast symmetry and shape, providing objec- for breast surgery. As 3D imaging becomes less
tive scores on the aesthetics of the breast [16]. expensive and more portable, it may become
Regarding the clinical utility of 3D-SI, studies more common for objective evaluation and pre-
following Losken et al. used the technology to diction of breast outcomes in aesthetic surgery.
Losken A, Seify H, Denson DD, Paredes AA, Carlson GW. Validating three-dimensional imaging of the breast. Ann
Plast Surg. 2005;54(5):471–6. discussion 477–478
Strengths • First application of 3dMD Torso technology to take volumetric measurements of the breast
• Comparative study between traditional methods and 3D imaging that shows reproducible and
reliable results
Limitations • Limited sample size
• Difficulty measuring large and ptotic breasts
Impact While the sample size was limited, the study was the first to utilize 3D technology for novel surgical
planning and assessment of post-operative outcomes, suggesting a more systematic and reproducible
way to monitor breast changes and perform anthropometric and volumetric analysis
7.6 Evaluating Skin-Flap concepts: (1) the decreasing distal perfusion of

Perfusion with Indocyanine axial-pattern flaps and (2) the utility in delaying a
Green Videoangiography flap to improve vascular efficiency. While postu-
lating that ICG angiography overpredicts the risk
Necrosis after a flap placement can be a devastat- of secondary healing, it was demonstrated that
ing complication in breast reconstruction. The ICG angiography is a valuable tool to reduce the
application of ICG imaging microsurgery in risk of skin necrosis in these flaps.
2002 by Holm et al. was impactful because it More recent evidence shows that ICG angi-
added a new tool to reduce the risk of skin flap ography has been used to evaluate perfusion in
complications post-operatively [17]. Prior to a variety of settings including microsurgical
ICG, methods such as thermography, capillary flaps and mastectomy skin flaps and has a sen-
refill, wound edge bleeding, photospectrometry, sitivity ranging from 80% to 100%, and speci-
and Doppler were used to evaluate the perfusion ficity ranging from 70% to 100%. [21] While it
of post-operative flaps. In 1994, Rübben et al. was initially slow to incorporate for routine use
demonstrated ICG as a technique to measure skin among surgeons, its popularity has grown sig-
perfusion in a rat cutaneous flap model with clin- nificantly in recent years. Development of
ical application in several patients with perfusion objective metrics continue to be optimized,
complications [18]. This was later applied to skin with development of clear cutoff values for
flap evaluation in 1999 by Still et al., showing its intraoperatively risk assessment [21]. As a
potential in predicting the success of surgical result, the introduction of ICG angiography has
flaps post-operatively [19]. changed the way microsurgeons assess skin
Holm et al. was the first study to confirm the flap viability, greatly reducing the risk of flap
use of ICG angiography for the evaluation of free failure and healing complications. It therefore
flap perfusion intraoperatively as a predictor of has allowed for safer and more predictable
secondary wound complication. Since its intro- autologous breast reconstructions. The discov-
duction in 2002, ICG angiography has frequently eries of ICG angiography continues to propel
been tested and utilized in determining flap per- the field of breast reconstruction forward, as it
fusion during surgery [20]. In this landmark not only has implications in predicting postop-
study, 15 flaps were evaluated intraoperatively erative complications in autologous reconstruc-
using ICG laser-induced fluorescence. ICG fill- tion, but its implant-based reconstruction as
ing defects were mapped and compared to well [22]. Due to its cost-effectiveness, ICG
secondary-wound complications 1 week postop- angiography has become an integral component
eratively. The study demonstrated that ICG fill- of imaging in breast reconstruction and will
ing defects consistently predict delayed wound likely continue to play a leading role in recon-
healing. The study also verified two important structive surgery.
Holm C, Mayr M, Höfter E, Becker A, Pfeiffer UJ, Mühlbauer W. Intraoperative evaluation of skin-flap viability
using laser induced fluorescence of indocyanine green. Br J Plast Surg. 2002;55(8):635–44
Strengths • Highly detailed and descriptive analysis of skin flap perfusion with follow-up evaluation
• Blind to the surgeon to accurately evaluate the predictability of ICG fluorescence in secondary
wound healing
Limitations • A limited sample size was used with no control group
Impact The study represents the first application of ICG fluorescence for the evaluation of skin perfusion in
skin flaps intraoperatively. This paper has led to a large body of literature examining perfusion with
this imaging technique in microsurgical, pedicled, and random flaps to reduce the risk of partial flap
loss and necrosis, which improved post-surgical outcomes in breast reconstruction
4. Di Benedetto G, Cecchini S, Grassetti L, et al.

7.7 Expert Concluding Comparative study of breast implant rupture using
Commentary mammography, sonography, and magnetic resonance
imaging: correlation with surgical findings. Breast J.
2008;14(6):532–7.
The modernization of technology and discovery 5. Cher DJ, Conwell JA, Mandel JS. MRI for detecting
of breast imaging techniques in plastic surgery silicone breast implant rupture: meta-analysis and
has pushed the field forward tremendously. This implications. Ann Plast Surg. 2001;47(4):367.
6. Veber M, Tourasse C, Toussoun G, Moutran M,
chapter assessed the most cited imaging-related Mojallal A, Delay E. Radiographic findings after
articles that have contributed to present-day prac- breast augmentation by autologous fat transfer. Plast
tices in breast surgery. Although the chapter is Reconstr Surg. 2011;127(3):1289–99.
not comprehensive, it highlights the role of vari- 7. Huch RA, Künzi W, Debatin JF, Wiesner W, Krestin
GP. MR imaging of the augmented breast. Eur Radiol.
ous imaging modalities in breast reconstruction, 1998;8(3):371–6.
including 3D imaging, monitoring of complica- 8. Herborn CU, Marincek B, Erfmann D, et al. Breast
tions, and perfusion mapping. While there are augmentation and reconstructive surgery: MR imag-
other important breast imaging modalities and ing of implant rupture and malignancy. Eur Radiol.
2002;12(9):2198–206.
landmark papers from the field not included in 9. Fiaschetti V, Pistolese CA, Fornari M, et al.
this chapter, we summarized the most cited Magnetic resonance imaging and ultrasound evalu-
imaging- related topics within plastic surgery ation after breast autologous fat grafting combined
with the most impactful contributions over recent with platelet-rich plasma. Plast Reconstr Surg.
2013;132(4):498e–509e.
decades. The role of imaging is critical in breast 10. Rha EY, Choi IK, Yoo G. Accuracy of the method for
surgery, and as technologies continue to advance, estimating breast volume on three-dimensional simu-
the use of imaging will continue to improve our lated magnetic resonance imaging scans in breast
surgical techniques and outcomes for breast reconstruction. Plast Reconstr Surg. 2014;133(1):14.
11. Fowler PA, Casey CE, Cameron GG, Foster MA,
reconstruction patients. Knight CH. Cyclic changes in composition and vol-
ume of the breast during the menstrual cycle, mea-
sured by magnetic resonance imaging. BJOG Int J
References Obstet Gynaecol. 1990;97(7):595–602.
12. Chae MP, Rozen WM, Spychal RT, Hunter-Smith
DJ. Breast volumetric analysis for aesthetic planning
1. Ahn CY, Shaw WW, Narayanan K, et al. Definitive in breast reconstruction: a literature review of tech-
diagnosis of breast implant rupture using mag- niques. Gland Surg. 2016;5(2):212–26.
netic resonance imaging. Plast Reconstr Surg. 13. De la Cruz-Ku G, Mallouh MP, Torres Roman
1993;92(4):681–91. JS, Linshaw D. Three-dimensional virtual real-
2. Ahn CY, DeBruhl ND, Gorczyca DP, Shaw WW, ity in surgical planning for breast cancer with
Bassett LW. Comparative silicone breast implant reconstruction. SAGE Open Med Case Rep.
evaluation using mammography, sonography, and 2023;11:2050313X231179299.
magnetic resonance imaging: experience with 59 14. Girard N, Gaillard T, Darrigues L, et al. Breast MRI
implants. Plast Reconstr Surg. 1994;94(5):620. analysis for surgeons using virtual reality: real-life
3. Juanpere S, Perez E, Huc O, Motos N, Pont J, Pedraza applications, clinical case reports. Surg Case Rep.
S. Imaging of breast implants—a pictorial review. 2022;2022(10):1–4.
Insights Imaging. 2011;2(6):653–70.
15. Losken A, Seify H, Denson DD, Paredes AA, Carlson using laser-induced fluorescence of indocyanine
GW. Validating three-dimensional imaging of the green. Ann Plast Surg. 1999;42(3):266–74.
breast. Ann Plast Surg. 2005;54(5):471–6.; discussion 20. Bigdeli AK, Thomas B, Falkner F, Gazyakan E,
477–478. Hirche C, Kneser U. The impact of indocyanine-green
16. O’Connell RL, Stevens RJG, Harris PA, Rusby fluorescence angiography on intraoperative decision-
JE. Review of three-dimensional (3D) surface imag- making and postoperative outcome in free flap sur-
ing for oncoplastic, reconstructive and aesthetic breast gery. J Reconstr Microsurg. 2020;36(08):556–66.
surgery—ClinicalKey. Breast. 2015;24(4):331–42. 21. Driessen C, Arnardottir TH, Lorenzo AR, Mani
17. Holm C, Mayr M, Höfter E, Becker A, Pfeiffer UJ, MR. How should indocyanine green dye angiog-
Mühlbauer W. Intraoperative evaluation of skin-flap raphy be assessed to best predict mastectomy skin
viability using laser-induced fluorescence of indocya- flap necrosis? A systematic review. J Plast Reconstr
nine green. Br J Plast Surg. 2002;55(8):635–44. Aesthet Surg. 2020;73(6):1031–42.
18. Rübben A, Eren S, Krein R, Younossi H, Böhler U, 22. Johnson AC, Colakoglu S, Chong TW, Mathes
Wienert V. Infrared videoangiofluorography of the DW. Indocyanine green angiography in breast
skin with Indocyanine green—rat random cutane- reconstruction: utility, limitations, and search for
ous flap model and results in man. Microvasc Res. standardization. Plast Reconstr Surg Glob Open.
1994;47(2):240–51. 2020;8(3):e2694.
19. Still J, Law E, Dawson J, Bracci S, Island T, Holtz
J. Evaluation of the circulation of reconstructive flaps
Evolution of Imaging in Flap
Reconstruction
8
Jeremy M. Sun and Takumi Yamamoto
Abstract Landmark Papers

Duplex Ultrasound
This chapter aims to discuss the evolution of
1. Rand RP, Cramer MM, Strandness DE Jr.
imaging in flap reconstruction using six key
Color-flow duplex scanning in the pre-opera-
landmark papers in three chosen imaging
tive assessment of TRAM flap perforators: a
modalities. These are computed tomography
report of 32 consecutive patients. Plast
angiography, duplex ultrasound, and indocya-
Reconstr Surg. 1994;93(3):453–9.
nine green angiography. While these modali-
2. Blondeel PN, Beyens G, Verhaeghe R, Van
ties have been used for many years in other
Landuyt K, Tonnard P, Monstrey SJ, Matton G.
fields before their adoption in plastic surgery,
Doppler flow metry in the planning of perfora-
these papers mark the birth and development
tor flaps. Br J Plast Surg. 1998;51(3):202–9.
of concepts that are now fundamental and
widely used in reconstructive flap surgery.
Computer Tomography Angiography
Papers that have expanded on their indications
3. Nagler RM, Braun J, Daitzman M, Laufer D.
and improved their efficacies are also cited in
Spiral CT angiography: an alternative vascu-
this paper so that surgeons get a more compre-
lar evaluation technique for head and neck
hensive overview of each option.
microvascular reconstruction. Plast Reconstr
Surg. 1997;100(7):1697–702.
Keywords
4. Masia J, Clavero JA, Larrañaga JR, Alomar X,
Imaging in flap reconstruction · Computed Pons G, Serret P. Multidetector-row computed
tomography (CT) angiography · Indocyanine tomography in the planning of abdominal per-
green (ICG) angiography · Duplex ultrasound forator flaps. J Plast Reconstr Aesthet Surg.
2006;59(6):594–9.
Indocyanine Green Angiography

5. Eren S, Rübben A, Krein R, Larkin G, Hettich
J. M. Sun
R. Assessment of microcirculation of an axial
Changi General Hospital, Singapore, Singapore
skin flap using indocyanine green fluores-
T. Yamamoto (*)
cence angiography. Plast Reconstr Surg.
National Centre for Global Health and Medicine,
Tokyo, Japan 1995;96(7):1636–49.

https://doi.org/10.1007/978-3-031-57132-9_8
64 J. M. Sun and T. Yamamoto
6. Holm C, Mayr M, Höfter E, Becker A, Pfeiffer a detailed map of dominant perforating blood
UJ, Mühlbauer W. Intraoperative evaluation of vessels, which arborized to form the principal
skin-flap viability using laser-induced fluores- vascular supply of the overlying soft tissue. This
cence of indocyanine green. Br J Plast Surg. discovery marked the era of the perforator flaps
2002;55(8):635–44. and the arrival of the age of imaging in flap
reconstruction.
Surgeons realized that to perform consistent
8.1 Introduction and effective flap reconstruction, they required
pre-operative information on the vascular anat-
The history of flap reconstruction begins in early omy, which has a high degree of individual vari-
antiquity, stretching back to 600 BC. This was ability. The handheld pen Doppler was a simple
the time of Sushruta, the great surgeon of ancient way to acquire basic knowledge about perforator
India who performed Rhinoplasty using random location [4]. However, there can be false positives,
pattern flaps [1]. His intimate knowledge of anat- and the most considerable disadvantage is the
omy helped him innovate through his surgery. inability to select dominant perforators based on
The main surgical text of the Vedas described his size, vessel course, and arborization pattern. This
method of understanding the human anatomy. book chapter aims to discuss the evolution of
Sushruta would submerge a cadaver in water and imaging in flap reconstruction since the handheld
allow it to decompose. Examining the decompos- Doppler through six key landmark papers in three
ing body at regular intervals allowed him to study chosen imaging modalities. They are computed
the structures layer by layer as they got exposed. tomography angiography, ultrasound duplex, and
The need to perform better and more efficient indocyanine green fluoroscopy. These six land-
flap reconstruction spurred our desire to investi- mark papers consist of the modality’s first descrip-
gate the anatomy of cutaneous and soft tissue tion in reconstructive flap surgery and the most
micro-circulation. French anatomist Michael cited paper, which aided in advancing the concept
Salmon advanced our understanding in 1936 and into its current popular form. To give our readers a
showed small blood vessels in great detail more comprehensive overview of each option, we
through intra-arterial injection of radio-opaque have included other references that have expanded
material [2]. The level of detail shown was much their initial indications and improved their effi-
more significant than his predecessors and also cacy. In our closing remarks, we will summarize
served as the foundation for the angiosome the- the pros and cons of each imaging tool for easy
ory described by Ian Taylor [3]. Taylor provided reference and understanding.
8.2 Duplex Ultrasound

Rand RP, Cramer MM, Strandness DE Jr. Color-flow duplex scanning in the pre-operative assessment of TRAM flap
perforators: a report of 32 consecutive patients. Plast Reconstr Surg. 1994;93(3):453–9
Strengths • The paper provides clear documentation of the technique used to localize perforators
Limitations • No control data to provide comparisons
Impact First large series paper to use duplex ultrasonography in the mapping of abdomen perforators for
abdominal-based breast reconstruction
In the late 1930s, Karl Theodore Dussik, a diagnosing breast, biliary tract, pancreatic, and
neurologist, was credited for being one of the first thyroid disease [5]. In 1994, duplex ultrasound
in medicine to utilize ultrasonography. It was not scanning was reported for the first time in the
until the 1970s that technological advances cul- Plastic Reconstructive Surgery literature. Chang
minated in the widespread use of ultrasound in et al. would show in a case report the feasibility
8 Evolution of Imaging in Flap Reconstruction 65
of using the two-dimensional color Doppler probe cranially on each side, tracing the course of
probe for imaging the periumbilical vascular per- the DIEA and noting the positions and character-
forators in the transverse rectus abdominis myo- istics of each perforator. In addition to publishing
cutaneous (TRAM) flap [6]. Shortly after, Rand his scanning technique, Rand made several
et al. published a paper about using color-flow important observations:
duplex scanning in the pre-operative assessment
of deep inferior epigastric artery (DIEA) and 1. Standard B mode could not visualize small
superior epigastric artery (SEA) perforators. perforators, so color duplex scans were used
In his study of 32 consecutive patients sched- to visualize vessels even less than 1 mm.
uled for TRAM flap surgery, he used duplex 2. Rand provided his guide to flow velocities
ultrasonography (DUS) to map out the perfora- within the perforator and advocated selecting
tors in the peri-umbilical region. His technique three perforators with more than 20 cm/s for a
described in the paper would lay the groundwork single pedicled flap. A peak flow velocity of
for future applications of duplex ultrasonography 20 cm/s would serve as a reference point for
in pre-operative flap planning. The duplex scan what would be considered one of the charac-
commenced with the identification of the deep teristics of dominant perforators.
inferior epigastric artery. The artery was then 3. Pre-operative duplex ultrasonography allowed
traced superiorly until the first perforator was adjustment of the flap design to ensure cen-
detected. Arterial perforators were identified by tralization of the perforator.
pulsatile vessels with consistent red or blue 4. Pre-operative duplex ultrasonography modi-
streaks on the Doppler screen. Peak systolic flow fied flap elevation techniques as “dominant”
velocities and arterial waveform analyzes were perforators can be selected and zoomed in
then recorded. The authors would then move the during dissection.
Blondeel PN, Beyens G, Verhaeghe R, Van Landuyt K, Tonnard P, Monstrey SJ, Matton G. Doppler flow metry in
the planning of perforator flaps. Br J Plast Surg. 1998;51(3):202–9
Strengths • Comparisons of different modalities were used. Modality was used for different flaps
demonstrating its wide-ranging application
Limitations • Protocol was not standardized across different types of imaging modalities
Impact Most cited paper on duplex ultrasound used in pre-operative planning of perforator flaps
Blondeel et al.’s paper is the most cited DUS Advantages

article in Plastic Reconstructive literature. This 1. Inexpensive.
represented the point where utilizing this modal- 2. Widely available.
ity in flap reconstruction started becoming popu- 3. Interchangeable probes for superficial
lar. The paper described the use of DUS in the scanning.
pre-operative mapping of perforators in 50 con- 4. User-friendly.
secutive deep inferior epigastric artery perforator
(DIEP) flaps. This was compared with the use of Disadvantages
a handheld pen Doppler (HHD) in mapping 30 1. It does not distinguish perforators from main
superior gluteal artery perforators (SGAP) flaps axial vessels, creating false positive
and 11 thoracodorsal artery perforators (TAP) localization.
flaps. 2. No information on its three-dimensional course.
The paper described the advantages and disad- 3. Semi-quantitative analysis of the caliber and
vantages of the HHD: flow.
Fig. 8.1 Top chart

shows the mean peak
flow velocities in the
internal mammary artery
(IMA), main deep
inferior epigastric artery
(DIEA), medial and
lateral branches of the
DIEA, perforators of the
DIEA larger than
0.5 mm, and perforators
of the DIEA at the
tendinous intersection
(TI). The bottom chart
shows the corresponding
size variations of these
vessels
The high false positive rate of the HHD was insight into the usefulness of DUS and its bene-
the primary motivation for transitioning to fits in planning perforator flaps.
DUS. The group preferred the usage of the DUS Similar to the paper by Rand et al., the authors
in planning DIEP and TAP flaps due to the investigated the peak systolic flow velocities and
variable vascular anatomy of the lower abdomi- vessel diameter (Fig. 8.1) of the abdominal perfo-
nal and dorso-lateral thoracic walls. The more rators, main DIEA, dominant DIEA branch, and
constant course of the superior gluteal artery internal mammary artery (IMA). The paper did
allowed the use of the cheaper HHD to plan the not mention the minimum flow velocity value
SGAP flap. These recommendations were based one should aim for when choosing perforators
on each modality’s sensitivity and positive pre- but from their quantitative data, the mean peak
dictive values (PPV). DUS in DIEP flaps had a velocities of the chosen DIEA perforators were
sensitivity of 96.2% and a PPV of 100%, while all above 20 cm/s.
HHD in the SGAP flap had comparable sensitiv- Blondeel et al. concluded that although the
ity and PPV of 80.6% and 91.9%, respectively. DUS took additional time to perform and incurred
Usage of the HHD was abandoned in TAP flaps extra costs, the benefits made it an indispensable
after the first six cases due to the high level of diagnostic tool in planning DIEP flaps. These
false positive and false negative signals. While benefits include the precise mapping of the DIEA
the paper did not provide a direct comparison of and its perforators, allowing surgeons to reduce
the sensitivities and PPV of DUS and HHD for intra-operative stress and streamline the decision-
each type of flap, the group’s work did provide making process.
8.3 The Present State of DUS ing curve and availability of machines. In lym-
in Flap Reconstruction phatic surgery, ultrasound and DUS have proven
reliable in identifying lymphatic and venules for
The papers from Rand et al. and Blondeel et al. lymphovenous anastomosis.
provided the foundations for current applica- With the current resurgence of interest and
tions of DUS. As perforator flaps become thin- expanding use-case of DUS and ultrasound tech-
ner, the need for precise real-time information nology in reconstructive flap surgery, it is no
about the perforator’s location in the subcutis wonder that it is now regarded as the reconstruc-
becomes greater. To harvest super-thin, ultra- tive surgeon’s stethoscope [11].
thin, or even pure skin perforator flaps [7], the
surgeon needs to know the point at which the
perforator pierces the superficial fascia and 8.4 Computed Tomography
enters the dermis. With the advent of high-fre- Angiography
quency and ultra-high- frequency ultrasound
technology, visualization of vessels with small Through the marriage of spiral computed tomog-
diameters <0.5 mm is possible. These cutting- raphy (CT) and graphical volumetric image pro-
edge ultrasound machines make raising such cessing, CT angiography (CTA) was born more
flaps safe and effective [8]. than 20 years ago. CTA quickly overtook conven-
With the popularization of super-microsurgery, tional angiography to be the diagnostic standard
surgeons aim for a “perforator to perforator” for characterizing vascular anatomy [12].
style of anastomosis to limit the amount of col- Spiral CT technology allowed radiologist to
lateral damage when dissecting the recipient ves- move away from the traditional “step and shoot”
sels [9]. DUS becomes an integral part of method of image acquisition to the continuous
pre-operative planning in not only choosing the acquisition of projections during table travel.
flap perforator but also the recipient perforators. This covered much larger volumes of data per
Yoshida et al. found that the rate of successful unit time. Subsequently, the advancement of
dissection of recipient perforators was the high- detector technology from single-detector to
est for perforators with a peak systolic flow multi-detector row scanners increased the vol-
velocity of ≥20 cm/s [10]. ume of coverage, improved spatial resolution to
DUS has also expanded beyond the boundar- the submillimeter scale, and quickened the scan
ies of pre-operative mapping of the vascular time. It was a tremendous leap forward as multi-
anatomy. While some surgeons use it for post- detector CT scanners can now have as many as
operative monitoring of flaps, this has yet to 320-detector rings, up from the 4-detector rings
become standard practice due to the steep learn- initially introduced in 1998 [13].
Nagler RM, Braun J, Daitzman M, Laufer D. Spiral CT angiography: an alternative vascular evaluation technique
for head and neck microvascular reconstruction. Plast Reconstr Surg. 1997;100(7):1697–702
Strengths • Clear demonstration of the benefits of CTA with comparison to digital subtraction
angiography
Limitations • Small study numbers
Impact First paper in the plastic reconstructive literature to document the use of spiral CT technology to
survey the recipient site vessels for free microvascular flap reconstruction. It was able to show
detailed information about the size and location of the perforator in relation to critical anatomical
landmarks. The resolution is still not high enough to visualize small perforators
In the Plastic Reconstructive literature, Nagler improvement over traditional angiography for
et al. were the first to report the use of CTA in flap several reasons:
reconstruction. Although the paper was published
before the advent of multi-detector row CT scan- 1. Spiral CTA is less time-consuming compared
ners, it set the stage by demonstrating its effec- to traditional angiography.
tiveness in mapping the size and location of small 2. Spiral CTA is noninvasive and avoids the need
arterial branches. This use would eventually for arterial canalization.
translate to the mapping of perforators in our sec- 3. Dense calcifications can cause misregistration
ond landmark paper. artifacts when digital subtraction angiography
The authors described using spiral CTA and is used.
conventional digital subtraction angiography in 4. Critical anatomical landmarks such as bones,
the microvascular reconstruction of head and veins, and cartilaginous structures can be left
neck defects. Ten external carotid arteries in in the CTA data set to provide reference points
five patients were studied pre-operatively. Four for surgeons to locate vessels of interest.
patients had undergone partial mandibulec- 5. CTA images can be reconstructed to give a
tomy, and one had extensive trauma and lacera- three-dimensional view. The images can then
tion of the temporalis muscle and skin on the be rotated to obtain the best view of any vessel
left side. CTA and conventional angiography in question.
were used to survey the external carotid 6. CTA has less dependence on the operator’s
branches for use as recipient vessels during free skill than conventional angiography.
tissue transfer.
Spiral CT angiography strongly correlated Spiral CTA presented a compelling case for
with digital subtraction angiography in their case recipient vessel survey and represented an evolu-
series. Two independent experts examined the tion from conventional angiography. The intro-
images gathered by the two modalities and duction of multi-detector row technology would
reported similar findings. The authors of the further seal the role of CTA as the most popular
study opined that CTA represented a significant form of imaging in flap surgery today.
Masia J, Clavero JA, Larrañaga JR, Alomar X, Pons G, Serret P. Multidetector-row computed tomography in the
planning of abdominal perforator flaps. J Plast Reconstr Aesthet Surg. 2006;59(6):594–9
Strengths • Comparative study in a large number of patients
Limitations • Publication limited to DIEP flaps with little quantitative analysis
Impact Most cited paper published on the use of CTA for precisely mapping abdominal perforators for
breast reconstruction
Masia et al. published the most cited article on gist and a plastic surgeon. The DIEA was traced
CTA and flap surgery in 2006. The authors used a from its origin, through the muscle, to 5 cm cra-
16-detector row CT scanner with non-ionic iodin- nial of the umbilicus. The three largest perfora-
ated contrast to obtain the angiogram. Sections tors on each side were marked on the abdomen
were obtained from 5 cm above the umbilicus to and classified based on their external caliber into
the lesser trochanter of the hip during a single three categories (small, medium, and large). The
breath hold. The image acquisition was less than superficial inferior epigastric artery (SIEA) was
15 seconds and the whole procedure took less also studied to examine its size and feasibility to
than 10 min. The volumetric data was then used be used for harvesting an SIEA flap. This proto-
to reconstruct images with a slice width of 1 mm col was completed in 66 consecutive DIEP flap
and a reconstruction interval of 0.8 mm. patients. CTA findings, HHD findings, and intra-
Assessment of the image was done by a radiolo- operative perforator findings were compared.
In addition to obtaining information about osteo-cutaneous fibular flaps modeled from CTA
perforator distribution, intra-muscular course, images [18] are just some of the tools reconstruc-
and branching anatomy, the authors found no tive surgeons now have at their disposal.
false positive or false negative results when cor- Although most of the CTA literature in flap
relating CTA-confirmed perforator locations with surgery centers around breast reconstruction,
intra-operative findings. They did mention that there is increasing application in more exotic
the group missed one good perforator on CTA in flaps such as gluteal artery perforator flaps, SIEA
an early case. This demonstrates that even for flaps, internal mammary artery perforator flaps,
CTA, a learning curve is required to interpret the posterior interosseous artery flaps, and thora-
images accurately. Precise pre-operative map- codorsal flaps [19]. CTA will likely remain the
ping of the perforator translated to tangible ben- imaging modality of choice for reconstructive
efits for the group: surgeons for many years to come.
1. There was an average operative time savings

of 1 h and 40 min per patient. 8.6 Indocyanine Green
2. There were reduced flap failure (0 vs. 1) and Angiography
partial necrosis (1 vs. 2) numbers in the last
30 patients who underwent CTA pre-operative Indocyanine green (ICG) is an anionic tricarbo-
planning vs. the last 30 patients who did not. cyanine molecule with fluorescent properties
when exposed to excitation light of 750–800 nm
The group concluded that CTA has a high sen- wavelengths. It was developed during the Second
sitivity, specificity, and a 100% positive predic- World War by Kodak Research Laboratories as a
tive value. Numerous studies have echoed similar dye for photoimaging. Following the approval by
findings since [14]. the United States Food and Drug Administration
in 1959, ICG was primarily used in hepatic func-
tion diagnostics. Its low toxicity and spectral
8.5 The Present State of CTA properties were the primary drivers that led to its
in Flap Reconstruction widespread application in nephrology, ophthal-
mology, cardiology, and now plastic surgery.
One of the main disadvantages of CTA is patients’ However, ICG is not the first fluorescent imaging
exposure to ionizing radiation. However, in technique used to assess microcirculation. In
recent years, radiologists have devised ways to 1962, Myers et al. used sodium fluorescein in
reduce radiation dosage while retaining much of reconstructive surgeries to predict skin necrosis
the image quality [15]. Another disadvantage by differentiating fluorescent and non-fluorescent
cited is the cost involved with performing the areas [20]. Thereafter, the development of dermo-
examination. As a result, several groups per- fluorometry allowed the quantification of the
formed cost-benefit analysis, which demon- intensity. Its pharmacokinetic properties would
strated cost savings from using CTA for ultimately prevent this method from being further
pre-operative planning [16]. This is attributed to established in clinical practice. Fluorescein dif-
the reduced hospital stay, complications, and the fused readily into the interstitium and had a lon-
decreased operation time that offered more sav- ger half-life, making serial examinations difficult.
ings than the price of the scan itself. Fluorescein is also known to underestimate skin
Branching out from traditional CTA applica- flap survival, and this effect is most pronounced
tions are various pre-operative planning methods when the injection is done soon after raising the
that are slowly gaining acceptance in reconstruc- skin flap [21].
tive practices worldwide. Methods such as aug- In contrast, ICG binds rapidly to plasma
mented reality for extremity reconstruction [17] proteins and stays intravasal with minimal
and printing three-dimensional cutting guides for leakage into the interstitial space. It also under-
goes biphasic plasma clearance, with more reconstruction, and we will discuss its evolu-
than 90% of the dye eliminated in the first tion beginning with the first landmark paper,
phase. This rapid elimination makes time-ori- which described its use in flap perfusion, and a
ented analysis of skin perfusion more likely second landmark paper which is one of the ear-
than fluorescein. ICG angiography (ICG-A) is lier, most cited clinical article on ICG-A and
a relatively newer imaging modality for flap flap reconstruction.
Eren S, Rübben A, Krein R, Larkin G, Hettich R. Assessment of microcirculation of an axial skin flap using
indocyanine green fluorescence angiography. Plast Reconstr Surg. 1995;96(7):1636–49
Strengths • Simple and effective study design. Attempts made to produce quantitative data for analysis
Limitations • Much effort was spent to generate quantitative data on influx and efflux flow dynamics but the
group was unable to assign any clinical significance to it due to the small numbers
Impact First paper published on ICG in the reconstructive flap literature
CTA and DUS have dominated imaging in pre- based on the left inferior epigastric neurovascular
operative flap planning. However, the need for bundle with 2 × 8 cm2 dimensions. The flaps
radiation for CTA and the relatively high learning would then be returned to their wound beds with
curve for DUS presented an opportunity for other collagen sheets sutured on to prevent revascular-
modalities to fill the void for intra-operative imag- ization and healing. The right femoral vein was
ing. In 1995, Eren et al. published the first paper punctured for injection of ICG at a dosage of
on using ICG to assess tissue microcirculation in 0.5 mg/kg of body weight. The specimens were
an experimental model that will inspire numerous divided into two groups for observation via
applications in the flap reconstructive world. The ICG-A on different days. The group devised a
group proposed that ICG-A would overcome formula to calculate the time course in seconds
some of the disadvantages inherent to clinical for the mean intensity to be acquired. The specif-
examination, thermography, laser Doppler flow- ics of this formula would be beyond the scope of
meter, and fluorescein dermo-fluorometry. this discussion.
In their experimental model, seven Sprague- The angiography and image processing meth-
Dawley rats had axial pattern skin flaps raised ods are highlighted in Fig. 8.2.
Fig. 8.2 A 2000-W

halogen lamp (1) with
an 850 nm long pass
barrier filter (3) and a
heat-dissipating water
filter (2) was used to
excite the ICG. A
charge-coupled device
camera (6) with a
750 nm excitation filter
(5) would be used to
capture the fluorescent
signal, which was then
entered into a digital
image processing unit
(7, 8)
The authors of the study classified the ICG viable in all animals, and this correlated with
flow into two distinct phases: the influx and the the fluorescence signal present in the most dis-
efflux phases. The influx phase shows the affer- tal portions of all flaps, albeit at a slower and
ent left inferior epigastric artery and the arboriza- lower intensity than the proximal portions.
tion pattern within 1–2 s. This short timing 2. Increasing vascularity (maximum signal
reflects the good macro-circulatory state of the intensity) in all flap zones was seen up to post-
study animals. The efflux phase showed different operative day 4, reflecting hemodynamic
structures, and this was hypothesized to show the homeostasis and delayed phenomenon.
venous system. Although the authors admitted 3. The quick influx and efflux of the dye enable
that the data related to the influx and efflux serial examinations.
dynamics would be challenging to interpret, there 4. ICG-A could show the flow dynamics within
were certain benefits to this study from the fol- the flap in real time.
lowing observations:
Although this experimental model involved a
1. Proof of concept that ICG-A demonstrates small number of specimens, it provided a sound
microcirculatory flow and hence was able to be basis for further developing ICG-A in flap recon-
used as a measure of perfusion. Skin flaps were structive surgery.
Holm C, Mayr M, Höfter E, Becker A, Pfeiffer UJ, Mühlbauer W. Intraoperative evaluation of skin-flap viability
using laser-induced fluorescence of indocyanine green. Br J Plast Surg. 2002;55(8):635–44
Strengths • Case series of different flaps used for different indications demonstrated the versatility of the
proposed imaging modality
Limitations • Case series with small numbers without any quantitative data
Impact One of the first highly cited clinical papers on ICG-A in free flaps
In reconstructing complex defects, distal por- ICG-A to assess perfusion of pedicled flaps and
tions of pedicled flaps are often used to cover free flaps [23]. Although both papers provided
critical portions of the wound. These distal por- excellent insights into the use of ICG in modern
tions are often the least perfused parts of the flap. day flap reconstruction, the paper on pedicled
Hence, surgeons have tried to use various modal- flaps was selected as our second ICG landmark
ities to assess tissue perfusion intra-operatively paper due to its higher citation.
over time. While sodium fluorescein never caught Fifteen pedicled flaps were raised in 13
on, ICG, on the other hand, is taking the Plastic patients, including two groin flaps, three sural
Reconstructive world by storm. The experimental island flaps, three vertical rectus abdominis flaps,
study by Eren et al. sparked much interest, and one reversed radial forearm flap, and four random
the first clinical paper regarding flap reconstruc- patterned skin flaps. The indications for flap sur-
tion and ICG-A was published in 1999 by Still gery included tumor resection, trauma, sternal
et al. [22]. In their study, Still would report their osteomyelitis, and an upper limb soft tissue
ICG findings in 21 locoregional flaps primarily defect from extravasation. Intra-operative ICG-A
performed for burns reconstruction. The group was performed for all cases to assess tissue perfu-
concluded that ICG-A could accurately predict sion of the flaps. Regional tissue perfusion defi-
flap demarcation and poor wound healing by pro- cits were defined as signal intensities of less than
viding information about tissue perfusion when 60% of normal skin. These were detected in four
clinical examination appeared satisfactory. These flaps: one sural island flap, one lateral cheek rota-
were promising results, but no further clinical tion flap, and two vertical rectus abdominis flaps.
studies confirmed these initial results until 2002 These four flaps eventually developed different
where Holm et al. published two papers on using degrees of delayed wound healing, like flap
demarcation, epitheliolysis, and partial sloughing. not standardized and should not be interpreted
ICG-A accurately predicted the areas of poor in a clinical setting. Instead, the trend and
wound healing in two of these four flaps. The speed of fluorescence probably have more
other two flaps had less extensive clinical mani- clinical significance.
festations than the ICG-A filling defects. In a few
cases, the authors had to modify the pedicled Holm et al. [23] published another study with
flaps’ traditional length-to-breadth ratio to extend a similar design that same year. This time it was
the reach of the flap to cover the critical defect. examining the utility of ICG-A in free flaps. The
ICG-A managed to predict the viability of the real-time dynamic nature of ICG-A was able to
distal tips of axial and random pattern flaps. detect transient arterial spasm, assess the patency
ICG-A was also used to show the difference in of the microvascular anastomosis, and predict the
perfusion between delayed and non-delayed two cases of flap loss. In both studies, there were
flaps. In a patient where two reverse sural flaps no complications from ICG injection.
were raised, the delayed flap showed a signifi-
cantly higher perfusion index compared with the
non-delayed flap. 8.7 The Present State
In summary, the study demonstrated that: of Indocyanine Green
Angiography
1. ICG-A is a highly sensitive tool to detect
regional compromises of nutritive blood flow. ICG-A has undergone a great transformation
Utilization helped to predict poor wound heal- since the publishing of the two landmark papers.
ing. However, the filling defects shown on Many centers around the world would now con-
ICG-A overestimated the severity of clinical sider an indocyanine green near-infrared camera
manifestations. In half of the filling defects, essential in not only flap reconstruction but also,
only minor wound sloughing was encoun- more recently, lymphatic reconstruction.
tered, which healed secondarily. Surgical Intraoperative assessment of flap perfusion is
resection may not be indicated when filling the most common indication for ICA-A, and
defects are seen. perhaps one of the most well-utilized areas is
2. Utilizing ICG-A helped plan the dimensions breast reconstruction [24]. Many surgeons rou-
of pedicled axial or random pattern flaps. This tinely use ICG-A to assess the zones of perfu-
proved to be especially useful in instances sion in a DIEP flap and the viability of the
where length to breadth ratio needs to be mastectomy skin flap. The use of ICG-A in
pushed past its traditional 3:1 limits. autologous and prosthetic reconstruction has
3. ICG-A demonstrated the beneficial effects of since been proven to reduce total early compli-
flap delay, increasing the perfusion index by cations significantly [25].
two times. The use of ICG-A in pre-operative flap plan-
4. Software can be used to apply various over- ning is relatively limited. Authors such as Lida
lays, like false color representations, to the et al. have used ICG-A to mark out the vascular
image that the operator interprets. Absolute territory of the flap before the actual flap harvest
fluorescence values and color intensities are [26]. Pestana and Zenn did a comparative study
between CTA and ICG-A in pre-operative imag- 8.8 Expert Concluding

ing of DIEP flaps and found that the blush seen Commentary
on ICG-A did not correspond well with the perfo-
rator locations seen on CTA [27]. Its utility in There are numerous modalities used in imaging
perforator localization is probably limited as ICG for flap reconstruction. Modalities like magnetic
penetration is prevented by soft tissue thickness resonance angiography (MRA), laser Doppler
of more than 15 mm. In lymphatic reconstruc- perfusion imaging, and infrared thermography
tion, ICG lymphography is an indispensable are not discussed in this chapter. These technolo-
imaging tool for planning vascularized lymph gies have been around for some time, but their
node flaps [28] and lymphatic channel transfers acceptance in the community is limited due to
[29]. certain drawbacks. For example, although MRA
ICG has been shown to have low toxicity and does not expose the patient to radiation, its long
low rates of adverse reactions when administered study time, high cost, and propensity for move-
intravenously [30]. This, together with its ease of ment artifacts limit its clinical efficacy. In clos-
use, may be one of the reasons why applications ing, we would like to direct our readers to Fig. 8.3
of ICG fluoroscopy are increasing. With no signs for a quick reference chart of the pros and cons of
of slowing down, it would be interesting to see our top three imaging modalities in flap
how the landscape evolves in the next decade. reconstruction.
Duplex Computer Tomography Indocyanine green

Ultrasound Angiography angiography
Inter-operator ++ – +
variability
Learning curve ++ + –
Three-dimensional – + –
imaging
Use of radiation – + –
Invasiveness – Intravenous Intravenous
cannulation cannulation
Image of superficial ++ + ++
vessels and perforators
Image of deep vessels + ++ –
Ability to repeat the test + – ++
in short intervals
Information on + ++ –
surrounding tissues
Ease of intra-operative + – ++
usage
Dynamic real-time + – ++
perfusion scan
Cost + ++ +
Fig. 8.3 A quick reference guide to the various pros and cons for each of our chosen modalities
References 16. Uppal RS, Casaer B, Van Landuyt K, Blondeel P. The

efficacy of pre-operative mapping of perforators in
reducing operative times and complications in per-
1. Champaneria MC, Workman AD, Gupta
forator flap breast reconstruction. J Plast Reconstr
SC. Sushruta: father of plastic surgery. Ann Plast
Aesthet Surg. 2009;62(7):859–64.
Surg. 2014;73(1):2–7.
17. Pratt P, Ives M, Lawton G, Simmons J, Radev N,
2. Cormack GC, Lamberty BG. The arterial anatomy of
Spyropoulou L, Amiras D. Through the HoloLens™
skin flaps. Edinburgh: Churchill Livingstone; 1994.
looking glass: augmented reality for extremity recon-
3. Taylor GI, Palmer JH. The vascular territories (angio-
struction surgery using 3D vascular models with per-
somes) of the body: experimental study and clinical
forating vessels. Eur Radiol Exp. 2018;2(1):2.
applications. Br J Plast Surg. 1987;40(2):113–41.
18. Kirke DN, Owen RP, Carrao V, Miles BA, Kass
4. Aoyagi F, Fujino T, Ohshiro T. Detection of small ves-
JI. Using 3D computer planning for complex recon-
sels for microsurgery by a Doppler flowmeter. Plast
struction of mandibular defects. Cancers Head Neck.
Reconstr Surg. 1975;55(3):372–3.
2016;1:17.
5. Newman PG, Rozycki GS. The history of ultrasound.
19. Pratt GF, Rozen WM, Chubb D, Ashton MW, Alonso-
Surg Clin North Am. 1998;78(2):179–95.
Burgos A, Whitaker IS. Pre-operative imaging for
6. Chang BW, Luethke R, Berg WA, Hamper UM,
perforator flaps in reconstructive surgery: a system-
Manson PN. Two-dimensional color Doppler imaging
atic review of the evidence for current techniques.
for precision pre-operative mapping and size determi-
Ann Plast Surg. 2012;69(1):3–9.
nation of TRAM flap perforators. Plast Reconstr Surg.
20. Myers MB. Prediction of skin sloughs at the time of
1994;93(1):197–200.
operation with the use of fluorescein dye. Surgery.
7. Yamamoto T, Yamamoto N, Fuse Y, Kageyama T,
1962;51(2):158–62.
Sakai H, Tsukuura R. Subdermal dissection for
21. Odland RM, Poole DV, Lessard GM, Ehresman D,
elevation of pure skin perforator flaps and super-
Goding GS. Fluorescein and acidosis: implications
thin flaps: the dermis as a landmark for the most
for flap perfusion studies. Arch Otolaryngol Head
superficial dissection plane. Plast Reconstr Surg.
Neck Surg. 1992;118(7):712–6.
2021;147(3):470–8.
22. Still J, Law E, Dawson J, Bracci S, Island T, Holtz
8. Visconti G, Bianchi A, Hayashi A, Cina A, Maccauro
J. Evaluation of the circulation of reconstructive flaps
G, Almadori G, Salgarello M. Thin and super-thin
using laser-induced fluorescence of indocyanine
perforator flap elevation based on pre-operative plan-
green. Ann Plast Surg. 1999;42(3):266–74.
ning with ultrahigh-frequency ultrasound. Arch Plast
23. Holm C, Tegeler J, Mayr M, Becker A, Pfeiffer UJ,
Surg. 2020;47(4):365–70.
Mühlbauer W. Monitoring free flaps using laser-
9. Hong JP. The use of supermicrosurgery in lower
induced fluorescence of indocyanine green: a prelimi-
extremity reconstruction: the next step in evolution.
nary experience. Microsurgery. 2002;22(7):278–87.
24. Burnier P, Niddam J, Bosc R, Hersant B, Meningaud
10. Yoshida S, Koshima I, Imai H, Uchiki T, Sasaki A,
JP. Indocyanine green applications in plastic surgery:
Nagamatsu S, Yokota K. Investigation of flow velocity
a review of the literature. J Plast Reconstr Aesthet
in recipient perforator artery for a reliable indicator
Surg. 2017;70(6):814–27.
for the flap transfer with perforator to perforator anas-
25. Komorowska-Timek E, Gurtner GC. Intraoperative
tomosis. Microsurgery. 2021;41(6):550–6.
perfusion mapping with laser-assisted indocyanine
11. Hong JP. The color duplex ultrasound: the reconstruc-
green imaging can predict and prevent complications
tive surgeon’s stethoscope. J Reconstr Microsurg.
in immediate breast reconstruction. Plast Reconstr
2022;38(3):169.
Surg. 2010;125(4):1065–73.
12. Rubin GD, Leipsic J, Joseph Schoepf U, Fleischmann
26. Iida T, Mihara M, Yoshimatsu H, Narushima M,
D, Napel S. CT angiography after 20 years: a transfor-
Koshima I. Versatility of the superficial circumflex
mation in cardiovascular disease characterization con-
iliac artery perforator flap in head and neck recon-
tinues to advance. Radiology. 2014;271(3):633–52.
struction. Ann Plast Surg. 2014;72(3):332–6.
13. Rubin GD, Shiau MC, Leung AN, Kee ST, Logan
27. Pestana IA, Zenn MR. Correlation between abdomi-
LJ, Sofilos MC. Aorta and iliac arteries: single ver-
nal perforator vessels identified with pre-operative CT
sus multiple detector-row helical CT angiography.
angiography and intraoperative fluorescent angiogra-
Radiology. 2000;215(3):670–6.
phy in the microsurgical breast reconstruction patient.
14. Teunis T, Heerma van Voss MR, Kon M, van Maurik
Ann Plast Surg. 2014;72(6):S144–9.
JF. CT-angiography prior to DIEP flap breast recon-
28. Dayan JH, Dayan E, Smith ML. Reverse lymphatic
struction: a systematic review and meta-analysis.
mapping: a new technique for maximizing safety in
Microsurgery. 2013;33(6):496–502.
vascularized lymph node transfer. Plast Reconstr
15. Niumsawatt V, Debrotwir AN, Rozen WM.
Surg. 2015;135(1):277–85.
Reducing radiation dose without compromising
29. Yamamoto T, Yamamoto N, Kageyama T, Sakai H,
image quality in pre-operative perforator flap imag-
Fuse Y, Tsukuura R. Lymph-interpositional-flap
ing with CTA using ASIR technology. Int Surg.
transfer (LIFT) based on lymph-axiality concept:
2014;99(4):485–91.
simultaneous soft tissue and lymphatic reconstruc- 30. Reinhart MB, Huntington CR, Blair LJ, Heniford
tion without lymph node transfer or lymphatic BT, Augenstein VA. Indocyanine Green: Historical
anastomosis. J Plast Reconstr Aesthet Surg. 2021; Context, Current Applications, and Future Consid
74(10):2604–12. erations. Surg. Innov. 2016;23(2):166–75.
Evolution of Imaging
in Cranio-Maxillo-Facial Surgery
9
Abstract 3. Hounsfield GN. Computerized transverse

In the realm of craniofacial surgery, where pre- axial scanning (tomography). 1. Description
cision and innovation are paramount, the evolu- of system. Br J Radiol. 1973;46(552):1016–22.
tion of imaging technology has played a 4. Cutting C, et al. Three-dimensional com-
significant role in improving surgical outcomes. puter-assisted design of craniofacial surgical
Over the past century, a series of pioneering procedures: optimization and interaction
studies have laid the foundation for personal- with cephalometric and CT-based models.
ized and minimally invasive craniofacial surgi- Plast Reconstr Surg. 1986;77(6):877–87.
cal techniques. In this article, we found five 5. Burke PH, Beard FH. Stereophotogrammetry
landmark papers which guide the evolution of of the face: A preliminary investigation into
imaging in craniofacial surgery from the dis- the accuracy of a simplified system evolved
covery of X-rays to current technology. for contour mapping by photography. Am J
Orthod. 1967;53:769–82.
Keywords
9.1 Introduction
Imaging technology · Cranio-maxillo-facial ·
X-rays · Cephalometry · Computed tomogra-
The intricate nature of the craniofacial region
phy · 3D imaging · 3D scanners
presents unique challenges to surgeons, necessi-
tating a comprehensive understanding of under-
The Five Most Impactful Papers lying anatomy, pathology, and surgical nuances.
1. Röntgen WC. On a new kind of rays. Advancements in medical imaging have been
1896;3(59):227–31. instrumental in bridging this gap, providing sur-
2. Broadbent BH. A new X-ray technique and its geons with comprehensive, real-time insights
application to orthodontia. 1931;1(2):45–66. into patients’ unique craniofacial anatomy,
enabling precise preoperative planning, and facil-
itating better postoperative assessments.
Over the past century, a series of pioneering
research papers have laid the foundation for per-
J.-W. (JW) Choi (*) · Y. C. Kim sonalized and minimally invasive craniofacial
Department of Plastic and Reconstructive Surgery, surgical techniques. In this article, we found five
University of Ulsan College of Medicine, Asan landmark papers that have shaped the course of
Medical Center, Seoul, South Korea

https://doi.org/10.1007/978-3-031-57132-9_9
78 J.-W. (JW) Choi and Y. C. Kim
craniofacial imaging and its impact on surgical Roentgen’s rigorous experiments and obser-
practice. These papers have contributed signifi- vations led to significant advancements in X-ray
cantly to the field by introducing novel imaging technology. He presented his findings in a his-
techniques and offering data that have revolution- toric paper titled ““On a New Kind of Rays,” out-
ized craniofacial surgical interventions. lining 17 essential properties of X-rays [1]. The
scientific community quickly recognized the
importance of his discovery, and Roentgen’s
9.2 Discovery of the X-rays work received widespread acclaim and admira-
tion worldwide. His humble and selfless approach
The history of cranio-maxillofacial imaging to science was evident, as he chose not to capital-
began with Dr. Wilhelm Conrad Roentgen, who ize on his findings or patent X-rays.
accidentally discovered X-rays in 1895. While The potential of X-rays for medical applica-
conducting experiments with cathode rays, he tions, particularly in craniofacial surgery, was
noticed a faint flicker of weak light coming from immediately recognized. X-rays provided a
a screen placed near an all-glass Hittorf-Crookes non-invasive means to visualize internal struc-
tube that he had energized with a current. This tures, diagnose craniofacial conditions, and plan
discovery led him to conclude that these new surgical interventions with greater accuracy.
rays, which he called X-rays, were highly pene- Roentgen’s X-rays revolutionized medicine and
trating and different from known cathode rays. enabled surgeons to assess fractures, injuries,
This ground-breaking discovery opened up a new and abnormalities in the head, face, and jaws,
era in medical imaging, including craniofacial leading to improved patient care and surgical
imaging. outcomes.
Röntgen WC. On a new kind of rays. 1896;3(59):227–31

Strengths • Descriptive study on finding of a new imaging tool
• Well-written comments on experimental outcomes
Limitations • Outcomes based on empirical results
Impact Roentgen’s accidental discovery of X-rays was a pivotal moment in the history of craniofacial
imaging. His findings have had far-reaching implications, transforming medical diagnosis, treatment,
and research. The significance of Roentgen’s work on the discovery of X-rays cannot be overstated, as
it continues to shape numerous aspects of modern life and remains an integral part of medical and
scientific practices to this day
9.3 Development ing. He perfected a roentgenographic technique

of Cephalometry to capture precise X-ray images of the internal
Radiographs and external cranial landmarks of the living head.
He inserted small pieces of lead at various cranial
Thirty-six years later after the discovery of X-rays points, which were then recorded on the X-ray
by Roentgen, Broadbent introduced standardized film to create reference points for measurements
methods for the production of cephalometric (Fig. 9.1).
radiographs. The article “A New X-Ray Technique Moreover, he conducted studies on children
and Its Application to Orthodontia” discusses the between the ages of 9 months and 20 years, tak-
development and application of a novel X-ray ing X-ray images at various intervals. By super-
technique for studying cranial and facial struc- imposing tracings of these X-rays, he measured
tures, and it remains a landmark paper [2]. and analyzed changes in the cranial base and face
In this paper, Dr. Broadbent designed a spe- over time. His technique allowed for accurate
cialized head holder to accurately position and and quantifiable measurements of growth and
immobilize the living head during X-ray imag- structural changes in the living head. He empha-
9 Evolution of Imaging in Cranio-Maxillo-Facial Surgery 79
Fig. 9.1 (Left) Specially designed craniostat for roent- “A New X-Ray Technique and Its Application to
genographic studies of skulls. (Right) Implementation of Orthodontia” by Broadbent, Burton Hamilton, Angle
cephalography by holding the head position oriented to Orthodontist, 1, 45–66)
the roentgenograms (figure is obtained from the article,
sized the importance of using unchanged areas of craniofacial procedures, incorporating precise
the cranial base as reference points for superim- anthropometric methods to study facial growth
posing X-ray tracings, thus providing a more reli- and cranial changes in living individuals. His
able and individual-specific comparison. research laid the foundation for more accurate
In summary, Broadbent’s work significantly and personalized orthodontic treatments based on
advanced the scientific basis of orthodontic and individual development and growth patterns .
Broadbent BH. A new X-ray technique and its application to orthodontia. 1931;1(2):45–66
Strengths • Excellent description of a new diagnosis method
• Well-written comments on experimental outcomes
Limitations • Views from orthodontists
Impact Broadbent’s work in cephalometry laid the foundation for objective and quantitative assessment of
craniofacial morphology, which has been instrumental in orthodontics, plastic surgery, maxillofacial
surgery, and other fields related to craniofacial anomalies. His research not only enhanced diagnostic
capabilities but also paved the way for the development of treatment planning and surgical approaches
tailored to individual patients
9.4 Invention of Computed involved combining X-ray data from multiple

Tomography Scan angles around the body and using computer algo-
rithms to reconstruct these data into detailed
The invention of the CT (computed tomography) cross-sectional images (Fig. 9.2).
scan is credited to British engineer Sir Godfrey In his article, he describes a technique called
Hounsfield and South African-born physicist computerized transverse axial scanning, com-
Allan M. Cormack. They independently devel- monly known as CT or computed tomography
oped the principles of CT imaging in the early [3]. The technique involves dividing the head
1970s. In 1972, Sir Godfrey Hounsfield, working into slices, each irradiated along its edges, and
at EMI Laboratories in England, built the first CT using computer algorithms to reconstruct cross-
scanner and performed the first clinical CT head sectional images. Unlike conventional X-ray
scan [3]. He devised a novel technique that methods, the CT scan provides unaffected infor-
These readings are processed by a digital

computer to create a matrix of picture points,
each representing the absorption coefficient of
corresponding tissue volumes in the slice. The
absolute values of absorption coefficients for
various tissues can be calculated with high accu-
racy. The CT scan is especially useful in diagnos-
ing ailments and evaluating tissue structures
without invasive procedures.
The technique’s accuracy allows for detection
of different tissue levels within a “window,” and
it can even be used to determine the atomic num-
ber of materials within the slice. The radiation
Fig. 9.2 Godfrey Hounsfield with the first commercial
CT scanner
dose in CT scans is confined to a narrow band,
resulting in an exposure level similar to conven-
tional skull X-ray examinations.
mation from within the slice, enabling detailed Overall, the CT scan’s development and
analysis of craniofacial structures. implementation marked a turning point in medi-
The CT scanner uses a narrow beam of X-rays cal imaging, opening new avenues for diagnosing
that rotates around the patient’s head, taking mul- and understanding craniofacial structures and
tiple readings of transmissions through the head. various medical conditions.
Hounsfield GN. Computerized transverse axial scanning (tomography). 1. Description of system. Br J Radiol.
1973;46(552):1016–22
Strengths • Excellent description of a new diagnosis method
• Informative illustrations describing its mechanism
Limitations • Technical terms may make it challenging to understand
Impact The invention of CT scanning revolutionized craniofacial imaging by providing detailed cross-
sectional images of the head and craniofacial structures. This non-invasive imaging technique allowed
for more precise and accurate diagnoses of various craniofacial anomalies, injuries, and conditions
9.5 Beginning of 3D Imaging Additionally, they developed a surgical simula-

in Craniofacial Surgery tion program based on computerized tomo-
graphic (CT) data, which can be linked to the
At the beginning of 1980s, clinicians used 3D cephalometric-based program.
imaging in craniofacial deformities. For cranio- The workflow involves the clinician selecting
facial surgical needs, first simulation software the number and type of osteotomies (bone cut-
was introduced in 1986. Cutting and McCarthy ting) to be performed on the patient. An auto-
et al. developed a computer program to assist cli- mated optimization program then calculates the
nicians in planning craniofacial surgical proce- postoperative positions of these bone fragments
dures [4]. The program uses a three-dimensional to best fit the appropriate normal cephalometric
landmark database created from posteroanterior form. The clinician can further modify the
and lateral cephalograms of the patient, com- design interactively to account for factors like
bined with Bolton normative standards. bone-graft resorption, relapse tendency, occlu-
Fig. 9.3 Preoperative views of a patient with hemifacial facial surgical procedures: optimization and interaction
microsomia using CT-based surgical simulation program with cephalometric and CT-based models.” Plast Reconstr
(figure is obtained from the article, Cutting, C., et al., Surg, 1986. 77(6): p. 877–87)
“Three-dimensional computer-assisted design of cranio-
sal disparities, and the condition of the overly- In response to this limitation, they developed
ing soft-tissue matrix. This study demonstrates the new quantitative CT-based surgical simula-
the capability to transfer osteotomy movement tion [5]. This version takes advantage of CT
specifications between the CT-based and cepha- scans, which provide a richer data set compared
lometrically based surgical simulation pro- to X-ray views. The software uses surface seg-
grams. This allows the automated positioning mentation to locate features on the skull, such as
step to be performed on the cephalometric ridges and landmarks, and guides a technician
model, while the interactive step is conducted through semi-automated localization of these
using the superior image provided by the features using a standard “mapfile.” This enables
CT-based model. more precise and consistent localization of ana-
Later, they stated that a CT-based program tomical structures (Fig. 9.3).
was less useful than the cephalometric one. In the Moreover, the new version employs advanced
earlier version, the cephalometric-based program statistical techniques to generate “averages” that
utilized X-ray views to locate facial landmarks, serve as criteria in surgical simulations. They use
and an interactive three-dimensional surgical a linearization of Kendall’s shape space to aver-
simulation was performed using a wireframe age landmark configurations and average curves
visual representation. However, the critical factor linking pairs of landmarks. This process allows
of automated positioning of bone fragments to fit each point on the skull to be assigned a standard
a normal form was missing, making it less parametric identity, enhancing the precision of
useful. surgical planning.
Cutting C, et al. Three-dimensional computer-assisted design of craniofacial surgical procedures: optimization and
interaction with cephalometric and CT-based models. Plast Reconstr Surg. 1986;77(6):877–87
Strengths • Discussion on historical perspectives on 3D simulation
Limitations • Technical terms may make it challenging to understand
Impact The computer program and its integration of cephalometric and CT data, automated optimization, and
interactive modifications represent a significant step forward in craniofacial surgical planning. The
improved accuracy and personalized approach offered by this technology have the potential to enhance
surgical outcomes, reduce complications, and contribute to the advancement of craniofacial surgery as
a whole
9.6 Shifting into External graphs of a posed face and to plot contour maps
Capturing by “3D Scanners” of the same face using the same optical system
Based on Stereo Camera (Fig. 9.4).
The study describes the process of posing the
With an invention of 3D scanner, which are safe subject’s face and capturing the stereo photo-
and convenient to use to measure a person’s body graphs, highlighting the importance of accurate
accurately, a new clinical application area is posing to obtain reliable measurements. The pho-
emerging, i.e. 3D scanning that has a high capa- tographs are then used to create contour maps of
bility of capturing 3D measurement. Unlike tra- the face, providing a three-dimensional analysis
ditional measurement methods that may require of its surface. The accuracy of the measurements
physical contact, 3D scanning allows for non- is investigated, and the minimal practical interval
invasive and contactless data capture. This between contour lines is determined.
reduces patient discomfort and stress during The authors tested the accuracy of the method
medical examinations and eliminates the risk of by using a plaster model of a face with a known
measurement errors caused by physical contact. volume. They measured the volume using the
In a historical perspective, three-dimensional contour mapping technique and compared it to
surface imaging was first clinically applied in the volume obtained by direct displacement of
1944 by Thalmann, who used stereophotogram- water and by computer analysis of the facial map.
metry to capture the 3D facial surface for orth- The results showed that the contour mapping
odontic diagnosis [6]. Later, Tanner and Weiner technique provided accurate measurements of
attempted to standardize 3D photography by the facial volume.
comparing anthropometric measurements to 3D Overall, this article demonstrates the potential
data [7]. Their efforts enabled Burke and Beard of stereophotogrammetry as a tool for accurate
to develop a system of stereophotogrammetry for quantitative analysis of facial features. It allows
analyzing facial morphology [8–10]. for detailed measurements of facial contours,
In this section, we would like to introduce Dr. including spot heights and volumetric assess-
Burke’s works on stereophotogrammetry which ments. The method has potential applications in
involves using two overlapping photographs to craniofacial field for documenting facial charac-
create a three-dimensional impression of an teristics, asymmetries, and postoperative 3D
object or surface. Notably, their work pioneered assessments. Their efforts contributed to the
the development of a 3D scanner that serves both development of current stereophotogrammetry
as a stereo camera and creates a three-dimensional system and led to the current four-dimensional
impression for surface analysis [8]. They devel- photogrammetry capable of capturing dynamic
oped a stereo camera to record a pair of photo- movements or changes over time.
Fig. 9.4 (Left)

Development of a stereo
camera for recording of
stereophotogrammetric
facial photographs.
(Right) Facial plot with
contour interval of 5 mm
and landmarks
placement (figure is
from the article, Burke,
P. and Beard, L.,
“Stereophotogrammetry
of the face: A
preliminary investigation
into the accuracy of a
simplified system
evolved for contour
mapping by
photography.” 1967.
53(10): p. 769–782)
Burke PH, Beard FH. Stereophotogrammetry of the face: A preliminary investigation into the accuracy of a
simplified system evolved for contour mapping by photography. Am J Orthod. 1967;53:769–82
Strengths • Comparing the results with direct displacement of water and computer analysis of the facial map
demonstrates the reliability and accuracy of their method
Limitations • Views from orthodontists
Impact The article by Burke and Beard is a pioneering study in the field of stereophotogrammetry for facial
analysis. They developed a stereo camera and contour mapping technique to create three-dimensional
impressions of facial surfaces. This methodology has had a significant impact on the development of
current stereophotogrammetry systems
9.7 Expert Concluding patients’ unique craniofacial structures, enabling

Commentary precise preoperative planning and better postop-
erative assessments. As technology continues to
In conclusion, the field of craniofacial imaging advance, the future of craniofacial imaging holds
has witnessed significant advancements over the even more promise for enhancing surgical out-
past century, driven by pioneering research papers comes and advancing the field further.
that have shaped the course of surgical practice.
The landmark papers discussed in this article have
been instrumental in revolutionizing craniofacial References
surgical techniques and patient care through the
introduction of novel imaging technologies and 1. Röntgen WC. On a new kind of rays. Science.
1896;3(59):227–31.
data-driven approaches. Overall, the integration 2. Broadbent BH. A new x-ray technique and its applica-
of advanced imaging technologies has facilitated tion to orthodontia. Angle Orthod. 1931;1(2):45–66.
a comprehensive understanding of craniofacial 3. Hounsfield GN. Computerized transverse axial scan-
anatomy, pathology, and surgical nuances. ning (tomography). 1. Description of system. Br J
Radiol. 1973;46(552):1016–22.
Surgeons now have real-time insights into
4. Cutting C, et al. Three-dimensional com- 7. Tanner JM, Weiner JS. The reliability of the photo-
puter-assisted design of craniofacial surgical grammetric method of anthropometry, with a descrip-
procedures: optimization and interaction with cepha- tion of a miniature camera technique. Am J Phys
lometric and CT-based models. Plast Reconstr Surg. Anthropol. 1949;7(2):145–86.
1986;77(6):877–87. 8. Burke P, Beard FH. Stereophotogrammetry of the
5. Cutting C, et al. Computer aided planning and execu- face: a preliminary investigation into the accuracy of
tion of craniofacial surgical procedures. In: 1992 14th a simplified system evolved for contour mapping by
annual international conference of the IEEE engineer- photography. Am J Orthod. 1967;53(10):769–82.
ing in medicine and biology society. IEEE. 1992. 9. Beard LF, Burke PH. Evolution of a system of stereo-
6. Thalmaan D. Die Stereogrammetrie: ein diag- photogrammetry for the study of facial morphology.
nostisches Hilfsmittel in der Kieferorthopaedie Med Biol Illus. 1967;17(1):20–5.
[Stereophotogrammetry: a diagnostic device in 10. Burke P. Four-dimensional facial change. Br J Orthod.
orthodontology]. 1944. 1984;11(4):170–84.
Part II
Head and Neck
Evolution of Craniofacial Trauma
Management
10
Abstract 3. Manson PN, et al. Su, structural pillars of the

Craniofacial trauma can have significant func- facial skeleton: an approach to the manage-
tional, psychological, and aesthetic implica- ment of LeFort fractures. Plast Reconstr
tions. The complexity of the craniofacial region Surg. 1980;66(1):54–61.
and the diverse range of injuries make it diffi- 4. Markowitz BL, et al. Management of the
cult to select five landmark papers. However, medial canthal tendon in nasoethmoid orbital
we have chosen the most influential five papers fractures: the importance of the central frag-
because they enlighten surgeons as to both how ment in classification and treatment. Plast
and why current practices have evolved. Reconstr Surg. 1991;87(5):843–53.
5. Ellis E III. A prospective study of 3 treatment
methods for isolated fractures of the man-
Keywords dibular angle. J Oral Maxillofac Surg.
2010;68:2743–54.
Orbital wall fracture · Zygomaticomaxillary
fracture · LeFort fracture · NOE fractures ·
Mandible fracture · Buttress 10.1 Introduction
The Five Most Impactful Papers The most important publication about facial
1. Smith B, Regan WF Jr. Blow out fracture of trauma would be Plastic Surgery of the Face
the orbit: Mechanism and correction of inter- written by Harold Gillies [1]. The Plastic Surgery
nal orbital fracture. Am J Ophthalmol. of the Face was published in 1920 and is consid-
1957;44(6):733–9. ered a landmark publication in the field of facial
2. Gruss JS, Mackinnon SE. Complex maxil- trauma [1]. In this book, Gillies describes his
lary fractures: role of buttress reconstruction experience in treating soldiers with facial injuries
and immediate bone graft. Plast Reconstr sustained during World War I. Gillies introduced
Surg. 1986;78(1):9–22. many novel techniques in facial reconstructive
surgery, including skin grafting, pedicle flaps,
and the use of tubes for drainage. He emphasized
J.-W. (JW) Choi (*) · Y. C. Kim the importance of precise surgical technique,
Department of Plastic and Reconstructive Surgery, careful planning, and attention to detail in achiev-
University of Ulsan College of Medicine, Asan ing good outcomes for patients with facial inju-
Medical Center, Seoul, South Korea ries. He also highlighted the psychological

https://doi.org/10.1007/978-3-031-57132-9_10
impact of facial trauma, noting that restoring a as one of the pioneer papers of the plastic surgery
patient’s facial appearance and function was per se, we will not describe the details in this
essential for their physical and emotional well- chapter.
being. However, as Gillies’ paper was regarded
10.2 Blow-Out Fracture of Orbit

Smith B, Regan WF Jr. Blow out fracture of the orbit: Mechanism and correction of internal orbital fracture. Am J
Ophthalmol. 1957;44(6):733–9
Strengths • Well-conducted experimental and clinical study
• Excellent illustrations
Limitations • Small study groups
Impact Most importantly, this paper turned out to be the most cited paper in facial trauma according to our
investigation. The number of citations proves the implication of this paper in understanding of the
blow-out fracture. Based on Pfeiffer’s concept that the force of the orbital contents against the floor
causes fractures, they explained why the eyeball is mostly preserved while avoiding eyeball ruptures
in the blow-out fracture and how to manage the blow-out fracture
Byron Smith and William Regan, Jr. were the tissues pressed into the orbital cavity penetrate.
first to recognize the mechanism of blow-out It would be different from the concept of LeFort
fracture with their paper entitled “Blow-out frac- and Lagrange who explain that the force is trans-
ture of the orbit: Mechanism and correction of mitted by bone conduction through the rigid
internal orbital fracture” on American Journal of orbital rim directly to the thin orbital floor
Ophthalmology in 1957 [2]. They defined “blow- (Fig. 10.1).
out or hydraulic fracture” as a fracture of the Most importantly, this paper turned out to be
orbital wall caused by a sudden increase in intra- the most cited paper in facial trauma according to
orbital pressure following the Pfeiffer’s view our investigation. The number of citations proves
about the reason why the fracture of the orbital the implication of this paper in understanding of
floor can occur without concomitant fracture of the blow-out fracture. This paper is about not
the orbital rim. They proved the theory about the only the clinical but also experimental study
mechanism of the blow-out fracture with the including proof of authors’ theory. They
cadaver study. Using hurling ball over the closed explained why the eyeball is mostly preserved
lids of the orbit, which was struck with hammer, while avoiding eyeball ruptures in the blow-out
they compared between the two groups with fracture and how to manage the blow-out frac-
orbital and without orbital contents. The famous ture. Especially, they also mentioned about the
figure about blow-out fracture mechanism was importance of immediate bone graft in order to
introduced in this paper. They concluded that minimize the postoperative enophthalmos com-
objects with a diameter larger than that of the plications. In addition, in spite of the deficiency
bony orbit, such as a baseball, fail to rupture the in imaging modality, the concept of these authors
globe because part of the force is absorbed by seems still valid and plays an important role in
the orbital rim. While the force is not great understanding the blow-out fractures even in
enough to fracture the heavy orbital rim, the soft modern plastic surgery era.
10 Evolution of Craniofacial Trauma Management 89
a b
Fig. 10.1 Mechanism of blow-out fracture: (a) External and fragments of the orbital floor depressed into the
pressure forcing a blow-out fracture of the orbital floor antrum. (Figures are reproduced or reprinted from the
with incarceration of the extraocular muscles. (b) Waters article, Byron Smith and William F. Regan, Jr., “Blow-out
view showing depressed fracture of the orbital floor with fracture of the orbit: Mechanism and correction of internal
comminuted fragments. (c) Experimental blow-out frac- orbital fracture.” American Journal of Ophthalmology,
ture model of the orbital floor with the orbital rim intact 1957. 44(6): p. 733–739)
10.3 Complex Maxillary Fractures
Gruss JS, Mackinnon SE. Complex maxillary fractures: role of buttress reconstruction and immediate bone graft.
Plast Reconstr Surg. 1986;78(1):9–22
Strengths • Large sample size
• Reasoned classification
• Establishment of buttress concept in facial bone fractures
Impact Joseph Gruss not only suggested the new concept titled “buttress reconstruction” in complex
maxillary fractures, but also recommended the ideal surgical techniques using immediate bone
grafting. More importantly, he described about how to restore not only the facial vertical and
horizontal projection, but also the facial height. He detailed how to restore the posterior facial height
in case of concomitant bilateral condyle neck fractures with the complex maxillary fractures
Plastic surgeons have been trying to come up with He conceptualized the medial, lateral, and
an effective strategy for maxillary fractures for a posterior buttresses while relating these to the
long time. Joseph Gruss, a pioneer of craniofacial cranial base above, the mandible below, and the
trauma surgery, was the first American surgeon to correct occlusion. He illustrated two anterior but-
suggest the standard strategy for maxillary frac- tress such as the medial buttress (nasomaxillary),
tures using buttress reconstruction with immedi- lateral buttress (zygomaticomaxillary), and one
ate bone grafts [3]. Joseph Gruss reported 558 posterior buttress (pterygomaxillary), very
patients with complex facial fractures between clearly which is still the core concept in modern
1978 and 1984 including 71 complex LeFort I facial bone fracture management. In addition, he
fractures of the maxilla. He recognized the impor- demonstrated the actual bony anatomy of the but-
tance of the medial and lateral maxillary buttress tress system. Thinness of the anterior maxillary
reconstruction on each side for reestablishing the buttresses in relation to the other facial bone was
facial height, projection, and width. Although visualized in this transilluminated skull.
most cases of his were fixated using immediate Diagrammatic representation to the four anterior
bone graft with wiring because the plate and maxillary buttress was an impactful analogue to
screw fixation system was not popular at that the supporting pillars of the roof of a building. He
time, he showed the excellent results in even emphasized not only the vertical projection but
severe maxillary fractures. The famous figures in also the horizontal projection with height of the
facial vertical buttress were included in this paper. maxilla. Considering he practiced in the era of
This was the breakthrough that was required wiring without the modern titanium plate and
and is the second landmark paper I have chosen screw systems, his immediate bone graft tech-
because the buttress reconstruction became the niques look feasible at that time and sometimes
most important concept in the management of in the modern era.
facial bone fractures in contemporary era. Based More importantly, he described how to restore
on 558 patients with complex facial fractures not only the facial vertical and horizontal projec-
between 1978 and 1984, Joseph Gruss not only tion, but also the facial height. He detailed how to
suggested the new concept titled “buttress recon- restore the posterior facial height in case of con-
struction” in complex maxillary fractures, but comitant bilateral condyle neck fractures with the
also recommended the ideal surgical techniques complex maxillary fractures. This paper’s impact
using immediate bone grafting (Fig. 10.2). looks still so huge even in the modern era.
a b
c d
Fig. 10.2 Maxillary buttress concept suggested by toured bone graft, resulting in normal maxillary height
Joseph Gruss. (a) Schematic presentation of maxillary and projection. (d) Repair of severely comminuted frac-
buttress, consisted of two anterior (medial or nasomaxil- tures with rib bone graft to restore orbital floor, both max-
lary, and lateral or zygomaticomaxillary) and posterior illary buttresses. (Figures are reproduced from the article,
(pterygomaxillary) buttress. (b) Diagrammatic represen- Joseph Gruss and Susan Mackinnon, “Complex Maxillary
tation of four anterior maxillary buttress, maintaining the Fractures: Role of Buttress Reconstruction and Immediate
position of the maxilla in relation to the cranium and cra- Bone Graft.” Plastic and Reconstructive Surgery, 1986.
nial base. (c) Buttress stabilization with carefully con- 78(1): p. 9–22)
10.4 LeFort Fractures

Manson PN, et al. Su, structural pillars of the facial skeleton: an approach to the management of LeFort fractures.
Plast Reconstr Surg. 1980;66(1):54–61
Strengths • Detailed description of modern buttress concept
• Listing of vertical and horizontal buttress
• Correlation of LeFort fractures with buttress
Limitations • How to manage the facial bone fractures only with wiring
Impact This paper was the first to present a detailed vertical and horizontal buttress based on the fracture
patterns as well as to correlate these to clinical situations. This allowed better interpretation of how to
manage the complex LeFort fractures with the buttress reconstructions. Different from the typical
description of the LeFort fractures, the illustrations of this figure is unilateral LeFort I, II, III fractures
which are common in real clinical situation. He emphasized not only the importance of buttress
reestablishment but also the impact of restoration of the vertical and horizontal dimensions of the
maxilla and mandible
Although Rene LeFort suggested the traditional This paper was the first to present a detailed
LeFort fracture patterns, I would like to recom- vertical and horizontal buttress based on the frac-
mend Paul Manson’s paper as an impactful arti- ture patterns as well as to correlate these to clini-
cle [4]. Because, this paper modernized the cal situations. This allowed better interpretation
horizontal and vertical buttress concept which is of how to manage the complex LeFort fractures
still a standard concept in the management of with the buttress reconstructions. More interest-
facial bone fractures. Paul Manson suggested the ingly, he suggested the most common fracture
three principal vertical buttress of the maxilla patterns in Fig. 10.1 in this paper. Different from
such as nasomaxillary buttress, zygomatic but- the typical description of the LeFort fractures, the
tress, and pterygomaxillary buttress. With regard illustrations of this figure is unilateral LeFort I,
to horizontal buttress, he suggested the maxillary II, III fractures which are common in real clinical
alveolus, palate, pyriform aperture, orbital rims, situation. I believe he already understood the
and the base of the skull. He emphasized that the common zygomaticomaxillary fracture patterns
reconstruction of complex LeFort fractures is associated with original LeFort fractures pattern.
accomplished by dividing the midface into upper In addition, considering Paul Manson was oper-
and lower regions and stabilizing each as func- ating in the era of wiring only without the plate
tional units. The lower midface is related through and screw fixation system, the way how to man-
proper occlusion to a stabilized mandible, which age the complex facial bone fractures he sug-
has been properly related to the cranial base. The gested is amazing. He emphasized not only the
orbital and nasoethmoid regions are stabilized by importance of buttress reestablishment but also
interfragment wiring and are related to an intact the impact of restoration of the vertical and hori-
frontal cranium. The mandible is the strongest of zontal dimensions of the maxilla and mandible.
the facial bones and a significant structural pillar In this way it was possible to ascertain that the
of the lower midface following fractures and cra- complex facial bone fractures could be managed
niomandibular relation can thus determine the properly based on the structural concept using
relation of the mandibular-maxillary complex buttress restoration even in complex LeFort
(Fig. 10.3). fractures.
Fig. 10.3 Buttress

concepts suggested by a
Paul Manson: (a)
Supporting pillars of
facial skeleton and their
relation to the frontal
and cranial attachment Frontal attachment
(b) Division of midface
reconstruction into ORBITAL BUTTRESS
upper and lower units
and their relation to
cranial attachment Cranial base Naso-ethmoia region
(figures are reproduced
from the article, Paul Naso-FRONTAL BUTTRESS
Manson, John Hoopes,
and C.T.Su, “Structural
Pillars of the Facial ZYGOMATIC BUTTRESS
Skeleton: an approach to
the management of PTERYGO-MAXILLARY
LeFort fractures,” Plastic BUTTRESS
and Reconstructive
Surgery, 1980. 66(1):
MANDIBULAR
p. 54–61)
BUTTRESS
LE FORT 2
LE FORT 3 Upper midface

LE FORT 1 stabilized to
frontal attachment
Lower midface
stabilized to
V mandible
D
Mandible O
stabilized to
cranial base
10.5 Nasoethmoid Orbital (NOE)

Fracture
Markowitz BL, et al. Management of the medial canthal tendon in nasoethmoid orbital fractures: the importance of
the central fragment in classification and treatment. Plast Reconstr Surg. 1991;87(5):843–53
Strengths • Well-documented
• Detailed description of technique with good figures
Limitations • Small number of patients (only 36 NOE fracture patients)
Impact This paper provided a technique to help avoid the telecanthus as a common and very difficult
complication of NOE fracture. This stimulated the importance of the central fragment with medial
canthal tendon in the management of NOE fractures
The landmark paper about nasoethmoid orbital The authors propose a classification system
(NOE) fracture is “Management of the medial for nasoethmoid fractures based on the involve-
canthal tendon in nasoethmoid orbital fractures: ment of the central fragment, which is defined as
The importance of the central fragment in classi- the portion of the nasal bone and ethmoid com-
fication and treatment” by Bernard Markowitz plex between the medial canthal tendon and the
and Paul Manson et al. [5]. This paper discusses cribriform plate. The classification includes three
the significance of the central fragment in the types: type I, which involves no disruption of the
classification and treatment of nasoethmoid central fragment; type II, which involves partial
orbital fractures. The medial canthal tendon plays disruption of the central fragment; and type III,
a crucial role in maintaining the position and sta- which involves complete disruption of the central
bility of the medial canthus and lacrimal system, fragment. They discuss various surgical tech-
and its disruption can lead to severe complica- niques for repair, including direct repair, transna-
tions (Fig. 10.4). sal wiring, and external fixation.
a b c
Fig. 10.4 Treatment of nasoethmoid fractures, suggested “Management of the medial canthal tendon in nasoeth-
by Paul Manson. (a) Type I injury. (b) Type II injury. (c) moid orbital fractures: The importance of the central frag-
Type III injury. (Figures are reproduced from the article, ment in classification and treatment.” Plastic and
Bernard Markowitz, Paul Manson, William Crawley et al. Reconstructive Surgery, Vol 87(5), May, 1991, 843–853)
10.6 Mandible Fracture
Ellis E III. A prospective study of 3 treatment methods for isolated fractures of the mandibular angle. J Oral
Maxillofac Surg. 2010;68:2743–54
• Relatively large sample size with a total of 200 patients enrolled over 12 years
Limitations • Study conducted at a single institution
• Did not include patients with more complex mandibular fractures
Impact The study has been cited over 300 times, demonstrating its impact and influence on the field of oral
and maxillofacial surgery. Overall, Edward Ellis III’s study is a valuable contribution to the field
In the management of mandibular fractures, there In this situation, one of the decisive investiga-
have been long-time debates about how to fix the tions that has helped with the understanding of
fractured segments ideally. There were two major the management of mandibular fractures was
approaches for this. One is “load-bearing” osteo- Edward Ellis’ paper entitled “A prospective
synthesis, mostly based on the strength of the plate study of 3 treatment methods for isolated frac-
and screw system itself for fixation. The other one tures of the mandibular angle” [7]. The purpose
is “load-sharing” osteosynthesis such as miniplate of this investigation was to evaluate treatment
monocortical fixation. With regard to the manage- outcomes prospectively when isolated fractures
ment of mandibular fractures, this controversy still of the mandibular angle are treated by (1) non-
rages between advocates of “rigid” fixation, which rigid fixation that includes 5–6 weeks of maxil-
usually requires application of two bone plates, lomandibular fixation, (2) nonrigid but
and those who use “nonrigid” but functionally functionally stable fixation using a single mini-
stable fixation by application of a single miniplate. plate, and (3) rigid fixation using two miniplates.
One group believes that plate and screw fixation This study was done over a 12-year period
should provide sufficient rigidity to the fragments sequentially assigned. Based on 185 patients
to prevent interfragmentary mobility during active who had sufficient follow-up for inclusion in this
use of the mandible (rigid fixation). In 1973, study, it turned out that the use of single mini-
Champy et al. reported the treatment of mandibu- plate was the easiest to perform and was associ-
lar fractures using small, easily bendable noncom- ated with the lowest number of complications. It
pression bone plates, placed transorally, attached was a surprising confirmative result which is
with monocortical screws [6]. Champy et al. per- contradictory to the conventional thought that
formed several investigations with a “miniplate” the more rigid the fixation, the better skeletal
system to validate the technique. stability (Fig. 10.5 and Table 10.1).
a b c
Fig. 10.5 Comparison of outcome among three types of Rigid fixation with two miniplates. The author proved that
mandible fixation: (a) Nonrigid fixation with wire appli- the use of single miniplate was the easiest to perform and
cation. (b) Nonrigid fixation with single miniplate. (c) was associated with the lowest number of complications
Table 10.1 Treatment outcome in the management of isolated mandible angle fracture
Treatment group
Treatment outcome Nonrigid Single miniplate Two miniplate
Wound problems Least Most
Final interincisal dimension (mm) 41.21 ± 9.9 44.59 ± 5.8 43.92 ± 6.2
Neurosensory dysfunction No significant difference
X-ray at last follow-up visit No significant difference
Occlusion at last follow-up visit No significant difference
10.7 Expert Concluding References

Commentary
1. Gillies HD. Plastic surgery of the face. London:
Hodder & Stoughton; 1920. p. 408.
We have tried to highlight the five papers that, in
2. Smith B, Regan WF Jr. Blow-out fracture of the orbit;
our estimation, have had the most impact in mechanism and correction of internal orbital fracture.
advancing the understanding and treatment of Am J Ophthalmol. 1957;44(6):733–9.
craniofacial bone fractures. We have cited other 3. Gruss JS, Mackinnon SE. Complex maxillary frac-
tures: role of buttress reconstruction and immedi-
papers in order to help put these chosen five in
ate bone grafts. Plast Reconstr Surg. 1986;78(1):
perspective. During the preparation of this writ- 9–22.
ing, we were repeatedly surprised at our pioneer 4. Manson PN, et al. Structural pillars of the facial
surgeons’ perspectives and insights into craniofa- skeleton: an approach to the management of Le
Fort fractures. Plast Reconstr Surg. 1980;66(1):
cial trauma. Many of their concepts are still very
54–61.
valid surprisingly even in this modern era. This 5. Markowitz BL, et al. Management of the medial
highlights the reason why classics survive more canthal tendon in nasoethmoid orbital fractures:
than several decades regardless of trends. If the importance of the central fragment in classifica-
tion and treatment. Plast Reconstr Surg. 1991;87(5):
present-day plastic surgeons could reconsider
843–53.
what these five landmark papers meant not only 6. Champy M, et al. Mandibular osteosynthesis by
at that time but also in the modern era, we are miniature screwed plates via a buccal approach. J
sure they will be able to find out the clues in order Maxillofac Surg. 1978;6(1):14–21.
7. Ellis E 3rd. A prospective study of 3 treatment meth-
to innovate and develop the current practices to
ods for isolated fractures of the mandibular angle. J
the next paradigm of practice. This is what we Oral Maxillofac Surg. 2010;68(11):2743–54.
have tried to achieve in this chapter.
Evolution of Cleft Care
11
Benjamin B. Massenburg and Raymond W. Tse

Care for patients with cleft lip and/or palate 1. Millard DR. A radical rotation in single hare-
begins in infancy and extends into adulthood. lip. Am J Surg. 1958;95(2):318–22.
Although surgery can restore normal anatomy, 2. Fisher DM. Unilateral cleft lip repair: an ana-
it involves general anesthesia and generates tomical subunit approximation technique.
scars which may impact facial growth and Plast Reconstr Surg. 2005;116(1):61–71.
function in the developing child. Thus, surgi- 3. Mulliken JB. Bilateral complete cleft lip and
cal techniques for cleft lip and palate repair nasal deformity: an anthropometric analysis of
have undergone continuous scrutiny with staged to synchronous repair. Plast Reconstr
many variations in techniques to maximize Surg. 1995;96(1):9–23.
functional and aesthetic outcomes while mini- 4. Furlow LT Jr. Cleft palate repair by double
mizing the number of interventions. In this opposing Z-plasty. Plast Reconstr Surg.
chapter, we discuss five landmark publications 1986;78(6):724–38.
which have resulted in significant shifts in 5. Sommerlad BC. A technique for cleft
clinical practice. These five publications have palate repair. Plast Reconstr Surg.
shaped modern practice and the landscape of 2003;112(6):1542–8.
both basic and clinical research.
11.1 Introduction
Keywords
Cleft lip and/or palate is one of the most common
Cleft lip · Cleft palate · Orofacial cleft
congenital anomalies, ranging between one in
500 and one in 1000 live births with some
regional variation [1]. Care for the child with a
cleft lip and/or palate requires a multidisciplinary
B. B. Massenburg team approach. Surgical interventions include lip
Division of Plastic Surgery, Department of Surgery, repair in infancy, palate repair around one year of
University of Washington, Seattle, WA, USA age, alveolar bone grafting in mixed dentition,
R. W. Tse (*) and possible orthognathic surgery and rhino-
Division of Craniofacial and Plastic Surgery, plasty at skeletal maturity, as indicated. In this
Department of Surgery, Seattle Children’s Hospital,
Seattle, WA, USA chapter, we will concentrate on landmark papers

https://doi.org/10.1007/978-3-031-57132-9_11
98 B. B. Massenburg and R. W. Tse
that have shaped surgical care for children with Gillies to avoid routine and treat each patient
cleft lip and/or palate. individually, Millard presented a surgical tech-
Although these papers are technical in descrip- nique that could be modified based upon the
tion with minimal high-level evidence to initially severity of the deformity. He noted that there was
support them, they are proposals that are based both missing tissue as well as distortion of the
on careful consideration, sound judgment, and existing tissue in his anatomic analysis. Due to
critical evaluation of outcomes and experience. the volume loss, he proposed that the surgeon
In turn, they have become the subject of consid- should not throw away any tissue and should use
erable subsequent study shaping both modern all tissue that is available in the repair. The named
practice and cleft research. movements in this repair are the “rotation,” of the
The future of research in cleft care will ulti- central philtral segment downward to level
mately involve critical analysis of our existing Cupid’s bow, and the “advancement,” of the cleft-
and proposed treatments with more objective sided tissue medially to fill the gap left by the
analysis to produce data-driven changes. rotation (Fig. 11.1). As each patient with a unilat-
eral cleft lip has differing severity, he noted that
the amount of rotation and advancement would
11.2 Unilateral Cleft Lip Repair differ in each case, supporting a “cut as you go”
philosophy.
Millard [2] revolutionized repair of the unilateral The approach has become the most utilized
cleft lip when he introduced his now eponymous method for repair of the unilateral cleft lip in the
repair. Stimulated by the teaching of Harold world [3]. Millard noted that for wide clefts, the
Fig. 11.1 Illustration of

Millard’s technique for
unilateral cleft lip repair.
(Image reproduced with
permission from:
Millard DR. A radical
rotation in single
harelip. Am J Surg.
1958 Feb;95(2):318–22)
11 Evolution of Cleft Care 99
cleft-sided philtral column remained short after technique [7], with Mohler wishing to create a
his repair, so he modified his technique, utilizing more symmetric scar [8], Noordhoff wishing to
a back cut and the C-flap to fill the resultant accentuate the pout of the lip and eliminate a
defect on the columella [4]. His original technical back cut on the alar crease [9], and Onizuka plac-
description represents the landmark publication, ing the scar along the nasal sill to respect this
though his continued extensions and refinements anatomic subunit [10], among others. A survey in
in technique solidified its potential for adoption 2008 revealed that 84% of cleft surgeons use
[4, 5]. Although these initial papers amount to some form of a rotation-advancement repair,
opinion and low-level “evidence,” they include though over half of those surgeons are using a
well-selected clinical examples with stunning modification of the technique [11]. Rigorous
outcomes and high-quality photography and comparative outcome studies of cleft lip repair
illustrations. Adoption of this technique was are limited, though there are case series reporting
facilitated by meetings, in-person interactions, favorable outcomes [12, 13] and a few cohort
and an extremely well-illustrated three-volume comparisons [14, 15] on various modifications of
textbook which is unprecedented in cleft care [6]. the technique. Additionally, the impact of this
Over the years, many prominent cleft sur- repair on facial growth has been studied over
geons have applied modifications of this general time [16].
Millard DR. A radical rotation in single harelip. Am J Surg. 1958;95(2):318–22

Strengths • A cleft lip repair that is simple to design and allows the surgeon to adjust during the repair in a
“cut-as-you-go” manner. As Dr. Mulliken explains, it “allows considerable technical latitude and
artistic virtuosity”
• The line of closure more closely follows anatomic borders than prior repairs
• The sequence of release and repair is easy to follow and, when effectively used, can produce
favorable outcomes
Limitations • The freestyle approach can result in a “learning curve” in which surgeons need experience or natural
instincts to achieve balance
• The repair sacrifices lateral lip width to produce adequate lateral lip height especially in the case of
more severe clefts. While lateral lip width can elongate with time and growth, the tension results in
loss of fullness of the free margin of the lip (i.e. the “red lip” vermilion and mucosa). Alternatively,
if a surgeon designs a repair that preserves lateral lip width, there will be a tendency to produce
vertically short lips
• The description of a “rotation-advancement” repair involving downward rotation of the medial
elements and advancement of the lateral elements is misleading. If only considering the nasolabial
region in isolation, that description seems simple and convincing. However, we are prone to optical
illusions that can result in erroneous goals [17]. When considering the context of the face, the cleft
results in uncoupled growth of the premaxilla that drives the prolabium, columella, and non-cleft
alar base lateral and leaves the cleft alar base posterior (but normal in medial-to-lateral position)
[18–20]. Correction of the deformity requires centralization of the prolabium, columella, and
non-cleft side alar base (i.e. the medial lip elements) and anterior advancement of the cleft alar base
(i.e. the lateral lip elements). A more accurate description would therefore involve advancement and
rotation of the medial elements and anterior advancement of the lateral elements
• “Harelip” is no longer an appropriate term in modern language for cleft lip
Impact This paper proposed a technique of repair that has become and continues to be the most common
method for cleft lip repair worldwide
The Anatomic Subunit Approximation approach natural pout of the lip [9]. He was also inspired
for unilateral cleft lip repair involves a consider- by Thomson’s repair [22] that leveraged the
able departure from Millard’s technique. Fisher Rose-Thompson effect [23, 24] to elongate lip
[21] was impressed by Noordhoff’s augmenta- height (diamond-shaped excision with closure as
tion triangle which provided tension at a point a vertical line). After thorough study of the anat-
just above the cutaneous roll and accentuated the omy and previous techniques, he applied the
a – b – 1 mm = c
cphs’ X’
X’’ b
Short
cphs
c
a b
Variable
b lateral lip
height
cphi
cphi’
b
cphi’’ Intermediate
(Noordhoff)
c
X X’ X’’
Alar-sill crease
Alar-sill crease
Tall
Philtral ridge b
Columellar-labial crease
c
Cutaneous roll
Red line
Fig. 11.2 Updated illustration of Fisher’s technique for and Nose Deformity and Anatomic Subunit
unilateral cleft lip repair in the Canadian Journal of Plastic Approximation. Plast Surg. 2024;32(1):138-47. https://
Surgery. (Reproduced with permission from: Tse RW, doi.org/10.1177/22925503221109069)
Fisher DM. State of the art: The Unilateral Cleft lip
principle of anatomic subunits [25] to cleft repair, subunit in a logical and well-orchestrated system
with the ideal line of repair ascending from the of surgical planning. It follows a specific
cleft-side peak of Cupid’s bow to the base of the sequence and includes critical checkpoints dur-
cleft-sided columella, mirroring the noncleft side ing which the surgeon needs to verify the design
(Fig. 11.2). The landmark paper describes an and adjust as needed. Those checkpoints are
algorithmic approach to unilateral cleft lip repair important in navigating the dynamic nature of
with excellent examples of post-operative out- repair that has been found to involve changes on
comes [21]. The clever system of landmarking the both cleft side and non-cleft side [18].
and the “measure twice, cut once” nature of the With less reliance upon experience and “artis-
repair have led to widespread adoption of this tic virtuosity” the approach may appeal to newer
technique. The design is a hybrid of many prior surgeons or to surgeons wishing to rely more on
approaches but carefully considers each anatomic a set design.
Based upon surveys of contemporary practice laypeople [32], and less asymmetry with out-
in 2008 [11] and 2020 [26], the Fisher repair is comes that are less dependent on the severity of
gaining adoption and is now the second most the preoperative deformity [33]. A prospective,
common approach for cleft lip repair. Its inclu- randomized, observer-blind study on unilateral
sion in major textbooks further attests to its cleft lip repair outcomes found better aesthetic
importance in modern practice [27, 28]. While results following the Fisher repair when com-
not all experienced surgeons feel the need to pared to a Millard type of repair [34].
adopt it, there is a younger generation of sur- Additionally, there is mounting three-dimen-
geons for which it has become the preferred sional morphometric analysis supporting the
repair, with several case series of surgeons’ first short- and long-term outcomes of this repair, as
experiences with this technique reporting favor- well as its impacts on facial growth over time
able outcomes [29, 30]. Several retrospective [18–20, 35–37].
cohort studies comparing the technique to The description of the repair has been updated
Millard repairs have reported better symmetry in with simpler nomenclature, additional features to
a shorter operative time [31], improved scoring help with design, and a desription of associated
of the postoperative result by both surgeons and nasal correction [27, 38].
Fisher DM. Unilateral cleft lip repair: an anatomical subunit approximation technique. Plast Reconstr Surg.
2005;116(1):61–71
Strengths • A surgical design that systematically utilizes non-cleft side and cleft side landmarks in a logical
sequence to produce a repair that attempts to approximate the borders of anatomic subunits. The
“measure twice, cut once” style appeals to some surgeons and the “check-points” during execution
allow for further adjustments and fine-tuning following surgical releases
• The design inherently accommodates the full spectrum of presentation because it is based upon
anatomic landmarks
• The design inherently accommodates the dynamic nature of the non-cleft side that changes through
the course of the repair (because it is based upon corresponding non-cleft features) [18]
• With Noordhoff’s point [9] considered a landmark that defines the lateral point of closure along the
lip, lateral lip width and fullness are preserved
Limitations • The many landmarks can be confusing and intimidating
• Markings and design can take more time
• There is a risk of creating a lip that is too long if checkpoints aren’t verified
• For more severe clefts, the inferior triangle can be large therefore producing a line of closure that
does not fully follow borders of the anatomic subunits
Impact This paper proposed a departure from the “cut-as-you-go” cleft lip repair and describes a methodical,
measured approach to repair that is gaining adoption and is supported by high-level evidence
11.3 Bilateral Cleft Lip Repair “forked flaps” that placed lip tissue into the colu-
mella [40], continued with a description of prin-
The literature on bilateral cleft lip is relatively ciples to guide repair [41], and was marked by a
sparse, likely because the presentation is less critical landmark paper that described a single-
common and because outcomes may not be as stage nasolabial repair [42]. Not only did that
favorable. The bilateral cleft lip has previously paper clearly illustrate the approach, demonstrate
been noted as “twice as difficult to repair, and the favorable example results, and set itself apart
results are only half as good” [39]. Through a from any other literature on bilateral cleft lip
series of papers, Mulliken has changed that senti- repair with the incorporation of longitudinal
ment and demonstrated that favorable outcomes anthropometric data, it was also instrumental in
can be achieved through single-staged treatment. steering our approach in correcting the nasal
The evolution started with a two-stage recon- deformity. The paper demonstrated that the “col-
struction of the lip and nose and the use of umella is in the nose,” meaning that there is no
need to add tissue to the columella that appears by other surgeons using the approach who report
short. Rather, by supporting the nasal cartilages, favorable outcomes [46–48], though comparative
a more natural nasal form can be achieved studies are rare.
(Fig. 11.3). Mulliken has continued to update the approach
The repair has been reaffirmed by several and reflect upon lessons learned [49–52], outlin-
other cleft surgeons [43, 44], and continues as the ing adaptations for complete clefts [50], incom-
standard [45]. There have been several case series plete clefts [52], and asymmetric clefts [53].
Fig. 11.3 Illustration of Mulliken’s technique for

single-stage bilateral cleft lip repair. (Image
reproduced with permission from: Mulliken
JB. Repair of Bilateral Cleft Lip. In: Neligan PC, ed.
Plastic Surgery 4th Edition: Volume 3: Craniofacial,
Head and Neck Surgery, and Pediatric Plastic
Surgery. 4th ed. Elsevier; 2018:Chapter 22)
Mulliken JB. Bilateral complete cleft lip and nasal deformity: an anthropometric analysis of staged to synchronous
repair. Plast Reconstr Surg. 1995;96(1):9–23
Strengths • Clinical examples set a high standard of quality for esthetic outcome
• The approach is well described and illustrated
• Principles are logically outlined
• While papers on bilateral cleft lip repair are rare, a precedent was set with the presentation of
anthropometric data
Limitations • Concerns that pin retained devices and active molding could contribute to reduced facial growth,
and those devices may not be available in all settings
• While the paper describes an external nose incision, that incision has subsequently been
eliminated
• Requires high level of skill
Impact This paper marks a paradigm from two-stage repair to single-stage repair. It also demonstrated that
the “columella is in the nose” and the nasal deformity could be corrected by addressing the cartilage
support, without the use of “forked flaps” (that transpose prolabial tissue to the columella)
11.4 Cleft Palate Repair magnification through an operating microscope

to facilitate dissection and repair [57]. The
Closure of a cleft palate not only involves sepa- approach has become the benchmark for
rating the oral and nasal cavities, it includes intra-velar veloplasty [58] and has become the
reconstruction of the soft palate’s dynamic most commonly applied technique for cleft pal-
sphincter mechanism to control airflow through ate repair in the United Kingdom [59, 60].
the nasopharynx for speech function while main- Following the proposed repair, there have
taining an open airway at rest to avoid obstructive been several case series that have reported accept-
sleep apnea. The main muscle responsible for able fistula rates with good speech outcomes
that sphincter mechanism is thought to be the [61–63]. The approach has been the subject of
levator veli palatini [54, 55]. With an origin at the comparative studies [64–66] and it has been the
cranial base, the muscle normally inserts trans- inspiration for further modification [67]. The
versely into the aponeurosis of the soft palate to Sommerlad radical intra-velar veloplasty is cur-
form a sling [54, 56]. In the case of a cleft, the rently being studied in an ongoing prospective
muscle is oriented longtiudinally (sagittally) and comparative, NIH-funded, multi-center study
inserts into the posterior border of the hard (CORNET Study).
palate. In addition to its use in primary repair, the
Intra-velar veloplasty involves releasing the approach has been found to be effective for
muscle and midline repair, however, the extent of secondary repair [68–70]. Velopharyngeal
that mobilization had previously been limited. In insufficiency is the inability to close the phar-
a crucial paper, Sommerlad described an exten- ynx during speech production and impairs
sive “radical” circumferential dissection of the speech quality. The application of the tech-
muscle and repair in transverse orientation along nique in secondary reconstruction is similarly
the posterior soft palate (Fig. 11.4). The paper being studied in another ongoing, prospective,
describes the muscular anatomy in detail, tensor NIH-funded, multi-center comparative study
veli palatini tenotomy, and the use of high power (VPI-OPS) [71].
Uvula Uvula
Tensor
palati
tendon
Hard palate
Left levator Right levator

palati muscle palati muscle
Sutured Levator palati
nasal muscles sutured
Stay mucosa in midline
stitch Sutured
in oral nasal
mucosa mucosa
Fig. 11.4 Illustration of Sommerlad’s radical intra-velar veloplasty technique for cleft palate repair. (Image reproduced
with permission from: Sommerlad BC. A technique for cleft palate repair. Plast Reconstr Surg. 2003 Nov;112(6):1542–8)
Sommerlad BC. A technique for cleft palate repair. Plast Reconstr Surg. 2003;112(6):1542–8
Strengths • Illustrates the intricate velar muscular anatomy associated with cleft palate and demonstrates how
the various velar muscles can be separately identified
• Describes a repair that is “anatomically correct”
• The paper was supported by fistula and speech/VPI outcome data
Limitations • Use of OR microscope isn’t available in all settings and can be cumbersome
• Requires high level of surgical skill
• Circumferential dissection can produce significant scar burden
Impact This paper clarifies the anatomy of the abnormal soft palate musculature and its correction to
facilitate closure of the velopharyngeal aperture that is needed for quality speech function
While the repair described by Sommerlad repair repositions the levator muscle into its more
involves an “anatomic repair,” Furlow proposed effective position, while simultaneously elongat-
an elegant but radically different approach to ing the soft palate (Fig. 11.5).
cleft palate repair [72]. In a landmark paper, Contracture of deadspace between the hard
Furlow described elongation of the soft palate palate and the retropositioned velar muscles can
through the course of primary repair via z-plasty result in the recurrence of sagittally oriented
of the oral mucosa with an opposing z-plasty of muscles and functional speech difficulties (velo-
the nasal mucosa. The design is simple, but pharyngeal insufficiency). The repair by Furlow
clever, in the inclusion of muscle in the posteri- may reduce those risks by leaving the muscle
orly based flaps so that the velar muscles are attached to the transposed mucosa and by placing
transposed into a transverse orientation. The the velar muscles from each side of the cleft into
Fig. 11.5 Illustration of Furlow’s double-opposing repair by double opposing Z-plasty. Plast Reconstr Surg.
Z-plasty technique for cleft palate repair. (Image repro- 1986 Dec;78(6):724–38)
duced with permission from: Furlow LT Jr. Cleft palate
an overlapping orientation. In contrast to intrave- rently the aim of a prospective, NIH-funded,

lar veloplasty that involves dissection of muscle multi-center study (CORNET).
from both oral and nasal layers, Furlow’s repair In the future it will be important to specifically
involves dissection of muscle from only one sur- compare Furlow palatoplasty to radical intravelar
face. Furlow also hypothesized that the overlap- veloplasty as described by Sommerlad. It will
ping muscle repair could produce a more effective also be important to weigh the risks of fistula
muscular sling. Recent studies have affirmed that associated with Furlow palatoplasty against its
hypothesis. Magnetic resonance imaging studies potential advantages in speech outcomes. A ran-
of oropharyngeal anatomy have demonstrated domized controlled trial reported high fistula
attenuated and elongated levator musculature in rates with Furlow palatoplasty when compared to
the setting of cleft palate relative to normal con- von Langenback palatoplasty [83]. Fistulas have
trols [73–75], thereby suggesting that overlap- cascading impact on patients as they can affect
ping muscle repair may better mimic normal speech, hygiene, and oral function. Treatment of
anatomy and functional muscle-tension fistulas involve significant burdens on patients
relationships. and the additional scar can impair growth and
Although the original description is most make future surgery more difficult. In addition,
commonly cited and easily available, Furlow has when a Furlow palatoplasty fails, it is anecdotally
published an in-depth technical description [76] known to occur in a “spectacular” fashion that
that includes details of muscular relationships can be difficult to salvage.
with eustachian tube and hamulus. Those details Regardless, the concepts introduced by
may be important for newer surgeons in design Furlow’s palatoplasty have inspired hybrid
and effective repair. repairs [67, 84] and other approaches that incor-
While Furlow has reported a limited series porate buccal myomucosal flaps [85, 86] with the
using the repair, others have reported large case original z-plasty incisions. The repair has also
series including long-term institutional experi- been adapted for secondary surgery in the treat-
ence with favorable outcomes for speech, midfa- ment of VPI with great efficacy [87–89], further
cial growth, and rates of secondary surgery reaffirming the utility of its concept.
[77–79]. Retrospective cohort studies have The accummulating evidence of Furlow pala-
reported better or similar results relative to more toplasty as a secondary procedure for VPI has
traditional repairs [80, 81] and a systematic involved several case series [90–92], and com-
review reported lower odds of secondary surgery parative studies [93]. Furlow palatoplasty for sec-
relative to straight line palatoplasty [82]. ondary speech surgery is also the focus of another
Comparison of Furlow palatoplasty to other ongoing, prospective, NIH-funded, multi-center
repairs involving intravelar veloplasty is cur- comparative study (VPI-OPS) [71].
Furlow LT Jr. Cleft palate repair by double opposing Z-plasty. Plast Reconstr Surg. 1986;78(6):724–38
Strengths • Clever design
• Means of elongating velum while re-orienting muscles into more functional position
• Avoids longitudinal scar that could be prone to contracture and velar shortening
Limitations • Non-anatomic repair
• May be more prone to fistulas
• Incisions make anterior ruggated palatal mucosa flaps almost island flaps and almost fully
dependent on pedicle for blood supply
• If it fails, it can be a “spectacular” failure that is difficult to salvage
Impact This paper describes a clever design to simply and elegantly close a cleft palate while translating the
musculature to create a musclular sling. The approach was a major departure from previous methods
and has become a common approach for primary repair and secondary repair to address
velopharyngeal insufficiency
11.5 Expert Concluding topharyngeal anatomy and changes that occur

Commentary through primary palatoplasty and secondary pro-
cedures for velopharyngeal insufficiency
The quality-of-life years provided by optimal [73–75]. Given that speech function has a greater
surgical cleft care is unparalleled in the field of impact on patient quality of life than appearance,
plastic surgery. Optimal form and function in ensuring optimal velopharyngeal function should
adulthood is the objective of treatment, and thus be the priority of future advances in cleft palate
it takes a career to follow patients adequately to repair.
fully understand their outcomes. In-utero repair has been espoused as a poten-
Contemporary practices have been shaped by tial avenue of “scarless healing”; however, it
five papers. Although each of the individual arti- bears considerable risks and challenges. If favor-
cles is limited in evidence, they mark shifts in able form and function can be provided through
practice, standards, and focus of clinical research. conventional approaches, those risks may be
Following each landmark, waves of evidence avoided. The remaining challenge will be to min-
have followed that have progressively risen in imize the impact of surgery on growth and the
quality and quantity. consequences to dental occlusion and facial pro-
The future will ideally blend further innova- portions. Although we have means to address
tion with data-driven insights. Studies of 3D those sequelae, each additional procedure or
images of infants with unilateral cleft lip have treatment that a child endures adds burden and
clarified “optical illusions” regarding the unre- psychological impacts.
paired deformity [17, 19, 20] and have revealed The marriage of technological advances,
previously unrecognized opposing alterations application of sound surgical principles, and
that occur with surgery [18]. It is not just the cleft thoughtful innovation may help us to optimize
side of the nasolabial region that is abnormal and form, function, growth, and patient well-being.
changes through surgery, the non-cleft side Ultimately, if we as surgeons heed the advice of
includes deformations that also change with our expert colleagues in the psychosocial realm
repair. Anticipating changes on both sides is criti- [94, 95], we may also make better clinical deci-
cal in achieving symmetry, balance, and har- sions and provide better longitudinal care.
mony. Future iterations of repair will need to
consider the dynamic nature of all of the tissues
involved and leverage objective insights regard-
References
ing the deformity.
In addition to leveraging three-dimensional 1. Massenburg BB, Hopper RA, Crowe CS, et al. Global
surface imaging, magnetic resonance imaging burden of orofacial clefts and the world surgical work-
will provide opportunities to study internal pala- force. Plast Reconstr Surg. 2021;148(4):568e–80e.
2. Millard DR. A radical rotation in single harelip. Am J metry: severity and outcome. Plast Reconstr Surg.
Surg. 1958;95(2):323–30. 2018;141(4):547e–58e.
3. Marcus JR, Allori AC, Santiago PE. Principles of cleft 20. Tse RW, Ettinger RE, Sitzman TJ, Mercan
lip repair: conventions, commonalities, and contro- E. Revisiting the unrepaired unilateral cleft lip and
versies. Plast Reconstr Surg. 2017;139(3):764e–80e. nasal deformity using 3D surface image analysis:
4. Millard DR. Extensions of the rotation-advancement a data-driven model and its implications. J Plast
principle for wide unilateral cleft lips. Plast Reconstr Reconstr Aesthet Surg. 2021;74:2694.
Surg. 1968;42(6):535–44. 21. Fisher DM. Unilateral cleft lip repair: an anatomi-
5. Millard DR. Refinements in rotation- advancement cal subunit approximation technique. Plast Reconstr
cleft lip technique. Plast Reconstr Surg. Surg. 2005;116(1):61–71.
1964;33:26–38. 22. Thomson HG. Unilateral cleft lip repair. Oper Tech
6. Ralph Millard D. Cleft craft: the evolution of its sur- Plast Reconstr Surg. 1995;2(3):175–81.
gery—volume I: the unilateral deformity, vol 1. Little 23. Thompson JE. An artistic and mathematically accu-
Brown and Company; 1976. rate method of repairing the defect in cases of harelip.
7. Stal S, Brown RH, Higuera S, et al. Fifty years Surg Gynecol Obstet. 1912;14:498–505.
of the Millard rotation-advancement: looking 24. Rose W. On harelip and cleft palate. London:
back and moving forward. Plast Reconstr Surg. H.K. Lewis; 1891.
2009;123(4):1364–77. 25. Burget GC, Menick FJ. The subunit principle
8. Mohler LR. Unilateral cleft lip repair. Plast Reconstr in nasal reconstruction. Plast Reconstr Surg.
Surg. 1987;80(4):511–7. 1985;76(2):239–47.
9. Noordhoff MS. Reconstruction of vermilion in uni- 26. Roberts JM, Jacobs A, Morrow B, Hauck R, Samson
lateral and bilateral cleft lips. Plast Reconstr Surg. TD. Current trends in unilateral cleft lip care: a
1984;73(1):52–61. 10-year update on practice patterns. Ann Plast Surg.
10. Onizuka T, Ichinose M, Hosaka Y, Usui Y, Jinnai T. The 2020;84(5):595–601.
contour lines of the upper lip and a revised method of 27. Tse RW. Chapter 19.4. Anatomic subunit repair for
cleft lip repair. Ann Plast Surg. 1991;27(3):238–52. unilateral cleft lip. In: Neligan PC, editor. Plastic sur-
11. Sitzman TJ, Girotto JA, Marcus JR. Current surgical gery, 5th ed. vol 3: Craniofacial, head and neck sur-
practices in cleft care: unilateral cleft lip repair. Plast gery, and pediatric plastic surgery. 5th ed. Elsevier;
Reconstr Surg. 2008;121(5):261e. 2022.
12. Cutting CB, Dayan JH. Lip height and lip width 28. Tse RW, Fisher DM. Unilateral cleft lip repair:
after extended Mohler unilateral cleft lip repair. Plast anatomic subunit approximation technique. In:
Reconstr Surg. 2003;111(1):17–23. Global cleft care in low-resource settings. Springer
13. Maull DJ, Grayson BH, Cutting CB, et al. Long-term International Publishing; 2021. pp. 129–141.
effects of nasoalveolar molding on three-dimensional 29. Mbuyi-Musanzayi S, Tshilombo Katombe F, Lukusa
nasal shape in unilateral clefts. Cleft Palate Craniofac Tshilobo P, Kalenga Mwenze Kayamba P, Devriendt
J. 1999;36(5):391–7. K, Reychler H. Anthropometric and aesthetic out-
14. Maggiulli F, Hinton C, Simpson L, et al. Lip symme- comes for the nasolabial region in 101 consecutive
try following rotation advancement cleft lip repair in African children with unilateral cleft lip one year
5-year-old children treated by Ralph Millard and Ron after repair using the anatomical subunit approxi-
Pigott. JPRAS Open. 2022;33:145–54. mation technique. Int J Oral Maxillofac Surg.
15. Dissaux C, Bodin F, Grollemund B, et al. Evaluation of 2017;46(10):1338–45.
5-year-old children with complete cleft lip and palate: 30. Tse R, Lien S. Unilateral cleft lip repair using the
multicenter study. Part 1: lip and nose aesthetic results. anatomical subunit approximation: modifications and
J Craniomaxillofac Surg. 2015;43(10):2085–92. analysis of early results in 100 consecutive cases.
16. Mulliken JB, Labrie RA. Fourth-dimensional Plast Reconstr Surg. 2015;136(1):119–30.
changes in nasolabial dimensions following rotation- 31. Mittermiller PA, Martin S, Johns DN, Perrault D,
advancement repair of unilateral cleft lip. Plast Jablonka EM, Khosla RK. Improvements in cleft
Reconstr Surg. 2012;129(2):491–8. lip aesthetics with the Fisher repair compared to
17. Isaac KV, Tan RA, Ganske IM, Mulliken JB. Beware the Mohler repair. Plast Reconstr Surg Glob Open.
the alar base optical illusion in assessment of unilat- 2020;8(6):E2919.
eral cleft lip nasal deformity. Plast Reconstr Surg. 32. Kwong JW, Cai LZ, Azad AD, et al. Assessing the
2019;143(4):1157–62. Fisher, Mohler, and Millard techniques of cleft lip
18. Massenburg BB, Mercan E, Ettinger RE, Tse RW. The repair surgery with eye-tracking technology. Ann
Yin and Yang of primary unilateral cleft lip and nose Plast Surg. 2019;82(5S Suppl 4):S313–9.
repair: balance through understanding the opposing 33. Patel TA, Patel KG. Comparison of the Fisher ana-
cleft and non-cleft side changes. Plast Reconstr Surg. tomical subunit and modified Millard rotation-
2023;151:838e. advancement cleft lip repairs. Plast Reconstr Surg.
19. Mercan E, Oestreich M, Fisher DM, et al. Objective 2019;144(2):238e–45e.
assessment of the unilateral cleft lip nasal defor- 34. Deshmukh M, Vaidya S, Deshpande G, Galinde J,
mity using three-dimensional stereophotogram- Natarajan S. Comparative evaluation of esthetic out-
comes in unilateral cleft lip repair between the Mohler 51. Mulliken JB, Wu JK, Padwa BL. Repair of bilateral
and Fisher repair techniques: a prospective, random- cleft lip: review, revisions, and reflections. J Craniofac
ized, observer-blind study. J Oral Maxillofac Surg. Surg. 2003;14(5):609–20.
2019;77(1):182.e1–8. 52. Mulliken JB, Kim DC. Repair of bilateral incom-
35. Wu J, Heike C, Birgfeld C, et al. Measuring symmetry plete cleft lip. Plast Reconstr Surg. 2013;132(4):
in children with unrepaired cleft lip: defining a stan- 923–32.
dard for the three-dimensional midfacial reference 53. Yuzuriha S, Oh AK, Mulliken JB. Asymmetrical
plane. Cleft Palate Craniofac J. 2016;53(6):695–704. bilateral cleft lip: complete or incomplete and
36. Tse R, Booth L, Keys K, et al. Reliability of naso- contralateral lesser defect (minor-form, micro-
labial anthropometric measures using three- form, or mini- microform). Plast Reconstr Surg.
dimensional stereophotogrammetry in infants with 2008;122(5):1494–504.
unrepaired unilateral cleft lip. Plast Reconstr Surg. 54. Huang MHS, Lee ST, Rajendran K. Anatomic basis of
2014;133(4):530–42. cleft palate and velopharyngeal surgery: implications
37. Tse RW, Knight R, Oestreich M, Rosser M, Mercan from a fresh cadaveric study. Plast Reconstr Surg.
E. Unilateral cleft lip nasal deformity: three- 1998;101(3):613–27.
dimensional analysis of the primary deformity and 55. Boorman JG, Sommerlad BC. Levator palati and pala-
longitudinal changes following primary correc- tal dimples: their anatomy, relationship and clinical
tion of the nasal foundation. Plast Reconstr Surg. significance. Br J Plast Surg. 1985;38(3):326–32.
2020;145(1):185–99. 56. Kriens OB. An anatomical approach to veloplasty.
38. Tse RW, Fisher DM. State of the art: the unilateral cleft Plast Reconstr Surg. 1969;43(1):29–41.
lip and nose deformity and anatomic subunit approxi- 57. Sommerlad BC. A technique for cleft palate repair.
mation. Plast Surg (Oakv). 2024;32(1):138–47. Plast Reconstr Surg. 2003;112(6):1542–8.
39. Brown JB, McDowell F, Byars LT. Double clefts of 58. Andrades P, Espinosa-De-Los-Monteros A, Shell DH,
the lip. Plast Reconstr Surg. 1948;3(3):380. et al. The importance of radical intravelar veloplasty
40. Mulliken JB. Principles and techniques of bilat- during two-flap palatoplasty. Plast Reconstr Surg.
eral complete cleft lip repair. Plast Reconstr Surg. 2008;122(4):1121–30.
1985;75(4):477–86. 59. Butterworth S, Hodgkinson EL, Sainsbury DCG,
41. Mulliken JB. Correction of the bilateral cleft lip nasal Hodgkinson PD. Surgical variation between con-
deformity: evolution of a surgical concept. Cleft sultant surgeons performing a Sommerlad radi-
Palate Craniofac J. 1992;29(6):540–5. cal intravelar veloplasty. Cleft Palate Craniofac J.
42. Mulliken JB. Bilateral complete cleft lip and 2021;58(12):1490–9.
nasal deformity: an anthropometric analysis of 60. Butterworth S, Hodgkinson EL, Stock NM,
staged to synchronous repair. Plast Reconstr Surg. Sainsbury DCG, Hodgkinson PD. Evolution of cleft
1995;96(1):9–23; discussion 24–6. lip and palate surgical training in the UK: a quali-
43. Chung KH, Lo L-J. One-stage versus two-stage repair tative study. Cleft Palate Craniofac J. 2023;60(2):
of asymmetric bilateral cleft lip. Plast Reconstr Surg. 197–210.
2018;141(5):1215–24. 61. Bschorer F, Hornig L, Schön G, Bschorer R. Speech
44. Bezuhly M, Fisher DM. Single-stage repair of asym- assessment following microsurgical soft palate repair.
metrical bilateral cleft lip with contralateral lesser J Craniomaxillofac Surg. 2023;51:199.
form defects. Plast Reconstr Surg. 2012;129(3):751–7. 62. Becker M, Hansson E. Low rate of fistula formation
45. Buchanan EP, Hollier LH. Bilateral cleft lip after Sommerlad palatoplasty with or without lateral
repair: lessons from history. Plast Reconstr Surg. incisions: an analysis of risk factors for formation of
2022;150:201–10. fistulas after palatoplasty. J Plast Reconstr Aesthet
46. Rottgers SA, Lim SY, Hall AM, Zurakowski D, Surg. 2013;66(5):697–703.
Mulliken JB. Longitudinal photogrammetric analy- 63. Lu Y, Shi B, Zheng Q, Hu Q, Wang Z. Incidence of
sis of the Columellar-labial angle following primary palatal fistula after palatoplasty with levator veli pala-
repair of bilateral cleft lip and nasal deformity. Plast tini retropositioning according to Sommerlad. Br J
Reconstr Surg. 2017;139(5):1190–9. Oral Maxillofac Surg. 2010;48(8):637–40.
47. Kim S-K, Lee J-H, Lee K-C, Park J-M. Mulliken 64. Wang K, Wang Q, He W, et al. The effect of zigzag
method of bilateral cleft lip repair: anthro- palatoplasty on the repair of cleft palate and its com-
pometric evaluation. Plast Reconstr Surg. parative study with Sommerlad palatoplasty and the
2005;116(5):1243–51. double opposing Z palatoplasty. J Craniofac Surg.
48. Kim S-K, Kim M-H, Kwon Y-S, Lee K-C. Long-term 2020;31(7):e717–20.
results in the bilateral cleft lip repair by Mulliken’s 65. Fan X, Liu W, Nie J, Chen X, Dong Y, Lu
method. J Craniofac Surg. 2009;20(5):1455–61. Y. Comparison of velopharyngeal morphology of two
49. Mulliken JB. Primary repair of bilateral cleft palatoplasty techniques in patients with hard and soft
lip and nasal deformity. Plast Reconstr Surg. cleft palate. Front Surg. 2023;9:9.
2001;108(1):181–94. 66. Sakran KA, Wu M, Yin H, et al. Evaluation of postop-
50. Mulliken JB. Repair of bilateral complete cleft lip erative outcomes in two cleft palate repair techniques
and nasal deformity—state of the art. Cleft Palate without relaxing incisions. Plast Reconstr Surg.
Craniofac J. 2000;37(4):342–7. 2023;14:145.
67. Nguyen DC, Patel KB, Skolnick GB, et al. Progressive Z-Palatoplasty with the Wardill-Kilner procedure for
tightening of the levator veli palatini muscle improves isolated clefts of the soft palate. Plast Reconstr Surg.
velopharyngeal dysfunction in early outcomes of pri- 1995;95(6):969–77.
mary palatoplasty. In: Plastic and reconstructive sur- 82. Timbang MR, Gharb BB, Rampazzo A, Papay F, Zins
gery, vol. 136. Philadelphia: Lippincott Williams and J, Doumit G. A systematic review comparing Furlow
Wilkins; 2015. p. 131–41. double-opposing Z-plasty and straight-line intrave-
68. Elsherbiny A, Amerson M, Sconyers L, Grant lar veloplasty methods of cleft palate repair. Plast
JH. Time course of improvement after re-repair pro- Reconstr Surg. 2014;134(5):1014–22.
cedure for VPI management. J Plast Reconstr Aesthet 83. Williams WN, Seagle MB, Pegoraro-Krook MI, et al.
Surg. 2018;71(6):895–9. Prospective clinical trial comparing outcome measures
69. Elsherbiny A, Amerson M, Sconyers L, Grant between Furlow and von Langenbeck palatoplasties
JH. Outcome of palate re-repair with radical repo- for UCLP. Ann Plast Surg. 2011;66(2):154–63.
sitioning of the levator muscle sling as a first-line 84. Sakran KA, Wu M, Alkebsi K, et al. The Sommerlad–
strategy in postpalatoplasty velopharyngeal incom- Furlow modified palatoplasty technique: postoperative
petence management protocol. Plast Reconstr Surg. complications and implicating factors. Laryngoscope.
2018;141(4):984–91. 2023;133(4):822–9.
70. Sommerlad BC, Mehendale FV, Birch MJ, Sell D, 85. Mann RJ, Martin MD, Eichhorn MG, et al. The double
Hattee C, Harland K. Palate re-repair revisited. Cleft opposing Z-plasty plus or minus buccal flap approach
Palate Craniofac J. 2002;39(3):295–307. for repair of cleft palate: a review of 505 consecutive
71. Kurnik NM, Weidler EM, Lien KM, et al. The effec- cases. Plast Reconstr Surg. 2017;139(3):735e–44e.
tiveness of palate re-repair for treating velopharyngeal 86. Mann RJ, Fisher DM. Bilateral buccal flaps with dou-
insufficiency: a systematic review and meta-analysis. ble opposing Z-plasty for wider palatal clefts. Plast
Cleft Palate Craniofac J. 2020;57(7):860–71. Reconstr Surg. 1997;100(5):1139–43.
72. Furlow LT. Cleft palate repair by double opposing 87. Chen PK, Wu JT, Chen YR, Noordhoff MS. Correction
Z-plasty. Plast Reconstr Surg. 1986;78(6):724–38. of secondary velopharyngeal insufficiency in cleft
73. Perry JL, Kuehn DP, Sutton BP. Morphology of the palate patients with the Furlow palatoplasty. Plast
levator veli palatini muscle using magnetic resonance Reconstr Surg. 1994;94(7):933–41; discussion 942–3.
imaging. Cleft Palate Craniofac J. 2013;50(1):64–75. 88. Sie KCY, Tampakopoulou DA, Sorom J, Gruss
74. Perry J, Kuehn D, Sutton B, Goldwasser M, Jerez JS, Eblen LE. Results with Furlow palatoplasty in
A. MRI and 3D computer modeling of the levator veli management of velopharyngeal insufficiency. Plast
palatini muscle before and after primary palatoplasty. Reconstr Surg. 2001;108(1):17–25.
Cleft Palate Craniofac J. 2010. 89. Perkins JA, Lewis CW, Gruss JS, Eblen LE, Sie
75. Perry JL, Kuehn DP. Three-dimensional computer KCY. Furlow palatoplasty for management of velo-
reconstruction of the levator veli palatini muscle in pharyngeal insufficiency: a prospective study of
situ using magnetic resonance imaging. Cleft Palate 148 consecutive patients. Plast Reconstr Surg.
Craniofac J. 2007;44(4):421–3. 2005;116(1):72–80.
76. Furlow LT. Cleft palate repair by double opposing 90. Nayar HS, Cray JJ, MacIsaac ZM, et al. Improving
Z-plasty. Plast Reconstr Surg. 1995;2:223. speech outcomes after failed palate repair. J Craniofac
77. Kirschner RE, Wang P, Jawad AF, et al. Cleft-palate Surg. 2014;25(2):343–7.
repair by modified Furlow double-opposing Z-plasty: 91. Koh KS, Kim SC, Oh TS. Management of velopha-
the Children’s Hospital of Philadelphia experience. ryngeal insufficiency using double opposing Z-plasty
Plast Reconstr Surg. 1999;104(7):1998–2010; discus- in patients undergoing primary two-flap palatoplasty.
sion 2011–4. Arch Plast Surg. 2013;40(2):97–103.
78. Jackson O, Stransky CA, Jawad AF, et al. The 92. Noorchashm N, Dudas JR, Ford M, et al.
Children’s Hospital of Philadelphia modification of Conversion Furlow palatoplasty. Ann Plast Surg.
the Furlow double-opposing Z-palatoplasty: 30-year 2006;56(5):505–10.
experience and long-term speech outcomes. Plast 93. Dailey SA, Karnell MP, Karnell LH, Canady
Reconstr Surg. 2013;132(3):613–22. JW. Comparison of resonance outcomes after pha-
79. LaRossa D, Jackson OH, Kirschner RE, et al. The ryngeal flap and Furlow double-opposing Z-plasty
Children’s Hospital of Philadelphia modification of for surgical management of velopharyngeal incom-
the Furlow double-opposing z-palatoplasty: long- petence. Cleft Palate Craniofac J. 2006;43(1):
term speech and growth results. Clin Plast Surg. 38–43.
2004;31(2):243–9. 94. Parens E. Surgically shaping children: technology,
80. Yu CC, Chen PK, Chen YR. Comparison of speech ethics, and the pursuit of normality. Baltimore: John
results after Furlow palatoplasty and von Langenbeck Hopkins University Press; 2006.
palatoplasty in incomplete cleft of the secondary pal- 95. Aspinall CL. Anticipating benefits and decreas-
ate. Chang Gung Med J. 2001;24(10):628–32. ing burdens: the responsibility inherent in pediat-
81. Brothers DB, Dalston RW, Peterson HD, Lawrence ric plastic surgery. J Craniofac Surg. 2010;21(5):
WT. Comparison of the Furlow double-opposing 1330–4.
Evolution of Orthognathic Surgery
12
Srinivas M. Susarla and R. Bruce Donoff
Abstract Keywords
In this chapter, the evolution of orthognathic Bilateral sagittal split osteotomy · Le Fort I
surgery is traced in the context of five publica- osteotomy · Virtual surgical planning
tions that highlight key events in the develop-
ment of contemporary techniques to address
skeletal malocclusions related to developmen- The Five Most Impactful Papers
tal or congenital conditions. While the articles 1. Trauner R, Obwegeser H. The surgical cor-
highlighted here may be considered seminal in rection of mandibular prognathism and
context, there are other contemporaneous retrognathia with consideration of genio-
works that have shaped current practice as plasty. I. Surgical procedures to correct
well. These five articles should be considered mandibular prognathism and reshaping of
anchors for the following critical events that the chin. Oral Surg Oral Med Oral Pathol.
remain relevant to current practice: (1) devel- 1957;10(7):677–89.
opment of the sagittal osteotomy of the man- 2. Bell WH, Fonseca RJ, Kenneky JW, Levy
dibular ramus, (2) understanding of the BM. Bone healing and revascularization after
biologic basis for the Le Fort I osteotomy, (3) total maxillary osteotomy. J Oral Surg.
basic principles for facial analysis as applied 1975;33:253–60.
to dentofacial deformities, (4) stability of jaw 3. Arnett GW, Bergman RT. Facial keys to orth-
positioning as a function of specific move- odontic diagnosis and treatment planning. Part
ments (with subsequent modification to I. Am J Orthod Dentofacial Orthop.
account for rigid fixation), and (5) develop- 1993;103:299–312.
ment of computer-assisted three-dimensional 4. Proffit WR, Turvey TA, Phillips C.
surgical planning. Orthognathic surgery: a hierarchy of stability.
Int J Adult Orthodon Orthognath Surg.
1996;11:191–204 and Proffit WR, Turvey TA,
S. M. Susarla (*) Phillips C. The hierarchy of stability and pre-
Craniofacial Center, Seattle Children’s Hospital, dictability in orthognathic surgery with rigid
Seattle, WA, USA fixation: an update and extension. Head Face
R. B. Donoff Med. 2007;3:21.
Harvard School of Dental Medicine,
Boston, MA, USA
https://doi.org/10.1007/978-3-031-57132-9_12
112 S. M. Susarla and R. B. Donoff
5. Gateno J, Xia JJ, Teichgraeber JF, Christensen [1–15]. Contemporary orthognathic surgery
AM, Lemoine JJ, Liebschner MA, Gliddon can trace its evolution to the following seminal
MJ, Briggs ME. Clinical feasibility of com- events: (1) development of the sagittal ramus
puter-aided surgical simulation (CASS) in the osteotomy of the mandible [16–22], (2) under-
treatment of complex cranio-maxillofacial standing of the biologic basis for the Le Fort I
deformities. J Oral Maxillofac Surg. osteotomy and it subsequent modification
2007;65:728–34. [23–32], (3) analysis of the facial soft tissue
and skeletal framework to assist with treatment
planning [33–41], (4) categorization of the sta-
12.1 Introduction bility of specific maxillary and mandibular
movements [42–53], and (5) development and
Orthognathic surgery remains a powerful tool integration of digitized, three-dimensional plat-
for addressing three-dimensional dysmorphol- forms for computerized surgical planning
ogy of affecting the midface and mandible (Fig. 12.1) [54–63].
100%
90%
80%
70%
60%
2001-2017
50%
1991-2000
1981-1990
40% 1971-1980
1961-1970
30% 1951-1960
20%
10%
0%
e
s
ns
SA
g
y
l
T
ia
ric
u
og
in
lit
/C
io
iq
oc
ai
O
nn
et
ol
at
n
ng
St
/
os
om
ay
ch
i
la
ic
ys
ni
n/
tP
h
pl
rw
Te
Ph
an
al
yc
tio
m
Ai
en
ph
Ps
Pl
xa
Co
tm
Ce
Fi
al
ea
rtu
Tr
Vi
Fig. 12.1 Distribution of most highly cited articles in focused on expanded indications for orthognathic surgery
orthognathic surgery from 1951–2017, by topic area. (e.g. obstructive sleep apnea) and virtual planning.
Articles related to surgical technique were most prevalent (Reprinted, with permission, from Reference 14)
from 1951–1990. More recent articles (1991–2017)
12 Evolution of Orthognathic Surgery 113
12.2 Dentofacial Deformities concomitant conditions (e.g. velopharyngeal

and Craniofacial Anomalies insufficiency, obstructive sleep apnea).
The origin of orthognathic surgery can be
Orthognathic surgery comes for the work traced to the middle of the nineteenth century.
“ortho” meaning straight and “gnathic” mean- The first documented operation to address skele-
ing jaws. In principle, orthognathic surgery tal malocclusion was an anterior mandibular
entails movement of the jaws to address osteotomy completed by Simon Hullihen in 1849
malalignment of the teeth. More specifically, to address dentoalveolar protrusion related to a
malocclusion of the dentition can be related to burn contracture [1–7]. Subsequent development
malpositioned teeth, malpositioned jaws, or a of the field was largely due to the result of col-
combination of the two. The biologic behavior laboration between Edward Angle (orthodontist)
of the teeth and periodontium is such that teeth and Vilray Blair (surgeon), who jointly described
will move toward each other to achieve con- a mandibular ramus osteotomy to address man-
tact. Such movements result in a “compen- dibular prognathism. While there remains a mat-
sated” occlusion. The focus of orthodontic ter of historical debate as to whether Angle and
treatment in anticipation of jaw surgery is to Blair were the first to describe this operation, it
“decompensate” the occlusion—to place the remains clear that Blair was among those who
teeth into the positions they would be in, cen- shepherded the field into the twentieth century. In
tered within the alveolar housing, if the jaws the first part of the twentieth century, advances by
were in the correct positions [64]. Once decom- Ernst, Kazanjian, and Schuchardt (among many
pensation has occurred, the jaws can be moved others) further developed techniques for mandib-
to the appropriate sagittal, transverse, and ver- ular osteotomies to optimize bone healing. These
tical dimensions, the degree of movement initial events catalyzed the rapid evolution of the
being determined by a combination of facial field, which began in the mid-twentieth century
aesthetics, stability, and the need to account for and continues today.
12.2.1 Sagittal Split Osteotomy [16–22]

Trauner R, Obwegeser H. The surgical correction of mandibular prognathism and retrognathia with consideration of
genioplasty. I. Surgical procedures to correct mandibular prognathism and reshaping of the chin. Oral Surg Oral
Med Oral Pathol. 1957;10(7):677–89
Strengths • Early, comprehensive description of sagittal splitting of the mandibular ramus to maximize bony
contact between the proximal (condyle-bearing) and distal (tooth bearing) segments via an intraoral
approach with preservation of the inferior alveolar nerve
Limitations • Limited outcome descriptions regarding mandibular bony healing, occlusal stability, and inferior
alveolar nerve function
Impact While there is some debate regarding whether Obwegeser was the first to perform the sagittal split
osteotomy, there is no doubt that its adoption as a core procedure in orthognathic surgery is due to his
description
The sagittal split osteotomy (SSO) remains the mandibular segments to allow three-dimensional
most versatile procedure for addressing mandibu- movement of the mandibular teeth, preserve the
lar deformities today [6, 16–22]. Though there inferior alveolar nerve, and allow for passive
have been a number of modifications since alignment of the ramus-condyle unit with the den-
Obwegeser’s initial description, the conceptual tate mandible. Popular modifications to the proce-
principles of the operation remain the same today dure include those of Hunsuck (terminating the
as in 1957: safely separate the proximal and distal medial horizontal osteotomy in the retrolingular
fossa rather than the posterior border) [19], [20], and Spiessel (rigid fixation) [64]. A more
Dalpont (carrying the lateral vertical osteotomy recent modification of the SSO is the infralingular
onto the buccal cortex of the mandible to allow for osteotomy, popularized by Posnick, wherein the
improved bony contact) [18], Epker (more limited medial horizontal osteotomy is placed at the level
dissection of the masseter and medial pterygoid of the mandibular occlusal plane [21, 22].
12.2.2 Le Fort I Osteotomy

Bell WH, Fonseca RJ, Kenneky JW, Levy BM. Bone healing and revascularization after total maxillary osteotomy. J
Oral Surg. 1975;33:253–60
Strengths • Described the biologic basis for healing and vascularity of the Le Fort I osteotomy
Limitations • Experimental animal study; thought findings were later corroborated by clinical observations in
human subjects
Impact Improved understanding of the blood supply to the downfractured maxilla enhanced not only the en
bloc movement of the maxilla, but the ability to segment the maxilla into two (or more) pieces to
address transverse discrepancies and biplanar occlusions [27–32]
Early maxillary osteotomies were segmental the first procedure wherein maxillary and man-
operations involving retropositioning of the pre- dibular osteotomies were performed synchro-
maxilla, as described by Gunther Cohn-Stock nously [3].
[1–5, 7]. Subsequent work by Wassamund and
Wunderer improved upon the mechanics of
repositioning the premaxillary segment [24]. 12.2.3 Treatment Planning
Complete downfracutre of the maxilla at the Le
Fort I level was first described by Cheever in With advances in the understanding of the biologic
1867 for extirpation of a maxillary tumor [23]. and surgical safety of osteotomies of the mandibu-
Fifty-five years later, Wassamund would be the lar ramus and mobilization of the midface at the
first to document a Le Fort I osteotomy to cor- Le Fort I level, surgeons had the tools necessary to
rect a malocclusion (open bite). Subsequent address the complete spectrum of dentofacial dif-
work by Axhausen and Schuchardt showed that ferences. Advancements in digital image capture
the maxilla could be sagittally advanced; this and cephalometric analyzes in the 1970s–1980s
application was extended to patients with cleft enhanced the ability of surgeons and orthodontists
palate by Harold Gillies and Norman Rowe, to comprehensively assess facial form and occlu-
with the use of adjunctive bone grafts to main- sion and develop treatment plans for single- or
tain position [1, 3, 5, 7]. Obwegeser subse- double-jaw surgery to maximize occlusal function
quently contributed to this specific domain with and improve facial aesthetics [33–41].
Arnett GW, Bergman RT. Facial keys to orthodontic diagnosis and treatment planning. Part I. Am J Orthod
Dentofacial Orthop. 1993;103:299–312
Strengths • Comprehensive article on facial analysis and soft tissue changes associated with orthodontic
treatment and jaw osteotomies. Emphasis on comprehensive facial assessment to enhance positive
traits and minimize negative traits, with a conceputal framework that is easy to understand and still
applicable today. Nineteen facial traits are assessed within the context of three essential questions:
(1) what is the quality of the existing trait? (2) how will orthodontic tooth movement affect the trait
(positively or negatively)? and (3) how will surgical movement affect the trait (positively or
negatively)?
Limitations • Low-quality evidence at the time of publication
Impact Enhanced understanding of the interplay between the dentition and facial form, not only insfoar as
skeletal malocclusion, but also how dental movements influence facial aesthetics. Perhaps most
importantly, this article emphasizes the critical role of collaboration between orthodontists and
surgeons when caring for patients with dentofacial deformities
While orthognathic surgery is an essential compo- first” protocols, wherein the osteotomized jaws are
nent of the management of malocclusion, pre-sur- placed in their correct anatomic position prior to
gical orthodontic preparation and post- surgical orthodontic treatment, as well as modifications in
orthodontic care are equally important to achieve orthodontic treatment with the use of clear aligner
an optimal result. More recent advances in orth- therapy, minimizing or obviating the need for fixed
odontic-surgical collaboration include “surgery- appliance therapy (e.g. metallic braces) [8].
12.2.4 Stability and Rigid Fixation

Proffit WR, Turvey TA, Phillips C. Orthognathic surgery: a hierarchy of stability. Int J Adult Orthodon Orthognath
Surg. 1996;11:191–204 and Proffit WR, Turvey TA, Phillips C. The hierarchy of stability and predictability in
orthognathic surgery with rigid fixation: an update and extension. Head Face Med. 2007;3:21
Strengths • Clear description of the various skeletal movements of the maxilla and mandible and their relative
stability. Subsequently modified to account for rigid fixation
Limitations • Expert synthesis rather than evidence-based data
Impact While representing a synthesis of clinical experience with orthognathic surgery and understanding of
the contemporaneous literature rather than a rigorous, evidence-based study, this work established
which jaw movements were stable versus unstable
Comprehensive analysis of stability afforded evolve as critical components for planning, a

surgeons the advantage of choosing the best comprehensive understanding of which move-
option for patients when more than one option ments were more likely to provide a stable
would be possible (e.g. maxillary advance- long-term result helped complete the para-
ment versus mandibular setback). While aes- digm for orthognathic surgery planning
thetic and dental considerations continued to [45–53].
12.2.5 Computer-Assisted Surgical

Planning
Gateno J, Xia JJ, Teichgraeber JF, Christensen AM, Lemoine JJ, Liebschner MA, Gliddon MJ, Briggs ME. Clinical
feasibility of computer-aided surgical simulation (CASS) in the treatment of complex cranio-maxillofacial
deformities. J Oral Maxillofac Surg. 2007;65:728–34
Strengths • Detailed description of early computer-based platform for virtual surgical planning
Limitations • Non-experimental study
Impact The evolution of orthognathic surgical practice, from 1850 to the present, began with the
development and understanding of the biology of maxillary and mandibular ostetomies, followed by
advances in understanding how dental and skeletal movements could be utilized to achieve
appropriate facial balance and then which movements would achieve these results with the best
long-term stability. The final step on the journey to modern orthognathic surgery was the ability to
plan surgical movements in the virtual environment and visualize, in three-dimensions, the
movement of the bones and teeth
The development of digital platforms for treatment has focused on the utility of patient-specific cut-
planning allowed greater appreciation for the intri- ting guides and fixation devices, as well as three-
cacy of movements in multiple dimensions, which dimensional analysis of hard and soft tissue
translated to improved operative efficiency and structures to assess the effects of jaw surgery on
accuracy. Subsequent development in this sphere facial proportions and airway physiology [54–67].
References 18. Dal Pont G. Retromolar osteotomy for the correction

of prognathism. J Oral Surg Anesth Hosp Dent Serv.
1961;19:42–7.
1. Posnick JC. Orthognathic surgery: past—present—
19. Hunsuck EE. A modified intraoral sagittal splitting
future. J Oral Maxillofac Surg. 2021;79(10):1996–8.
technic for correction of mandibular prognathism. J
2. Steinhäuser EW. Historical development of
Oral Surg. 1968;26(4):250–3.
orthognathic surgery. J Craniomaxillofac Surg.
20. Epker BN. Modifications in the sagittal osteotomy of
1996;24(4):195–204.
the mandible. J Oral Surg. 1977;35(2):157–9.
3. Obwegeser HL. Orthognathic surgery and a tale
21. Posnick JC, Choi E, Liu S. Occurrence of a ‘bad’ split
of how three procedures came to be: a letter to
and success of initial mandibular healing: a review of
the next generations of surgeons. Clin Plast Surg.
524 sagittal ramus osteotomies in 262 patients. Int J
2007;34(3):331–55.
Oral Maxillofac Surg. 2016;45(10):1187–94.
4. Bell RB. A history of orthognathic surgery
22. Susarla SM, Cho DY, Ettinger RE, Dodson TB. The
in North America. J Oral Maxillofac Surg.
low medial horizontal osteotomy in patients with atyp-
2018;76(12):2466–81.
ical ramus morphology undergoing sagittal Split oste-
5. Patel PK, Novia MV. The surgical tools: the LeFort
otomy. J Oral Maxillofac Surg. 2020;78(10):1813–9.
I, bilateral sagittal split osteotomy of the man-
23. Cheever DW. Displacement of the upper jaw. Med
dible, and the osseous genioplasty. Clin Plast Surg.
Surg Rep Boston City Hosp. 1870;1:156.
2007;34(3):447–75.
24. Wassamund M. Frakuren und Luxationen des
6. Monson LA. Bilateral sagittal split osteotomy. Semin
Gesichtsschadels. Leipzig: Meusser; 1927.
Plast Surg. 2013;27(3):145–8.
25. Axhausen G. Zur Behandlung veralteter dislozi-
7. Buchanan EP, Hyman CH. LeFort I osteotomy. Semin
ert geheilter Oberkieferbruche. Dstch Zahn Mund
Plast Surg. 2013;27(3):149–54.
Kieferheilkd. 1934;1:334.
8. Naran S, Steinbacher DM, Taylor JA. Current con-
26. Converse JM, Horowitz SL. The surgical-orthodontic
cepts in orthognathic surgery. Plast Reconstr Surg.
approach to the treatment of dentofacial deformities.
2018;141(6):925e–36e.
Am J Orthod. 1969;55(3):217–43.
9. Farrell BB, Franco PB, Tucker MR. Virtual surgical
27. Bell WH, Fonseca RJ, Kenneky JW, Levy BM. Bone
planning in orthognathic surgery. Oral Maxillofac
healing and revascularization after total maxillary
Surg Clin North Am. 2014;26(4):459–73.
osteotomy. J Oral Surg. 1975;33(4):253–60.
10. Apostolakis D, Michelinakis G, Kamposiora P,
28. Turvey TA, Fonseca RJ. The anatomy of the inter-
Papavasiliou G. The current state of computer assisted
nal maxillary artery in the pterygopalatine fossa:
orthognathic surgery: a narrative review. J Dent.
its relationship to maxillary surgery. J Oral Surg.
2022;119:104052.
1980;38(2):92–5.
11. Roy T, Steinbacher DM. Virtual planning and 3D
29. Quejada JG, Kawamura H, Finn RA, Bell WH. Wound
printing in contemporary orthognathic surgery. Semin
healing associated with segmental total maxillary oste-
Plast Surg. 2022;36(3):169–82.
otomy. J Oral Maxillofac Surg. 1986;44(5):366–77.
12. Li DTS, Leung YY. Patient-specific implants in
30. Bell WH, McBride KL. Correction of the long face
orthognathic surgery. Oral Maxillofac Surg Clin
syndrome by Le Fort I osteotomy. A report on some
North Am. 2023;35(1):61–9.
new technical modifications and treatment results.
13. Chen J, Abousy M, Girard A, Duclos O, Patel V,
Oral Surg Oral Med Oral Pathol. 1977;44(4):493–520.
Jenny H, Redett R, Yang R. The impact of virtual
31. Bell WH. Le Forte I osteotomy for correction of max-
surgical planning on orthognathic surgery: con-
illary deformities. J Oral Surg. 1975;33(6):412–26.
tributions from two specialties. J Craniofac Surg.
32. Bell WH. Biologic basis for maxillary osteotomies.
2022;33(5):1418–23.
Am J Phys Anthropol. 1973;38(2):279–89.
14. Susarla SM, Tveit M, Dodson TB, Kaban LB, Hopper
33. Arnett GW, Bergman RT. Facial keys to orthodontic
RA, Egbert MA. What are the defining characteristics
diagnosis and treatment planning. Part I. Am J Orthod
of the most cited publications in orthognathic surgery?
Dentofacial Orthop. 1993;103(4):299–312.
Int J Oral Maxillofac Surg. 2018;47(11):1411–9.
34. Arnett GW, Bergman RT. Facial keys to orthodon-
15. Grillo R. Orthognathic surgery: a bibliometric anal-
tic diagnosis and treatment planning—Part II. Am J
ysis of the top 100 cited articles. J Oral Maxillofac
Orthod Dentofacial Orthop. 1993;103(5):395–411.
Surg. 2021;79(11):2339–49.
35. Arnett GW, Jelic JS, Kim J, Cummings DR, Beress
16. Trauner R, Obwegeser H. The surgical correction
A, Worley CM Jr, Chung B, Bergman R. Soft tis-
of mandibular prognathism and retrognathia with
sue cephalometric analysis: diagnosis and treatment
consideration of genioplasty. I. Surgical procedures
planning of dentofacial deformity. Am J Orthod
to correct mandibular prognathism and reshap-
Dentofacial Orthop. 1999;116(3):239–53.
ing of the chin. Oral Surg Oral Med Oral Pathol.
36. Ajmera DH, Singh P, Leung YY, Gu M. Three-
1957;10(7):677–89.
dimensional evaluation of soft-tissue response to
17. Aziz SR, Simon P. Hullihen and the origin of
osseous movement after orthognathic surgery in
orthognathic surgery. J Oral Maxillofac Surg.
patients with facial asymmetry: a systematic review. J
2004;62(10):1303–7.
Craniomaxillofac Surg. 2021;49(9):763–74.
37. San Miguel Moragas J, Oth O, Büttner M, Mommaerts 51. Al-Moraissi EA, Al-Hendi EA. Are bicortical screw
MY. A systematic review on soft-to-hard tissue ratios and plate osteosynthesis techniques equal in provid-
in orthognathic surgery part II: Chin procedures. J ing skeletal stability with the bilateral sagittal split
Craniomaxillofac Surg. 2015;43(8):1530–40. osteotomy when used for mandibular advancement
38. Olate S, Zaror C, Mommaerts MY. A systematic surgery? A systematic review and meta-analysis. Int J
review of soft-to-hard tissue ratios in orthognathic Oral Maxillofac Surg. 2016;45(10):1195–200.
surgery. Part IV: 3D analysis—Is there evidence? J 52. Al-Moraissi EA, Ellis E. Stability of bicortical screw
Craniomaxillofac Surg. 2017;45(8):1278–86. versus plate fixation after mandibular setback with
39. Olate S, Zaror C, Blythe JN, Mommaerts MY. A the bilateral sagittal split osteotomy: a systematic
systematic review of soft-to-hard tissue ratios review and meta-analysis. Int J Oral Maxillofac Surg.
in orthognathic surgery. Part III: double jaw 2016;45(1):1–7.
surgery procedures. J Craniomaxillofac Surg. 53. Susarla SM, Ettinger R, Preston K, Kapadia H,
2016;44(10):1599–606. Egbert MA. Two-point nasomaxillary fixation of
40. San Miguel Moragas J, Van Cauteren W, Mommaerts the Le Fort I osteotomy: assessment of stability at
MY. A systematic review on soft-to-hard tissue one year postoperative. Int J Oral Maxillofac Surg.
ratios in orthognathic surgery part I: maxillary 2020;49(4):466–70.
repositioning osteotomy. J Craniomaxillofac Surg. 54. Gateno J, Xia JJ, Teichgraeber JF, Christensen AM,
2014;42(7):1341–51. Lemoine JJ, Liebschner MA, Gliddon MJ, Briggs
41. Shindoi JM, Matsumoto Y, Sato Y, Ono T, Harada ME. Clinical feasibility of computer-aided surgi-
K. Soft tissue cephalometric norms for orthogna- cal simulation (CASS) in the treatment of complex
thic and cosmetic surgery. J Oral Maxillofac Surg. cranio-maxillofacial deformities. J Oral Maxillofac
2013;71(1):e24–30. Surg. 2007;65(4):728–34.
42. Proffit WR, Phillips C, Turvey TA. Stability after 55. Xia JJ, Gateno J, Teichgraeber JF, Yuan P, Li J, Chen
surgical-orthodontic corrective of skeletal class III KC, Jajoo A, Nicol M, Alfi DM. Algorithm for plan-
malocclusion. 3. Combined maxillary and mandibular ning a double-jaw orthognathic surgery using a
procedures. Int J Adult Orthodon Orthognath Surg. computer-aided surgical simulation (CASS) protocol.
1991;6(4):211–25. Part 2: three-dimensional cephalometry. Int J Oral
43. Costa F, Robiony M, Sembronio S, Polini F, Politi Maxillofac Surg. 2015;44(12):1441–50.
M. Stability of skeletal class III malocclusion after 56. Xia JJ, Gateno J, Teichgraeber JF, Yuan P, Chen
combined maxillary and mandibular procedures. Int J KC, Li J, Zhang X, Tang Z, Alfi DM. Algorithm for
Adult Orthodon Orthognath Surg. 2001;16(3):179–92. planning a double-jaw orthognathic surgery using a
PMID: 12387609. computer-aided surgical simulation (CASS) protocol.
44. Proffit WR, Turvey TA, Phillips C. The hierarchy of Part 1: planning sequence. Int J Oral Maxillofac Surg.
stability and predictability in orthognathic surgery 2015;44(12):1431–40.
with rigid fixation: an update and extension. Head 57. Hsu SS, Gateno J, Bell RB, Hirsch DL, Markiewicz
Face Med. 2007;3:21. MR, Teichgraeber JF, Zhou X, Xia JJ. Accuracy of
45. Proffit WR, Turvey TA, Phillips C. Orthognathic sur- a computer-aided surgical simulation protocol for
gery: a hierarchy of stability. Int J Adult Orthodon orthognathic surgery: a prospective multicenter study.
Orthognath Surg. 1996;11(3):191–204. J Oral Maxillofac Surg. 2013;71(1):128–42.
46. Dolce C, Hatch JP, Van Sickels JE, Rugh JD. Rigid 58. Xia JJ, Phillips CV, Gateno J, Teichgraeber JF,
versus wire fixation for mandibular advancement: Christensen AM, Gliddon MJ, Lemoine JJ, Liebschner
skeletal and dental changes after 5 years. Am J Orthod MA. Cost-effectiveness analysis for computer-aided
Dentofacial Orthop. 2002;121(6):610–9. surgical simulation in complex cranio-maxillofacial
47. Van Sickels JE, Dolce C, Keeling S, Tiner BD, Clark surgery. J Oral Maxillofac Surg. 2006;64(12):1780–4.
GM, Rugh JD. Technical factors accounting for sta- 59. Xia JJ, Gateno J, Teichgraeber JF. Three-dimensional
bility of a bilateral sagittal split osteotomy advance- computer-aided surgical simulation for maxillofacial
ment: wire osteosynthesis versus rigid fixation. Oral surgery. Atlas Oral Maxillofac Surg Clin North Am.
Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;13(1):25–39.
2000;89(1):19–23. 60. Chen Z, Mo S, Fan X, You Y, Ye G, Zhou N. A meta-
48. Van Sickels JE, Richardson DA. Stability of orthog- analysis and systematic review comparing the effec-
nathic surgery: a review of rigid fixation. Br J Oral tiveness of traditional and virtual surgical planning
Maxillofac Surg. 1996;34(4):279–85. for orthognathic surgery: based on randomized clini-
49. Mavili ME, Canter HI, Saglam-Aydinatay cal trials. J Oral Maxillofac Surg. 2021;79(2):471.
B. Semirigid fixation of mandible and maxilla in e1–471.e19.
orthognathic surgery: stability and advantages. Ann 61. Şenyürek SA, Ajami S, Ruggiero F, Van de Lande L,
Plast Surg. 2009;63(4):396–403. Caron CJJM, Schievano S, Dunaway DJ, Padwa B,
50. Yoon HJ, Rebellato J, Keller EE. Stability of the Koudstaal MJ, Borghi A. The accuracy of computer-
Le Fort I osteotomy with anterior internal fixa- assisted surgical planning in predicting soft tissue
tion alone: a case series. J Oral Maxillofac Surg. responses after Le Fort I osteotomy: retrospective
2005;63(5):629–34. analysis. J Craniofac Surg. 2023;34(1):131–8.
62. Knoops PGM, Borghi A, Breakey RWF, Ong J, cases]. SSO Schweiz Monatsschr Zahnheilkd.
Jeelani NUO, Bruun R, Schievano S, Dunaway DJ, 1976;86(2):167–185.
Padwa BL. Three-dimensional soft tissue predic- 65. Tremont TJ, Posnick JC. Selected orthodontic prin-
tion in orthognathic surgery: a clinical comparison ciples for management of cranio-maxillofacial
of Dolphin, ProPlan CMF, and probabilistic finite deformities. Oral Maxillofac Surg Clin North Am.
element modelling. Int J Oral Maxillofac Surg. 2020;32(2):321–38.
2019;48(4):511–8. 66. Steegman R, Hogeveen F, Schoeman A, Ren Y. Cone
63. Alkaabi S, Maningky M, Helder MN, Alsabri beam computed tomography volumetric airway
G. Virtual and traditional surgical planning in orthog- changes after orthognathic surgery: a systematic
nathic surgery—systematic review and meta-analysis. review. Int J Oral Maxillofac Surg. 2023;52(1):60–71.
Br J Oral Maxillofac Surg. 2022;60(9):1184–91. 67. Shokri A, Ramezani K, Afshar A, Poorolajal J,
64. Schmoker R, Spiessl B, Tschopp H M, Prein J, Ramezani N. Upper airway changes following differ-
Jaques W A. [Functionally stable osteosynthesis ent orthognathic surgeries, evaluated by cone beam
of the mandible by means of an excentric-dynamic computed tomography: a systematic review and meta-
compression plate. Results of a follow-up of 25 analysis. J Craniofac Surg. 2021;32(2):e147–52.
Evolution of Head and Neck
Cancer Management
13
Abstract It aims to provide insight into the relevant

From the historical introduction of microsur- history, challenges encountered, and mile-
gery and free flap reconstruction to the adop- stones achieved in the field. The topics of vir-
tion of robotic surgery and virtual surgical tual surgical planning per se and mandibular
planning in the modern era, ablative and reconstruction are discussed elsewhere.
reconstructive surgery for head and neck
cancer continues to improve in reliability
Keywords
and sophistication with commensurate
improvement in functional and aesthetic out- Head and neck · Anterolateral thigh flap ·
comes. This chapter will discuss five key Perforator flaps · Microsurgery · Virtual
landmark papers and explore how they, surgical planning · Robotic surgery · Skull
together with other important supporting base reconstruction · Nasoseptal flap · Neck
publications, have shaped contemporary dissection · Reconstruction surgery
practice in head and neck cancer surgery,
specifically in:
The Five Most Impactful Papers
• Perforator free flap in head and neck 1. Song YG, Chen GZ, Song YL. The free thigh
reconstruction flap: a new free flap concept based on the sep-
• Maxillary reconstruction tocutaneous artery. Br J Plast Surg.
• Skull base reconstruction and nasoseptal 1984;37:149–59.
flap 2. Hidalgo DA. Fibula free flap: a new method of
• Transoral robotic surgery mandible reconstruction. Plast Reconstr Surg.
• Treatment of cervical node metastasis 1989;84:71–9.
3. O’Malley BW Jr, Weinstein GS, Snyder W,
Hockstein NG. Transoral robotic surgery
(TORS) for base of tongue neoplasms.
S. Ch’Ng (*) Laryngoscope. 2006;116:1465–72.
The University of Sydney, 4. Hadad G, et al. A novel reconstructive tech-
Camperdown, NSW, Australia nique after endoscopic expanded endonasal
Y. J. Jeong approaches: vascular pedicle nasoseptal flap.
Royal Prince Alfred Hospital, Laryngoscope. 2006;116:1882–6.
Camperdown, NSW, Australia
https://doi.org/10.1007/978-3-031-57132-9_13
120 S. Ch’Ng and Y. J. Jeong
5. Shah JP. Patterns of cervical lymph node tubed pedicle flap [1]. This has enabled head and
metastasis from squamous carcinomas of the neck surgeons to take a more aggressive approach
upper aerodigestive tract. Am J Surg. to tumor ablation, resulting in superior local dis-
1990;160:405–9. ease control compared with the era before the
routine use of free flaps [1–3].
Following description of the first free (groin)
13.1 Introduction flap by Daniel and Taylor in 1973 [4], the devel-
opment of free flaps progressed exponentially
The field of head and neck cancer has witnessed after the classification of vascular anatomy of
rapid advancements over the past few decades muscles by Mathes and Nahai in 1981 [5]. Flaps,
and continues to evolve today. The present chap- including the latissimus dorsi myocutaneous free
ter will explore five key landmark papers and flap [6], radial forearm free flap [7], and scapular
how they have transformed current practice in free flap [8], were described in swift succession.
this field, with a focus on the development of Notably, the radial free flap was particularly well
microsurgery and perforator flaps, maxillary suited for head and neck reconstruction given its
reconstruction, robotic-assisted surgery, and the ability to provide a pliable thin skin paddle, but
evolving role of neck dissection in the manage- admittedly was limited by its significant donor
ment of head and neck cancer. site morbidity [9–11].
In 1984, Song et al. introduced the anterolat-
eral thigh free flap (ALT) as a novel technique
13.2 Perforator Free Flaps in Head for head and neck soft tissue reconstruction [12].
and Neck Reconstruction Their article detailed anatomical and planning
considerations for the ALT, anteromedial thigh
The introduction of microvascular free tissue (AMT) and posterior thigh (PT) free flaps, and
transfer in the late 1970s revolutionized the man- described operative methods for the ALT free
agement of head and neck cancers. With micro- flap specifically. They presented their results of
surgical techniques, free flaps allow for 15 free thigh flap (ALT, n = 9; AMT, n = 4; PT,
reconstruction of complex head and neck defects n = 2) transfers in patients with head and neck
in a single-stage procedure. Free flaps have dem- burn contractures. Despite all 15 flaps requiring
onstrated greater versatility, aesthetic outcomes, secondary thinning procedures, all contractures
and reliability compared with previous work- were corrected, and no flap failures were
horses of head and neck reconstruction, e.g., reported.
Song YG, Chen GZ, Song YL. The free thigh flap: a new free flap concept based on the septocutaneous artery. Br J
Plast Surg. 1984;37:149–59
Strengths • Introduces the concept of a free thigh flap based on the septocutaneous artery. Comprehensive
description of anatomical considerations, operative technique for ALT free flap harvest, and
potential modifications to tailor the flap
Limitations • Small cohort (n = 9 for ALT flap). Limited discussion of post-operative complications and
follow-up data, and no patient-reported outcomes
Impact Song et al.’s work besides pioneering ALT free flap’s utility for the reconstruction of head and neck
defects also heralded the perforator free flap technique. The ALT free flap is now considered the
‘work-horse’ flap for reconstruction of soft tissue defects in the head and neck region
13 Evolution of Head and Neck Cancer Management 121
Despite that Koshima and Soeda first coined the was risky [14]. However, as greater confidence
term “perforator flap” in 1989 [13], and despite developed with retrograde dissection of intra-
that Song et al. erroneously proffered that the muscular perforators and irreversible donor site
dominant blood supply of the ALT free flap was morbidity became negligible with sparing of
from septocutaneous “cutaneous arteries” donor site muscles and preservation of motor
(which have evolved to be known now as “perfo- and cutaneous nerves, the popularity of ALT free
rators”). Song et al. did in essence describe a flaps rose rapidly fulfilling the reconstructive
perforator free flap detailing the “occasional” needs of many head and neck defects, ultimately
necessity of dissection of musculocutaneous sealing its position as the workhorse flap for con-
perforators for ALT free flaps in their 1984 land- temporary head and neck reconstruction
mark paper. Uptake of the ALT free flap was ini- (Table 13.1) [25, 26]. The number of other perfo-
tially hampered by the difficulty associated with rator free flaps described for head and neck
intramuscular dissection of perforators, and the reconstruction has also increased correspond-
perception that skeletonization of perforators
ingly (Table 13.2).
Table 13.1 Uses of the ALT flap in head and neck reconstruction
Indication Notes
Scalp defects The ALT flap provides the advantage of large volume, sufficient length of pedicle for
anastomosis in the neck, and the option of fascia lata as vascularized dural replacement [15,
16]. Indications include large-scalp defects, defects with bone or dural loss, and if a long
vascular pedicle length is required [15]
Laryngopharyngeal The tubed ALT free flap is an excellent option for conduit restoration besides being able to
defects provide additional tissue volume if required in the form of a chimeric flap to obliterate the
potential dead space and protect the great vessels [17]. It has largely superseded the jejunal and
radial forearm free flaps for laryngopharyngectomy reconstruction [18]
Tongue defects The ALT free flap provides substantial volume for reconstructing larger tongue defects and is
often used preferentially over the radial forearm free flap in advanced tongue cancer (subtotal
glossectomy or total glossectomy) [19]
Skull base defects Large and complex skull base defects can be reconstructed with composite ALT free flaps with
skin, muscle, and fascial components [20]. The ALT free flap also has a long vascular pedicle
with reliable blood supply suitable for dural reconstruction [21]
Contour defects of The ALT flap offers excellent contour restoration of the neck and face, including
the neck parotidectomy defects. The ALT flap can be de-epithelialized for placement as a buried flap for
contour restoration in defects with little or no skin component [22]. Chimeric vastus lateralis
and ALT free flap can be used to restore dynamic reanimation in radical parotidectomy with
facial nerve palsy [23]
Oromandibular In reconstruction of an extensive composite oromandibular defects, the ALT flap can be
defects combined with a fibula free flap [24]
Abbreviations: ALT anterolateral thigh
Table 13.2 Common perforator flaps used in head and neck reconstruction
Perforator flap Donor artery Indications Notes
ALT (Song et al., Descending branch of Face, oral cavity, Useful for large defects
1984) [12] lateral femoral tongue, neck Can be used as a chimeric flap
circumflex artery Minimal donor site morbidity
AMT (Song et al., Medial circumflex Face, oral cavity, Good alternative to ALT
1984) [12] femoral artery tongue, neck Minimal donor site morbidity Variable
vascular anatomy
UAP (Song et al., 1982; Ulnar artery Oral cavity, tongue, Less hairy and enables superior
Becker and Gilbert, face, neck, periorbital concealment of the donor site scar
1988) [9, 27] compared with its radial counterpart
SIEA (Grotting, Superficial inferior Nose, lip, cheeks, Useful for smaller defects
1991) [28] epigastric artery tongue Most commonly used for breast
reconstruction
No muscular dissection required
Submental (Martin Submental artery Face, tongue, oral Good color match for cutaneous
et al., 1993) [29] cavity reconstruction
Short pedicle therefore suitable for
reconstruction of lower face and oral
cavity defect
TDAP (Angrigiani Thoracodorsal artery Face, oral cavity, Thin and pliable. Large skin paddle
et al., 1995) [30] skull base dimensions possible
Useful for resurfacing shallow defects or
filling contour deformities. Relatively
well concealed donor site
DCIA (Safak et al., Deep circumflex iliac Mandible, intraoral Can be used as chimeric flap
1997) [31] artery Commonly harvested with bone
Small skin paddle
SCIA (Koshima Superficial circumflex Oral cavity, tongue, Evolution of the free groin flap.
et al., 2004) [32] iliac artery oropharynx, maxilla Concealed donor site
Can be elevated with nerves, lymph
nodes, and bone (iliac crest)
Note Song et al. first described the ulnar forearm flap as a free flap in 1982, but the true UAP flap was described later
by Becker and Gilbert in 1988
Abbreviations: ALT anterolateral thigh, DCIA deep circumflex iliac artery, TDAP thoracodorsal artery perforator, SCIA
superficial circumflex iliac artery, SIEA superficial inferior epigastric artery, UAP ulnar artery perforator
The ALT free flap has also demonstrated its ver- demonstrated promising efficacy [36–38]. These
satility in flap design. It can be harvested as a sen- technologies, in addition to enabling position of
sate flap with the inclusion of the lateral femoral perforator(s) to be identified for planning of skin
cutaneous nerve, a conjoint flap with AMT or ten- incisions, can also be used to confirm patency of
sor fascia lata flap, and as a chimeric flap with anastomosis or detect kinking/compression of the
separate skin, muscle, and bone components [33, vascular pedicle during flap inset, enabling early
34]. Additionally, the thickness of the ALT flap can intervention if necessary. While yet to be widely
be tailored according to the defect to reduce the adopted in clinical practice, these imaging
need of subsequent debulking, including ultra-thin modalities are likely to enhance the reliability of
(through the superficial fat), super- thin (at the perforator flap reconstruction.
superficial fascia), thin (above the deep fascia), in
addition to the standard (including the deep fascia),
flap [35] or by incorporating the vastus lateralis 13.3 Maxillary Reconstruction
muscle to add bulk to suit the head and neck defect.
Intraoperative monitoring techniques, includ- Maxillary defects present a unique challenge for
ing infrared (IR) thermography, near-IR fluores- plastic surgeons. Given the complex three-
cent angiography, and near-IR spectroscopy have dimensional anatomy of the maxilla, its contigu-
ous relationship to critical surrounding structures, used for maxillary reconstruction over a five-year
and the variable shapes and sizes of tumors period were reviewed and classified as the fol-
affecting the midface, various reconstruction lowing: type I, limited maxillectomy (n = 7);
methods following oncological resection have type II, subtotal maxillectomy (n = 10); type IIIa,
been described and the best option must be care- total maxillectomy with preservation of the
fully considered for each patient. orbital contents (n = 13); type IIIb, total
A classification system that effectively cate- maxillectomy with orbital exenteration (n = 18);
gories the various maxillectomy defects can and type IV, orbitomaxillectomy (n = 10). These
facilitate clear communication and decision- classifications were used to construct a recon-
making in the reconstructive algorithm. In 2000, struction algorithm based on the surface area-to-
Cordeiro and Santamaria introduced a classifica- volume requirements of the defect, the need for
tion system and an algorithm for the reconstruc- palatal closure, and need for orbital
tion of maxillectomy defects [39]. Sixty flaps reconstruction.
Cordeiro PG, Santamaria E. A classification system and algorithm for reconstruction of maxillectomy and midfacial
defects. Plast Reconstr Surg. 2000;105:2331–46; discussion 2347–2338
Strengths • Classification is simple to follow
• Provides a clear guideline for flap reconstruction of various complex maxillectomy defects
Limitations • Does not address composite defects. Limited discussion of the need for functional dental
reconstruction
Impact Cordeiro and Santamaria’s classification system is widely adopted in clinical practice due to its
simple, systematic approach for the reconstruction of complex maxillectomy defects, and heralded
more complex algorithms
Cordeiro and Santamaria offered a practical clas- microsurgery (e.g., deep circumflex iliac artery,
sification system for the effective comparison radial, and fibular free flaps) has permitted single-
and discussion of maxillary and midfacial recon- stage reconstruction of complex midfacial defects
structions in literature [40, 41]. It also provided a with improved functional and aesthetic out-
basis for the development of other more exten- comes. Recently, there has been a growing inter-
sive classification systems, such as Gastman, for est in the scapular angle osseomuscular free flap
extremely complicated defects best addressed [45]; its popularisation is largely attributed to its
with facial allo-transplantation [42]. Despite its long pedicle and its shape and natural contour,
significance, Cordeiro and Santamaria’s work which can provide excellent form for reconstruc-
was not universally accepted. As with various tion of the palate, orbital floor, or the anterior
other classification systems, including Brown maxillary face depending on its orientation [46].
(2000) [43] and Okay (2001) [44], no single sys- In addition, the chimeric nature of the subscapu-
tem is comprehensive enough to cater for the lar vascular system allows for its use in complex
unlimited permutations of defects possible in composite defects with large soft-tissue require-
such a multifaceted structure as the maxilla. In ments [46].
contemporary practice, reconstructive surgeons Maxillary reconstructions have undergone
aim to critically analyze the oncologic defect in considerable refinement with the advent of vir-
terms of its extent, involvement of the palate and tual surgical planning (VSP) and computer-
the infraorbital rim, need for preoperative or assisted design/modelling (CAD/CAM). While
anticipated postoperative radiation, and make osseous free flaps for maxillary reconstruction
patient and defect-centric customized choices. were initially shaped in a free-hand manner based
Reconstructive methods for maxillary defects on the patient’s contralateral anatomy, fine-cut
also continue to evolve. While past techniques computed tomography scans can now be used to
have been dominated by prosthetic obturation, create three-dimensional virtual models of the
patient’s maxillofacial and donor site anatomy. approaches to management of OPSCC but each
Using these virtual models, precise osteotomies has its own limitations. Chemoradiotherapy has
to contour the osseous free flap can be designed,been associated with late complications, includ-
and physical cutting guides and customized tita- ing osteoradionecrosis, xerostomia, mucositis,
nium plates can be generated via stereolitho- loss of taste, and pharyngeal and esophageal ste-
graphic modelling. Occlusion-based guides have noses, and is no longer considered standard treat-
been proven to produce more accurate osteoto- ment for early stage resectable OPSCC tumors
mies and improve bony apposition over guides [53, 54]. TLM, meanwhile, is widely regarded as
based on bony landmarks [47, 48]. Advantages of a technically challenging procedure with a steep
VSP-CAD/CAM-guided maxillary reconstruc- learning curve, and the restricted visualization
tion include greater accuracy in the three- afforded by the laryngoscope limits the size of
dimensional position of the osseous flap, the tumor that can be resected en bloc [55, 56].
improved aesthetic contour, shorter operating In 2006, O’Malley et al. investigated the feasi-
time and greater patient satisfaction [49, 50]. The
bility of transoral robotic surgery (TORS) using
feasibility of a one-stage VSP-guided “jaw-in-a-the DaVinci Surgical Robot for the resection of
day” reconstructions with immediate osseointe- base of tongue neoplasms [56]. Preceding ini-
grated implants has also been described [51, 52].tially with exposure study in cadavers, and base
of tongue resections in cadavers as well as live
canines, they proceeded to perform TORS sur-
13.4 Transoral Robotic Surgery gery of OPSCC on three human patients with
T1–T2 tumors under a prospective clinical trial.
Over recent decades, there have been increasing In cadavers and live canines, TORS was demon-
emphasis on quality of life (QOL) on top of sur- strated to achieve sufficient pharyngeal and base
vival, and greater efforts to reduce treatment- of tongue access with excellent three-dimensional
related toxicities associated with treatment of visualization for complete resection to negative
oropharyngeal squamous cell carcinoma surgical margins and adequate hemostatic con-
(OPSCC). Traditional open surgery requires lip trol. O’Malley et al. described in detail their
split and cervical incisions with mandibulotomy operative technique for TORS, including set-up
and pharyngotomy, which leaves patients with time, choice of retractors, and method of en bloc
significant cosmetic deformity as well as speech resection for OPSCC tumors. At follow-up, all
and swallowing dysfunction. The degree of dis- three patients reported minimal postoperative
figurement and functional morbidity associated pain with no bleeding, airway edema, or other
with open surgery provided impetus for develop- complications, and all patients were able to toler-
ment of alternative treatments for OPSCC. ate a solid diet 6 weeks postoperatively without
Definitive chemoradiotherapy and transoral percutaneous endoscopic gastrostomy (PEG)
laser microsurgery (TLM) are alternative tubes.
O’Malley BW Jr, Weinstein GS, Snyder W, Hockstein NG. Transoral robotic surgery (TORS) for base of tongue
neoplasms. Laryngoscope. 2006;116:1465–72
Strengths • Prospective clinical trial. Detailed description of operative procedure including technique for
complete en bloc tumor resection. Good follow-up with patient-reported outcomes
Limitations • Small cohort (three human patients)
Impact This paper is the first to demonstrate the safety and efficacy of TORS with the DaVinci System in a
clinical setting, offering an effective and reliable management approach without the significant
morbidity associated with open surgery
The emergence of TORS has transformed the to each patient, and the therapeutic strategy
management of resectable OPSCC. The robotic requires evaluation by a multidisciplinary team.
surgical platform allows for improved ergonom- Today, the potential applications of TORS
ics, tremor filtration, motion scaling, and greater have extended to include total laryngectomies,
precision of movement during base of tongue resection of parapharyngeal tumors, and skull
procedures [57]. Compared to open surgery, base surgery, and robotic technological innova-
TORS eliminates the need for lip split/cervical tions continue to advance the management of
incisions with mandibulotomy and pharyngot- head and neck cancer [67]. The most recent gen-
omy, improving functional and cosmetic out- eration of the DaVinci System, the Single Port or
comes while reducing the risk of infection and SP, holds specific potential for use in head and
blood loss [58]. This has translated to lower rates neck surgery as it offers three fully articulating
of intensive care unit admission and reduced instruments and camera all confined within a
length of hospitalization for TORS [53, 58]. In single 25 mm cannula port. This single flexible
addition, robotic optics offer three-dimensional robotic arm enables surgical access beyond the
visualization which significantly reduces the oropharynx to tumors of the hypopharynx and
working space constraints compared with TLM, larynx, and overcomes several limitations of pre-
enabling an easier en bloc tumor resection [56]. vious models (Si, Xi) described elsewhere [68].
Nguyen et al. recently performed a retrospective Multiple prospective trials have now confirmed
study of 9745 patients with cT1–T2 OPSCC to the feasibility of the DaVinci SP system for use
demonstrate that TORS was associated with sig- in head and neck surgery [68–70]. The success of
nificantly lower rates of margin positivity, use of the DaVinci System has catalyzed the develop-
adjuvant chemoradiotherapy, and improved over- ment of other robotic devices for head and neck
all survival compared with non-robotic surgical surgery, including K-Flex Surgical Robot [71],
approaches [59]. This finding, however, has yet Flex Robotic System [72], and Symani Surgical
to be validated in large-scale prospective studies. System [73] for microsurgery. While further clin-
The choice between TORS and definitive ical validation of these devices is required, it is
radiotherapy for early stage (T1–T2) OPSCC likely that these advances will contribute to
remains a point of contention. Literature cur- advance the application of robotic-assisted sur-
rently demonstrates comparable 5-year overall gery in head and neck cancer management.
survival rates between TORS (84–94%) and
definitive radiotherapy (81–96%), with no statis-
tical difference in survival outcomes by treatment 13.5 Skull Base Reconstruction
selection in either HPV positive or negative sub- and the Nasoseptal Flap
types [60–63]. Several guidelines, e.g., the UK
NCCN [64], recommend both definitive radio- Endoscopic techniques have transformed certain
therapy and TORS as single-modality treatments head and neck cancer ablation. While skull base
for patients with early stage OPSCC. Whilst sev- malignancies were traditionally managed by cra-
eral retrospective studies suggested superior niotomy, advances in surgical instrumentation
functional outcomes with TORS compared with and neuronavigation have facilitated the adoption
definitive (chemo)radiotherapy [61, 62], long- of endoscopic endonasal approaches. This has
term results from a recent randomized trial allowed for reduced brain retraction, manipula-
(ORATOR) suggested that radiotherapy con- tion of neural structures, and brain edema com-
ferred a slightly higher swallowing QOL as per pared with open surgery, significantly reducing
the MD Anderson Dysphagia Inventory (MDADI) the morbidity and mortality [74, 75]. Today, the
score [65, 66]. However, this difference was not expanded endoscopic endonasal approach
clinically meaningful and became less pro- (EEEA) allows the entire ventral skull base (ante-
nounced over time. Ultimately, the modern man- rior, middle, and posterior cranial fossae) to be
agement of early stage OPSCC must be tailored surgically accessible [76].
Initially, widespread uptake of EEEA was hin- post-operative CSF leaks after EEEA. Hadad
dered by the inability to re-establish a barrier et al. reported the results of a retrospective
between the intracranial structures and the sino- study investigating outcomes in patients who
nasal cavity, which is essential to prevent postop- underwent skull base reconstruction with NSF
erative cerebrospinal fluid (CSF) leaks and (n = 43) at two institutions. After a minimum
ascending bacterial meningitis [77], via the endo- follow-up of 2 months, two patients (4.5%)
scopic method. were found to have transient CSF leaks, two
In 2006, Hadad et al. established the naso- patients (4.5%) had CSF leaks which required
septal flap (NSF) with the vascular pedicle repair with focal fat grafts, and one patient
comprised of the posterior septal artery, a ter- (2.3%) experienced posterior epistaxis that was
minal branch of the sphenopalatine artery [78]. controlled with electrocautery. Importantly,
This chapter details the bimanual surgical tech- flap blood supply in all patients was preserved,
nique to harvest the NSF, potential modifica- and no other infectious or wound complications
tions to the flap (e.g., including the was encountered. The donor site on the nasal
mucoperiosteum of the nasal floor for a wider septum became mucosalized within several
flap), and adjunctive techniques to minimize weeks in all patients.
Hadad G, et al. A novel reconstructive technique after endoscopic expanded endonasal approaches: vascular pedicle
nasoseptal flap. Laryngoscope. 2006;116:1882–6
Strengths • Detailed description of the surgical technique to harvest and tailor the nasoseptal flap to the skull
base defect. Reproducibility of results demonstrated at two institutions. Good follow-up data
including record of postoperative complications
Limitations • Retrospective study. Small patient cohort
Impact This paper enabled the widespread adoption of EEEA by providing a reliable and versatile
reconstructive technique for extensive skull base defects, sufficiently mitigating the risk of post-
operative CSF leaks and infection
Today, the NSF is the mainstay reconstructive success of the NSF. Bilateral NSFs (termed
option for all large skull base defects, and is “Janus flap”) evolved as an option for even
widely considered the most significant advance- larger dural defects of the anterior and ventral
ment in skull base reconstruction over the past skull base [84]. The nasoseptal “rescue” flap
decade by decreasing the incidence of CSF leak (NSRF) approach involves only partial harvest
postoperative complication [79]. This flap has of the most superior and posterior aspect of the
several advantages including a robust vascular NSF at the beginning of surgery so as to mini-
supply, ease of harvest, and a long pedicle which mize unnecessary septal donor site morbidity
allows for a wide arc of rotation. In addition, the from a full flap harvest should it become appar-
large surface area of the NSF enables ready cus- ent that there is no intraoperative CSF leak and
tomization of shape for various defects, and is hence no need for skull base reconstruction
large enough to cover defects extending from the [85]. Other vascularized flaps such as the mid-
cribriform to the clivus [80]. Overall, the NSF dle and inferior turbinate pedicled flaps, palatal
enjoys a high degree of success after skull base flap, and the temporoparietal fascia flap have
reconstruction and has shown consistent results emerged as viable alternatives when prior radia-
across institutions worldwide [81–83]. tion or surgery has damaged the NSF blood sup-
Additional pedicled flaps for skull base onco- ply or when there is direct tumor invasion of the
logical reconstruction were borne out of the nasal septum [86].
13.6 Treatment of Cervical Node facial edema. For these reasons, a modified neck
Metastasis dissection was established and popularized by
Byers [89, 90] and Bocca et al. [91], who proved
Management of the cervical lymph nodes in head that sparing of the non-lymphatic structures, i.e.,
and neck cancer has undergone several paradigm SAN, SCM and IJV, reduced the morbidity of
shifts in the last few decades, and exemplifies the RND while preserving its oncologic
notion that radical surgery does not always trans- effectiveness.
late into better survival outcomes. A node posi- In 1990, Shah published an article investigat-
tive neck has long been recognized as the single ing the patterns of cervical lymph node metasta-
most important prognostic factor for head and sis from squamous carcinomas of the upper
neck cancer, and the presence of cervical lymph aerodigestive tract [92]. Using a consecutive
nodal involvement has been reported to decrease series of 1081 previously untreated patients
the overall survival rate of head and neck carci- undergoing RNDs (oral cavity, n = 501; oro-
nomas by 50% [87]. pharynx, n = 207; hypopharynx, n = 126; lar-
Historically, radical neck dissection (RND) ynx, n = 247), Shah demonstrated that cervical
has been the standard of care for head and neck metastases in the vast majority of patients with a
cancer cervical node metastasis [88]. While RND clinically node-negative neck will occur in level
has proven to be a reliable method of treating the I–III nodes for carcinomas of the oral cavity,
neck, especially with the addition of pre- or post- and in level II–IV nodes for carcinomas of the
operative radiotherapy, it is also associated with oropharynx, hypopharynx, and larynx. These
significant morbidity. Sacrifice of the spinal patterns of cervical lymph node metastases sup-
accessory nerve (SAN) was complicated by ported the adoption of a supraomohyoid END
“shoulder syndrome,” a classical pattern of pain (clearing levels I–III) for patients with cN0 oral
and decreased range of shoulder abduction fol- cancer, and an anterolateral END (clearing lev-
lowing RND, while removal of the sternocleido- els II–IV) for cN0 patients with squamous carci-
mastoid muscle (SCM) and internal jugular veins nomas of the oropharynx, hypopharynx, and
(IJV) led to cosmetic deformity and significant larynx.
Shah JP. Patterns of cervical lymph node metastasis from squamous carcinomas of the upper aerodigestive tract. Am
J Surg. 1990;160:405–9
Strengths • Well-conducted study with large cohort (n = 1081)
• First study to report the distribution of metastasis within cervical lymph nodes in previously
untreated patients undergoing RND for primary tumors of the aerodigestive tract
Impact This paper facilitated the transition from radical and modified neck dissections to a more selective
approach to lymphadenectomy for cN0 squamous carcinomas of the head and neck
Shah’s publication was pivotal for providing a Perhaps one of the most contentious topics of
scientific basis for the adoption of a less invasive contemporary head and neck cancer management
approach to lymphadenectomy in head and neck has been the role of elective neck dissection
cancer patients, and formed the foundation for (END) in patients with early stage, clinically
future prospective trials to confirm the efficacy of node-negative (cT1-T2N0) oral squamous cell
selective neck dissection [93, 94]. Today, selec- cancer (OSCC). Several studies have reported that
tive neck dissection and modified RND are the END confers decreased relapse rates and superior
gold standards for resectable neck disease, while survival outcomes [95–97]. Notably, D’Cruz et al.
classical RNDs are reserved only for very conducted a prospective, randomized clinical trial
advanced disease involving the SCM, IJV and of 500 patients with cT1–T2N0 OSCC, and found
SAN. that END improved the rate of disease-free sur-
vival (69.5% vs. 45.9%, p < 0.001) and overall skull base reconstruction, and treatment of
survival (80.0% vs. 67.5%, p = 0.01) at 3-year cervical lymph node metastasis. These develop-
follow-up compared with no END [98]. However, ments have affected significant paradigm shifts in
the “watchful-waiting” approach might prevent the management of head and neck cancer over
unnecessary surgical intervention in up to 70–80% the last few decades. Yet, to ensure continued
of node-negative patients [99]. Support for the innovation within this field and to optimize
survival benefit of END has been mixed amongst patient outcomes, it is imperative that researchers
recent prospective trials and systematic reviews and surgeons continue to address the ongoing
[100–103]. Significant variability thus remains in challenges of head and neck cancer. In recent
the approach to the clinically node-negative neck years, we have seen exciting progress propelling
worldwide. us to greater precision and even more customized
Recently, sentinel lymph node biopsy (SLNB) treatment plans, including the development of
has emerged as an alternative to END in the man- more intricate, specialized robotic systems, e.g.,
agement of the node negative neck. SLNB offers K-Flex Surgical Robot [71] and Symani Surgical
the advantage of high sensitivity and excellent System [73] hold promise to greater precision
negative predictive value to detect occult lymph and efficiency in surgical execution; the advent of
node metastases in OSCC, which has been proven ultra-thin [35] and super-thin [111] flaps are
in recent multicenter studies and meta-analyzes likely to improve the contour and aesthetic out-
[104–107]. In addition, SLNB has been reported comes of perforator flap reconstruction, and the
to confer lower complication rates, postoperative widespread application of VSP and CAD/CAM
morbidity, and greater cost-effectiveness over to reconstruction in the head and neck including
END procedures [99]. Due to these promising the skull [112, 113].
findings, SLNB has been rapidly adopted as a
diagnostic staging method and incorporated into
several national guidelines for the management References
of OSCC, including the US NICE [108] and UK
NCCN [64] guidelines. 1. Wong C-H, Wei F-C. Microsurgical free flap
in head and neck reconstruction. Head Neck.
As with all fields in head and neck cancer, our 2010;32:1236–45.
approach to the management of cervical lymph 2. Silverberg E, Boring CC, Squires TS. Cancer statis-
nodes continues to evolve. Technical advance- tics, 1990. CA Cancer J Clin. 1990;40:9–26.
ments in MR and CT lymphography, contrast- 3. Blair EA, Callender DL. Head and neck cancer. The
problem. Clin Plast Surg. 1994;21:1–7.
enhanced lymphosonography, and PET 4. Daniel RK, Taylor GI. Distant transfer of an island
lymphoscintigraphy are currently under investi- flap by microvascular anastomoses. A clinical tech-
gation to enhance the diagnostic accuracy of nique. Plast Reconstr Surg. 1973;52:111–7.
SLNB [109], while minimally invasive 5. Mathes SJ, Nahai F. Classification of the vascular
anatomy of muscles: experimental and clinical cor-
approaches, such as superselective neck dissec- relation. Plast Reconstr Surg. 1981;67:177–87.
tion have been described for the surgical manage- 6. Watson JS, Craig RD, Orton CI. The free latissi-
ment of the neck [110]. Although large-scale mus dorsi myocutaneous flap. Plast Reconstr Surg.
studies for these techniques are limited, prelimi- 1979;64:299–305.
7. Yang G. Forearm free skin flap transplantation;
nary data is promising and holds potential to report of 56. Natl Med J China. 1981;61:139–41.
transform contemporary practice. 8. Hamilton SG, Morrison WA. The scapular free flap.
Br J Plast Surg. 1982;35:2–7.
9. Song R, Gao Y, Song Y, Yu Y, Song Y. The forearm
flap. Clin Plast Surg. 1982;9:21–6.
13.7 Expert Concluding 10. Santamaria E, Granados M, Barrera-Franco
Commentary JL. Radial forearm free tissue transfer for head
and neck reconstruction: versatility and reli-
This chapter discusses five landmark articles and ability of a single donor site. Microsurgery.
2000;20:195–201.
supporting literature pertaining to perforator 11. Richardson D, Fisher SE, Vaughan ED, Brown
flaps and microsurgery, robotic-assisted surgery, JS. Radial forearm flap donor-site complications and
morbidity: a prospective study. Plast Reconstr Surg. 27. Becker C, Gilbert A. The ulnar flap. Handchir
1997;99:109–15. Mikrochir Plast Chir. 1988;20:180–3.
12. Song YG, Chen GZ, Song YL. The free thigh flap: a 28. Grotting JC. The free abdominoplasty flap for
new free flap concept based on the septocutaneous immediate breast reconstruction. Ann Plast Surg.
artery. Br J Plast Surg. 1984;37:149–59. 1991;27:351–4.
13. Koshima I, Soeda S. Inferior epigastric artery skin 29. Martin D, et al. The submental island flap: a new
flaps without rectus abdominis muscle. Br J Plast donor site. Anatomy and clinical applications
Surg. 1989;42:645–8. as a free or pedicled flap. Plast Reconstr Surg.
14. Kimata Y, Uchiyama K, Ebihara S, Nakatsuka T, 1993;92:867–73.
Harii K. Anatomic variations and technical problems 30. Angrigiani C, Grilli D, Siebert J. Latissimus dorsi
of the anterolateral thigh flap: a report of 74 cases. musculocutaneous flap without muscle. Plast
Plast Reconstr Surg. 1998;102:1517–23. Reconstr Surg. 1995;96:1608–14.
15. Lin PY, Miguel R, Chew KY, Kuo YR, Yang JC. The 31. Safak T, Klebuc MJ, Mavili E, Shenaq SM. A new
role of the anterolateral thigh flap in complex design of the iliac crest microsurgical free flap with-
defects of the scalp and cranium. Microsurgery. out including the “obligatory” muscle cuff. Plast
2014;34:14–9. Reconstr Surg. 1997;100:1703–9.
16. Zaretski A, et al. Anterolateral thigh perforator flaps 32. Koshima I, et al. Superficial circumflex iliac artery
in head and neck reconstruction. Semin Plast Surg. perforator flap for reconstruction of limb defects.
2006;20:64–72. Plast Reconstr Surg. 2004;113:233–40.
17. Park CW, Miles BA. The expanding role of the 33. Collins J, Ayeni O, Thoma A. A systematic review
anterolateral thigh free flap in head and neck recon- of anterolateral thigh flap donor site morbidity. Can
struction. Curr Opin Otolaryngol Head Neck Surg. J Plast Surg. 2012;20:17–23.
2011;19:263–8. 34. Koshima I, Fukuda H, Soeda S. Free combined
18. Yu P, et al. Pharyngoesophageal reconstruction with anterolateral thigh flap and vascularized iliac bone
the anterolateral thigh flap after total laryngopharyn- graft with double vascular pedicle. J Reconstr
gectomy. Cancer. 2010;116:1718–24. Microsurg. 1989;5:55–61.
19. Cai YC, et al. Comparative analysis of radial fore- 35. Cha HG, Hur J, Ahn C, Hong JP, Suh HP. Ultra-
arm free flap and anterolateral thigh flap in tongue thin anterolateral thigh free flap: an adipocutaneous
reconstruction after radical resection of tongue flap with the most superficial elevation plane. Plast
cancer. ORL J Otorhinolaryngol Relat Spec. Reconstr Surg. 2023;152:718e.
2019;81:252–64. 36. de Weerd L, Mercer JB, Setså LB. Intraoperative
20. Liu H-J, et al. Free flap transfer, a safe and efficient dynamic infrared thermography and free-flap sur-
method for reconstruction of composite skull base gery. Ann Plast Surg. 2006;57:279–84.
defects after salvage resection of advanced intracra- 37. Lee BT, et al. Intraoperative near-infrared fluores-
nial and extracranial communicating tumors. World cence imaging in perforator flap reconstruction:
Neurosurg. 2021;152:e62–70. current research and early clinical experience. J
21. Bianchi B, et al. The free anterolateral thigh muscu- Reconstr Microsurg. 2010;26:59–65.
locutaneous flap for head and neck reconstruction: 38. Chen Y, Shen Z, Shao Z, Yu P, Wu J. Free flap moni-
one surgeon’s experience in 92 cases. Microsurgery. toring using near-infrared spectroscopy: a systemic
2012;32:87–95. review. Ann Plast Surg. 2016;76:590–7.
22. Cannady SB, Seth R, Fritz MA, Alam DS, Wax 39. Cordeiro PG, Santamaria E. A classification sys-
MK. Total parotidectomy defect reconstruction tem and algorithm for reconstruction of maxillec-
using the buried free flap. Otolaryngol Head Neck tomy and midfacial defects. Plast Reconstr Surg.
Surg. 2010;143:637–43. 2000;105:2331–46; discussion 2347–2338.
23. Hasmat S, et al. Chimeric vastus lateralis and antero- 40. Sarukawa S, et al. Immediate maxillary reconstruc-
lateral thigh flap for restoring facial defects and tion after malignant tumor extirpation. Eur J Surg
dynamic function following radical parotidectomy. Oncol. 2007;33:518–23.
Plast Reconstr Surg. 2019;144:853e–63e. 41. Hanasono MM, Silva AK, Yu P, Skoracki RJ. A com-
24. Wei FC, Celik N, Chen HC, Cheng MH, Huang prehensive algorithm for oncologic maxillary recon-
WC. Combined anterolateral thigh flap and vascu- struction. Plast Reconstr Surg. 2013;131:47–60.
larized fibula osteoseptocutaneous flap in recon- 42. Gastman B, Djohan R, Siemionow M. Extending
struction of extensive composite mandibular defects. the Cordeiro maxillofacial defect classifica-
Plast Reconstr Surg. 2002;109:45–52. tion system for use in the era of vascularized
25. Wei FC, et al. Have we found an ideal soft-tissue composite transplantation. Plast Reconstr Surg.
flap? An experience with 672 anterolateral thigh 2012;130:419–22.
flaps. Plast Reconstr Surg. 2002;109:2219–26; dis- 43. Brown JS, Rogers SN, McNally DN, Boyle M. A
cussion 2227–2230. modified classification for the maxillectomy defect.
26. Yu P. Characteristics of the anterolateral thigh flap in Head Neck. 2000;22:17–26.
a Western population and its application in head and 44. Okay DJ, Genden E, Buchbinder D, Urken
neck reconstruction. Head Neck. 2004;26:759–69. M. Prosthodontic guidelines for surgical reconstruc-
tion of the maxilla: a classification system of defects. 61. Yeh DH, et al. Transoral robotic surgery vs. radio-
J Prosthet Dent. 2001;86:352–63. therapy for management of oropharyngeal squamous
45. Brown JS, Shaw RJ. Reconstruction of the max- cell carcinoma—a systematic review of the litera-
illa and midface: introducing a new classification. ture. Eur J Surg Oncol. 2015;41:1603–14.
Lancet Oncol. 2010;11:1001–8. 62. Ling DC, et al. Oncologic outcomes and patient-
46. Miles BA, Gilbert RW. Maxillary reconstruction with reported quality of life in patients with oropharyn-
the scapular angle osteomyogenous free flap. Arch geal squamous cell carcinoma treated with definitive
Otolaryngol Head Neck Surg. 2011;137:1130–5. transoral robotic surgery versus definitive chemora-
47. Seikaly H, et al. The Alberta reconstructive tech- diation. Oral Oncol. 2016;61:41–6.
nique: an occlusion-driven and digitally based jaw 63. Morisod B, Simon C. Meta-analysis on survival of
reconstruction. Laryngoscope. 2019;129:S1–S14. patients treated with transoral surgery versus radio-
48. Rohner D, et al. Maxillofacial reconstruction therapy for early-stage squamous cell carcinoma
with prefabricated osseous free flaps: a 3-year of the oropharynx. Head Neck. 2016;38(Suppl
experience with 24 patients. Plast Reconstr Surg. 1):E2143–50.
2003;112:748–57. 64. National Comprehensive Cancer Network. Head and
49. Zhang WB, et al. Reconstruction of maxillary defects neck cancers (Version 1.2023). 2022.
with free fibula flap assisted by computer techniques. 65. Nichols AC, et al. Radiotherapy versus transoral
J Craniomaxillofac Surg. 2015;43:630–6. robotic surgery and neck dissection for oropha-
50. Alwadeai MS, Al-aroomy LA, Shindy MI, Amin ryngeal squamous cell carcinoma (ORATOR): an
AA-W, Zedan MH. Aesthetic reconstruction of open-label, phase 2, randomised trial. Lancet Oncol.
onco-surgical maxillary defects using free scapular 2019;20:1349–59.
flap with and without CAD/CAM customized oste- 66. Nichols AC, et al. Randomized trial of radiotherapy
otomy guide. BMC Surg. 2022;22:362. versus transoral robotic surgery for oropharyngeal
51. Levine JP, et al. Jaw in a day: total maxillofa- squamous cell carcinoma: long-term results of the
cial reconstruction using digital technology. Plast ORATOR trial. J Clin Oncol. 2022;40:866–75.
Reconstr Surg. 2013;131:1386–91. 67. Boehm F, et al. Current advances in robotics for head
52. Runyan CM, et al. Jaw in a day: state of the art and neck surgery—a systematic review. Cancers
in maxillary reconstruction. J Craniofac Surg. (Basel). 2021;13:1398.
2016;27:2101–4. 68. Holsinger FC, et al. A next-generation single-port
53. Kelly K, Johnson-Obaseki S, Lumingu J, Corsten robotic surgical system for transoral robotic sur-
M. Oncologic, functional and surgical outcomes of gery: results from prospective nonrandomized
primary transoral robotic surgery for early squamous clinical trials. JAMA Otolaryngol Head Neck Surg.
cell cancer of the oropharynx: a systematic review. 2019;145:1027–34.
Oral Oncol. 2014;50:696–703. 69. Chan JYK, et al. Prospective clinical trial to evaluate
54. Nguyen NP, et al. Prevalence of pharyngeal and safety and feasibility of using a single port flexible
esophageal stenosis following radiation for head robotic system for transoral head and neck surgery.
and neck cancer. J Otolaryngol Head Neck Surg. Oral Oncol. 2019;94:101–5.
2008;37:219–24. 70. Park YM, et al. The first human trial of transoral
55. Rubinstein M, Armstrong WB. Transoral laser micro- robotic surgery using a single-port robotic system
surgery for laryngeal cancer: a primer and review of in the treatment of laryngo-pharyngeal cancer. Ann
laser dosimetry. Lasers Med Sci. 2011;26:113–24. Surg Oncol. 2019;26:4472–80.
56. O’Malley BW Jr, Weinstein GS, Snyder W, 71. Hwang M, Kwon DS. K-FLEX: a flexible robotic
Hockstein NG. Transoral robotic surgery (TORS) platform for scar-free endoscopic surgery. Int J Med
for base of tongue neoplasms. Laryngoscope. Robot. 2020;16:e2078.
2006;116:1465–72. 72. Lang S, et al. A european multicenter study evaluat-
57. Mucksavage P, Kerbl DC, Lee JY. The da Vinci(®) ing the flex robotic system in transoral robotic sur-
surgical system overcomes innate hand dominance. gery. Laryngoscope. 2017;127:391–5.
J Endourol. 2011;25:1385–8. 73. Innocenti M, Malzone G, Menichini G. First-in-
58. Dean NR, et al. Robotic-assisted surgery for pri- human free-flap tissue reconstruction using a dedi-
mary or recurrent oropharyngeal carcinoma. Arch cated microsurgical robotic platform. Plast Reconstr
Otolaryngol Head Neck Surg. 2010;136:380–4. Surg. 2023;151:1078.
59. Nguyen AT, et al. Comparison of survival after 74. Prosser JD, Vender JR, Alleyne CH, Solares
transoral robotic surgery vs nonrobotic surgery in CA. Expanded endoscopic endonasal approaches
patients with early-stage oropharyngeal squamous to skull base meningiomas. J Neurol Surg B Skull
cell carcinoma. JAMA Oncol. 2020;6:1555–62. Base. 2012;73:147–56.
60. Baliga S, et al. Utilization of transoral robotic sur- 75. Hardesty DA, et al. Complications after 1002 endo-
gery (TORS) in patients with oropharyngeal squa- scopic endonasal approach procedures at a single
mous cell carcinoma and its impact on survival and center: lessons learned, 2010–2018. J Neurosurg.
use of chemotherapy. Oral Oncol. 2018;86:75–80. 2022;136:393–404.
76. Snyderman CH, et al. What are the limits of 92. Shah JP. Patterns of cervical lymph node metastasis
endoscopic sinus surgery?: the expanded endo- from squamous carcinomas of the upper aerodiges-
nasal approach to the skull base. Keio J Med. tive tract. Am J Surg. 1990;160:405–9.
2009;58:152–60. 93. Guo CB, et al. Supraomohyoid neck dissection and
77. Kassam A, Carrau RL, Snyderman CH, Gardner P, modified radical neck dissection for clinically node-
Mintz A. Evolution of reconstructive techniques fol- negative oral squamous cell carcinoma: a prospec-
lowing endoscopic expanded endonasal approaches. tive study of prognosis, complications and quality of
Neurosurg Focus. 2005;19:E8. life. J Craniofac Surg. 2014;42:1885–90.
78. Hadad G, et al. A novel reconstructive technique 94. Brazilian Head and Neck Study Group. End results
after endoscopic expanded endonasal approaches: of a prospective trial on elective lateral neck dissec-
vascular pedicle nasoseptal flap. Laryngoscope. tion vs type III modified radical neck dissection in
2006;116:1882–6. the management of supraglottic and transglottic car-
79. Kassam AB, et al. Endoscopic reconstruction of cinomas. Head Neck. 1999;21:694–702.
the cranial base using a pedicled nasoseptal flap. 95. Yuen AP, Wei WI, Wong YM, Tang KC. Elective
Neurosurgery. 2008;63:ONS44–52; discussion neck dissection versus observation in the treat-
ONS52–43. ment of early oral tongue carcinoma. Head Neck.
80. Pinheiro-Neto CD, et al. Improving the design of 1997;19:583–8.
the pedicled nasoseptal flap for skull base recon- 96. Haddadin KJ, et al. Improved survival for patients
struction: a radioanatomic study. Laryngoscope. with clinically T1/T2, N0 tongue tumors undergo-
2007;117:1560–9. ing a prophylactic neck dissection. Head Neck.
81. El-Sayed IH, Roediger FC, Goldberg AN, Parsa AT, 1999;21:517–25.
McDermott MW. Endoscopic reconstruction of skull 97. Capote A, et al. Elective neck dissection in early-
base defects with the nasal septal flap. Skull Base. stage oral squamous cell carcinoma—does it
2008;18:385–94. influence recurrence and survival? Head Neck.
82. Thakur B, et al. Transnasal trans-sphenoidal endo- 2007;29:3–11.
scopic repair of CSF leak secondary to invasive 98. D’Cruz AK, et al. Elective versus therapeutic neck
pituitary tumours using a nasoseptal flap. Pituitary. dissection in node-negative oral cancer. N Engl J
2011;14:163–7. Med. 2015;373:521–9.
83. Zanation AM, et al. Nasoseptal flap reconstruction 99. de Bree R, et al. What is the role of sentinel
of high flow intraoperative cerebral spinal fluid leaks lymph node biopsy in the management of oral
during endoscopic skull base surgery. Am J Rhinol cancer in 2020? Eur Arch Otorrinolaringol.
Allergy. 2009;23:518–21. 2021;278:3181–91.
84. Nyquist GG, Anand VK, Singh A, Schwartz 100. Vandenbrouck C, et al. Elective versus therapeutic
TH. Janus flap: bilateral nasoseptal flaps for anterior radical neck dissection in epidermoid carcinoma of
skull base reconstruction. Otolaryngol Head Neck the oral cavity: results of a randomized clinical trial.
Surg. 2010;142:327–31. Cancer. 1980;46:386–90.
85. Rivera-Serrano CM, et al. Nasoseptal “rescue” 101. Fakih AR, Rao RS, Borges AM, Patel
flap: a novel modification of the nasoseptal flap AR. Elective versus therapeutic neck dissection
technique for pituitary surgery. Laryngoscope. in early carcinoma of the oral tongue. Am J Surg.
2011;121:990–3. 1989;158:309–13.
86. Patel MR, et al. How to choose? Endoscopic skull 102. Kligerman J, et al. Supraomohyoid neck dissection
base reconstructive options and limitations. Skull in the treatment of T1/T2 squamous cell carcinoma
Base. 2010;20:397–404. of oral cavity. Am J Surg. 1994;168:391–4.
87. Som PM. Detection of metastasis in cervical lymph 103. Yuen AP, et al. Prospective randomized study of
nodes: CT and MR criteria and differential diagno- selective neck dissection versus observation for
sis. AJR Am J Roentgenol. 1992;158:961–9. N0 neck of early tongue carcinoma. Head Neck.
88. Martin H, Del Valle B, Ehrlich H, Cahan WG. Neck 2009;31:765–72.
dissection. Cancer. 1951;4:441–99. 104. Flach GB, et al. Sentinel lymph node biopsy in clini-
89. Byers RM. Modified neck dissection. A study cally N0 T1-T2 staged oral cancer: the Dutch multi-
of 967 cases from 1970 to 1980. Am J Surg. center trial. Oral Oncol. 2014;50:1020–4.
1985;150:414–21. 105. Schilling C, et al. Sentinel European node trial
90. Byers RM, Wolf PF, Ballantyne AJ. Rationale for (SENT): 3-year results of sentinel node biopsy in
elective modified neck dissection. Head Neck Surg. oral cancer. Eur J Cancer. 2015;51:2777–84.
1988;10:160–7. 106. Liu M, Wang SJ, Yang X, Peng H. Diagnostic effi-
91. Bocca E, Pignataro O, Oldini C, Cappa C. Functional cacy of sentinel lymph node biopsy in early oral
neck dissection: an evaluation and review of 843 squamous cell carcinoma: a meta-analysis of 66
cases. Laryngoscope. 1984;94:942–5. studies. PLoS One. 2017;12:e0170322.
107. Yang Y, Zhou J, Wu H. Diagnostic value of senti- of the literature. Laryngoscope Investig Otolaryngol.
nel lymph node biopsy for cT1/T2N0 tongue squa- 2020;5:672–6.
mous cell carcinoma: a meta-analysis. Eur Arch 111. Hong JP, et al. A new plane of elevation: the super-
Otorrinolaringol. 2017;274:3843–52. ficial fascial plane for perforator flap elevation. J
108. National Institute for Health and Care Excellence. Reconstr Microsurg. 2014;30:491–6.
Cancer of the upper aerodigestive tract: assessment 112. Riordan E, et al. Modeling methods in craniofa-
and management in people aged 16 and over. 2018. cial virtual surgical planning. J Craniofac Surg.
109. Mahieu R, et al. New developments in imaging 2023;34:1191.
for sentinel lymph node biopsy in early-stage oral 113. Bartella AK, Hoshal SG, Lethaus B, Strong
cavity squamous cell carcinoma. Cancers (Basel). EB. Computer assisted skull base surgery: a contem-
2020;12:3055. porary review. Innov Surg Sci. 2022;8:149.
110. Verma A, Chen AY. Indications and outcomes of
superselective neck dissection: a review and analysis
Evolution of Bony Microsurgical
Reconstruction of the Jaws
14
Rushil R. Dang, Shao-Yu Hung, and Fu-Chan Wei

In this chapter on the evolution of bony micro- 1. Taylor GI. Reconstruction of the mandible
surgical reconstruction with emphasis on the with free composite iliac bone grafts. Ann
head and neck region, we have discussed the Plast Surg. 1982 Nov;9(5):361–76.
journey to modern-day fibular jaw reconstruc- 2. Hidalgo DA. Fibula free flap: a new method of
tion using safe and reliable techniques in the mandible reconstruction. Plast Reconstr Surg.
context of five landmark publications that 1989;84(1):71–9.
have guided this evolution. Other references 3. Wei FC, et al. Fibular osteoseptocutaneous
are cited to provide some perspective as it is flap: anatomic study and clinical application.
impossible to cover such a large topic with Plast Reconstr Surg. 1986;78(2):191–200.
just five references. Though individual tech- And
niques are not discussed in detail, their impact Wei FC, et al. Fibula osteoseptocutaneous flap
in shifting clinical practice and assisting the for reconstruction of composite mandibular
reconstructive surgeon to deliver improved defects. Plast Reconstr Surg.
outcomes cannot be understated. 1994;93(2):294–306.
4. Urken ML, et al. Oromandibular reconstruc-
tion using microvascular composite flaps:
Keywords report of 210 cases. Arch Otolaryngol Head
Neck Surg. 1998;124(1):46–55.
Free fibular osteocutaneous flap · Dental
5. Bell RB, et al. Computer planning and intra-
implants · Virtual surgical planning · Jaw in
operative navigation for palatomaxillary and
a day
mandibular reconstruction with fibular free
flaps. J Oral Maxillofac Surg.
2011;69(3):724–32.
R. R. Dang
Department of Plastic and Reconstruction Surgery,
14.1 Introduction
Chang Gung Memorial Hospital, Linkou, Taiwan
Initially, microsurgical bony reconstruction of
S.-Y. Hung · F.-C. Wei (*)
Department of Plastic and Reconstructive Surgery, the jaws used to be a challenge for reconstruc-
Chang Gung Memorial Hospital and Chang Gung tive microsurgeons with limited options. In
University Medical College, Linkou, Taiwan due course of time, free composite iliac crest
https://doi.org/10.1007/978-3-031-57132-9_14
134 R. R. Dang et al.
bone flap and free fibular flap were introduced. but associated oral soft tissue/mucosal defects
Eventually, the fibular free flap became standard limited their widespread applicability. It was
of care for patients with segmental jaw defects G. Ian Taylor who in his 1982 publication of
owing to demonstration of reliability of skin eight cases of mandibular reconstruction with
paddle with continued evolution of techniques free composite iliac bone grafts demonstrated a
and staged dental implantation. Further advance- single staged reconstruction with a composite
ment saw addition of simultaneous placement vascularized bone reconstruction [1]. A majority
of dental implants, use of custom hardware with of the patients in the study had malignant disease
the dawn of CAD/CAM technology and vir- and he was able to re-establish mandibular conti-
tual surgical planning, and finally, jaw in a day nuity along with soft tissue coverage in all cases
or jaw-during- admission reconstruction. This using appropriate pre-operative planning of the
journey of more than three decades now allows anticipated defects. He outlined a protocol to
us to perform highly reliable, customized and assist in designing the flap from ipsilateral or
functional reconstruction for our patients as contra-lateral hip along with a detailed dissection
a single staged procedure. In this chapter, we technique. Results showed a success rate of 87%
take the reader through this expedition and with one flap failure (due to arterial thrombosis),
arrive at the footsteps on modern-day total jaw bony union was seen in all remaining patients,
reconstruction. with acceptable esthetic outcomes and minimal
donor site morbidity.
Today, several centers still continue/prefer to
14.2 Reconstruction of the Jaw use the iliac crest free flap based on the deep cir-
with Iliac Crest Bone cumflex iliac artery for reconstruction of jaw
Composite Free Flaps defects. With advent of virtual surgical planning,
opportunities to shape the bone using templates
Reconstruction of continuity defects of the jaw and techniques to increase pedicle length have
used to pose a challenging situation for recon- increased its versatility. Appropriate donor site
structive surgeons. Initial reports of using corti- closure with careful resuturing of the abdominal
cocancellous autologous bone grafts particularly muscles has decreased hernia risks reported in
from the iliac crest and ribs seemed promising initial studies [2].
Taylor GI. Reconstruction of the mandible with free composite iliac bone grafts. Ann Plast Surg. 1982
Nov;9(5):361–76
Strengths • Detailed description of surgical technique and pre-operative planning
• Able to demonstrate coverage of both hard and soft tissue defects
Limitations • Small case series (n = 8) and not all cases received single staged reconstruction
Impact This is the first case series to demonstrate successful use of composite osseous free flaps for
reconstruction of the jaws. A deatiled dissection technique along with recommendations for pre-
operative planning are presented
14.3 Fibula Free Flap he reported a 100% flap success rate with com-
for Reconstruction plete healing of the bony osteotomies (as deter-
of Segmental Mandibular mined on follow up imaging). All the patients in
Defects the series had malignant disease with four
patients having small composite defects requir-
David A. Hidalgo in 1989 was the first to use ing a skin paddle. Reconstruction was performed
fibular free flaps for reconstruction of segmental using a two-team approach and minimal donor
mandibular defects [3]. In a series of 12 patients, site morbidity was noted. However, he encoun-
14 Evolution of Bony Microsurgical Reconstruction of the Jaws 135
tered significant problems with the skin paddle by Wei et al., where he demonstrated the
when it was harvested with the fibula. In authors’ reliability of the fibular skin paddle in cases of
opinion at that time, the skin paddle was not long bone reconstructions [4].
deemed to be reliable and was often excised. It Several key advantages were reported includ-
was partly explained on the basis of small skin ing adequate length of fibular bone for large
paddle compared to extremity cases, compres- defects, robust periosteal blood supply support-
sion of the perforator between floor of mouth and ing multiple osteotomies and adequate size of
mandible and twisting of the septum. This was in blood vessels to assist with microvascular
contrast to a study previously published in 1986 anastomosis.
Hidalgo DA. Fibula free flap: a new method of mandible reconstruction. Plast Reconstr Surg. 1989;84(1):71–9
Strengths • First case series for jaw reconstruction using fibula free flap
• Detailed harvest technique has been described
Limitations • Unable to demonstrate reliability of skin paddle leading to limited application in composite defects
reconstruction
Impact This study reliably demonstrated the use of fibula free flaps to reconstruct segmental defects of the
mandible, which paved the way for widespread use of the flap
14.4 Free Fibular ings on a total of 27 case of composite mandibu-

Osteoseptocutaneous Flap lar reconstruction. A success rate of 96.3% was
for Reconstruction reported with no cases of loss of skin paddle (par-
of Composite Jaw Defects tial or total) and a 100% success rate of primary
healing at the osteotomy sites. Additionally, they
Although the utility of the free fibular osteocuta- also showcased a standardized technique for har-
neous flap for jaw reconstruction was first pro- vesting and insetting of the flap. As reliability of
posed by Hidalgo [3], it was Wei et al., through the skin island of the fibula osteoseptocutaneous
their anatomical study in 1986 [4] followed by a flap was reconfirmed, its clinical applications
clinical series of jaw reconstructions in 1993 that greatly expanded to include composite jaw
popularized its use [5]. In their anatomical study, defects which required oral mucosa and/or facial
septocutaneous blood vessel(s) from the peroneal skin resurfacing. Currently, it has become the
artery to the skin paddle in the lateral leg was standard of care for reconstruction of isolated/
demonstrated and its reliability confirmed with compound/composite segmental jaw defects,
clinical cases of long bone reconstruction. In the though several variations in harvest techniques
following article, Wei et al. presented their find- have been reported since these landmark papers.
Wei FC, et al. Fibular osteoseptocutaneous flap: anatomic study and clinical application. Plast Reconstr Surg.
1986;78(2):191–200
And
Wei FC, et al. Fibula osteoseptocutaneous flap for reconstruction of composite mandibular defects. Plast Reconstr
Surg. 1994;93(2):294–306
Strengths • First large case series
• All patients with skin paddle harvest and 100% skin flap survival
• Double Barrel configration in long bone cases
Limitations • Long term follow up not reported
• Minimal details on complications
Impact This was the first large case series to reliably show safe harvest of the FFOF skin paddle with 100%
survival of skin flaps [5]. The study also reported a standardized technique for harvest of the FFOF
with skin paddle for reconstruction of composite defects and presents a protocol for reconstruction
14.5 Jaw Reconstruction Using were reported which lend credence to the tech-
Microvascular Composite nique and its applicability [9]. The paper dis-
Flaps and Placement cusses outcomes in 210 mandibular
of Endo-osseous Dental reconstructions using bony free flaps during an
Implants 11-year period by a single surgeon. A key com-
ponent of this study was reporting a 92% overall
After jaw reconstruction with bony free flaps, a success rate of dental implant placement with
critical component to restore patients’ oral func- well-defined success criteria consisting of
tion and improve quality of life is to replace absence of peri-implantitis on follow-up and
lost/missing dentition using endo-osseous radiographic evidence of osteointegration.
implants. This allows the prosthodontist to ade- Nearly 70% of the patients with placement of
quately restore the dentition with a dental pros- dental implants received dental prosthesis, but
thesis which in turn also improves speech and prosthesis-related complications were not
appearance. Though initial reports on endo- reported.
osseous implant placement in the fibular free This study provided us with the necessary evi-
flaps have come from Urken, Wei and Mounsey’s dence base and presently, dental implants are
teams [6–8], it wasn’t until 1998 paper by Urken routinely placed at the time of single staged free
et al. that long-term follow-up and success rates flap reconstruction with success rates of >90%.
Urken ML, et al. Oromandibular reconstruction using microvascular composite flaps: report of 210 cases. Arch
Otolaryngol Head Neck Surg. 1998;124(1):46–55
Strengths • Large number of patients (n = 210) with single surgeon and long-term follow up
• Dental implant success criteria are well defined
Limitations • Implant specific mean follow up is not reported
• Other implant and dental prosthesis complications not reproted
• Retrospective study
Impact This paper presents long-term data on success rate of endo-osseous dental implant placement in free
flap patients. They delineate a well-defined success criteria giving credibility to their findings with a
majority of the patients eventually restored with dental prosthesis
cutting guides, stereolithographic models to pre-

14.6 Virtual Surgical Planning, bend plates, and fibular custom guide stents.
CAD/CAM and Intraoperative They further added intraoperative navigation to
Navigation for Free Flap assist in maxillary reconstructions and to verify
Reconstruction resections. Their prospective study included 16
patients undergoing reconstruction for malignant
With the advent of computer planning and cus- tumors or osteoradionecrosis. Four of those
tom surgical guides/hardware, digital technology patients included use of intraoperative navigation
has increasingly been used to optimize surgical for adherence to computer-assisted presurgical
outcomes. A landmark study by Bell and col- planning. This study was critical to bring virtual
leagues in 2011 had provided us with early clini- surgical planning and CAD/CAM technology to
cal experience and protocols for its use in the forefront by equipping the reconstructive sur-
maxillary/mandibular reconstructions [10]. Their geons with a step-by-step protocol from preop-
protocol included recommendations from a pre- erative CT to construction of the neomaxilla/
vious smaller study by Hirsh et al. [11], such as neomandible, making this applicable to wide-
virtual preoperative planning, custom surgical scale clinical practice.
14 Evolution of Bony Microsurgical Reconstruction of the Jaws 137
Today several centers utilize virtual surgical gery, commonly known as jaw in a day or jaw-
planning and CAD/CAM technology, to perform during-admission [12–15]. This allows for a total
simultaneous placement of dental implants with maxillofacial reconstruction with replacement of
immediate dental prosthesis during the same sur- lost bone, soft tissue and teeth.
Bell RB, et al. Computer planning and intraoperative navigation for palatomaxillary and mandibular reconstruction
with fibular free flaps. J Oral Maxillofac Surg. 2011;69(3):724–32
Strengths • Prospective pilot study
• Initially, the largest sample size
• Clinically applicable
• Included role of intra-operative navigation in reconstructive surgery
Limitations • Intraoperative complications or technical challenges not mentioned
• Minimal follow up
Impact • Detailed step-by-step protocols for maxillary and mandibular computer-assisted presurgical
planning and intraoperative reconstruction
• Use of intraoperative navigation in maxillary reconstructions to assist with adherence to presurgical
planning

Commentary
1. Taylor GI. Reconstruction of the mandible with
free composite iliac bone grafts. Ann Plast Surg.
There are numerous studies that have signifi-
1982;9(5):361–76.
cantly impacted the field of microsurgical bony 2. Taylor GI, Corlett RJ, Ashton MW. The evolution of
reconstruction of the jaws. We have strived to free vascularized bone transfer: a 40-year experience.
highlight the five papers that have had the most Plast Reconstr Surg. 2016;137(4):1292–305.
3. Hidalgo DA. Fibula free flap: a new method of
impact in bringing about change to clinical prac-
mandible reconstruction. Plast Reconstr Surg.
tice and advancing this field. Several other arti- 1989;84(1):71–9.
cles have been cited in text to assist the reader for 4. Wei FC, et al. Fibular osteoseptocutaneous flap: ana-
a more detailed background on the topic. From tomic study and clinical application. Plast Reconstr
Surg. 1986;78(2):191–200.
non-vascularized bone reconstruction to bony
5. Wei F-C, et al. Fibula osteoseptocutaneous flap for
free flaps becoming standard of care, and to now, reconstruction of composite mandibular defects. Plast
customized and patient specific implants and Reconstr Surg. 1994;93(2):294–304.
planning, a great deal of progress has been made 6. Mounsey RA, Boyd JB. Mandibular reconstruction
with osseointegrated implants into the free vascular-
in this field. Currently, several surgical centers
ized radius. Plast Reconstr Surg. 1994;94(3):457–64.
around the world offer their patients total maxil- 7. Urken ML, et al. Primary placement of osseointegrated
lofacial reconstruction using jaw in a day or jaw implants in microvascular mandibular reconstruction.
during admission techniques. With continued Otolaryngol Head Neck Surg. 1989;101(1):56–73.
8. Wei FC, et al. Mandibular reconstruction with fibu-
endeavors being made in the sphere of tissue
lar osteoseptocutaneous free flap and simultane-
engineered artificial free flaps and bone engi- ous placement of osseointegrated dental implants. J
neering using bone marrow aspirates, bony jaw Craniofac Surg. 1997;8(6):512–21.
reconstruction is a moving target and we will 9. Urken ML, et al. Oromandibular reconstruc-
tion using microvascular composite flaps: report
continue to see other impactful papers appear on
of 210 cases. Arch Otolaryngol Head Neck Surg.
the topic in the near future. 1998;124(1):46–55.
10. Bell RB. Computer planning and intraoperative 13. Qaisi M, et al. Fibula jaw in a day: state of the art in
navigation in cranio-maxillofacial surgery. Oral maxillofacial reconstruction. J Oral Maxillofac Surg.
Maxillofac Surg Clin North Am. 2010;22(1):135–56. 2016;74(6):1284.e1–1284.e15.
11. Hirsch DL, et al. Use of computer-aided design and 14. Levine JP, et al. Jaw in a day: total maxillofa-
computer-aided manufacturing to produce orthogna- cial reconstruction using digital technology. Plast
thically ideal surgical outcomes: a paradigm shift in Reconstr Surg. 2013;131(6):1386–91.
head and neck reconstruction. J Oral Maxillofac Surg. 15. Chang Y-M, Tsai C-Y, Wei F-C. Fibula jaw-
2009;67(10):2115–22. during-
admission. J Plast Reconstr Aesthet Surg.
12. Williams FC, et al. Immediate teeth in fibulas: 2023;82:247.
expanded clinical applications and surgical technique.
J Oral Maxillofac Surg. 2021;79(9):1944–53.
Evolution of Reconstruction
in Facial Paralysis
15
Alan Tom, Gerald J. Wu, Ronald M. Zuker,
and Gregory H. Borschel

1. Gillies H. Experiences with Fascia Lata
Facial paralysis impairs the aesthetics and
Grafts in the Operative Treatment of
function of the face. Facial movement is nec-
Facial Paralysis: (Section of Otology and
essary for conveying emotion, socialization,
Section of Laryngology). Proc R Soc Med.
ocular protection, oral competence, and the
1934;27(10):1372–82. PMID: 19989927;
formation of certain words and sounds. There
PMCID: PMC2205492.
are a multitude of causes for facial paralysis,
2. Anderl H. Cross-face nerve transplan-
which need to be identified in order to discuss
tation in facial palsy. Proc R Soc Med.
options for reconstruction. This chapter will
1976;69(10):781–3. PMID: 995930; PMCID:
discuss several breakthroughs that led to sig-
PMC1864675.
nificant historical advances in the surgical
3. Harii K, Ohmori K, Torii S. Free gracilis mus-
management of the paralyzed face.
cle transplantation, with micro neurovascular
anastomoses for the treatment of facial paraly-
Keywords
sis. A preliminary report. Plast Reconstr Surg.
Facial palsy · Facial paralysis · Facial 1976;57(2):133–43.
reanimation · Cross face nerve graft 4. Terzis JK. ‘Babysitters’: an exciting new con-
Innervated muscle flap · Botulinum toxin cept in facial reanimation. In: Castro D, edi-
Facial spasm tor. Proceedings of the Sixth International
Symposium on the Facial Nerve. Rio de
Janeiro, Brazil. Berkeley, CA: Kugler &
A. Tom · G. J. Wu
Ghedini; 1988. p. 525.
Division of Plastic Surgery, Indiana University
School of Medicine, Indianapolis, IN, USA 5. Biglan AW, May M, Bowers RA. Management
of facial spasm with Clostridium botulinum
R. M. Zuker
The Hospital for Sick Children and University of toxin, type A (Oculinum). Arch Otolaryngol
Toronto, Toronto, ON, Canada Head Neck Surg. 1988;114(12):1407–12.
G. H. Borschel (*)
Division of Plastic Surgery, Indiana University
School of Medicine, Indianapolis, IN, USA
Riley Hospital for Children, Indianapolis, IN, USA
https://doi.org/10.1007/978-3-031-57132-9_15
140 A. Tom et al.
15.1 Introduction (64%) and motor vehicle crashes (22%) [1, 2].
The facial nerve has a long course with multiple
The facial nerve contains motor axons serving locations for injury: intracranial (iatrogenic
mimetic musculature, visceral nerves to the sali- injury for acoustic neuroma resection), intratem-
vary glands, sensory nerves to the ear, and special poral (temporal bone fracture), extracranial (pen-
sensory nerves for taste to the anterior two-thirds etrating trauma, facelifts, parotid surgery).
of the tongue. The nerve courses from the pons Trauma commonly results in facial nerve injury
through the temporal bone, to exit the stylomas- when it is associated with temporal bone frac-
toid foramen and then split into branches between tures in adults [3] as the facial nerve is relatively
the superficial and deep lobes of the parotid gland large compared to the labyrinthine segment
as it spreads across the face. Roughly 8–15 nerve through which it courses. In children, trauma
branches exit the parotid with multiple arcades may occur during delivery, with rates of 0.8–7.5
and communications distally. Notably, there is a cases per 1000 births [4]. Prolonged labor, for-
lack of overlap for the branch to the frontalis, ceps delivery, hemotympanum, or marks over the
which can be injured during rhytidectomy and ear/mastoid can suggest birth trauma; however,
temporal artery biopsy, resulting in unilateral 1/3 of obstetric palsies occur in spontaneous vag-
brow ptosis. inal deliveries without instrumentation [4]. Most
There are many different etiologies of facial are mild and will recover without intervention.
paralysis, which have been well categorized in In the office, all patients should be questioned
prior textbooks and articles. We will only briefly on the timeline of their initial symptoms, any iden-
touch on these in this chapter. It is important to tifying etiology, and delineate between birth trauma
understand the etiology of facial paralysis before and developmental causes of facial paralysis.
considering treatment options and customizing Imaging, either high-resolution CT or MRI, may
treatment plans for each patient. be required to assess intracranial and intratemporal
Facial paralysis may be present at birth (devel- causes. Electroneurography (ENoG) may be con-
opmental/congenital facial palsy). It may be uni- sidered to provide an objective record of evoked
lateral or bilateral. Several syndromes are action potentials and quantify nerve degeneration,
associated with facial paralysis including hemifa- along with needle electromyography (EMG), nerve
cial microsomia, CHARGE, 22q11 deletion syn- conduction, and nerve excitability testing.
drome, and Moebius syndrome. Moebius Similarly, a standardized exam should be per-
syndrome refers to a typically bilateral, congeni- formed to allow for comparison between patients.
tal facial palsy that is also associated with addi- The commonly accepted grading system, adopted
tional cranial nerve deficits, most commonly CN as the universal standard of the American Academy
VI; however, it can be unilateral as well. of Otolaryngology-Head and Neck Surgery on rec-
Congenital paralysis accounts for less than 10% ommendation of the Facial Nerve Disorders
of all cases and will not show improvement, Committee, has been the House–Brackmann Facial
whereas traumatic palsy often does. Nerve Grading System [5]. This system is most
Acquired facial paralysis may be secondary to useful for post-Bell’s facial paralysis.
Idiopathic causes, where it is referred to as Bell’s The goals of reconstructive surgery for facial
palsy. Bell’s palsy is a diagnosis of exclusion, as it is paralysis include ocular protection, oral compe-
an idiopathic paralysis of sudden onset that resolves tence, and generation of a smile for social inter-
in a majority of cases (75–85%) and is the most action. Each patient may have individual
common diagnosis of facial paralysis in adults. priorities within these goals.
Bell’s palsy is unlikely to be the diagnosis for insidi- Ocular protection is critical. Patients with
ous, waxing/waning, or bilateral facial palsy. paralysis of the brow may have obstructional pto-
Another common cause of acquired facial sis affecting their vision. Lagophthalmos occurs
paralysis is trauma, most commonly from falls due to loss of the resting tone of the orbicularis
15 Evolution of Reconstruction in Facial Paralysis 141
oculi and unopposed levator palpebrae superioris disease. Poor oral continence will lead to poor
activity. Paralytic ectropion occurs to the lower lid nutrition and poor dentition, with decay due to oral
as resting orbicularis tone is lost and the eyelid desiccation and bacterial overgrowth.
falls away from the eye. This leads to a paradoxi- Finally, and possibly most concerning to the
cal epiphora as the lower lid is malpositioned and patient, is the social stigma of facial muscle
the lacrimal duct does not collect the tears result- paralysis. Facial muscle activity is essential for
ing in overflow. However, the eye is commonly dry regular social interaction. Peer social judgment
with associated ulcers due to poor blink and spread can lead to social withdrawal, decreased aca-
of tears. Patients need to be evaluated for a Bell’s demic performance, psychosocial stress, and
phenomenon, which refers to the upward and out- insecurity. Depression is a common side effect of
ward rotation of the eye with attempted eyelid clo- patients with paralysis. Psychological distress,
sure which can decrease risks of corneal damage. rather than functional impairment, has been
Nearly 61% of patients with Bell’s palsy had signs determined to be the critical factor in predicting
of corneal ulceration at 1 year [6], which, if left social impairment and is the primary reason for
untreated, leads to permanent blindness. patients requesting surgery [7, 8]. It is for this
Speech sounds that are most affected by facial reason that restoration of both a symmetric smile,
paralysis are the bilabial plosive sounds like ‘p’ and as well as a functional face, is the critical goal in
‘b’. Hyperacusis may occur from failure of func- reanimation surgery.
tion of the nerve to the stapedius resulting in the
inability to dampen loud noises, which may also
result in developmental delays. Facial paralysis can 15.2 Landmark Articles
lead to poor oral feeding and failure to thrive in the
neonate, particularly when associated with bilateral 15.2.1 Temporalis Muscle Flaps
Gillies H. Experiences with Fascia Lata Grafts in the Operative Treatment of Facial Paralysis: (Section of Otology
and Section of Laryngology). Proc R Soc Med. 1934;27(10):1372–82. PMID: 19989927; PMCID: PMC2205492
Initial approaches to functional reconstruction of the face naturally fell towards local muscle flaps or grafts. For
some time, static slings and tensor fascia lata grafts had been described to support a paralyzed and sagging facial
structure to provide symmetry. Currently, static slings remain a useful tool for the reconstructive surgeon. To
decrease donor site morbidity, many authors favor tendon grafts (palmaris, EDL) from the upper extremity, or the
use of synthesized materials. Static slings provide improved facial symmetry and can resolve issues with oral
incompetence; however, they do not offer any muscular control.
Gillies was the first to describe turning over the temporalis muscle as a functional flap for both eye closure and
elevation of the oral commissure to simulate a smile. For the mouth, a central slip of temporalis muscle and deep
fascia are raised, preserving an inferior neurovascular supply that enters deep to the muscle and tunneling this
towards the mouth. The reach of the muscle was extended using a fascia lata graft that was split and tunneled
beyond the commissure and into the upper and lower lip, such that at rest the mouth and nose were straight, and
upon contraction it would elevate the commissure providing a volitional smile. For eyelid closure, a similar
technique is utilized. A more anterior segment of temporal muscle and fascia was taken and split, tunneled in the
upper and lower eyelid to meet at the inner canthus. Contraction would lead to eyelid closure and provide ocular
protection.
Today several modifications of the procedure [9] have been described to decrease the bulkiness of the overturned
muscle that can be prominent over the zygoma. Additionally, authors have used the insertion of the temporal muscle
at the coronoid and moved it to the corner of the mouth instead of turning over the muscle origin, occasionally
alleviating the need for a graft. This is commonly referred to as the temporalis sling. These procedures can require
further dissection, and may require osteotomy of the coronoid or zygoma to improve the vector of the muscle.
L’Abbe’s version has been adopted by many for its reliable results [10].
Strengths • This was the first case series using temporalis as a functional facial reanimation flap with a
detailed operative description.
142 A. Tom et al.
Limitations • The tunneled muscle can produce a visible bulge over the zygomatic arch which produces facial
asymmetry. The muscle, or graft needed for length, may stretch over time decreasing the
long-term effectiveness of the procedure. There will also inherently be some temporal
asymmetry at donor site, which may be camouflaged if the resected muscle segment is thin and
the donor site can be closed. This did not provide emotional muscle control.
Impact This was the first reproducible series of a local functional flap that provided conscious animation
to the lower face and eyelid.
15.2.2 Cross Face Nerve Graft

Anderl H. Cross-face nerve transplantation in facial palsy. Proc R Soc Med. 1976;69(10):781–3. PMID: 995930;
PMCID: PMC1864675
Gillies concluded his series on the temporalis muscle turnover citing that he hopes for nerve grafting to improve “by
leaps and bounds,” knowing that a nerve deficit would best be served through a reinnervation procedure. One of the
most promising methods of achieving reinnervation comes in the form of cross face nerve grafting. The first cross
face nerve graft was described in 1971 by Scaramella [11] and Smith, though many texts cite Anderl too.
The cross-face nerve graft is a treatment for the patient with hemifacial paralysis. It is a two-stage procedure that
uses a harvested nerve graft, commonly the sural nerve for its length and forgivable donor site deficit, to bridge the
gap between the unaffected face and the paralyzed face. The reconstructive surgeon in stage 1 isolates redundant
zygomatic and buccal nerve branches using electrical stimulation that correlate to the unaffected side’s orbicularis,
smile muscles, zygomaticus, and levator labii superioris, and/or blink depending on the goal of the transfer. After
identifying the donor nerve, a tunnel is made for the graft to sit on the paretic side. The nerve is then left and
monitored post-operatively through a propagating Tinel sign.
At approximately 6–9 months, the second stage is undertaken. The distal nerve end is identified and may be used for
direct reinnervation of the paretic main branches of the facial nerve correlating to the donor’s function. In the
original descriptions, the nerve graft was coapted either directly to a paralyzed muscle belly, or to a terminal branch
of paralyzed facial nerve. Once regeneration occurs, the unaffected facial nerve will control bilateral facial
musculature, allowing for a natural symmetric response when stimulated.
Anderl’s initial experience with the procedure yielded promising results as well as several obstacles. One problem is
that there is a significant amount of time that passes during propagation of the nerve through the nerve graft. During
this time the muscle is not receiving stimulation and will atrophy. Patients that did not present within the first
1–2 years of symptoms were not candidates for isolated CFNG as the muscle had undergone irreversible fibrosis by
this time. In an effort to combat this, Anderl championed early cutaneous electrical stimulation techniques. In his
initial series, 15 patients underwent CFNG with a patient reported “satisfying result” of greater than 50%.
Strengths • A well-described two-stage procedure offers natural, emotional control of facial muscles.
Limitations • The procedure requires multiple operations with an extended period of time required between
stages for nerve propagation to occur. Due to this time delay, there can be atrophy and fibrosis of
the native facial muscles that occur before their reinnervation resulting in decreased strength.
Logistically finding patients early enough for isolated CFNG reconstruction can be difficult,
particularly as the diagnoses of many forms of facial paralysis inherently utilizes a period of
watchful waiting as patients are monitored for spontaneous recovery.
Impact The cross-face nerve graft technique remains the gold standard for facial reanimation with
emotional control.
15.3 Free Functional Gracilis Muscle

Transplantation
Harii K, Ohmori K, Torii S. Free gracilis muscle transplantation, with micro neurovascular anastomoses for the
treatment of facial paralysis. A preliminary report. Plast Reconstr Surg. 1976;57(2):133–43
In the early 1970s, while cross-face nerve graft was being developed, multiple surgeons around the world began
experimenting with free muscle transplants. There was an explosion of literature at this time as microvascular free
tissue transfer was being discovered and the methods became reliably reproducible through 10–0 sutures and
operative microscopy. To choose one article during this publishing boom does not fully encompass all of the
contributing surgeon scientists.
Harii et al. are commonly cited for the first use of the gracilis for the treatment of facial paralysis, and the gracilis
remains one of the most used muscles today. The technique of free functional muscle transfers is well described.
The original technique described by Harii remains conceptually similar to contemporary techniques. Briefly, a donor
muscle is selected and the neurovascular pedicle is isolated and preserved. Recipient vessels and a donor nerve must
also be selected in the face. The donor nerve is important to identify pre-operatively, to ensure it is in working order
for the paralyzed patient. A microvascular anastomosis is created as well as a nerve coaptation. Anchoring of the
muscle at the commissure to recreate a nasolabial crease without puckering, as well as appropriate tensioning of the
muscle in the temporal fascia are the critical steps in obtaining optimal postoperative appearance. Then the patient is
monitored as nerve regeneration occurs resulting in facial movement.
Multiple muscles have been described for the free functional reinnervation of paralyzed face: gracilis, pectoralis
minor, latissimus, serratus, extensor digitorum brevis, platysma and others. Many nerves have also been utilized,
including deep temporal, as in Harii’s original article, CFNG, ipsilateral masseter nerve, complete and partial
ipsilateral hypoglossal, and the accessory nerve. The goal of any muscle, nerve combination should be to utilize a
muscle with a consistent neurovascular pedicle with minimal donor site morbidity for both the donor muscle and
recipient nerve. Retraining and post-operative physical therapy will be required for conscious symmetric smile
creation for all nerves besides the CFNG from an unaffected facial nerve. In the case of a masseter donor nerve, the
patient will consciously attempt jaw contracture to activate the transferred gracilis. Children may tolerate this
retraining better than adults, owing to increased brain plasticity.
The authors favor using the masseter nerve in cases of facial paralysis when ipsilateral innervation is required. The
use of the motor nerve to the masseter incurs minimal donor site morbidity, can be reliably identified by landmarks
and with stimulation, and is commonly available in patients with Moebius syndrome who will require bilateral free
functional muscle transplants for reinnervation [12]. The masseter nerve can be reliably found 3 cm anterior and
1 cm inferior to the tragus on the deep surface of the masseter muscle [13]. This dissection is shown in Fig. 15.1. It
has also been shown that when comparing the strength of excursion between a free gracilis innervated by an
ipsilateral masseter nerve or a CFNG, the masseter innervated muscle shows a stronger force of contraction [14].
Strengths • The first step-by-step description of one of the most common, contemporary free muscle
transfers for facial reanimation, particularly for children.
Limitations • In Harii’s series the deep temporal nerve was used as the donor nerve, and current practice favors
CFNG, ipsilateral masseteric nerve, and hypoglossal. Surgeons now frequently debulk the
muscle to prevent excess volume in the face. Some patients may excel, while others struggle
with post-operative rehabilitation to maximize appearance and function.
Impact The cross-face nerve graft technique in combination with a free muscle transfer is the current
standard procedure to achieve facial reanimation with emotional control, and free muscle transfer
remains the leading treatment for patients seeking surgical correction.
a b c d
Fig. 15.1 Placement of segmental gracilis muscle

144 A. Tom et al.
15.4 The Babysitter Procedure

Terzis JK. ‘Babysitters’: an exciting new concept in facial reanimation. In: Castro D, editor. Proceedings of the Sixth
International Symposium on the Facial Nerve. Rio de Janeiro, Brazil. Berkeley, CA: Kugler & Ghedini; 1988. p. 525
One of the challenges of paralysis of the facial nerve is chronic denervation of the ipsilateral target muscles and their
motor nerves. Ideally, a CFNG to native muscles would be utilized to achieve natural symmetric emotional control
over the facial muscles. For patients presenting at 6 months–2.5 years, Dr. Terzis utilized a local nerve transfer to the
denervated facial nerve to arrest the progression of atrophy and allow time for propagation of the contralateral facial
nerve through a CFNG. This was termed the “babysitter procedure.”
In the first stage of the babysitter procedure, 40% of the hypoglossal nerve was transferred, end to side, with the
paretic facial nerve, and, at the same time, several CFNGs were placed from the unaffected facial nerve towards the
paralyzed face [15]. This method enabled early reinnervation of the paralyzed muscles while the contralateral axons
grew through the CFNG. The second stage was performed 6 months later, in which the CFNGs were transferred to
the facial nerve branches to enable emotionally spontaneous motor control.
Babysitter procedures are common in other peripheral nerve reconstructions with long regeneration distances, such
as brachial plexus reconstructions, where target muscle atrophy may occur before full reinnervation. In facial
reanimation, the patients must be treated early to obtain the most benefit. If patients are unsatisfied with the overall
reconstruction, they will remain candidates for free muscle transfer using the previously placed CFNG, as well as
other reconstructive techniques.
Strengths • Well described and reproducible technique that is able to overcome previous obstacles of facial
muscle atrophy that plagued early attempts of CFNG. When successful, it provides native facial
muscle movement. This technique can avoid a free flap in a patient who is not a candidate.
Limitations • This procedure still requires early referral, but allows for more time than an isolated CFNG
technique to recipient facial muscles. Synkinesis is common in hypoglossal nerve transfers.
Patients may still require local or free muscle transfer for full functional recovery.
Impact The babysitter provides early reinnervation to the paralyzed muscles with strong motor fibers
preserving muscle bulk for future cross-face nerve grafting to provide the most harmonious
emotional and symmetric facial response. The procedure is not commonly used, since many
patients may be reluctant to sacrifice the function gained by the XII–VII transfer.
15.5 The Use of Botulinum Toxin

in Facial Paralysis
Carruthers JD. Ophthalmologic use of botulinum A exotoxin. Can J Ophthalmol. 1985;20(4):135–41. PMID:
4052862 [16]
Synkinesis is a common and vexing problem facing patients in which partial facial nerve recovery has occurred. It
can be difficult to decide how to manage partial paralysis, bulk facial contraction, and muscles that spasm following
inappropriate reinnervation. Approximately, 30% of those with Bell’s palsy experience incomplete recovery.
Upwards to 15% of patients with Bell’s palsy have long-term debilitating facial dyskinesia after post-paretic
recovery [17]. Post-paretic synkinesis is postulated to arise from aberrant nerve regeneration, insufficient nerve
myelination, and hypersensitivity of the facial nucleus [18]. Ocular-oral synkinesis, the most common pattern of
post-paretic synkinesis, describes involuntary midface movements with voluntary eye closure. Oral-ocular
synkinesis involves troublesome involuntary eye closure with voluntary mouth movements, such as Duchenne’s
smile or lip puckering. Synkinesis can also often involve the platysma and mentalis. For years exploratory neurolysis
and myectomy were the only treatment options for this complex collection of symptoms.
Botulinum toxin injections were first described for the treatment of strabismus in 1980 [19]. It has rapidly expanded
its use receiving US Food and Drug Administration approval for treatment in essential blepharospasm in 1989 [20].
The applications of botulinum toxin injections to treat essential blepharospasm naturally expanded to include
hemifacial spasm, Meige’s syndrome and eventually post-paretic synkinesis. Biglan et al. stands as one of the
earliest accounts in the literature reporting their use of botulinum toxin to treat synkinesis and hyperkinesis resulting
from Bell’s palsy.
Biofeedback and other rehabilitation therapy modalities can be used alongside botulinum toxin injection for the
treatment of post-paretic synkinesis. Together, older surgical modalities including neurolysis, selective neurectomy
and myectomy can also help in refractory cases. The contralateral nonparetic facial musculature contributes to facial
asymmetry through unopposed unilateral pull, commonly referred to as hyperkinesis. Over time, this leads to
worsening facial asymmetry through contralateral hypertrophy, deepened wrinkles and furrows, and eventual
deviation of the nose and mouth. Botulinum toxin application to the contralateral normal side decreases opposing
vectors on the weaker ipsilateral muscles, improving facial symmetry, relative strength and fine motor control of the
affected side [21]. While facial nucleus disorganization has been demonstrated in rat and primate models, further
research is warranted on the proposed effects of facial nucleus reorganization and central cortex retraining by
balancing opposing facial forces with bilateral botulinum toxin injections [21–23].
Botulinum toxin can provide reliable results for patients without requiring surgery, but does impart a recurring cost,
and need for routine treatments throughout a patient’s lifetime.
Duration of relief varies from 4 to 7 months, with the duration of optimal effect even shorter as synkinesis
symptoms slowly return. May et al. reported reliable results within the first injection, but half of study participants
dismissed subsequent reinjections citing inconvenience, pain and lack of durable results [24]. Dose-dependent
complications were noted in early trials. Biglan et al. observed that overtreatment of the zygomaticus and levator
labii muscle groups led to ablation of the nasolabial crease, oral/buccal incompetence and inadvertent biting of
buccal mucosa. Overtreatment of the orbicularis oculi can result in transient blepharoptosis.
Strengths • Botulinum provides predictable and reliable results for control of post-paretic synkinesis. There
is low morbidity and can be administered easily in the clinic. With correct dosage, patients were
able to achieve satisfactory and reproducible reduction in spasm symptoms while still retaining
some functional use of the treated muscles, all without requiring complex surgery.
Limitations • The most significant downside of botulinum injections stems from the transient nature of the
medication.
Impact Today, botulinum toxin has led to a noticeable reduction of patients undergoing exploratory
neurolysis and myectomy procedures for complex synkinesis and spasm symptoms, in favor of
minor office-based injection therapy.
15.6 Expert Concluding tain facial tone. Through the birth of free muscle
Commentary transfers, we can introduce a functioning muscle
from anywhere in the body, into an otherwise
Facial paralysis can be a devastating diagnosis non-functional location. Finally, we have wid-
for patients affecting facial aesthetics, ocular and ened our armamentarium for treating spasm and
oral function, speech, and socialization. Facial synkinetic complications through the use of
paralysis can result in depression and avoidance injectable botulinum therapy in the clinic to
in patients with fear of stigmatization. We could reproduce symmetry with minimal invasiveness.
not summarize all of the techniques in the litera- Future study will likely focus on the improve-
ture focused on treating these patients. Early ment in axonal coaptation technique, nerve selec-
static procedures like gold weights, lower eyelid tion, and pre- and post-operative nerve stimulation
canthoplasty and sling procedures are still com- to produce optimal outcomes. It is our current
monplace and essential for comprehensive care practice to stimulate the donor nerve branch intra-
of the paretic face. operatively; however, the length and strength of
Here we looked beyond static procedures to stimulation is a source of ongoing study.
select several major advancements in facial rean- Consideration should be given towards a standard
imation in hopes of providing a comprehensive assessment tool for muscle excursion, which can
summary of historical and current surgical tech- avoid some of the subjective values in the House–
niques. Initially, local muscles were utilized, like Brackmann scale. Similarly, consideration should
the temporalis muscle, followed by nerve- be given to a standard psychosocial assessment
grafting techniques, aimed at revitalizing a tool for clinicians, as this is a primary concern of
paretic face and babysitter procedures to main- many patients seeking surgical correction.
146 A. Tom et al.
References facial reanimation. J Plast Reconstr Aesthet Surg.

2012;65(3):363–6.
14. Bae YC, Zuker RM, Manktelow RT, Wade S. A
1. Eggensperger Wymann NM, Hölzle A, Zachariou
comparison of commissure excursion following
Z, Iizuka T. Pediatric craniofacial trauma. J Oral
gracilis muscle transplantation for facial paraly-
Maxillofac Surg. 2008;66(1):58–64.
sis using a cross-face nerve graft versus the motor
2. Odebode TO, Ologe FE. Facial nerve palsy after head
nerve to the masseter nerve. Plast Reconstr Surg.
injury: case incidence, causes, clinical profile and out-
2006;117(7):2407–13.
come. J Trauma. 2006;61(2):388–91.
15. Terzis JK, Tzafetta K. The “babysitter” proce-
3. Yetiser S, Hidir Y, Gonul E. Facial nerve problems
dure: minihypoglossal to facial nerve transfer and
and hearing loss in patients with temporal bone frac-
cross-facial nerve grafting. Plast Reconstr Surg.
tures: demographic data. J Trauma Acute Care Surg.
2009;123(3):865–76. PMID: 19319050.
2008;65(6):1314–20.
16. Carruthers JD. Ophthalmologic use of botulinum
4. Hughes CA, Harley EH, Milmoe G, et al. Birth
A exotoxin. Can J Ophthalmol. 1985;20(4):135–41.
trauma in the head and neck. Arch Otorhinolaryngol
PMID: 4052862.
Head Neck Surg. 1999;125:193–9.
17. Husseman J, Mehta RP. Management of synkinesis.
5. House JW, Brackmann DE. Facial nerve grading sys-
Facial Plast Surg. 2008;24(2):242–9.
tem. Otolaryngol Head Neck Surg. 1985;93(2):146–7.
18. Markey JD, Loyo M. Latest advances in the manage-
6. Wepman B, Baum JL. Ocular findings in Bell’s palsy.
ment of facial synkinesis. Curr Opin Otolaryngol
Ophthalmology. 1979;86:1943–50.
Head Neck Surg. 2017;25:265–72.
7. Vanswearingen JM, Cohn JF, Turnbull J, Mrzai T,
19. Scott AB. Botulinum toxin injection into extraocu-
Johnson P. Psychological distress: linking impair-
lar muscles as an alternative to strabismus surgery.
ment with disability in facial neuromotor disorders.
Ophthalmology. 1980;87(10):1044–9.
Otolaryngol Head Neck Surg. 1998;118(6):790–6.
20. Mehdizadeh OB, Diels J, White WM. Botulinum
8. Bradbury ET, Simons W, Sanders R. Psychological
toxin in the treatment of facial paralysis. Facial Plast
and social factors in reconstructive surgery for
Surg Clin N Am. 2016;24(1):11–20.
hemi-facial palsy. J Plast Reconstr Aesthet Surg.
21. Choi KH, Rho SH, Lee JM, Jeon JH, Park SY, Kim
2006;59(3):272–8.
J. Botulinum toxin injection of both sides of the
9. McLaughlin CR. Surgical support in permanent facial
face to treat post-paralytic facial synkinesis. J Plast
paralysis. Plast Reconstr Surg. 1953;11(4):302–14.
Reconstr Aesthet Surg. 2013;66(8):1058–63. Epub
10. Nduka C, Hallam MJ, Labbe D. Refinements in smile
2013 May 15.
reanimation: 10-year experience with the lengthening
22. Choi D, Raisman G. Disorganization of the facial
temporalis myoplasty. J Plast Reconstr Aesthet Surg.
nucleus after nerve lesioning and regeneration in the
2012;65(7):851–6. Epub 2012 Mar 24.
rat: effects of transplanting candidate reparative cells
11. Scaramella LF. Preliminary report on facial nerve
to the site of injury. Neurosurgery. 2005;56:1093–100.
anastomosis. In: 2nd International symposium on
23. Baker RS, Stava MW, Nelson KR, May PJ, Huffman
facial nerve surgery, Osaka, Japan; 1970.
MD, Porter JD. Aberrant reinnervation of facial mus-
12. Zuker RM, Goldberg CS, Manktelow RT. Facial
culature in a subhuman primate: a correlative analysis
animation in children with Mobius syndrome after
of eyelid kinematics, muscle synkinesis, and moto-
segmental gracilis muscle transplant. Plast Reconstr
neuron localization. Neurology. 1994;44:2165–73.
Surg. 2000;106(1):1–8.
24. May M, Croxson GR, Klein SR. Bell’s palsy: manage-
13. Borschel GH, Kawamura DH, Kasukurthi R, et al.
ment of sequelae using EMG rehabilitation, botuli-
The motor nerve to the masseter muscle: an anatomic
num toxin, and surgery. Am J Otol. 1989;10(3):220–9.
and histomorphometric study to facilitate its use in
Part III
Breast Surgery
Evolution of Reconstructive
Implant Breast Surgery
16
Danielle H. Rochlin and Joseph J. Disa

1. Cronin TD, Gerow FJ. Augmentation mam-
This chapter highlights five landmark papers
maplasty: a new ‘natural feel’ prosthesis.
that exemplify the evolution of implant-based
Transactions of the Third International
breast reconstruction from inception to pres-
Congress of Plastic Surgery. Amsterdam:
ent day. We begin with Cronin and Gerow’s
Excerpta Medica; 1964.
foundational paper describing the advent of
2. Radovan C. Breast reconstruction after mas-
silicone breast implants, followed by a discus-
tectomy using the temporary expander. Plast
sion of tissue expansion and the development
Reconstr Surg. 1982;69(2):195–208.
of two-stage tissue expander-to-implant
3. Cunningham B. The Mentor Core Study on
reconstruction. We next discuss concerns
Silicone MemoryGel Breast Implants. Plast
regarding breast implant safety and the Mentor
Reconstr Surg. 2007;120(7 Suppl
Core Study that led to the reinstitution of
1):19S–29S.
breast implants in the US marketplace. Finally,
4. Breuing K, Warren S. Immediate bilateral
we conclude with two papers that represent
breast reconstruction with implants and infer-
advancements in modern-day surgical tech-
olateral AlloDerm slings. Ann Plast Surg.
nique: the use of acellular dermal matrix, and
2005;55(3):232–9.
the related resurgence of prepectoral breast
5. Sbitany H, Piper M, Lentz R. Prepectoral
reconstruction.
breast reconstruction: a safe alternative to sub-
muscular prosthetic reconstruction following
Keywords
nipple-sparing mastectomy. Plast Reconstr
Breast implants · Silicone implants · Silicone Surg. 2017;140(3):432–43.
gel · Tissue expansion · Delayed-immediate
reconstruction · Breast implant safety
Acellular dermal matrix · Prepectoral · Direct 16.1 Introduction
to implant · Landmark
Implant-based breast reconstruction is the most
popular method of postmastectomy reconstruc-
tion in the United States [1], and has come full
D. H. Rochlin · J. J. Disa (*) circle since its inception in the early 1960s. The
Plastic and Reconstructive, Surgery Service, original immediate prepectoral reconstructions
Department of Surgery, Memorial Sloan Kettering that were abandoned in favor of two-stage sub-
Cancer Center, New York, NY, USA
https://doi.org/10.1007/978-3-031-57132-9_16
150 D. H. Rochlin and J. J. Disa
pectoral placement have once again gained popu- sponges, all of which produced misshapen,
larity as technologies and surgical techniques uncomfortable, and unnatural breasts [2].
have improved to mitigate the historical adverse Injectables were also attempted, including petro-
complication profile. Concurrently, there has leum jelly, beeswax, shellac, putty, and silicone
been an increasingly organized effort to system- fluid and oil; however, these materials similarly
atically track events key to understanding breast led to unfavorable aesthetic and functional results
implant safety. The following chapter details the in addition to serious complications such as tis-
trajectory of implant-based breast reconstruction sue necrosis, adult respiratory distress syndrome,
through the lens of five papers that have played a and death [2].
fundamental role in shaping its evolutionary The Dow Corning Corporation developed the
course. first widespread silicone product for use in the
aircraft industry during World War II; this was
soon followed by various uses of silicone in med-
16.2 The Advent of Silicone Gel ical equipment and consumer products [3].
Breast Implants Cronin envisioned a “breast-shaped bag or con-
tainer filled with viscous fluid material” as an
Cronin and Gerow heralded the modern era of alternative to prior failed breast prostheses and
implant-based breast reconstruction with their worked with the Dow Corning Center for Aid to
introduction of silicone breast implants in 1964. Medical Research to realize this concept using
In the first half of the twentieth century, surgeons silicone elastomer. In this landmark paper [4], the
attempted to augment or reconstruct breasts using authors describe their experimental and clinical
a variety of implantable synthetic materials; these work that led to the development of the first sili-
included ivory, glass balls, cartilage, wool, and cone breast implant.
Cronin TD, Gerow FJ. Augmentation mammaplasty: a new ‘natural feel’ prosthesis. Transactions of the Third
International Congress of Plastic Surgery. Amsterdam: Excerpta Medica; 1964
Strengths • Introduced a novel concept and device
• First effort to develop a prosthesis with a “natural feel”
Limitations • Expert opinion (Level V evidence)
• No systematic report of outcomes or long-term patient follow up
• Dismissive of safety concerns
• Publication in a low-impact journal limits readership
Impact This paper marked the beginning of the modern era of implant-based reconstruction with the
introduction of a pioneering construct that remains the dominant method of breast reconstruction to
date
Cronin and Gerow’s silicone implant—now methods. However, the paper is anecdotal in
known as first-generation silicone implants— nature (Level V evidence), lacking any system-
consisted of a moderately viscous silicone gel atic or longitudinal report of patient outcomes. In
enclosed in a thick silicone elastomer shell. This terms of implant safety, the authors claim that
was a two-part construct with seams along the they experimentally confimed that the silicone
periphery, and a dacron patch on the posterior gel is “essentially leak proof” and would cause
surface to facilitate tissue ingrowth and prevent no harm if a leak were to occur. As we now know
malposition. In their seminal paper, the authors and will discuss shortly, despite the proven safety
report favorable aesthetic results in addition to a of later generation implants, this claim is not
soft feel, in stark contrast to previous alloplastic entirely accurate.
16 Evolution of Reconstructive Implant Breast Surgery 151
First generation silicone implants were manu- 16.3 Tissue Expansion and Staged
factured from approximately 1964 to 1968 with Breast Reconstruction
capsular contracture as the primary reported
complication. Believing that the thick shell and Cronin and Gerow describe their implant use in
viscous gel were the cause of capsular contrac- the context of breast augmentation and recon-
ture, second-generation silicone implants had a struction after “simple amputation.” However, in
thinner shell, less viscous silicone gel, and no surgical management of breast cancer beyond
seams or dacron fixation patches; the result was a that of a simple mastectomy, reconstructive sur-
high risk of “silicone bleed” without an improve- geons were and continue to be left with inade-
ment in the capsular contracture rate [2, 5]. In the quate vascularized soft tissue to accommodate a
1980s, third-generation silicone implant design breast implant. Even in cases of simple mastec-
reverted to a thicker multilayer silicone elastomer tomy, the breast envelope cannot accommodate
shell with a thicker cross-linked silicone gel to the size and pressure of a permanent implant if
minimize the risk of gel spillage. Fourth- and the skin flaps are poorly vascularized.
fifth-generation implants that were conceived in Accordingly, early reconstructions that were per-
the 1990s and continue to the present day are formed in a direct-to-implant fashion were char-
characterized by thick low-bleed shells with gels acterized by poor aesthetic results and high rates
that vary from viscous to enhanced cohesive and of skin necrosis and capsular contracture [7, 8].
form-stable [6]. Despite multiple adjustments With his introduction of the tissue expander in
over the past 60 years, silicone gel-filled breast the 1970s, Radovan ushered in the era of two-
implants remain remarkably similar in concept stage breast reconstruction that largely replaced
and design to Cronin and Gerow’s initial proto- single-stage immediate reconstruction as the pre-
type, attesting to the lasting impact of this land- ferred method of breast reconstruction for several
mark paper. ensuing decades.
Radovan C. Breast reconstruction after mastectomy using the temporary expander. Plast Reconstr Surg.
1982;69(2):195–208
Strengths • Introduced a novel device and concept
• Established tissue expansion as a key reconstructive method in plastic surgery
Limitations • Level IV evidence
• Limited patient outcomes and long-term follow up
• High complication rate
• Incorrect understanding of capsular contracture
Impact This paper introduced the two-stage approach to breast reconstruction that broadened eligibility for
implant-based reconstruction to patients with inadequate breast skin at the time of mastectomy to
accommodate an implant. Later on, the temporary expander would also facilitate reconstruction in
patients undergoing postmastectomy radiation therapy
In this landmark paper, Radovan reports a tracture, attributed to expanding the pocket
series of 68 patients who were reconstructed with 150–200 cc larger than the size of the permanent
a temporary prepectoral tissue expander follow- implant. It is now common practice to either
ing mastectomy, with later exchange to a perma- overfill or underfill the breast envelope on a case-
nent implant. Complications included hematoma by-case basis to meet the needs of the patient. In
(three patients), infection (five patients), skin addition, though the precise etiology of capsular
necrosis in patients with preoperative radiation contracture continues to be debated [9], the size
(two patients), and tissue expander deflation (one of the breast envelope in relation to the implant
patient). At an average follow-up of 1–2 years, placed is no longer thought to be a contributory
Radovan reported a “low” rate of capsular con- factor.
Expander technology and applications have definitive implant or autologous-based recon-

evolved in the decades since introduction. struction, while those who do require PMRT
Radovan’s initial device consisted of a silicone undergo radiation prior to definitive reconstruc-
balloon and a self-sealing removable subcutane- tion [12]. In this manner, surgeons can avoid the
ous port, gradually expanded with saline over an adverse aesthetic and functional complications
average of 8–10 sessions. Subsequent innova- that accompany radiating an autologous or
tions have included the development of a remote implant-based reconstruction [13], and radiation
port, suture tabs, shaped expanders, and direc- oncologists have the option of deflating the
tional expansion, all of which have helped to expander to optimize radiation. Though part of
improve the complication profile, aesthetic Kronowitz et al.’s original protocol, deflation of
results, and patient experience [10]. Radovan the expander prior to radiation is not obligatory
subsequently demonstrated the broader applica- in all circumstances, and there is currently no
tion of tissue expanders in soft tissue reconstruc- best practice consensus among radiation oncolo-
tion, publishing a series of 130 patients with gists [14]. Regardless, this broader indication of
defects of the scalp, face and neck, extremity, or tissue expansion in reconstructive breast surgery
trunk that were reconstructed with use of tissue has improved reconstructive options and out-
expansion [11]. In the present day, tissue expan- comes for breast cancer patients.
sion not only facilitates the majority of implant-
based breast reconstruction, but also has an
established role as a workhorse in plastic surgery 16.4 Breast Implant Safety
[10].
In breast reconstruction, while expanders con- Amid public fear of a link between silicone breast
tinue to be used to gradually stretch deficient implants and connective tissue disorders, in addi-
native chest tissue to accommodate an implant tion to a historical lack of data on silicone gel
following mastectomy, expanders have addition- implant safety and efficacy, the FDA placed a
ally become essential placeholders in the recon- moratorium on silicone implants in 1992, remov-
struction of patients undergoing postmastectomy ing these devices from the US marketplace [2, 5].
radiation therapy (PMRT). In 2004, Kronowitz This regulatory intervention not only led to years
et al. first described the technique of “delayed- of research and technical parameters that
immediate reconstruction” as a means of provid- informed subsequent generation of implants, but
ing a temporary reconstruction to preserve the also was the impetus for several coordinated
breast envelope while the need for PMRT is studies by US implant manufacturers designed to
determined based on pathological review; systematically evaluate the safety of silicone
patients who do not require PMRT proceed to breast implants.
Cunningham B. The Mentor Core Study on Silicone MemoryGel Breast Implants. Plast Reconstr Surg. 2007;120(7
Suppl 1):19S–29S
Strengths • Foundational paper in breast implant safety research
• Tangible impact on federal policy
Limitations • Not designed to evaluate cause-and-effect associations
• Question of an association with connective tissue disorder remains unanswered
• Lacks long-term data
• Underpowered to detect BIA-ALCL
Impact This paper provided foundational evidence on silicone gel implant safety and efficacy that led to FDA
approval in 2006 for augmentation in women aged 22 years or older and reconstruction in women of
any age. As a direct consequence of this study, silicone breast implants were reintroduced on the US
marketplace
The Mentor Core MemoryGel Study demon- Style 410 highly cohesive silicone implants, pub-
strated the safety and efficacy of silicone breast lishing their results in late 2007 [6].
implants, leading to FDA approval in 2006 [15]. The conversation about breast implant safety
This was a 10-year multicenter study involving at the time of Cunningham’s landmark publica-
1007 women who underwent breast augmentation looks very different than that of the present
tion (551 primary, 146 revision) or reconstruction day, which is largely focused on three diagnoses:
(251 primary, 59 revision). Cunningham’s 2007 Breast Implant-Associated Anaplastic Large Cell
landmark study reports safety assessments in Lymphoma (BIA-ALCL), Breast Implant-
terms of rates of complications and/or reopera- Associated Squamous Cell Carcinoma (BIA-
tion at 3 years: 36.6% for primary augmentation, SCC), and Breast Implant Illness (BII).
50.1% for revision augmentation, 49.4% for pri- Particularly with regards to the first two disease
mary reconstruction, and 47.5% for revision processes, neither was detected in Mentor or
reconstruction. Among the augmentation cohort, Allergan’s 3-year outcomes studies, likely
the leading reasons for reoperation were capsular because the follow-up timeframe was too short,
contracture and patient request for style and/or the studies were underpowered, and the diagno-
size change, while reconstructive patients com- ses were too obscure at the time to be recognized
monly were reoperated due to asymmetry, biopsy, as an outcome of interest. To date, the most com-
or capsular contracture. There were eight cases of prehensive epidemiologic assessment of BIA-
suspected rupture in six patients based on MRI ALCL is from the Patient Registry and Outcomes
imaging; two implants were explanted and confor Breast Implants and Anaplastic Large Cell
firmed to be ruptured, without findings of gel Lymphoma Etiology and Epidemiology
migration. The study, however, lacked a control (PROFILE) registry; a 2018 publication of regis-
group and thus was not designed to evaluate an try data included 186 cases in the US since 2012,
association with connective tissue disorders, an average of 11 years from implant placement to
leaving this question unanswered. Subsequent diagnosis, and an association with textured
studies have suggested that this association is devices [20]. A few months after publication, at
unlikely [16], though this still remains an active the request of the FDA, Allergan recalled Natrelle
area of research within the plastic surgery BIOCELL® “macrotextured” breast implants and
literature. tissue expanders in response to both epidemio-
Cunningham’s 2007 Mentor Core Study is logic and pathophysiologic evidence corrorborat-
symbolic of a larger evidence-based medicine ing a link with textured devices [21]. Moving
movement within alloplastic breast reconstruc- forward, PROFILE and similar centralized data
tion to systematically track and evaluate safety registries will be instrumental in navigating
and efficacy of marketed devices with large pro- implant safety and powering more meaningful
spective cohort studies. In addition to the Core studies on rare outcomes.
Study, Cunningham published a companion
study in 2007 that demonstrated the safety and
efficacy of Contour Profile Gel (CPG) silicone 16.5 Acellular Dermal Matrix
MemoryGel implants, which in comparison to and Modern Techniques
the Core Study implants, were shaped instead of in Implant-Based Breast
round and had both greater gel cross-linking and Reconstruction
surface texture [17]. Patients with MemoryGel
implants have continued to be followed over time The first implant-based breast reconstructions in
with comparable results demonstrating safety the early 1960s involved implant placement in
and efficacy at 6 and 10 years [18, 19]. Beginning the prepectoral plane. Prepectoral placement was
in 2001, Allergan (formerly Inamed) similarly soon abandoned in favor of subpectoral place-
tracked complication and satisfaction rates of the ment due to complications that included implant
malposition (“bottoming out”), palpability, visi- deformity, greater early postoperative pain,
bility, and wrinkling, in addition to risk of extru- increased donor site morbidity, and restricted
sion following breakdown of mastectomy skin lower pole expansion [22–24]. Partial muscle
flaps [22]. In addition, capsular contracture was coverage, in which pectoralis major covers the
commonly seen with early silicone implants and implant superiorly and leaves the inferior aspect
their associated gel bleed. Subpectoral placement in the subcutaneous plane, remedied this latter
was felt to lower the rate of capsular contracture. drawback, allowing for improved lower pole
With subpectoral placement, the implant is either expansion [25]. However, partial muscle cover-
fully or partially covered by muscle. Full muscle age reintroduced several of the disadvantages
coverage involves recruitment of serratus anterior historically associated with prepectoral p lacement
and rectus abdominis sheath to supplement pec- in the region of the lower pole with the added
toralis major muscle coverage laterally and infe- complication of superior migration of the pecto-
riorly; however, compared to prepectoral ralis major (“window-shading”) in the absence of
placement, disadvantages include animation inferior attachment [22].
Breuing K, Warren S. Immediate bilateral breast reconstruction with implants and inferolateral AlloDerm slings.
Ann Plast Surg. 2005;55(3):232–9
Strengths • Introduced a novel concept
• Detailed description of new technique and rationale
Limitations • Case series (Level IV evidence)
• Limited outcomes reported
Impact The was the first description of acellular dermal matrix as an adjunct to breast reconstruction. It
heralded a new era of “internal support” in breast reconstruction that served as the foundation for
several downstream innovations in implant-based breast reconstruction (e.g. dual-plane and
prepectoral implant placement, direct-to-implant reconstruction) that have improved reconstructive
outcomes for breast cancer patients
Breuing and Warren’s introduction of acellu- facilitating inferior pole expansion without the
lar dermal matrix (ADM) as an adjunct to drawbacks of direct subcutaneous implant place-
implant-based breast reconstruction addressed ment [29, 30]. Reported disadvantages include a
several of the disadvantages associated with par- higher risk of infection and seroma [31, 32].
tial muscle coverage. In their 2005 paper [26], Evidence is mixed regarding acceleration of
the authors review their experience with 10 lower pole expansion in two-stage tissue
patients (20 breasts) in which they supplemented expander-to-implant reconstruction [33, 34], cap-
partial muscle coverage with an AlloDerm sling sular contracture risk reduction [29, 35–37], and
to reestablish the lower pole. Though lacking sci- aesthetic and health-related quality of life out-
entific study design and long-term outcomes, this comes [33, 34, 38, 39].
paper introduced the concept of “internal sup- Now nearly two decades after Breuing and
port” that inspired several downstream innova- Warren’s landmark paper, a majority of surgeons
tions in implant-based surgical techniques that performing implant-based breast reconstruction
have expanded reconstructive options and use ADM [40], with 25 different products from
improved outcomes for breast cancer patients. 14 countries on the market as of 2017 [41].
Nearly two decades after this landmark paper, a Human-derived biologic ADMs, such as
sizable body of literature on ADM now exists AlloDerm, remain the most popular products in
demonstrating utility in improving implant posi- the US, though various forms of xenografts are
tioning and projection in both a primary and sec- also available [41]. Compared to Breuing and
ondary fashion [27, 28]; stabilizing the pectoralis Warren’s AlloDerm, modern biologic ADMs are
major muscle to limit window-shading [22]; and increasingly user-friendly with shaped, perfo-
rated, prehydrated variants [41]. Permanent or since the early 2000s, with the most concentrated
absorbable synthetic mesh has also gained popu- growth occurring around 2017–2018 [44]. In
larity as a more cost-effective alternative that addition to less aggressive mastectomies, technol-
avoids many of the regulatory barriers associated ogy to assess mastectomy skin flap perfusion,
with biologics, especially outside of the US improvements in implant design, and refinements
[41–43]. in fat grafting technique [22, 45, 46], ADM has
enabled a return to prepectoral implant placement
without many of the drawbacks seen in earlier
16.5.1 Prepectoral Reconstruction iterations. Sbitany et al.’s 2017 paper on prepec-
toral breast reconstruction was one of the first
Use of ADM has been critical to the resurgence of well-designed studies to demonstrate the safety
prepectoral breast reconstruction. Interest in pre- and efficacy of prepectoral alloplastic breast
pectoral reconstruction has grown exponentially reconstruction in conjunction with ADM [47].
Sbitany H, Piper M, Lentz R. Prepectoral breast reconstruction: a safe alternative to submuscular prosthetic
reconstruction following nipple-sparing mastectomy. Plast Reconstr Surg. 2017;140(3):432–43
Strengths • Solidified prepectoral reconstruction as a safe and effective technique
• Provided detailed information on surgical technique
• Level III evidence—study with a control/comparison group
Limitations • All patients had nipple-sparing mastectomy, limiting generalizability
• Only appropriate in selected patients with well-perfused skin flaps
• Limited examination of technique in setting of PMRT
Impact This paper influenced the return to prepectoral breast reconstruction in a safer and more effective
way than previously employed, leading to more anatomic and less painful reconstructions in women
undergoing implant-based breast reconstruction
In this landmark study, Sbitany et al. compare reconstruction is a safe an effective reconstruc-
51 patients (84 breasts) who underwent immedi- tive alternative that avoids the functional draw-
ate prepectoral reconstruction with tissue backs of subpectoral placement, notably the pain
expander placement to 115 patients (186 breasts) and deformity associated with manipulation of
who underwent submuscular tissue expander chest wall muscles.
placement. All patients underwent nipple-sparing Though pivotal in re-establishing prepectoral
mastectomy (NSM), and all reconstructions reconstruction as a leading technique for
involved use of ADM. Largely based on surgeon expander placement, this study is not without
preference, ADM may be placed in conjunction shortcomings that limit generalizability. All
with an expander or implant in a variety of con- patients underwent NSM, which though shown to
figurations including anterior coverage, middle be oncologically safe, may not be the standard of
and lower third coverage, and partial or full wraps care at many centers and is not feasible in all
[48, 49]. Sbitany et al.’s preference is to create a patients. Additionally, the study has limited long-
“cuff” of ADM at the inframammary fold to bol- term follow-up, and only a minority of patients
ster lower pole support, and to fold the remainder underwent PMRT (17 patients in the subpectoral
of the ADM over the anterior surface of the group, 7 in the prepectoral group), limiting con-
expander. Mean follow-up time was 12.5 (range clusions about the efficacy of this technique in
7–28) months in the submuscular group and 11.1 irradiated patients. Most importantly, the authors
(range 5–23) months in the prepectoral group. selected patients for pre- versus subpectoral
Based on data illustrating no significant differ- expander placement based on the viability of skin
ence in overall complication rate between the two flaps after mastectomy. Regardless of use of
cohorts, the authors conclude that prepectoral ADM, prepectoral placement is only an appropri-
ate alternative for patients whose skin flaps are two stages. Importantly, DTI was selectively per-
well-vascularized and is thus not appropriate in formed on patients who desired a breast size
all reconstructive circumstances. Areas of ongo- smaller or similar to their baseline breast size
ing study include the relationship between pre- with an adequately vascularized mastectomy skin
pectoral placement and capsular contracture in flap [8]. In terms of cost, the authors found no
radiated patients, methods of improving upper significant differences between DTI with ADM
pole aesthetics in light of the recent shift to and tissue expander reconstruction without
smooth round implants from textured anatomic ADM, though their tabulated costs involved only
implants, and determining whether ADM is nec- hospital, anesthesia, and surgeon charges. An
essary from an outcomes standpoint in prepec- ensuing cost-utility analysis with a more encom-
toral breast reconstruction [50]. passing definition of outcomes and input costs
found that DTI reconstruction can indeed be
cost-effective [54].
16.5.2 Direct-to-Implant Subsequent authors have reproduced Colwell
Reconstruction et al.’s results with varying degrees of success. It
is worth mentioning a contemporaneous study by
Like prepectoral reconstruction, direct-to-Salzberg et al. from 2011, in which the authors
implant (DTI) reconstruction was originally describe 260 patients (466 breasts) who under-
practiced with the earliest implant-based breast went DTI with ADM reconstruction with a simi-
reconstructions. Due to poor aesthetic results and lar low rate of complications; unlike Colwell
high rates of skin necrosis and capsular contrac- et al.’s study, this paper does not include a com-
ture, two-stage tissue expander/implant recon- parison group [55]. While some groups have
struction largely replaced single-stage immediate reported higher rates of nipple and mastectomy
reconstruction as the preferred method of breast skin flap necrosis with DTI compared to tissue
reconstruction for several subsequent decades [7, expander/implant reconstruction [56], others
8]. The advent of ADM, in addition to skin- and have shown similarly comparable rates of com-
nipple-preserving mastectomy techniques [8, 30, plications between these two reconstructive
51, 52], has enabled a return to DTI with a more methods irrespective of ADM use [57, 58]. In this
favorable complication profile. landmark paper, Colwell et al.’s finding that a
Though not selected as a landmark study, higher complication rate with single-stage recon-
Colwell et al.’s 2011 paper on DTI reconstruction struction was significantly associated with a sur-
[8] deserves an honorable mention. The authors geon’s first year performing this reconstruction
describe 211 patients (311 reconstructions) who highlights the learning curve that may be associ-
underwent DTI reconstruction with AlloDerm ated with DTI reconstruction and the consequent
after nipple-sparing or skin-sparing mastectomy, variable outcomes among surgical groups. As
in comparison to 158 two-stage expander/implant prepectoral DTI reconstructions start to become
reconstructions without AlloDerm. For DTI more commonplace [58, 59], it will be interesting
reconstruction, the authors position the implant to see how these reconstructions compare in
in a partial subpectoral plan with AlloDerm cre- terms of both clinical and patient-reported
ating an inferolateral hammock that is anchored outcomes.
to the chest wall and anterior rectus abdominis
fascia inferiorly, and the inferior border of the
pectoralis muscle superiorly, as described in 16.6 Expert Concluding
Colwell’s prior publication [53]. The authors Commentary
report a similar complication rate between DTI
and tissue expander cohorts, establishing that Given the popularity of implant-based breast
comparable reconstructive outcomes can be reconstruction, it is no surprise that an extensive
achieved in a single-stage operation instead of body of research surrounds this topic. While each
of these papers propels the field forward in its 12. Kronowitz SJ, Hunt KK, Kuerer HM, et al. Delayed-
own way, we have selected five papers that immediate breast reconstruction. Plast Reconstr Surg.
2004;113(6):1617–28.
encompass key events in the history of implant- 13. Wilkins EG, Hamill JB, Kim HM, et al.
based breast reconstruction that have clearly Complications in postmastectomy breast reconstruc-
impacted the trajectory of this reconstructive tion: 1-year outcomes of the mastectomy reconstruc-
modality. Future growth is contingent upon ongo- tion outcomes consortium (MROC) study. Ann Surg.
2018;267(1):164–70.
ing investigation. We look forward to reading the 14. Ho A, Cordeiro P, Disa J, et al. Long-term outcomes in
next series of landmark papers in the years to breast cancer patients undergoing immediate 2-stage
come. expander/implant reconstruction and postmastectomy
radiation. Cancer. 2012;118(9):2552–9.
15. Cunningham B. The Mentor Core Study on silicone
MemoryGel breast implants. Plast Reconstr Surg.
References 2007;120(Supplement 1):19S–29S.
16. Barbosa MR, Makris UE, Mansi IA. Association of
1. Albornoz CR, Bach PB, Mehrara BJ, et al. A paradigm Breast Implants with nonspecific symptoms, con-
shift in U.S. breast reconstruction: increasing implant nective tissue diseases, and allergic reactions: a
rates. Plast Reconstr Surg. 2013;131(1):15–23. retrospective cohort analysis. Plast Reconstr Surg.
2. Young VL, Watson ME. Breast implant research: 2021;147(1):42e–9e.
where we have been, where we are, where we need to 17. Cunningham B. The Mentor study on contour pro-
go. Clin Plast Surg. 2001;28(3):451–83. file gel silicone MemoryGel breast implants. Plast
3. Feder BJ. All about: silicone products; a war Reconstr Surg. 2007;120(7 Suppl 1):33S–9S.
baby, versatile silicone now shows up every- 18. Cunningham B, McCue J. Safety and effectiveness of
where. The New York Times. https://www.nytimes. Mentor’s MemoryGel implants at 6 years. Aesth Plast
com/1991/12/29/business/all-a bout-s ilicone- Surg. 2009;33(3):440–4.
products-war-baby-versatile-silicone-now-shows-up- 19. Caplin DA, Calobrace MB, Wixtrom RN, Estes MM,
everywhere.html. Accessed 9 May 2023. Canady JW. MemoryGel breast implants: final safety
4. Cronin T, Gerow F. Augmentation mammaplasty: a and efficacy results after 10 years of follow-up. Plast
new ‘natural feel’ prosthesis. Elsevier; 1964. Reconstr Surg. 2021;147(3):556–66.
5. Kaoutzanis C, Winocour J, Unger J, Gabriel A, 20. McCarthy CM, Loyo-Berríos N, Qureshi AA,
Maxwell GP. The evolution of breast implants. Semin et al. Patient registry and outcomes for breast
Plast Surg. 2019;33(4):217–23. implants and anaplastic large cell lymphoma etiol-
6. Bengtson BP, Van Natta BW, Murphy DK, Slicton A, ogy and epidemiology (PROFILE): initial report
Maxwell GP. Style 410 highly cohesive silicone breast of findings, 2012–2018. Plast Reconstr Surg.
implant Core study results at 3 years. Plast Reconstr 2019;143(3S):65S–73S.
Surg. 2007;120(Supplement 1):40S–8S. 21. FDA. Allergan voluntarily recalls BIOCELL® tex-
7. Clarke-Pearson EM, Lin AM, Hertl C, Austen WG, tured breast implants and tissue expanders. U.S. Food
Colwell AS. Revisions in implant-based breast recon- and Drug Administration. 2020. https://www.fda.
struction: how does direct-to-implant measure up? gov/safety/recalls-market-withdrawals-safety-alerts/
Plast Reconstr Surg. 2016;137(6):1690–9. allergan-voluntarily-recalls-biocellr-textured-breast-
8. Colwell AS, Damjanovic B, Zahedi B, Medford- implants-and-tissue-expanders. Accessed 28 Dec 2022.
Davis L, Hertl C, Austen WG. Retrospective review 22. Sigalove S, Maxwell GP, Sigalove NM, et al.
of 331 consecutive immediate single-stage implant Prepectoral implant-based breast reconstruction:
reconstructions with acellular dermal matrix: indica- rationale, indications, and preliminary results. Plast
tions, complications, trends, and costs. Plast Reconstr Reconstr Surg. 2017;139(2):287–94.
Surg. 2011;128(6):1170–8. 23. Spear SL, Schwartz J, Dayan JH, Clemens
9. Bachour Y, Bargon CA, De Blok CJM, Ket JCF, Ritt MW. Outcome assessment of breast distortion fol-
MJPF, Niessen FB. Risk factors for developing capsu- lowing submuscular breast augmentation. Aesth Plast
lar contracture in women after breast implant surgery: Surg. 2009;33(1):44–8.
a systematic review of the literature. J Plast Reconstr 24. Nelson JA, Shamsunder MG, Vorstenbosch J,
Aesthet Surg. 2018;71(9):e29–48. et al. Prepectoral and subpectoral tissue expander-
10. Pacella SJ. Evolution in tissue expander design for based breast reconstruction: a propensity-matched
breast reconstruction: technological innovation to analysis of 90-day clinical and health-related
optimize patient outcomes. Plast Reconstr Surg. quality-of-life outcomes. Plast Reconstr Surg.
2018;142:21S–30S. 2022;149(4):607e–16e.
11. Radovan C. Tissue expansion in soft-tissue recon- 25. Serra-Renom JM, Fontdevila J, Monner J, Benito
struction. Plast Reconstr Surg. 1984;74(4):482–92. J. Mammary reconstruction using tissue expander and
partial detachment of the pectoralis major muscle to with breast cancer: a randomized clinical trial. JAMA
expand the lower breast quadrants. Ann Plast Surg. Netw Open. 2021;4(10):e2127806.
2004;53(4):317–21. 40. Ibrahim AMS, Koolen PGL, Ashraf AA, et al.
26. Breuing KH, Warren SM. Immediate bilateral Acellular dermal matrix in reconstructive breast
breast reconstruction with implants and inferolateral surgery: survey of current practice among plas-
AlloDerm slings. Ann Plast Surg. 2005;55(3):232–9. tic surgeons. Plast Reconstr Surg Glob Open.
27. Spear SL, Seruya M, Clemens MW, Teitelbaum 2015;3(4):e381.
S, Nahabedian MY. Acellular dermal matrix 41. Kim JYS, Mlodinow AS. What’s new in acellu-
for the treatment and prevention of implant- lar dermal matrix and soft-tissue support for pros-
associated breast deformities. Plast Reconstr Surg. thetic breast reconstruction. Plast Reconstr Surg.
2011;127(3):1047–58. 2017;140:30S–43S.
28. Spear SL, Sher SR, Al-Attar A, Pittman 42. Tessler O, Reish RG, Maman DY, Smith BL,
T. Applications of acellular dermal matrix in revision Austen WG. Beyond biologics: absorbable mesh
breast reconstruction surgery. Plast Reconstr Surg. as a low-cost, low-complication sling for implant-
2014;133(1):1–10. based breast reconstruction. Plast Reconstr Surg.
29. Sbitany H, Sandeen SN, Amalfi AN, Davenport MS, 2014;133(2):90e–9e.
Langstein HN. Acellular dermis—assisted prosthetic 43. Ganz OM, Tobalem M, Perneger T, et al. Risks and
breast reconstruction versus complete submuscular benefits of using an absorbable mesh in one-stage
coverage: a head-to-head comparison of outcomes. immediate breast reconstruction: a comparative study.
Plast Reconstr Surg. 2009;124(6):1735–40. Plast Reconstr Surg. 2015;135(3):498e–507e.
30. Sobti N, Ji E, Brown RL, et al. Evaluation of 44. Safran T, Al-Halabi B, Dionisopoulos T. Prepectoral
acellular dermal matrix efficacy in prosthesis- breast reconstruction: a growth story. Plast Reconstr
based breast reconstruction. Plast Reconstr Surg. Surg. 2019;144(3):525e–7e.
2018;141(3):541–9. 45. Cil TD, McCready D. Modern approaches to the sur-
31. Chun YS, Verma K, Rosen H, et al. Implant-based gical management of malignant breast disease. Clin
breast reconstruction using acellular dermal matrix Plast Surg. 2018;45(1):1–11.
and the risk of postoperative complications. Plast 46. Duggal CS, Madni T, Losken A. An outcome
Reconstr Surg. 2010;125(2):429–36. analysis of intraoperative angiography for post-
32. Kim JYS, Davila AA, Persing S, et al. A meta- mastectomy breast reconstruction. Aesthet Surg J.
analysis of human acellular dermis and submuscular 2014;34(1):61–5.
tissue expander breast reconstruction. Plast Reconstr 47. Sbitany H, Piper M, Lentz R. Prepectoral breast recon-
Surg. 2012;129(1):28–41. struction: a safe alternative to submuscular prosthetic
33. McCarthy CM, Lee CN, Halvorson EG, et al. The use reconstruction following nipple-sparing mastectomy.
of acellular dermal matrices in two-stage expander/ Plast Reconstr Surg. 2017;140(3):432–43.
implant reconstruction: a multicenter, blinded, 48. Sigalove S. Options in acellular dermal matrix–device
randomized controlled trial. Plast Reconstr Surg. assembly. Plast Reconstr Surg. 2017;140:39S–42S.
2012;130:57S–66S. 49. Sayegh F, Zoghbi Y, Jacobs J, Salzberg CA. The
34. Sorkin M, Qi J, Kim HM, et al. Acellular dermal “empanada” construct: prepectoral technique refine-
matrix in immediate expander/implant breast recon- ment utilizing a composite acellular dermal matrix
struction: a multicenter assessment of risks and ben- mesh wrap. Plast Reconstr Surg. 2021;147(6):1082–3.
efits. Plast Reconstr Surg. 2017;140(6):1091–100. 50. Campbell CA, Losken A. Understanding the evidence
35. Basu CB, Jeffers L. The role of acellular dermal and improving outcomes with implant-based pre-
matrices in capsular contracture: a review of the evi- pectoral breast reconstruction. Plast Reconstr Surg.
dence. Plast Reconstr Surg. 2012;130:118S–24S. 2021;148(3):437e–50e.
36. Vardanian AJ, Clayton JL, Roostaeian J, et al. 51. Colwell AS, Christensen JM. Nipple-sparing mas-
Comparison of implant-based immediate breast tectomy and direct-to-implant breast reconstruction.
reconstruction with and without acellular dermal Plast Reconstr Surg. 2017;140:44S–50S.
matrix. Plast Reconstr Surg. 2011;128(5):403e–10e. 52. Colwell AS, Tessler O, Lin AM, et al. Breast recon-
37. Salzberg CA. Nonexpansive immediate breast reconstruction following nipple-sparing mastectomy:
struction using human acellular tissue matrix graft predictors of complications, reconstruction out-
(AlloDerm). Ann Plast Surg. 2006;57(1):1–5. comes, and 5-year trends. Plast Reconstr Surg.
38. DeLong MR, Tandon VJ, Farajzadeh M, et al. 2014;133(3):496–506.
Systematic review of the impact of acellular dermal 53. Breuing KH, Colwell AS. Inferolateral AlloDerm
matrix on aesthetics and patient satisfaction in tis- hammock for implant coverage in breast reconstruc-
sue expander-to-implant breast reconstructions. Plast tion. Ann Plast Surg. 2007;59(3):250–5.
Reconstr Surg. 2019;144(6):967e–74e. 54. Krishnan NM, Fischer JP, Basta MN, Nahabedian
39. Lohmander F, Lagergren J, Johansson H, Roy PG, MY. Is single-stage prosthetic reconstruction cost
Brandberg Y, Frisell J. Effect of immediate implant- effective? A cost-utility analysis for the use of direct-
based breast reconstruction after mastectomy with to-implant breast reconstruction relative to expander-
and without acellular dermal matrix among women
implant reconstruction in postmastectomy patients. tion: 2-year risks and patient-reported outcomes from
Plast Reconstr Surg. 2016;138(3):537–47. a prospective, multicenter study. Plast Reconstr Surg.
55. Salzberg CA, Ashikari AY, Koch RM, Chabner- 2017;140(5):869–77.
Thompson E. An 8-year experience of direct-to- 58. Urban C, González E, Fornazari A, et al. Prepectoral
implant immediate breast reconstruction using human direct-to-implant breast reconstruction without
acellular dermal matrix (AlloDerm). Plast Reconstr placement of acellular dermal matrix or mesh after
Surg. 2011;127(2):514–24. nipple-sparing mastectomy. Plast Reconstr Surg.
56. Frey JD, Choi M, Salibian AA, Karp NS. Comparison 2022;150(5):973–83.
of outcomes with tissue expander, immediate implant, 59. Safran T, Al-Halabi B, Viezel-Mathieu A, Hazan J,
and autologous breast reconstruction in greater than Dionisopoulos T. Direct-to-implant prepectoral breast
1000 nipple-sparing mastectomies. Plast Reconstr reconstruction: patient-reported outcomes. Plast
Surg. 2017;139(6):1300–10. Reconstr Surg. 2021;148(6):882e–90e.
57. Srinivasa DR, Garvey PB, Qi J, et al. Direct-to-implant
versus two-stage tissue expander/implant reconstruc-
Evolution of Reconstructive
Autologous Breast Surgery
17
Nakul Gamanlal Patel and Venkat Ramakrishnan

1. Holmstrom H. The free abdominoplasty flap
In this chapter, the ‘Evolution of breast recon-
and its use in breast reconstruction. An experi-
struction’ is discussed in the context of five
mental study and clinical case report. Scand J
landmark papers that have guided its develop-
Plast Reconstr Surg. 1979;13:423–7.
ment. For many years, mastectomy was a
2. Hartrampf CR, Scheflan M, Black PW. Breast
common treatment for breast cancer, but
reconstruction with a transverse abdominal
reconstructive options were not available
island flap. Plast Reconstr Surg.
until relatively recently. This review exam-
1982;69(2):216–25.
ines the history of autologous breast recon-
3. Allen RJ, Treece P. Deep inferior epigastric
struction although the details of the individual
perforator flap for breast reconstruction. Ann
reconstructive options are not discussed in
Plast Surg. 1994;32(1):32–8.
detail. The lower abdomen has become the
4. Blondeel PN, Morris SF, Hallock GG, et al.
preferred autologous donor reconstructive
The versatility of the deep inferior epigastric
site impact in autologous breast reconstruc-
perforator flap: a prospective study of 100
tion. The papers are discussed in detail includ-
consecutive patients. Plast Reconstr Surg.
ing their strengths and weaknesses and overall
1998;102(6):1788–96. discussion 1797–802.
impact.
5. Schneider WJ, Hill HL, Brown RG. Latissimus
dorsi myocutaneous flap for breast reconstruc-
Keywords
tion. Br J Plast Surg. 1977;30:277–81.
Autologous-based reconstruction · DIEP ·
TRAM · Latissimus dorsi
17.1 Introduction
Breast reconstruction is crucial to restoring the

aesthetic appearance of the breast after surgical
N. G. Patel (*) · V. Ramakrishnan tumour resection, trauma or congenital abnor-
Department of Plastic Surgery and Burns, The Royal malities. There are many options when consider-
Infirmary Hospital, University Hospitals of Leicester, ing breast reconstruction including surgery of the
Leicester, UK contralateral breast for symmetrisation
St. Andrew’s Centre for Plastic Surgery and Burns, (Fig. 17.1). The evolution in breast reconstruc-
Broomfield Hospital, Chelmsford, Essex, UK tion techniques is discussed in this chapter.
https://doi.org/10.1007/978-3-031-57132-9_17
162 N. G. Patel and V. Ramakrishnan
Fig. 17.1 Breast reconstructive options
17.2 Historical Perspective ment of tubed pedicle flap techniques by Gillies

during the world war. The shortcoming of these
Halsted [1] was the first to perform and advocate operations was the long inpatient stay, multiple
for radial mastectomies in 1889. His belief was operations and donor site scars.
that this was the only way in which to control the
disease and reduce recurrence. This aggressive
approach delayed the advent of reconstructive 17.3 Latissimus Dorsi
options by several decades. Over time, however, Myocutaneous Flap
these theories have been disproved and shown to
be overly aggressive thereby leading to a shift Schneider et al. [4] published a seminal paper on
towards more breast conserving approaches the use of the latissimus dorsi myocutaneous flap
especially for early breast cancers. for breast reconstruction, a technique that
Czerny [2] first attempted breast reconstruc- involves transferring a flap of skin, fat and mus-
tion with the first transplantation of a fist-sized cle from the back to the chest to create a new
lipoma from a patient’s flank. Tanzini [3] under- breast mound. This paper became widely adopted.
took transfer of the latissimus dorsi flap to close The latissimus dorsi flap can be used with under-
a mastectomy defect. These early techniques lying implants or less commonly as an autolo-
were refined over time, leading to the develop- gous only flap.
Schneider WJ, Hill HL, Brown RG. Latissimus dorsi myocutaneous flap for breast reconstruction. Br J Plast Surg.
1977;30:277–81
Strengths • First paper describing use of the latissimus dorsi myocutaneous flap for breast reconstruction
• Detailed description of the surgical technique, including the anatomy, vascular supply and
surgical steps
• Clinical case series of ten patients
• No comparison to other reconstruction methods
• No long-term follow up
Impact At the time of publication, there were limited options for breast reconstruction. The paper was an
important milestone in the field of breast reconstruction and provided significant improvements in
the options available to women who had undergone mastectomy. The procedure was relatively
simple and reliable given good cosmetic results. The technique quickly gained popularity and
became one of the standard methods for breast reconstruction. The latissimus dorsi myocutaneous
flap has since been refined and still widely used around the world
17 Evolution of Reconstructive Autologous Breast Surgery 163
There have been several refinements that have surgical options, this flap remains a valuable
been made to the latissimus dorsi flap technique to option, particularly in cases where the abdomen
address specific challenges and further optimise is not suitable for tissue transfer and microsurgi-
results. For example, to increase the volume, con- cal techniques are not possible.
current fat grafting into the muscle, or taking the
extended latissimus dorsi flap in which a number of
additional fat compartments can be taken have been 17.4 Abdominal-Based Flaps—
proposed. Furthermore, advancements in perforator From TRAM to DIEP Flaps
flap techniques have led to the development of the
muscle-sparing latissimus dorsi flap, which pre- Serafin and Georgiade [5] undertook the first free
serves the muscle while utilising only the skin and tissue transfer for breast reconstruction using a
fat for reconstruction typically for smaller defects. groin flap with an implant. A year later, Holmström
The latissimus dorsi flap is well-established [6] published an article which discussed the ‘free
and remains a widely used technique in breast abdominoplasty flap’ that examined the availabil-
reconstruction surgery. It offers several advan- ity of the abdominal pannus for breast reconstruc-
tages, such as reliable blood supply, good tissue tion using microsurgical techniques. The
match, and versatility in achieving satisfactory technique of transferring a flap of skin, fat and
aesthetic outcomes. Despite advances with muscle from the lower abdomen to the chest to
implant-based reconstruction, ADMs or micro- create a new breast mound was adopted.
Holmstrom H. The free abdominoplasty flap and its use in breast reconstruction. An experimental study and clinical
case report. Scand J Plast Reconstr Surg. 1979;13:423–7
Strengths • First to describe the use of the free abdominoplasty flap for breast reconstruction
• Detailed description of the surgical technique, including the anatomy, vascular supply, and the
surgical steps
Limitations • Only a single patient
• No comparison to other breast reconstruction techniques
• No long-term follow up
Impact Holmstrom’s paper had a significant impact on the field of breast reconstruction, as it introduced a
new surgical technique that provided an alternative to other breast reconstruction methods such as
the latissimus dorsi flap and the pedicled transverse rectus abdominis myocutaneous (TRAM) flap.
The free abdominoplasty flap technique has since been refined and improved upon, and it is now
considered the gold standard option for breast reconstruction
Hartrampf and his colleagues conducted a ence with the transverse abdominal island flap
series of studies in the late 1970s and early 1980s technique for breast reconstruction [7].
that eventually led to the development of the In 1982, Hartrampf described the pedicled
transverse rectus abdominis myocutaneous transverse rectus abdominis myocutaneous
(TRAM) flap technique for breast reconstruction. (TRAM) flap for breast reconstruction with a fur-
Hartrampf and colleagues described their experi- ther paper on 300 cases of breast reconstruction
using the TRAM flap with a high rate of success. TRAM flap [8] and subsequently the muscle-
Refinement to this technique included the free sparing TRAM flaps.
Hartrampf CR, Scheflan M, Black PW. Breast reconstruction with a transverse abdominal island flap. Plast Reconstr
Surg. 1982;69(2):216–25
Strengths • Large sample of 300 cases
• Prospective case series
• Detailed descriptions of the surgical technique, including diagrams and photographs, allowing
for replication of the procedure by others
Limitations • No direct comparison to other techniques
• No long-term follow-up on outcomes
Impact The TRAM flap has become a widely used and well-established method for breast reconstruction,
with high success rates. The publication helped develop the the free TRAM flap as a viable option
for breast reconstruction and paved the way for further research and development for the DIEP flap
Allen and Treece [9] published the first paper on Allen and Treece reported on 32 cases of
the DIEP flap. In comparison to the TRAM flap this breast reconstruction, using the DIEP flap, report-
flap included none of the rectus abdominus muscle. ing a low rate of complications and high patient
Interestingly, although published first by Allen and satisfaction. The natural evolution of pedicled
Treece, the first free DIEP flap was undertaken by TRAM to DIEP is shown in Fig. 17.2.
the senior author and published more recently [10].
Allen RJ, Treece P. Deep inferior epigastric perforator flap for breast reconstruction. Ann Plast Surg.
1994;32(1):32–8
Strengths • First published paper on the DIEP flap
• Discusses the radiographic evaluation of the abdominal vasculature
• Describes the surgical steps
Limitations • Retrospective study without a control group
• Follow up was limited to 6–24 months post-operatively
Impact The DIEP flap has become a widely used and the gold standard for autologous breast reconstruction,
with high success rates and patient satisfaction
The paper served as a foundation for subsequent research on further refinements for the DIEP flap
with modifications and refined being developed
Pedicled TRAM Free TRAM MS DIEP DIEP
Fig. 17.2 Natural evolution of the abdominal-based flaps

Since the development of the DIEP flap, there 1. Lower risk of abdominal muscle weakness
have been many studies comparing the effective- and hernia due to muscle-sparing dissection.
ness and safety to the TRAM flap. Blondeel [11] 2. More aesthetically pleasing results due to less
describes a prospective study of 100 consecutive abdominal wall distortion.
patients who underwent breast reconstruction 3. Less postoperative pain and shorter hospital
using the deep inferior epigastric perforator stay.
(DIEP) flap, and it includes comparative analyzes
with the transverse rectus abdominis myocutane- Overall, the study concluded that the DIEP
ous (TRAM) flap. The study found that the DIEP flap was a safe and reliable option for breast
flap had several advantages over the TRAM flap, reconstruction, with superior outcomes com-
including: pared to the TRAM flap.
Blondeel PN, Morris SF, Hallock GG, et al. The versatility of the deep inferior epigastric perforator flap: a
prospective study of 100 consecutive patients. Plast Reconstr Surg. 1998;102(6):1788–96. discussion 1797–802
Strengths • Prospective analysis of 100 consecutive patients
• Comparison of outcomes of two commonly used flap techniques for breast reconstruction
• Detailed analysis of the advantages and disadvantages of each technique
• Long-term follow up of up to 3 years
Limitations • Not a randomised controlled trial
• No analysis of the cost-effectiveness of the two techniques
Impact This paper popularised the DIEP flap as the gold standard technique for autologous breast
reconstruction. It also highlighted the morbidity associated with TRAM flaps. The study has
influenced the development of further perforator flaps for breast reconstruction
It is noteworthy that in a proportion of patients 17.5 Secondary Choices

the superficial inferior epigastric artery (SIEA) for Autologous Breast
flap can be utilised to further reduce abdominal Reconstruction
donor site morbidity as this does not require any
incisions through the anterior rectus sheath and When the abdomen is not available as a donor
dissection through the muscle which may lead to site, there are a number of secondary donor sites;
damage to the nerves. This flap was first used in the medial thigh, buttock and back.
breast reconstruction by Grotting [12] and
described this as ‘free abdominoplasty flap’. This
flap, however, has not been as popular as the 17.5.1 Medial Thigh
DIEP flap given the smaller calibre of pedicle
vessels and poorer vascular perfusion past the The medial thigh is a reliable option for breast
midline of the abdomen. reconstruction and includes the transverse upper
gracilis (TUG) flap [13] and the profunda artery
(PAP) flap [14]. The TUG flap is well estab- yet gained popularity given the complexity of
lished; however, the PAP flap has recently additional grafts required and potential donor site
gained more popularity given that this does not complications.
sacrifice any muscles and is able to recruit more
tissue than the TUG flap. The TUG flap is more
anterior and typically more cranial compared to 17.5.3 Combination Flaps
the PAP flap which is a little more posterior and
caudal. The scars here can be relatively conceal- There are also many papers on combinations of
able but occasionally can migrate lower and be two flaps for one breast reconstruction including
visible. The vascular anatomy for both flaps is combining the DIEP with the Deep Circumflex
consistent and reliable. The main challenge with Iliac Artery Perforator Flap for greater volume
these flaps is delayed healing when too much [19] and double flaps for one breast. Apart from
tissue is harvested. Thus, for the TUG flap, vari- bipedicled and stacked abdominal-based flaps for
ous modifications have been suggested includ- single breast reconstruction, other combination
ing the use of a double TUG to increase volume flaps have not gained mainstream popularity
and reduce the tissue harvested from each thigh. given the complexity of the microsurgery
The double TUG flaps can be anastomosed ‘in- involved.
parallel’ to two separate recipients or ‘in-series’
when a sufficient adductor branch of the gracilis
pedicle is available [15]. These options remain a 17.6 Expert Concluding
reliable secondary choice for breast Commentary
reconstruction.
This chapter reviews the historical development
of autologous breast reconstruction in the context
17.5.2 Buttock and Lower Back of five landmark papers. The chapter discusses
the evolution of autologous breast reconstruction,
The buttock tissue has two potential donor sites: although the individual reconstructive options are
superior and inferior gluteal artery perforator not discussed in detail (Fig. 17.3).
flaps, also known as the SGAP [16] and IGAP Despite significant advances in secondary
flap [9]. These two flaps have become less popu- choices for autologous breast reconstruction,
lar given the difference in consistency of the firm the preferred donor site is the lower abdomen
buttock tissue when compared to the breast tissue with the DIEP flap being the gold standard
and the difficulty in raising the short vascular option. The latissimus dorsi remains a reliable
pedicle. choice and especially in centres that do not offer
Most recently, the lumbar artery perforator free tissue transfer. Of the secondary choices for
(LAP) flaps have become a more popular choice autologous breast reconstruction, the thigh flaps
given the tissue consistency of this tissue being (TUG and PAP) remain a good choice with the
more similar to breast tissue and often ample vol- LAP flap being a new contender that yields a
ume available at this donor site [17]. The main larger volume of tissue. The main challenge
drawback of this flap is the short pedicle length with this option is the additional vascular grafts.
that requires grafts to elongate the pedicle. The The buttock flaps have become unpopular with
deep inferior epigastric artery and vein are the these new options as the fat is typically firmer
mainstay vascular grafts, which are harvested than breast tissue and the microsurgery is more
through a separate lower transverse abdominal challenging. It remains to be seen which of
incision [18]. This remains a promising choice these secondary choices will gain the most pop-
for secondary breast reconstruction but has not ularity over the coming years.
Fig. 17.3 Timeline of significant publications for breast reconstruction
17.7 Future Evolution increase the surgery time by 8–38 min, but the
advantages of faster and improved sensory recov-
In recent years, breast reconstruction has evolved ery are persuading more surgeons to use this. The
significantly, with numerous technological results also suggest that the reconstructed flap
advancements of which there are several areas has a more even distribution of sensation than
worthy of discussion. breasts without neurotization.
17.7.1 Preoperative Imaging 17.7.3 Robotic Harvest of Flaps

Techniques
Further advancements have been focused on
Preoperative imaging techniques have signifi- reducing abdominal wall morbidity, with robotic
cantly improved from the use of simple Doppler harvest of the DIEP flap [22, 23]. This involves
ultrasound to Computed Tomographic the smallest fascial incisions and reduces abdom-
Angiography (CTA) and Magnetic Resonance inal wall morbidity, donor site pain, and hernia
Angiography (MRA) [20]. This has allowed bet- formation. While this technique is not an option
ter visualization of the perforators and their intra- for every patient, preoperative CTA planning can
muscular course and thus reduced donor site help identify which patients would benefit from
morbidity and operative times. The better under- using it. Its limitations of longer surgery time and
standing of anatomy has also meant better utili- higher costs have prevented it from becoming
zation of the tissues through perforator to more common.
perforator flaps.
17.7.4 Tissue Engineering and

17.7.2 Neurotization of Flaps Bioengineering
Several researchers have commenced work on Tissue engineering and bioengineering also have
neurotization of reconstructed breast flaps. There many potential applications for breast recon-
are various described approaches including direct struction, such as improving the skin layer qual-
coaptation, coaptation with nerve conduit, and ity, boosting the fat transfer outcomes, forming
coaptation with nerve allograft [21]. This may breast shape and volume by bio-printing, and
improving nipple reconstruction with engineer- 12. Grotting J. The free abdominoplasty flap for
immediate breast reconstruction. Ann Plast Surg.
ing methods [24]. 1991;27(4):351–4.
In conclusion, the field of breast reconstruc- 13. Schoeller T, Wechselberger G. Breast reconstruction
tion has undergone significant evolution in terms by the free transverse gracilis (TUG) flap. Br J Plast
of new technology and techniques that have Surg. 2004;57:481–2.
14. Van Landuyt K, Blondeel P, Hamdi M,
enabled the creation of contemporary methods. Vanderstraeten G, Monstrey S. The profunda artery
These improvements have altered the landscape perforator flap: an additional tool in the recon-
of breast reconstruction. structive ladder. J Plast Reconstr Aesthet Surg.
2003;56(7):691–700.
15. Hunter JE, Mackey SP, Boca R, Harris
Disclosure The authors have nothing to disclose.
PA. Microvascular modifications to optimize the
transverse upper gracilis flap for breast reconstruc-
tion. Plast Reconstr Surg. 2014;133(6):1315–25.
References 16. Allen RJ, Tucker C Jr. Superior gluteal artery perfora-
tor free flap for breast reconstruction. Plast Reconstr
Surg. 1995;95(7):1207–12.
1. Halsted WSI. The results of operations for the cure of
17. Blondeel PN, Van Landuyt K, Monstrey SJ, Hamdi
cancer of the breast performed at the Johns Hopkins
M, Matton GE, Allen RJ. The lumbar artery perfora-
Hospital from June 1889, to January 1894. Ann Surg.
tor flap: the anatomical basis of a new flap. J Plast
1894;20:497–555.
Reconstr Aesthet Surg. 2004;57(4):381–5.
2. Czerny V. Plastischer ersatz der brustdrüse durch ein
18. Peters KT, Blondeel PN, Lobo F, van Landuyt
lipom. Zentralbl Chir. 1895;27(3):72–5.
K. Early experience with the free lumbar artery per-
3. Tanzini I. Nuovo processo per l’amputazione della
forator flap for breast reconstruction. J Plast Reconstr
mammaella per cancer. Reforma Med. 1896;12:3.
Aesthet Surg. 2015;68(8):1112–9.
4. Schneider WJ, Hill HL, Brown RG. Latissimus dorsi
19. Elzinga K, Buchel E. The deep circumflex iliac artery
myocutaneous flap for breast reconstruction. Br J
perforator flap for breast reconstruction: Un lam-
Plast Surg. 1977;30:277–81.
beau perforateur de l'artère iliaque circonflexe pro-
5. Serafin D, Georgiade NG. Transfer of free flaps to
fonde pour la reconstruction mammaire. Plast Surg.
provide well-vascularized, thick cover for breast
2018;26(4):229–37.
reconstructions after radical mastectomy. Plast
20. Rodkin B, Hunter-Smith DJ, Rozen WM. A review
Reconstr Surg. 1978;62:527–36.
of visualized preoperative imaging with a focus
6. Holmström H. The free abdominoplasty flap and its
on surgical procedures of the breast. Gland Surg.
use in breast reconstruction. An experimental study
2019;8(Suppl 4):S301–9.
and clinical case report. Scand J Plast Reconstr Surg.
21. Shiah E, Laikhter E, Comer CD, Manstein SM,
1979;13(4):423–7.
Bustos VP, Bain PA, Lee BT, Lin SJ. Neurotization in
7. Hartrampf CR, Scheflan M, Black PW. The transverse
innervated breast reconstruction: a systematic review
abdominal island flap technique for breast reconstruc-
of techniques and outcomes. J Plast Reconstr Aesthet
tion. Plast Reconstr Surg. 1981;68(6):912–7.
Surg. 2022;75(9):2890–913.
8. Koshima I, Soeda S. Free abdominal TRAM
22. Selber JC. The robotic DIEP flap. Plast Reconstr
flap for breast reconstruction. J Microsurg.
Surg. 2020;145(2):340–3.
1989a;10(4):247–52.
23. Khan MTA, Won BW, Baumgardner K, Lue M,
9. Allen RJ, Treece P. Deep inferior epigastric perfo-
Montorfano L, Hosein RC, Wang HT, Martinez
rator flap for breast reconstruction. Ann Plast Surg.
RA. Literature review: robotic-assisted harvest of
1994;32(1):32–8.
deep inferior epigastric flap for breast reconstruction.
10. Arya R, Healy C, Frame JD, Ramakrishnan V. 21 year
Ann Plast Surg. 2022;89(6):703–8.
follow up of a DIEP (deep inferior epigastric perfo-
24. Berkane Y, Oubari H, van Dieren L, Charlès L, Lupon
rator) flap: a tale of a “nulltiple”. J Plast Reconstr
E, McCarthy M, Cetrulo CL Jr, Bertheuil N, Uygun
Aesthet Surg. 2014;67(10):1436–9.
BE, Smadja DM, Lellouch AG. Tissue engineering
11. Blondeel PN. One hundred free DIEP flap breast
strategies for breast reconstruction: a literature review
reconstructions: a personal experience. Br J Plast
of current advances and future directions. Ann Transl
Surg. 1999;52(2):104–11. PMID: 10434888.
Med. 2024;12(1):15.
Evolution of Aesthetic Breast
Surgery
18
Maurizio Bruno Nava, Alberto Rancati,
Patrick Mallucci, and Nicola Rocco
Abstract Keywords
This chapter delves into five pivotal mile- Cosmetic breast surgery · Breast augmenta-
stones in the aesthetic breast surgery litera- tion · Breast reduction · Mastopexy · Fat
ture, shaping the field across the last century grafting
and into the present. These seminal papers
have fundamentally influenced the evolution
of aesthetic breast surgery. Deemed as The Five Most Impactful Papers
Copernican revolutions in their impact, these
1. Tebbetts JB. Dual plane breast augmentation:
works have not only molded subsequent
optimizing implant-soft-tissue relationships in
research and surgical methodologies but con-
a wide range of breast types. Plast Reconstr
tinue to exert a profound influence on today’s
Surg. 2001;107(5):1255–72.
clinical practice. Without these ground-
2. Burkhardt BR, Dempsey PD, Schnur PL,
breaking contributions, the landscape of aes-
Tofield JJ. Capsular contracture: a prospective
thetic breast surgery would be markedly
study of the effect of local antibacterial agents.
different.
3. Wise RJ. A preliminary report on a method of
planning the mammaplasty. Plast Reconstr
M. B. Nava Surg (1946). 1956;17(5):367–75.
G.RE.T.A. Group for Reconstructive and Therapeutic 4. Ribeiro L, Backer E. Mastoplastia com pedi-
Advancements, Milan, Naples, Catania, Italy culo de. siguridad. Rev Esp Cir Plast.
Plastic and Reconstructive Surgery Department, 1973;16:223–7.
University of Buenos Aires, Buenos Aires, Argentina 5. Khouri RK, Rigotti G, Cardoso E, Khouri RK
A. Rancati Jr, Biggs TM. Megavolume autologous fat
Plastic and Reconstructive Surgery Department, transfer: part II. Practice and techniques. Plast
University of Buenos Aires, Buenos Aires, Argentina Reconstr Surg. 2014;133(6):1369–77.
P. Mallucci
Mallucci London, London, UK
N. Rocco (*)
G.RE.T.A. Group for Reconstructive and Therapeutic
Department of Advanced Biomedical Sciences,
University of Naples “Federico II”, Naples, Italy
https://doi.org/10.1007/978-3-031-57132-9_18
170 M. B. Nava et al.
18.1 Breast Augmentation must be tailored to the individual woman to avoid

compromises, complications or sub-optimal
18.1.1 Dual Plane Breast results. Even when choosing the best option
Augmentation within the traditional portfolio, the surgeon could
often not reach the best results if not using the
John Tebbetts has changed the world of breast dual plane technique (i.e. glandular ptotic breast
augmentation presenting the “dual plane” tech- or constricted lower pole breast in thin patients).
nique in 2001. Traditionally, in breast augmenta- John Tebbets first proposed the “combination”
tion, surgeons could choose to position the between different pocket locations in the same
implant behind the breast parenchyma (retro- breast, thus taking the best from each technique,
mammary), partially behind the pectoralis major minimizing trade-offs, risks and complications.
muscle (partial retropectoral) or totally behind Moreover, he showed how the technique could be
pectoralis major and serratus (total submuscular). further tailored to the single patient adjusting the
These different techniques for breast augmenta- position of the pectoralis major muscle relative to
tion have specific indications and each pocket has the implant with different degrees of detachment
its own limitations. In particular, a breast with a of the parenchyma from the muscle in the retro-
constricted lower pole could not always be ade- mammary plane. In this way, John Tebbets
quately approached with a retromammary, or described three types of dual plane augmenta-
total sub-muscular pocket. The dual plane tech- tions according to the level of parenchyma-
nique allowed the plastic surgeon to improve the muscle interface dissection: type 1—no dissection
relationship between the implant and patient’s in the retromammary plane; type 2—dissection
tissues, optimizing implant-soft-tissue dynamics, in the retromammary plane to approximately the
thus offering better outcomes compared to the inferior border of the areola; type 3—dissection
traditional techniques in a wide range of breast of the retromammary plane to approximately the
types. Most of the trade-offs of previously superior border of the areola (Fig. 18.1).
described implant pocket locations for breast Each of the three dual plane techniques could
augmentation in specific breast types have been be selected according to the desired implant-soft-
overcome with the dual plane technique. tissue dynamics required, with the aim of maxi-
Glandular ptotic breasts, with thin soft tissues mizing soft-tissue coverage, minimizing forces
in the superior pole of the breast, are associated that could cause implant displacement and allow-
with high risk of a “double bubble” deformity. ing a proper expansion of the lower pole, reduc-
This results from gland sliding inferiorly off the ing the risk of inferior displacement of breast
pectoralis and implant with a partial retropectoral parenchyma sliding off the pectoralis. John
or total submuscular approach. Similarly, a con- Tebbets made a Copernican revolution in the
stricted lower pole breast in a thin patient could “flat” world of breast augmentation, highlighting
not be approached properly with a total muscular the importance of impact-soft-tissue dynamics in
coverage that could inferiorly impair adequate the short- and long-term results of breast aug-
expansion of the lower pole. John Tebbets high- mentation. Even though the surgeon could not
lighted how there is not one optimal pocket loca- change the genetic and aging characteristics of
tion for all patients undergoing breast patients’ tissues, they could recognize how these
augmentation. All patients have different charac- factors influenced the choice of the best tech-
teristics in terms of soft tissues, breast tissues and nique to achieve long-lasting results and mini-
wishes. This means that the surgical technique mizing trade-offs and risks.
18 Evolution of Aesthetic Breast Surgery 171
Fig. 18.1 The three types of dual plane augmentations plane to approximately the superior border of the areola.
according to the level of parenchyma–muscle interface [From Tebbetts JB. Dual plane breast augmentation: opti-
dissection described by John Tebbetts: type 1—no dissec- mizing implant-soft-tissue relationships in a wide range of
tion in the retromammary plane; type 2—dissection in the breast types. Plast Reconstr Surg. 2001 Apr
retromammary plane to approximately the inferior border 15;107(5):1255–72]
of the areola; type 3—dissection of the retromammary
Tebbetts JB. Dual plane breast augmentation: optimizing implant-soft-tissue relationships in a wide range of breast
types. Plast Reconstr Surg. 2001;107(5):1255–72
Strengths • The paper reports the results of the dual plane technique in more than 900 breasts (468 patients),
describing the technique step by step
Limitations • The follow up ranged from 3 months to 6 years. Follow up at 3 months was obtained in 92% of
the patients, while 2-year or longer follow up in only 46% of patients
Impact • The dual plane technique allowed the plastic surgeon to improve the relationship between the
implant and patient’s tissues, optimizing implant-soft-tissue dynamics, thus offering better
outcomes compared to the traditional techniques in a wide range of breast types.
• The dual plane technique allowed plastic surgeons to obtain better results, in particular, with
breasts with a constricted lower pole and with thin soft tissues in the superior pole.
• The dual plane technique has also significantly enhanced outcomes in breast reconstruction,
particularly in immediate post-mastectomy cases. This approach involves covering the upper pole
of the breast implant with the pectoralis major fibers and the lower pole with an ADM or synthetic
mesh. The mesh or ADM is skillfully sutured superiorly to the partially detached pectoralis major
muscle’s inferior edge and inferiorly to the superficial fascia at the inframammary fold. This
reconstructive method proves highly effective, especially for patients classified as type 2 according
to the Breast Tissue Coverage Classification developed by Rancati and colleagues in [1]
18.2 The Bacterial/Biofilm Theory This pattern robustly supports the bacterial
for Capsular Contracture theory as the primary cause of capsular contrac-
ture development, in contrast to numerous other
Burkhardt, with his randomized controlled trial theories emphasizing host-implant response or
published in June 1986, was the first to provide systemic reactivity to the prosthesis. Under
unequivocal evidence that the cause of capsular standing capsular contracture’s bacterial origin,
contracture in retromammary augmentation is peri- the authors emphasized the illogical nature of
prosthetic bacterial contamination. This was the prevalent methods used to control it, such as
first level I evidence confirming the bacterial the- intraprosthetic steroids, displacement exercises,
ory as the basis of the etiopathogenesis of the most or systemic vitamin E, given the bacterial etiol-
frequent complication in breast augmentation. This ogy of the condition.
is particularly relevant in the present day when the In order to reduce breast implant bacterial
etiopathogenesis of Breast Implant-Associated contamination and biofilm formation, Adams
Anaplastic Large Cell Lymphoma (BIA-ALCL) is suggested to follow the 14-point plan, highlight-
highly debated and bacterial antigens/biofilm as ing how the use of intravenous antibiotic prophy-
“primum movens” of a dysregulated immune laxis at the time of anesthetic induction could be
response in genetically predisposed subjects is one useful. He also suggested to avoid periareolar or
of the most accredited theories (Nava 2017). trans-axillary incisions, to use nipple shields,
Burkhardt is the forerunner of the min perform careful atraumatic dissections to mini-
imization of bacterial contamination around mize de-vascularized tissues, careful prospective
breast implants, stated by Adams with the so- hemostasis, avoiding dissection into the breast
called 14-point plan, defining all the techniques to parenchyma, performing pocket irrigation with
reduce the number of bacteria around implants, triple-antibiotic solution or Povidone Iodine
thus reducing, according to Adams and colleagues solution, minimizing implant open time, chang-
[2], the occurrence of both capsular contracture ing surgical gloves before implant handling and
and BIA-ALCL [3]. Burkhardt showed how cap- use of new or clean instruments and drapes,
sular contracture occurred in a random pattern avoiding drains and performing a layered
consistent with a breast-based rather than a closure.
patient-based etiology and the use of local antibac- The other paper published by Adams in 2017,
terials caused an average sevenfold reduction in after more than 30 years form the report by
the incidence of early onset capsular contracture. Burkhardt and colleagues, highlighted how the
intuition of these researchers significantly theory, thus having a strong impact on the surgi-
changed the plastic surgery community’s way of cal approach to all breast implant procedures up
thinking, giving strength to the bacterial/biofilm to now.
Burkhardt BR, Dempsey PD, Schnur PL, Tofield JJ. Capsular contracture: a prospective study of the effect of local
antibacterial agents. Plast Reconstr Surg. 1986;77(6):919–32
Strengths • The authors reported on 124 patients using identical surgical technique, using different
antibacterial treatments
• The antibacterial treatment was selected preoperatively based on sequential entry into a
predetermined protocol, with equal numbers in each group
• Treatment selection was not disclosed to the surgeon until immediately prior to closure so that
there could be no influence on the extent of dissections
Limitations • Only some antibacterial treatments have been investigated
Impact The paper confirmed the infectious etiology for capsular contracture, paving the way to all the
researches aiming at reducing contaminations in implant-based breast surgery in order to improve
outcomes.
The findings of this study represent the basis for demonstrating and understanding the impact of
chronic inflammation and T-cell lymphocytic proliferation in the etiopathogenesis of capsular
contracture, BIA-ALCL and Breast Implant Illness (BII).
18.3 Breast Reduction and sub-optimal aesthetic results. The devices

described by Wise are the first aids to improve the
18.3.1 The Wise Pattern and Vertical planning of the reduction, shaping and fixation of
Mammoplasties the skin flaps in a reduction mammoplasty.
In the years following the 1956 report from
When a plastic surgeon plans a breast reduction, Wise, several modifications of this technique
the “Wise pattern” is often the first technique that have been described to approach reduction mam-
comes to mind. This technique is widely used all maplasty. The most relevant through the years
over the world to approach breast reduction for have been the vertical mammoplasty described
aesthetic purposes and also for breast cancer by Madeleine Lejour [4] and the modification
treatments as an oncoplastic procedure, the so- described by Elizabeth Hall-Findlay [5]
called therapeutic mammaplasty. In 1956, Robert (Fig. 18.2). The idea of Madeleine Lejour started
Wise first described a flexible latex pattern to from the thought that the ideal breast reduction
help the planning of skin flaps in reduction mam- should create a beautiful breast without scars.
maplasties, to be used together with a plastic ring This is obviously unfeasible and sometimes the
outlining the base of the breast. Starting from this scars, visible sequelae of the reduction, become
plastic device, the use of the Wise pattern passed another source of distress for patients seeking for
through the years, coming to our days with sev- breast reduction because of problems with self-
eral adjustments. The typical preoperative draw- esteem because of their large or ptotic breasts.
ing for a mammaplasty is done according to the Madeleine Lejour noted how the techniques
Wise pattern. that were developed to produce minimal breast
The author developed this approach, stimu- scars and avoid the classic T-inverted incision
lated by the challenges and uncertainties encoun- showed some limitations (Ribeiro, Peixoto,
tered in the size reduction in his experience. He Staub) [6–8]. Techniques in which tissue at the
experienced challenges in symmetrical planning base of the breast is excised through either a sub-
when dealing with breasts of different sizes, mammary incision or a peri-areolar and lower
vague uncertainties in the drawing, high ischemic vertical incision showed a disadvantage, that is,
rates of skin flaps, nipple and glandular tissue the development of secondary ptosis. On the
Fig. 18.2 (a) Lejour technique; (b) Hall-Findlay (figures Jul;94(1):100–14; 2. Hall-Findlay EJ. A simplified verti-
on the left side) and Lejour technique (figures on the right cal reduction mammaplasty: shortening the learning
side). [From: 1. Lejour M. Vertical mammaplasty and curve. Plast Reconstr Surg. 1999 Sep;104(3):748–59]
liposuction of the breast. Plast Reconstr Surg. 1994
Fig. 18.2 (continued)

other hand, techniques in which the skin is under- She analyzes the reasons why the technique
mined widely after an ellipse of skin around the described by Madeleine Lejour did not achieve
areola is excised could be associated with chal- widespread acceptance in Northern America. She
lenges in the interpretations of mammograms showed how many surgeons believed that the ver-
because of the multiple sutures used for the tical reduction was only applicable to smaller
reshaping of the gland. Moreover, these tech- breast reductions and that the learning curve was
niques often produce small flat breasts with a sig- difficult. She described some modifications to the
nificant tension on the periareolar closure and standard Lejour technique that simplified it, mak-
result in an unpleasant scar at the most visible ing it more reliable and easier to perform. The
location in the breast. Furthermore, the wide skin main modifications introduced were the use of a
undermining may result in an area of permanent medial or lateral dermoglandular pedicle, not
insensitivity around the areola. undermining the skin, using liposuction only
Starting from these assessments, Madeleine rarely to reduce breast volume and not using pec-
Lejour concluded that the areola should be ele- toralis fascia sutures.
vated on an upper pedicle with a minimal amount The modifications described by Hall Findlay
of dissection and scarring. This was the best solu- improved the results previously described with the
tion because the main challenge is with the lower vertical scar reduction techniques, whilst also
excessive, pendulous part of the breast. The key reducing complications. The medial or lateral ped-
elements of the Lejour technique that made it icles solved the problem of insetting, especially
unique are the larger pedicle for the areola; the with larger reductions. Vascularity of the nipple
absence of undermining of the skin surround the areola complex was more reliable because the ped-
areola (increasing the quality of peri-areolar icle design could be shortened and the ease of
scar); the strong suturing of the lower gland to insetting allows the pedicle to be thicker. The supe-
create a stable shape and eliminate tension on the rior pedicle often needed to be thinned to avoid
vertical scar; a wide lower skin undermining to constriction with the infolding required. Moreover,
allow gathering of the skin along the vertical the thicker medial or lateral dermoglandular pedi-
suture, thus reducing its length, and no reliance cle may maintain a good sensation postoperatively.
on the skin envelope to shape the breast. Furthermore, not clearing off the pectoralis fascia
Madaleine Lejour also proposed the combination contributes to preserving sensitivity. The elimina-
of her technique with a breast liposuction to fur- tion of skin undermining facilitated skin closure
ther improve results. and reduced healing problems. Avoiding pectoralis
Elizabeth Hall Findlay in 1999 made another fascia sutures facilitated the insetting of the pedi-
step forward in finding the less invasive way to cle. Avoiding routine liposuction also reduced
reshape the breast in reduction mammaplasties. bruising and shortened recovery time.
Wise RJ. A preliminary report on a method of planning the mammaplasty. Plast Reconstr Surg (1946).
1956;17(5):367–75
Strengths • The author identified the challenges in breast reduction
• The author describes some devices that could help the planning and the execution of a
reduction mammoplasty
Limitations • This is only the first report on a small group of women of a technique that has been tested in
several other subsequent studies in larger cohort of patients
Impact • The technique described by Robert Wise in 1956 is currently widely used all over the world to
approach breast reduction for aesthetic purposes and also for breast cancer treatment as an
oncoplastic procedure, the so-called therapeutic mammaplasty. All the techniques for breast
reduction that developed throughout the years are derived from the technique described by
Robert Wise.
• The technique described by Wise also had a significant impact on the development of
oncoplastic breast conserving surgery, through the use of this kind of approach for the
treatment of breast cancer, paving the way to the diffusion of the so-called therapeutic
mammaplasties.
18.4 Mastopexy According to Ribeiro’s technique, the lower

pole of the breast, that is usually resected in a supe-
Mastopexy is a simple surgical procedure with rior pedicle breast reduction, is designed and used
reported low complication rates, but long-term as an autologous implant to be fixed to the pectora-
cosmetic outcomes and upper pole adequate full- lis major muscular plane, representing a light-
ness have been questioned by some authors. weight flap with good outcomes in the long-term
Several techniques have been proposed to achieve follow up not being affected by bottoming out. This
a better stability of the results and upper pole paper represents a milestone in aesthetic surgery of
fullness, such as parenchymal redistribution, the breast describing a technique that changed out-
parenchymal fixation to the pectoralis fascia or comes in mastopexy, allowing stable results on the
under a loop of fibers of pectoralis major muscle long term, in particular as far as the upper pole full-
or use of synthetic meshes [9–11]. ness of the breast is concerned, this being the great-
Some other authors described several tech- est challenge when performing a mastopexy.
niques of “autoaugmentation” with the use of dif- This flap was originally described topographi-
ferent types of de-epithelialized flaps [12–14], cally. Today, we know that its perfusion and vital-
but the technique that significantly changed long- ity is based on the fifth intercostal artery
term outcomes in mastopexy is the one described perforator. This perforator gives rise to several
by Liacyr Ribeiro in 1973 [6]. Ribeiro’s tech- branches that traverse in all directions. The
nique is a parenchymal rearrangement technique, ascending branches of the fifth anterior intercos-
combining a superior pedicle for the NAC and an tal artery perforator are directed toward the
inferiorly based parenchymal flap, the so-called nipple-areola complex and course within the sub-
autoprosthesis to allow better upper pole fullness cutaneous layer between the skin and the paren-
and NAC projection. chyma [15].
Ribeiro L, Backer E. Mastoplastia com pediculo de. siguridad. Rev Esp Cir Plast. 1973;16:223–7
Strengths • The author identified the limits in the long-term outcomes of mastopexy, identifying a new
technique to obtain better stability of the results
Limitations • This study represents the first experience with this technique on a small number of patients
• This study does not offer an anatomical description of the vascularity of the flap
Impact • The technique described by Liacyr Ribeiro in 1973 still represents a milestone in mastopexy,
allowing stable results in terms of upper pole fullness of the breast and being widely used all
around the world.
• The technique described by Ribeiro also contributed to the development and diffusion of the
skin-reducing mastectomy for the treatment of breast cancer in large and ptotic breasts. An
inferiorly based dermal-adipose flap is used in this technique for the coverage of the inferior
pole of the implant [16].
described by Roger Khouri, Gino Rigotti, and

18.5 Autologous Fat Grafting Thomas Biggs, with the so-called megavolume
autologous fat transfer.
Another milestone in aesthetic surgery of the The authors presented their fat transfer tech-
breast is the use of autologous fat to improve the nique and reported on excellent results in the fat
results of implant-based procedures or even as transfer of more than 250 cc in a landmark paper
the only method to enhance the volume of the published in 2014. Usually when large volumes
breast. Many techniques have been described are grafted into tight spaces, the interstitial fluid
through the years for fat processing and transfer pressure increases impairing capillary blood flow
to improve fat intake and survival, but the best and the crowded graft adipocytes coalesce into
results have been achieved with the methods lakes, with poor graft-to-recipient interface.
These are the reasons why traditionally there is a larger collections. They also avoid creating and
restriction on the maximum amount of fat that grafting into cavities: in the cavities graft dies
can be grafted into the breast. The decreased and turns into necrotic cysts.
interface increases the distance oxygen must dif- Beyond a certain injection volume, the com-
fuse to reach the grafted adipocytes leading to pliance of tissue rapidly decreases and the inter-
central necrosis before neovascularization. stitial fluid pressure suddenly increases. As
The authors first described the use of external interstitial pressure rises, capillary circulation
expansion devices to preoperatively increase the drops precipitously, inhibiting oxygen delivery,
volume and vascularity of the recipient site allow- neovascularization and subsequent graft survival.
ing megavolumes of fat to be grafted without sig- Even if utmost care is taken in dispersing the
nificantly decreasing graft-to-recipient interface microfat droplets, too much fat stuffed into too
or increasing interstitial fluid pressure. The results little space creates a choke effect and some if not
obtained by Khouri and Rigotti with fat grafting all of the fat cells will not survive. The limit on
are far superior to those achieved by other plastic how much can be grafted, even with extreme
surgeons around the world. They highlighted how care, according to the authors’ experience, is the
the key for success of their technique was in the interstitial fluid pressure of the recipient site.
knowledge of what is behind fat graft survival, The authors show how tissues have different
summarized in two principles: graft-to-recipient volume-to-pressure compliance curves, with sub-
interface and interstitial fluid pressure limit. cutaneous tissue being the most compliant, whilst
Composite tissue blocks could survive as free scarred, irradiated tissue being the least compliant.
nonvascularized grafts if placed in small por- The evidence presented by the authors changed the
tions, never exceeding 2 mm in radius. They way autologous fat transfer is performed and repre-
showed how the graft should be meticulously dis- sents a benchmark for aesthetic and reconstructive
persed to avoid coalescence of the droplets into surgeons from all around the world.
Khouri RK, Rigotti G, Cardoso E, Khouri RK Jr, Biggs TM. Megavolume autologous fat transfer: part II. Practice
and techniques. Plast Reconstr Surg. 2014;133(6):1369–77
Strengths • The authors laid the ground for the standardization of the technique for autologous fat grafting
• The study meticulously describes the technique for fat grafting making it reproducible
Limitations • An adequate learning curve is required to obtain the results described by the authors even if the
technique has been adequately and meticulously described
Impact The standardization of the technique for autologous fat grafting contributed to the spread of the use
of lipofilling in both aesthetic and reconstructive surgery all around the world with significant
advantages for the outcomes of patients in terms of cosmetic results and quality of life
Fat grafting currently represents a reliable technique to be used in association with breast implants
for so-called hybrid approaches, improving the outcomes and the stability of the results
Fat grafting significantly contributed to improve the outcomes of pre-pectoral approaches both in
aesthetic and reconstructive surgery, extending the indications of this technique to a broader group
of patients
18.6 Expert Concluding ling through the use of autologous tissues (i.e.
Commentary autoprosthesis and autologous fat). Some of these
papers were published in the early 1950s of the
We have discussed the five papers that, in our twentieth century and the concepts and tech-
view, have had the strongest impact in advancing niques are still valid and used today in our surgi-
the approach towards the use of implants in aes- cal practice for breast reduction. Others are more
thetic breast surgery and specifically for breast recent but have had a significant impact on the
augmentation and breast reduction and remodel- way we perform breast augmentation and fat
grafting nowadays. The study by Burkhardt first 4. Lejour M. Vertical mammaplasty and liposuction of
proposed the etiopathogenetic theory of bacterial the breast. Plast Reconstr Surg. 1994;94(1):100–14.
5. Hall-Findlay EJ. A simplified vertical reduction
contamination for capsular contracture develop- mammaplasty: shortening the learning curve. Plast
ment and paved the way for the subsequent stud- Reconstr Surg. 1999;104(3):748–59.
ies on BIA-ALCL and Breast Implant Illness. 6. Ribeiro L. A new technique for reduction mamma-
The study of these milestones is vital to properly plasty. Plast Reconstr Surg. 1975;55(3):330–4.
7. Peixoto G. Reduction mammaplasty: a personal tech-
manage basic techniques in aesthetic breast sur- nique. Plast Reconstr Surg. 1980;65(2):217–26.
gery and develop further knowledge in the field 8. Staub S, Bzowski A, Vilain R. Hypertrophie mam-
of aesthetic breast surgery. maire juvénile. Traitement chirurgical précoce [juve-
nile mammary hypertrophy. Early surgical treatment].
Ann Chir Plast Esthet. 1989;34(3):269–72.
Sources of Funding The authors received no funding for 9. Flowers RS, Smith EM Jr. “Flip–flap” mastopexy.
this work. Aesth Plast Surg. 1998;22(6):425–9.
10. Ritz M, Silfen R, Southwick G. Fascial suspension
mastopexy. Plast Reconstr Surg. 2006;117(1):86–94.
11. Graf R, Reis de Araujo LR, Rippel R, Neto LG, Pace
References DT, Biggs T. Reduction mammaplasty and mastopexy
using the vertical scar and thoracic wall flap tech-
1. Rancati AO, Angrigiani CH, Hammond DC, Nava nique. Aesth Plast Surg. 2003;27(1):6–12.
MB, Gonzalez EG, Dorr JC, Gercovich GF, Rocco 12. de la Plaza R, de la Cruz L, Moreno C. Mastopexy uti-
N, Rostagno RL. Direct to implant reconstruction in lizing a dermoglandular hammock flap. Aesthet Surg
nipple sparing mastectomy: patient selection by pre- J. 2005;25(1):31–6.
operative digital mammogram. Plast Reconstr Surg 13. Losken A, Holtz DJ. Versatility of the superomedial
Glob Open. 2017;5(6):e1369. pedicle in managing the massive weight loss breast:
2. Adams WP Jr, Culbertson EJ, Deva AK, et al. the rotation-advancement technique. Plast Reconstr
Macrotextured breast implants with defined steps to Surg. 2007;120(4):1060–8.
minimize bacterial contamination around the device: 14. Foustanos A, Zavrides H. A double-flap technique: an
experience in 42,000 implants. Plast Reconstr Surg. alternative mastopexy approach. Plast Reconstr Surg.
2017;140(3):427–31. 2007;120(1):55–60.
3. Nava MB, Adams WP Jr, Botti G, Campanale A, 15. Nahabedian MY, Angrigiani C, Rancati A, Irigo M,
Catanuto G, Clemens MW, Del Vecchio DA, De Acquaviva J, Rancati A. The importance of fifth ante-
Vita R, Di Napoli A, Hall-Findlay E, Hammond D, rior intercostal vessels following nipple-sparing mas-
Heden P, Mallucci P, Martin Del Yerro JL, Muti E, tectomy. Plast Reconstr Surg. 2022;149(3):559–66.
Rancati A, Randquist C, Salgarello M, Stan C, Rocco 16. Nava MB, Cortinovis U, Ottolenghi J, Riggio E,
N. MBN 2016 aesthetic breast meeting BIA-ALCL Pennati A, Catanuto G, Greco M, Rovere GQ. Skin-
consensus conference report. Plast Reconstr Surg. reducing mastectomy. Plast Reconstr Surg.
2018;141(1):40–8. 2006;118(3):603–10.
Science of Breast Implants
19
Jose Foppiani, Angelica Hernandez Alvarez,
Lacey Foster, Mark Clemens, and Samuel J. Lin
Abstract of science on the topic of the science of breast

implants.
In this chapter, the evolution of the science of
breast implants is discussed in the context of
Keywords
five landmark publications that have guided
that evolution. Other references are cited to Breast implants · Breast implant-associated
provide some perspective as it is challenging anaplastic large-cell lymphoma
to cover such a large topic with just five refer- Postapproval studies · Nipple-sparing
ences. Based upon a systematic approach, five mastectomy · Acellular dermal matrix
consequential papers that have had a major
influence on the direction of the use of breast
implants are discussed in detail and the rea-
1. Gabriel SE, Woods JE, Ofallon M, Beard CM,
sons why they are impactful and led to seismic
Kurland LT, Melton LJ. Complications lead-
changes in the standard of care are examined.
ing to surgery after breast implantation. N
The landmark paper selection was accom-
Engl J Med. 1997;336(10):677–82.
plished by querying the highest total number
2. Breuing KH, Warren SM. Immediate bilateral
of citations and citations per year during five
breast reconstruction with implants and infer-
individual sub-topic searches within the web
olateral AlloDerm slings. Ann Plast Surg.
2005;55(3):232–9.
3. de Alcantara FP, Capko D, Barry JM, Morrow
M, Pusic A, Sacchini VS. Nipplesparing mas-
J. Foppiani · A. H. Alvarez · S. J. Lin (*)
Division of Plastic and Reconstructive Surgery, Beth
tectomy for breast cancer and risk-reducing
Israel Deaconess Medical Center, Harvard Medical surgery: the Memorial Sloan-Kettering Cancer
School, Boston, MA, USA Center experience. Ann Surg Oncol.
L. Foster 2011;18(11):3117–22.
Keck School of Medicine, University of Southern 4. Clemens MW, Medeiros LJ, Butler CE, et al.
California, Los Angeles, CA, USA Complete surgical excision is essential for the
M. Clemens management of patients with breast implant-
MD Anderson Cancer Center, The University of associated anaplastic large-cell lymphoma. J
Texas, Austin, TX, USA
Clin Oncol. 2016;34(2):160–8.
https://doi.org/10.1007/978-3-031-57132-9_19
182 J. Foppiani et al.
5. Coroneos CJ, Selber JC, Offodile AC 2nd, et utilized in two circumstances; for alloplastic
al. US FDA breast implant postapproval stud- breast reconstruction or cosmetic breast augmen-
ies: long-term outcomes in 99,993 patients. tation. According to the American Society of
Ann Surg. 2019;269(1):30–6. Plastic Surgeons (ASPS), in 2020, there were
approximately 66,000 alloplastic breast recon-
structions (39% of all breast reconstruction proce-
19.1 Introduction dures) and 446,000 breast augmentation
procedures performed in the United States [4].
The history of breast implants can be traced back For many women, breasts are an essential part
to the late nineteenth century when reconstruc- of their physical and emotional well-being [5].
tive surgery was first developed [1]. However, it Whether it is for enhancing self-esteem or restor-
was not until the twentieth century that breast ing the breast after a mastectomy, breast implants
implants as we know them today began to take play a crucial role in patient care and satisfaction.
shape. The first modern breast implant procedure The use of implants has its own set of indications,
was performed in the 1960s using silicone gel- risks, and existing adjuncts [6]. This chapter
filled implants [2]. These implants quickly attempts to highlight five papers that were pivotal
became popular, and by the 1970s, breast aug- in the evolution of breast implants, their use, and
mentation was one of the most common cos- advancing the standard of care for patients. It cov-
metic surgical procedures performed in the ers the initial largest report on local complications
United States [2]. However, concerns about the of breast implants, [7] the introduction of acellu-
safety and reliability of silicone gel-filled lar dermal matrices (ADM) in breast reconstruc-
implants emerged in the 1980s and 1990s, lead- tion, [8] the adoption of nipple-sparing
ing to a moratorium within the United States on mastectomy [9], the evolution of Breast Implant-
their use in 1992 [2, 3]. This ban was eventually Associated Anaplastic Large-Cell Lymphoma
lifted in 2006, but the outcomes of silicone (BIA-ACL) treatment, [10] and lastly, long-term
implants remain a topic of ongoing study, and outcomes of breast implant safety [11].
research on breast implants has seen a tremen-
dous evolution since their inception [3].
Currently, breast implants are widely used and 19.1.1 Local Complications
are a mainstay tool within plastic surgeons’ aes- Following the Use of Breast
thetic and reconstructive arsenal. They are mainly Implants
Gabriel SE, Woods JE, Ofallon M, Beard CM, Kurland LT, Melton LJ. Complications leading to surgery after breast
implantation. N Engl J Med. 1997;336(10):677–82
Strengths • This is a comprehensive study of local complications following breast implantation
• This is a retrospective study of 749 patients over 27 years long-term follow up
Limitations • While retrospective studies can provide valuable insights, small sample size and limited
follow-up of a still-emerging disease can be limited by several factors, such as selection bias,
recall bias, confounding variables, lack of control over variables, lack of standardization in
treatment strategies, incomplete data, and confirmatory bias
• As an older study, some of the complications described have decreased over the years with
better techniques and more advanced implants
Impact This paper was the first comprehensive paper looking at long and short-term local complications
following breast implantation. This paper showed that local complications following breast
implantations are not to be underestimated, showing nearly a 25% complication rate, with the most
common being capsular contracture, implant rupture, and hematoma. These findings have guided the
field of the science of breast implants over the year, which led to the development of implants and
adjuncts to decrease the rate of capsular contracture and implant rupture as well as improved surgical
techniques to decrease the risk of hematoma
19 Science of Breast Implants 183
Prior to the seminal study conducted in plexity of breast implant complications, but also
Olmsted County, Minnesota, and published in catalyzed a paradigm shift in the field of plastic
1997, the landscape of breast implantation was surgery. At the time of publication, the field of
fraught with uncertainties and contentious debate breast implantation was grappling with uncer-
regarding the complications engendered by the tainties and controversies, leading to regulatory
procedure, even leading to a ban on silicone actions and heated debates. Against this back-
breast implants in 1992 by the FDA [7, 12, 13]. drop, Gabriel et al.’s study played a crucial role in
The medical community and the broader public elucidating the spectrum of complications and
have long grappled with divergent viewpoints setting the stage for further advancements. The
and unresolved questions surrounding the safety study paved the way for a renaissance in implant
of breast implantation. It was against this back- technology and surgical practice, ultimately con-
drop of ambiguity that the study delineated the tributing to the advancement of medical science
spectrum of local complications that may arise in and the betterment of patient care. Moreover,
the aftermath of breast implantation. Gabriel et al.’s study emphasized the need for
Crucially, the study illuminated the high inci- ongoing vigilance and the development of stan-
dence of capsular contracture and implant rup- dardized protocols for follow-up and surveillance
tures—two complications that would become the of breast implant patients. This recognition of the
focus of concerted efforts to ameliorate the safety importance of accurate monitoring has further
profile of breast implants. In the ensuing decades, shaped clinical practice and patient management
the study served as a bedrock for the continued strategies. It is important to acknowledge that as
evolution and refinement of breast implant an older study, some of the complications
technology. described may have evolved with advancements
The scientific research engendered by the in surgical techniques and implant technology.
study coalesced into a multifaceted approach Nevertheless, the foundational insights provided
aimed at reducing the incidence of adverse out- by Gabriel et al.’s work remain significant, as it
comes. Innovations in implant design, materials, laid the groundwork for subsequent research and
and surgical techniques were promulgated, with a innovation in the field of breast implantation. The
particular emphasis on mitigating the risk of cap- study’s enduring legacy lies in its contribution to
sular contracture and implant ruptures following the ongoing pursuit of safer and more effective
this study. The development of adjuncts, such as breast implant procedures.
biocompatible coatings and optimized implant
surfaces, further bolstered the quest to enhance
patient safety and satisfaction. 19.1.2 Acellular Dermal Matrices
In summary, the study not only provided an (ADM) in Breast
empirical foundation for understanding the com- Reconstruction
Breuing KH, Warren SM. Immediate bilateral breast reconstruction with implants and inferolateral AlloDerm slings.
Ann Plast Surg. 2005;55(3):232–9
Strengths • First report of AlloDerm use as scaffold to provide better lower pole projection in thin
patients avoiding having to release the serratus anterior muscle
Limitations • Small study sample with only ten patients mentioned with no actual report of long-term
follow-up or complications
Impact This paper provides a new technique to achieve a better lower pole projection in thin patients
without having to release the serratus anterior muscle. This manuscript would directly lead to a
growing interest in the use of ADM (acellular dermal matrix) mesh to aid in soft tissue support
during breast reconstruction and a shift away from total muscle coverage of implants.
Subsequently, the addition of ADM mesh to breast reconstruction was shown to have several
benefits: to prevent implant malposition and displacement, which can occur when there is
insufficient soft tissue coverage over the implant and to reduce the risk of capsular contracture
Some young women in need of prophylactic suspension and the need for soft tissue support,
breast reconstruction look for tissue expansion ultimately ushering in a new era of surgical tech-
given the lack of fat necessary for autologous niques. This departure from conventional think-
reconstruction. During tissue expansion, to ing forced the plastic surgeons to reconsider
achieve adequate lower pole projection, the pecto- long-held beliefs on the muscle as protective, and
ralis muscle must be released and/or expanded in embrace a paradigm shift in reconstructive
the inferolateral origin. However, most of the strategies.
time, this coverage is not adequate. In these cases, The legacy of this work can be seen in the
the serratus anterior muscle is usually elevated to enduring popularity of mesh-assisted reconstruc-
complete the submuscular pocket. However, when tion and a reevaluation of prepectoral reconstruc-
creating this pocket, a muscle–skin paradox is tion, a technique that has gained significant
created. The submuscular pocket needs to be traction and transformed the field of breast sur-
expanded gradually to achieve lower-pole fullness gery. The use of inferolateral mesh slings not only
while the mastectomy skin flaps will begin to con- provides an additional layer of tissue support but
tract during the latency period prior to the expan- also minimizes complications associated with tra-
sion [8]. The publication by Breuing and Warren ditional approaches, and provides profound appli-
in 2005 introduced a novel technique for immedi- cations in aesthetic revisionary surgery. It has
ate bilateral breast reconstruction using implants allowed surgeons to achieve more natural-looking
and inferolateral AlloDerm slings. The strength of breast contours, mitigating issues such as implant
this study lies in its pioneering approach, being malposition and capsular contracture.
the first to report the use of AlloDerm as a scaffold Beyond the immediate clinical implications,
to achieve better lower pole projection in thin Breuing and Warren’s study served as a catalyst
patients without the need to release the serratus for innovation and inspired further research in the
anterior muscle. realm of breast reconstruction. It sparked a wave
The use of the AlloDerm sling technique of curiosity, stimulating surgeons to explore
avoids or shortens the tissue expansion/implant alternative techniques and materials, both
reconstructive process, avoids mastectomy flap synthetic and biologic, seeking to refine and

contraction during the latency period of expan- improve upon the initial breakthrough. Their
sion, provides an additional layer of tissue work embodies the spirit of innovation and serves
between the skin and the implant, and offers an as a reminder that true progress often arises from
additional option for immediate, single-stage the willingness to question and reimagine estab-
breast-implant reconstruction. By providing lished conventions.
additional soft tissue coverage, ADM mesh can In the end, Breuing and Warren’s pioneering
create a more natural-looking breast contour article not only transformed the mechanics of
compared to total muscle coverage, and ulti- breast reconstruction, but also encapsulated the
mately renewed popularity in prepectoral recon- essence of surgical innovation. Their legacy lives
struction. Breuing and Warren’s article disrupted on, in the hands of breast reconstruction sur-
the established dogma by departing from the tra- geons, and also in the lives of countless cancer
ditional reliance on muscle coverage of implants, patients who have benefitted from their visionary
and altered our perceptions of the mechanics of approach.
19.1.3 Nipple-Sparing Mastectomy

and Its Impact on Alloplastic
Breast Reconstruction
de Alcantara FP, Capko D, Barry JM, Morrow M, Pusic A, Sacchini VS. Nipplesparing mastectomy for breast cancer
and risk-reducing surgery: the Memorial Sloan-Kettering Cancer Center experience. Ann Surg Oncol.
2011;18(11):3117–22
Strengths • This is one of the largest studies looking at nipple-sparing mastectomy and its effect on
oncological outcomes with patients who underwent alloplastic breast reconstruction
• This is a prospective study of 200 patients, over a 10-year period, highly cited
Limitations • Prospective databases may have restricted scope and representativeness, affecting applicability
to broader populations due to selection bias
• Human errors, missing data, and inconsistent data collection can introduce inaccuracies and
gaps in prospective databases
Impact It has been used to justify the use of nipple-sparing mastectomy in institutions that did not perform it at
the time and paved the way for significant practice changes and evolution in the oncologic management
of breast malignancies for breast surgical oncologists and widened the indications for prosthetic
reconstruction for plastic surgeons. Nipple-sparing mastectomy is a safe approach that enhances breast
reconstruction and limits morbidity without putting patients at increased oncologic risk
The ultimate goal of breast surgery is to valuable physical and psychological properties
achieve effective cancer treatment while mini- that cannot be replicated with reconstruction.
mizing the physical and emotional burdens This chapter discussed the available literature for
imposed on patients. NSM, as explored in this NSM and immediate prosthetic reconstruction in
study, exemplifies the collaborative efforts of two clinical scenarios: prophylactic and thera-
breast and reconstructive surgeons to provide a peutic to indications, contraindications, and pro-
seamless and integrated approach that addresses vide evidence of oncologic safety [15].
both the oncological aspect and the impact of the While NSM technique was first introduced in
surgery on a patient’s appearance and well-being. the 1990s, this manuscript had a significant effect
The disfigurement from breast cancer surgery has to popularize and refine the procedure. By pre-
been a significant factor in the high morbidity serving the nipple, surgeons are able to poten-
rate from this disease affecting nearly 260,000 tially maintain a more natural-looking breast for
new women each year in the US alone [14]. Over their patients, which can have a positive impact
the past 40 years, less invasive treatments have on their body image and self-esteem.
been developed, including nipple-sparing mas- Ultimately, this chapter had a significant impact
tectomy [15]. However, the combined treatments on the lives of many women who have undergone
still carry substantial hardships for patients. The mastectomy and breast reconstruction, by preserv-
challenge for medical professionals is to continue ing the nipple and using implants to create breasts
to find equally effective treatments with less col- that look and feel more natural, which can have a
lateral damage and coordinate those treatments profound impact on the quality of life for many
across multidisciplinary teams. Breast surgeons women. NSM is a safe approach that enhances
focus on removing the cancer and ensuring the breast reconstruction and limits morbidity without
patient’s health, while reconstructive surgeons putting patients at increased oncologic risk. For
focus on restoring the appearance and function of therapeutic mastectomy, the procedure is best
the breast [15]. By working together, they can suited for women with tumors 3 cm in diameter or
provide a seamless, integrated approach that less, 2 cm away from the center of the nipple, neg-
addresses both the cancer and the physical and ative axillae or sentinel node, no skin involvement,
emotional impact of the surgery. Nipple-sparing and no inflammatory breast cancer.
mastectomy (NSM) offers the possibility to save Safeguarding the nipple, an ancient symbol
the nipple and areola, which have unique and of femininity, allows for the creation of a breast
that speaks not only of survival but also of iden- mising oncological integrity. It is within this con-
tity, body image, and grace restored. This study text of constant progress and refinement that their
stands as one of the largest and most compre- work assumes its rightful place, where the focus
hensive investigations into the oncological out- has shifted towards preserving not just life but
comes and patient experiences associated with also quality of life, we witness a profound trans-
NSM in conjunction with prosthetic reconstruc- formation. De Alcantara Filho et al. navigate this
tion. The nipple and areola hold unique physical complex terrain with scientific rigor, striving to
and psychological significance for many strike a delicate balance between eradicating can-
patients. By maintaining these natural features, cer and mitigating the disfigurement that often
surgeons can achieve more aesthetically pleas- accompanies traditional approaches.
ing results and contribute to the overall well- Through collaboration and a commitment to
being and body image of their patients. This evidence-based practice, we can aspire to provide
study played a pivotal role in justifying the use breast cancer patients with the best possible
of NSM in institutions that were initially hesi- care—one that not only prioritizes their physical
tant to adopt this approach. The findings pre- health but also acknowledges the importance of
sented in this manuscript have helped shift the their emotional well-being and sense of self. De
practice patterns and management of breast Alcantara Filho reminds us that progress is not a
malignancies, empowering breast surgical solitary endeavor but a collective pursuit—a jour-
oncologists and plastic surgeons to widen the ney marked by incremental advancements and a
indications for prosthetic reconstruction and relentless commitment to improving the lives of
optimize patient outcomes. those affected by breast cancer.
In the ever-evolving landscape of breast sur-
gery, the study conducted by de Alcantara Filho
et al. emerges as a significant milestone, propel- 19.1.4 Breast Implant-Associated
ling us forward on the continuum from William Anaplastic Large-Cell
Halsted’s radical mastectomy to the pursuit of Lymphoma
improved aesthetic outcomes without compro-
Clemens MW, Medeiros LJ, Butler CE, et al. Complete surgical excision is essential for the management of patients
with breast implant-associated anaplastic large-cell lymphoma. J Clin Oncol. 2016;34(2):160–8
Strengths • This is the largest, most comprehensive study on the treatment, outcomes, and prognosis of
BIA-ALCL
• Principally, this manuscript established the critical central role for complete surgical ablation in
the treatment of BIA-ALCL
• This study was the first to define BIA-ALCL as a “solid tumor,” stratify the outcomes of
BIA-ALCL by therapies administered to the patients, and define a new staging system with
better clinical correlate
Limitations • While retrospective studies can provide valuable insights, small sample size and limited follow
up of a still emerging disease can be limited by several factors, such as selection bias, recall
bias, confounding variables, lack of control over variables, lack of standardization in treatment
strategies, incomplete data, and confirmatory bias
• At the time of the manuscript, extrapolation to patients with advanced disease was challenging
considering the very small number of cases encountered at that time
• Subsequent papers focusing on aggressive variants were able to provide specific indications for
adjunct measures such as chemotherapy, targeted immune therapy, radiation therapy, and stem
cell transplant
Impact This chapter not only created a staging system that identified the prognosis of patients more
accurately than the previously available tool but also established the mainstay of treatment of
BIA-ACL as we know it today (complete surgical excision)
Breast implants are commonly used for cos- tial to ensure that the cancer is treated at an early
metic or reconstructive purposes, with an esti- stage when it is most responsive to treatment. A
mated 450,000 placed annually in the US with an prompt diagnosis can also help prevent the can-
estimated 10–20 million worldwide [4, 16]. cer from spreading to other parts of the body.
Breast implant-associated anaplastic large-cell Proper staging of BIA-ALCL is essential for
lymphoma (BI-ALCL) is a uncommon and still determining the extent of the cancer and develop-
emerging disease first reported in 1997 as a novel ing an appropriate treatment plan. Complete sur-
T cell lymphoma caused by textured surface gical excision was established as the primary
breast implants [10]. In recent years, the number mainstay treatment for BIA-ALCL, involving
of reported cases has greatly increased, suggest- removal of the breast implant, the scar capsule,
ing that it was underdiagnosed in the past. The associated masses, and involved lymph nodes
US Food and Drug Administration has issued with negative margins. Incomplete surgical exci-
annual safety communications warning to women sion leads to the cancer returning or spreading to
with breast implants of the increased risk of other parts of the body. The findings presented by
developing BIA-ALCL [17]. Some patients with Clemens et al. served as a clarion call for a stan-
BIA-ALCL have clinically indolent disease, but dardized disease approach to the surgical com-
there is a subset of patients who have progressive munity and regulatory bodies alike.
disease that can result in death, indicating a This chapter directly led to the World Health
broader disease spectrum. A number of therapeu- Organization classification of BIA-ALCL spe-
tic approaches and proposed staging were cifically citing this manuscript, and establish-
reported in the literature, but without consensus ment of National Comprehensive Cancer
until the publication of this chapter. Network (NCCN) Guidelines on BIA-ALCL,
Clemens et al. represents a pivotal moment in the current standard of care for diagnosis and
our understanding and management of breast treatment of the disease worldwide. Ultimately,
implant-associated anaplastic large-cell lym- Clemens et al. study reinforces the critical
phoma (BIA-ALCL). At its core, this manuscript need for a multidisciplinary approach, combin-
not only confirms the central role of complete ing the expertise of surgeons, oncologists, and
surgical excision in the management of BIA- researchers in a concerted effort to ensure opti-
ALCL but also introduces a novel staging system mal outcomes for patients. By shedding light
that refines our ability to assess patients’ progno- on the superiority of complete surgical exci-
sis accurately. By characterizing BIA-ALCL as a sion over limited surgery, chemotherapy, or
“solid tumor” rather than a “liquid tumor,” and radiation therapy, this research held the poten-
stratifying outcomes based on different therapeu- tial to save lives, ensure the right treatment at
tic approaches, this study provides a more the right stage, and enhance the overall well-
nuanced understanding of the disease and paves being of individuals affected by BIA-
the way for improved clinical correlates achieved ALCL. Through continued research,
by surgical ablation alone. Indeed, accurate diag- collaboration, and a commitment to patient-
nosis, proper staging, and complete excision of centered care, we can navigate the complexi-
BIA-ALCL are all essential for ensuring breast ties of BIA-ALCL and make significant strides
implant safety in affected individuals. This man- in improving the lives of those at risk or
uscript established that early diagnosis is essen- affected by this disease.
19.1.5 Long-Term Outcomes

of Breast Implant Safety
Coroneos CJ, Selber JC, Offodile AC 2nd, et al. US FDA breast implant postapproval studies: long-term outcomes in
99,993 patients. Ann Surg. 2019;269(1):30–6
Strengths • This is the largest, most comprehensive study of aesthetic and reconstructive breast implant
patient safety and outcomes
• Within this prospective study from 3215 centers across the United States of nearly 100,000
patients over a 7-year follow-up period, the authors found that there were connective tissue
disorders statistically higher than predicted in the general population, and when compared to an
internal control of saline implants
Limitations • The study is limited to the analysis of large post approval studies (LPAS) summary data, and
thus, cannot account for differences in Mentor and Allergan study protocols (Mentor was
physician-reported outcomes, while Allergan allowed for patient-reported outcomes to be
tracked), and the Mentor cohort of patients had a considerable loss to follow-up, for which they
were reprimanded by the FDA
• Due to the nature of LPAS, the patients could not be analyzed on an individual patient level nor
could the implants characteristics and operative details be reviewed
Impact The day after publication of this article, FDA commissioner Scott Gottlieb responded to this highly
cited paper by empaneling an FDA safety advisory committee on breast implants, and
simultaneously the French ANSM declared a similar breast implant safety advisory committee. This
precipitated increased scrutiny on breast implant outcomes worldwide from news articles from over
250 journalists in 36 countries by the International Consortium of Investigative Journalists (ICIJ), an
FDA class I device recall of BIOCELL textured implants due to a disproportionate risk of BIA-
ALCL, and both national and international changes in breast implant “black box” warnings, updated
package inserts, mechanisms for device tracking, patient notification, and standardized informed
consents for breast implants
The United States Food and Drug 5.35–6.62). Independently, the Allergan cohort
Administration (FDA) prohibited the use of sili- had a 7-year follow-up period, was based on
cone gel-filled breast implants in 1992 due to physician-confirmed diagnoses, and achieved an
emerging media focus on unsupported concerns acceptable 60% follow-up rate. Patients that
of silicone toxicity. In 2000, the Institute of underwent breast reconstruction revision simi-
Medicine found that outcomes data on local com- larly had incidence ratios greater than 2.0 for
plications was sufficient to establish silicone scleroderma, Sjögren syndrome, and both derma-
implant safety and efficacy, but recommended tomyositis and polymyositis at 7-year follow-up
that further evidence was warranted on the long- even after statistically accounting for confound-
term systemic effects of silicone gel-filled ers. These results were congruent with the largest
implants. This prompted the FDA to approve sec- meta-analysis to date written by Balk and Raman
ond generation, Allergan and Mentor, implants in that pooled outcomes from 32 observational
2006 with the establishment of large post studies, and was also later corroborated by a
approval studies (LPAS) to focus on the long- 2018 cross-sectional study of 125,000 patients
term systemic effects of breast implants [18]. that found a statistically association between sili-
LPAS enrolled nearly 100,000 patients with cone breast implants and autoimmune/rheumatic
breast implants for both aesthetic and reconstruc- disorders, Sjögren syndrome, systemic sclerosis,
tive indications [11]. After a 7-year long-term and sarcoidosis [19, 20]. It is important to note
follow-up, the Mentor cohort demonstrated an that Coroneos and colleagues demonstrated
association with Sjögren syndrome (standardized breast implants remain very safe in the vast
incidence ratio, 8.14; 95% CI, 6.24–10.44), majority of patients with high patient satisfaction
scleroderma (standardized incidence ratio, 7.00; at long-term follow up, and that any systemic
95% CI, 5.12–9.34), and rheumatoid arthritis sequelae were very minor statistical associations
(standardized incidence ratio, 5.96; 95% CI, without evidence of causation.
In their chapter, Coroneos et al. were able to implant-host interactions, with the aim of opti-
analyze LPAS data from both Mentor and mizing implant performance and minimizing
Allergan demonstrating the risk of rare systemic immune-related risks.
harms in patients with silicone gel-filled breast Coroneos et al. was significant because it both
implants. As noted by the authors, study limita- confirmed breast implant safety, but also shed
tions included inability to account for differences light on a number of uncommon and rare issues
in Mentor and Allergan’s differences in reporting related to breast implants. This landmark paper
procedures, sources of bias, and considerable helped to bring these issues to the attention of
loss to follow-up for the Mentor cohort of policymakers, regulators, manufacturers, and the
patients. These limitations highlight the need for public, and played a key role in prompting regu-
improved collection of evidence regarding long- latory agencies to take action worldwide for bet-
term outcomes, safety, and efficacy of breast ter transparency of outcomes, improved clinical
implants and participation in national breast trial design, and the expanded use of prospective
implant registries [18]. In collaboration with the registries. Overall, this research had a significant
FDA, the Plastic Surgery Foundation and the impact on the field of plastic surgery, and raised
American Society of Plastic Surgeons has devel- awareness of important safety concerns related to
oped and promoted the National Breast Implant these devices ensuring physician awareness and
Registry to improve the post-market surveillance patient safety. Presenting to the 2005 US FDA
infrastructure for breast implant devices and the panel on breast implant safety, Dr. Scott Spear
PROFILE registry for detailed tracking of remarked, “As doctors, we have a unique and
BIA-ALCL. special responsibility to the patient and to the
In addition to its impact on patient safety and truth. You have got to be honest with patients. If
regulatory actions, the article by Coroneos et al. you exercise that privilege as a surgeon, in the
has also made notable contributions to the field of long run you can win the confidence and respect
breast implant research, particularly in under- of the public, the media, your colleagues, and
standing the interaction between implants and the even the government.” Senior author Dr. Clemens
immune system, as well as driving improvements echoed these sentiments presenting this manu-
in implant design. Coroneos et al. spurred script to the 2019 FDA Breast Implant Safety
researchers to delve deeper into the immune- Advisory Committee, “Data possesses remark-
mediated pathways that may be involved. This able neutrality. It is neither good nor bad, right
has led to a growing body of research exploring nor wrong, while awaiting our examination. It
the biocompatibility of breast implant materials, cannot fail us, unless we falter in our duty to
the inflammatory response at the implant-tissue learn from it.” Let us heed this call, recognizing
interface, and potential immunological reactions that our capacity to learn from large data sets
that could contribute to adverse outcomes. increasingly shapes our collective journey
Moreover, the publication of this study has driven towards improved patient outcomes, guided by
efforts to improve implant design. The findings the pursuit of excellence.
encouraged manufacturers and researchers to
explore alternative materials, surface textures,
and implant configurations that may have a more 19.2 Expert Concluding
favorable immune profile and lower risk of Commentary
adverse reactions. The increased scrutiny on
breast implant outcomes and safety prompted by The field of breast implant science has undergone
this chapter has fostered a more proactive a remarkable evolution, marked by significant
approach to implant research and development. It advancements in surgical techniques, implant
has encouraged collaboration between regulatory design, and a deepened understanding of the
agencies, manufacturers, and the scientific com- associated complications and long-term out-
munity resulting in ongoing advancements in comes. The journey of breast implant develop-
implant technology, biomaterial science, and ment and use, spanning from the 1960s to the
present day, has witnessed the convergence of allowing for the timely identification and
innovative technologies, rigorous scientific response to safety signals.
inquiry, and an unwavering commitment to In summary, the field of breast implant sci-
improving patient safety and satisfaction. ence is dynamically evolving and holds immense
Landmark publications have served as vital potential for transformative impact. Guided by
milestones guiding the field’s progress, including scientific rigor and a dedication to patient care,
Gabriel et al.’s comprehensive exploration of the field will continue to shape the landscape of
local complications, Breuing and Warren’s semi- aesthetic and reconstructive surgery, enhancing
nal work on acellular dermal matrices (ADM) in the lives of individuals worldwide.
breast reconstruction, and De Alcantara Filho
et al.’s pivotal study on nipple-sparing mastec-
tomy to define and expand prosthetic indications. References
The standard of care has been further refined to
address uncommon and rare sequelae of breast 1. Homsy A, Rüegg E, Montandon D, Vlastos G,
Modarressi A, Pittet B. Breast reconstruction: a cen-
implants through Clemens et al.’s investigation of tury of controversies and progress. Ann Plast Surg.
breast implant-associated anaplastic large-cell 2018;80:457–63.
lymphoma (BIA-ALCL). Finally, prospective 2. Champaneria MC, Wong WW, Hill ME, Gupta
clinical trials have expanded exponentially both SC. The evolution of breast reconstruction: a histori-
cal perspective. World J Surg. 2012;36:730–42.
in volume of patients and long-term outcomes 3. Cole NM. Consequences of the U.S. Food and Drug
with Coroneos et al.’s analysis of long-term Administration-directed moratorium on silicone gel
safety outcomes in nearly 100,000 patients. This breast implants: 1992–2006. Plast Reconstr Surg.
has ushered a new renaissance in implant safety, 2018;141:1137–41.
4. Plastic Surgery Statistics Report. In: American
device invention, breast implant registries, as Society of Plastic Surgeons. Websites: American
well as informed consent for shared decision Society of Plastic Surgeons; 2020, p. 5.
making. 5. Spencer KW. Significance of the breast to the indi-
As we look to the future, the field of breast vidual and society. Plast Surg Nurs. 1996;16:131–2.
6. Schrager S, Lyon SM, Poore SO. Breast implants:
implant science is poised for continued growth common questions and answers. Am Fam Physician.
and innovation. Enhanced implant designs, 2021;104:500–8.
biocompatible coatings, and optimized surgi- 7. Gabriel SE, Woods JE, O'Fallon WM, Beard CM,
cal techniques promise to mitigate the risk of Kurland LT, Melton LJ 3rd. Complications leading
to surgery after breast implantation. N Engl J Med.
capsular contracture, implant rupture, and 1997;336:677–82.
other complications. Furthermore, a patient- 8. Breuing KH, Warren SM. Immediate bilateral
centric approach to care underscores the breast reconstruction with implants and inferolateral
importance of understanding the psychological AlloDerm slings. Ann Plast Surg. 2005;55:232–9.
9. de Alcantara FP, Capko D, Barry JM, Morrow M,
and emotional well-being of individuals seek- Pusic A, Sacchini VS. Nipple-sparing mastectomy for
ing breast augmentation or reconstruction. breast cancer and risk-reducing surgery: the Memorial
Advancements in the field will be driven by Sloan-Kettering Cancer Center experience. Ann Surg
multidisciplinary collaboration and evidence- Oncol. 2011;18:3117–22.
10. Clemens MW, Medeiros LJ, Butler CE, Hunt KK,
based research, ensuring that patients receive Fanale MA, Horwitz S, Weisenburger DD, Liu J,
optimal outcomes. Morgan EA, Kanagal-Shamanna R, Parkash V, Ning
The field will also continue to confront emerg- J, Sohani AR, Ferry JA, Mehta-Shah N, Dogan A,
ing challenges, such as the management of BIA- Liu H, Thormann N, Di Napoli A, Lade S, Piccolini
J, Reyes R, Williams T, McCarthy CM, Hanson SE,
ALCL and the long-term systemic effects of Nastoupil LJ, Gaur R, Oki Y, Young KH, Miranda
silicone gel-filled implants and the emerging RN. Complete surgical excision is essential for
breast implant illness, a constellation of patient the management of patients with breast implant-
symptoms still ill defined. National breast implant associated anaplastic large-cell lymphoma. J Clin
Oncol. 2016;34:160–8.
registries and robust post-market surveillance 11. Coroneos CJ, Selber JC, Offodile AC 2nd, Butler CE,
will be central to addressing these concerns, Clemens MW. US FDA breast implant postapproval
studies: long-term outcomes in 99,993 patients. Ann 17. Marra A, Viale G, Pileri SA, Pravettoni G, Viale
Surg. 2019;269:30–6. G, De Lorenzi F, Nolè F, Veronesi P, Curigliano
12. Fissette J. Breast implants: state of the controversy. G. Breast implant-associated anaplastic large cell
Bull Mem Acad R Med Belg. 2000;155:301–8. dis- lymphoma: a comprehensive review. Cancer Treat
cussion 8–9. Rev. 2020;84:101963.
13. Gladfelter J. Safely re-integrating silicone breast 18. Ashar BS. Assessing the risks of breast implants and
implants into the plastic surgery practice. Plast Surg FDA’s vision for the National Breast Implant Registry.
Nurs. 2006;26:128–31. Ann Surg. 2019;269:37–8.
14. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer 19. Balk EM, Earley A, Avendano EA, Raman G. Long-
statistics, 2022. CA Cancer J Clin. 2022;72:7–33. term health outcomes in women with silicone gel
15. Spear SL, Hannan CM, Willey SC, Cocilovo breast implants: a systematic review. Ann Intern Med.
C. Nipple-sparing mastectomy. Plast Reconstr Surg. 2016;164:164–75.
2009;123:1665–73. 20. Watad A, Rosenberg V, Tiosano S, Cohen Tervaert
16. ISAPS International Survey on Aesthetic/Cosmetic JW, Yavne Y, Shoenfeld Y, Shalev V, Chodick G,
Procedures. ISAP International Study on Aesthetic/ Amital H. Silicone breast implants and the risk of
Cosmetic Procedures Performed in 2017. In The autoimmune/rheumatic disorders: a real-world analy-
International Society of Aesthetic Plastic Surgery’s sis. Int J Epidemiol. 2018;47:1846–54.
website: the International Society of Aesthetic Plastic
Surgery; 2017.
Part IV
Hand and Upper Extremity
Evolution of Upper Extremity
Trauma Management
20
Ronald D. Brown, Stefan Czerniecki,
and Amy Moore
Abstract nerves. J Bone Joint Surg Am.

1972;54(4):727–50.
In this chapter, we highlight five landmark
4. Godina M. Early microsurgical reconstruction
papers that dramatically influenced the care of
of complex trauma of the extremities. Plast
patients with hand and upper extremity
Reconstr Surg. 1986;78(3):285–92.
trauma. We discuss the historical context in
5. Tamai S. Twenty years’ experience of limb
which these techniques evolved, provide an
replantation–review of 293 upper extremity
overview of the methodology used by the
replants. J Hand Surg Am. 1982;7(6):549–56.
authors, and examine the subsequent impact
of the works on the practice of hand and upper
extremity surgery.
20.1 Introduction
Keywords
The management and reconstruction of hand
Landmark · Upper extremity trauma · Distal and upper extremity trauma are complex and
radius · Nerve · Zone II · Replant have evolved substantially due to pioneering
work of innovators in both plastic and ortho-
pedic surgeries. Successful and comprehen-
The Five Most Impactful Papers sive management of these injuries often
1. Orbay JL, Fernandez DL. Volar fixation for requires consideration of bone, tendon, and
dorsally displaced fractures of the distal peripheral nerve injuries, as well as soft tissue
radius: a preliminary report. J Hand Surg Am. reconstruction. With this in mind, we selected
2002;27(2):205–15. one landmark publication from each of these
2. Small JO, Brennen MD, Colville J. Early subsets that advanced operative or post-opera-
active mobilisation following flexor tendon tive care. Our final selection addresses upper
repair in zone 2. J Hand Surg Br. extremity replantation—a combination of
1989;14(4):383–91. these four anatomic areas. Not to be underem-
3. Millesi H, Meissl G, Berger A. The interfas- phasized is the role of hand and occupational
cicular nerve-grafting of the median and ulnar therapy in the return to function following
upper extremity injuries. Changes to protocol
R. D. Brown (*) · S. Czerniecki · A. Moore in this realm can be as effective as changes in
Department of Plastic and Reconstructive Surgery,
The Ohio State University, Columbus, OH, USA
https://doi.org/10.1007/978-3-031-57132-9_20
196 R. D. Brown et al.
surgical techniques for improving patient out- point. The following year he detailed his technique
comes [1]. [9] via the “extended flexor carpi radialis (FCR)
approach,” and in 2002, along with Dr. Diego
Fernandez, authored the first prospective case
20.2 Fracture Fixation series of patients who underwent volar fixation for
dorsally displaced fractures [10]. We selected this
Distal radius fractures are the most common frac- case series as our first landmark paper.
tures in adults [2]. As recently as the 1960s, In this seminal work, Orbay and Fernandez
nearly all distal radius fractures were managed outline their treatment of 29 consecutive patients
non-operatively [3]. In the following decades, with 31 distal radius fractures using a volar fixed
surgeons began to utilize various fixation tech- angle plate. Inclusion criteria were wide, includ-
niques with the goal of improving functional out- ing a broad range of fracture patterns, all ages,
comes. Early techniques included percutaneous and even those which failed prior ORIF through a
fixation (pinning, screws), external fixators, and dorsal approach. Post-operative follow-up was at
internal fixation with dorsal plates [4]. By the least 12 months for all patients and included
1990s, dorsal buttress plating had become the radiographic measurements of volar tilt, radial
standard for open reduction and internal fixation inclination, radial shortening, and articular con-
(ORIF) of most unstable distal radius fractures gruity, as well as wrist range of motion, strength,
despite large multi-center studies demonstrating and return to work or activities of daily living. All
high rates of hardware-related complications outcomes were good or excellent, and only one
necessitating hardware removal [5, 6]. Volar but- case required hardware removal due to dorsal
tress plates were occasionally used for volar- tendon irritation from a long screw.
displaced fractures, and extensor tendon This chapter is important because it chal-
complications such as irritation, adhesions, and lenged the paradigm of distal radius management
rupture were not observed [7]. and opened the door to subsequent technological
In 2000, Dr. Jorge Orbay first described the use advances that have come with distal radius fixa-
of a fixed-angle volar plate for unstable distal tion and hardware. Today, volar plating of distal
radius fractures [8]. This method allowed for sta- radius fractures remains the standard approach
ble internal fixation and early motion—a goal that for most hand and upper extremity surgeons.
had been otherwise difficult to achieve up to that
Orbay JL, Fernandez DL. Volar fixation for dorsally displaced fractures of the distal radius: a preliminary report. J
Hand Surg Am. 2002;27(2):205–15
• Broad inclusion criteria
• Detailed surgical technique
• Standardized outcome measurements
• Long follow-up
Limitations • Relatively small sample size
Impact Prior to this paper, dorsal buttress plating was used for fixation of most distal radius fractures
despite high rates of complications and hardware removal. This was the first case series showing
outcomes from volar fixation of dorsally displaced distal radius fractures. Overall outcomes were
good or excellent, and volar fixation has since become the standard approach for most distal radius
fractures requiring operative repair
20.3 Tendon Repair good reason. As R. Guy Pulvertaft astutely pro-

claimed, “It is not difficult to suture tendons and
The evolution of flexor tendon repair over the last prepare the ground for sound union; the real prob-
century has been the focus of a tremendous amount lem is to obtain a freely sliding tendon capable of
of basic science and clinical investigation, and for restoring good function.” Zone II flexor tendon
20 Evolution of Upper Extremity Trauma Management 197
injuries, which extend from the proximal A1 pul- This paper describes outcomes from 98 patients
ley to the FDS insertion distally [11], are widely with 117 zone II injuries treated with their early
recognized as the most challenging injuries to active range of motion protocol during a 34-month
repair [12]. In 1918, when Sterling Bunnell popu- period. Tendon repair was performed with a Kessler-
larized the term “no man’s land” to describe these Mason-Allen core suture and a running epitendinous
injuries, zone II primary repair was routinely for- suture, and a dorsal blocking splint was applied with
saken due to unacceptably high rates of complica- the wrist slightly flexed and the metacarpal phalan-
tions, including infections, adhesions, and geal joints flexed at 90 degrees. Active range of
contractures. But as repair techniques and suture motion therapy was begun within 48 h after surgery
technology advanced, so too did the management and performed every 2 h under the supervision of a
of zone II injuries. By the 1960s, surgeons began to hand therapist. Patients remained hospitalized for an
realize that post-operative management of these average of 3 days. Final outcomes were measured at
injuries was also integral to the overall functional a minimum of 6 months after surgery with 77% and
outcomes. Controlled passive motion protocols 75% of patients achieving good or excellent range of
were first reported by Kleinert in 1967 [13], fol- motion, respectively. Notably, repair failure rate was
lowed by Duran and Houser in 1975, which dra- 9.4%, with 64% of those patients eventually reach-
matically improved range of motion following ing good or excellent results following repeat repair.
flexor tendon repairs [13, 14]. In the search for con- The literature supporting flexor tendon repair
tinued improvement, some surgeons began to continues to grow, particularly with the advent of
experiment with early active range of motion pro- “Wide Awake Local Anesthetic No Tourniquet”
tocols. This transition was supported by animal and (WALANT) surgery [17, 18]. However, Small’s
human biomechanical studies that demonstrated contribution was instrumental in demonstrating
the feasibility and safety of early active range of that early active range of motion is a safe and effec-
motion [15]. However, there were no published tive protocol for rehabilitation of zone II flexor ten-
large case series at that time. Despite the relatively don injuries. Subsequent randomized controlled
small body of evidence, Mr. James Small FRCS studies comparing early active range of motion and
and colleagues in Belfast adopted early active passive range of motion have since demonstrated a
range of motion for all flexor tendon injuries in the significant increase in range of motion with the
hand and wrist. Their description of this seminal active protocol, and greater satisfaction scores
protocol is our second landmark paper [16]. without an increased rupture rate [19].
Small JO, Brennen MD, Colville J. Early active mobilisation following flexor tendon repair in zone 2. J Hand Surg
Br. 1989;14(4):383–91
• Large sample size
Limitations • Intensive inpatient therapy protocol
Impact Prolonged immobilization after tendon repair leads to adhesions and reduced finger range of
motion. Initial results with controlled passive range of motion showed improved functional
outcomes, though concern remained that active motion could lead to increased rates of rupture. This
is the first large study of early active mobilization for flexor tendon repairs, showing largely good
and excellent functional outcomes without an increased incidence of rupture
20.4 Nerve Repair vailing thought that nerve grafting was universally
inferior to a direct repair achieved by any means.
Although the first nerve graft was performed in Every effort was made to avoid grafting and facil-
1876 [20], early clinical outcomes were disap- itate direct end-to-end nerve repair, including
pointing. Nearly a century passed with the pre- prolonged immobilization of joints, bone short-
ening, or extensive neurolysis of the proximal “The interfascicular Nerve-Grafting of the Median
and distal nerve ends. These techniques infre- and Ulnar Nerves,” which stands as our third land-
quently resulted in a tension-free repair, and so mark paper [20]. In total they presented case data
nerve repairs under moderate tension were from 43 median nerves and 42 ulnar nerves that
accepted. Grafting was still used as a second-line had been repaired with autografts. Sixteen of the
technique for large nerve gaps that were other- median nerve repairs and 18 of the ulnar nerve
wise unable to be closed, but partial functional repairs were complete transections with total loss
recovery rates (Medical Research Council [MRC] of function and had follow-up greater than
Grade 3 or greater and protective sensation) 12 months. All those patients had some return of
remained low [21]. motor function with a minimum return of protec-
Dr. Hanno Millesi—a pioneer of peripheral tive sensation. MRC Grade 4 or 5 was achieved in
nerve surgery—believed that the success of nerve 69% of median and 44% of ulnar nerve repairs,
repair was more dependent upon the lack of ten- and MRC Grade 3 was achieved in nearly all
sion at the repair site rather than the direct end- remaining repairs. Return of sensation was simi-
to-end coaptation. To test his theory, he studied larly successful, with 56% of median and 39% of
sciatic nerve repairs in cats and rabbits and dem- ulnar nerve repairs regaining two-point discrimi-
onstrated that tension-free autograft performed nation and the remainder regaining protective sen-
functionally equal to direct tension-free repairs sation. In 1976, Millesi expanded upon this
and far superior to direct repairs under tension. original work, publishing extended follow-up on
This success in an animal model prompted him to all patients from his original paper and including
utilize nerve autografts in the clinical setting, radial nerve repairs. His previously reported high
combined with a new technique he developed in rates of functional recovery were upheld [22].
1964 [20]. Interfascicular nerve grafting, as he Millesi’s work is important because it stands
called it, involved the removal of an epineural as a paradigm shift in the study and clinical prac-
strip from the nerve endings under a dissecting tice of peripheral nerve repair. He demonstrated
microscope, identifying matching groups of fas- that nerve autografts can lead to excellent func-
cicles proximally and distally, and bridging these tional outcomes and introduced a novel technique
gaps with small-caliber nerve autografts in a for repairing gaps in large peripheral nerves.
tension-free manner. This differed from the more Furthermore, he articulated several key principles
prevalent technique of larger trunk or cable grafts of nerve repair that remain in use today—the pri-
secured by epineural sutures alone, which had oritization of a tension-free repair, the use of
poor revascularization due to the large diameter. minimal suture material to reduce scar, and the
In 1972, Millesi and colleagues presented this avoidance of tight sutures that cause buckling at
technique and early outcomes in a paper titled the coaptation.
Millesi H, Meissl G, Berger A. The interfascicular nerve-grafting of the median and ulnar nerves. J Bone Joint Surg
Am. 1972;54(4):727–50
Strengths • Detailed inclusion criteria
• Clearly outlined technique
• Thorough reporting of case data
Limitations • Lack of historical control population
Impact Early attempts at nerve grafting frequently led to poor functional outcomes. Dr. Millesi
demonstrated that tension-free microscopic repairs with a short nerve autograft can lead to
excellent functional outcomes. Additionally, he introduced “interfascicular nerve grafting,” a
technique used for the repair of large peripheral nerves utilizing multiple smaller-caliber grafts to
bridge matching fascicular groups across a nerve gap
20.5 Soft Tissue Reconstruction in 1986 [24]. This landmark paper was instru-
mental in establishing early reconstruction as the
Development of reconstructive microsurgery in new standard of care following traumatic extrem-
the 1960s opened new avenues for management ity injuries.
of traumatic extremity wounds that previously Godina’s study included outcomes from 532
may have required amputation. Prior to the mid- patients who underwent free tissue transfer for
to late 1970s, all free tissue transfer reconstruc- reconstruction of traumatic extremity injuries.
tions were performed in a delayed or “late” These patients were divided into 3 groups—those
manner for various upper extremity injuries, who underwent reconstruction within 72 h of injury
including sequelae of burns, chronic wounds or (134 patients), between 72 h and 3 months (167
deformities, and following failure of local or patients), and those treated after 3 months (231
regional soft tissue reconstructions [23]. As patients). Patients were followed until full weight
knowledge and utility of microsurgery spread, bearing was initiated, and outcomes included flap
plastic surgeons were involved earlier in the failure rates, time to bone healing, hospital length
reconstructive timeline—within weeks of the of stay, and number of surgeries. They found
original injury. However, these subacute wounds decreased flap failure rates, infection, time to bone
were often colonized with bacteria and had a bur- healing, hospital length of stay, and number of sur-
den of necrotic tissue, making successful recon- geries in the early reconstruction group.
struction challenging. In 1976, Dr. Marko Since the publication of Godina’s work, the
Godina—a leader in early reconstructive micro- landscape of reconstructive microsurgery has
surgery—began challenging the dogma of changed significantly. This is due in large parts to
delayed and late extremity reconstruction. the development of negative pressure wound
Following the development of a microsurgery therapy, the increased technical skill of surgeons,
service at the University of Ljubljana Hospital in and the availability of skin substitutes. More
Slovenia, he was able to facilitate early (i.e., recent research demonstrates that the delay prior
within 72 h) and immediate free tissue transfer to soft tissue coverage can be extended to 10 days
reconstruction of large traumatic soft tissue without increased rates of flap compromise [25].
extremity wounds in concert with orthopedic sur- Nonetheless, the basic principles described in
geons managing the osseous injuries. Clinical Godina’s pivotal paper were revolutionary in the
outcome results from his patients treated in this clinical care of patients with upper extremity
early period of microsurgery, from 1976 through trauma and remain key for their successful man-
1983, were published posthumously on his behalf agement today.
1986;78(3):285–92
Strengths • Largest single-center series of free flap outcomes at the time
• Changed the paradigm for management of severe soft tissue injuries
Limitations • Lack of functional outcomes beyond weightbearing
• Retrospective review
Impact This paper was one of the earliest to describe a shared management model by orthopedic and
plastic surgeons for treatment of traumatic wounds. This model involved aggressive debridement,
fracture fixation, and wound coverage with free flaps if necessary, as early as allowed by the
patient’s condition. It showed that this early management led to significantly improved outcomes
compared with delayed reconstruction and helped shift the standard of care toward earlier
reconstruction
20.6 Replantation ischemia <6 h; thumb or multiple digits; ampu-

tation through the hand or more proximal—
In the decades following the first successful reat- remain strong relative indications to this day.
tachment of a completely amputated digit in His technique and stepwise approach are widely
1965, the field of upper extremity replantation practiced in replantation centers. And his over-
and revascularization experienced explosive all replant survival rate of 87% is consistent
growth and innovation. Several groups worked to with modern reported survival rates of 77–93%.
define classification schemes for upper extremity Tamai’s results and conclusions were also
amputations [26], as well as indications [27, 28], extremely detailed. He reported failure rates
techniques [29], and outcome measures for relative to both warm and cold ischemia time
replantation. Initial published case series were and found that overall failure rates were elevated
small, and reported outcomes were relatively with warm ischemia (17.8%) versus cold isch-
basic. In 1978 and 1980, the first two large cases emia (4.0%). He described his complications
series were published [30, 31]. However, these and number and type of secondary reconstruc-
only described replant survival rates, level of tions that were later required. He even imple-
amputation, and functional recovery on a basic mented a scoring system to evaluate the function
scale of 1–4. In 1982, Dr. Susumu Tamai pub- of a replanted digit or extremity. Finally, this
lished his review of 293 upper extremity replants publication further popularized Tamai’s simple
performed at Nara Medical University in Japan anatomical classification for finger
over a 15-year period between 1965 and 1980 amputations.
[32]. His work serves as our final landmark paper Dr. Tamai was a trailblazer in the realm of
and addresses many of the shortcomings of ear- extremity replantation. His work was innova-
lier publications, representing a significant step tive and ahead of its time in terms of cohort
forward in the quality of replantation literature. size, detail of reported results, and development
In many ways, Tamai’s work was ahead of its of tools that could be applied to advance his
time. His indications for replantation—warm field.
Tamai S. Twenty years’ experience of limb replantation–review of 293 upper extremity replants. J Hand Surg Am.
1982;7(6):549–56
Strengths • Large sample size
• Simple classification of digit amputations
• Detailed functional and patient reported outcomes
Limitations • Lack of statistical analysis
Impact This paper was an important piece of early literature that helped characterize and advance the
field of upper extremity replantation. The reported results were incredibly detailed and
thorough at the time of publication, and the author developed a functional outcome score that
included quantitative and qualitative measures. Finally, the Tamai anatomical classification of
finger amputations, popularized in this paper, remains one of the most frequently used
classification systems today
20.7 Expert Concluding in management [33]. Over the last 50 years, these
Commentary challenges have been met with innovative contri-
butions from a multidisciplinary group of plastic
The study of upper extremity trauma is necessar- surgeons, orthopedic surgeons, and occupational
ily broad. These injuries occur by a wide variety therapists, among others. Their curiosity and col-
of mechanisms, and the unique anatomical rela- laboration resulted in countless publications that
tionships between neurovascular structures, skel- advanced the understanding and treatment of
etal anatomy, and skin create complex challenges upper extremity trauma. Many such publications
are deserving of the title “Landmark.” However, future for upper extremity trauma management
few have been as impactful as the five landmark remains bright, and we will surely see exponen-
papers we described above. Each of these marked tial growth in this field over the next 50 years.
a pivotal moment in the management of upper
extremity bone, tendon, nerve, soft tissue, and
amputation injuries, respectively, while simulta- References
neously propelling the discipline forward and
laying a foundation by which it could grow. 1. Krishnan J, Chung KC. Access to hand therapy fol-
lowing surgery in the United States: barriers and facil-
Today the field of upper extremity trauma itators. Hand Clin. 2020;36(2):205–13.
evolves in leaps and bounds, often in stride with 2. Court-Brown CM, Caesar B. Epidemiology of adult
technology. Computer-assisted surgery (CAS) fractures: a review. Injury. 2006;37(8):691–7.
planning and 3D technology now offer personal- 3. Older TM, Stabler EV, Cassebaum WH. Colles frac-
ture: evaluation and selection of therapy. J Trauma.
ized patient care and improved outcomes [34, 1965;5:469–76.
35]. The use of adjunct wound care treatments 4. Haus BM, Jupiter JB. Intra-articular fractures of the
like vacuum wound care devices and collagen distal end of the radius in young adults: reexamined as
matrix substrates has allowed temporary or evidence-based and outcomes medicine. J Bone Joint
Surg Am. 2009;91(12):2984–91.
definitive treatment for upper extremity wounds 5. Carter PR, Frederick HA, Laseter GF. Open reduction
that would have previously required free flap and internal fixation of unstable distal radius fractures
reconstruction [36, 37]. These modalities are with a low-profile plate: a multicenter study of 73
expanding the surgical options for patients and fractures. J Hand Surg Am. 1998;23(2):300–7.
6. Ring D, Jupiter JB, Brennwald J, Buchler U, Hastings
increasing limb salvage following devastating H 2nd. Prospective multicenter trial of a plate for dor-
upper extremity injuries. Meanwhile, upper sal fixation of distal radius fractures. J Hand Surg Am.
extremity surgeons continue to push the boundar- 1997;22(5):777–84.
ies of WALANT surgery beyond flexor tendon 7. Keating JF, Court-Brown CM, McQueen MM. Internal
fixation of volar-displaced distal radial fractures. J
repair and carpal tunnel release. Now, hand-based Bone Joint Surg Br. 1994;76(3):401–5.
soft tissue reconstructions [38], small joint 8. Orbay JL. The treatment of unstable distal
arthroscopy [39, 40], and fracture fixation in the radius fractures with volar fixation. Hand Surg.
hand and wrist [41, 42] are safely performed in 2000;5(2):103–12.
9. Orbay JL, Badia A, Indriago IR, et al. The extended
this manner with lower costs, lower waste pro- flexor carpi radialis approach: a new perspective for
duction, and high patient satisfaction [17, 43]. the distal radius fracture. Tech Hand Up Extrem Surg.
As we look toward the future, the manage- 2001;5(4):204–11.
ment of peripheral nerve injury remains one of 10. Orbay JL, Fernandez DL. Volar fixation for dorsally
displaced fractures of the distal radius: a preliminary
the most innovative and exciting aspects of upper report. J Hand Surg Am. 2002;27(2):205–15.
extremity care. The use of regenerative periph- 11. Kleinert HE, Verdan C. Report of the committee on
eral nerve interfaces (RPNI) and targeted muscle tendon injuries (international federation of societies
reinnervation (TMR) has demonstrated a dra- for surgery of the hand). J Hand Surg Am. 1983;8(5
Pt 2):794–8.
matic reduction in post-op neuroma pain [44–50] 12. Dy CJ, Daluiski A. Update on zone II flexor tendon
and opened the door for more functional pros- injuries. J Am Acad Orthop Surg. 2014;22(12):791–9.
thetics [51–56], shifting the focus of amputation 13. Lister GD, Kleinert HE, Kutz JE, Atasoy E. Primary
management toward maximizing functional out- flexor tendon repair followed by immediate controlled
mobilization. J Hand Surg Am. 1977;2(6):441–51.
comes [57]. Intraoperative electrical stimulation 14. Strickland JW, Glogovac SV. Digital function follow-
to peripheral nerves is a promising surgical ing flexor tendon repair in zone II: a comparison of
adjunct being studied as an efficacious therapy to immobilization and controlled passive motion tech-
improve patient outcomes [58, 59], and other niques. J Hand Surg Am. 1980;5(6):537–43.
15. Gelberman RH, Woo SL, Lothringer K, Akeson WH,
emerging techniques like advances in nerve coap- Amiel D. Effects of early intermittent passive mobili-
tation and targeted gene therapy to promote nerve zation on healing canine flexor tendons. J Hand Surg
regeneration are on the horizon as well [59]. The Am. 1982;7(2):170–5.
16. Small JO, Brennen MD, Colville J. Early active 35. Bodansky DMS, Sandow MJ, Volk I, Luria S,
mobilisation following flexor tendon repair in zone 2. Verstreken F, Horwitz MD. Insights and trends
J Hand Surg Br. 1989;14(4):383–91. review: the role of three-dimensional technology
17. Lalonde DH. Latest advances in wide awake hand sur- in upper extremity surgery. J Hand Surg Eur Vol.
gery. Hand Clin. 2019;35(1):1–6. 2023;48(5):383–95.
18. Tang JB, Zhou X, Pan ZJ, Qing J, Gong KT, Chen 36. Hofmeister EP, Mazurek M, Ingari J. Injuries sus-
J. Strong digital flexor tendon repair, extension- tained to the upper extremity due to modern war-
flexion test, and early active flexion: experience in fare and the evolution of care. J Hand Surg Am.
300 tendons. Hand Clin. 2017;33(3):455–63. 2007;32(8):1141–7.
19. Trumble TE, Vedder NB, Seiler JG 3rd, Hanel DP, 37. Ali E, Raghuvanshi M. Treatment of open upper limb
Diao E, Pettrone S. Zone-II flexor tendon repair: a injuries with infection prevention and negative pres-
randomized prospective trial of active place-and-hold sure wound therapy: a systematic review. J Wound
therapy compared with passive motion therapy. J Care. 2017;26(12):712–9.
Bone Joint Surg Am. 2010;92(6):1381–9. 38. Xing SG, Tang JB. Extending applications of local
20. Millesi H, Meissl G, Berger A. The interfascicular anesthesia without tourniquet to flap harvest and
nerve-grafting of the median and ulnar nerves. J Bone transfer in the hand. Hand Clin. 2019;35(1):97–102.
Joint Surg Am. 1972;54(4):727–50. 39. Liu B, Ng CY, Arshad MS, Edwards DS, Hayton
21. Seddon HJ. The use of autogenous grafts for the MJ. Wide-awake wrist and small joints arthroscopy of
repair of large gaps in peripheral nerves. Br J Surg. the hand. Hand Clin. 2019;35(1):85–92.
1947;35(138):151–67. 40. Hagert E, Lalonde DH. Wide-awake wrist arthroscopy
22. Millesi H, Meissl G, Berger A. Further experi- and open TFCC repair. J Wrist Surg. 2012;1(1):55–60.
ence with interfascicular grafting of the median, 41. Gregory S, Lalonde DH, Fung Leung LT. Minimally
ulnar, and radial nerves. J Bone Joint Surg Am. invasive finger fracture management: wide-awake
1976;58(2):209–18. closed reduction, K-wire fixation, and early protected
23. Brenner P, Lassner F, Becker M, Berger A. Timing of movement. Hand Clin. 2014;30(1):7–15.
free microsurgical tissue transfer for the acute phase 42. Huang Y, Chen C, Lin K, Yang S, Tarng Y, Chang
of hand injuries. Scand J Plast Reconstr Surg Hand W. Comparison of wide-awake local anesthesia no
Surg. 1997;31(2):165–70. tourniquet with general anesthesia with tourniquet for
24. Godina M. Early microsurgical reconstruction of volar plating of distal radius fracture. Orthopedics.
complex trauma of the extremities. Plast Reconstr 2019;42(1):e93–8.
Surg. 1986;78(3):285–92. 43. Kurtzman JS, Etcheson JI, Koehler SM. Wide-awake
25. Lee Z, Stranix JT, Rifkin WJ, et al. Timing of micro- local anesthesia with no tourniquet: an updated review.
surgical reconstruction in lower extremity trauma: an Plast Reconstr Surg Glob Open. 2021;9(3):e3507.
update of the Godina’s paradigm. Plast Reconstr Surg. 44. Souza JM, Cheesborough JE, Ko JH, Cho MS, Kuiken
2019;144(3):759–67. TA, Dumanian GA. Targeted muscle reinnervation: a
26. Biemer E. Definitions and classifications in replanta- novel approach to postamputation neuroma pain. Clin
tion surgery. Br J Plast Surg. 1980;33(2):164–8. Orthop Relat Res. 2014;472(10):2984–90.
27. O'Brien BM, MacLeod AM, Miller GD, Newing RK, 45. Hoyt BW, Gibson JA, Potter BK, Souza JM. Practice
Hayhurst JW, Morrison WA. Clinical replantation of patterns and pain outcomes for targeted muscle rein-
digits. Plast Reconstr Surg. 1973;52(5):490–502. nervation: an informed approach to targeted muscle
28. Frykman GK, Wood VE. Saving amputated digits. reinnervation use in the acute amputation setting. J
Current status of replantation of fingers and hands. Bone Joint Surg Am. 2021;103(8):681–7.
West J Med. 1974;121(4):265–9. 46. Cheesborough JE, Souza JM, Dumanian GA, Bueno
29. Tamai S, Hori Y, Tatsumi Y, et al. Microvascular RAJ. Targeted muscle reinnervation in the initial
anastomosis and its application on the replantation of management of traumatic upper extremity amputation
amputated digits and hands. Clin Orthop Relat Res. injury. Hand (N Y). 2014;9(2):253–7.
1978;133:106–21. 47. Janes LE, Fracol ME, Dumanian GA, Ko JH. Targeted
30. Chung-Wei C, Yun-Qing Q, Zhong-Jia Y. Extremity muscle reinnervation for the treatment of neuroma.
replantation. World J Surg. 1978;2(4):513–24. Hand Clin. 2021;37(3):345–59.
31. Kleinert HE, Jablon M, Tsai TM. An overview 48. O'Brien AL, Jordan SW, West JM, Mioton LM,
of replantation and results of 347 replants in 245 Dumanian GA, Valerio IL. Targeted muscle reinner-
patients. J Trauma. 1980;20(5):390–8. vation at the time of upper-extremity amputation for
32. Tamai S. Twenty years' experience of limb replanta- the treatment of pain severity and symptoms. J Hand
tion--review of 293 upper extremity replants. J Hand Surg Am. 2021;46(1):72.e1–72.e10.
Surg Am. 1982;7(6):549–56. 49. Hooper RC, Cederna PS, Brown DL, et al.
33. Ilyas AM. Complex trauma management of the upper Regenerative peripheral nerve interfaces for the man-
extremity. Hand Clin. 2018;34(1):xi. agement of symptomatic hand and digital neuromas.
34. Zhang D, Bauer AS, Blazar P, Earp BE. Three- Plast Reconstr Surg Glob Open. 2020;8(6):e2792.
dimensional printing in hand surgery. J Hand Surg 50. Santosa KB, Oliver JD, Cederna PS, Kung
Am. 2021;46(11):1016–22. TA. Regenerative peripheral nerve interfaces for
prevention and management of neuromas. Clin Plast 55. Gart MS, Souza JM, Dumanian GA. Targeted muscle
Surg. 2020;47(2):311–21. reinnervation in the upper extremity amputee: a tech-
51. Vu PP, Vaskov AK, Irwin ZT, et al. A regenerative nical roadmap. J Hand Surg Am. 2015;40(9):1877–88.
peripheral nerve interface allows real-time control of 56. Agrawal N, Olafsson S, Pickrell BB, Heng M, Valerio
an artificial hand in upper limb amputees. Sci Transl IL, Eberlin KR. The octopus procedure combined
Med. 2020;12(533):eaay2857. with targeted muscle reinnervation for elective trans-
52. Cheesborough JE, Smith LH, Kuiken TA, humeral amputation. Plast Reconstr Surg Glob Open.
Dumanian GA. Targeted muscle reinnervation 2021;9(11):e3931.
and advanced prosthetic arms. Semin Plast Surg. 57. Prucz RB, Friedrich JB. Upper extremity replan-
2015;29(1):62–72. tation: current concepts. Plast Reconstr Surg.
53. Johnson CC, Loeffler BJ, Gaston RG. Targeted 2014;133(2):333–42.
muscle reinnervation: a paradigm shift for neu- 58. Juckett L, Saffari TM, Ormseth B, Senger J, Moore
roma management and improved prosthesis control AM. The effect of electrical stimulation on nerve
in major limb amputees. J Am Acad Orthop Surg. regeneration following peripheral nerve injury.
2021;29(7):288–96. Biomol Ther. 2022;12(12):1856.
54. Morgan EN, Kyle Potter B, Souza JM, Tintle SM, 59. O'Brien AL, West JM, Saffari TM, Nguyen M,
Nanos GP 3rd. Targeted muscle reinnervation for tran- Moore AM. Promoting nerve regeneration: electrical
sradial amputation: description of operative technique. stimulation, gene therapy, and beyond. Physiology
Tech Hand Up Extrem Surg. 2016;20(4):166–71. (Bethesda). 2022;37(6):0.
Innovations in Care for Congenital
Hand Differences
21
Shimpei Ono and Kevin C. Chung
Abstract shortening of the digits, leading not only to

improved function but also appearance of the
Innovations in congenital hand differences
hand.
(CHD) are discussed in the context of five
landmark publications that have guided that
Keywords
innovation. The five landmark publications
include (1) the Swanson classification, (2) Congenital hand · Classification ·
pollicization, (3) prosthetics, (4) digital Pollicization · Prosthetics · Toe-to-hand
lengthening, and (5) toe-to-hand transfer. transfer · Digital lengthening
The Swanson classification system pro-
vides a universal framework for understanding
the range of CHD and helps guide treatment The Five Most Impactful Papers
planning and management. Pollicization, in 1. Swanson AB. A classification for congenital
which a finger (usually the index) is relocated malformations of the hand. N J Bull Acad
to function as a thumb, has been a significant Med. 1964;10:166–9.
innovation in the treatment of thumb hypopla- 2. Buck-Gramcko D. Pollicization of the index
sia. The field of prosthetics for CHD has seen finger. Method and results in aplasia and
numerous innovations such as 3D Printing and hypoplasia of the thumb. J Bone Joint Surg
myoelectric prosthetics and they have the Am. 1971;53:1605–17.
potential to significantly improve quality of 3. Sörbye R. Myoelectric prosthetic fitting in
life of children with CHD. Ideas and innova- young children. Clin Orthop Relat Res.
tions in surgical techniques such as toe-to- 1980;148:34–40.
hand transfer and digital lengthening have 4. Kessler I, Baruch A, Hecht O. Experience
expanded treatment options for congenital with distraction lengthening of digital rays in
congenital anomalies. J Hand Surg.
1977;2A:394–401.
S. Ono (*) 5. O’Brien BM, Black MJ, Morrison WA, et al.
Department of Plastic, Reconstructive and Aesthetic Microvascular great toe transfer for congenital
Surgery, Nippon Medical School, Tokyo, Japan
absence of the thumb. Hand. 1978;10:113–24.
K. C. Chung
Department of Surgery, The University of Michigan
Health System, Ann Arbor, MI, USA
https://doi.org/10.1007/978-3-031-57132-9_21
206 S. Ono and K. C. Chung
21.1 Introduction one of six categories. Then the International

Federation of Societies for Surgery of the Hand
Hand surgeons are constantly researching to (IFSSH) proposed a seven-category classification
improve the effectiveness and safety of care for by expanding the proposed classification of
congenital hand differences (CHD). This includes Swanson in 1976 [2], which was termed the
exploring new methods of diagnosis, devising Swanson/IFSSH classification (Table 21.1).
new surgical techniques, and developing novel Although this classification is comprehensive, it
prosthetic and reconstructive options with medi- has been criticized because of its inconsistent
cal–engineering collaboration. In this chapter, categorization (Group I and II based on causation
innovations in care for CHD are discussed in the whereas III to VI based on appearance) and dif-
context of five landmark publications that have ficulty classifying complex conditions such as
guided that innovation. cleft hand and symbrachydactyly. Therefore, new
classification based on a dysmorphology frame-
work can be helpful to adapt to increasing
21.2 Classification knowledge.
In 2010, Dr. Kerby Oberg, Paul Manske, and
Classification systems of CHD are essential for Michael Tonkin (OMT) proposed a new classifi-
predicting treatment need, planning clinical cation for CHD based on dysmorphology con-
interventions, and evaluating treatment out- cepts, placing conditions in one of three groups:
comes. It is not possible to satisfy all criteria to malformations, deformations, and dysplasias
define an ideal classification system because of (Table 21.2) [3]. Malformations are abnormali-
the wider range of manifestations of the anoma- ties of formation and/or differentiation of tissues.
lies; however, classification is necessary to culti- Deformations are abnormalities that occur after
vate a common language. Advances in tissue is formed. Dysplasias are abnormalities
understanding genetics and embryology have resulting from a lack of normal organization of
changed the classification system for CHD. The cells into tissue [4]. Each group is further sub-
Swanson classification, proposed by Swanson in classified according to whether they involve the
the 1960s [1], has been universally used by hand hand alone or the whole of the upper limb. In
surgeons for decades. The Swanson classification 2014, the IFSSH recommended the adopting of
system is first internationally recognized congen- the OMT classification to replace the Swanson/
ital hand classification. It is based on a morpho- IFSSH classification [5]. The OMT classification
logical rather than etiological system and grouped provides a comprehensive classification of every
according to parts of the limb that have been CHD, as well the most commonly associated
affected during development. In this classifica- syndromes. Balancing dysmorphology with eti-
tion, each limb malformation is grouped based on ology, the OMT classification remains flexible
the most predominant anomaly and is placed into enough to allow changes, following discovery of
Table 21.1 Swanson Swanson category Description

classification Type I Failure of formation
Transverse failure
Longitudinal failure: True phocomelia, pre-axial,
central post-axial
Type II Failure of differentiation or separation
Type III Duplication
Type IV Overgrowth
Type V Undergrowth
Type VI Congenital constriction band syndrome
Type VII Generalized skeletal abnormalities
21 Innovations in Care for Congenital Hand Differences 207
Table 21.2 The OMT classification of hand and upper limb anomalies
I. Malformations
A. Failure of axis formation/differentiation: Entire upper limb
1. Proximal-distal axis Brachymelia with brachydactyly
Symbrachydactyly
Transverse deficiency
Intersegmental deficiency
2. Radial-ulnar (anterior-posterior) axis Radial longitudinal deficiency
Ulnar longitudinal deficiency
Ulnar dimelia
Radioulnar synostosis
Humeroradial synostosis
3. Dorsal-ventral axis Nail patella syndrome
B. Failure of axis formation/differentiation: Hand plate
1. Radial-ulnar (anterior-posterior) axis Radial polydactyly
Triphalangeal thumb
Ulnar polydactyly
2. Dorsal-ventral axis Dorsal dimelia (palmar nail)
Hypoplastic/aplastic nail
C. Failure of hand plate formation/differentiation: Unspecified axis
1. Soft tissue Syndactyly
Camptodactyly
2. Skeletal deficiency Brachydactyly
Clinodactyly
Kirner’s deformity
Metacarpal and carpal synostoses
3. Complex Cleft hand
Synpolydactyly
Apert hand
II. Deformations
A. Constriction ring sequence
B. Arthrogryposis
C. Trigger digits
D. Not otherwise specified
III. Dysplasias
A. Hypertrophy Macrodactyly
Upper limb
Upper limb and macrodactyly
B. Tumorous conditions
Adapted from Oberg et al. 2010
new knowledge in the fields of developmental the Swanson classification. The Swanson classifi-
biology or genetics. Based on the advantages cation is considered a landmark paper in the his-
described above, the OMT classification has been tory of the congenital hand treatment in that it
universally accepted. An assessment of the OMT provided a standard common language that
classification demonstrates acceptable inter- and enables international information exchange for
intra-observer reliability [6]. the first time in the world. Hand surgeons who
Overall, the OMT classification, which is treat CHD need to know its historical transition
widely used at present, was originally based on and be familiar with it.
Swanson AB. A classification for congenital malformations of the hand. N J Bull Acad Med. 1964;10:166–9
Strengths • The Swanson classification system is first internationally recognized congenital hand
classification
Limitations • Because the Swanson classification is based on morphological framework, the categorization
is inconsistent and there is difficulty in classifying complex conditions
Impact Based on a dysmorphology framework and flexibility to support future modification, the OMT
classification has been universally accepted at present. However, the classification is originally
based on the Swanson classification, based on a morphological system. The Swanson classification
provided a universal framework for understanding the range of CHD and helped guide treatment
planning and management during previous decades
21.3 Pollicization Pollicization is an important innovation in the

treatment of thumb hypoplasia. The progression
Thumb hypoplasia is a malformation involving of the technique over the years, starting from
abnormal development and differentiation in the Guermonprez’s initial pedicled transfer of the
longitudinal radial axis. In 1967, Blauth classi- long finger in 1887 to Gosset’s [10] and
fied hypoplastic thumb into five grades as fol- Hilgenfeldt’s [11] refinements in the mid-
lows; type I: minor hypoplasia of the thenar twentieth century, shows the continuous develop-
muscles with normal skeletal structure; type II: ment in this field. The contribution of
tight web space with hypoplastic thenar muscles Buck-Gramcko is indeed monumental in this
and skeletal deficiencies; type III: severe hypo- field, with his vast experience and his landmark
plasia with deficient carpometacarpal (CMC) work in 1971 [12], which helped to popularize the
joint, but the presence of a remnant metacarpal; index finger for pollicization. His technique of
type IV: thumb aplasia with the presence of a pollicization involves relocating the index finger
remnant proximal metacarpal; type V: complete to the position of the thumb, with meticulous con-
absence of the thumb, also known as thumb apla- sideration given to the appropriate rotation, align-
sia [7]. In 1992, type III was further subdivided ment, and positioning to maximize the functional
by Manske and McCarroll [8] into IIIA and IIIB, outcome (Fig. 21.1). His 1971 publication on pol-
depending on whether a proximal metacarpal licization not only introduced a transformative
was present or not. Moreover, Buck-Gramcko technique but also showcased his dedication to
added an additional subcategory, IIIC, for thumbs scientific rigor and thorough outcome analysis.
with only a remnant metacarpal head in 2002 [9]. His willingness to scrutinize his own work and
In treating thumb hypoplasia, functional continually refine his methods based on evidence-
reconstruction is required according to the degree based results has significantly contributed to the
of severity. In mild cases in which the belly of the progress and refinement of this surgical procedure
abductor pollicis brevis is relatively preserved, [13]. Since his significant contributions, there
reconstruction of the opposition of the thumb is have been few changes to the fundamental tech-
possible by transferring the insertion of the nique of this procedure, demonstrating the effec-
APB. For Blauth II and IIIA with severe hypopla- tiveness of his approach. This procedure has since
sia of the thenar muscle, reconstruction with become a mainstay treatment for patients with
abductor digiti minimi is selected. In severe cases thumb hypoplasia, providing them with a func-
of Blauth IIIB or higher, index finger polliciza- tional, opposable thumb, and significantly
tion is generally recommended. improving hand function (Table 21.3).
a b c d
e f
Fig. 21.1 Pollicization surgery. (a, b) Skin incision design. (c) Index finger separated at growth plate and portion of
index finger removed. (d) Index finger relocated. (e, f) Post-operative view
Table 21.3 Modified Blauth Type Findings

classification of thumb hypoplasia Type I Minor generalized hypoplasia
Type II Absence of intrinsic thenar muscles
First web space narrowing
Ulnar collateral ligament insufficiency
Type III Similar findings as type II plus:
Extrinsic muscle and tendon abnormalities
Skeletal deficiency
A: Stable carpometacarpal joint
B: Unstable carpometacarpal joint (Manske)
C: Remnant head of metacarpal only (Buck-Gramcko)
Type IV Pouce flottant or floating thumb
Type V Aplasia
Littler said that “It is not the full length of the enables the child to have considerably better
thumb, nor its great strength and movement, but hand function than a four-fingered hand with no
rather its strategic position relative to the fingers thumb. Pollicization can greatly improve the
and the integrity of the specialized terminal pulp function of the thumb hypoplasia and is a major
tissue which determines the prehensile status.” A breakthrough in the history of treatment for
three-fingered hand with a thumb by pollicization CHD.
Buck-Gramcko D. Pollicization of the index finger. Method and results in aplasia and hypoplasia of the thumb. J
Bone Joint Surg Am. 1971;53:1605–17
Strengths • Large sample size (100 operations in 73 patients)
• Tips and pitfalls of pollicization are well described
Limitations • Level 4 case series

• It is difficult to evaluate the treatment outcome due to minor changes in the surgical method
during the 12 years of author’s surgical experience
Impact Author’s vast experience in 100 operations and his landmark work in 1971, which helped to
popularize the index finger for pollicization. Since the publication, the pollicization technique
has become a mainstay of treatment for patients with thumb hypoplasia
21.4 Prosthetics and prosthetics to fit the patient’s specific needs.

Three-dimensional printing technologies brought
Prosthetic technology has progressed remarkably significant developments, particularly in pros-
in the past few decades. However, overall rejec- thetics for children. Three-dimensional printing
tion rate of upper limb prosthetics in children is provides the ability to fabricate easily replaced,
still high—approximately 30–50% [14]. The rea- lightweight, low-cost, durable prosthetics that
sons for prosthetics rejection in children group can be modified to fit an individual child’s
are: (1) limited functionality, (2) discomfort, (3) physical growth as well as changing needs due to
too heavy, and (4) unattractive appearance [15]. If psychosocial development.
the prosthetic does not perform the necessary Another advancement of prosthetics in the
functions or meet the children’s needs, they may field of CHD is the myoelectric prosthetics. The
reject it. Children need prosthetics to help them pioneering work of Sörbye, a Swedish prosthe-
participate in activities. Children are more sensi- tist, in the 1970s greatly expanded the possibili-
tive to discomfort than adults, and if the prosthetic ties for fitting myoelectric prostheses in children,
is uncomfortable or heavy, the child may refuse to even at very young ages, the youngest being
wear it. Additionally, conventional prosthetics are 16 months of age [17]. Before this, it was gener-
expensive, body-powered prosthetics can range ally believed that children had to be much older
from $4000 to $10,000 and myoelectric prosthet- before they could successfully use such devices.
ics from $25,000 to $75,000 [16], and hard for His work challenged this notion. He showed that,
many patients to access via insurance. The aver- with the appropriate training and support, even
age lifespan of a prosthetic is approximately very young children could learn to use myoelec-
5 years, but in that time, children are continually tric prosthetics effectively. His approach involved
changing size due to physical growth that they not only fitting the prosthetics but also providing
need new prosthetics frequently. extensive support and training to help the child
One of the advancements of prosthetics in the learn how to use them. This was a major innova-
field of CHD is three-dimensional (3D) printing. tion in the field of prosthetics, as it expanded the
Three-dimensional printing technologies have population that could benefit from these devices
been applied in various medical fields over the and demonstrated the adaptability and resilience
last few decades and hand surgery is no excep- of young children. His work helped establish the
tion. Representative 3D technologies applied in principle that early fitting of prosthetics could
the field of hand surgery are customized implants provide significant benefits in terms of the child’s
that fit perfectly to a patient’s unique anatomy, development and quality of life. This early inter-
surgical guides to help with precise placement of vention approach set forth by Sörbye has since
implants or for cutting bones during surgery, been widely adopted and is considered a standard
training tools for surgeons and medical students, part of care for children with CHD.
Overall, 3D-printed prosthetics and myoelec- tion of these types of devices at present. It is
tric prosthetics are promising solutions for indi- important to work closely with a qualified health-
viduals with CHD, and they have the potential to care professional to ensure that the prosthetic
significantly improve their quality of life. device is properly designed and fitted to meet the
However, there is limited knowledge on the func- individual’s specific needs.
Sörbye R. Myoelectric prosthetic fitting in young children. Clin Orthop Relat Res. 1980;148:34–40
Strengths • First report of an attempt to apply myoelectric prosthetics to children with CHD
Limitations • Level 4 case series
• No endpoints have been set for evaluating outcomes
Impact Before this report, it was generally believed that children had to be much older before they could
successfully use myoelectric prosthetics. The author’s work greatly expanded the possibilities for
fitting myoelectric prosthetics in children and it was widely adopted and considered a standard part
of care for children with CHD
21.5 Digital Lengthening digital length can be obtained with intact sensa-
tion and retained mobility.
Lengthening of a digital ray by osteotomy and Ogino et al. reported distraction lengthening
gradual distraction was first reported by Matev of metacarpals for congenitally short digits in six
et al. [18] in 1967 to lengthen the thumb metacar- children using the Kessler’s two-stage procedure
pal bone with an external fixator in patients with [20]. The average gain in length was 16.3 mm,
traumatic amputation at the metacarpophalangeal range from 12 to 30 mm, and all patients reported
(MCP) joint. The Matev’s procedure requires an increase in function after digital lengthening.
osteotomy separating the affected digits and then Matev et al. reported distraction lengthening of
gradually distraction with external fixators. This metacarpals for congenitally short thumbs in
distraction process stimulates the growth of bone seven children using the single-stage procedure
and soft tissue, gradually lengthening the affected without secondary bone graft [21]. The average
digits over a period of several months. gain in length was between 25 and 38 mm. Seitz
Congenital shortening of the digits that can be et al. reported two case series of distraction
seen in congenital absent digits in radial, central, lengthening of proximal phalanx and/or metacar-
and ulnar deficiencies, symbrachydactyly, and pals for congenitally short digits in five children,
congenital constriction ring syndrome, is due to 11 digits, using single-stage procedure [22, 23].
the abnormal development of phalanges and/or The average gain in length was 27.7 mm, range
metacarpals. In 1977, Kessler et al. first applied from 20 to 35 mm. Complications include mild
digital lengthening to the treatment of patients syndactyly of web space in one and partial con-
with congenital shortening of the digits [19]. solidation which required bone graft in one digit.
Eleven children, ages 5 to 11 years, underwent Matsuno et al. reported distraction lengthening
distraction lengthening of one or more digits. for 23 digits in 15 children with congenital short-
Kessler’s procedure uses a two-stage procedure ening of the digits using the single-stage proce-
of distraction lengthening after osteotomy or dure [24]. The average distraction was 10 mm,
articular detachment of rudimentary metacarpal and the mean follow-up period was relatively
bones followed by iliac crest bone grafting and long; 59 months. They revealed that in the cases
internal fixation, which facilitates early union of older patients, the bone length changed little
and a relatively short period of immobilization. and the growth plates of these patients closed
The paper proved that distraction lengthening naturally soon after lengthening. On the other
was well tolerated by children and that increased hand, in the cases of younger patients less than
7 years old, the lengthened bones grew lengthening, one of the innovations in care of
continuously. CHD, is a useful and reliable treatment option for
The treatment of CHD is challenging because congenital shortening of the digits in order to
it is difficult to correct the hand for both complete achieve both functional and aesthetic improve-
function and satisfactory appearance. Distraction ment without the loss of other tissues.
Kessler I, Baruch A, Hecht O. Experience with distraction lengthening of digital rays in congenital anomalies. J
Hand Surg. 1977;2A:394–401
Strengths • This is the first paper that applied digital lengthening to the treatment of congenitally short
digits
Limitations • Small study groups (11 cases)
• The study did not quantify the amount lengthened, duration of lengthening, or incidence of
complications
Impact This is the first historical paper that applied distraction lengthening to congenitally short digits. The
paper proved that distraction lengthening was well tolerated by children and that increased digital
length could be obtained with intact sensation and retained mobility
21.6 Toe-to-Hand Transfer toes have been acceptable [30]. The transferred
toes usually have minimal active motion at the
The first toe-to-hand transfer was performed by distal interphalangeal (DIP) joint and extension
Nicoladoni et al. in 1990 [25]. This is a staged lag at the proximal interphalangeal (PIP) joint
toe-to-hand transplantation of the second toe to [31]. Van Holder et al. reported their 28 cases of
replace an amputated thumb by using the distant toe-to-hand transfers and presented a mean exten-
flap concept. Advances in microsurgery made sion lag of 20° and active compound flexion of
one stage toe-to-hand transfer possible, and it the PIP and DIP joints of 80° [32]. Foucher et al.
was first successfully performed on a monkey by reported their 65 toe-to-hand transfers with a
Buncke et al. [26] in 1966, and on a human by mean active range of motion of 38° and a mean
Cobbett et al. [27] in 1969. Since then, several extension lag of 25° [33]. In terms of sensory
authors have reported their series of toe-to-hand recovery, most patients ultimately can achieve a
transfers, mainly in adults for posttraumatic two-point discrimination of less than 10 mm
reconstruction. [33–36]. Although concerns about this technique
For CHD populations with digital deficien- for CHD are epiphyseal disruption and premature
cies, non-microsurgical techniques such as non- closure, Kay et al. revealed that the length of the
vascularized toe phalangeal bone grafts and transferred toes could reach between 70% and
second toe–metatarsal bone transfer have been 104% (mean, 91%) of the contralateral toe and
attempted; however, postoperative outcomes with normal growth [36].
were not predictable because of bone resorption Overall, toe-to-hand transfer has a long and
and insufficient growth of the transferred pha- successful history and is a major advance in the
lanx. The first microsurgical toe-to-hand transfer field of CHD treatment. However, toe-to-hand
for CHD was applied by O’Brien et al. [28] in transfer is technically demanding and has the risk
1978. After the first report, many surgeons have of failure, and results in unavoidable donor site
reported excellent results with toe-to-hand trans- morbidity. Recent advancement of bone and soft
fer for CHD. Good indications for toe-to-hand tissue engineering may overcome the drawbacks
transfer for CHD are congenital thumb absence, and expand operative indications for CHD in the
constriction ring syndrome, transverse arrest, future. Systematic evaluation of the outcomes of
longitudinal deficiency, and symbrachydactyly toe-to-hand transfer, not only functional out-
[29]. The survival rates are greater than 96% and comes but also including aesthetic and psychoso-
growth, function, and sensation of the transferred cial aspects, will be required.
O’Brien BM, Black MJ, Morrison WA, et al. Microvascular great toe transfer for congenital absence of the thumb.
Hand. 1978;10:113–24
Strengths • Detailed description of surgical technique of toe-to-hand transfer
• Proved possible to transfer toe for CHD with digital deficiencies
Limitations • Small study groups (two cases)
• Short follow-up (not described in detail, but identified until at least 1 year after surgery)
Impact This is the first historical paper that applied one-staged toe-to-hand transfer with microvascular
technique to CHD. Two cases of great toe transfer to replace hypoplastic thumb was presented
21.7 Expert Concluding Disclosure None of the authors has a financial interest to
declare in relation to the content of this article.
Commentary
Innovations in the treatment of CHD have been

guided by five landmark publications: (1) the
References
Swanson classification, (2) pollicization, (3) 1. Swanson AB. A classification for congenital mal-
prosthetics, (4) digital lengthening, and (5) toe- formations of the hand. N J Bull Acad Med.
to-hand transfer. These innovations have greatly 1964;10:166–9.
advanced treatment in the CHD field. 2. Swanson AB. A classification for congenital limb
malformations. J Hand Surg. 1976;1:8–22.
Conventional treatment for CHD has mainly 3. Oberg KC, Feenstra JM, Manske PR, Tonkin
focused on the recovery of hand function, but in MA. Developmental biology and classification of
the future, we believe that the focus will be not congenital anomalies of the hand and upper extrem-
only on the functional aspect but on aesthetic as ity. J Hand Surg. 2010;35A:2066–76.
4. Tonkin MA. Classification of congenital anoma-
well. Assessing the patient-reported outcome lies of the hand and upper limb. J Hand Surg.
measure can provide valuable information about 2017;42E:448–56.
hand function, mobility, and overall quality of 5. Ezaki M, Baek GH, Horii E, Hovius SE. IFSSH sci-
life. Valid and reliable assessment tools specifi- entific committee on congenital conditions. J Hand
Surg. 2014;39E:676–8.
cally designed for CHD in pediatric patients are 6. Bae DS, Canizares MF, Miller PE, Roberts S,
essential for accurate evaluation and tracking of Vuillermin C, Wall LB, Waters PM, Goldfarb
treatment outcomes. CA. Intraobserver and Interobserver reliability of the
In addition, it is highly likely that new treat- Oberg-Manske-Tonkin (OMT) classification: estab-
lishing a registry on congenital upper limb differ-
ments will be established as technology advances. ences. J Pediatr Orthop. 2018;38:69–74.
For example, advancements in neuro-prosthetics 7. Blauth W. The hypoplastic thumb. Arch Orthop
and brain-computer interfaces may enable direct Unfallchir. 1967;62:225–46.
communication between the brain and artificial 8. Manske PR, McCarroll HR. Reconstruction of the con-
genitally deficient thumb. Hand Clin. 1992;8:177–96.
limbs. This technology could potentially allow 9. Buck-Gramcko D. Congenital malformations of the
individuals with CHD to control their prosthetic hand and forearm. Chir Main. 2002;21:70–101.
hands with their thoughts, providing a more intu- 10. Gosset I. La pollicisation de l’index. J Chir.
itive and natural experience. Regenerative medi- 1949;65:403.
11. Hilgenfeldt O. Operativer Daumenersatz und
cine approaches, such as tissue engineering and Beseitigung von Greifstörungen bei Fingerverlusten.
stem cell therapies, may hold promise for the Stuttgart: Enke; 1950.
regeneration of damaged or missing tissues in 12. Buck-Gramcko D. Pollicization of the Index Finger.
CHD. Researchers are exploring the potential of Method and results in aplasia and hypoplasia of the
thumb. J Bone Joint Surg Am. 1971;53:1605–17.
using biocompatible scaffolds and growth factors 13. Buck-Gramcko D. Complications and bad results in
to stimulate tissue regeneration and promote pollicization of the index finger (in congenital cases).
functional hand development. Ann Chir Main Memb Super. 1991;10:506–12.
As our predecessors have created many inno- 14. Davids JR, Wagner LV, Meyer LC, Blackhurst
DW. Prosthetic management of children with unilat-
vations, we need to constantly strive to develop eral congenital below-elbow deficiency. J Bone Joint
better treatments for children with CHD who will Surg. 2006;88A:1294e–300e.
be born in the future.
15. Vasluian E, de Jong IG, Janssen WG, Poelma MJ, 25. Nicoladoni C. Editor. The classic: plastic surgery of
van Wijk I, Reinders-Messelink HA, van der Sluis the thumb and organic substitution of the fingertip
CK. Opinions of youngsters with congenital below- (anticheiroplastic surgery and finger plastic surgery).
elbow deficiency, and those of their parents and pro- By Carl Nicoladoni, 1900. Clin Orthop Relat Res.
fessionals concerning prosthetic use and rehabilitation 1985;195:3–6.
treatment. PLoS One. 2013;8:e67101. 26. Buncke HJ Jr, Buncke CM, Schulz WP. Immediate
16. Resnik L, Meucci MR, Lieberman-Klinger S, Fantini Nicoladoni procedure in the rhesus monkey, or hallux-
C, Kelty DL, Disla R, Sasson N. Advanced upper to-hand transplantation, utilising microminiature vas-
limb prosthetic devices: implications for upper limb cular anastomoses. Br J Plast Surg. 1966;19:332–7.
prosthetic rehabilitation. Arch Phys Med Rehabil. 27. Cobbett JR. Free digital transfer. Report of a case of
2012;93:710–7. transfer of a great toe to replace an amputated thumb.
17. Sörbye R. Myoelectric prosthetic fitting in young J Bone Joint Surg. 1969;51B:677–9.
children. Clin Orthop Relat Res. 1980;148:34–40. 28. O’Brien BM, Black MJ, Morrison WA, MacLeod
18. Matev IB. Gradual elongation of the first metacar- AM. Microvascular great toe transfer for congenital
pal as a method of thumb reconstruction (Lausanne, absence of the thumb. Hand. 1978;10:113–24.
1967). In: Stack HG Bolton H the second hand club. 29. Waljee JF, Chung KC. Toe-to-hand transfer: evolv-
London: British Society for Surgery of the Hand; ing indications and relevant outcomes. J Hand Surg.
1975. p. 431. 2013;38A:1431–4.
19. Kessler I, Baruch A, Hecht O. Experience with dis- 30. Jones NF, Hansen SL, Bates SJ. Toe-to-hand trans-
traction lengthening of digital rays in congenital fers for congenital anomalies of the hand. Hand Clin.
anomalies. J Hand Surg. 1977;2A:394–401. 2007;23:129–36.
20. Ogino T, Kato H, Ishii S, Usui M. Digital lengthen- 31. Eaton CJ, Lister GD. Toe transfer for congenital hand
ing in congenital hand deformities. J Hand Surg. defects. Microsurgery. 1991;12:186–95.
1994;19B:120–9. 32. Van Holder C, Giele H, Gilbert A. Double second toe
21. Matev IB. Thumb reconstruction in children through transfer in congenital hand anomalies. J Hand Surg.
metacarpal lengthening. Plast Reconstr Surg. 1999;24B:471–5.
1979;64:665–9. 33. Foucher G, Medina J, Navarro R, , Nagel D. Toe
22. Seitz WH Jr, Froimson AI. Callotasis lengthening in transfer in congenital hand malformations. J Reconstr
the upper extremity: indications, techniques, pitfalls. Microsurg 2001;17:1–7.
J Hand Surg. 1991;16A:932–9. 34. Nyarady J, Szekeres P, Vilmos Z. Toe-to-thumb trans-
23. Seitz WH Jr, Froimson AI. Digital lengthen- fer in congenital grade III thumb hypoplasia. J Hand
ing using the callotasis techniques. Orthopedics. Surg. 1983;8A:898–901.
1995;18:129–38. 35. May JW, Smith RJ, Peimer CA. Toe-to-hand free tis-
24. Matsuno T, Ishida O, Sunagawa T, Ichikawa M, Ikuta sue transfer for thumb construction with multiple digit
Y, Ochi M. Bone lengthening for congenital differ- aplasia. Plast Reconstr Surg. 1981;67:205–13.
ences of the hands and digits in children. J Hand Surg. 36. Kay SP, Wiberg M. Toe to hand transfer in chil-
2004;29A:712–9. dren. Part 1: technical aspects. J Hand Surg.
1996;21B:723–34.
Inflammatory and Degenerative
Disease of the Hand and Upper
22
Extremity
Krystle R. Tuaño, Jonathan Lans,

Ophelie Lavoie-Gagne, Justin J. Koh,
and Kyle R. Eberlin
Abstract Keywords
This chapter provides an overview of common Inflammatory · Degenerative · Autoimmune

causes and conditions associated with inflam- Tendinopathy · Rheumatoid · Arthritis · Gout
matory and degenerative diseases of the hand Pseudogout · Arthroplasty · Arthrodesis
and wrist. The topics discussed span several
decades in order to provide a comprehensive
pathoanatomical approach to this broad topic. The Five Most Impactful Papers
Throughout the synopsis, we reference emi- 1. Henderson ED, Lipscomb PR. Surgical
nent articles that have significantly contrib- treatment of rheumatoid hand. JAMA.
uted to our understanding of modern treatment 1961;175:431–6.
options and pathophysiology in autoimmune 2. Eaton RG, Littler JW. Ligament reconstruction
inflammatory conditions and degenerative for the painful thumb carpometacarpal joint. J
arthropathies. We believe that these five key Bone Joint Surg Am. 1973;55(8):1655–66.
articles have provided substantial influence in 3. Watson HK, Ballet FL. The SLAC wrist:
this topic and are therefore explored in detail. Scapholunate advanced collapse pattern
of degenerative arthritis. J Hand Surg Am.
1984;9(3):358–65.
4. Knirk JL, Jupiter JB. Intra-articular fractures
K. R. Tuaño · K. R. Eberlin (*) of the distal end of the radius in young adults.
Hand and Upper Extremity Service, Department of J Bone Joint Surg Am. 1986;68(5):647–59.
Orthopaedic Surgery, Massachusetts General 5. Carroll RE, Hill NA. Small joint arthrodesis
Hospital, Boston, MA, USA
in hand reconstruction. J Bone Joint Surg Am.
Division of Plastic and Reconstructive Surgery, 1969;51(6):1219–21.
Department of Surgery, Massachusetts General
Hospital, Boston, MA, USA
J. Lans · O. Lavoie-Gagne
Hand and Upper Extremity Service, Department of 22.1 Introduction
Orthopaedic Surgery, Massachusetts General
Hospital, Boston, MA, USA Inflammatory and degenerative diseases of the
J. J. Koh hand and upper extremity pose a unique chal-
Department of Orthopaedic Surgery, Cedars-Sinai lenge in the field of hand surgery as clinical pre-
Medical Center, Los Angeles, CA, USA sentation and severity can vary greatly, and
https://doi.org/10.1007/978-3-031-57132-9_22
216 K. R. Tuaño et al.
medical management of systemic disease has early contributions are well summarized in a his-
improved drastically in the last few decades. The torical review, paraphrased below, from
hand surgeon may be the first to suspect an Henderson and Lipscomb’s original article
inflammatory condition, or the first to predict Surgical Treatment of the Rheumatoid Hand,
degenerative disease by identifying predisposing which we selected as our first landmark paper
factors or injuries. As such, a thorough under- [14].
standing of these conditions is key for early diag- In RA tendon ruptures resulting from chronic
nosis, preventative care, and long-term tenosynovitis or attrition due to bony promi-
management. Patient outcomes are optimized nences may be the first presenting symptom to a
under the thoughtful and collaborative care of a hand surgeon. The first successful surgical repair
multidisciplinary team, often including rheuma- of a ruptured tendon (transfer of extensor carpi
tology, hand therapy, radiology, midlevel provid- radialis longus to the distal end of the ruptured
ers, and hand surgeons. extensor pollicis longus) was described in 1876
As medical management options continue to by Duplay [15], after detailing that spontaneous
expand to treat autoimmune diseases and related tendon rupture could occur in a diseased state
inflammatory conditions affecting the wrist and [13, 15]. This was further confirmed by McMaster
hand, so have surgical options for treatment of [16] and Mason [17] who described tendon
anatomic and biomechanical sequelae of long- pathology with regard to spontaneous rupture
standing systemic inflammatory diseases. These and surgical treatment [13]. Later, in 1948,
surgical advances have carried over into the man- Vaughan-Jackson [11] suggested that the primary
agement strategies for degenerative disease. In cause of tendon rupture in rheumatoid arthritis
the modern era, synergistic medical and muscu- (RA) was mechanical attrition due to bony spurs
loskeletal management has led to improved treat- from underlying rheumatoid joints [13]. This is
ment of chronic inflammatory diseases, preventing still referred to as Vaughan-Jackson syndrome,
possible debilitating sequelae which were more where there is an attritional tendon rupture of the
common in the past. Similarly, recognition of extensor digiti minimi (EDM) due to a prominent
pathologic biomechanical injury or imbalance distal ulnar head followed by further extensor
that may lead to chronic degenerative conditions tendon ruptures from ulnar to radial. In 1950,
has also contributed to improved preventative Kellgren and Ball [18] described fibroid degen-
care strategies and surgical techniques to opti- eration of collagen fibers within tendons as the
mize hand and wrist function. primary pathological change putting them at risk
for rupture [13]. Metacarpophalangeal joint
(MCP) deformities of the fingers and thumb due
22.2 Rheumatoid Arthritis to RA received attention in 1946 when Kestler
[19] described resection of the metacarpal heads
22.2.1 Historical Perspective and placement of mold arthroplasties [13].
Similar concepts were reported by Steindler [7]
Rheumatoid arthritis (RA) has played a central in a series of metacarpal head excisions in 1951,
role in the evolution of nonoperative, medical, and by Bunnell [2] who suggested arthroplasty of
and surgical management in hand surgery. the MCP joint and resection of the base of the
Understanding of the pathoanatomical changes involved metacarpal in 1955 [13]. The pathogen-
associated with this condition has advanced the esis of associated deformities and their treatment
knowledge of applied anatomy of the hand in an options were further described by Laine [8] and
attempt to recreate a balanced hand through oper- Brewerton [6] in 1957, helping our understand-
ative and non-operative treatment. [1–13] These ing today of how chronic synovitis weakens the
22 Inflammatory and Degenerative Disease of the Hand and Upper Extremity 217
ligamentous support leading to volar subluxation system [1, 32–38]. Once rheumatoid arthritis is
of the proximal phalanges and ulnar deviation of suspected, evaluation by a rheumatologist is
the fingers [13]. Similarly, in 1958, Riordan and advised to consider initiating medical manage-
Fowler [20] discussed the deforming pathologi- ment [1, 38–41].
cal factors and surgical procedures effective for
hands affected by RA [13]. Surgical rehabilita-
tion of the arthritic hand was reviewed by Flatt 22.2.3 Medical Management
[21] in 1959, with references to Straub and
Wilson [12], Littler, Fowler, Jacobs and col- Systemic treatment for patients with RA gener-
leagues [10], Howard [5], and Lipscomb in ally focuses on decreasing chronic inflammation
applying these to patients with RA and its various and providing structural protection of the affected
manifestations [13]. joints. Three main classes of medication are used
in RA, including corticosteroids, non-steroidal
anti-inflammatory drugs (NSAIDs), and disease-
22.2.2 Diagnosis modifying antirheumatic drugs (DMARDs) [1,
37]. Both NSAIDs and corticosteroids reduce
Early identification and treatment of RA remains acute inflammation, which can result in decreased
a diagnostic and long-term management chal- pain and improved function. However, neither
lenge since its characterization in the early 1900s alters the disease course nor prevents mechanical
and the American Rheumatism Association destruction. In general, corticosteroids can be
(ARA) proposed diagnostic criteria in 1956 [2, used chronically when NSAIDs are no longer
4, 12, 13, 22–27]. Ideally, medical management able to mitigate symptoms successfully or as an
is initiated prior to the development of erosive adjunct for symptomatic flares. Unfortunately,
changes seen in advanced disease. The differen- use of these medications is not without conse-
tial diagnosis of inflammatory arthropathies in quence, and both can cause significant systemic
the hand and wrist is broad, including infections side effects with short- and long-term use.
and non-rheumatoid arthropathies such as hemo- In contrast, DMARDs can effectively result in
chromatosis, gout, calcium pyrophosphate dihy- symptom relief, halt mechanical destruction, and
drate crystal deposition disease, and hepatitis improve radiographic and functional outcomes
C-related autoimmune disease [3, 4, 11, 22, [1, 32–34, 36, 37]. Therefore, their use has been
28–31]. The variable presentation of autoim- advocated early after diagnosis to reduce struc-
mune disease adds further complexity to estab- tural damage [32–34, 36, 37, 40]. While signifi-
lishing a diagnosis prior to initiating medical cant advances have been made in this class of
treatment that may eventually manifest as upper medication, they similarly impart a risk of side
extremity symptoms. In an effort to identify effects that are not negligible. For this reason,
patients with rheumatoid disease prior to the they are not routinely prescribed as an empiric
development of chronic pathologic changes, the treatment [1, 33, 35–41]. Rather, careful evalua-
American College of Rheumatology updated tion by a rheumatologist of prior immunosuppres-
diagnostic criteria in 2010 [32]. The criteria sion, immunosuppression- related complications,
includes consideration of synovitis symptoms, timeline of symptoms, treatment plan adherence,
type of joint involvement, serology (autoanti- and disease activity is completed prior to indicat-
bodies, such as rheumatoid factor (RF) and anti- ing a patient for immunomodulator initiation [1,
citrullinated protein antibody (ACPA), tested as 32, 36]. The balance of cost-effectiveness, safety,
anti-cyclic citrullinated peptide [anti-CCP]), and treatment efficacy is reassessed in conjunc-
acute phase reactants (erythrocyte sedimentation tion with patient functionality in order to deter-
rate [ESR], C-reactive protein [CRP]), and dura- mine the role of adjunctive nonoperative and
tion of symptoms within a scored classification operative treatment options.
22.2.4 Surgical Management plasty has been explored in the past, there is no
current evidence of superiority of a total wrist
Surgical management is often indicated in the set- arthrodesis [43]. To address pathology of the
ting of persistent synovitis causing ligamentous DRUJ, the Darrach and Sauvé-Kapandji proce-
incompetence of the hand or wrist in addition to dures are generally the procedure of choice.
integral and attritional damage to the tendons [37, In the fingers, a common intervention is a sili-
42]. In the wrist, distal radioulnar joint (DRUJ) cone prosthesis MCP arthroplasty, which is per-
instability leads to dorsal subluxation of the ulnar formed if degenerative changes are present or
head. Consequently, the ulnar head becomes promi- when there is chronic volar subluxation [37]. This
nent dorsally which can lead to EDM attrition and has been shown to improve range of motion and
additionally, ulnocarpal impaction occurs. Synovitis ulnar deviation of the fingers, with minimal effect
also affects the intrinsic intercarpal ligaments caus- on grip or pinch strength, with a 5-year survival of
ing carpal supination with ulnar carpal subluxation. 92% [44, 45]. At the time of surgery, ulnar sagittal
This is the result of incompetence of the scapholu- band contracture should often be released and the
nate ligament, leading to collapse of the radial car- radial sagittal bands imbricated. In scenarios
pus, and ulnar collateral ligament incompetence where the silicone implants are too large, a volar
leading to weakened support of the ulnar column. plate interposition arthroplasty can be considered
This wrist deformity subsequently leads to radial instead. Specifically for the small finger, the
deviation of the metacarpals changing the vector abductor digiti minimi should be released as this
pull of the extensor tendons leading to ulnar devia- adds to the ulnar deviation of the finger. In early
tion of the fingers. At the metacarpophalangeal and well-controlled disease, ulnar deviation can
joints, volar subluxation of the proximal phalanx, be addressed by cross-intrinsic transfers.
along with ulnar deviation of the fingers, occurs as Further surgical procedures such as tendon
the synovitis causes laxity of the soft tissues. As a transfers may be necessary to address tendon rup-
result, patients have difficulty extending the fingers, tures. A common tendon transfer is an extensor
and key-pinch strength is decreased. When consid- indicis proprius to ring and small finger extensor
ering operative procedures, surgeons must be aware digitorum communis (EDC) transfer. Other options
that RA patients have a poor soft tissue envelope include using the ring or middle finger flexor digi-
and are at an increased risk of infection. torum superficialis or flexor carpi radialis to address
The main goals of surgical management loss of MCP extension. In brief, the other finger
include deformity correction/prevention and pain joints may also be affected, resulting in Boutonniere
control in an attempt to maintain function. At the or Swan-neck deformities which can be challeng-
level of the wrist, treatments include total or lim- ing to address. Options include soft tissue proce-
ited wrist fusions, depending on the involvement dures (flexible Swan-neck/Boutonniere), implant
of the radiocarpal joints. Although wrist arthro- arthroplasty, or arthrodesis.
Henderson ED, Lipscomb PR. Surgical treatment of rheumatoid hand. JAMA. 1961;175:431–6
Strengths • Foundation of early treatment with emphasis on restoration of function elucidated
• Effective application of reconstructive techniques used in trauma used in prevention and
correction in RA
• Focus on careful patient selection with appropriate motivation and resources
• Emphasis on supplementary operative intervention rather than replacement of conservative
treatment measures
Limitations • Modern clinical application (prior to widespread use of early, systemic treatment, arthroplasty)
• Short-term follow-up
Impact Prior to the publication of this paper, the role of reconstructive surgery in RA was not yet
well-established. The included historical review details the contributions of some of the giants in
hand surgery and the application of techniques formerly used primarily in the trauma setting.
Despite short-term follow-up at the time of the paper’s publication, the reported form and function
were good, and these continue to be the foundation of surgical treatments for patients with RA and
inflammatory arthropathies today with the addition of systemic treatment.
22.3 Thumb Carpometacarpal selection of the second landmark paper by Eaton

Joint Arthritis and Littler, as detailed below.
In 1973, Eaton et al. described the pathophysi-
Osteoarthrosis or osteoarthritis is a common ology of thumb CMC arthritis and identified that
problem in the hand, with the joint between the creation of an orthogonal support to the joint
trapezium and base of the thumb being com- would yield much higher strength than even the
monly affected, second only in incidence to the strongest reinforcement within a single plane.
distal interphalangeal (DIP) joints [46, 47]. The They postulated that augmentation of the ana-
thumb carpometacarpal (CMC) joint’s mobility tomically weak radial aspect of the thumb CMC
due to its diarthrodial condylar anatomy puts it at joint, perpendicular to the stout volar ligament,
an increased risk for degenerative arthritis. The would allow for greater stability of the joint and
orthogonal position of the trapezium in relation thus relieve the symptoms of pain experienced
to the metacarpal allows for flexion–extension as due to hypermobility and consequential point
well as adduction–abduction. However, in rota- loading of the joint. After harvesting a strip of
tional motions such as opposition and pinch, the FCR at the proximal wrist crease, the tendon was
joint faces are no longer directly congruent and passed volar to dorsal through the first metacar-
stability of the joint relies on joint capsule tight- pal, which remains the basis of the modern day
ening and ligamentous constraints. Minimal lax- suspensionplasty technique. The tendon was then
ity of ligaments may allow for further incongruity tunneled deep to EPB dorsally, deep and proxi-
and even higher concentration of joint reactive mal to the APL insertion, and looped around the
forces onto the dorsoradial aspect of the trape- intact FCR then secured to the dorsoradial peri-
zium, eventually leading to degeneration with osteum of the first metacarpal. Their long-term
repetitive use. Attenuation of the volar ligament, results in a case series of eighteen patients with
described by Kaplan [48], Lanz and Wachsmuth stage one through three CMC arthritis were
[49], and Napier [50] may additionally lead to excellent. All patients experienced at partial relief
progressive metacarpal subluxation. of pain and weakness, with most rating their clin-
The exact understanding of why not all ical outcomes as excellent. [53]
patients with similar degrees of arthritis are This procedure went on to influence Burton
symptomatic is unclear. Pain and weakness of and Pellegrini [54] in their description of opera-
pinch and grip strength related to these condi- tive treatment for “advanced osteoarthritis of the
tions can be debilitating given the substantial thumb CMC joint,” involving resection of the tra-
contribution of the thumb to hand and overall pezium and base of the first metacarpal, with a
extremity function [47, 51]. Treatment of this stabilization procedure they termed the “flexor
condition in the modern era still includes nonop- carpi radialis sling suspension interposition.” [47,
erative treatment with lifestyle modifications, 52] Since then, there have been a multitude of
hand therapy, splinting, and corticosteroid injec- variations and modifications of this technique,
tion [47, 52]. However, these treatment modali- influenced by reconstruction or support of the
ties do not eliminate the mechanical problem or deep anterior oblique ligament. There has been
underlying disease process. The mainstay of continued development in the field, with interest
operative treatment involves a trapeziectomy, a in the role of arthroscopy [55–57], the use of
girdlestone of the CMC joint, with or without allograft interposition [58, 59], and a potential
suspensionplasty of the thumb. This leads to our role for denervation [60].
Eaton RG, Littler JW. Ligament reconstruction for the painful thumb carpometacarpal joint. J Bone Joint Surg Am.
1973;55(8):1655–66
Strengths • Foundation of the anatomic and biomechanical concepts of the thumb CMC joint
• Remains keystone description of radiographic staging for thumb CMC arthritis
• Initial surgical technique description for volar ligament reconstruction
• Retrospective cohort
Impact This article described the foundational radiographic classification of CMC arthritis and described one
of the first surgical techniques for treatment of symptomatic thumb CMC arthritis. Eaton and Littler’s
volar ligament reconstruction technique with FCR allograft has since evolved into the myriad of
techniques available in the modern day for treatment of CMC arthritis, including ligament
reconstruction with APL or palmaris longus, tendon interposition, and suspensionplasty with allograft,
or more recently, with suture anchors.
22.4 Small Joint Arthritis junction of the distal articular surface, which are
connected by hand with a small osteotome. The
Our third landmark paper by Carroll et al. [61] proximal condyle cartilage is removed and
addresses small joint arthrodesis in hand recon- shaped into a gently rounded spike. The “cone-
struction. Pathology that results in symptomatic shaped” defect then has the “spike” placed into it.
degenerative changes to the small joints, proxi- A K-wire is then drilled retrograde out through
mal interphalangeal (PIP) and distal interpha- the middle of the distal segment and a small awl
langeal (DIP) that cannot be anatomically hole is placed at the desired angle in the proximal
restored or corrected with arthroplasty is gener- spike to receive the K-wire. A single wire is used
ally treated with arthrodesis in a position of to allow final adjustment of rotation and
function. The principal indication for small joint impaction.
arthrodesis is degenerative or post-traumatic In their experience from 1952 to 1967, 635
arthritis [47]. Though there are many described MCP and interphalangeal joints were fused with
techniques for small joint arthrodesis [62–65], overall pseudarthrosis rate of 5%, and 2% with
the primary goal of any of these techniques, as exclusion of spastic paralysis patients. All
stated by Moberg [66], is to achieve a “solid, patients were followed for at least one year. There
painless arthrodesis in proper position in a rea- were four revisions required, all for rotational
sonable time.” [61] deformities, and all but four patients that required
Carroll et al. described a 15-year experience refusion for pseudarthrosis eventually developed
with Kirschner (K-wire) wire technique for bone union.
arthrodesis that affords both excellent bone-to- Replacement of arthritic proximal interpha-
bone contact and adjustment of the position in langeal (PIP) joints has been used since to poten-
three planes prior to final fixation. This was in tially avoid the functional impairment that is
contrast to “squaring off” the bone ends, which associated with fusion [25–27, 67]. Over the last
commits a single position after the initial cut is six decades, there have been varying designs and
made. Misjudgment of the angle can result in loss implants introduced and the consistent variety of
of critical apposition and unintentional shorten- devices on the market reflects the continued
ing of the affected digit. After a standard incision search for an ideal implant [67]. The longevity of
approach and resection of the collateral liga- the arthrodesis method described by Carroll et al.
ments, this technique instead recommends cre- serves as a testament to the reliability of the
ation of multiple awl holes at the osteocartilaginous technique.
Carroll RE, Hill NA. Small joint arthrodesis in hand reconstruction. J Bone Joint Surg Am. 1969;51(6):1219–21
Strengths • Large series
• Novel operative technique
• No direct comparison to other techniques of fixation
Impact Though digital K-wire arthrodesis operative techniques had already been previously reported [66],
this paper proposed a modification that is still in widespread use today. Results were overall good,
with low complication rates, even in the presence of comorbidities such as RA and spastic
paralysis, and prior to the common use of adjunctive systemic or focal treatment therapies.
22.5 Arthritis in Carpal Instability ther characterized in the influential work by

Watson and Ballet in 1984 [69]. This pattern of
Carpal instability can occur due to a variety of degeneration was termed the “SLAC” (scapholu-
wrist injuries. The degree of carpal instability nate advanced collapse) pattern [69]. Of 4000
that is associated with these injuries had not been radiographs reviewed, they identified 141 with
previously anatomically documented until it was unequivocal degenerative changes, of which 120
described by Mayfield et al. [68] in 1979. This had degenerative changes in the radioscaphoid or
paper clarified the nature of degenerative inter- lunocapitate articulations. Progression of joint
carpal and radiocarpal arthritis, highlighting the space narrowing, subchondral sclerosis, cystic
impact of limited options for reconstructive pro- changes, osteophyte development, and alteration
cedures. This is evident in the prolonged disabil- of normal anatomic contours was quantified.
ity experienced by many of these patients, who They noted patients with SLAC patterns of
are primarily young adults [68–70]. Clinical degeneration reliably developed a progression of
evaluation of suspected wrist osteoarthritis begins radioscaphoid arthritis at the radial styloid (stage
with a thorough evaluation of the patient’s his- I), followed by degeneration at the waist level of
tory in order to elicit underlying etiologies of the scaphoid and scaphoid facet (stage II), and
degeneration such as prior injuries and systemic finally degeneration at the capitolunate joint
causes of arthritis [71, 72]. Pain with radial devi- (stage III). Degenerative changes at the radiolu-
ation or tenderness to palpation over specific nate articulation were very rarely involved while
areas of the wrist, such as the scapholunate liga- “triscaphe” joint changes in the scaphoid, trape-
ment, the scaphotrapeziotrapezoid joint, or the zoid, and trapezium were involved in 14% of
radial border of the scaphoid can be the first signs cases. Similarly, scaphoid fractures and a resul-
of an early SLAC wrist [72]. Watson described a tant non-union can lead to a progressive form of
maneuver where a clunk is felt when the wrist is wrist arthritis, with the tip of the radial styloid
deviated from ulnar to radial and while applying initially involved, and eventual progression to
pressure over the scaphoid tubercle. Identification pancarpal arthritis. This has been termed the
of ligamentous injury is key as midcarpal insta- “SNAC” pattern (scaphoid nonunion advanced
bility leads to altered point pressures throughout collapse) [69, 74, 75].
the carpus and subsequent degeneration [73]. The operative technique described involved
Therefore, the seminal work by Watson and stabilization of the wrist with 0.045 K-wires,
Ballet was chosen as our fourth landmark paper. such that the lunate transmits the load of the
The sequence of degenerative changes seen in functioning hand through the preserved radiolu-
wrist osteoarthritis as a result of proximal carpal nate joint via a capitate–lunate arthrodesis, with
row instability due to changed biomechanics or without inclusion of the hamate and trique-
between the scaphoid, lunate, and radius was fur- trum. The scaphoid was then excised and replaced
with a silastic implant. Postoperative follow-up removal of the implant. The wrist flexion–exten-
was for an average of 24 months and no patients sion arc and radial-ulnar deviation showed
found it necessary to change vocations. marked improvement postoperatively.
Radiographic follow-up had no evidence of The impact of this paper was significant, and
degenerative changes in the radius-lunate joint or influenced the understanding and treatment of
other carpal joints that had not undergone carpal instability, degenerative wrist disease, and
arthrodesis. Two cases of postoperative dystro- posttraumatic arthritis. Advances in nonoperative
phy responded to a stress program, one non- management, surgical techniques, and treatment
union was successfully treated with repeat radial options were made possible by this impactful
bone grafting, and one silastic implant was dislo- work. Today, treatment algorithms are still based
cated, but replaced without subsequent issues. on the classification system that was originally
There was one deep infection that required described and its modifications.
Watson HK, Ballet FL. The SLAC wrist: Scapholunate advanced collapse pattern of degenerative arthritis. J Hand
Surg Am. 1984;9(3):358–65
Strengths • Large series
• Novel operative technique and anatomical description of wrist degenerative arthritis
• Single surgeon
Impact This paper characterized and established a pattern of sequential changes in degenerative wrist
arthritis with a classification system that is still in use today in determining treatment algorithms.
The proposed operative intervention described resulted in considerable improvement in wrist
flexion–extension and radial–ulnar deviation arcs. This led to the more widespread use,
advancement, and application of modern surgical techniques for treatment of degenerative wrist.
22.6 Posttraumatic Arthritis ther identified that anatomic reduction and main-
Following Distal Radius tenance of reduction of complex intra-articular
Fractures distal radius fractures led to better functional out-
comes and lower incidence of radiographic
Posttraumatic wrist arthritis is a known sequela osteoarthritis. This paper captures a chapter of
of distal radius fractures, either as a result of the history of hand surgery prior to the wide-
chronic carpal malalignment or intra-articular spread application of volar locked plating as a
incongruence leading to progressive chondroly- treatment option for distal radius fractures. While
sis and osteoarthritis. The management of distal the specific treatment modalities and fixation
radius fractures has evolved significantly over the options have changed, the core principles of
past several decades [76–81]. While many stud- achieving anatomic reduction with more rigid
ies have demonstrated that nonsurgical treatment fixation remain salient today.
of distal radius fractures in elderly patients con- This series identified 75 distal radius fractures
fers noninferior functional outcomes compared in 72 patients under the age of 40 who sustained
to surgical treatment [82–85], higher energy intra-articular fractures of the distal radius, with
intra-articular distal radius fractures in younger 43 fractures in 40 patients completing long-term
patients significantly increase the risk of develop- follow-up at an average of 6.7 years. These inju-
ing radiographic and clinically debilitating post- ries were largely as a result of high energy trauma
traumatic arthritis. This was characterized by with falls from substantial height, motor vehicle
Jupiter [70] in our fifth landmark paper that fur- accidents, and industrial accidents. These injuries
were treated variously with closed reduction and arbitrary cut-off made by the authors, but still
plaster cast immobilization, closed reduction and often cited in today’s literature as a benchmark for
pin fixation with plaster casting (“pins-in-plaster” articular reduction. By contrast, posttraumatic
construct), external fixation, and three patients arthrosis was limited to just 11% of patients who
with open reduction and internal fixation (prior to healed with a congruent joint surface.
the utilization of volar locked plating). Loss of Compared to previous studies, this paper cor-
reduction at final follow-up was more common roborated the impact of radiocarpal incongruence
for patients treated with closed reduction and on later posttraumatic arthritis associated with
casting alone compared to more rigid fixation more unstable fracture patterns (Frykman Type
options. At final follow-up, patients who went on VII and VIII) [86], but also highlighted the
to develop posttraumatic arthrosis (65%) demon- importance of restoration of articular congruence
strated worse functional outcomes. This was cor- in the management of intra-articular distal radius
related with “Failure to achieve or maintain fractures, particularly in a younger patient popu-
congruity of the articular surface of the distal part lation where both the time frame to develop and
of the radius until the time of union” and was par- cope with symptomatic posttraumatic radiocar-
ticularly identified in 91% of patients who had pal arthritis remain significant. More recent lit-
any articular incongruence and in all patients who erature has shown that these radiographic
had an incongruence of 2 mm or greater. However, parameters may not be as critical in patients
it is important to recall that this was a somewhat >60 years of age [82].
Knirk JL, Jupiter JB. Intra-articular fractures of the distal end of the radius in young adults. J Bone Joint Surg Am.
1986;68(5):647–59
Strengths • Long-term follow-up
• Both objective and patient-reported outcomes
Limitations • Retrospective
• Single-center
• Moderate sample size
Impact This paper, which focused on the effect of the articular surface of the radius on the development
of posttraumatic arthritis, highlighted the importance of anatomic reduction and rigid fixation in a
way that had not previously been described. Long follow-up after good anatomic reduction
revealed better motion compared to prior studies. This influenced future management of high
energy distal radius fractures in young patients, as internal fixation with volarlocked plating
became a standard treatment approach and with more common use of arthroscopic-assistance [78,
87, 88].
22.7 Expert Concluding arthropathies. This has benefited patients greatly

Commentary with advanced or end-stage disease becoming
less common.
Since the emergence of hand surgery as a spe- Interestingly, the principles of managing
cialty and its evolution, our understanding of the thumb CMC arthritis have not changed drasti-
pathophysiology of degenerative and inflamma- cally since Eaton and Littler’s description in their
tory arthropathies of the wrist has evolved sub- landmark paper from the 1970s [53]. More
stantially. The experience and knowledge gained recently, implants, such as suture buttons,
through treating RA has led to better understand- anchors, and/or high strength sutures have been
ing of hand and wrist anatomy and mechanics. implemented to suspend the thumb. However, the
However, the role of the hand surgeon has evolved principles remain the same, based on a founda-
with the advent of systemic treatment for RA, tion that was elucidated in the original descrip-
such as DMARDs, and other inflammatory tion of the technique.
In patients with carpal instability, Watson 5. Howard LD. Surgical treatment of rheumatic tenosy-
expounded upon the anatomical description detailed novitis. Am J Surg. 1955;89(6):1163–8.
6. Brewerton DA. Hand deformities in rheumatoid dis-
by Mayfield et al. [68] to inform patients regarding ease. Ann Rheum Dis. 1957;16(2):183–97.
anticipated progressive osteoarthritis associated 7. Steindler A. Arthritic deformities of the wrist and fin-
with certain injury patterns. Although the originally gers. J Bone Joint Surg Am. 1951;33-A(4):849–62.
described operative management with K-wire fixa- 8. Laine VAI, Sairanen E, Vainio K. Finger deformi-
ties caused by rheumatoid arthritis. J Bone Jt Surg.
tion has been modified to include ligamentous and 1957;39(3):527–33.
soft tissue reconstruction, the intent to halt progres- 9. Harris C, Riordan DC. Intrinsic contracture in the
sion of the disease process remains the same. By hand and its surgical treatment. J Bone Joint Surg Am.
elucidating the impact of ensuring and maintaining 1954;36-A(1):10–20.
10. Jacobs JH, Hess EV, Beswick IP. Rheumatoid arthri-
anatomic reduction in intra-articular distal radius tis presenting as tenosynovitis. J Bone Joint Surg Br.
fractures, Jupiter similarly established a precedent 1957;39-B(2):288–92.
for care and management of a common injury that 11. Vaughan-Jackson OJ. Rupture of extensor tendons by
can lead to the development of potentially clinically attrition at the inferior radio-ulnar joint. J Bone Joint
Surg Br. 1948;30-B(3):528–30.
impactful posttraumatic arthritis. 12. Straub LR, EHJ W. Spontaneous rupture of extensor
This is again exemplified in the treatment of tendons in the hand associated with rheumatoid arthri-
small joint arthritis. Despite innovations in tis. J Bone Joint Surg Am. 1956;38-A(6):1208–17.
implant design for arthrodesis and arthroplasty, 13. Henderson ED, Lipscomb PR. Surgical treatment of
rheumatoid hand. JAMA. 1961;175:431–6.
the fundamental principles of surgical technique 14. Lipscomb PR. Surgical treatment of rheumatoid
remain the same, as were described in the 1960s arthritis in the hands. Calif Med. 1971;114(1):27.
by Carroll and Hill [61]. 15. Duplay SE. Rupture sous-cutanee du tendon du long
This chapter serves to provide a focused his- extenseur du pouce de la main droite, au niveau de la
tabatiere anatomique. Bull Mém Société Chir Paris.
torical review of innovation and evolution in the 1876;2:788–91.
treatment of inflammatory and degenerative dis- 16. McMaster PE. Tendon and muscle ruptures: clini-
eases of the hand and wrist; the key principles cal and experimental studies on causes and loca-
continue to guide our contemporary treatment. tion of subcutaneous ruptures. J Bone Jt Surg.
1933;15:705–22.
17. Mason ML. Rupture of tendons of hand with study
Disclosures The authors have no disclosures related to of extensor tendon insertions in fingers. Surg Gynecol
this manuscript. Obstet. 1930;50:611–24.
18. Kellgren JH, Ball J. Tendon lesions in rheumatoid
arthritis. Ann Rheum Dis. 1950;9(1):48–65.
19. Kestler OC. Surgical procedure for painful arthritic
References hand. Bull Hosp Joint Dis. 1946;7:114–20.
20. Riordan DC, Fowler SB. Surgical treatment of rheu-
1. O’Shaughnessy MA, Kannas S, Ernste F, Rizzo matoid deformities of the hand, read before the joint
M. Team approach: role of medical and surgical meeting of the orthopaedic associations of the Eng-
Management in Rheumatoid Arthritis of the hand and lish-speaking world. Washington, DC; 1958.
wrist. JBJS Rev. 2019;7(8):e10. 21. Flatt AE. Surgical rehabilitation of the arthritic hand.
2. Bunnell S. Surgery of the rheumatic hand. J Bone Arthritis Rheum. 1959;2(3):278–83.
Joint Surg Am. 1955;37-A(4):759–66. 22. Bunnell S. Hand surgery. J Bone Joint Surg Am.
3. Pulvertaft RG. Tendon grafts for flexor tendon inju- 1947;29(3):824.
ries in the fingers and thumb. J Bone Joint Surg Br. 23. Arnett FC, Edworthy SM, Bloch DA, et al. The Amer-
1956;38-B(1):175–94. ican Rheumatism Association 1987 revised criteria
4. Platt H. POSTGRADUATE LECTURES ON for the classification of rheumatoid arthritis. Arthritis
ORTHOPEDIC DIAGNOSIS AND INDICA- Rheum. 1988;31(3):315–24.
TIONS. By Arthur Steindler, M.D., F.A.C.S. Profes- 24. Bennett GA, Cobb S, Jacox R, Jessar RA, Ropes
sor of Orthopedic surgery, State University of Iowa, MW. Proposed diagnostic criteria for rheumatoid
Iowa City, Iowa. Volume II. Section a: paralytic dis- arthritis. Bull Rheum Dis. 1956;7(4):121–4.
abilities. Section B: static disabilities. 10 x 7 in. Pp. 25. Flatt AE. Restoration of rheumatoid finger-joint func-
xiv+198, with 140 figures. Index. 1951. Springfield, tion: interim report on trial of prosthetic replacement.
Illinois: Charles C. Thomas, Publisher. Oxford: JBJS. 1961;43(5):753–74. https://journals.lww.com/
Blackwell scientific publications. Price 45s. J Bone jbjsjournal/Fulltext/1961/43050/Restoration_of_
Joint Surg Br. 1952;34-B(3):532. Rheumatoid_Finger_Joint_Function_.11.aspx.
26. Flatt AE. Restoration of rheumatoid finger-joint func- 44. Notermans BJW, Lans J, Arnold D, Jupiter JB,
tion. J Bone Joint Surg Am. 1963;45:1101–3. Chen NC. Factors associated with reoperation
27. Flatt AE. Prosthetic substitution for rheumatoid finger after silicone metacarpophalangeal joint arthro-
joints. Plast Reconstr Surg. 1967;40(6):565–70. plasty in patients with inflammatory arthritis. Hand.
28. Nalebuff EA. Surgery of systemic lupus erythematosus 2020;15(6):805–11.
arthritis of the hand. Hand Clin. 1996;12(3):591–602. 45. Waljee JF, Chung KC. Objective functional outcomes
29. Nalebuff EA, Patel MR. Flexor digitorum sub- and patient satisfaction after silicone metacarpopha-
limis transfer for multiple extensor tendon rup- langeal arthroplasty for rheumatoid arthritis. J Hand
tures in rheumatoid arthritis. Plast Reconstr Surg. Surg. 2012;37(1):47–54.
1973;52(5):530–3. 46. Haugen IK, Englund M, Aliabadi P, et al. Prevalence,
30. Gardenier J, Garg R, Mudgal C. Upper extremity incidence and progression of hand osteoarthritis in
tendon transfers: a brief review of history, common the general population: the Framingham osteoarthritis
applications, and technical tips. Indian J Plast Surg study. Ann Rheum Dis. 2011;70(9):1581–6.
Off Publ Assoc Plast Surg India. 2020;53(2):177–90. 47. Hunt TR, Wiesel SW. Operative techniques in
31. Lans J, Machol JA, Deml C, Chen NC, Jupiter hand, wrist, and elbow surgery. Wolters Klu-
JB. Nonrheumatoid arthritis of the hand. J Hand Surg. wer Health; 2016. https://books.google.com/
2018;43(1):61–7. books?id=qxxRCwAAQBAJ.
32. Aletaha D, Neogi T, Silman AJ, et al. 2010 rheu- 48. Kaplan EB. Functional and surgical anatomy of the
matoid arthritis classification criteria: an American hand. 2d ed. Lippincott; 1965.
College of Rheumatology/European league against 49. von Lanz T, Lang J, Wachsmuth W. Praktische
rheumatism collaborative initiative. Ann Rheum Dis. Anatomie: Ein Lehr- Und Hilfsbuch Der Anato-
2010;69(9):1580–8. mischen Grundlagen Ärztlichen Handelns.
33. Sudoł-Szopińska I, Teh J, Cotten A. Rheumatoid Springer-Verlag; 1959. https://books.google.com.gi/
hand and other hand-deforming rheumatic conditions. books?id=erenugEACAAJ
Semin Musculoskelet Radiol. 2021;25(02):232–45. 50. NAPIER JR. The form and function of the
34. Żelnio E, Taljanovic M, Mańczak M, Sudoł-Szopińska carpo-metacarpal joint of the thumb. J Anat.
I. Hand and wrist involvement in seropositive rheu- 1955;89(3):362–9.
matoid arthritis, seronegative rheumatoid arthritis, 51. Flatt AE. Our thumbs. Bayl Univ Med Cent Proc.
and psoriatic arthritis—the value of classic radiogra- 2002;15(4):380–7.
phy. J Clin Med. 2023;12(7):2622. 52. Wolfe SW, Pederson WC, Kozin SH, Cohen
35. Chim HW, Reese SK, Toomey SN, Moran SL. Update MS. Green’s operative hand surgery: Green’s
on the surgical treatment for rheumatoid arthri- operative hand surgery E-book. Elsevier Health
tis of the wrist and hand. J Hand Ther. 2014;27(2): Sciences; 2021. https://books.google.com/
134–42. books?id=IOVSEAAAQBAJ.
36. Thorsness RJ, Hammert WC. Perioperative Man- 53. Eaton RG, Littler JW. Ligament reconstruction for
agement of Rheumatoid Medications. J Hand Surg. the painful thumb carpometacarpal joint. J Bone Joint
2012;37(9):1928–31. Surg Am. 1973;55(8):1655–66.
37. Chung KC, Pushman AG. Current concepts in the 54. Burton RI, Pellegrini VD. Surgical management of
Management of the Rheumatoid Hand. J Hand Surg. basal joint arthritis of the thumb. Part II. Ligament
2011;36(4):736–47. reconstruction with tendon interposition arthroplast. J
38. Rizzo M, Cooney WP. Current concepts and Hand Surg. 1986;11(3):324–32.
treatment for the rheumatoid wrist. Hand Clin. 55. Barrera J, Yao J. Arthroscopic Management of Thumb
2011;27(1):57–72. Carpometacarpal Joint Arthritis and Pathology. Hand
39. Alderman AK, Chung KC, Kim HM, Fox DA, Ubel Clin. 2022;38(2):183–97.
PA. Effectiveness of rheumatoid hand surgery: con- 56. Huang SH, Chou SH, Lu CK, et al. Arthroscopic
trasting perceptions of hand surgeons and rheuma- partial Trapeziectomy for thumb carpometacarpal
tologists. J Hand Surg. 2003;28(1):3–11. joint osteoarthritis: 5-year follow-up. Orthopedics.
40. Chung KC, Kotsis SV. A 16-Year Journey in the Study 2022;45(3):e140–7.
of Rheumatoid Hand Disease. Plast Reconstr Surg. 57. Spielman AF, Sankaranarayanan S, Lessard AS. Joint
2017;140(1):109–15. preserving treatments for thumb CMC arthritis. Hand
41. Gogna R, Cheung G, Arundell M, Deighton C, Clin. 2022;38(2):169–81.
Lindau TR. Rheumatoid hand surgery: is there a 58. Adams JE. Does arthroscopic Débridement with or
decline? A 22-year population-based study. Hand. without interposition material address carpometacar-
2015;10(2):272–8. pal arthritis? Clin Orthop. 2014;472(4):1166–72.
42. Trieb K. Treatment of the wrist in rheumatoid arthri- 59. McCullough MC, Minasian R, Tanabe K, Rodriguez
tis. J Hand Surg. 2008;33(1):113–23. S, Kulber D. Functional outcomes for basilar joint
43. Cavaliere CM, Chung KC. A systematic review of arthroplasty with meniscus allograft compared with
total wrist arthroplasty compared with total wrist Trapeziectomy alone. Hand. 2023;18(1):89–97.
arthrodesis for rheumatoid arthritis. Plast Reconstr 60. Suresh V, Frost CM, Lifchez SD. Selective thumb
Surg. 2008;122(3):813–25. carpometacarpal joint denervation for painful arthri-
tis: follow-up of long-term clinical outcomes. J Hand 77. Huetteman HE, Shauver MJ, Malay S, Chung TT,
Surg Glob Online. 2023;5(1):108–11. Chung KC. Variation in the treatment of distal radius
61. Carroll RE, Hill NA. Small joint arthrodesis in hand fractures in the United States: 2010 to 2015. Plast
reconstruction. J Bone Jt Surg. 1969;51(6):1219–21. Reconstr Surg. 2019;143(1):159–67.
62. Capo JT, Melamed E, Shamian B, et al. Biome- 78. Shihab Z, Sivakumar B, Graham D, Del Piñal F. Out-
chanical evaluation of 5 fixation devices for proxi- comes of arthroscopic-assisted distal radius frac-
mal interphalangeal joint arthrodesis. J Hand Surg. ture volar plating: a meta-analysis. J Hand Surg.
2014;39(10):1971–7. 2022;47(4):330–340.e1.
63. Engel J, Tsur H, Farin I. A comparison between 79. Del Piñal F, Moraleda E, Rúas JS, De Piero GH, Cer-
K-wire and compression screw fixation after arthode- ezal L. Minimally invasive fixation of fractures of the
sis of the distal interphalangeal joint. Plast Reconstr phalanges and metacarpals with intramedullary can-
Surg. 1977;60(4):611–4. nulated headless compression screws. J Hand Surg.
64. Pellegrini VD, Burton RI. Osteoarthritis of the proxi- 2015;40(4):692–700.
mal interphalangeal joint of the hand: arthroplasty or 80. Chen NC, Jupiter JB. Management of distal radial
fusion? J Hand Surg. 1990;15(2):194–209. fractures. J Bone Jt Surg. 2007;89(9):2051–62.
65. Allende BT, Engelem JC. Tension-band arthrodesis in 81. Orbay JL, Fernandez DL. Volar fixation for dorsally
the finger joints. J Hand Surg. 1980;5(3):269–71. displaced fractures of the distal radius: a preliminary
66. Moberg E, Henrikson B. Technique for digital report. J Hand Surg. 2002;27(2):205–15.
arthrodesis. A study of 150 cases. Acta Chir Scand. 82. Lawson A, Naylor J, Mittal R, Kale M, Xuan W, Har-
1960;118:331–8. ris IA. Does radiographic alignment correlate with
67. Adams J, Ryall C, Pandyan A, et al. Proximal inter- patient-reported functional outcomes and Posttreat-
phalangeal joint replacement in patients with arthritis ment complications in older patients treated for wrist
of the hand: a meta-analysis. J Bone Joint Surg Br. fractures? J Hand Surg. 2023;48(6):533–43.
2012;94-B(10):1305–12. 83. Chung KC, Kim HM, Malay S, Shauver MJ. The wrist
68. Mayfield JK, Johnson RP, Kilcoyne RK. Carpal dis- and radius injury surgical trial: 12-month outcomes
locations: Pathomechanics and progressive perilunar from a multicenter international randomized clinical
instability. J Hand Surg. 1980;5(3):226–41. trial. Plast Reconstr Surg. 2020;145(6):1054e–66e.
69. Watson HK, Ballet FL. The SLAC wrist: scapholu- 84. Südow H, Severin S, Wilcke M, Saving J, Skölden-
nate advanced collapse pattern of degenerative arthri- berg O, Navarro CM. Non-operative treatment or
tis. J Hand Surg. 1984;9(3):358–65. volar locking plate fixation for dorsally displaced dis-
70. Knirk JL, Jupiter JB. Intra-articular fractures of the tal radius fractures in patients over 70 years—a three
distal end of the radius in young adults. J Bone Joint year follow-up of a randomized controlled trial. BMC
Surg Am. 1986;68(5):647–59. Musculoskelet Disord. 2022;23(1):447.
71. Laulan J, Marteau E, Bacle G. Wrist osteoarthritis. 85. Chung KC, Cho HE, Kim Y, Kim HM, Shauver MJ,
Orthop Traumatol Surg Res. 2015;101(1):S1–9. for the WRIST Group. Assessment of anatomic res-
72. Peterson B, Szabo RM. Carpal Osteoarthrosis. Hand toration of distal radius fractures among older adults:
Clin. 2006;22(4):517–28. a secondary analysis of a randomized clinical trial.
73. Schmitt R, Hesse N, Goehtz F, Prommersberger JAMA Netw Open. 2020;3(1):e1919433.
KJ, De Jonge M, Grunz JP. Carpal Instability: 86. Frykman G. Fracture of the distal radius including
I Pathoanatomy. Semin Musculoskelet Radiol. sequelae-shoulder–Handfinger syndrome, distur-
2021;25(02):191–202. bance in the distal radio-ulnar joint and impairment
74. Talwalkar SC, Hayton MJ, Stanley JK. Wrist Osteoar- of nerve function: a clinical and experimental study.
thritis. Scand J Surg. 2008;97(4):305–9. Acta Orthop Scand. 1967;38(sup108):1–61.
75. Grunz JP, Gietzen CH, Christopoulos G, et al. 87. Kastenberger T, Kaiser P, Schmidle G, Schwendinger
Osteoarthritis of the wrist: pathology, radiol- P, Gabl M, Arora R. Arthroscopic assisted treatment
ogy, and treatment. Semin Musculoskelet Radiol. of distal radius fractures and concomitant injuries.
2021;25(02):294–303. Arch Orthop Trauma Surg. 2020;140(5):623–38.
76. Garg R, Mudgal CS. When a volar locking plate is not 88. Del Piñal F. Technical tips for (dry) arthroscopic
the right choice in fractures of the distal radius: case reduction and internal fixation of distal radius frac-
based technical considerations. J Clin Orthop Trauma. tures. J Hand Surg. 2011;36(10):1694–705.
2020;11(4):542–53.
Part V
Nerve Surgery
Landmark Studies in Nerve
Surgery
23
Jenna-Lynn Senger, Kitty Y Wu,
Amy Moore, and Susan E. Mackinnon
Abstract • The third study involves the quantification of

functional motoneurons required for meaning-
This chapter describes five landmark studies
ful recovery. Identification that only 20% of
that have played a pivotal role in the conceptu-
motoneurons are necessary for motor function
alization, investigation, and application of
suggested that fascicles could be safely taken
nerve transfers as a surgical technique aimed
from healthy nerves and only a limited number
at restoring function following peripheral
of axons are required for target reinnervation.
nerve injuries.
• The fourth study investigates the topographi-
cal arrangement of nerve fascicles, uncovering
• The first study explores the development of
the intricate organization and connectivity
Green Fluorescent Protein (GFP) as a vital
within peripheral nerves. This knowledge
tool for neuronal labeling and tracking. GFP
facilitated precise targeting for identifying
revolutionized the field by enabling research-
donor and recipient fascicles.
ers to visualize the regrowth and reinnervation
• The final study explores the clinical transla-
of nerves during early animal models of distal
tion of distal nerve transfers. By examining
nerve transfers, providing valuable insights
the outcomes of distal nerve transfer surgeries
into nerve regeneration and functional
in a clinical setting, researchers provided valu-
recovery.
able evidence of its efficacy and applicability
• The second study focuses on retrograde label-
in real-world scenarios.
ing techniques. The ability to map connec-
tions between distal nerves and proximal
These five landmark studies paved the way for
targets provided essential guidance to evaluat-
advanced surgical techniques, better patient out-
ing regeneration through nerve transfers.
comes, and the widespread adoption of nerve
transfers as a valuable treatment modality.
J.-L. Senger A. Moore

Division of Plastic Surgery, Vancouver General Department of Plastic and Reconstructive Surgery,
Hospital, Vancouver, BC, Canada The Ohio State University, Columbus, OH, USA
K. Y. Wu S. E. Mackinnon (*)
Division of Plastic Surgery, Mayo Clinic, Rochester, Division of Plastic and Reconstructive Surgery,
MN, USA St. Louis, MO, USA
https://doi.org/10.1007/978-3-031-57132-9_23
230 J.-L. Senger et al.
The Five Most Impactful Papers nerve anatomy and physiology, with significant
1. Chalfie M, Tu Y, Euskirchen G, Ward WW, advancements in clinical care. Microscopy
Prasher DC. Green fluorescent protein as evolved to allow for the visualization of nerves,
a marker for gene expression. Science. leading to landmark discoveries by neuroscien-
1994;263:802–5. tists such as Waller, Ranvier, Cahal, Golgi, and
2. Brushart TME, Seiler WA. Selective reinner- Cruikshank. These giants in nerve science made
vation of distal motor stumps by peripheral significant strides in establishing the fundamen-
motor axons. Exp Neurol. 1987;97:289–300. tals of the nerve response to injury and regenera-
3. Gordon T, Yang JF, Ayer K, Stein RB, Tyreman tion. In addition to a time of scientific discovery,
N. Recovery potential of muscle after partial this period also encompassed the American Civil
denervation: a comparison between rats and War and the first and second World Wars.
humans. Brain Res Bull. 1993;30:477–82. Hundreds of thousands of wounded soldiers pro-
4. Jabaley ME, Wallace WH, Heckler FR. vided surgeons with an unprecedent number of
Internal topography of major nerves of the traumatic wounds, including peripheral nerve
forearm and hand: a current view. J Hand injuries. Surgeons soon recognized the unsatis-
Surg. 1980;5(1):1–18. factory outcomes of non-operative management
5. Brandt KE, Mackinnon SE. A technique strategies, leading to an era of innovation in
for maximizing biceps recovery in bra- peripheral nerve reconstruction [1]. By the end of
chial plexus reconstruction. J Hand Surg. the second world war, surgical techniques for pri-
1993;18A:726–33. mary nerve coaptations and reconstructive tech-
niques such as autologous nerve grafting, tendon
transfers, limb shortening, and preliminary nerve
23.1 Introduction transfers were well described [6].
Today, nerve surgery is a rapidly expanding
Nerve surgery has a rich history spanning centu- field, built upon a foundation of innovation in
ries of medical advancements. Dating back to both basic and clinical science research.
ancient Greece, Hippocrates and Galen believed Numerous neuroscientists have contributed to
that injured nerves were irreparable and that revolutionizing our understanding of the anatomy
attempted repair would lead to “unbearable pain, and physiology of peripheral nerve regeneration
spasms, and a cruel death” [1]. Treatment for and repair. This led to the emergence of novel
nerve injuries consisted of topical application of surgical techniques to address innate challenges
herbs, heat, and even ground earthworms [2]. Not in the length and speed of regeneration.
all ancient healers, however, agreed with these Interestingly many of the surgical techniques
early philosophies. Some of the first nerve repairs described in past decades find their roots in anti-
can be traced to Paulus Aeginatus (626–696 AD) quated textbooks. First descriptions of nerve
who approximated nerve endings with “aggluti- crossing techniques, the ancestors of the modern
natives,” and Rhazes (850–932 AD) who per- distal nerve transfer, date as far back as Woolsey’s
formed suture repair [3]. Throughout the description of end-to-end and end-to-side nerve
following decades, reports of nerve coaptations transfers in 1907 [7]. However, it was not until
were published. In 1608, the first technical recently that distal nerve transfers have become
description of how to suture a transected nerve more widely investigated and incorporated into
was reported by Gabriele Ferrara [4]. Despite clinical practice. By redirecting functional nerves
these early attempts at nerve coaptation, the field to the injured area, distal nerve transfers facilitate
of nerve repair and reconstruction failed to gain nerve regeneration and promote earlier interven-
traction through to the early 1800s, as it was tion. This offers a valuable alternative to tradi-
commonly accepted that nerve function would tional methods and enhances the chances of
spontaneously recover [5]. functional recovery. In this chapter, we describe
The mid-1800s to 1900s marked a time of five landmark studies that led to the development
considerable growth in our understanding of both and clinical translation of distal nerve transfers.
23 Landmark Studies in Nerve Surgery 231
23.1.1 Discovery of Green Fluorescent

Protein (GFP)
Chalfie M, Tu Y, Euskirchen G, Ward WW, Prasher DC. Green fluorescent protein as a marker for gene expression.
Science. 1994;263:802–5
Strengths • First study to demonstrate GFP labeling of specific cells
• Effectiveness of GFP demonstrated in both prokaryotic and eukaryotic organisms
• Fluorescence requires only exposure to UV light, allowing for in vivo visualization of target
tissue
Limitations • Study limited to very simple organisms
• Initial GFP-construct produced relatively weak fluorescence. Later, modifications were required
to improve brightness and stability
• Did not address auto-fluorescence, which can interfere with imaging
Impact This landmark paper was one in a series of studies that described, for the first time, GFP as a
biological tool for imaging structures and tracking cells. Within the field of neurosciences, GFP is
an invaluable tool for studying development, structure, and regeneration of peripheral nerves by
visualizing and tracking specific nerve cells and their regenerating processes with unparalleled
precision
Green fluorescent protein (GFP) was first iso- cific promoters and gene sequences of interest in
lated in the 1960s by Dr. Osamu Shimomura, C. elegans and E. coli. Authors observed that GFP
PhD, a Japanese chemist and marine biologist. expression emitted green fluorescence in the tar-
Recognizing the scientific potential of harnessing get cells, allowing for direct visualization of gene
the natural bioluminescence properties of the expression. Of particular interest, the first pro-
Aequorea victoia jellyfish, Shimomura collected moter targeted in the nematode model was the
thousands of these species and extracted a protein mec-7 gene, which encodes for beta-tubulin. GFP
termed aequorin. When aequorin is combined was therefore expressed in neuronal cell bodies of
with calcium, it emits blue luminescence. Though embryonically derived touch receptor neurons,
his initial manuscript focused on aequorin, emis- thus establishing immediately at its conception
sion of a concurrent green fluorescence was also the importance of GFP in advancing the field of
described [8]. The link between these two phe- neuroscience. Further work by Dr. Roger Tsien
nomena would later be described as a chromo- altering the amino acid composition of the peptide
phore of the GFP protein that absorbs the blue enhanced the brightness of the fluorescence, fine-
light to cause green fluorescence. Thirty years tuned the color emission, and stabilized the pro-
after Shimomura’s initial protein extraction, Dr. tein [11, 12]. These pioneering studies precipitated
Douglas Prasher first sequenced the GFP gene profound developments in neurosciences, genet-
[9]; however, due to a perceived lack of relevance ics, biochemistry, proteomics, and molecular,
to society, Dr. Prasher’s funding was not renewed developmental, and cellular biology. This signifi-
and he could no longer support his research. He cant, widespread impact of GFP was recognized
distributed the cDNA to other interested labora- by a Nobel Prize in Chemistry awarded to
tories prior to pursuing other interests. Shimomura, Chalfie, and Tsien in 2008.
One such laboratory was that of Dr. Martin Prior to the discovery of GFP, evaluation of
Chalfie. In 1994, his study titled “Green fluores- neural tissue necessitated labor-intensive, often
cent protein as a marker for gene expression” [10] destructive techniques to visualize and study
was the first to introduce GFP as a tool for visual- axons and their cell bodies. GFP transgenic mod-
izing gene expression in living organisms. In this els allowed, for the first time, a non-invasive cell-
milestone study, the GFP gene was fused to spe- specific technique for analyzing the growth,
development, structure, and regeneration of of neuromuscular junctions [13]. As such,

nerves in living organisms. The ability to selec- researchers can directly assess the effectiveness of
tively target GFP expression to specific cell popu- surgical techniques and evaluate the integrity and
lations allowed differentiation between cellular functionality of motor and sensory targets on a
population (motoneurons, sensory nerves, glia, cellular level. The further development of a novel
immune cells) and tracking regenerating axons to thy1-GFP transgenic rat overcame the challenges
trace pathways of growth. This allowed for direct of small caliber nerves and limitations in nerve
visualization of regenerating axons, synapse for- gap lengths in mice, providing a powerful new
mation at the target tissue, monitoring axonal model for hindlimb studies of nerve regeneration
transportation, and evaluation of the glial [14]. Together, this knowledge has contributed to
response. GFP labeling of motor axons and con- the development of surgical techniques and peri-
current staining of post-synaptic membranes pro- operative strategies aimed at promoting nerve
vided the ability to directly visualize synapse regeneration for patients undergoing nerve
formation and the development and regeneration reconstruction.
23.1.2 Retrograde Labeling

Brushart TME, Seiler WA. Selective reinnervation of distal motor stumps by peripheral motor axons. Exp Neurol.
1987;97:289–300
Strengths • Eloquent, well-designed surgical model and methods of assessment
• Controls confirm HRP is reliably confined to the intended pathway
• Evaluated numerous outcomes (microarchitecture, HRP retrograde labeling, myelination) to
define fiber-type
Limitations • HRP is less sensitive/specific than modern retrograde tracers
• Only assessed motor nerve preferential regeneration (not sensory)
Impact In addition to providing early evidence of preferential motor reinnervation, this landmark study
establishes retrograde tracing as an effective tool to visually assess regeneration outcomes
following nerve injury. Retrograde labeling has become an invaluable tool for tracing nerve
pathways, assessing regeneration specificity, discriminating between sensory and motor axons, and
evaluating regenerative potential
Retrograde tracing, a technique in which a that the HRP had been retrogradely transported
label is applied to distal nerve/tissue and trans- from its distal site of injection. This ground-
ported proximally toward the cell body, is an breaking technique allowed, for the first time, a
important technique for mapping neural circuits method of visually identifying the innervating
and studying neural connections. The first retro- neuronal cell bodies of distal targets and for map-
grade tracer described was horseradish peroxi- ping neural circuits.
dase (HRP). In a series of studies by Kristensson One of the first researchers to harness the
and Olsson in the early 1970s, [15–17] distal tar- power of retrograde labeling to assess the speci-
gets, including the tongue (hypoglossal nerve) ficity of nerve regeneration was Dr. Thomas
and the gastrocnemius muscle (tibial nerve) were Brushart. In this landmark paper, [18] the motor
injected with HRP. Twenty-four hours later, the and sensory branches of the femoral nerve were
brain (hypoglossal nerve model) or spinal cord transected proximally. The proximal stump of the
(tibial nerve model) was processed in hydrogen motor branch was sutured into a Y-shaped sili-
peroxidase and diaminobenzidine, chemicals that cone tube and the distal stumps of the motor and
react with the peroxidase to turn the labeled tis- sensory branches were sutured to the other two
sue brown. Authors showed that by using light arms of the silicone tubing, maintaining a gap
microscopy, the marker could be visually identi- between nerves within the tubing. Two months
fied within the neuronal cell bodies, supporting later, either the distal sensory or the distal motor
branch was severed, and that nerve end bathed in

HRP. After 48 h, the lumbar spinal cord was har-
vested and processed for HRP within the motor
cell bodies. By tracing axons proximally from
either the motor or the sensory femoral nerve
branches, Brushart could determine what number
of axons within the individual nerve branches
were derived from the ventral horn of the spinal
cord, and thus motoneurons; he could thus deter-
mine whether motoneurons were regenerating
down the motor (correct) or the sensory (incor-
rect) pathways [18]. His results concluded that
motoneurons will preferentially regenerate down
the motor branch, a process termed ‘preferential
motor reinnervation’ (PMR). A series of subse-
quent studies investigating PMR all used HRP Fig. 23.1 Retrograde labeling with Fluorogold (FG).
retrograde labeling, further establishing the util- Spinal cord sections with FG retrograde labeling of motor
ity of this technique for evaluating the specificity neurons using the silicone cap technique (CAP) as com-
pared to the standard well technique (WELL), demon-
of nerve regeneration [19–22]. strating comparable intensity. In the silicone cap
Since these landmark studies, techniques for technique, the nerve stump is placed within a cap filled
retrograde labeling have expanded beyond with FG crystals and secured with fibrin glue. Labeling
HRP. The discovery of fluorescent molecules, in intensity between the two techniques was similar for
motor neurons but more intense for sensory neurons.
a similar method as described above, provided a (Reproduced with permission from [23])
novel agent for retrograde labeling that, when
compared to HRP, is less labor-intensive or dam- length of individual axons proximally to their cell
aging to the tissue, with a faster transport time, bodies using a highly specific fluorescent marker
greater resolution, and improved selectivity. The provided a powerful technique for axonal tracing
silicone cap retrograde labeling technique, devel- that, in the first distal nerve transfers, would be
oped by Dr. Thomas Brushart, MD, improved imperative in demonstrating the successful regen-
labeling efficiency and intensity of sensory neu- eration from the proximal stump of one nerve
rons [23] (Fig. 23.1). The ability to trace the into the distal stump of another.
23.1.3 Motor Nerve Sprouting

Gordon T, Yang JF, Ayer K, Stein RB, Tyreman N. Recovery potential of muscle after partial denervation: a
comparison between rats and humans. Brain Res Bull. 1993;30:477–82
Strengths • Includes both human and animal models
• Animal study included two established models of partial denervation: Ventral root injury and
spinal cord injury
• Elegant study design with numerous outcomes assessed (electrophysiology, twitch force,
tetanic force, muscle immunohistochemistry)
Limitations • Small sample size (11 humans, number of animals not reported)
• Limited to a single (and different) muscle evaluated in the human vs. animal cohorts
• Different methods of assessment between the human and the animal cohorts
Impact This landmark study was the first to quantify the minimum percentage of axons required to
innervate a muscle, revealing the extent of the innate plasticity possible in motor reinnervation.
This knowledge was fundamental to the development of the distal nerve transfer. Further, it
provided early evidence that spinal cord injury does not preclude motoneurons below the injury
site from enlarging, which would be fundamental for the use of nerve transfers in the spinal cord
injury population
The motor response to partial or complete the total number of motor units are required to ade-
denervation has long been an area of interest and quately power the target muscle. This finding was a
investigation. Partial motor denervation triggers an key observation in the development of d istal nerve
adaptive process in which the surviving motor transfers. These conclusions provided evidence
units expand and collateral sprouting occurs. that (a) donor nerve fascicles could be harvested
Through a complex cascade of molecular and cel- from neurologically intact, functioning muscle
lular events that still remains to be elucidated, new without compromising strength or downgrading
nerve connections are recruited and communica- function, and (b) only a small number of regenerat-
tion with denervated muscle fibers is re-established. ing axons successfully reinnervating neuromuscu-
The foundations of this process were first described lar junctions should be necessary to provide
in the 1950s, [24–26] but investigations continued. adequate innervation to restore function. Based on
McComas et al. found remarkable functional com- the results of this study, it therefore was proposed
pensation in patients with chronic motor neuron that a single fascicle could be safely harvested from
diseases, where partially denervated muscles an otherwise neurologically intact muscle and
would exert twitch tensions within the normal could be used to reinnervate a denervated motor
range, until fewer than 10% motor axons were targeted with minimal to no donor site morbidity,
remaining [27]. Subsequent research confirmed and a possibility of adequate reinnervation to sup-
similar processes in other animal and human mod- port functional recovery.
els, while garnering mechanistic insights [28, 29]. A second important conclusion from this
This 1993 landmark study by Dr. Tessa Gordon, study was that interruption of descending input
PhD, was the first to quantify the extent of compen- does not preclude motor reinnervation and
sation possible in both rodent and human models of enlargement of motor units originating from
partial denervation injuries. This study included a below the level of spinal cord injury. Animals
cohort of patients with spinal cord injuries and a treated with transection of T12 and a partial
cohort of rodents who underwent sectioning of the denervation injury had similar motor unit expan-
L4 ventral root or a T12 transection. In both humans sion and twitch force as animals with an isolated
and animals, motor unit numbers were quantified denervation (L4 ventral root) injury. These obser-
and found to enlarge corresponding to the degree of vations provided early evidence supporting the
denervation. Results showed that a single motor use of distal nerve transfers in patients with spi-
unit can enlarge up to five times their original size, nal cord injury, suggesting the possibility of suc-
compensating for up to 80% motoneuron loss. This cessful motor unit enlargement and thus greater
provided evidence that only a small proportion of function despite a paucity of descending input.
23.1.4 Understanding Intraneural Topography

Jabaley ME, Wallace WH, Heckler FR. Internal topography of major nerves of the forearm and hand: a current view.
J Hand Surg. 1980;5(1):1–18
Strengths • Detailed examination of the median, ulnar, and radial nerves in the forearm based on serial
sections and microscopic interfascicular dissections
• Figure drawings of the feasible extraneural and intraneural dissection distances for each motor
branch of the median, ulnar, and radial nerves
Limitations • Serial sections and microscopic histology only performed for the median nerve
• Proximal extent of dissection was 12 cm above the medial epicondyle so descriptions of
intraneural topography may apply only within the forearm
Impact This landmark paper detailed the consistent and organized intraneural topography of major nerves in
the forearm, allowing for safe interfascicular dissection over much longer distances than previously
believed. This established the clinical basis of intraneural neurolysis, fascicular nerve repairs,
interfascicular nerve grafting, and subsequently nerve transfers
Fig. 23.2 Intraneural a b

topography. (a)
Sunderland’s
representative drawing
of a 3 cm segment of the
musculocutaneous nerve
illustrating the extensive
intraneural plexus
connections. (b)
Jabaley’s illustration of
a 3 cm section of the
median nerve in the
mid-forearm
demonstrating that the
fascicles maintain a
fairly organized
topography and constant
course over a
considerable distance,
which would allow for
interfascicular
dissection. (Reproduced
with permission from
[32])
In 1945, Sunderland described the internal and thus may be isolated surgically” [32]
architecture of nerves, based on meticulous and (Fig. 23.2). The anterior interosseous motor
detailed serial microscopic sectioning studies, as branch could be safely dissected for 147 mm and
being “continually modified along the entire length the pronator teres for 100 mm within the main
[…] by repeated divisions, anastomosis, and migra- median nerve [32]. They also note that fascicles
tion of the bundles. The longest section of any take a “purposeful” path, maintaining similar
nerve with a constant pattern was 15 mm” [30]. relative position and organized topography within
This constantly changing, complex, and capricious the nerve, despite portions of intraneural plexal
nature of nerves (Fig. 23.2) provided a pessimistic connections. For example, in the median nerve,
view of a surgeon’s ability to re-align fascicles the motor branches to the extrinsic muscles of the
across nerve gaps and was used as a possible expla- median nerve were found to lie within the periph-
nation for poor outcomes following repair [31]. ery and the sensory branches to the hand, thenar
This landmark paper by Dr. Michael E Jabaley, motor branch, and palmar cutaneous branch to
MD, in 1980, changed this perception [32]. While reside within the central and dorsal portion of the
it confirmed the findings of intricate interfascicu- nerve [32].
lar plexus connections, these were not as exten- The authors discuss the clinical applications
sive as to preclude safe intraneural dissection. of these findings, which include the ability to
This anatomic study examined the detailed intra- safely perform internal neurolysis of the median
neural topography of the median, ulnar, and nerve in carpal tunnel syndrome, match similar
radial nerves in the forearm through serial sec- fascicles based on fascicular topography in nerve
tions (three median nerves) and microscopic repairs, and use interfascicular grafting to bridge
interfascicular dissections (four median, four nerve gaps. Awarded the Emanuel Kaplan Award
ulnar, and two radial nerves). The authors confor best paper on an anatomic subject at the 1979
clude based on their findings that portions of American Society for Surgery of the Hand meet-
nerves may “proceed for considerable distances ing, this impact of this paper was already recog-
with no major change in position or composition nized at the time of its publication. The
significance of this paper is further amplified Viterbo’s 1993 animal studies demonstrating suc-
with the perspective of hindsight. By demonstrat- cessful axonal growth in an end-to-side neurrora-
ing the safety of interfascicular dissections and phy [33], set the groundwork for a major
ability to utilize selected donor fascicles within a paradigm shift in the management of nerve
main nerve, this landmark paper, along with injuries.
23.1.5 Era of Nerve Transfers

Brandt KE, Mackinnon SE. A technique for maximizing biceps recovery in brachial plexus reconstruction. J Hand
Surg. 1993;18A:726–33
Strengths • Detailed anatomic and histomorphometric analysis of the musculocutaneous nerve, including
its branching pattern, cross-sectional area, and nerve fiber counts
• Anatomy studies supported by clinical data demonstrating the feasibility of primary nerve
transfer and excellent outcomes
Limitations • Variable follow-up on a small initial cohort of five patients, including one with short-term
follow-up not yet achieving reinnervation
Impact This landmark paper spearheaded the resurgence of nerve transfers and their use in brachial plexus
reconstruction. The authors describe a novel transfer of the medial pectoral nerves to the biceps
motor branch of the musculocutaneous nerve for reconstruction of elbow flexion in patients with
C5–6 level injuries. The clinical outcomes in five patients demonstrated superior results compared to
previously attempted nerve transfers. This highlighted the importance of selecting donor nerves that
were close to the recipient motor end plates to shorten the time to reinnervation. This study, along
with three subsequent papers outlined in this section, led to an exponential rise in the number of new
innovative nerve transfer combinations and expanded the use of nerve transfers to lower extremity
nerve injuries, spasticity and spinal cord injuries, acute flaccid myelitis, oncologic reconstruction,
and targeted muscle reinnervation for both prosthetic control and neuroma management
Although described in the early 1900s, nerve eral antebrachial cutaneous (LABC) nerve back
transfers were reintroduced over the last two to the biceps muscle to redirect all possible motor
decades and have led to a paradigm shift in the fibers toward muscle reinnervation. This study
management of complex nerve injuries [34, 35]. included anatomic dissections and histomorpho-
This was mirrored by a similar dramatic increase logic analysis of the musculocutaneous nerve in
in the number of publications on nerve transfers 21 cadaveric specimens and clinical outcomes of
in the mid-2000s which has exceeded those on this nerve transfer in five patients. Three patients
nerve graft or repair, and also resulted in the achieved ≥M4 elbow flexion, one patient had M3
increased use of nerve transfers by both orthope- recovery, and one patient did not have long
dic and plastic surgeons [34–36]. This landmark enough follow-up for expected functional recov-
paper by Keith Brandt and Susan Mackinnon, ery. These results were superior to previously
published in 1993, spearheaded the use of nerve attempted nerve transfers using the intercostal,
transfers in brachial plexus reconstruction and spinal accessory, and phrenic nerves as donors.
was followed by three subsequent papers that This emphasized the importance of selecting a
marked the tipping point for a paradigm shift donor nerve close to the recipient motor end
from autologous nerve grafting to nerve plates, and when possible, pursuing distal dissec-
transfers. tion of the donor nerve to facilitate a primary
Drs. Keith Brandt, MD, and Susan Mackinnon, nerve coaptation.
MD, described transferring the medial pectoral A year later, Oberlin et al. introduced the con-
nerves to the biceps motor branch of the cept of performing internal neurolysis and using
musculocutaneous nerve in order to reconstruct donor motor fascicles within major nerve-for-
elbow flexion in patients with C5–6 level inju- nerve transfers. He described the transfer of 10%
ries. This was combined with transfer of the lat- of the ulnar nerve to the biceps motor branch for
restoration of elbow flexion in patients with C5–6 two decades identified the addition of the DFT
level root avulsions [37]. This fascicular nerve in the second decade as one of the key factors
transfer technique expanded the available possi- that led to more reliable and consistent results
ble donors, beyond those at specific motor of patients obtaining M4 elbow flexion [45].
branching points, and allowed for the use of However, the fact that reinnervation of the
major nerves at more proximal levels. The ability biceps alone could obtain M3 anti-gravity
to select a donor at any level within the upper arm elbow flexion strength in 79–88% of patients
provides the benefit of shorter regeneration dis- [43, 45], despite brachialis being the strongest
tances and time to reinnervation. In a follow-up elbow flexor, meant that the latter could possi-
patient series, 94% of patients undergoing this bly be used as a donor nerve without losing
nerve transfer achieved M3 and M4 elbow flex- critical function. This would especially be the
ion strength; however, 10 of the 32 patients still case in patients with normal biceps function.
required a secondary Steindler flexorplasty [38]. With this knowledge, Wilson et al. described
This led Mackinnon et al. to target reinnerva- the brachialis to anterior interosseous nerve
tion of both the biceps and brachialis with a dou- (AIN) transfer for reconstruction of hand func-
ble fascicular transfer from the median and ulnar tion in isolated lower brachial plexus injuries
nerves (Fig. 23.3). This was feasible with direct [46]. They demonstrated good results and all
nerve coaptation and without any resulting motor patients maintained M5 elbow flexion strength
or sensory donor deficits [39]. Single and double post-operatively [46]. Use of the brachialis to
fascicular nerve transfers to restore elbow flexion AIN nerve transfer would also become a cru-
in C5–6 upper trunk brachial plexus injuries have cial nerve transfer to restore hand function in
become one of the most reliable and predictable patients with spinal cord injuries (SCI)
sets of nerve transfers [40, 41]. [47–49]. Mackinnon et al. reported its use that
There is debate whether a Mackinnon dou- same year in a patient with ASIA A C7 level
ble fascicular transfer (DFT) provided greater SCI who underwent bilateral brachialis to AIN
recovery of elbow flexion compared to a single nerve transfers and recovery of M3 flexor pol-
fascicular transfer [42–44]. A recent large
licis longus and flexor digitorum profundus
study comparing a total of 237 patients over function 15 months post-operatively [50].
Fig. 23.3 Double Musculocutaneous nerve

fascicular nerve transfer
of a redundant donor
motor fascicle from the Redundant FCU
ulnar nerve to the biceps fascicle of ulnar nerve
motor branch and from
the median nerve to the
brachialis motor branch
Ulnar
to restore elbow flexion. Biceps
nerve
FCU flexor carpi branch
ulnaris. (Reproduced
with permission from
[39])
Median Brachialis
nerve branch
Redundant motor
fascicle of median nerve
Brandt and Mackinnon’s landmark paper pro- eration, connectivity, and clinical outcomes.
vided the kindling that ignited an exponential rise Together, they have revolutionized nerve surgery
in the number of innovative nerve transfer combi- and paved the way for advanced surgical tech-
nations. Furthermore, the idea of redirecting niques and better patient outcomes.
axons from within the same nerve, with transfer-
ring the LABC for direct muscle neurotization of
the biceps, was the earliest glimmer of the idea of References
‘turbocharging’ nerves. This concept would re-
emerge and become refined 30 years later in 1. Standring S. The history of nerve repair. In: Peripheral
nerve tissue engineering and regeneration; 2019.
patients with severe ulnar neuropathy as the super p. 1–32.
turbocharged end-to-side (STETS) transfer, where 2. Friedman AH. An eclectic review of the history of
the abductor digiti minimi branch in transferred in peripheral nerve surgery. Neurosurgery. 2009;65(4
end-to-side (ETS) fashion to the deep motor Suppl):A3–8.
3. Souayah N, Greenstein JI. Insights into neurologic
branch of the ulnar nerve to direct the maximum localization by Rhazes, a medieval Islamic physician.
number of axons toward the most critical target Neurology. 2005;65:125–8.
[51]. This is performed in addition to a super- 4. Artico M, Cervoni L, Nucci F, Giuffré R. Birthday of
charged ETS transfer of the AIN to ulnar motor peripheral nervous system surgery: the contribution of
Gabriele Ferrara. Neurosurgery. 1996;39:380–3.
nerve, which differs from turbocharging as it redi- 5. Browne KM. Surgery of peripheral nerves. A history
rects axons from a different nerve in ETS fashion. of neurological surgery. Williams & Wilkins; 1951.
The paradigm shift to utilizing nerve transfers 6. Silber W. Surgery of the peripheral nerves. S Afr Med
has provided renewed enthusiasm in the func- J. 1946;20(19):634–9.
7. Woolsey G. The surgery of the nerves. In: Surgery: its
tional reconstruction of complex and challenging principles and practice. Saunders; 1907.
nerve injuries. Currently, the use of nerve trans- 8. Shimomura O, Johnson FH, Saiga Y. Extraction, puri-
fers has further expanded to the management of fication and properties of Aequorin, a bioluminescent
lower extremity injuries [52–55], spasticity and protein from the luminous hydromedusan, Aequorea.
J Cell Comp Physiol. 1962;59(3):223–39.
spinal cord injuries [49, 56, 57], acute flaccid 9. Prasher DC, Eckenrode VK, Ward WW, Prendergast
myelitis [58, 59], oncologic reconstruction [60, FG, Cormier MJ. Primary structure of the
61], and targeted muscle reinnervation for both Aequorea victoria green-fluorescent protein. Gene.
prosthetic control [62] and neuroma management 1992;111:229–33.
10. Chalfie M, Tu Y, Euskirchen G, Ward WW, Prasher
[63–65]. DC. Green fluorescent protein as a marker for gene
expression. Science. 1994;263(5148):802–5.
11. Heim R, Cubitt AB, Tsien RY. Improved green fluo-
rescence. Nature. 1995;373(6516):663–4.
23.2 Expert Concluding 12. Tsien RY. The green fluorescent protein. Annu Rev
Commentary Biochem. 1998;67:509–44.
13. Lichtman JW, Sanes JR. Watching the neuromuscular
These five landmark papers outline the key step- junction. J Neurocytol. 2003;32(5–8):767–75.
14. Moore AM, Borschel GH, Santosa KB, et al. A trans-
ping stones of a paradigm shift toward the use of
genic rat expressing green fluorescent protein (GFP)
nerve transfers for the treatment of nerve injuries. in peripheral nerves provides a new hindlimb model
GFP neuronal labeling visualized nerve regener- for the study of nerve injury and regeneration. J
ation; retrograde labeling then allowed us to map Neurosci Methods. 2012;204(1):19–27.
15. Kristensson K, Olsson Y. Uptake and retrograde axo-
nerve connections; analysis of motor unit com-
nal transport of peroxidase in hypoglossal neurons.
pensation quantified the requirements for func- Electron microscopical localization in the neuronal
tional recovery; understanding intraneural perikaryon. Acta Neuropathol. 1971;19:1–9.
topography allowed for safe interfascicular dis- 16. Kristensson K, Olsson Y. Retrograde axonal transport
of protein. Brain Res. 1971;29:363–5.
section, and fascicular nerve transfers propelled
17. Olsson Y, Kristensson K. The perineurium as a dif-
the clinical application of nerve transfers. These fusion barrier to protein tracers following trauma to
studies expanded our knowledge of nerve regen- nerves. Acta Neuropathol. 1973;23:105–11.
18. Brushart TM, Seiler WA. Selective reinnervation of 37. Oberlin C, Béal D, Leechavengvongs S, Salon A,
distal motor stumps by peripheral motor axons. Exp Dauge MC, Sarcy JJ. Nerve transfer to biceps muscle
Neurol. 1987;97:289–300. using a part of ulnar nerve for C5-C6 avulsion of the
19. Brushart TME. Preferential reinnervation of motor brachial plexus: anatomical study and report of four
nerves by regenerating motor axons. J Neurosci. cases. J Hand Surg. 1994;19(2):232–7.
1988;8(3):1026–31. 38. Teboul F, Kakkar R, Ameur N, Beaulieu JY,
20. Brushart TME. Preferential motor reinnervation: Oberlin C. Transfer of fascicles from the ulnar
a sequential double-labeling study. Restor Neurol nerve to the nerve to the biceps in the treatment of
Neurosci. 1990;1:281–7. upper brachial plexus palsy. J Bone Joint Surg Am.
21. Brushart TME. Motor axons preferentially reinner- 2004;86(7):1485–90.
vate motor pathways. J Neurosci. 1993;13(6):2730–8. 39. Mackinnon SE, Novak CB, Myckatyn TM, Tung
22. Brushart TM, Gerber J, Kessens P, Chen YG, TH. Results of reinnervation of the biceps and bra-
Royall RM. Contributions of pathway and neu- chialis muscles with a double fascicular transfer for
ron to preferential motor reinnervation. J Neurosci. elbow flexion. J Hand Surg Am. 2005;30(5):978–85.
1988;18(21):8674–81. 40. Maldonado AA, Bishop AT, Spinner RJ, Shin
23. Catapano J, Willand MP, Zhang JJ, Scholl D, Gordon AY. Five operations that give the best results
T, Borschel GH. Retrograde labeling of regenerat- after brachial plexus injury. Plast Reconstr Surg.
ing motor and sensory neurons using silicone caps. J 2017;140(3):545–56.
Neurosci Methods. 2016;259:122–8. 41. Vernon Lee CY, Cochrane E, Chew M, Bains RD,
24. Edds MV. Collateral regeneration of residual motor Bourke G, Wade RG. The effectiveness of different
axons in partially denervated muscles. J Exp Zool. nerve transfers in the restoration of elbow flexion
1950;113:517–32. in adults following brachial plexus injury: A sys-
25. Edds MV. Collateral nerve regeneration. Q Rev Biol. tematic review and meta-analysis. J Hand Surg Am.
1953;28:260–76. 2023;48(3):236–44.
26. Edds MV, Small WT. The behaviour of residual axons 42. Carlsen BT, Kircher MF, Spinner RJ, Bishop AT, Shin
in partially denervated muscles of the monkey. J Exp AY. Comparison of single versus double nerve trans-
Med. 1951;93:207–16. fers for elbow flexion after brachial plexus injury.
27. McComas AJ, Sica RE, Campbell MJ, Upton Plast Reconstr Surg. 2011;127(1):269–76.
AR. Functional compensation in partially dener- 43. Sneiders D, Bulstra LF, Hundepool CA, Treling WJ,
vated muscles. J Neurol Neurosurg Psychiatry. Hovius SER, Shin AY. Outcomes of single versus
1971;34(4):453–60. double fascicular nerve transfers for restoration of
28. Brown MC, Ironton R. Sprouting and regression of elbow flexion in patients with brachial plexus inju-
neuromuscular synapses in partially denervated mam- ries: A systematic review and meta-analysis. Plast
malian muscle. J Physiol. 1978;278:325–48. Reconstr Surg. 2019;144(1):155–66.
29. Gordon T. Muscle plasticity during sprouting and 44. Chuang DC. Discussion: outcomes of single versus
reinnervation. Am Zool. 1987;27:1055–66. double fascicular nerve transfers for restoration of
30. Sunderland S. Intraneural topography of nerves in elbow flexion in patients with brachial plexus inju-
forearm. Brain. 1945;68(4):243–99. ries: A systematic review and meta-analysis. Plast
31. Sunderland S. Nerves and nerve injuries. Livingstone Reconstr Surg. 2019;144(1):167–9.
Ltd; 1968. 45. Lee YH, Lu JC, Wong A, Chang TN, Chuang DC. The
32. Jabaley ME, Wallace WH, Heckler FR. Internal evolution of the reconstructive strategy for elbow flex-
topography of major nerves of the forearm and hand: ion for acute C5, C6 brachial plexus injuries over two
A current view. J Hand Surg. 1980;5(1):1–18. decades. J Reconstr Microsurg. 2023;40(2):139–44.
33. Viterbo F, Trindade JC, Hoshino K, Mazzoni 46. Ray WZ, Yarbrough CK, Yee A, Mackinnon SE. Clinical
NA. End-to-side neurorrhaphy with removal of the outcomes following brachialis to anterior interosseous
epineurial sheath: an experimental study in rats. Plast nerve transfers. J Neurosurg. 2012;117(3):604–9.
Reconstr Surg. 1994;94(7):1038–47. 47. Fox IK, Novak CB, Kahn LC, Mackinnon SE,
34. Varagur K, Jacobson L, Teixeira R, Patterson JMM, Ruvinskaya R, Juknis N. Using nerve transfer to
Skolnick GB, Mackinnon SE. Following a surgical restore prehension and grasp 12 years following spi-
paradigm shift through the adoption of nerve transfers nal cord injury: a case report. Spinal Cord Ser Cases.
among board-eligible and practicing plastic surgeons. 2018;4:37.
Hand (N Y). 2023:15589447231167582. 48. Fox IK, Davidge KM, Novak CB, et al. Use of periph-
35. Domeshek LF, Novak CB, Patterson JMM, et al. Nerve eral nerve transfers in tetraplegia: evaluation of feasi-
transfers-A paradigm shift in the reconstructive lad- bility and morbidity. Hand (N Y). 2015;10(1):60–7.
der. Plast Reconstr Surg Glob Open. 2019;7(6):e2290. 49. van Zyl N, Hill B, Cooper C, Hahn J, Galea
36. Morris M, Brogan DM, Boyer MI, Dy CJ. Trends MP. Expanding traditional tendon-based techniques
in nerve transfer procedures among board- eligible with nerve transfers for the restoration of upper limb
orthopedic hand surgeons. J Hand Surg Glob Online. function in tetraplegia: a prospective case series.
2021;3(1):24–9. Lancet. 2019;394(10198):565–75.
50. Mackinnon SE, Yee A, Ray WZ. Nerve transfers for flexion in patients with acute flaccid myelitis. J Hand
the restoration of hand function after spinal cord Surg Am. 2022;47(1):91 e1–8.
injury. J Neurosurg. 2012;117(1):176–85. 59. Moore AM, Bettlach CR, Tung TT, West JM, Russo
51. Peters BR, Jacobson L, Pripotnev S, Mackinnon SA. Lower extremity nerve transfers in acute flaccid
SE. Abductor digiti minimi and anterior interosse- myelitis patients: a case series. Plast Reconstr Surg
ous to ulnar motor nerve transfer: the super turbo- Glob Open. 2021;9(7):e3699.
charge end-to-side transfer. Plast Reconstr Surg. 60. Jawad AM, Duraku LS, Susini F, Chaudhry T, George
2023;151(4):815–20. S, Jester A, Power DM. Resect, rewire, and restore:
52. Duraku LS, Buijnsters ZA, Power DM, George S, nerve transfer salvage of neurological deficits asso-
Walbeehm ET, de Jong T. Motor and sensory nerve ciated with soft tissue tumours in a restrospective
transfers in the lower extremity: systematic review of cohort series at a tertiary reconstructive Centre. J Plast
current reconstructive possibilities. J Plast Reconstr Reconstr Aesthet Surg. 2023;85:523–33.
Aesthet Surg. 2023;84:323–33. 61. O'Brien AL, West JM, Zewdu A, Grignol VP,
53. Peters BR, Ha AY, Moore AM, Tung TH. Nerve trans- Scharschmidt TJ, Moore AM. Nerve transfers to
fers for femoral nerve palsy: an updated approach and restore femoral nerve function following onco-
surgical technique. J Neurosurg. 2022;136(3):856–66. logic nerve resection. J Surg Oncol. 2021;124(1):
54. Moore AM, Krauss EM, Parikh RP, Franco MJ, 33–40.
Tung TH. Femoral nerve transfers for restoring 62. Simon AM, Turner KL, Miller LA, et al. Myoelectric
tibial nerve function: an anatomical study and clini- prosthesis hand grasp control following targeted
cal correlation: A report of 2 cases. J Neurosurg. muscle reinnervation in individuals with transradial
2018;129(4):1024–33. amputation. PLoS One. 2023;18(1):e0280210.
55. Tung TH, Chao A, Moore AM. Obturator nerve 63. Goodyear EG, O'Brien AL, West JM, et al. Targeted
transfer for femoral nerve reconstruction: anatomic muscle reinnervation at the time of amputation
study and clinical application. Plast Reconstr Surg. decreases recurrent symptomatic neuroma formation.
2012;130(5):1066–74. Plast Reconstr Surg. 2023;153(1):154–63.
56. Zheng MX, Hua XY, Feng JT, et al. Trial of contra- 64. Dumanian GA, Potter BK, Mioton LM, et al. Targeted
lateral seventh cervical nerve transfer for spastic arm muscle Reinnervation treats neuroma and phantom
paralysis. N Engl J Med. 2018;378(1):22–34. pain in major limb amputees: A randomized clinical
57. Javeed S, Dibble CF, Greenberg JK, et al. Upper limb trial. Ann Surg. 2019;270(2):238–46.
nerve transfer surgery in patients with tetraplegia. 65. Janes LE, Fracol ME, Dumanian GA, Ko JH. Targeted
JAMA Netw Open. 2022;5(11):e2243890. muscle Reinnervation for the treatment of neuroma.
58. Rabinovich RV, Pino PA, Aversano M, Kozin SH, Hand Clin. 2021;37(3):345–59.
Zlotolow DA. Nerve transfers for restoration of elbow
Part VI
Skin Cancer Management
Evolution of Melanoma
and Non-Melanoma Skin Cancer
24
Management
Abstract • Neoadjuvant immune checkpoint blockade

in squamous cell carcinoma.
The landscape of skin cancer treatment has
changed dramatically over the past two
This review will focus on five key studies and
decades. While radical surgical resection has
explore how they, together with supporting publi-
traditionally been the default approach,
cations, have shaped each of the above domains
advancements in multidisciplinary manage-
in contemporary skin cancer management.
ment has enabled more nuanced, personal-
ized approaches that minimize morbidity
Keywords
without compromising oncological efficacy.
In this chapter, five key conceptual advances Melanoma · Cutaneous squamous cell
that have engendered a paradigm shift in the carcinoma · Breslow thickness · Margins of
management of melanoma and non-mela- excision · Sentinel-node biopsy · Immune
noma skin cancer will be discussed, checkpoint inhibitors · Targeted therapy
including: Neoadjuvant therapy
• Emergence of Breslow thickness as a prog-

nostic indicator for cutaneous melanoma.
• Surgical margins in the resection of cutane-
1. Breslow A. Thickness, cross-sectional areas
ous melanoma.
and depth of invasion in the prognosis of cuta-
• Sentinel-node biopsy replacing elective
neous melanoma. Ann Surg.
nodal dissection as the gold standard in
1970;172(5):902–8.
melanoma management.
2. Cascinelli N. Margin of resection in the man-
• Neoadjuvant immune checkpoint blockade
agement of primary melanoma. Semin Surg
and targeted therapy in melanoma.
Oncol. 1998;14:272–5.
3. Morton DL, et al. Final Trial Report of
Sentinel-Node Biopsy versus Nodal
S. Ch’Ng (*) Observation in Melanoma. N Engl J Med.
The University of Sydney, 2014;370:599–609.
Camperdown, NSW, Australia 4. Eggermont AMM, et al. Adjuvant ipilimumab
Y. J. Jeong versus placebo after complete resection of
Royal Prince Alfred Hospital, high-risk stage III melanoma (EORTC 18071):
Camperdown, NSW, Australia
https://doi.org/10.1007/978-3-031-57132-9_24
a randomised, double-blind, phase 3 trial. Table 24.1 Clark levels for prognostic staging of cutane-
ous melanoma
Lancet Oncol. 2015;16:522–30.
5. Gross ND, et al. Neoadjuvant cemiplimab for Clark level Description
stage II to IV cutaneous squamous-cell carci- I Tumour confined within the epidermis
(melanoma in situ)
noma. N Engl J Med. 2022;387:1557–68. II Invasion into the papillary dermis
III Invasion to the junction of the papillary
and reticular dermis
24.1 Introduction IV Invasion into the reticular dermis
V Invasion into the subcutaneous fat
Melanoma and non-melanoma skin cancers
(NMSC) constitute a significant healthcare bur-
den. An estimated 1.5 million cases of skin can- that survival outcomes were related to the
cer were diagnosed in 2020 worldwide, and the depth of invasion of malignant melanoma
incidence of both melanoma and NMSC is pro- [3–5]. In their retrospective analysis of 208
jected to increase [1]. This chapter will explore cases assigned to a definite anatomic level of
advancements in skin cancer management, invasion, Clark et al. observed a stepwise
including the validation of Breslow thickness as a increase in melanoma-specific mortality when
prognostic factor in cutaneous melanoma, opti- tumours were stratified from level II (8.3%) to
mization of excisional margins in the resection of level V (52.0%), and reported an associated
cutaneous melanoma, the evolving role of decline in median survival time from 6.83 years
sentinel-
node biopsy in an era of effective to 3.50 years [2]. Uniform decline in disease-
immune checkpoint inhibitor therapy, and cus- free survival rates (72.2% and 12.0% for level
tomized systemic (neo)adjuvant therapies to min- II and V, respectively) was also observed [2].
imize adverse effects and improve survival Clark’s level of invasion has since been vali-
outcomes. In addition, this review will highlight dated by numerous univariate analyzes as a
future directions in the advancement of skin can- strong prognostic indicator for survival [6, 7],
cer treatment. and was recognized as a principal determinant
of prognosis in melanoma staging systems for
over 40 years [8].
24.2 Breslow’s Thickness Meanwhile, in 1970, Breslow demonstrated
as a Prognostic Indicator that tumour thickness was a reliable measure of
for Cutaneous Melanoma prognosis in cutaneous melanoma [9]. The ver-
tical dimensions of primary melanomas (n = 98)
Risk-based stratification of cutaneous melanoma were measured from the skin surface to the
is critical in providing clinicians and patients deepest point of invasion with an ocular microm-
with prognostic information, guiding manage- eter, and analyzed alongside other parameters of
ment strategies, and directing clinical trials. tumour size (maximal diameter and cross-
While staging systems continue to undergo sectional area of the lesion) and level of inva-
refinement with greater insight in prognostic fac- sion. Breslow demonstrated that tumour
tors for melanoma, the enduring significance of thickness was the most useful measurement of
Clark’s level and Breslow’s thickness must be tumour size, with all patients with a lesion less
recognized. than 0.76 mm thickness (n = 38) remaining free
In 1969, Clark et al. proposed a microstag- of disease after 5 years. When analyzed in con-
ing classification system for cutaneous mela- junction with Clark level of invasion, stage II
noma defined by five anatomic levels of lesions and stage III lesions less than 0.76 mm
invasion (Table 24.1) [2]. This was built upon in thickness identified in 45 patients, only one
previous observations by Allen [3] and others of whom (a thick stage II lesion) developed
24 Evolution of Melanoma and Non-Melanoma Skin Cancer Management 245
recurrent or metastatic disease [9]. Breslow and stage of invasion, and advocated for both
concluded that the prognosis of cutaneous mela- parameters to be assessed in the histopathologi-
nomas was a function of both tumour thickness cal evaluation of melanomas.
Breslow A. Thickness, cross-sectional areas and depth of invasion in the prognosis of cutaneous melanoma. Ann
Surg. 1970;172(5):902–8
Strengths • This publication established the value of tumour thickness in the prognostication of
cutaneous melanomas
Limitations • Retrospective study with small sample size (n = 98), limiting statistical evaluation and
generalizability of findings
Impact Breslow’s thickness is currently accepted as the single most important prognostic factor for
primary melanoma. Tumour thickness has now been incorporated into all national guidelines
for tumour staging of melanoma
Importantly, studies using multivariate analy- findings, the current eighth edition of the
sis have consistently demonstrated that tumour American Joint Committee on Cancer (AJCC)
thickness is a much more powerful prognostica- staging criteria utilizes only Breslow’s thickness
tor of survival than Clark’s level in patients with as a primary prognostic variable, and omits
melanoma [10, 11]. A seminal publication led by Clark’s level of invasion from its T-category cri-
Balch (n = 339) demonstrated that while both terion [20].
tumour thickness (p < 0.00001) and level of inva- Today, Breslow’s thickness is widely recog-
sion (p = 0.003) held strong prognostic value in nized as the principal determinant of prognosis
single factor analysis, the level of invasion of the for clinically localized melanoma, and has been
tumour held no additional predictive influence used to guide treatment, including excision mar-
after thickness was accounted for in a multivari- gins [21] and sentinel-node biopsy [22].
ate model (p = 0.7105) [12]. Further, in Thompson Nonetheless, staging systems that have adopted
et al.’s multivariate analysis of 10,233 patients Breslow’s thickness continue to undergo refine-
with localized cutaneous melanoma, tumour ment and modifications to improve their prognos-
thickness conferred the greatest statistical signifi- tic value. Optimization of cut-offs for tumour
cance of all analyzed prognostic factors, includ- thickness constitutes a challenging task.
ing patient age, ulceration, and mitotic rate (all Currently, the AJCC staging system segregates
p < 0.001), while Clark’s level of invasion was melanomas into 1.0 mm, 2.0 mm, and 4.0 mm
not statistically correlated with survival [20, 23, 24]. Based on data from several publica-
(p = 0.37) [11]. Although some publications have tions, T1 tumours are further sub-stratified at
shown that Clark’s level is an independent prog- 0.8 mm in the current eighth edition of the AJCC
nostic factor for melanoma, many of these stud- staging system [16, 25–27]. In addition, tumour
ies only report prognostic significance for ‘thin’ ulceration has been shown to confer a more
melanomas (i.e. <1.0 mm) [13–15]; yet, in this aggressive tumour phenotype, and its presence
regard, recent studies have now demonstrated has been demonstrated to predict for metastasis
superior correlation with survival when T1 and negatively impacts on survival beyond mela-
tumours are sub-stratified by mitotic rate (and noma thickness alone [13, 28, 29]. This finding
later, by a 0.8 mm cut-off) than level of invasion was validated by a seminal multifactorial analy-
[10, 16]. In addition, the reproducibility and sis led by Balch (n = 13,851), in which tumour
interobserver agreement of Breslow’s thickness thickness [relative risk (RR) = 1.558;
has been widely demonstrated to be superior to p < 0.00001] and ulceration (RR = 1.901,
that of Clark’s level [17–19]. As a result of these p < 0.00001) were identified as the two most sig-
nificant independent prognostic factors of pri- for the excision of two inches (approx. 5 cm) of
mary melanoma [13]. The AJCC staging system subcutaneous tissue radially from the edge of the
has adopted tumour ulceration status as a malignant melanoma [33] and down to the mus-
T-category criterion modifier since its sixth cle fascia. This recommendation, supported by
iteration. the works of Pringle [35] and Petersen [4],
Multiple clinical and histopathological fac- informed early management practices which pri-
tors, including age, mitotic rate, and site of the oritized wide excision for recurrence prevention.
primary tumour, have also been shown to be However, following landmark publications by
independent predictors of survival [11, 30]. Clark [2] and Breslow [9] demonstrating favour-
While not included in the current eighth edition able prognosis of thin melanomas, growing con-
of the AJCC staging system, these variables are cerns emerged amongst surgeons regarding the
nonetheless important determinants of prognosis; excess morbidity associated with such large exci-
indeed, the AJCC staging system has garnered sion defects.
increasing criticism for its inability to reflect In 1980, the World Health Organization
additional tumour factors that extend beyond the (WHO) Melanoma Group commenced an inter-
anatomic TNM categories. These variables are national, prospective, randomized controlled trial
likely to represent important parameters for con- (RCT) (n = 612) to compare survival outcomes in
sideration of inclusion in future prognostication patients treated with wide (3 cm) versus narrow
tools, to allow for more nuanced, precise, and (1 cm) excision of primary melanomas not thicker
individualized approaches to risk assessment for than 2 mm [35–37]. Long-term follow up data
patients with melanoma [31, 32]. (median follow-up, 90 months) from this study
demonstrated no statistically significant differ-
ence in overall survival (89.6% vs 90.3%,
24.3 Optimal Margins in Surgical p = 0.64) or disease-free survival (81.6% vs
Resection of Cutaneous 84.4%, p > 0.74) between narrow versus wide
Melanoma excision margins. In addition, a similar frequency
of adverse events was observed between the two
In 1907, the Lancet published a series of two lec- groups when regional, in-transit, and distant
tures delivered by W. Sampson Handley on rec- metastases were taken into consideration [36].
ommendations for excision margins of cutaneous While the frequency of local recurrences in
melanoma [33, 34]. Based on his observations of patients submitted to narrow and wide excision
atypical melanocytes spreading centrifugally in (2.6% and 0.1%, respectively) appeared higher
the lymphatic plexus of the deep fascia from a numerically (1.8% of the 612 patients), this find-
metastatic tumour deposit, Handley advocated ing was not statistically significant [37].
Cascinelli N. Margin of resection in the management of primary melanoma. Semin Surg Oncol. 1998;14:272–5
Strengths • RCT with large sample size (n = 612). Long-term data available (median follow-up,
90 months)
Limitations • Did not include patients with primary melanomas of the face, fingers, and toes. Neither
participants nor assessors were blinded, incurring a risk of bias
Impact This publication is the first RCT to investigate narrow versus wide surgical excision margins for
cutaneous melanoma. On the basis of the findings of this study (as well as subsequent RCTs),
national and professional organizations now recommend narrow excision margins for melanoma
<2 mm thick
The results of this publication, together with sub- ≤1 mm (WHO Trial [36–38]; Swedish I Trial [39,
sequent RCTs, have defined current guidelines 40]; French Trial [41]), 1.0–2.0 mm (WHO [36–38]
regarding the surgical management of melanomas of Trial; Swedish I Trial [39, 40]; Intergroup Trial
[42–44]; French Trial [41]), 2.0–4 mm (Intergroup Overall, these studies have largely cemented the
Trial [42–44]; UKMSG Trial [45, 46]; Swedish II safety of narrower margins for primary cutaneous
Trial [47, 48]) and > 4 mm (UKMSG Trial [45, 46]; melanoma, and have improved outcomes for patients
Swedish II Trial [47, 48]) thickness (Table 24.2). by decreasing the morbidity of surgery associated
Survival and recurrence data from all published with excessive excision margins whilst not compro-
RCTs (as of date) are summarized in Table 24.3. mising preserved oncologic outcomes [21, 53].
Table 24.2 National guidelines recommendations for surgical excision of cutaneous melanoma
National guideline Recommended excision margin
Breslow’s thickness ≤1.0 mm >1.0–2.0 mm >2.0–4.0 mm >4 mm
National Comprehensive Cancer Network (NCCN), 1 cm 1–2 cm 2 cm 2 cm
2023 [49]
National Institute for health and care excellence 1 cm 1–2 cm 2 cm 2 cm
(NICE), 2022 [50]
Cancer council Australia (CCA), 2020 [51] 1 cm 1–2 cm 1–2 cm 2 cm
European Consensus-Based Interdisciplinary 1 cm 1 cm 2 cm 2 cm
Guideline, 2020 [52]
The European Consensus-Based Interdisciplinary Guideline for Melanoma is formed by the European Dermatology
Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization for Research
and Treatment of Cancer (EORTC)
Table 24.3 Clinical trials investigating surgical excision margins in melanoma

Surgical Survival and recurrence
Trial (Author, year) Description margins outcomes
WHO Patients with primary melanomas 1 cm vs. 3 cm No significant differences
Veronesi (1988)[38]; ≤2 mm (n = 612). Mean follow-up reported in OS (p = 0.64) or DFS
Veronesi (1991) duration of 90 months. Patients with (p > 0.74).
[36], Cascinelli multiple primary melanomas, history of
(1998) [37] cancer, and primary sites of face, fingers,
toes were excluded.
Swedish trial I Patients with primary melanoma 2 cm vs. 5 cm No significant differences
Ringborg (1996) 0.8–2.0 mm of the trunk or extremities reported in OS (p = 0.77), MSS
[39], Cohn- (n = 989). Mean follow-up duration of (p = 0.24), locoregional
Cedermark (2000) 11 years for survival and 8 years for recurrence (p = 0.22), distant
[40] recurrent disease. Patients with metastasis (p = 0.29), or
melanoma satellites, metastatic disease, intercurrent death (p = 0.31).
previous malignant disease (except BCC)
were excluded.
Intergroup trial Patients with primary melanomas 2 cm vs. 4 cm No significant differences
Balch (1993) [42] 1–4 mm (n = 468 randomized; n = 272 in local recurrence (p = 0.72) or
Karakousis (1996) receiving 2 cm radial excision margin). 10-year DFS (p = 0.074) within
[43], Balch (2001) Median follow-up duration of 10 years. the randomized portion of the
[44] Patients with metastatic melanoma, trial. Findings corroborated by
lentigo maligna melanoma, history of pooled analysis with non-
cancer, or who had received randomized cohort.
chemotherapy or radiotherapy were
excluded.
French Trial Khayat Patients with primary melanomas <2 mm 2 cm vs. 5 cm No significant difference in
(2003) [41] (n = 326). Median follow-up duration of 10-year OS (p = 0.56) or DFS
192 months. Patients with toe, nail, or (p = 0.83).
finger lesions, melanomas arising from
melanosis, lentigo, acral lesions, and
patients older than 70 years were
excluded.
(continued)
Table 24.3 (continued)

Surgical Survival and recurrence
Trial (Author, year) Description margins outcomes
UK MSG trial Patients with primary melanoma >2 mm 1 cm vs. 3 cm Statistically significant increased
Thomas (2004)[46], in trunk or limbs (n = 900). Median risk of melanoma-specific death
Hayes (2016)[45] follow-up duration of 106 months. (HR 1.24, p = 0.041) and
Patients with primary melanoma in soles locoregional recurrence (HR
of feet, palms of hands, and 1.26, p = 0.05) in patients treated
age < 18 years were excluded. with narrow excision margins.
No significant difference in OS
(p = 0.14).
Swedish Trial II Patients with primary melanoma >2 mm 2 cm vs. 4 cm No significant difference
Gillgren (2011) [47], in trunk or extremities (n = 936). Median reported in in OS (p = 0.75) or
Utjés (2019) [48] follow-up duration of 19.6 years. MSS (p = 0.61).
Patients with primary melanoma in head
and neck, hands, feet, anogenital region,
history of cancer (other than BCC and in
situ carcinoma of cervix) were excluded.
MelMarT Trial Patients with primary melanoma >1 mm 1 cm vs. 2 cm Feasibility study reports
Moncrieff (2018) (n = 337). Median follow-up duration of increased rates of reconstruction
[53] 12 months reported in feasibility study (p < 0.0001) and wound necrosis
(note, ongoing study). All patients were (p = 0.036) in the wide excision
required to undergo SLNB at time of group, with no differences in
excision of the primary melanoma for QoL. Ongoing survival outcomes
staging purposes. to be assessed include OS, MSS,
and locoregional recurrence.
Abbreviations: BCC basal cell carcinoma, DFS disease free survival, MSS melanoma specific survival, OS overall sur-
vival, QoL quality of life, RFS recurrence-free survival, SLNB sentinel lymph node biopsy, UKMSG United Kingdom
Melanoma Study Group, WHO World Health Organization
However, some discrepancies remain in exci- tocol deviation that occurred after commence-
sion margin recommendations between national ment of the trial (i.e. was not a pre-defined
guidelines (Table 24.2), and most organizations endpoint). Finally, it remains difficult to interpret
caution conflicting evidence be taken into consid- the implications of modest improvement in MSS
eration when planning treatment for patients [49, in the absence of any significant difference in
51]. Specifically, the UKMSG Trial, which overall survival reported by the study (p = 0.14).
compared 1 cm versus 3 cm margins in the man- More recently, an increasing body of evidence
agement of melanomas >2 mm thick arising on from systematic reviews and meta-analyzes has
the trunk or limbs (n = 900) [45, 46], found that supported the adoption of narrow excision mar-
patients treated with narrow excision margins gins in the management of melanoma. In the lat-
had a significantly greater risk of melanoma- est meta-analysis of all seven published RCTs
specific mortality [hazard ratio (HR) = 1.24; (n = 4579), Hanna et al. reported no significant
p = 0.041] and locoregional recurrence difference in measures of survival when narrow
(HR = 1.26; p = 0.05). Importantly, however, the (1–2 cm) versus wide (3–5 cm) excision margins
limitations of this study must be recognized. were compared, including locoregional recur-
First, as the trial had excluded the use of sentinel rence (RR = 1.09, p = 0.12), distant metastasis
node biopsy (SNB), it is not possible to deter- (RR = 0.95, p = 0.68), death from melanoma
mine if different rates of positive SNB between (RR = 1.11, p = 0.16), and overall survival
treatment arms may have incurred bias. Secondly, (RR = 1.00, p = 0.97) [21]. Subgroup analysis by
locoregional recurrence was calculated by com- margin size (1 cm vs. 3 cm, 2 cm vs. 4–5 cm)
bining the rates of local or in-transit recurrences showed no significant difference in outcomes. In
with the rate of nodal recurrence, and was a pro- addition, significantly increased rates of complex
surgical reconstruction were reported for patients the majority of clinically node-negative patients
treated with wide excision margins (RR = 3.33, [60–62].
p < 0.0001) [21]. These findings are largely in Morton and others introduced the technique of
concordance with previously published system- lymphatic mapping and sentinel-node biopsy as a
atic reviews and meta-analyzes [54–56]. Of note, minimally invasive, low-morbidity alternative to
one 2016 meta-analysis of six RCTs concluded ELND [63–65]. Sentinel-node biopsy aims to
that narrow margins (1–2 cm) resulted in worse evaluate the tumour status of the first-tier (i.e.
melanoma-specific survival (HR = 1.17, sentinel) node(s) to receive lymph from the pri-
p = 0.02), but the risk of bias from selective mary melanoma site, so as to predict the tumour
reporting of the UKMSG trial must be recog- status of the remaining nodes within the regional
nized as most other trials did not report this end- lymphatic basin [22]. Thompson and Morton
point [57, 58]. have since confirmed that sentinel-node status is
The Melanoma Margins Trial (MelMarT, a reliable indicator of regional nodal metastasis
NCT02385214) is an ongoing phase III multicen- [66, 67]. This raised the question of whether
tre trial investigating disease free survival, overall biopsy-based staging could identify which
survival, and risk of melanoma recurrence in patients were likely to require completion lymph
patients treated with a 1 versus 2 cm excision mar- node dissection (CLND), and which patients
gin for AJCC pT2-pT4 (greater than 1 mm thick- could be managed via nodal observation alone.
ness) primary cutaneous melanoma [53]. Data In 1994, the phase III Multicenter Selective
from the pilot study, while not mature enough to Lymphadenectomy Trial (MSLT-I) was com-
report on primary survival outcomes, suggest that menced to assess the prognostic utility of
patients treated with wide excision were subjected sentinel-node biopsy for clinically node-negative
to significantly higher rates of complex recon- melanomas [22]. Patients were randomly
struction (34.9% vs. 13.65, p < 0.0001) and suf- assigned to undergo sentinel-node biopsy, with
fered more wound necrosis (3.6% vs. 0.5%, immediate CLND for nodal metastases detected
p = 0.036) compared with patients treated with on biopsy, or nodal observation, with therapeutic
narrow margins [53]. The final results of the lymph node dissection (TLND) carried out only
MelMarT are anticipated to further nuance exci- for patients with subsequent nodal relapse [22].
sion margin recommendations. MSLT-I showed that sentinel-node biopsy signif-
icantly improved disease-free survival in both
intermediate-thickness melanomas [defined in
24.4 Management of Regional MSLT-1 as 1.20–3.50 mm in Breslow thickness;
Node Metastasis HR = 0.76; p = 0.01] and thick melanomas
in Melanoma (defined in MSLT-1 as >3.50 mm in Breslow
thickness; HR = 0.70; p = 0.03) as compared to
Over the past two decades, much debate has cen- nodal observation alone [22]. Additionally, in
tred on the appropriate management of regional multivariate analysis of patients with
lymph nodes in melanoma. The regional lymph intermediate-thickness melanoma, sentinel-node
nodes are the most common site of melanoma status was the strongest prognostic indicator of
metastasis [59], thus the initial rationale was for melanoma-specific survival (HR = 2.40;
all patients to undergo lymph node dissection p < 0.001) [22]. In patients with intermediate-
(LND) regardless of whether there was any clini- thickness melanoma and nodal metastasis, early
cal evidence of regional metastasis [22, 59]. CLND as guided by sentinel-node biopsy was
However, while elective lymph node dissection also associated with improved distant disease-
(ELND) was associated with improved outcomes free survival (HR = 0.62; p = 0.02) and
in certain subgroups of patients [60], multiple melanoma- specific survival (HR = 0.56;
RCTs failed to establish any survival benefit for p = 0.006) [22].
Morton DL, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med.
2014;370:599–609
Strengths • Prospective, international, randomized trial with robust sample size (n = 2001). The MSLT-I is
the first and (currently) only RCT to establish the prognostic value of biopsy-based staging in
intermediate-thickness and thick primary melanomas
Limitations • Limited information regarding the significance of sentinel-node biopsy for thin melanomas
(<1.20 mm) due to limited cohort size
Impact On the basis of the findings of the MSLT-I study, guidelines of national and professional
organizations now recommend the inclusion of sentinel-node biopsy in the staging of cutaneous
melanoma
On the basis of the findings of the MSLT-1 entirely on a reduction in regional nodal recur-
RCT, guidelines of national and professional rence (HR = 0.31; p < 0.001), without a differ-
organizations now recommend sentinel-node ence in distant metastasis-free survival
biopsy for the prognostic staging of intermediate- (HR = 1.10; p = 0.31) [76]. Several retrospective
thickness and thick melanomas [49, 68–70]. studies support the lack of survival benefit con-
Biopsy-based staging is also suggested for thin ferred by CLND in measures of overall survival
melanomas associated with high-risk histopatho- [77, 78], disease-free survival [79], and
logical features (e.g. ulceration) [49, 68–70]. melanoma- specific survival [78, 80–82].
Multiple retrospective cohort studies have since Furthermore, a significantly greater risk of
corroborated sentinel-node status as the most sig- lymphedema was confirmed in the CLND arm
nificant prognostic indicator of melanoma- over the observation arm (with TLND in case of
specific survival in patients with nodal relapse) in MSLT-II (24.1% vs. 6%,
intermediate-thickness or thick melanomas p < 0.001 [76]), while the DeCOG trial classified
[71–73]. 13% of adverse events in the CLND arm as grade
More recently, the role of immediate CLND in 3 or 4 toxicity [75].
patients with a positive sentinel-node status has Given the overall lack of survival benefit and
become a topic of significant debate. While morbidity associated with immediate CLND, cur-
immediate CLND was previously recommended rent guidelines acknowledge the role of both
for all patients with sentinel-node metastases active surveillance and CLND in sentinel-node
(consistent with the intervention arm in the positive patients [49, 68]. Within this cohort,
MSLT-I trial [22]), evidence from two multicen- efforts are now focused on identifying high-risk
tre RCTs (Dermatologic Cooperative Oncology subpopulations that are most likely to benefit
Group [DeCOG] trial [74, 75] and MSLT-II [76]) from more aggressive follow-up, early CLND, or
showed no significant differences in survival out- adjuvant systemic therapy [68]. Several clinico-
comes between sentinel-node positive patients pathologic factors (including extracapsular exten-
who were treated with CLND versus active nodal sion, involvement of multiple nodal basins,
surveillance with ultrasound. The survival end- primary tumour microsatellitosis, or greater than
points in the DeCOG trial [75] were defined as 3 positive nodes in sentinel-node biopsy) have
distant metastases-free survival (HR = 1.09; been defined as ‘high-risk’ features and were
p = 0.87), overall survival (HR = 0.99; p = 0.94) excluded from the MSLT-II RCT [76]. Some of
and recurrence-free survival (HR = 1.01; these adverse risk factors have since been corrob-
p = 0.94), and in the MSLT-II [76] melanoma- orated by retrospective studies [83, 84]. Sentinel-
specific survival (HR = 1.08; p = 0.42). While node tumour burden [84–86] and presence of
MSLT-II found a borderline-significant differ- ulceration in the primary tumour [87] have also
ence in disease-free survival in favour of the been recognized as important predictors of sur-
CLND arm (68 ± 1.7% vs. 63 ± 1.7% at 3-years; vival. Efforts are ongoing to incorporate these fac-
p = 0.05), this significance appeared to be based tors into a validated, standardized risk model, e.g.
the Non-Sentinel Node Risk Score (N-SNORE) shifted to leveraging these clinical advances to
[88], to further refine management of regional dis- adjuvant therapy for patients with high-risk stage
ease for cutaneous melanoma. III disease.
In 2008, the EORTC 18071 trial was estab-
lished to assess whether adjuvant ipilimumab
24.5 Adjuvant and Neoadjuvant (anti-CTLA-4) could improve survival in patients
Systemic Therapy with resected, high-risk stage III melanoma
in Melanoma (n = 945) [99, 100]. Primary data from the
EORTC trial showed significantly prolonged
While surgical management remains the corner- median recurrence-free survival in patients
stone of locoregional control [49], it is well treated with adjuvant ipilimumab as compared to
established that stage III disease confers a high placebo (26.1 vs 17.1 months; HR = 0.75;
risk of distant metastasis and death [16]. Data p = 0.0013) [99]. Mature data has since demon-
from the AJCC eighth edition (2017) demonstrated improved 5-year recurrence-free survival
strates that 5-year and 10-year melanoma-specific (40.8% vs. 30.3%; HR = 0.76; p < 0.001) and
survival for patients with stage III disease were 5-year overall survival (65.4% vs. 54.4%;
77% and 69%, respectively, reaching 32% and HR = 0.72; p = 0.001) in patients treated with
24% in the stage IIID subgroup [16]. With the adjuvant ipilimumab [100]. However, 41.6% of
success of immune checkpoint inhibitors (e.g. patients in the ipilimumab group experienced
anti-CLTA-4 [89, 90], anti-PD-1 [91–93]) and immune-related adverse effects of grade 3 or 4
molecularly targeted therapy (e.g. BRAF and (vs. 2.7% in the placebo group), with 5 deaths
MEK inhibitors [94–98]) in the setting of unre- (1.1%) reported in the ipilimumab group owing
sectable and metastatic melanoma, efforts then to immune-related adverse events [100].
Eggermont AMM, et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III
melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015;16:522–30
Strengths • International, randomized, prospective trial with robust sample size (n = 951). Long-term
follow-up available (median follow-up, 6.9 years in final analysis) [101]
Limitations • Of the 471 patients who started ipilimumab, 251 (53.3%) patients discontinued treatment
owing to an adverse event, with approximately 40% discontinuing before initiation of
maintenance therapy. Does not address whether maintenance treatment with ipilimumab is
needed
Impact The EORTC 18071 trial was the first phase III trial to establish a significant survival benefit with
the use of an immune checkpoint inhibitor in the adjuvant setting
The EORTC 18071 trial spearheaded multiple KEYNOTE 054 trial provided further support for
phase III studies that have changed the modern PD-1 inhibitors, demonstrating improved 1-year
therapeutic landscape of high-risk resected mela- recurrence-free survival (75.4% vs. 61.0%;
noma. Notably, the Checkmate 238 trial later HR = 0.57; p < 0.001) in stage III patients treated
demonstrated superior 4-year recurrence-free with adjuvant pembrolizumab over placebo [104,
survival in patients with stage IIB–IV melanoma 105]. A similar rate of grade 3–4 TRAE was
treated with adjuvant nivolumab (anti-PD-1) as noted with pembrolizumab (14.5%) compared
compared to ipilimumab (51.7% vs. 41.2%; with nivolumab [104, 105]. The superiority of
HR = 0.71; p = 0.0003), with greater tolerability anti-PD-1 immunotherapy in terms of efficacy
[grade 3–4 treatment-related adverse events and tolerability as compared to other systemic
(TRAE), 14.4% vs. 45.9%] and lower rate of dis- agents was confirmed by a recent systematic
continuance (9.7% vs. 42.6%) [102, 103]. The review of 27 RCTs (n = 16,709) [106]. This
meta-analysis noted that although combined responses compared with its use in the adjuvant
adjuvant nivolumab–ipilimumab therapy con- setting, and may facilitate surgical resection by
ferred the highest rates of disease-free survival downstaging the tumour [116, 117]. This theory
(HR = 0.44) and overall-survival (HR = 0.67), was supported by the OpACIN trial, which dem-
these advantages were tempered by the signifi- onstrated improved 5-year recurrence-free sur-
cant risk of grade 3–5 adverse events (odds vival (70% vs. 60%) and 5-overall survival (90%
ratio = 0.46) [106]. Finally, the COMBI-AD trial vs. 70%) for patients treated with neoadjuvant
showed that adjuvant dabrafenib–trametinib ipilimumab–nivolumab versus adjuvant ipilim-
(BRAF and MEK inhibitors, respectively) con- umab–nivolumab [118, 119]. In a pooled analysis
ferred superior 3-year relapse-free survival (58% of 6 clinical trials (n = 192) by Menzies et al.
vs. 39%; HR = 0.47; p < 0.001) and 3-year over- clinical stage III melanoma demonstrated patho-
all survival (86% vs. 77%, p = 0.0006) as com- logic complete response rates of 47% and 37% to
pared to placebo for patients with stage III neoadjuvant BRAF/MEK targeted therapy and
melanoma harbouring BRAF V600E or V600K anti-PD-1 immunotherapy, respectively, with
mutations [107, 108]. On the basis of these clini- 2-year overall survival of 86% and 88%, and
cal trials, both adjuvant anti-PD-1 and BRAF- 2-year relapse-free survival of 47% and 75%,
targeted therapies have now been accepted as respectively [120]. In line with that of stage IV
standard-of-care in patients with high-risk melanoma [114], ipilimumab–nivolumab combi-
resected melanoma [49, 109]. nation immunotherapy appears to confer the
Current evidence suggests greater durability highest pathologic complete response rates and
of responses achieved with first-line anti-PD-1 longest relapse-free survival in the neoadjuvant
immunotherapy compared with BRAF/MEK setting, with acceptable tolerability [117, 118,
inhibitors in the setting of advanced melanoma, 120]. In addition, recent data from the phase II
regardless of BRAF-mutation status. While phase trial led by Patel et al. demonstrated that treat-
III clinical trials demonstrate high objective ment of resectable stage III–IV melanoma with
response rates (63–70%) associated with BRAF/ neoadjuvant-adjuvant pembrolizumab was asso-
MEK inhibitors [110–112], acquired resistance ciated with significantly longer event-free sur-
to targeted therapies appears to limit progression- vival than treatment with adjuvant-only
free survival (11.0–14.9 months) [110–113] and pembrolizumab (p = 0.004) [121]. Several phase
5-year overall survival (34%, 95% CI, 30–38%) II and III clinical trials are currently underway to
[113]. In contrast, 5-year follow-up analysis of investigate optimal neoadjuvant combinations
the CheckMate 067 trial showed durable clinical and dosing regimens [122], and are anticipated to
benefit with nivolumab in advanced melanoma further advance modern management of high-
(5-year overall survival, 44%), which was sus- risk stage III melanomas (NCT04949113;
tained in BRAF-mutation subgroup analyzes NCT03698019; NCT04949113; NCT02858921).
(46%) [114]. Combination therapy with ipilim- Pathologic response following neoadjuvant
umab/nivolumab further increased 5-year overall systemic therapy has been proven to be a strong
survival rates (52% and 60%, respectively) [114]. early surrogate endpoint of survival in the treat-
The superiority of BRAF/MEK inhibitor or anti- ment of melanoma [120]. The PRADO trial
PD-1 therapy (or their synergistic effect as com- assessed feasibility of using pathologic response
bined therapy) within the adjuvant setting has not after neoadjuvant ipilimumab–nivolumab ther-
been established, and remains an area of signifi- apy as a criterion to direct further treatment
cant clinical interest [115]. (Fig. 24.1). This study showed that personalized
Neoadjuvant systemic therapy for patients response-directed management based on the
with high-risk melanoma is the latest paradigm- index lymph node alone enabled de-escalation of
shifting advancement in melanoma treatment. treatment for 55/60 patients achieving major
Upfront neoadjuvant immunotherapy is posited pathologic response to neoadjuvant therapy
to stimulate stronger anti-tumour immune (n = 60/90; 66%), sparing patients from the sig-
MPR Follow-up FU2

(pCR/near-pCR) No CT + ultrasound
(≤10% viable tumor) TLND q12w
Stage IIIB/C
de novo or
2
recurrent IPI 1 mg kg–1 + Index pPR
Follow-up
FU
melanoma NIVO 3 mg kg–1 node (>10 to ≤50% viable TLND
CT q12w
RECIST 2 cycles q3w resection tumor)
1.1-measurable,
PA proven
2
NIVO q4w or Dab+Tram FU
pPR
TLND for BRAF + patients ± RT1
(>50% viable tumor)
Index node CT q12w
marker placement
Week 0 6 12 64
Fig. 24.1 Study design of the PRADO trial. Dab, dab- non-response; pPR, pathologic partial response; RT,
rafenib; FU, follow-up; IPI, ipilimumab; MPR, major radiotherapy; Tram, trametinib; TLND, therapeutic lymph
pathologic response; NIVO, nivolumab; PA, pathology; node dissection
pCR, pathologic complete response; pNR, pathologic
nificant morbidity associated with TLND and/or strate mixed survival benefits, and outcomes for
adjuvant therapy with improved quality of life this subgroup of patients remain poor [129].
[123]. No compromise to recurrence-free sur- Given its high tumour mutational burden
vival or distant metastasis-free survival (93% and [130], cSCC has been widely hypothesized to be
98%, respectively) was observed for patients in responsive to immune checkpoint inhibitor
this cohort [123]. Whilst further validation is immunotherapy. The EMPOWER-CSCC-1 trial
required, the PRADO trial provides a strong confirmed the efficacy of cemiplimab (an anti-
rationale for future RCTs to explore the value of PD-1 agent) in patients with locally advanced or
response-directed treatment personalization after metastatic cSCC, reporting an objective response
neoadjuvant systemic therapy. rate of 44.9%–50.8% and complete response
rates of 12.8%–20.3% with a median duration of
response ≥41.3 months [131, 132]. The
24.6 Management of High-Risk KEYNOTE-629 and CARSKIN trial subse-
Cutaneous Squamous Cell quently established the efficacy of pembroli-
Carcinoma zumab, with objective response rates of
34.3%–42% and durable disease control rates
Cutaneous squamous cell carcinoma (cSCC) is (52.4%–56.6% at week 12 in KEYNOTE-629
the second most common skin cancer worldwide trial; 60% at week 15 in CARSKIN trial)
after basal cell carcinoma (BCC). While the sur- [133–135]. Recent studies, including several pro-
gical cure rate for cSCC is ≥95%, aggressive or spective multicentre trials, provide further evi-
‘high-risk’ cSCC have substantially higher rates dence for the efficacy of anti-PD-1 agents
of locoregional recurrence (13–41%) and distant [136–139]. Anti-PD-1 immunotherapy are now
metastases (7%–16%) [124, 125]. Importantly, recommended by most guidelines as first-line
conventional management strategies for patients therapy for unresectable or advanced cSCC
with high-risk cSCC with postoperative adjuvant [140].
radiotherapy [126, 127] with chemotherapy The success of immune-checkpoint inhibi-
added for a small subgroup [128, 129] demon- tors for locally advanced and metastatic cSCC
generated interest in their application as neoad- establish the efficacy of neoadjuvant cemiplimab
juvant therapy for high-risk cSCC. In 2021, data in patients with resectable stage II–IV cSCC
from a single-institution pilot study (n = 20) [142]. In this study, a pathologic complete
showed that neoadjuvant cemiplimab for response was observed in 40/79 patients (51%;
patients with resectable, stage III–IVA cSCC 95% CI, 39%–62%) and a pathologic major
was feasible, reporting a pathologic complete response (<10% viable tumour) was observed in
response rate of 55% with no reports of serious 10/79 patients (13%; 95% CI, 6%–22%). Grade
adverse effects on follow-up (median follow-up 3–5 adverse events of any cause were observed
22.6 months) [141]. On the basis of these find- in 14/79 patients (18%), with one death consid-
ings, Gross et al. conducted a confirmatory mul- ered by the investigator to be possibly related to
ticentre phase II clinical trial (n = 79) to treatment [142].
Gross ND, et al. Neoadjuvant cemiplimab for stage II to IV cutaneous squamous-cell carcinoma. N Engl J Med.
2022;387:1557–68
Strengths • Prospective study with multicentre design
Limitations • With the absence of a control group and no randomization, the possibility of selection bias
cannot be excluded. Owing to the relatively short median follow-up (9.7 months), mature data
regarding disease-free survival is not yet available
Impact This was the first phase II trial to establish the efficacy of neoadjuvant cemiplimab in patients with
resectable stage II–IV (M0) cutaneous squamous cell carcinoma
Gross et al.’s landmark study signifies the first Currently, several phase II clinical trials are
phase II trial to demonstrate the high therapeutic ongoing, assessing various anti-PD-1 therapies in
activity of cemiplimab in patients with resectable the neoadjuvant setting (NCT05025813;
high-risk cSCC. This is of critical significance NCT04620200; NCT04632433; NCT05110781;
given that the current standard-of-care for NCT03565783; NCT04315701). In addition,
patients with high-risk cSCC (surgical excision given that the role of adjuvant systemic therapy
with postoperative adjuvant radiotherapy and/or for cSCC has yet to be defined, data from two
platinum-based chemotherapy, e.g. cisplatin) is large phase III trials exploring cemiplimab
largely based on retrospective and low-powered (NCT03969004) and pembrolizumab
studies [126, 129, 143–145]. A prospective phase (NCT03833167, KEYNOTE-630) as adjuvant
III trial (n = 321) conducted to assess the role of therapies for cSCC are widely anticipated.
adjuvant chemoradiotherapy in cSCC failed to Finally, several trials investigating the efficacy of
establish a significant improvement in disease- anti-PD-1 agents combined with EGFR inhibi-
free survival (p = 0.44) or overall survival tors (NCT03944941; NCT03082534) and con-
(p = 0.86) over adjuvant radiotherapy alone current radiotherapy (NCT03737721) are
[128]. No comparisons to surgery alone was underway. These studies aim to confirm the syn-
reported [128]. In addition, although epidermal ergistic anti-tumour activity of anti-PD-1 agents
growth factor receptor (EGFR) inhibitors (e.g. in combination with other modalities [148, 149]
cetuximab) have occasionally produced useful in the treatment of high-risk cSCC.
responses in cSCC [146, 147], existing data sug- The accurate identification of patients most
gests rates of response are low in high-risk likely to require more aggressive treatment (i.e.
cSCC. A phase II study (n = 22) of neoadjuvant [neo]adjuvant therapy) is crucial so that patients
gefitinib reported limited complete and partial are not subjected to the potential immune-related
response rates of 18.2% and 27.3%, respectively, adverse effects of immunotherapy unnecessarily.
with 6 (27.3%) patients reported having died of While most trials define ‘high-risk’ cSCC based
disease [146]. on clinicopathologic features as per the AJCC or
Brigham and Women’s Hospital (BWH) staging ment will arise, further minimizing treatment
systems [150, 151], the predictive value of these associated morbidity without compromising
staging systems for metastasis is poor [152] and a oncological efficacy for patients with skin
uniformly accepted prognostic tool for cSCC has cancer.
yet to be developed. Recently, a 40-gene expres-
sion profile (40-GEP) test panel was shown to
confer a superior positive predictive value for References
metastasis (60%) compared with the AJCC and
BWH staging systems (31.5% and 32.8%, respec- 1. Arnold M, et al. Global burden of cutaneous mel-
anoma in 2020 and projections to 2040. JAMA
tively), highlighting the need for further investi- Dermatol. 2022;158:495–503.
gation as to whether the 40-GEP can improve 2. Clark WH Jr, From L, Bernardino EA, Mihm
risk stratification further when combined with MC. The histogenesis and biologic behavior of
traditional clinicopathologic risk factors [152, primary human malignant melanomas of the skin.
Cancer Res. 1969;29:705–27.
153]. With standardization of risk assessment for 3. Allen AC, Spitz SM, melanoma. A clinicopathologi-
cSCC, there is the potential to standardize treat- cal analysis of the criteria for diagnosis and progno-
ment recommendations across different national sis. Cancer. 1953;6:1–45.
and professional guidelines, which is crucial to 4. Petersen NC, Bodenham DC, Lloyd OC. Malignant
melanomas of the skin: A study of the origin, devel-
reduce the variability currently seen in the man- opment, ˦tiology, spread, treatment, and prognosis.
agement of high-risk cSCC [140, 143]. Br J Plast Surg. 1962;15:49–94.
5. Mehnert JH, Heard JL. Staging of malignant mel-
anomas by depth of invasion: a proposed index to
prognosis. Am J Surg. 1965;110:168–76.
24.7 Expert Concluding 6. Morton DL, Davtyan DG, Wanek LA, Foshag LJ,
Commentary Cochran AJ. Multivariate analysis of the relation-
ship between survival and the microstage of primary
This chapter has explored the relevant history, melanoma by Clark level and Breslow thickness.
Cancer. 1993;71:3737–43.
challenges encountered, and milestones achieved 7. Garbe C, et al. Primary cutaneous melanoma.
in the field of skin cancer management with a Identification of prognostic groups and estimation
specific focus on five key landmark publications of individual prognosis for 5093 patients. Cancer.
that have shaped contemporary practice. To 1995;75:2484–91.
8. Edge SB, B.D., Compton CC, Fritz AG, Greene
ensure continued innovation and improved out- FL, Trotti A. AJCC cancer staging manual. 7th ed.
comes within this field, it is essential to maintain New York, NY: Springer; 2010.
ongoing clinical trials to refine management 9. Breslow A. Thickness, cross-sectional areas and
guidelines. Studies currently in progress include depth of invasion in the prognosis of cutaneous mel-
anoma. Ann Surg. 1970;172:902–8.
the MelMarT study evaluating 1 versus 2 cm 10. Balch CM, et al. Final version of 2009 AJCC mel-
excision margins for pT2-pT4 melanoma anoma staging and classification. J Clin Oncol.
(NCT02385214), the Phase III NADINA trial 2009;27:6199–206.
comparing neoadjuvant ipilimumab/nivolumab 11. Thompson JF, et al. Prognostic significance of mitotic
rate in localized primary cutaneous melanoma:
versus standard adjuvant nivolumab for stage III an analysis of patients in the multi-institutional
melanoma (NCT04949113), and the American joint committee on cancer melanoma
KEYNOTE-630 trial exploring the efficacy of staging database. J Clin Oncol. 2011;29:2199–205.
adjuvant pembrolizumab in patients with high- 12. Balch CM, et al. A multifactorial analysis of mela-
noma: prognostic histopathological features com-
risk cSCC (NCT03833167). We anticipate that paring Clark's and Breslow's staging methods. Ann
with ongoing surgical innovations, improved Surg. 1978;188:732–42.
understanding of the molecular biology of skin 13. Balch CM, et al. Prognostic factors analysis of 17,600
cancers, and more prospective data from clinical melanoma patients: validation of the American joint
committee on cancer melanoma staging system. J
trials, the landscape of our contemporary practice Clin Oncol. 2001;19:3622–34.
will continue to evolve. It is our hope that more 14. Büttner P, et al. Primary cutaneous melanoma.
nuanced and personalized approaches to manage- Optimized cutoff points of tumor thickness and
importance of Clark's level for prognostic classifica- noma: comparison of nodal micrometastases versus
tion. Cancer. 1995;75:2499–506. macrometastases. J Clin Oncol. 2010;28:2452–9.
15. Månsson-Brahme E, et al. Prognostic factors in 31. Egger ME, Gershenwald JE. Melanoma clinical
thin cutaneous malignant melanoma. Cancer. staging (Historical and Current). In: Fisher DE,
1994;73:2324–32. Bastian BC, editors. Melanoma. New York, NY:
16. Gershenwald JE, et al. Melanoma staging: evidence- Springer New York; 2017. p. 1–16.
based changes in the American joint committee on 32. Thompson JF, Shaw HM, Hersey P, Scolyer RA. The
cancer eighth edition cancer staging manual. CA history and future of melanoma staging. J Surg
Cancer J Clin. 2017;67:472–92. Oncol. 2004;86:224–35.
17. Breslow A. Problems in the measurement of tumor 33. Handley WS. The pathology of melanotic growths
thickness and level of invasion in cutaneous mela- in relation to their operative treatment (lecture II).
noma. Hum Pathol. 1977;8:1–2. Lancet. 1907;169:996–1003.
18. Prade M, Sancho-Garnier H, Cesarini JP, Cochran 34. Handley WS. The pathology of melanotic growths
A. Difficulties encountered in the application of in relation to their operative treatment (lecture I).
Clark classification and the Breslow thickness mea- Lancet. 1907;169:927–33.
surement in cutaneous malignant melanoma. Int J 35. Pringle JH. A method of operation in cases of
Cancer. 1980;26:159–63. Melanotic Tumours of the skin. Edinb Med J.
19. Colloby PS, West KP, Fletcher A. Observer variation 1908;23(6):496.
in the measurement of Breslow depth and Clark's 36. Veronesi U, Cascinelli N. Narrow excision (1-cm
level in thin cutaneous malignant melanoma. J margin). A safe procedure for thin cutaneous mela-
Pathol. 1991;163:245–50. noma. Arch Surg. 1991;126:438–41.
20. Amin MB, Edge S, Greene F, Byrd DR, Brookland 37. Cascinelli N. Margin of resection in the manage-
RK, Washington MK, Gershenwald JE, Compton ment of primary melanoma. Semin Surg Oncol.
CC, Hess KR, et al. AJCC cancer staging manual. 1998;14:272–5.
8th ed. New York, NY: Springer; 2017. 38. Veronesi U, et al. Thin stage I primary cutane-
21. Hanna S, Lo SN, Saw RPM. Surgical excision mar- ous malignant melanoma. Comparison of exci-
gins in primary cutaneous melanoma: A system- sion with margins of 1 or 3 cm. N Engl J Med.
atic review and meta-analysis. Eur J Surg Oncol. 1988;318:1159–62.
2021;47:1558–74. 39. Ringborg U, et al. Resection margins of 2 versus
22. Morton DL, et al. Final trial report of sentinel-node 5 cm for cutaneous malignant melanoma with a
biopsy versus nodal observation in melanoma. N tumor thickness of 0.8 to 2.0 mm: randomized study
Engl J Med. 2014;370:599–609. by the Swedish Melanoma Study Group. Cancer.
23. Buzaid AC, et al. Critical analysis of the current 1996;77:1809–14.
American joint committee on cancer staging system 40. Cohn-Cedermark G, et al. Long term results
for cutaneous melanoma and proposal of a new stag- of a randomized study by the Swedish mela-
ing system. J Clin Oncol. 1997;15:1039–51. noma study group on 2-cm versus 5-cm resection
24. Balch CM, et al. A new American joint committee margins for patients with cutaneous melanoma
on cancer staging system for cutaneous melanoma. with a tumor thickness of 0.8-2.0 mm. Cancer.
Cancer. 2000;88:1484–91. 2000;89:1495–501.
25. Gimotty PA, et al. Identification of high-risk patients 41. Khayat D, et al. Surgical margins in cutaneous mela-
among those diagnosed with thin cutaneous melano- noma (2 cm versus 5 cm for lesions measuring less
mas. J Clin Oncol. 2007;25:1129–34. than 2.1-mm thick). Cancer. 2003;97:1941–6.
26. Green AC, Baade P, Coory M, Aitken JF, Smithers 42. Balch CM, et al. Efficacy of 2-cm surgical margins
M. Population-based 20-year survival among people for intermediate-thickness melanomas (1 to 4 mm).
diagnosed with thin melanomas in Queensland, Results of a multi-institutional randomized surgi-
Australia. J Clin Oncol. 2012;30:1462–7. cal trial. Ann Surg. 1993;218:262–267; discussion
27. Lo SN, Scolyer RA, Thompson JF. Long-term sur- 267–269.
vival of patients with thin (T1) cutaneous mela- 43. Karakousis CP, et al. Local recurrence in malignant
nomas: A Breslow thickness cut point of 0.8 mm melanoma: long-term results of the multiinstitu-
separates higher-risk and lower-risk tumors. Ann tional randomized surgical trial. Ann Surg Oncol.
Surg Oncol. 2018;25:894–902. 1996;3:446–52.
28. Balch CM, et al. The prognostic significance 44. Balch CM, et al. Long-term results of a prospective
of ulceration of cutaneous melanoma. Cancer. surgical trial comparing 2 cm vs. 4 cm excision mar-
1980;45:3012–7. gins for 740 patients with 1-4 mm melanomas. Ann
29. McGovern VJ, Shaw HM, Milton GW, McCarthy Surg Oncol. 2001;8:101–8.
WH. Ulceration and prognosis in cutaneous malig- 45. Hayes AJ, et al. Wide versus narrow excision mar-
nant melanoma. Histopathology. 1982;6:399–407. gins for high-risk, primary cutaneous melanomas:
30. Balch CM, et al. Multivariate analysis of prognostic long-term follow-up of survival in a randomised
factors among 2,313 patients with stage III mela- trial. Lancet Oncol. 2016;17:184–92.
46. Thomas JM, et al. Excision margins in high- of routine elective lymphadenectomy in manage-
risk malignant melanoma. N Engl J Med. ment of malignant melanoma Preliminary results.
2004;350:757–66. Cancer. 1978;41:948–56.
47. Gillgren P, et al. 2-cm versus 4-cm surgical excision 63. Morton DL, et al. Technical details of intraoperative
margins for primary cutaneous melanoma thicker lymphatic mapping for early stage melanoma. Arch
than 2 mm: a randomised, multicentre trial. Lancet. Surg. 1992;127:392–9.
2011;378:1635–42. 64. Cochran AJ, et al. Sentinel lymph nodes show pro-
48. Utjés D, et al. 2-cm versus 4-cm surgical excision found downregulation of antigen-presenting cells of
margins for primary cutaneous melanoma thicker the Paracortex: implications for tumor biology and
than 2 mm: long-term follow-up of a multicentre, treatment. Mod Pathol. 2001;14:604–8.
randomised trial. Lancet. 2019;394:471–7. 65. Morton DL, Cochran AJ. The case for lymphatic
49. National Comprehensive Cancer Network (NCCN). mapping and sentinel lymphadenectomy in the
Melanoma: Cutaneous (Version 2.2023). (2023). management of primary melanoma. Br J Dermatol.
50. National Institute for Health and Care Excellence 2004;151:308–19.
(NICE). Melanoma: assessment and management. 66. Thompson JF, et al. Sentinel lymph node status as
(2022). an indicator of the presence of metastatic mela-
51. Sladden M, et al. Clinical question: what are the noma in regional lymph nodes. Melanoma Res.
recommended safety margins for radical excision of 1995;5:255–60.
primary melanoma? In: Clinical practice guidelines 67. Morton DL, et al. Validation of the accuracy of intra-
for the diagnosis and management of melanoma. operative lymphatic mapping and sentinel lymphad-
Sydney: Melanoma Institute Australia; 2020. enectomy for early-stage melanoma: a multicenter
52. Garbe C, et al. European consensus-based interdisci- trial. Multicenter selective lymphadenectomy trial
plinary guideline for melanoma. Part 2: treatment— group. Ann Surg. 1999;230:453–463; discussion
update 2019. Eur J Cancer. 2020;126:159–77. 463–455.
53. Moncrieff MD, et al. 1 versus 2-cm excision mar- 68. Wong SL, et al. Sentinel lymph node biopsy and
gins for pT2-pT4 primary cutaneous melanoma Management of Regional Lymph Nodes in mela-
(MelMarT): A feasibility study. Ann Surg Oncol. noma: American Society of Clinical Oncology
2018;25:2541–9. and Society of Surgical Oncology clinical practice
54. Haigh PI, DiFronzo LA, McCready DR. Optimal guideline update. J Clin Oncol. 2017;36:399–413.
excision margins for primary cutaneous melanoma: 69. Gyorki DE, et al. When is sentinel lymph node
a systematic review and meta-analysis. Can J Surg. biopsy (SLNB) indicated? In: Clinical practice
2003;46:419–26. guidelines for the diagnosis and management of
55. Sladden MJ, et al. Surgical excision margins for pri- melanoma; 2020.
mary cutaneous melanoma. Cochrane Database Syst 70. Garbe C, et al. European consensus-based interdis-
Rev. 2009;4:Cd004835. ciplinary guideline for melanoma. Part 2: treatment -
56. Lens MB, Nathan P, Bataille V. Excision margins update 2022. Eur J Cancer. 2022;170:256–84.
for primary cutaneous melanoma: updated pooled 71. Teixeira V, et al. Prediction of sentinel node status
analysis of randomized controlled trials. Arch Surg. and clinical outcome in a melanoma Centre. J Skin
2007;142:885–891; discussion 891–883. Cancer. 2013;2013:904701.
57. Madu M, van Akkooi ACJ. Response to Wheatley 72. Azimi F, et al. Tumor-infiltrating lymphocyte grade
et al., “Surgical excision margins in primary cuta- is an independent predictor of sentinel lymph node
neous melanoma: A meta-analysis and Bayesian status and survival in patients with cutaneous mela-
probability evaluation”, cancer treatment reviews. noma. J Clin Oncol. 2012;30:2678–83.
Cancer Treat Rev. 2016;45:76. 73. Gyorki DE, et al. Sentinel lymph node biopsy in T4
58. Wheatley K, Wilson JS, Gaunt P, Marsden melanoma: an important risk-stratification tool. Ann
JR. Surgical excision margins in primary cutaneous Surg Oncol. 2016;23:579–84.
melanoma: A meta-analysis and Bayesian probabil- 74. Leiter U, et al. Complete lymph node dissection
ity evaluation. Cancer Treat Rev. 2016;42:73–81. versus no dissection in patients with sentinel lymph
59. Hochwald SN, Coit DG. Role of elective lymph node biopsy positive melanoma (DeCOG-SLT):
node dissection in melanoma. Semin Surg Oncol. a multicentre, randomised, phase 3 trial. Lancet
1998;14:276–82. Oncol. 2016;17:757–67.
60. Balch CM, et al. Efficacy of an elective regional 75. Leiter U, et al. Final analysis of DeCOG-SLT trial:
lymph node dissection of 1 to 4 mm thick melano- no survival benefit for complete lymph node dissec-
mas for patients 60 years of age and younger. Ann tion in patients with melanoma with positive sentinel
Surg. 1996;224:255–63. ;discussion 263–256. node. J Clin Oncol. 2019;37:3000–8.
61. Veronesi U, et al. Delayed regional lymph node dis- 76. Faries MB, et al. Completion dissection or observa-
section in stage I melanoma of the skin of the lower tion for sentinel-node metastasis in melanoma. N
extremities. Cancer. 1982;49:2420–30. Engl J Med. 2017;376:2211–22.
62. Sim FH, Taylor WF, Ivins JC, Pritchard DJ, Soule 77. Melstrom LG, et al. International multi-institutional
EH. A prospective randomized study of the efficacy management and outcome of melanoma patients
with positive sentinel lymph nodes in more than one 93. Robert C, et al. Pembrolizumab versus Ipilimumab
nodal basin. Ann Surg Oncol. 2014;21:4324–9. in Advanced Melanoma. N Engl J Med.
78. Klemen ND, et al. Completion lymphadenectomy 2015;372:2521–32.
for a positive sentinel node biopsy in melanoma 94. Chapman PB, et al. Improved survival with vemu-
patients is not associated with a survival benefit. J rafenib in melanoma with BRAF V600E mutation.
Surg Oncol. 2019;119:1053–9. N Engl J Med. 2011;364:2507–16.
79. Gyorki DE, et al. Incidence and location of positive 95. Hauschild A, et al. Dabrafenib in BRAF-mutated
nonsentinel lymph nodes in head and neck mela- metastatic melanoma: a multicentre, open-label,
noma. Eur J Surg Oncol (EJSO). 2014;40:305–10. phase 3 randomised controlled trial. Lancet.
80. Bamboat ZM, et al. Observation after a positive sen- 2012;380:358–65.
tinel lymph node biopsy in patients with melanoma. 96. Flaherty KT, et al. Combined BRAF and MEK inhi-
Ann Surg Oncol. 2014;21:3117–23. bition in melanoma with BRAF V600 mutations. N
81. Mosquera C, Vora HS, Vohra N, Fitzgerald Engl J Med. 2012;367:1694–703.
TL. Population-based analysis of completion lymph- 97. Larkin J, et al. Combined vemurafenib and cobi-
adenectomy in intermediate-thickness melanoma. metinib in BRAF-mutated melanoma. N Engl J
Ann Surg Oncol. 2017;24:127–34. Med. 2014;371:1867–76.
82. Wong SL, et al. Melanoma patients with positive 98. Robert C, et al. Improved overall survival in mela-
sentinel nodes who did not undergo completion noma with combined dabrafenib and trametinib. N
lymphadenectomy: a multi-institutional study. Ann Engl J Med. 2015;372:30–9.
Surg Oncol. 2006;13:809–16. 99. Eggermont AMM, et al. Adjuvant ipilimumab
83. Bredbeck BC, et al. Management of the positive versus placebo after complete resection of high-
sentinel lymph node in the post-MSLT-II era. J Surg risk stage III melanoma (EORTC 18071): a ran-
Oncol. 2020;122:1778–84. domised, double-blind, phase 3 trial. Lancet Oncol.
84. Namikawa K, et al. Correlation of tumor burden in 2015;16:522–30.
sentinel lymph nodes with tumor burden in nonsen- 100. Eggermont AMM, et al. Prolonged survival in stage
tinel lymph nodes and survival in cutaneous mela- III melanoma with Ipilimumab adjuvant therapy. N
noma. Clin Cancer Res. 2019;25:7585–93. Engl J Med. 2016;375:1845–55.
85. Guggenheim M, et al. The influence of sentinel 101. Eggermont AMM, et al. Ipilimumab versus placebo
lymph node tumour burden on additional lymph after complete resection of stage III melanoma:
node involvement and disease-free survival in cuta- Long-term follow-up results the EORTC 18071
neous melanoma—a retrospective analysis of 392 double-blind phase 3 randomized trial. J Clin Oncol.
cases. Br J Cancer. 2008;98:1922–8. 2019;37:2512.
86. Palve J, Ylitalo L, Luukkaala T, Jernman J, Korhonen 102. Ascierto PA, et al. Adjuvant nivolumab versus ipi-
N. Sentinel node tumor burden in prediction of prog- limumab in resected stage IIIB-C and stage IV
nosis in melanoma patients. Clin Exp Metastasis. melanoma (CheckMate 238): 4-year results from a
2020;37:365–76. multicentre, double-blind, randomised, controlled,
87. Verver D, et al. Risk stratification of sentinel node– phase 3 trial. Lancet Oncol. 2020;21:1465–77.
positive melanoma patients defines surgical manage- 103. Weber J, et al. Adjuvant Nivolumab versus
ment and adjuvant therapy treatment considerations. Ipilimumab in resected stage III or IV melanoma. N
Eur J Cancer. 2018;96:25–33. Engl J Med. 2017;377:1824–35.
88. Murali R, Desilva C, Thompson JF, Scolyer 104. Eggermont Alexander MM, et al. Five-year
RA. Non-sentinel node risk score (N-SNORE): a analysis of adjuvant Pembrolizumab or pla-
scoring system for accurately stratifying risk of non- cebo in stage III melanoma. NEJM Evidence.
sentinel node positivity in patients with cutaneous 2022;1:EVIDoa2200214.
melanoma with positive sentinel lymph nodes. J Clin 105. Eggermont AMM, et al. Adjuvant Pembrolizumab
Oncol. 2010;28:4441–9. versus placebo in resected stage III melanoma. N
89. Hodi FS, et al. Improved survival with ipilimumab Engl J Med. 2018;378:1789–801.
in patients with metastatic melanoma. N Engl J Med. 106. Ba H, Zhu F, Zhang X, Mei Z, Zhu Y. Comparison
2010;363:711–23. of efficacy and tolerability of adjuvant ther-
90. Schadendorf D, et al. Pooled analysis of Long-term apy for resected high-risk stage III-IV cutane-
survival data From phase II and phase III trials of ous melanoma: a systemic review and Bayesian
Ipilimumab in Unresectable or metastatic mela- network meta-analysis. Ther Adv Med Oncol.
noma. J Clin Oncol. 2015;33:1889–94. 2023;15:17588359221148918.
91. Larkin J, et al. Combined Nivolumab and Ipilimumab 107. Dummer R, et al. Five-year analysis of adjuvant
or monotherapy in untreated melanoma. N Engl J Dabrafenib plus Trametinib in stage III melanoma.
Med. 2015;373:23–34. N Engl J Med. 2020;383:1139–48.
92. Robert C, et al. Nivolumab in previously untreated 108. Long GV, et al. Adjuvant Dabrafenib plus Trametinib
melanoma without BRAF mutation. N Engl J Med. in stage III BRAF-mutated melanoma. N Engl J
2015;372:320–30. Med. 2017;377:1813–23.
109. Carlino M, et al. Clinical question:what is the role of 124. Sun L, et al. Association of Disease Recurrence with
adjuvant systemic therapy in patients with resected Survival Outcomes in patients with cutaneous squa-
melanoma? Clinical practice guidelines for the diag- mous cell carcinoma of the head and neck treated
nosis and management of melanoma: In; 2018. with multimodality therapy. JAMA Dermatol.
110. Long GV, et al. Dabrafenib and trametinib versus 2019;155:442–7.
dabrafenib and placebo for Val600 BRAF-mutant 125. Yung AE, et al. Benchmarking survival outcomes
melanoma: a multicentre, double-blind, phase 3 ran- following surgical management of pT3 and pT4
domised controlled trial. Lancet. 2015;386:444–51. cutaneous squamous cell carcinoma of the head and
111. Ascierto PA, et al. Cobimetinib combined with neck. Ann Surg Oncol. 2022;29:5124–38.
vemurafenib in advanced BRAF(V600)-mutant 126. Harris BN, et al. Association of Adjuvant Radiation
melanoma (coBRIM): updated efficacy results from Therapy with Survival in patients with advanced
a randomised, double-blind, phase 3 trial. Lancet cutaneous squamous cell carcinoma of the head
Oncol. 2016;17:1248–60. and neck. JAMA Otolaryngol Head Neck Surg.
112. Dummer R, et al. Encorafenib plus binimetinib 2019;145:153–8.
versus vemurafenib or encorafenib in patients with 127. Zhang J, Wang Y, Wijaya WA, Liang Z, Chen
BRAF-mutant melanoma (COLUMBUS): a multi- J. Efficacy and prognostic factors of adjuvant radio-
centre, open-label, randomised phase 3 trial. Lancet therapy for cutaneous squamous cell carcinoma: A
Oncol. 2018;19:603–15. systematic review and meta-analysis. J Eur Acad
113. Robert C, et al. Five-year outcomes with Dabrafenib Dermatol Venereol. 2021;35:1777–87.
plus Trametinib in metastatic melanoma. N Engl J 128. Porceddu SV, et al. Postoperative concurrent
Med. 2019;381:626–36. Chemoradiotherapy versus postoperative radio-
114. Larkin J, et al. Five-year survival with combined therapy in high-risk cutaneous squamous cell carci-
Nivolumab and Ipilimumab in advanced melanoma. noma of the head and neck: the randomized phase III
N Engl J Med. 2019;381:1535–46. TROG 05.01 trial. J Clin Oncol. 2018;36:1275–83.
115. De Meza MM, et al. Adjuvant BRAF-MEK inhibi- 129. Trosman SJ, Zhu A, Nicolli EA, Leibowitz JM,
tors versus anti PD-1 therapy in stage III melanoma: Sargi ZB. High-risk cutaneous squamous cell can-
A propensity-matched outcome analysis. Cancers. cer of the head and neck: risk factors for recurrence
2023;15:409. and impact of adjuvant treatment. Laryngoscope.
116. Jung S, Johnson DB. Management of Acral and 2021;131:E136–e143.
Mucosal Melanoma: medical oncology perspective. 130. Chalmers ZR, et al. Analysis of 100,000 human can-
Oncologist. 2022;27:703–10. cer genomes reveals the landscape of tumor muta-
117. Amaria RN, et al. Neoadjuvant immune checkpoint tional burden. Genome Med. 2017;9:34.
blockade in high-risk resectable melanoma. Nat 131. Migden MR, et al. PD-1 blockade with Cemiplimab
Med. 2018;24:1649–54. in advanced cutaneous squamous-cell carcinoma. N
118. Blank CU, et al. Neoadjuvant versus adjuvant ipi- Engl J Med. 2018;379:341–51.
limumab plus nivolumab in macroscopic stage III 132. Migden MR, et al. 814P phase II study of
melanoma. Nat Med. 2018;24:1655–61. cemiplimab in patients with advanced cutaneous
119. Versluis JM, et al. Survival update of neoadjuvant squamous cell carcinoma (CSCC): final analysis
ipilimumab plus nivolumab in macroscopic stage III from EMPOWER-CSCC-1 groups 1, 2 and 3. Ann
melanoma in the OpACIN and OpACIN-neo trials. Oncol. 2022;33:S918–9.
Ann Oncol. 2023;34:420–30. 133. Grob J-J, et al. Pembrolizumab monotherapy
120. Menzies AM, et al. Pathological response and sur- for recurrent or metastatic cutaneous squa-
vival with neoadjuvant therapy in melanoma: a mous cell carcinoma: A single-arm phase II trial
pooled analysis from the international Neoadjuvant (KEYNOTE-629). J Clin Oncol. 2020;38:2916–25.
melanoma consortium (INMC). Nat Med. 134. Hughes BGM, et al. Pembrolizumab for locally
2021;27:301–9. advanced and recurrent/metastatic cutaneous squa-
121. Patel SP, et al. Neoadjuvant–adjuvant or adjuvant- mous cell carcinoma (KEYNOTE-629 study): an
only pembrolizumab in advanced melanoma. N Engl open-label, nonrandomized, multicenter, phase II
J Med. 2023;388:813–23. trial. Ann Oncol. 2021;32:1276–85.
122. Lucas MW, et al. The NADINA trial: A multi- 135. Maubec E, et al. Phase II study of Pembrolizumab
center, randomised, phase 3 trial comparing the as first-line, single-drug therapy for patients with
efficacy of neoadjuvant ipilimumab plus nivolumab Unresectable cutaneous squamous cell carcinomas.
with standard adjuvant nivolumab in macroscopic J Clin Oncol. 2020;38:3051–61.
resectable stage III melanoma. J Clin Oncol. 136. Migden MR, et al. Cemiplimab in locally advanced
2022;40:TPS9605-TPS9605. cutaneous squamous cell carcinoma: results from an
123. Reijers ILM, et al. Personalized response-directed open-label, phase 2, single-arm trial. Lancet Oncol.
surgery and adjuvant therapy after neoadjuvant ipi- 2020;21:294–305.
limumab and nivolumab in high-risk stage III mela- 137. Rischin D, et al. Integrated analysis of a phase 2
noma: the PRADO trial. Nat Med. 2022;28:1178–88. study of cemiplimab in advanced cutaneous squa-
mous cell carcinoma: extended follow-up of out- 146. Lewis CM, et al. A phase II study of gefitinib for
comes and quality of life analysis. J Immunother aggressive cutaneous squamous cell carcinoma of the
Cancer. 2021;9:e002757. head and neck. Clin Cancer Res. 2012;18:1435–46.
138. Seiwert TY, et al. Safety and clinical activity of 147. Maubec E, et al. Phase II study of cetuximab as
pembrolizumab for treatment of recurrent or meta- first-line single-drug therapy in patients with unre-
static squamous cell carcinoma of the head and neck sectable squamous cell carcinoma of the skin. J Clin
(KEYNOTE-012): an open-label, multicentre, phase Oncol. 2011;29:3419–26.
1b trial. Lancet Oncol. 2016;17:956–65. 148. Formenti SC, Demaria S. Combining radiotherapy
139. Amaral T, et al. Advanced cutaneous squamous cell and cancer immunotherapy: A paradigm shift. JNCI
carcinoma: real world data of patient profiles and J Natl Cancer Inst. 2013;105:256–65.
treatment patterns. J Eur Acad Dermatol Venereol. 149. Yi M, et al. Combination strategies with PD-1/
2019;33(Suppl 8):44–51. PD-L1 blockade: current advances and future direc-
140. National Comprehensive Cancer Network. tions. Mol Cancer. 2022;21:28.
Squamous Cell Skin Cancer (Version 1.2023). 150. Karia PS, et al. Evaluation of American joint com-
(2023). mittee on cancer, International Union against
141. Ferrarotto R, et al. Pilot phase II trial of Neoadjuvant Cancer, and Brigham and Women's Hospital tumor
immunotherapy in Locoregionally advanced, staging for cutaneous squamous cell carcinoma. J
Resectable cutaneous squamous cell carcinoma of the Clin Oncol. 2014;32:327–34.
head and neck. Clin Cancer Res. 2021;27:4557–65. 151. Ruiz ES, Karia PS, Besaw R, Schmults
142. Gross ND, et al. Neoadjuvant Cemiplimab for stage CD. Performance of the American joint commit-
II to IV cutaneous squamous-cell carcinoma. N Engl tee on cancer staging manual, 8th edition vs. the
J Med. 2022;387:1557–68. Brigham and Women’s hospital tumor classifica-
143. Kim Y, et al. Adjuvant radiotherapy may not signifi- tion system for cutaneous squamous cell carcinoma.
cantly change outcomes in high-risk cutaneous squa- JAMA Dermatol. 2019;155:819–25.
mous cell carcinomas with clear surgical margins: 152. Wysong A, et al. Validation of a 40-gene expression
A systematic review and meta-analysis. J Am Acad profile test to predict metastatic risk in localized
Dermatol. 2022;86:1246–57. high-risk cutaneous squamous cell carcinoma. J Am
144. Jambusaria-Pahlajani A, et al. Surgical monotherapy Acad Dermatol. 2021;84:361–9.
versus surgery plus adjuvant radiotherapy in high- 153. Au JH, Hooper PB, Fitzgerald AL, Somani
risk cutaneous squamous cell carcinoma: a sys- AK. Clinical utility of the 40-gene expression pro-
tematic review of outcomes. Dermatologic Surg. file (40-GEP) test for improved patient management
2009;35:574–85. decisions and disease-related outcomes when com-
145. Tanvetyanon T, et al. Postoperative concurrent che- bined with current Clinicopathological risk factors
motherapy and radiotherapy for high-risk cutaneous for cutaneous squamous cell carcinoma (cSCC): case
squamous cell carcinoma of the head and neck. Head series. Dermatol Ther (Heidelb). 2022;12:591–7.
Neck. 2015;37:840–5.
Part VII
Burn Surgery
Evolution of Burn Surgery
25
August Schaeffer, Laxmi Dongur,
and Steven E. Wolf

1. Herndon DN, Barrow RE, Rutan RL, Rutan
The field of burn surgery is a complex disci-
TC, Desai MH, Abston S. A comparison of
pline. Like others, it has evolved tremendously
conservative versus early excision: therapies
over the past century with the development of
in severely burned patients [1]. Ann Surg.
new scientific knowledge and technologies,
1989;209:547–53.
but to address all of the landmark changes is
2. Heimbach DM, Luterman A, Burke J, Cram
challenging. However in this vein, we chose
A, Herndon DN, Hunt J, Jordan M, McManus
five papers which we feel had the most histori-
W, Solem L, Warden G. Artificial dermis for
cal impact on the evolution of modern burn
major burns. A multi-center randomized clini-
surgery. These were chosen based on their
cal trial. Annals of Surgery. 1988;208:313–20.
validation of burn surgery principles which
3. Baxter CR, Shires GT. Physiological response
still define the field today. These principles are
to crystalloid resuscitation of severe burns
divided into the following categories: early
[10]. Ann N Y Acad Sci. 1968.
excision and grafting, topical antiseptic appli-
4. Moyer CA, Brentano L, Gravens DL, Margraf
cation, use of skin substitutes, fluid resuscita-
HW, Monafo WW. Treatment of large human
tion, and nutritional support.
burns with 0.5% silver nitrate solution [17].
Arch Surg. 1965;90:812–67.
Keywords
5. Blocker TG, Levin WC, Nowinski WW, Lewis
Wound care · Excision · Grafting · Burn SO, Blocker V. Nutrition studies in the
surgery · Nutrition · Resuscitation severely burned [22]. Ann Surg.
Homograft · Autograft · Xenograft 1955;13:295–7.
Antibiotics.
A. Schaeffer · L. Dongur · S. E. Wolf (*)

Department of Surgery, University of Texas Medical
Branch, Galveston, TX, USA
https://doi.org/10.1007/978-3-031-57132-9_25
264 A. Schaeffer et al.
25.1 Early Excision and Grafting

Herndon DN, Barrow RE, Rutan RL, Rutan TC, Desai MH, Abston S. A comparison of conservative versus early
excision: therapies in severely burned patients [1]. Ann Surg. 1989;209:547–53
Strengths • This was a prospective, randomized trial validating existing techniques supported by less robust
studies
Limitations • The population size of the study was limited without granular stratification in the burn sizes of the
patients. The results of the study cannot be extrapolated to make clinical decisions for those
patients excluded from the study, such as those over age 55
Impact The study validated the already available technique of early excision and grafting in burn surgery with
a prospective, randomized trial. Publication of this trial spurred further development of the technique
and established it as the standard of care worldwide
At the time of publication, the technique of be noted that the pediatric patients were used as
early excision of thermal injuries was already the positive treatment control for early excision as
known and described originally in reports from these were all treated with early excision. The
Zora Janzekovic in the early 1970s [2]. However, arms of the study randomized and compared
it had not yet been accepted as standard practice. adults-only group. One arm (n = 54) had patients
Limiting the appeal of the technique was a lack treated with traditional conservative measures
of a comparative study of outcomes for those which involved daily antimicrobial dressings and
treated with early excision and grafting and those wound care. Once the burn eschars began to sepa-
who were treated with the traditional practice of rate from the underlying granulation tissue, the
wound care and grafting after eschar separation. patients underwent homografting. In the other arm
Publication of this work then provided firm evi- (n = 38) of the study, patients received fascial exci-
dence of the benefits of early excision and graft- sion of burned tissue within 72 h followed by
ing and set a precedent in the field, both by either cadaveric homograft or autografting.
providing evidence from a prospective random- The results of the study showed that among
ized trial and showing mortality benefit for early adult patients without smoke inhalation injury
surgical intervention. between ages 17 and 30, a significant decrease in
The underlying principles of early excision and mortality was found for early excision compared
grafting arose from the ability to reduce the burden to conservative intervention (9% vs. 45%,
of the inflammatory cascade which ultimately p < 0.05). However, the benefits of early surgical
leads to infection and organ failure [3]. Studies in intervention began to disappear in patients with
the 1970s and 1980s by Jack Burke, Ron Tompkins, concomitant inhalational injuries or increasing
and others from the Boston Shriners’ Pediatric age. This was attributed to the decreasing physio-
Burn Hospital showed a move toward improving logic reserve of the patients. Among the secondary
survival with early fascial excision, which drove outcomes, rates of sepsis, length of stay, and num-
growing interest in early surgical intervention [4]. ber of procedures in the adult population were not
However, it would not be until the late 1980s that significantly different. Blood use, however, was
early excision and grafting was definitively shown significantly lower (0.7 vs. 2.1 cc/cm2 excised,
to be of benefit for outcomes [5]. The study com- p < 0.05) in adult patients managed conservatively
pared 85 adult (17–55 years) and 259 pediatric compared to those that underwent early excision.
(1 month–16 years.) patients with greater than By the time this paper was published, early
20% third-degree burns and/or 30% second-degree excision of burn patients was already a mainstay of
admitted to the University of Texas Medical treatment in some centers, especially in pediatric
Branch (UTMB) Blocker Burn Unit and Galveston populations (Tomkins RL, 1986). Dr. Monafo
Shriners’ Paediatric Burn Hospital. Those older went as far as to call the practice of conservative
than 55, TBSA >98%, with electrical and chemi- treatment “prehistoric” [5]. However, this trial
cal burns, or who sustained injuries more than definitively showed the benefit of early excision
3 days prior to admission were excluded. It should within the adult population in a rigorous scientific
25 Evolution of Burn Surgery 265
fashion. This practice of surgical intervention con- live on and subsequently surpassed fascial exci-
tinues to define our surgical practice today. sion as the surgical intervention of choice [6].
Notably, Dr. Janzekovic’s tangential excision Regardless, the principles of source control with
techniques developed in the 1960s continued to early grafting were cemented with this paper.
25.2 Artificial Skin

Heimbach DM, Luterman A, Burke J, Cram A, Herndon DN, Hunt J, Jordan M, McManus W, Solem L, Warden G.
Artificial dermis for major burns. A multi-center randomized clinical trial. Annals of Surgery. 1988;208:313–20
Strengths • This was a prospective, randomized, controlled, multicenter prospective trial
Limitations • The utilization of this material is limited by its price and a two-stage surgical intervention
Impact This was the first trial utilizing an artificial skin substitute, which opened the door for further
research into the area of artificial skin substitutes
A fundamental principle of surgery in this fish skin, were also developed as temporary grafts
field is excision and grafting. While simple in in a similar fashion.
theory, the area of development surrounding both The first randomized controlled trial of an artifi-
these aspects of the procedure have undergone cially created dermal skin substitute was performed
tremendous changes over the past century. Prior in 1988 [7]. Dr. Heimbach and colleagues used a sili-
to the 1930s and the advent of the first derma- con matrix with a collagen interior developed by Drs.
tome and other devices allowing for split thick- Yannas and Burke [8]. In the trial, the artificial dermis
ness harvesting, all skin grafts were full-thickness was used in a fashion comparable to the aforemen-
with closure of the freshly created wound in order tioned homo- and xenografts, i.e., as a temporizing
to graft other sites. Split thickness grafting after measure until definitive autograft could be per-
the invention of the dermatome allowed for donor formed. In this study of 106 patients across 11 burn
sites to heal on their own, and these donor sites centers, the artificial dermis (AD) had inferior take
could also be harvested multiple times in compared to all types of traditional graft types (80%
sequence. The invention of the dermatome and vs. 95%, p < 0.05); the artificial dermal skin substi-
proliferation of split thickness grafting proved to tute “took” less readily than widely meshed auto-
be a powerful and influential boon for the field of graft, but was non-inferior to allograft. The cosmetic
burn surgery. This would prove true for multiple results were also comparable 1 year after injury.
reasons, including production of consistent thick- While this silicone dermis marketed as
ness grafts to be harvested multiple times, pro- “Integra” was not triumphantly superior to tradi-
viding a large volume of skin grafts which could tional graft options, the most groundbreaking
then facilitate closure of open wounds in a staged aspect of the study was the introduction of a com-
fashion. pletely artificial skin substitute in the treatment of
As previously mentioned, early treatment of burn patients. While artificial dermis used in this
burn grafts involved allowing the burn eschar to trial was only a temporizing measure, it opened
separate spontaneously. However, as the tech- the door for further investigations into nonorganic
nique of early excision took hold, the need for and nontraditional methods to close excised burn
reliable and regenerating autografts increased. wounds, especially in those with large TBSA
However, due to many factors, including concern burned, thereby limiting the surface area for auto-
for graft failure from infection or continued limi- grafting during staged procedures. The creation of
tation of donor site availability, alternatives to a definitive artificial skin substitute was and still is
autografting came into vogue, including cadav- currently considered as a “Holy Grail” of burn
eric homograft, which could be placed on freshly surgery to remove one of the rate-limiting reagents
excised burns to provide for temporary wound of the field, autograft. This study then provided a
closure. Xenografts, including both porcine and step in the right direction.
Currently, this is a field undergoing numerous order to maximize surface area [9]. Stem cell cul-
advancements, including a trial of cultured cells tures are also being actively investigated. This is
with a collagen matrix as a skin alternative [3] undoubtedly a field that will continue to see
and in more recent years, reconstituted autolo- tremendous change and impact in the coming
gous cells which can be applied in a spray in decades.
25.3 Fluid Resuscitation

Baxter CR, Shires GT. Physiological response to crystalloid resuscitation of severe burns [10]. Ann N Y Acad Sci.
1968
Strengths • This was an extensive and comprehensive multidisciplinary study, including both case reports
and animal models
Limitations • The study is a case series without blinding, randomization, or traditional comparison groups
Impact This study developed the modern framework for early, aggressive, balanced crystalloid resuscitation
in the acutely burned patient
One of the defining changes in the field of sur- contents of the blisters were rich in sodium, chlo-
gery in the twentieth century was the adoption ride, other electrolytes, and proteins. This early
and expansion of fluid resuscitation. The role that research allowed him to propose the use of com-
resuscitation plays in severe burns is so integral bined resuscitative fluids using both electrolytes
that the great benefits this intervention has and colloids.
brought can be easily taken for granted. Burn sur- In his research lab at Harvard University, Drs.
gery has been the area for which the study of fluid Cope and Moore also speculated that fluid loss
resuscitation has played an invaluable role for all was not only into these blisters, but also into the
fields of surgery, and continues to define the extracellular space leading to the edema that we
acute treatment of critically ill patients, including find in the severely burned [13]. He would go on
those with severe burns. to recommend additional fluid resuscitation in
It was long established that two peaks in the order to account for this additional extravasation
mortality curve of burn patients are present, death of fluid.6
from early “burn shock,” and later deaths from However, it would be Drs. Baxter and Shires
acute multiorgan dysfunction and the delayed at Parkland Hospital in Dallas TX, USA, that
burn sepsis [11]. We now know that acute deteri- would not only make improvements on the exist-
oration during the first phase is caused by hypo- ing research but also make defining changes in
volemic shock driven by the release of the field of fluid resuscitation that are still inte-
inflammatory mediators from the damaged tissue gral to burn care worldwide. The surgeons began
and loss of intravascular volume into the intersti- their research project by experiments on dogs and
tium and cells. This is related to increased capil- rhesus monkeys, using several radiotracers to
lary permeability and decreased function of the observe the changes in hemoconcentration,
sodium–potassium channels that causes fluid to plasma volume, and extracellular fluid volume
shift into the “third space.” Coincident vasodila- following severe burns. Additionally, hemody-
tion also contributes. Resulting hypoperfusion namics, including central venous pressure and
causes renal and hepatic dysfunction and failure, cardiac output, was closely monitored in order to
and ultimately cardiovascular collapse. All of us assess the clinical response to fluids. Arterial
involved in the field of acute care surgery are well blood gases were also regularly taken in order to
aware of this, but to surgeons in the early twenti- assess the metabolic response to resuscitation.
eth century it was not. The first definitive investi- Their pre-clinical experiments concluded that the
gations done by Dr. Underhill at Yale University amount of fluid for resuscitation of burned
investigated the fluid contents of blisters in patients was significantly underestimated, and
acutely burned patients [12]. He found that the that which was traditionally given was inade-
quate to normalize hemodynamics and correct function and were still susceptible to hemody-
metabolic derangements in response to the acute namic collapse [10].
volume shifts associated with acute burns [10]. While still likely, one of the most prevalent
During this period, similar work was being done and globally used formulas in the treatment of
at the Brooke Army Medical Centre in San acutely burned patients, further research by sur-
Antonio TX, USA [14], making this a race to the geons including Drs. Wolf, Cancio, and others
finish line. have trended toward the use of goal-directed ther-
From Baxter and Shires’ research, they gener- apy in order to avoid the serious complications of
ated the now famous Parkland formula of 4 cc of over-resuscitation, including cardiovascular
lactated Ringer’s per percent TBSA burned per overload, pulmonary edema, and the rightfully
kilogram, with half given in the first 8 h of burn dreaded abdominal compartment syndrome [15].
and the second half given over the following Their work has shown that computer-aided
16 h. Of note, unlike previously mentioned, the decision-making, which factors in the patient’s
researchers used a balanced crystalloid resuscita- urine output, can reduce the total amount of fluid
tion without colloid in the form of lactated given while still appropriately resuscitating
Ringer’s solution. patients with acute burns.
They went on to replicate this research in the The Parkland formula remains as the pri-
series of 11 patients with severe burns. They con- mary means of burn resuscitation for many, and
cluded that early and aggressive fluid resuscita- its development was fundamental in shaping
tion within the first 24 h was vital for patient the role of early and aggressive fluid resuscita-
survival. Metabolic and hemodynamic stabilization and the use of easily accessible crystalloid
tion was dependent on fluid resuscitation, which solutions to resuscitate patients. Recent interest
was crucial due to the shifts in volume into the has returned to the use of colloid, and in par-
extracellular spaces. Unfortunately, it appeared ticular fresh plasma in burn resuscitation, as
that patients with greater than 60% burns often this may further reduce the volume of fluids
failed to have lasting improvement in cardiac given [16].
25.4 Topical Antisepsis

Moyer CA, Brentano L, Gravens DL, Margraf HW, Monafo WW. Treatment of large human burns with 0.5% silver
nitrate solution [17]. Arch Surg. 1965;90:812–67
Strengths • This was an extensive and comprehensive multidisciplinary study, including both case reports
and microbiologic bench work
Limitations • The study is a case series without blinding, randomization, or traditional comparison groups
Impact This study validated both the use of silver nitrate and also the use of topical antiseptics in burn
patients to prevent burn sepsis
The burn patient has often been described as In the early days of burn surgery, the large
the prototype of a patient in shock. The severely fluid shifts often leading to renal and pulmonary
burned patient presents with hemodynamic insta- failure had partially been attenuated by the adop-
bility from hypovolemia, requiring aggressive tion of fluid resuscitation, generally with plasma.
resuscitation. Often, there are concomitant inju- These patients with large percentage of burns
ries or sequela of the shock that require further who had previously perished now faced a new
support, including intubation and ventilation, challenge in the form of infectious disease. The
renal replacement therapies, and even extracor- disruption of the primary defense of the human
poreal membrane oxygenation in severely burned body against infection led to unacceptably high
patients. rates of mortality from sepsis.
As often occurs during war, the First World 5. It should be nonantigenic.

War accelerated the investigation in the field of 6. Resistant strains of pathogenic organisms
burns. Dr. Henry Dakins developed his famous should not develop during its use.
sodium hypochlorite solution [18]. He generated 7. It should be readily procurable.
protocols and studies that validated the use of
0.025% NaClO in the treatment of these severely In the subsequent 56-page paper, he uses
injured patients. Further research by Drs. Limberg numerous case reports and microbiologic data to
and Moncrief on mafenide acetate, also known as show the dramatic improvement in mortality
sulfamylon, further advanced the field of burn among his patients. He showed that in patients
infection control [19]. Dr. Fox would also go on that suffered >40% burns, they decreased mortal-
to develop silver sulfadiazine, also known as sil- ity by almost 60% with the advent of appropriate
vadine, around roughly the same time [20]. antimicrobial control.
However, Dr. Moyer’s 1965 paper on the use of He was also explicit in warning of the risks of
silver nitrate at a 0.5% concentration would be electrolyte derangements, including hyponatre-
groundbreaking in developing silver nitrate solu- mia and black staining, also known as argyria. Of
tion as a mainstay of topical burn treatment [17]. note, Moyer recommends separate laundering of
Dr. Moyer’s study was a combination of case stud- burn equipment due to the side effect. His con-
ies and microbiologic data that, in addition to other cerns about the aesthetic harm that comes from
topics, including metabolic status and wound heal- his intervention is a testament to the complete-
ing, laid out his seven requirements for a safe anti- ness of the physicians at this time to the care of
septic, which he found in silver nitrate. At the time both the physical and mental well-being of their
that he was writing his study, he was treating patients.
patients at his Hartford Burn Unit with more his- The extremely productive work of all these
toric methods of burn wound management. scientists allowed us to develop an arsenal of
Patients were bathed and provided wound care topical antiseptic solutions that can be used in
while allowing burn eschars to separate from ways to limit the well-known side effects along
underlying healthy granulation tissue before per- with maximizing each strength. Silver sulfadia-
forming autografting. Though the patients were zine is free of metabolic side effects and has
successfully being treated in the initial stages of been described as soothing but has poor eschar
their disease with resuscitation and later by nutri- penetration and may lead to neutropenia.
tional support, mortality rates remained unaccept- Mafenide acetate has excellent eschar and carti-
ably high in severely burned patients due to lage penetration but is a carbonic anhydrase
invasive bacterial species, with Pseudomonas inhibitor that leads to metabolic acidosis and is
aeruginosa and Staphylococcus aureus being the also described as uncomfortable when applied.
prime culprits. Though Dr. Moyer and his team And, as previously stated, silver nitrate has
were initially hesitant to adopt topical antiseptics, excellent broad-spectrum activity but has poor
they found their aforementioned silver nitrate eschar penetration and may lead to electrolyte
solution met the criteria that they laid out for an derangements and black staining of tissue and
appropriate antiseptic. Their criteria were: equipment.
The work done on silver nitrate dressings
1. It must be nontoxic if absorbable. would continue to develop and improve. In the
2. It must be soluble in water, saline, or lipid in coming decades, several silver-based dressings
order that vaporizational heat loss be mini- for the treatment of burns were developed,
mized while antisepsis is being affected. including Mepilex Ag and Mepitel Ag. These
3. The antiseptic action must be prolonged. dressings have the advantage of only requiring
4. It must not kill viable tissue in the cells of the dressing changes after several days. They also
wound nor interfere with the proliferation of have reduced costs, discomfort from dressing
epidermis or skin grafts. changes, and the speed of healing [21].
This groundbreaking paper continues to define limited to patients with active sepsis and topical
the treatment of burn surgery to this day with antimicrobials being the mainstay of infection
administration of systemic antimicrobials being control.
25.5 Nutritional Support

Blocker TG, Levin WC, Nowinski WW, Lewis SO, Blocker V. Nutrition studies in the severely burned [22]. Ann
Surg. 1955;13:295–7
Strengths • This paper used a combination of basic science and case studies to demonstrate common
nutritional problems in burn patients
Limitations • The study is a case series consisting of subjective data without blinding, randomization, or
traditional comparison groups
Impact This study contraindicated the dogma of many surgeons at the time that early nutritional support was
not helpful and perhaps even harmful to acutely burned patients
The old adage “food is medicine” is well- He used positive nitrogen balance as a goal for
known to the modern practice of surgery. Early feeding. He also showed that the protein in the
initiation of feeding in pancreatitis, early initiation feeds were being used by the patient using amino
of total parenteral nutrition in patients unable to acid radiotracers that were avidly taken up in the
tolerate oral intake, and the role of the microbiome tissue. Between 1950 and 1954, he and his col-
in health is well established. However, we can take laborators showed significant success in wound
for granted the steps that our predecessors in the healing and overall patient health in over 600
field of surgery took to make these truths evident. patients by utilizing vitamin- and mineral-
Early discoveries in the field of biochemistry fortified and protein-rich formulas to treat his
allowed us to identify the role that macromole- acutely burned patients.
cules played in nutritional science. The ability to Over the course of the case series, the impor-
quantify the total nitrogen balance in a patient tance of positive nitrogen balance was estab-
allowed the creation of a surrogate for total pro- lished in correlation to the total body weight loss
tein utilization [22]. With the assumption that from admission to discharge date. All patients
nitrogen-containing amino groups are the funda- underwent appropriate wound care with eventual
mental building blocks of protein, detection of excision and grafting. Caloric intake did not
positive net excretion of nitrogen indicates that definitively prove to be impactful in terms of
the patient is receiving more protein than they are weight gain, given the patients had wide ranges
using. By this method, it can be ensured that the in their caloric intake over the course of their
patient is receiving an adequate amount of pro- admission. Protein intake and correlated nitrogen
tein nutrition. balance aligned appropriately with the changes to
Much in the same way that formulas like the patient weight, thereby showing the importance
aforementioned Parkland formula developed by of maintaining nutritionally valuable positive
Drs. Baxter and Shires, the nutritional balance nitrogen balance, especially during hospital
equation allowed surgeons to quantify the amount admission.
of substance to give with a clear set goal. Later work by surgeons generated numerous
Prior research by Dr. Frannie Moore at equations for goal-directed feeding therapy based
Harvard University suggested that catabolism in on patient’s size, age, and percentage of burn.
the first 3 weeks after acute trauma or burns While nitrogen balance is no longer commonly
arrested wound healing [23]. With this in mind, used in the treatment of our acute care surgery
Dr. Truman Blocker at the University of Texas patients, as they have been superseded by formula-
Medical Branch attempted to overcome this based approaches, this early work by Dr. Blocker
impediment to wound healing by early and helped cement the necessity of proper nutritional
aggressive feeding [22]. support in acutely injured burn patients.
References 11. Boehm D, Menke H. Sepsis in burns - lessons learnt

from developments in the management of septic
shock. Medicina. 2021;58:26.
1. Herndon DN, Barrow RE, Rutan RL, Rutan TC, Desai
12. Underhill FP. The significance of anhydremia in
MH, Abston S. A comparison of conservative versus
extensive superficial burns. JAMA J Am Med Assoc.
early excision: therapies in severely burned patients.
1930;95(12):852–7.
Ann Surg. 1988;209:547–53.
13. Cope O, Moore FD. The redistribution of body water
2. Janzekovic Z. A new concept in the early exci-
and the fluid therapy of the burned patient. Ann Surg.
sion and immediate grafting of burns. J Trauma.
1947;126(6):1010–45.
1970a;10:1103–8.
14. Pruitt BA Jr, Mason AD Jr, Moncrief JA. Hemodynamic
3. Hansbrough JF. Burn wound closure with cultured
changes in the early postburn patient: the influence of
autologous keratinocytes and fibroblasts attached
fluid administration and of a vasodilator (hydrala-
to a collagen-glycosaminoglycan substrate. JAMA.
zine). J Trauma. 1971;11:36–46.
1989;262(15):2125–30.
15. Salinas J, Chung KK. Computerised decision support
4. Tomkins RL, Burke JF. Prompt eschar excision:
system improves fluid resuscitation following severe
a treatment system contributing to reduced burn
burns: an original study. Crit Care Med. 2011;39:2031–8.
mortality: a statistical evaluation of burn care the
16. Greenhalgh DG, C. R. Burn resuscitation practices in
Massachusetts General Hospital (1974-1984). Ann
North America: results of the acute burn resuscitation
Surg. 1986;204:272–81.
multicentre prospective trial (ABRUPT). Ann Surg.
5. Herndon HN. A comparison of conservative versus
2023;277:512–9.
early excision: therapies in severely burned patients.
17. Moyer C, Brentano L, Gravens D, Margraf H, Monafo
Ann Surg. 1989;209(5):547–52.
W. Treatment of large human burns with 0.5% silver
6. Janzekovic Z. A new concept in the early exci-
nitrate solution. Arch Surg. 1965;90:812–67.
sion and immediate grafting of burns. J Trauma.
18. Dakin H. On the use of certain antiseptic substances
1970b;10(12):1103–8.
in the treatment of infected wounds. Br Med J.
7. Heimbach DM. Artificial dermis for major burns:
1915;2:318–20.
a multi-center randomized clinical trial. Ann Surg.
19. Lindberg RB, Moncrief JA, Switzer WE, Order SE,
1988;208(3):313–20.
Mills W Jr. The successful control of burn wound sep-
8. Burke JF, Yannas IV, Quinby WC Jr, Bondoc CC,
sis. J Trauma Acute Care Surg. 1965;5(5):601–16.
Jung WK. Successful use of a physiologically accept-
20. Fox C, Rappole B, Stanford W. Control of pseudo-
able artificial skin in the treatment of extensive burn
monas infection in burns by silver sulfadiazine. Surg
injury. Ann Surg. 1981;194:413–28.
Gynecol Obstet. 1969;128(5):1021–6.
9. Holmes JH IV, Molnar JA, Shupp JW, Hickerson
21. Gotschall CS, Morrison MI, Eichelberger
WL, King BT, Foster KN, Cairns BA, Carter
MR. Prospective, randomized study of the efficacy
JE. Demonstration of the safety and effectiveness of
of Mepitel on children with partial-thickness scalds.
the RECELL system combined with split-thickness
J Burn Care Rehabil. 1998;19(4):279–83.
meshed autografts for the reduction of donor site
22. Blocker T, Levin W, Nowinski W, Lewis S, Blocker
skin to treat mixed-depth burn injuries. Burns.
V. Nutrition studies in the severely burned. Ann Surg.
2019;45:772–82.
1955;13(10):295–7.
10. Baxter CR, Shires T. Physiological response to crys-
23. Moore F, Ball M. The metabolic response to surgery.
talloid resuscitation of severe burns. Ann N Y Acad
Springfield IL: Charles C Thomas; 1952.
Sci. 1968;150(3):874–94.
Part VIII
Trunk Reconstruction
Evolution of Trunk Reconstruction
26
Geoffrey G. Hallock
Abstract given patient, and that will depend on the

unique extent of their defect, tissue require-
For practical purposes, the trunk can be
ments, and then careful scrutiny of potential
divided anatomically into the anterior chest
possibilities.
and the back, the latter better termed the pos-
terior trunk, as these two regions in common
Keywords
encompass the thoracic cavity. Their primary
responsibility is the maintenance of respira- Anterior chest · Posterior trunk · Sternum
tory function, which must be minimally com- Upper thorax · Back · Lumbar · Pectoralis
promised by any reconstructive maneuvers major · Latissimus dorsi · Rectus abdominis
that would be considered. In addition, in the Trapezius · Perforator flap
posterior trunk, the spinal column must be
protected so that neurological capabilities are
retained intact. Most often, only external cov- The Five Most Impactful Papers
erage is necessary which can best be accom- 1. Maxwell GP. Iginio tansini and the origin of
plished by the transposition of vascularized the latissimus dorsi musculocutaneous flap.
flaps. No shortage of relatively simple pedi- Plast Reconstr Surg. 1980;65:686–92.
cled flap alternatives are available, whose 2. Jurkiewicz MJ, Bostwick J III, Hester TR,
attributes as well as detriments need to be well Bishop JB, Craver J. Infected median sternot-
understood. Always remember that every omy wound: successful treatment by muscle
muscle has a function, even if just as a second- flaps. Annal Surg. 1980;191:738–44.
ary or accessory means for respiration. A per- 3. Arnold PG, Pairolero PC. Chest-wall recon-
forator flap may then become a preferable struction: an account of 500 consecutive
choice. Both regions can be arbitrarily broken patients. Plast Reconstr Surg. 1996;98:804–10.
down into anatomical subunits that serve as a 4. Kroll SS, Rosenfield L. Perforator-based flaps
guide to inherent flap selection, whether it be for low posterior midline defects. Plast
a muscle or perforator flap. The best course of Reconstr Surg. 1988;81:561–6.
action must always be individualized for the 5. Angrigiani C, Grilli D, Siebert J. Latissimus
dorsi musculocutaneous flap without muscle.
Plast Reconstr Surg. 1995;96:1608–14.
G. G. Hallock (*)
Division of Plastic Surgery, St. Luke’s Hospital,
Sacred Heart Division, Allentown, PA, USA
https://doi.org/10.1007/978-3-031-57132-9_26
274 G. G. Hallock
26.1 Anterior Chest coverage [7, 8]. Isaac, et al. [4] have better sum-
marized their approach to this in a detailed algo-
The bony landmarks defining the anterior chest rithm differentiated on the basis of defect
begin superiorly at the manubrium that is readily composition, size, and specific characteristics
palpated in the midline, then proceed laterally such as a contaminated or previously radiated
along the first ribs which are usually under the wound.
cover of the clavicle [1]. This region extends cau- Suffice it to say that assurance of skeletal sta-
dally along the sternum to the xiphosternal junc- bility no longer is usually achieved using autoge-
tion, then follows along the costal margins to the nous tissues, but instead today with various
inferior aspect of the 12th ribs [2]. From these prosthetic materials that will normally be handled
subsidiary structures arise fibers that contribute by the thoracic surgeon [4–6]. The same would be
to the diaphragm, which separates the thoracic true for a partial diaphragm repair, unless so large
cavity from that of the abdomen [3]. a functional muscle transfer would be best [9]. To
Deformities of the anterior chest, whether accomplish all the remaining aforementioned
congenital or acquired, will need reconstruction goals for anterior chest reconstruction will demand
depending on the defect encountered. In general, some form of flap. Long ago, so-called random
it is fair to say that this will always require that local rotation or tubed skin flaps could be waltzed
respiratory function be sustained; and that best or jumped from the abdomen to accomplish at
without alteration of respiratory mechanics, least external coverage for the anterior chest wall
which may require stabilization of thoracic skel- subunits [Fig. 26.1a.]. These have been supplanted
etal components, maintenance of diaphragm by pedicled muscle flaps which have superior vas-
function, and preservation of both primary and cularity and are malleable enough to obliterate
secondary muscles of respiration to ensure ade- intrathoracic dead spaces or wrap around vital
quate capacity during increased ventilation organ repairs [6, 7]. Tansini was the first to recog-
demands [4]. Other goals include the obliteration nize the enhanced capability of the latissimus dorsi
of intrathoracic dead spaces as in chronic empy- [LD] muscle as a flap for anterior chest wall cover-
ema [5, 6], protection of vital organs and struc- age, which, at the time, was usually used following
tures, and provision of viable external soft tissue mastectomy for breast cancer [10–12].
a b
Fig. 26.1 (a) Subunits of the anterior chest. (b) Reliable IMAP internal mammary artery perforator, LICAP lateral
muscle flap options [left]—EO external oblique, LD latis- intercostal artery perforator, SEAP superior epigastric
simus dorsi + serratus anterior, PM pectoralis major, RA artery perforator, TAAP thoracoacromial artery perforator,
rectus abdominis. Available perforator flap options TDAP thoracodorsal artery perforator
[right]— AICAP anterior intercostal artery perforator,
26 Evolution of Trunk Reconstruction 275
Maxwell GP. Iginio tansini and the origin of the latissimus dorsi musculocutaneous flap. Plast Reconstr Surg.
1980;65:686–92
Strengths • Superb history of the Italian surgeon who when realizing that a narrow based back flap
randomly pedicled on the axilla for mastectomy defect coverage too often had significant
necrosis, then personally dissected cadavers to find that this region had cutaneous vessels from
the “scapular circumflex” and latissimus dorsi muscle [11], and if the latter were included
ensured survival of all the skin, thereby arising the origin of the musculocutaneous flap
Limitations • The original work by Tansini [11, 12] cannot be assessed unless one is conversant in Italian, but
this English historical reminiscence did not include any data as to the efficacy of this technique
Impact Tansini strongly advocated “principles for the surgical management of breast cancer … based on the
prevention of metastatic spread of the tumor by means of lymphatics and direct extension” [12]—not
so different today
Although at the time widely accepted in Europe, probably the Halstedian method of radical
mastectomy with preservation of thinned breast skin flaps required instead at most a skin graft if
wound closure was not possible. Today, this then flap alternative has become a “workhorse” for the
reconstructive surgeon, as a pedicled flap or microsurgical tissue transfer throughout the body
Campbell reintroduced the role of the LD mus- ment of the infected median sternotomy created a
cle to the Americas in 1950 [13], but muscle flaps demand for better control using primarily the pec-
in general did not become the vogue until the toralis major and occasionally the LD muscles
1970s. With the concomitant explosion of cardio- [14], but also the rectus abdominis muscle more
thoracic interventions during this period, treat- often for the xiphoid region Fig. 26.1b.] [7, 15].
Jurkiewicz MJ, Bostwick J III, Hester TR, Bishop JB, Craver J. Infected median sternotomy wound: successful
treatment by muscle flaps. Annal Surg. 1980;191:738–44
Strengths • In a single institutional study where the usual prior therapy of debridement and closed catheter
irrigation for infected mediastinitis was unsuccessful, this approach was replaced by extensive
debridement and obliteration of dead space with pectoralis major muscle flaps; or occasionally
use of the rectus abdominis muscle and omentum, especially if the xiphoid region remained
open. Such “flap closure was shown to result in a fourfold decrease in mortality” when compared
to their prior techniques [15]
Limitations • Would often use multiple muscle flaps simultaneously, including turnover pectoralis flaps to
obliterate the sternal defect. Presently, it is considered better to use one flap to then maintain
muscle function as well as retain an option in reserve to treat any possible future recidivism.
Their method pre-dated significant use of the internal mammary artery as a vascular conduit,
where now “reversed” pectoralis muscle flaps would not at all be possible
Impact Beginning as a secondary treatment when traditional therapy was unsuccessful, the authors
transitioned this to be their primary treatment, often in a single stage with radical debridement and
immediate flap closure. As such, mortality became almost non-existent; and morbidity, including
excessive length of hospital stay markedly reduced, as has now become the accepted approach
throughout the United States
In general though, the LD [8, 16, 17], pectora- became the tour de force for overall external
lis major [18], and sometimes the serratus ante- anterior chest wall coverage [8], if not intratho-
rior [19] and external oblique [20] muscles racic solutions [5, 6].
276 G. G. Hallock
Arnold PG, Pairolero PC. Chest-wall reconstruction: an account of 500 consecutive patients. Plast Reconstr Surg.
1996;98:804–10
Strengths • Restoration simultaneously of skeletal stability as well as soft tissue coverage for oncologic,
traumatic, infectious, and radiation necrosis defects is overviewed in an unparalleled two
decade consecutive experience. The dominating era of the muscle flap had begun, as used in
81.4% of patients. Of these 611 muscle flaps, the pectoralis major (58.1%) and latissimus dorsi
(23.1%) were by far the workhorses. The omentum in 51 patients served as a “security blanket”
either as the planned procedure or for salvage of complications [16]
Limitations • Muscle flaps were used for both intrathoracic as well as external coverage indications, but no
tabulation of frequency nor preferable muscle donor site selection was given. No comments
were made about any adverse sequela on respiratory mechanics when using muscle flaps
Impact Indeed, this pair were the pioneers of the concept of the “thoracoplastic team”
A 3% perioperative mortality rate was observed; but at last follow-up or time of death, 83.1% of
patients had healed. Thus, in these patients typically with multiple co-morbidities, their conclusion
“that chest wall reconstruction is safe, durable, and associated with long-term survival” [16]
deserves respect
The prior use of autogenous tissues for restoration of the bony thorax was more safely accomplished
in their later experience by the use of prosthetic materials
The references included in this manuscript by themselves outline the history of the evolution of the
muscle flap in the reconstructive thoracic surgeons’ armamentarium
Yet the sacrifice of any muscle function now may also be limited in versatility, often applica-
some may consider deplorable, as not only do all ble only to the upper anterolateral chest subunit;
these regional muscle flaps have a role in upper but the internal mammary artery perforator flap
and lower limb function but also in respiratory [IMAP], reminiscent of the deltopectoral flap
mechanics [4, 21]. The thoracoepigastric [sic. [27], can be designed to reach all subunits and
thoracoabdominal] fasciocutaneous flap was an even include the anterior mediastinum [28–30].
early more acceptable alternative [22], although The lateral intercostal artery perforator flap [31]
no discrete arterial supply was specifically identi- from the flank or the thoracodorsal artery perfo-
fied. That changed with the perforator flap con- rator flap [32] from the back usually will have
cept, as not only could overall function be better reach restricted to the more lateral anterior chest
retained but better flap vascularity ensured due to wall dilemmas.
more precise source vessel dissection. The perfo- As would be expected, if local flaps of any
rator flap can sometimes also have longer pedi- kind are not available and transposition of the
cles to permit reach even greater than their muscle pedicled omentum [33] considered too risky, a
flap counterparts [Fig. 26.1b] [21]. A good exam- free flap can close any defect whether for intra-
ple is the deep superior epigastric artery perfora- thoracic or external coverage purposes [7, 34].
tor [SEAP] flap that captures the territory of the Unlike the posterior trunk, recipient vessels to
upper abdomen or along the costal margin much allow this option for the anterior chest will not be
as did the thoracoepigastric flap, but differs in so much an issue.
that it relies on isolated musculocutaneous perfo-
rators of the rectus abdominis muscle [23, 24]. As
such, the SEAP flap has replaced its muscle 26.2 Posterior Trunk
counterpart to close the xyphoid region, often a
difficult task when treating the infected median Although more familiarly known as just the
sternotomy wound [23, 24]. Not quite as robust “back,” the posterior trunk may be better
an option in this same area would be the anterior restricted to be that anatomical complex com-
intercostal artery perforator flap [25]. Some, like prising the upper back and lumbar regions. The
the thoracoacromial artery perforator flap [26], upper back is encompassed by a line superiorly
that joins the spinous process of the seventh cer- found. These regions here can be subdivided into
vical vertebra bilaterally with the acromial the upper thoracic [encompasses the scapula and
angle, then progresses inferiorly to the lower intervening area], mid-thoracic [tip of scapula to
border of the twelfth rib [35]. Just below this, costal margin of the 12th rib]; and lumbar territo-
the lumbar region proceeds caudally to a line ries, as already defined [Fig. 26.2a.] [36].
joining the posterior superior iliac spines, that in The past history of posterior trunk coverage
turn follows along the iliac crests [35]. Both also has seen the attempted use of random skin
regions extend laterally to the mid-axillary flaps wherever needed; but to be more pragmatic,
lines, whereupon the anterior chest would be again flaps with a known circulation will always
encountered. be more reliable. The traditional selection of
Inherent skeletal stability of the posterior muscle and musculocutaneous flaps often will
trunk also cannot be overlooked, as the ribcage still be preferred [Fig. 26.2b.], as their malleabil-
must be maintained as in the anterior chest so that ity better permits fill of 3-dimensional defects
pulmonary ventilation will not be impeded. In such as exposed vertebrae or orthopedic hard-
addition, the spinal column must be protected to ware [35]. The synergistic action of the numerous
preserve neurological function and concomitant muscles that exist here limits the possibility of a
locomotion. The overlying skin and subcutane- significant function loss when employed for the
ous fat here are relatively thin, albeit reinforced otherwise healthy individual. The most superfi-
by the dorsal thoracic fascia and fascial septa as cial group of posterior trunk muscles includes the
well as multiple muscle groups so that deep latissimus dorsi and trapezius, and both readily
defects and skeletal instability will rarely be reach the upper thoracic zone [36]. The latissi-
encountered [5]. Instead, reconstructive require- mus dorsi can also reach the mid-thoracic zone,
ments in the posterior trunk most routinely will but often as a reversed flap based on secondary
be for no more than coverage of exposed bony paraspinal or intercostal segmental vessels that
structures or iatrogenic devices that may have rarely permit reach beyond the upper lumbar area
been introduced. All this can be accomplished [37]. The deep muscles are the erector spinae
using a variety of available local flaps, best muscles, better known as the paraspinous mus-
selected using guidelines differentiated accord- cles. The principal advantage of the paraspinal
ing to the topographic site where they may be muscles would be as the primary choice for the
Fig. 26.2 (a) Subunits

of the posterior trunk.
a b
(b) Reliable muscle flap
options [left]—GM
gluteus maximus, LD
latissimus dorsi, P
paraspinal, T trapezius.
Available perforator flap
options [right]—CSAP
circumflex scapular
artery perforator, DSAP
dorsal scapular artery
perforator, ICAP
intercostal artery
perforator, LAP lumbar
artery perforator, SGAP
superior gluteal artery
perforator, TDAP
thoracodorsal artery
perforator
278 G. G. Hallock
lumbar area [38, 39]. These muscles, according from view. The intercostal neurovascular island
to Manstein et al. [38], also have a secondary role flap of Kerrigan and Daniel [41] was intended to
for buttressing repairs of the thoracic region be a sensate skin flap, but actually retained some
where reinforced by the superficial muscles for muscle so in a sense was still a myocutaneous
more definitive coverage. Note rarely that the flap. However, strictly, fasciocutaneous flaps like
superior gluteal muscle can also be an alternative the transverse lumbosacral flap were totally inde-
for the lower lumbar defect [40]. pendent of muscle and based on presumed para-
If muscle function preservation takes prece- spinal perforators [42]. Kroll and Rosenfield [43]
dence to better ensure respiratory mechanics, for- took this a step further by actually identifying
tunately numerous reliable cutaneous flaps are these lumber perforators to make their low poste-
possible selections [21]. Unlike a skin grafted rior midline flaps “true” perforator flaps, as
muscle flap, these also will provide a superior described in their landmark article where the
aesthetic result, perhaps of limited value since word “perforator” was included for the first time
this body region remains for the most part hidden in the actual title of a manuscript [Fig. 26.2b].
Kroll SS, Rosenfield L. Perforator-based flaps for low posterior midline defects. Plast Reconstr Surg. 1988;81:561–6
Strengths • Provided a solution for the difficult lumbar wound with a skin flap based on identified
“free-style” cutaneous perforators. In so doing, argued that giving a skin flap an improved blood
supply now comparable to a myocutaneous flap “one could have the best of both worlds.” [43]
of course, since no muscle was harvested, all muscle function would be preserved
Limitations • Flaps were based on unnamed perforators found near the midline of the lower back. Only two
cases were specifically reported for the lumbar area, plus an additional flap based also on
paraspinous perforators for the midback
Impact The concept that a perforator-based flap was possible would allow “any tissue to be made into a [sic.
Custom designed] flap if its blood supply can be identified and surgically isolated so that the tissue
can be safely mobilized” [43]
Although the use of the word “perforator” has been used for centuries in various communications,
here the word “perforator” was first used in an article’s “title.” and incredibly rapidly thereafter, the
number of manuscripts entitled “perforator flap” has inundated the reconstructive literature
Not long afterwards, Angrigiani et al. [44] could be retained without the muscle, and allowed
proved that the cutaneous territory of the latissimus the same range of coverage as would the latissimus
dorsi muscle could be captured by a single muscu- dorsi muscle itself by what today is known as the
locutaneous perforator. The thoracodorsal pedicle thoracodorsal artery perforator [TDAP] flap [45].
Angrigiani C, Grilli D, Siebert J. Latissimus dorsi musculocutaneous flap without muscle. Plast Reconstr Surg.
1995;96:1608–14
Strengths • Anatomical study in fresh cadavers demonstrating the consistent existence of latissimus dorsi
musculocutaneous perforators that interconnected with surrounding skin territories via a
subcutaneous plexus. This clinically allowed the safe harvest of large cutaneous flaps of the
upper thoracic region without including any muscle, such that “the size of the skin area
available for transfer is directly related to the diameter of the cutaneous perforator of the
thoracodorsal artery”
Limitations • Only 5 clinical cases were done, with only one reported as a pedicled flap for the anterior
chest. No table was provided for the evaluation of the clinical data upon which the stated
conclusions were made
Impact Today this is known as the thoracodorsal artery perforator flap, which has become one of the
“workhorse” perforator flaps
Rightfully acknowledged the few other references at the time on musculocutaneous flaps without
the muscle. With the continued anatomical studies by Angrigiani [46], he was to become an
international force in the acceptance of the perforator flap concept as a distinct entity
In similar fashion, the dorsal scapular artery per- addition, in the posterior trunk, preservation of
forator flap of Angrigiani et al. [46] was based spinal function must also be considered. The
instead on a musculocutaneous perforator of the tra- modern capability for accomplishing such results
pezius muscle, that can have an even greater range has had few worthwhile precedents. The most
in the upper back than could the muscle itself. pragmatic approach presently still is to use autog-
An exception to the inherent nature of anatom- enous tissues in the form usually as a vascular-
ical anomalies existing for most perforator flap ized flap. The evolution in the potential for such
donor sites may be the consistency of the circum- alternatives reflects simultaneously the evolution
flex scapular artery perforator flap [47], capturing of flap choices. Fortunately, many local flaps in
the same territory where previously called the this region exist that can be simply transferred
scapular [48] and/or parascapular [49] flap, which without the complexity and added risk of micro-
have long proven reliability for the upper thoracic surgery. Muscle flaps were initially the sole
region. As the perforator flap concept evolved, the choice for this purpose, as relatively straightfor-
numerous intercostal perforators throughout the ward to undertake; and even now should not be
posterior trunk, whether of dorsal or lateral inter- considered passé, as they still have attributes that
costal origin, can sustain not only island flaps but will always remain invaluable such as their intrin-
also so called free-style propeller flaps [50] to sic flexibility and perhaps superior intrinsic vas-
allow virtually unlimited possibilities to solve cularity. Nevertheless, muscles taken from either
nearby local issues [31]. More caudally, just as the anterior chest or posterior trunk cannot escape
Kroll and Rosenfield predicted [43], a series of the risk of impacting upon upper extremity
lumbar perforators allow perforator flap coverage mobility. Since perforator flaps by definition
of the typical lumbar region wound [40]. Yet one impinge minimally on muscle function, these
cannot overlook the intrinsic mobility of the sub- often have gradually become the “workhorses,”
cutaneous layer of the posterior trunk and the relying only on the presence of an adequate per-
innumerous presence of even miniscule perfora- forator and its corresponding perforator angio-
tors that can sustain a “keystone” flap. This trap- some, whose vast numbers have exploded the
ezoidal designed flap requires no actual number of potential donor sites. But as the afore-
identification of a perforator, harvest consequently mentioned tissues evolved in their reliability, so
is simple and quick, the vascularity ensured to be too will the future as yet be unknown. Stem cell
robust, all regions of the posterior trunk can be a therapy or gene editing may someday conduce
potential donor site; and all this with the absence recipient chimerism so vascularized composite
of any need even for microsurgical technique allotransplants may become immunologically
much less a microanastomosis [51]. practical. Perhaps instead three-dimensional bio-
Just as for the anterior chest, the omentum can printing or some other form of regenerative
serve as another local flap solution [52]. As medicine will prove less risky. Either pathway
always, when no local flap would be sufficient, a may someday allow rapid access to solutions that
free tissue transfer may be the best alternative. can just be taken off the shelf without causing
However, recipient site possibilities in the poste- any autogenous donor site morbidity. Any sur-
rior trunk are exceedingly limited, in contradis- geon intent on conquering the challenges in this
tinction to that of the anterior chest [53]. region must always remain vigilant, as this trans-
formation seeking better outcomes will inevita-
bly proceed onward.
26.3 Expert Concluding
Commentary
References
The primary goal for any reconstructive effort
either in the anterior chest or posterior trunk 1. Woodburne RT. Essentials of human anatomy. 4th ed.
New York: Oxford University Press; 1969. p. 68.
regions, since both involve the bony thorax, must 2. Woodburne RT. Essentials of human anatomy. 4th ed.
be the maintenance of respiratory mechanics. In New York: Oxford University Press; 1969. p. 304.
280 G. G. Hallock
3. Woodburne RT. Essentials of human anatomy. 4th ed. (axilla, posterolateral chest, and posterior trunk). Plast
New York: Oxford University Press; 1969. p. 442. Reconstr Surg. 2009;124:427e–35e.
4. Isaac KV, Elzinga K, Buchel EW. The best of chest 22. Davis WM, McCraw JB, Carraway JH. Use of a
wall reconstruction: principles and clinical applica- direct, transverse, thoracoabdominal flap to close dif-
tion for complex oncologic and sternal defects. Plast ficult wounds of the thorax and upper extremity. Plast
Reconstr Surg. 2022;149:547e–62e. Reconstr Surg. 1977;60:526–33.
5. Althubaiti G, Butler CE. Abdominal wall and 23. Hamdi M, Van Landuyt K, Ulens S, Van Hedent E,
chest wall reconstruction. Plast Reconstr Surg. Roche N, Monstrey S. Clinical applications of the
2014;133:688e–701e. superior epigastric artery perforator (SEAP) flap: ana-
6. Arnold PG, Pairolero PC. Intrathoracic muscle tomical studies and preoperative perforator mapping
flaps: a 10-year experience in the management of with multidetector CT. J Plast Reconstr Aesthet Surg.
life-
threatening infections. Plast Reconstr Surg. 2009;62:1127–34.
1989;84:92–8. 24. Oni G, Sharma R, Rao R, Unger J, Saint-Cyr
7. Netscher DT, Baumholtz MA. Chest reconstruction: M. Bilateral superior epigastric pedicle perforator
I. Anterior and anterolateral chest wall and wounds flaps for total chest wall coverage. J Plast Reconstr
affecting respiratory function. Plast Reconstr Surg. Aesthet Surg. 2011;64:1104–7.
2009;124:240e–52e. 25. Carrasco-López C, Ibañez JFJ, Vilà J, Rodriguez-
8. Bakri K, Mardini S, Evans KK, Carlsen BT, Arnold Baeza A, Carrera-Burgaya A, Reina-de-la-Torre F,
PG. Workhorse flaps in chest wall reconstruction: the Damaso-Margelí-Cervera V, Fernandez-Llamazares-
pectoralis major, latissimus dorsi, and rectus abdomi- Rodriguez J, Higueras-Suñe C. The anterior intercos-
nis flaps. Semin Plast Surg. 2011;25:43–54. tal artery flap: anatomical and radiologic study. Plast
9. Kato S, Sakuma H, Fujii T, Tanaka I, Matsui Reconstr Surg. 2017;139:613e–9e.
J. Reconstruction of extensive diaphragmatic defects 26. Kosutic D, Krajnc I, Pejkovic B, Anderhuber F,
by the rectus abdominis muscle and fascial flap. Arch Solman L, DjukicE SM. Thoraco–acromial artery
Plast Surg. 2023;50(2):166–70. perforator ‘propeller’ flap. J Plast Reconstr Aesthet
10. Maxwell GP. Iginio Tansini and the origin of the latis- Surg. 2010;63:e491–3.
simus dorsi musculocutaneous flap. Plast Reconstr 27. Neligan PC, Gullane PJ, Vesely M, Murray D. The
Surg. 1980;65:686–92. internal mammary artery perforator flap: new
11. Tansini I. Sopra il mio nuovo processo di amputazione variation on an old theme. Plast Reconstr Surg.
della mammella. Gazz Med Ital Torino. 1906;57:141. 2007;119:891–3.
12. Tansini I. Nuovo proceso per l’amputazione della 28. Karabulut AB, Kalender V. Internal mammary artery
mammaella per cancre. Reforma Medica. 1896;12:3. pedicled Island flap for the treatment of chest wall
13. Campbell DA. Reconstruction of the anterior thoracic radionecrosis. Plast Reconstr Surg. 2001;108:583–4.
wall. J Thorac Surg. 1950;19:456–61. 29. Faini G, Pierazzi DM, Arleo S, Calabrese S, Alfieri
14. Jurkiewicz MJ, Bostwick J III, Hester TR, Bishop JB, EP, Cigna E. Internal mammary artery perforator flap
Craver J. Infected median sternotomy: successful treat- for anterior thoracic and upper abdominal wall recon-
ment by muscle flaps. Ann Surg. 1980;191:738–44. struction: 16 case series. J Plast Reconstr Aesthet
15. Nahai F, Rand RP, Hester TR, Bostwick J III, Surg. 2022;75:2413–5.
Jurkiewicz MJ. Primary treatment of the infected ster- 30. Koulaxouzidis G, Orhun A, Stavrakis T, Witzel
notomy wound with muscle flaps: a review of 211 con- C. Second intercostal internal mammary artery
secutive cases. Plast Reconstr Surg. 1989;84:434–41. perforator (IMAP) fasciocutaneous flap as an alterna-
16. Arnold PG, Pairolero PC. Chest-wall reconstruction: tive choice for the treatment of deep sternal wound
an account of 500 consecutive patients. Plast Reconstr infections (DSWI). J Plast Reconstr Aesthet Surg.
Surg. 1996;98:804. 2015;68:1262–7.
17. McCraw JB, Penix JO, Baker JW. Repair of major 31. Hamdi M, Van Landuyt K, de Frene B, Roche N,
defects of the chest wall and spine with the latissi- Blondeel P, Monstrey S. The versatility of the inter-
mus dorsi myocutaneous flap. Plast Reconstr Surg. costal artery perforator (ICAP) flaps. J Plast Reconstr
1978;62:197–206. Aesthet Surg. 2006;59:644–52.
18. Arnold PG, Pairolero PC. Use of pectoralis major 32. Hamdi M, Van Landuyt K, Hijjawi JB, Roche N,
muscle flaps to repair defects of the anterior chest Blondeel P, Monstrey S. Surgical technique in ped-
wall. Plast Reconstr Surg. 1979;63:205–13. icled thoracodorsal artery perforator flaps: a clinical
19. Arnold PG, Pairolero PC, Waldorf JC. The serratus experience with 99 patients. Plast Reconstr Surg.
anterior muscle: intrathoracic and extrathoracic utili- 2008;121:1632–41.
zation. Plast Reconstr Surg. 1984;73:240–6. 33. Jurkiewicz MJ, Arnold PG. The omentum: an account
20. Matros E, Disa JJ. Uncommon flaps for chest wall of its use in the reconstruction of the chest wall. Ann
reconstruction. Semin Plast Surg. 2011;25:55–9. Surg. 1977;185:548–54.
21. Netscher DT, Baumholtz MA, Bullocks J. Chest 34. Georgiou I, Ioannou CI, Schmidt J, Eschborn J,
reconstruction: II. Regional reconstruction of chest Mostofizadeh-Haghighi G, Infanger M, Ghods M,
wall wounds that do not affect respiratory function Kruppa P. Free flaps in sternal osteomyelitis after
median sternotomy: a center’s 12-year experience. J anatomic basis and clinical application. Ann Plast
Reconstr Microsurg. 2023;39(8):601–15. Surg. 2003;51:23–9.
35. Hallock GG. Reconstruction of posterior trunk 46. Angrigiani C, Grilli D, Karanas YL, Longaker MT,
defects. Semin Plast Surg. 2011;25:78–85. Sharma S. The dorsal scapular Island flap: an alter-
36. Mathes DW, Thornton JF, Rohrich RJ. Management native for head, neck, and chest reconstruction. Plast
of posterior trunk defects. Plast Reconstr Surg. Reconstr Surg. 2003;111:67–78.
2006;118:73e–83e. 47. Dabernig J, Sorensen K, Shaw-Dunn J, Hart AM. The
37. Bostwick John III, Scheflan M, Nahai F, Jurkiewicz thin circumflex scapular artery perforator flap. J Plast
MJ. The “reverse” latissimus dorsi muscle and mus- Reconstr Aesthet. 2007;60:1082–96.
culocutaneous flap: anatomical and clinical consider- 48. Urbaniak JR, Koman LA, Goldner RD, Armstrong
ations. Plast Reconstr Surg. 1980;65:395–9. NB, Nunley JA. The vascularized cutaneous scapular
38. Manstein ME, Manstein CH, Manstein G. Paraspinous flap. Plast Reconstr Surg. 1982;69:772–8.
muscle flaps. Ann Plast Surg. 1998;40:458–62. 49. Nassif TM, Vidal L, Bovet JL, Baudet J. The para-
39. Wilhelmi BJ, Snyder N, Colquhoun T, Hadjipavlou A, scapular flap: a new cutaneous microsurgical free flap.
Phillips LG. Bipedicle paraspinous muscle flaps for Plast Reconstr Surg. 1982;69:591–600.
spinal wound closure: an anatomic and clinical study. 50. Oh TS, Hallock G, Hong JP. Freestyle propeller flaps
Plast Reconstr Surg. 2000;106:1305–11. to reconstruct defects of the posterior trunk. Ann Plast
40. Roche NA, Van Landuyt K, Blondeel PN, Matton Surg. 2012;68:79–82.
G, Monstrey SJ. The use of pedicled perforator flaps 51. Khouri JS, Egeland BM, Daily SD, Harake MS, Kwon
for reconstruction of lumbosacral defects. Ann Plast S, Neligan PC, Kuzon WM Jr. The keystone Island
Surg. 2000;45:7–14. flap: use in large defects of the trunk and extremities
41. Kerrigan CL, Daniel RK. The intercostal flap: an ana- in soft-tissue reconstruction. Plast Reconstr Surg.
tomical and hemodynamic approach. Ann Plast Surg. 2011;127:1212–21.
1979;2:411–21. 52. Giordano PA, Griffet J, Argenson C. Pedicled
42. Hill HL, Brown RG, Jurkiewicz MJ. The trans- greater omentum transferred to the spine in a case
verse lumbosacral back flap. Plast Reconstr Surg. of postoperative infection. Plast Reconstr Surg.
1978;62:177–84. 1994;93:1508–11.
43. Kroll SS, Rosenfield L. Perforator-based flaps for 53. Karakawa R, Yoshimatsu H, Kamiya K, Fuse Y, Yano
low posterior midline defects. Plast Reconstr Surg. T, Muro S, Akita K. An anatomical study of posterior
1988;81:561–6. trunk recipient vessels, and comparisons of outcome
44. Angrigiani C, Grilli D, Siebert J. Latissimus dorsi following pedicled- and free-flap transfers for treat-
musculocutaneous flap without muscle. Plast Reconstr ment of sarcoma in the posterior trunk. J Reconstr
Surg. 1995;96:1608–14. Microsurg. 2022;38:683–93.
45. Heitmann C, Guerra A, Metzinger SW, Levin LS,
Allen RJ. The thoracodorsal artery perforator flap:
Part IX
Abdominal Wall Reconstruction
Evolution of Abdominal Wall
Reconstruction
27
Rami Elmorsi, Abbas Hassan, Jeffrey E. Janis,
and Charles E. Butler
Abstract Keywords
Abdominal wall reconstruction has served as Hernia · Abdominal wall reconstruction

the proving grounds for surgical innovation. Component separation · Laparoscopic
Over time, the approach to this challenge Acellular dermal matrix · Mesh · Transversus
shifted from open and invasive to more mini- abdominis repair · Artificial intelligence
mally invasive techniques. Advancements in Landmark · Review
our comprehension of anatomy and the devel-
opment of newer techniques as well as mesh
technologies have been pivotal to this progres- The Five Most Impactful Papers
sion. Herein, we explore five landmark studies 1. Ramirez OM, Ruas E, Dellon AL.
that have shaped modern practices. In addi- “Components separation” method for closure
tion, we cite other relevant studies to provide a of abdominal-wall defects: an anatomic and
comprehensive context and deeper insight into clinical study. Plast Reconstr Surg.
these developments. 1990;86(3):519–26.
2. Luijendijk RW, Hop WC, van den Tol MP,
et al. A comparison of suture repair with mesh
Jeffrey E. Janis, MD receives royalties from Thieme and repair for incisional hernia. N Engl J Med.
Springer Publishing 2000;343(6):392–8.
3. Butler CE, Campbell KT. Minimally invasive
component separation with inlay bioprosthetic
R. Elmorsi · C. E. Butler (*) mesh (MICSIB) for complex abdominal wall
Department of Plastic Surgery, The University of reconstruction. Plast Reconstr Surg.
Texas MD Anderson Cancer Center, 2011;128(3):698–709.
Houston, TX, USA
4. Novitsky YW, Elliott HL, Orenstein SB,
A. Hassan Rosen MJ. Transversus abdominis muscle
Division of Plastic Surgery, Department of Surgery,
release: a novel approach to posterior compo-
Indiana University School of Medicine,
Indianapolis, IN, USA nent separation during complex abdominal
J. E. Janis
The Ohio State University Wexner Medical Center,
Columbus, OH, USA
https://doi.org/10.1007/978-3-031-57132-9_27
286 R. Elmorsi et al.
wall reconstruction. Am J Surg. physiologic tension closure while reestablishing

2012;204(5):709–16. dynamic muscle support [5, 6]. Recurrence serves
5. Booth JH, Garvey PB, Baumann DP, et al. as the cornerstone outcome measure, with estimates
Primary fascial closure with mesh reinforce- between 8.7% and 32%, depending on patient
ment is superior to bridged mesh repair for comorbidities, use of mesh, length of follow-up,
abdominal wall reconstruction. J Am Coll and surgical technique itself [7–10]. In recent years,
Surg. 2013;217(6):999–1009. there have been rapid advancements in AWR, but
the future is likely to result in further innovations in
the field. In this chapter, we discuss five studies that,
27.1 Introduction in our opinion, have guided the directionality of this
innovation.
The abdomen is a dynamic pressurized compart-
ment with a rigid posterior wall. Spikes in intra-
abdominal pressure are promptly counteracted by 27.2 Landmark 1: The Anterior
increased muscle tone of the abdominal wall in Component Separation
healthy individuals. However, disruption of this
equilibrium can give rise to bulges, diastasis, and Until the late nineteenth century, the prevailing
hernias. Bulges can arise from denervation of approach to IVH involved mobilizing and pri-
intact musculature due to surgery or neuromus- marily closing the abdominal wall musculofas-
cular disease, or from partial loss of the anatomi- cia [11]. If this was not feasible or was
cal integrity in innervated abdominal musculature, complicated by excessive tension, a bridging
as seen in flank hernias with intact external mesh was used [12]. The concept of “component
oblique but disrupted internal oblique or trans- separation” refers to the creation of an intermus-
versus abdominis. Diastasis recti, on the other culofascial plane that allows for additional
hand, is a widening of the linea alba with resul- medial mobilization of the rectus abdominis
tant lateralization of the abdominal recti, without complex. The lateral abdominal wall muscula-
a fascial defect [1]. In contrast, ventral hernias ture has redundancy with three distinct layers.
are due to true defects in the fascia or muscula- Generally, one of the three layers can be dis-
ture, through which intra-abdominal contents can rupted without causing clinically relevant weak-
protrude, risking incarceration and strangulation, ness. Component separation takes advantage of
if left uncorrected. While traditionally approached this redundancy to increase the surface area of
as a single entity, it is crucial to differentiate pri- the abdominal wall for hernia repairs. This
mary from incisional ventral hernias (IVH), as approach includes two variations: “anterior com-
their respective patient populations and outcomes ponent separation” (ACS) and “posterior com-
vary as well [2]. Primary hernias are rare and ponent separation” (PCS). ACS involves dividing
arise from a congenital weakness or deficiencies the external oblique aponeurosis and dissecting
in the abdominal wall, whereas IVH, the most between the external and internal oblique mus-
commonly encountered by surgeons, result from cle. PCS involves division of the posterior
failure in an abdominal wall closure. lamella of the internal oblique as well as the
Approximately two million laparotomies are transversus abdominis muscle and dissecting
performed annually in the United States alone, and between the muscle and transversalis fascia (or
IVH occur in approximately 13% of these cases, peritoneum). Both ACS and PCS, albeit signifi-
resulting in approximately 350,000 abdominal wall cantly different, share the common goal of medi-
reconstructions (AWR) each year [3, 4]. Despite alizing musculofascia and reapproximating the
this substantial volume, there is not yet a consensus linea alba [13, 14]. Both can be performed with
regarding indications and choice of repair tech- low complication rates, as well, in properly opti-
nique. In general, the goal of AWR is to achieve a mized patients [15].
27 Evolution of Abdominal Wall Reconstruction 287
The term “component separation,” later popular-

ized as ACS, was first coined by Ramirez et al. in
1990 [13]. In their landmark study, they dissected
the abdominal walls of ten fresh cadavers and
reported on the significant ability to mobilize mus-
culofascial tissue to the midline. They noted that the
interoblique plane was relatively avascular and easy
to dissect through, and that the external oblique
muscle was a major restrictor of rectus medializa-
tion due to its fascial rigidity. Thereupon, by cutting
the external oblique aponeurosis and freeing the
rectus muscle from its posterior sheath, each rectus
complex could be advanced medially up to 5, 10,
and 3 cm at the superior, middle, and inferior thirds
of the abdomen, respectively (Fig. 27.1) [16].
Encouraged by these findings, they applied their
technique to 11 ventral hernia patients and success-
fully reconstructed defects of up to 15 × 25 cm
without the need for autologous flaps.
Although Ramirez et al. reported zero recur-
rences, their small sample size and dispersed
follow-up periods, ranging from 4 months to
3.5 years, were insufficient to draw conclusions
Fig. 27.1 A schematic presentation of the first compo-
regarding the technique’s reliability and compli- nent separation performed by Ramirez et al. Reproduced
cations. With increased adoption of their tech- with permission from Ramirez OM, Ruas E, Dellon
nique, it was found to feature multiple limitations. AL. “Components separation” method for closure of
Their invasive approach involved significant abdominal-wall defects: an anatomic and clinical study.
Plast Reconstr Surg. 1990;86(3):519–526. https://doi.
mobilization of lipocutaneous tissue and resulted org/10.1097/00006534-199,009,000-00023
in a large wound involving much of the central
abdominal wall, thereby predisposing it to com-
plications such as hematomas, seromas, and tial midline skin necrosis and wound dehiscence.
infections [17]. In addition, the transection of Moreover, navigating around enterostomies to
rectus perforators reduced the perfusion to the access the external oblique aponeurosis was
central abdominal skin that could result in poten- challenging.
Ramirez OM, Ruas E, Dellon AL. “Components separation” method for closure of abdominal-wall defects: an
anatomic and clinical study. Plast Reconstr Surg. 1990;86(3):519–26
Strengths • Novel, groundbreaking technique that revolutionized the paradigm of AWR
• Anatomical discoveries in cadavers were validated through a prospective clinical trial
Limitations • Small sample size and short, variable follow-up periods
• Deficient description of methods and results in regards to the 11 clinical cases
Impact This landmark study marked the beginning of the component separation era, which has been
significantly advanced into less traumatic and minimally invasive techniques, as will be
highlighted later in this chapter
27.3 Landmark 2: Mesh Repair Is an overlap of 2–4 cm. The mesh was then sutured
Superior to Suture Repair in the retrofascial plane, after closure of any peri-
toneal defects to minimize visceral contact with
Until the 1990s, and despite multiple reports on the mesh. The patients were followed up for
the use of sutures or mesh for IVH repair, there 3 years, and a remarkable 57% reduction in
was no consensus on the superiority of either recurrence rate was achieved with mesh repair. In
entities due to the uncontrolled or nonrandom- another follow-up study, the same group reported
ized designs of available studies. Luijendijk et al. a 10-year cumulative recurrence rate of 63% for
conducted the first prospective, multicenter, con- suture repair versus 32% for mesh repair, high-
trolled, randomized trial, where they enrolled lighting the long-term benefits of mesh repair
154 patients with primary or first recurrence IVH [19]. Additionally, mesh repair was associated
of less than 6 cm in length or width [18]. The with a reduced postoperative abdominal pain
patients were randomized to undergo either compared to suture repair. This finding has sig-
suture repair or mesh repair. Suture repair nificantly contributed to establishing mesh repair
involved approximating fascial edges using a as a standard approach for almost all IVH. Some
continuous polypropylene suture, while mesh recent studies have recommended the use of a
repair involved freeing the dorsal side of fascia prophylactic mesh for laparotomies at high risk
and suturing a tailored polypropylene mesh with for IVH [20].
Luijendijk RW, Hop WC, van den Tol MP, et al. A comparison of suture repair with mesh repair for incisional
hernia. N Engl J Med. 2000;343(6):392–8
Strengths • Well-designed, randomized, controlled, prospective study
• Established the superiority of mesh repair to suture repair
Limitations • No blinding measures were taken at any of the study stages, possibly causing a Pygmalion
bias
Impact This landmark research provided compelling evidence supporting the superiority of mesh repair
over suture repair for primary or first recurrence incisional ventral hernias
27.4 Landmark 3: Minimally Following laparotomy and adhesiolysis, the

Invasive Components minimally invasive component separation begins
Separation with Inlay by creating a 3-cm wide horizontal subcutaneous
Bioprosthetic Mesh (MICSIB) tunnel just below the costal margin, extending
from the midline to the linea semilunaris. A 2-cm
The Minimally Invasive Components Separation incision in the external oblique aponeurosis
with Inlay Bioprosthetic Mesh (MICSIB) was allows a dissector such a suction handle or uter-
pioneered by Butler in 2008, and its early out- ine sound to be inserted between the internal and
comes were reported in 2011 [21]. As the title external oblique muscles. Blunt dissection in
implies, bioprosthetic (biologic) mesh was ini- sweeping motions is used to separate the internal
tially used for all cases, but with additional exten- and external oblique muscles. Similar blunt dis-
sive experience, synthetic mesh was used for section is used to create a subcutaneous tunnel
appropriate cases. Thus, this minimally invasive over the semilunar line. Now with space above
components separation (MICS) technique is very and below the external oblique aponeurosis, it
versatile with any mesh able to be used based on can be safely incised from costal margin to pubis.
surgeon selection. This technique aims to reduce These maneuvers are performed entirely through
subcutaneous dead space and preserve rectus per- the horizontal tunnel and require meticulous
forators, while providing reinforcement with lighting and retraction (Fig. 27.2). Mesh is then
mesh. inset via a preperitoneal technique, involving
sutures that pass through the mesh and then back repair. To reduce any dead space and risk of
through the musculofascial complex, creating seroma, resorbable quilting sutures are placed
“U” stitches (Fig. 27.3). The musculofascia is between any undermined subcutaneous fat and
then closed in the midline creating a “reinforced” musculofascia [22–24]. If complete musculofas-
Fig. 27.2 A diagram of

the narrow subcutaneous
tunnels and line of
release of external
oblique aponeurosis.
Reproduced with
permission from Butler
CE, Campbell
KT. Minimally invasive
component separation
with inlay bioprosthetic
mesh (MICSIB) for
complex abdominal wall
reconstruction. Plast
Reconstr Surg.
2011;128(3):698–709.
https://doi.org/10.1097/
PRS.0b013e318221dcce
Fig. 27.3 A cross section of the reconstructed abdominal sion from Butler CE, Campbell KT. Minimally invasive
wall following minimally invasive component separation component separation with inlay bioprosthetic mesh
with inlay bioprosthetic mesh (MICSIB). The biopros- (MICSIB) for complex abdominal wall reconstruction.
thetic mesh is inset in the preperitoneal, retrorectus, or Plast Reconstr Surg. 2011;128(3):698–709. https://doi.
intraperitoneal plane. Subcutaneous tunnels dead space is org/10.1097/PRS.0b013e318221dcce
obliterated by quilting sutures. Reproduced with permis-
cial midline closure is absolutely not achievable, requiring larger meshes, they experienced fewer
“bridged” repair is performed where the mesh complications. The MICS group had roughly
spans the defect between the musculofascial half the incidence of skin dehiscence and
edges. This bridged repair is, however, inferior to wound-healing complications. They also had a
primary fascial repair with much higher recur- lower hernia recurrence rate. These outcomes
rence rates [25]. can be attributed to the meticulous preservation
In a comparative follow-up study, the long- of vascularity of overlying skin, eliminating the
term outcomes of MICS were evaluated in con- need for undermined skin flaps, and the reduc-
trast to the classic ACS [26]. Despite MICS tion of paramedian dead space achieved through
patients having significantly larger defects and MICS.
Butler CE, Campbell KT. Minimally invasive component separation with inlay bioprosthetic mesh (MICSIB) for
complex abdominal wall reconstruction. Plast Reconstr Surg. 2011;128(3):698–709
Strengths • Innovative, minimally traumatic approach to AWR reconstruction in challenging patients
• Does not require expensive laparoscopic equipment or expertise
• Easily able to perform component separation in patients with enterostomies
Limitations • Absence of a control group
• Single surgeon experience
Impact The MICS technique represents a milestone in the ongoing evolution toward minimally invasive
AWR. Due to its established benefits and ability to use any mesh, MICSIB is currently widely
adopted by surgeons worldwide
27.5 Landmark 4: The Transversus oblique is incised 0.5 cm medial to the segmen-
Abdominis Release tal neurovascular bundles near the semilunar
line, exposing the underlying transversus
The transversus abdominis release (TAR) tech- abdominis muscle, which is then divided along
nique, pioneered by Novitsky et al. [27] falls its entire medial edge. By further dissecting a
under the category of PCS, which was first
coined by Carbonell et al. in 2008 [28]. Building
on the principles of the Rives-Stoppa repair,
TAR allows for the advancement of the rectus
abdominis muscles to facilitate midline closure,
along with the placement of a retromuscular
mesh that can extend far laterally, without the
Fig. 27.4 A cross section of the reconstructed abdomi-
need for dissection of the subcutaneous tissues
nal wall following Transversus Abdominis Release
(Fig. 27.4). (TAR). Note the mesh extending far beyond the confines
The procedure begins with a retrorectus dis- of the rectus complex with minimal or no suturing
section to the semilunar line. This allows visual- needed for fixation. Reproduced with permission from
Novitsky YW, Elliott HL, Orenstein SB, Rosen
ization of the junction between the ventral
MJ. Transversus abdominis muscle release: a novel
lamella of the posterior sheath and the perforat- approach to posterior component separation during com-
ing neurovascular bundles, which are carefully plex abdominal wall reconstruction. Am J Surg.
preserved. The posterior lamella of the internal 2012;204(5):709–716. https://doi.org/10.1016/j.
amjsurg.2012.02.008
plane between the divided transversus abdomi- subcutaneous dead space and preserves the vas-
nis muscle and the underlying transversalis fas- cularization of abdominal skin, which can reduce
cia (and sometimes peritoneum), the surgeon the occurrence of wound complications. Criss
creates a continuous retromuscular space that et al. also reported a significantly improved
can be extended laterally to the psoas muscle, torque of the recti following TAR [30]. However,
cranially to the dome of the diaphragm, and cau- TAR may not provide as much medialization of
dally to Cooper’s ligament, Space of Retzius, the rectus complexes as seen in ACS, thereby
and pubic bone The posterior sheath is mobilized leading to potentially more “bridged” repairs,
and reapproximated at the midline, thus exclud- which risks higher recurrence in comparison to
ing the abdominal viscera from the mesh to be the reinforced closure [29]. In addition, the place-
placed. As a result, restoration of the midline is ment of a large amount of mesh into the abdomi-
possible and a large mesh is inset as a sublay, nal wall poses the threat of devastating infections
over which the anterior rectus complexes are that may require surgical excision and resultant
reapproximated to restore the linea alba. In injury of the lateral abdominal wall. A recent
instances where approximation of the anterior meta-analysis favored PCS over ACS techniques
rectus sheaths is not possible, the gap can be in terms of wound morbidities, which aligns with
“bridged” with the mesh [30]. the inclusion of perforator-dissecting ACS in the
TAR has enabled closure of large midline comparison [31]. On the other hand, a retrospec-
defects and the placement of a sublay mesh that tive study comparing TAR with perforator-
extends far laterally, eliminating the need for sparing ACS showed no significant differences in
extensive mesh fixation. Since the mesh lies wound complications, in addition to highlighting
anterior to a reconstructed posterior rectus sheath, the versatility of perforator-sparing ACS in clos-
the use of uncoated, macroporous mesh is possi- ing larger hernia defects [15]. Further well-
ble without the risk of bowel contact and adhe- designed studies are needed to objectively
sion. Furthermore, TAR results in minimal compare MICS and TAR.
Novitsky YW, Elliott HL, Orenstein SB, Rosen MJ. Transversus abdominis muscle release: a novel approach to
posterior component separation during complex abdominal wall reconstruction. Am J Surg. 2012;204(5):709–16
Strengths • Creation of a large retromuscular plane allows the use of large sublay mesh without risk of
bowel exposure to mesh
• Minimal subcutaneous dissection results in less wound complications
Limitations • Absence of a control group
• Short follow-up period
Impact TAR represents another milestone in the ongoing evolution of AWR, newer robotic modifications
of TAR are now being adopted and popularized, with initial reports showing improved outcomes
[29]
27.6 Landmark 5: Primary Fascial patients with a follow-up of 4 years experienced

Closure with Mesh a recurrence. Additionally, they had six- fold
Reinforcement Is the “Gold increase in the overall complications resulting in
Standard” a longer length of hospital stay. Although the
authors acknowledged the larger defects and
Plastic surgeons manage large IVH that are often higher incidence of rectus complex violation in
difficult to close under physiologic tension with- their bridged repair group, regression analyzes
out resorting to component separation. Despite established that bridged repair alone was a strong
the introduction of MICS in 2008, which enabled independent risk factor for hernia recurrence and
a robust and minimally invasive medialization of abdominal wall complications.
the recti, some surgeons still opted for bridged Although primary fascial closure is crucial, it is
repairs instead of component separation when even more critical to be mindful of the serious com-
direct closure was not feasible. A bridged repair plications of high-tension closures. These can
involves suturing the opposing fascia onto an range from fascial dehiscence and hernia recur-
underlying mesh if they cannot be approximated rence to a potentially fatal abdominal compartment
under physiologic tension. However, the 2013 syndrome. To identify a high-tension closure, an
study by Booth et al. marked a significant turning increase in peak airway pressure by 12 mmHg or a
point in AWR, where they established the rise in plateau airway pressure by 4.4 mmHg above
unmatched superiority of reinforced mesh repair baseline can serve as indicators [31]. Khansa and
compared to bridged mesh repair in IVH [25]. Janis [6] described an a lgorithm to approach this
Booth et al. conducted a retrospective analysis challenge; if standard maneuvers failed to achieve
of 222 IVH patients treated and followed up for a tension-free primary closure, component separa-
at least 1 year at a major US cancer center, from tion should be considered. Initially, a unilateral
2000 to 2011. Out of these patients, 195 under- component separation can be attempted, followed
went primary mesh-reinforced fascial closure, by reassessment and a contralateral component
while 27 underwent bridged mesh repair. In com- separation if needed. Should the resultant tension
parison to the primary fascial closure group, the remain inadequate, a temporary dressing is applied
bridged repair group had over seven-fold the and the closure is deferred until swelling subsides.
recurrence rate and developed these recurrences However, if this is not feasible, the bridged repair
nine-fold earlier. In fact, all bridged repair becomes an acceptable last resort.
Booth JH, Garvey PB, Baumann DP, et al. Primary fascial closure with mesh reinforcement is superior to bridged
mesh repair for abdominal wall reconstruction. J Am Coll Surg. 2013;217(6):999–1009
Strengths • Reliable data from a prospectively maintained database and surgeries performed by highly
experienced faculty
• Adequate mean follow-up period of 31 months
Limitations • Small number of patients in the bridged-repair group
Impact Established the importance of attaining a primary closure of fascia and only resorting to bridged
closures as a last resort
27.7 Expert Concluding (2) the study by Luijendijk et al. established the
Commentary superiority of mesh compared to sutures in IVH
repair; (3) Butler’s MICS technique proved
In this chapter, we discussed five key studies that robust and versatile in challenging IVH patients;
have shaped the current paradigms of AWR: (1) (4) Novitsky et al.’s TAR enabled the placement
The study by Ramirez et al. marked the begin- of mesh beyond the borders of the rectus com-
ning of the component separation era in AWR; plex with minimal or no required fixations; and
(5) the establishment of importance of primary nia (IH) repair is no more acceptable: results of a sys-
fascial closure in AWR by Booth et al. tematic review and metanalysis of current literature.
Hernia. 2019;23(5):831–45.
Building upon these advancements, future 3. Carney MJ, Weissler JM, Fox JP, Tecce MG, Hsu JY,
research can focus on one of three areas. First, Fischer JP. Trends in open abdominal surgery in the
the development of an “ideal” mesh that com- United States-observations from 9,950,759 discharges
bines favorable properties from both biologic using the 2009-2013 National Inpatient Sample (NIS)
datasets. Am J Surg. 2017;214(2):287–92.
and synthetic meshes. This mesh should be dura- 4. Bosanquet DC, Ansell J, Abdelrahman T, et al.
ble, lightweight, porous, and resistant to infec- Systematic review and meta-regression of factors
tion [32]. Secondly, the innovation in surgical affecting midline incisional hernia rates: analysis of
techniques, such as the application of robotic 14,618 patients. PLoS One. 2015;10(9):e0138745.
5. Butler CE, Baumann DP, Janis JE, Rosen
surgery to IVH repair, which holds promise MJ. Abdominal wall reconstruction. Curr Probl Surg.
given its low wound complications, reduced hos- 2013;50(12):557–86.
pital stays, and reported ease of defect closure 6. Khansa I, Janis JE. The 4 principles of complex
[33, 34]. Unfortunately, this approach faces key abdominal wall reconstruction. Plast Reconstr Surg
Glob Open. 2019;7(12):e2549.
limitations, including the need for extended 7. Recurrent KF, Overview IHR-A. Front Surg.
training and the associated technology costs, in 2019;6:26.
addition to its limited applicability in large 8. Awaiz A, Rahman F, Hossain MB, et al. Meta-analysis
defects compared to MICS and open and systematic review of laparoscopic versus open
mesh repair for elective incisional hernia. Hernia.
TAR. Thirdly, optimizing patient selection and 2015;19(3):449–63.
perioperative patient rehabilitation should 9. Christoffersen MW, Brandt E, Helgstrand F, et al.
become an integral part of future patient care Recurrence rate after absorbable tack fixation of mesh
[35]. Risk stratification can already be achieved in laparoscopic incisional hernia repair. Br J Surg.
2015;102(5):541–7.
by grading systems such as the ventral hernia 10. Köckerling F. Onlay technique in incisional hernia
work group (VHWG) score [36]. However, repair-a systematic review. Front Surg. 2018;5:71.
machine learning may provide more dynamic 11. Ger R, Duboys E. The prevention and repair of large
and individualized predictions, with the added abdominal-wall defects by muscle transposition: a
preliminary communication. Plast Reconstr Surg.
advantage of incremental learning and improved 1983;72(2):170–8.
predictions over time [37]. 12. Voyles CR, Richardson JD, Bland KI, Tobin GR,
Plastic surgery is built upon unmatched inno- Flint LM, Polk HC. Emergency abdominal wall
vation and revolutionary techniques, which is reconstruction with polypropylene mesh: short-term
benefits versus long-term complications. Ann Surg.
why the future of AWR may very well lie beyond 1981;194(2):219–23.
the scope of our discussion or anticipation. 13. Ramirez OM, Ruas E, Dellon AL. “Components sepa-
Nonetheless, our intention for this chapter is two- ration” method for closure of abdominal-wall defects:
fold: to provide a comprehensive review of an anatomic and clinical study. Plast Reconstr Surg.
1990;86(3):519–26.
advancements in AWR, and to offer a guide for 14. Maman D, Greenwald D, Kreniske J, Royston A,
innovators and surgeons in order to tackle exist- Powers S, Bauer J. Modified rives-Stoppa technique
ing challenges and address them. for repair of complex incisional hernias in 59 patients.
Ann Plast Surg. 2012;68(2):190–3.
15. Sacco JM, Ayuso SA, Salvino MJ, et al. Preservation
Financial Disclosure Jeffrey E. Janis, MD receives roy- of deep epigastric perforators during anterior compo-
alties from Thieme and Springer Publishing. nent separation technique (ACST) results in equiva-
lent wound complications compared to transversus
abdominis release (TAR). Hernia. 2023;27(4):819–27.
References 16. Shestak KC, Edington HJ, Johnson RR. The sepa-
ration of anatomic components technique for the
reconstruction of massive midline abdominal wall
1. ElHawary H, Abdelhamid K, Meng F, Janis JE. A defects: anatomy, surgical technique, applica-
comprehensive, evidence-based literature review tions, and limitations revisited. Plast Reconstr Surg.
of the surgical treatment of rectus diastasis. Plast 2000;105(2):731–8; quiz 739.
Reconstr Surg. 2020;146(5):1151–64. 17. Girotto JA, Ko MJ, Redett R, Muehlberger T, Talamini
2. Stabilini C, Cavallaro G, Dolce P, et al. Pooled data M, Chang B. Closure of chronic abdominal wall
analysis of primary ventral (PVH) and incisional her- defects: a long-term evaluation of the components sep-
aration method. Ann Plast Surg. 1999;42(4):385–94; 28. Carbonell AM, Cobb WS, Chen SM. Posterior com-
discussion 394. ponents separation during retromuscular hernia repair.
18. Luijendijk RW, Hop WC, van den Tol MP, et al. A Hernia. 2008;12(4):359–62.
comparison of suture repair with mesh repair for inci- 29. Dewulf M, Hiekkaranta JM, Mäkäräinen E, et al.
sional hernia. N Engl J Med. 2000;343(6):392–8. Open versus robotic-assisted laparoscopic posterior
19. Burger JWA, Luijendijk RW, Hop WCJ, Halm JA, component separation in complex abdominal wall
Verdaasdonk EGG, Jeekel J. Long-term follow- repair. BJS Open. 2022;6(3):zrac057.
up of a randomized controlled trial of suture ver- 30. Alkhatib H, Tastaldi L, Krpata DM, et al. Outcomes of
sus mesh repair of incisional hernia. Ann Surg. transversus abdominis release (TAR) with permanent
2004;240(4):578–83; discussion 583. synthetic retromuscular reinforcement for bridged
20. Jairam AP, Timmermans L, Eker HH, et al. Prevention repairs in massive ventral hernias: a retrospective
of incisional hernia with prophylactic onlay and sub- review. Hernia. 2020;24(2):341–52.
lay mesh reinforcement versus primary suture only in 31. Blatnik JA, Krpata DM, Pesa NL, et al. Predicting
midline laparotomies (PRIMA): 2-year follow-up of severe postoperative respiratory complications fol-
a multicentre, double-blind, randomised controlled lowing abdominal wall reconstruction. Plast Reconstr
trial. Lancet. 2017;390(10094):567–76. Surg. 2012;130(4):836–41.
21. Butler CE, Campbell KT. Minimally invasive com- 32. Warren JA, McGrath SP, Hale AL, Ewing JA,
ponent separation with inlay bioprosthetic mesh Carbonell AM, Cobb WS. Patterns of recurrence and
(MICSIB) for complex abdominal wall reconstruc- mechanisms of failure after open ventral hernia repair
tion. Plast Reconstr Surg. 2011;128(3):698–709. with mesh. Am Surg. 2017;83(11):1275–82.
22. Janis JE. Use of progressive tension sutures in com- 33. LeBlanc KA, Gonzalez A, Dickens E, et al. Robotic-
ponents separation: merging cosmetic surgery tech- assisted, laparoscopic, and open incisional hernia
niques with reconstructive surgery outcomes. Plast repair: early outcomes from the prospective hernia
Reconstr Surg. 2012;130(4):851–5. study. Hernia. 2021;25(4):1071–82.
23. Khansa I, Janis JE. Management of skin and subcuta- 34. Forester B, Attaar M, Donovan K, et al. Short-term
neous tissue in complex open abdominal wall recon- quality of life comparison of laparoscopic, open,
struction. Hernia. 2018;22(2):293–301. and robotic incisional hernia repairs. Surg Endosc.
24. Janis JE, Khansa L, Khansa I. Strategies for postop- 2021;35(6):2781–8.
erative seroma prevention: a systematic review. Plast 35. Joslyn NA, Esmonde NO, Martindale RG, Hansen
Reconstr Surg. 2016;138(1):240–52. J, Khansa I, Janis JE. Evidence-based strategies for
25. Booth JH, Garvey PB, Baumann DP, et al. Primary the Prehabilitation of the Abdominal Wall recon-
fascial closure with mesh reinforcement is superior to struction patient. Plast Reconstr Surg. 2018;142(3
bridged mesh repair for abdominal wall reconstruc- Suppl):21S–9S.
tion. J Am Coll Surg. 2013;217(6):999–1009. 36. Ventral Hernia Working Group, Breuing K, Butler CE,
26. Ghali S, Turza KC, Baumann DP, Butler et al. Incisional ventral hernias: review of the litera-
CE. Minimally invasive component separation results ture and recommendations regarding the grading and
in fewer wound-healing complications than open technique of repair. Surgery. 2010;148(3):544–58.
component separation for large ventral hernia repairs. 37. Hassan AM, Lu S-C, Asaad M, et al. Novel machine
J Am Coll Surg. 2012;214(6):981–9. learning approach for the prediction of hernia recur-
27. Novitsky YW, Elliott HL, Orenstein SB, Rosen rence, surgical complication, and 30-day readmission
MJ. Transversus abdominis muscle release: a novel after Abdominal Wall reconstruction. J Am Coll Surg.
approach to posterior component separation during 2022;234(5):918–27.
complex abdominal wall reconstruction. Am J Surg.
2012;204(5):709–16.
Part X
Lower Extremity
Evolution of Lower Limb
Orthoplastic Management
28
Dominik Kaiser, Stephen Kovach,
and L. Scott Levin
Abstract Keywords
In this chapter, we discuss the evolution of Landmark · Orthoplastic · Lower limb

orthoplastic management spanning 45 years in salvage · Upper limb salvage · Free flap
limb salvage in three different fields in the Tissue transfer
context of five landmark publications that
have guided this evolution and continuously
catalyze further advances and innovation. The Five Most Impactful Papers
Additionally, it is our goal to present an over- 1. Godina M. Early microsurgical reconstruc-
view of this collaborative and rapidly develop- tion of complex trauma of the extremities.
ing field. The entirety of the field cannot be Plast Reconstr Surg. 1986;78(03):285–92.
covered by five references, which is why fur- 2. Godina M. Preferential use of end-to-side
ther references are cited to provide additional arterial anastomoses in free flap transfers.
sources highlighting the field. The selected Plast Reconstr Surg. 1979;64(5):673–82.
five references, however, have led to pivotal 3. Cierny GI. A clinical staging system for
conceptual advancements in limb salvage adult osteomyelitis. Contemp Orthop.
management, describe the applications of 1985;10:17–37.
orthoplastic concepts, and are emblematic of 4. Farzaliyev F, Steinau HU, Touma A, Karadag
the orthoplastic “thought process.” HI, Hamacher R, Podleska LE. Long-term
oncological and functional outcome after
multimodal treatment for sarcomas of the
hand and wrist of 168 patients. Orthoplast
Surg. 2020;1:3–10.
5. Levin LS. The reconstructive ladder: an
orthoplastic approach. Orthop Clin North
Am. 1993;24:393–409.
D. Kaiser (*) · L. S. Levin

Department of Orthopaedic Surgery, Penn Medicine
28.1 Introduction
S. Kovach
Orthoplastic surgery is by definition, “the principle
Division of Plastic Surgery, Perelman Center for and practice of both specialties (plastic and ortho-
Advanced Medicine, Philadelphia, PA, USA paedic surgery) applied to clinical problems simul-
https://doi.org/10.1007/978-3-031-57132-9_28
298 D. Kaiser et al.
taneously.” The term orthoplastic approach has 28.1.1 Early Microsurgical

been described and popularized by LS Levin in Reconstruction of Complex
1993 [1]. The concepts, however, had already been Trauma of the Extremities
successfully applied by surgical pioneers for many
years. In limb salvage, this concept has resulted in Marko Godina was a pioneer and innovator in the
improved quality of life, decreased morbidity and field of reconstructive surgery. He made several
mortality for many diseases, and challenged the significant contributions to lower extremity
guiding principle in the care of extremity injuries trauma care [6]. One of his most noteworthy con-
of “life before limb.” Orthoplastic extremity recon- tributions was the “Godina method” of treating
structive surgery may be categorized in the treat- complex lower extremity trauma, consisting of
ment of traumatic, septic, and oncologic conditions radical debridement of contaminated open frac-
of the lower (upper) limb [2]. To highlight these tures followed by immediate or early free tissue
categories, we have included 1 (−2) reference(s) transfer for wound closure. His hallmark paper,
for each concept. In addition to understanding the published in 1986, is a testament and foundation
indications for amputations and the alternatives to for the principles of orthoplastic surgery [6]. The
limb salvage such as prosthetics, limb salvage also paper challenged the gold standard of that time of
includes optimizing treatment options of amputees waiting for the soft tissue to heal and propagated
by optimizing residual limb length and function aggressive soft tissue management and early
using microsurgical techniques [3, 4]. “What wound coverage.
should be salvaged?” has become the more com- He was able to demonstrate in a retrospective
mon debate than “What can be salvaged?” [5] as analysis of 532 free tissue transfers that an early
the overall goal of either limb salvage or amputa- reconstruction, defined as within 72 hours of
tion is improvement in quality of life. If any effort injury, had a greater success rate than a delayed
is to be made in favor of limb salvage, the result of or late reconstruction regarding flap survival,
reconstruction should be a limb that functions as postoperative infection, bone healing time, as
well if not better than a prosthesis. well as average length of hospital stay.
1986;78(03):285–92
Strengths • Large sample size N = 532 patients in three distinctive groups (early, delayed, late)
• Significant advantages favoring early coverage in all investigated outcomes (transfer failures,
postoperative infections, bone healing time, hospitalization time)
• Single institution
Limitations • Retrospective study design
Impact This was the first study to demonstrate the significant advantages of aggressive management of soft
tissue coverage as opposed to the usual approach at that time of waiting for the soft tissue to heal.
Additionally, it demonstrates the importance of an adequate soft tissue envelope on bony healing
interrelating the work of the orthopedic and the reconstructive surgeon and emphasizing the
importance of an “orthoplastic” approach
A landmark paper leading to a paradigm shift 28.1.2 End-to-Side Anastomosis

in the treatment of complex lower limb trauma. in Free Tissue Transfer
Additional studies have since confirmed the to the Lower Limb
importance of adequate and early soft tissue cov-
erage [7]. While during the 72-h timeline, the The gold standard and preference for microvas-
“emergency free flap” does not seem to be man- cular arterial anastomoses was end-to-end as this
datory, an early reconstruction up to 7–10 days technique is simpler and readily learned.
after injury with diligent wound debridement and Theoretically, it was also thought of as the most
irrigation seems preferable [8]. efficient and most logical approach to restoring
28 Evolution of Lower Limb Orthoplastic Management 299
blood flow to the transferred tissue. Introducing form and describe end-to-side anastomosis in
the technically more difficult technique of the free tissue transfers [10], his landmark publica-
arterial end-to-side anastomosis despite increased tion established its use in the microvascular com-
theoretical doubts about the hemodynamic effi- munity. He presents a case series of 41 consecutive
ciency is yet another remarkable contribution of free flaps without failures using the described
the gifted microsurgeon Marko Godina [9]. The end-to-side arterial anastomosis technique high-
conviction and courage to fundamentally change lighting four advantages (preservation of the ves-
a critical aspect of the free tissue transfer, namely sels distal to the anastomosis, easier planning,
the arterial anastomosis in an era of failure rates avoidance of retraction and spasm in the recipient
of more than 30% reflect his pioneering charac- artery, and avoidance of gross disturbance in the
ter. While Marko Godina was not the first to per- resulting flow).
Godina M. Preferential use of end-to-side arterial anastomoses in free flap transfers. Plast Reconstr Surg.
1979;64(5):673–82
Strengths • First study advocating for end-to-side anastomosis in an era of high failure rates
• At that time, large series of consecutive successful free flaps, utilizing the proposed
end-to-side technique
Limitations • Bias of different free flap likely to overestimate influence of arterial anastomosis technique
Impact A pioneering and bold step establishing a new arterial anastomosis technique challenging the
at-that-time-established end-to-end anastomosis
While newer studies demonstrate equivalent in their algorithm, leading to different treatment
complication rates of end-to-end and end-to-side protocols [13]. While this work and new classifi-
anastomoses [11, 12], end-to-side anastomoses cation did not fundamentally change the surgical
remains the preferred technique for extremities at management of osteomyelitis, it did introduce a
risk for vascular insufficiency and large size mis- new important factor (host condition) and still
matches of the vessels [8]. forms the basis of osteomyelitis classification in
adults at many institutions today. Additionally, it
also forms the basis for many further improve-
28.1.3 A Clinical Staging System ments and optimizations in the treatment of adult
for Adult Osteomyelitis osteomyelitis [14, 15]. George Cierny III and Jon
Mader present their results of 357 patients that
In 1985, George Cierny III and Jon Mader pub- were evaluated for adult osteomyelitis between
lished a paper presenting a new staging system June 1981 and December 1983. Of these 357
for adult osteomyelitis not only appreciating patients, 63 patients entered the limb salvage pro-
local factors but including the condition of the gram and were followed for a minimum of
host and the functional impairment of the disease 2 years.
Cierny GI. A clinical staging system for adult osteomyelitis. Contemp Orthop. 1985;10:17–37
Strengths • New classification for adult osteomyelitis that considers the whole patient (host condition
and functional impairment)
• Remains the most widespread classification till date
• Classification correlates with prognosis
Limitations • Only 63 patients of the 357 patients that were evaluated are included in the limb salvage
protocol with a minimum follow-up of 2 years
Impact George Cierny III and Jon Mader introduce a new classification for adult osteomyelitis in 1985,
which remains the most widespread classification in use today. The classification includes host
factors and correlates with the prognosis making it clinically very useful. Moreover, this work
and the classification presented in it have enabled a common classification and thus made
osteomyelitis research more uniform and comparable
28.1.4 Long-Term Oncological in orthopedic oncology to achieve safe sarcoma

and Functional Outcome After resection while immediately aiming to optimize
Multimodal Treatment the postoperative function of the upper limb. This
for Sarcomas of the Hand case series of 168 consecutive patients is the larg-
and Wrist of 168 Patients est till date, focusing on a rare disease (sarcoma)
in a rare site (5% of all sarcomas of the extremi-
Limb salvage and limb reconstruction after tumor ties) [17, 18]. All surgeries were performed by a
resection is another important field of orthoplas- single surgeon (H.U. Steinau), increasing its
tic surgery. In this landmark paper, Farzaliyev power.
et al. present the long term oncological and func- This study demonstrates that while the term of
tional outcome after sarcoma resection of the the orthoplastic approach was established and
hand and wrist, all performed by one senior sur- popularized in 1993 by LS Levin [1], its concepts
geon [16]. We have included this paper as it high- have already been applied in orthopedic oncol-
lights the importance of an orthoplastic approach ogy for many years.
Farzaliyev F, Steinau HU, Touma A, Karadag HI, Hamacher R, Podleska LE. Long-term oncological and functional
outcome after multimodal treatment for sarcomas of the hand and wrist of 168 patients. Orthoplast Surg.
2020;1:3–10
Strengths • Largest consecutive case series of sarcomas of the upper distal extremity using limb-
preserving therapy by one senior surgeon over 34 years
• Largest case series presenting long-term results of the treatment of a rare disease
Limitations • Retrospective analysis
Impact This publication summarizes the life’s work of a single surgeon in the treatment of an extremely
rare disease using orthoplastic principles prior to its popularization. Large case series for rare
diseases are critical in supporting the decision-making for a treatment plan in select patients
28.1.5 The Reconstructive Ladder plastic approach” in trauma care will allow opti-
mal repair processes to take place, avoid adverse
The treatment of soft-tissue injuries associated sequelae, and increase the limb salvage rate. In
with extremity trauma has been discussed since this original paper, the author, who first described
ancient times [19]. Wound treatment concepts for the “orthoplastic approach,” discusses his ratio-
simple and contaminated wounds were already nale and application of the reconstructive ladder
distinguished at that time. Many years have in extremity reconstruction. In this publication,
passed, and physicians have developed many new algorithms not only for soft tissue management
treatment methods to treat even the most com- but also for segmental bone loss and combined
plex soft tissue injuries. Nonetheless the empha- soft tissue injury and fractures are presented,
sis on soft tissue biology and protection of the arguing that optimally, the reconstructive surgeon
soft tissue from further damage remains decisive may go from one level to another and, in many
for the success of the treatment of lower and instances, simultaneously employ different
upper limb trauma. Simultaneous management of aspects of the ladder for different problems in the
the soft-tissue and the bone the so called “ortho- same surgery.
Levin LS. The reconstructive ladder: an orthoplastic approach. Orthop Clin North Am. 1993;24:393–409
Strengths • First description of the “orthoplastic approach”
• Provides a widely used algorithm for the “orthoplastic approach” for combined soft tissue
and bone management in upper and lower limb trauma
• Discusses the importance of soft tissue management while raising awareness among the
community of orthopedic surgeons
Limitations • Expert opinion and review
Impact A comprehensive summary of the importance of soft tissue management for complex trauma to
the upper and lower extremity focusing on raising awareness in the orthopedic community
28 Evolution of Lower Limb Orthoplastic Management 301
This combined approach of appreciating not the last decade have focused on defining new
only the bone but also the soft-tissue envelope indications as well as solving difficult clinical
has led to the field of orthoplastic surgery and to problems [26–29]. Increasingly successful treat-
multiple improvements in the treatment of ment of complex injuries resulting in limb sal-
severely injured limbs [20–22]. vage, will elevate patient expectations regarding
The mutually stimulating cooperation among esthetic outcomes and the return to “normalcy”
orthopedic surgeons and reconstructive surgeons [30].
ultimately benefits the patient’s quality of life by The field of secondary esthetic refinement,
improving function, reducing infection rate, especially in younger patients, has evolved and
increasing bony union rate, and expediting the should increasingly be included as part of the
return of extremity form and function [23]. optimal treatment algorithm.
The field of orthoplastic surgery is still evolv-
ing and the limits of what is possible have yet to
28.2 Expert Concluding be defined. The basis remains a collaboration
Commentary between the orthopedic and plastic surgeons.
Ultimately, the main goal of reconstructing a
Five landmark papers highlighting key elements limb that is at least as good as a prosthetic
of orthoplastic management of the lower (upper) replacement must not be lost sight of. The ortho-
limb have been presented. Key discoveries plastic approach will help meet this goal.
regarding the timing of free tissue coverage as
well as new microsurgical anastomosis tech-
niques for free tissue transfers, both challenging References
the gold standard of those times, have been dis-
cussed. This paradigm shift led to a significantly 1. Levin LS. The reconstructive ladder: an orthoplastic
approach. Orthop Clin N Am. 1993;24(3):393–409.
increased limb salvage rate and thus the success 2. Levin LS. From replantation to transplantation: the
of the highest of all rungs on the reconstructive evolution of orthoplastic extremity reconstruction. J
ladder. We have discussed two algorithms stan- Orthop Res. 2022;41:1587.
dardizing the treatment of adult osteomyelitis as 3. Erdmann D, et al. Microsurgical free flap transfer to
amputation sites: indications and results. Ann Plast
well as soft tissue management with and without Surg. 2002;48(2):167–72.
associated fractures both forming the basis for 4. Bibbo C, et al. Maintaining levels of lower extremity
continued academic discussion and innovation. amputations. J Surg Orthop Adv. 2017;25(3):137–48.
Finally, a life’s work in the treatment of rare dis- 5. Lerman OZ, Kovach SJ, Levin LS. The respective
roles of plastic and orthopedic surgery in limb sal-
eases, namely sarcomas of the hand and wrist, vage. Plast Reconstr Surg. 2011;127:215S–27S.
has been presented highlighting another area 6. Godina M. Early microsurgical reconstruction of
where the orthoplastic approach can improve the complex trauma of the extremities. Orthop Trauma
quality of life. Of course, these five publications Directions. 2006;4(05):29–35.
7. Fischer MD, Gustilo RB, Varecka T. The timing
only represent a small area of this rapidly devel- of flap coverage, bone-grafting, and intramedul-
oping subspecialty. lary nailing in patients who have a fracture of the
Major technical advancements like the intro- tibial shaft with extensive soft-tissue injury. JBJS.
duction of the operating microscope have largely 1991;73(9):1316–22.
8. Colen DL, et al. Godina’s principles in the twenty-
increased the technical possibilities for the first first century and the evolution of lower extrem-
free tissue transfers [24]. The next decades ity trauma reconstruction. J Reconstr Microsurg.
focused on perfecting surgical techniques which 2018;34(08):563–71.
have led to flap survival rates of over 95% and the 9. Godina M. Preferential use of end-to-side arterial
anastomoses in free flap transfers. Plast Reconstr
discovery of many new flaps such as perforators Surg. 1979;64(5):673–82.
flaps, which have proven to be as reliable as mus- 10. Ikuta Y, et al. Free flap transfers by end-to-side arte-
cle flaps or axial pattern flaps [25]. Advances of rial anastomosis. Br J Plast Surg. 1975;28(1):1–7.
11. Samaha FJ, et al. A clinical study of end-to-end versus 22. Mathews JA, et al. Single-stage orthoplastic recon-
end-to-side techniques for microvascular anastomo- struction of Gustilo–Anderson Grade III open tibial
sis. Plast Reconstr Surg. 1997;99(4):1109–11. fractures greatly reduces infection rates. Injury.
12. Khouri RK, Shaw WW. Reconstruction of the lower 2015;46(11):2263–6.
extremity with microvascular free flaps: a 10-year 23. Klifto KM, et al. The value of an orthoplastic approach
experience with 304 consecutive cases. J Trauma to management of lower extremity trauma: systematic
Acute Care Surg. 1989;29(8):1086–94. review and meta-analysis. Plast Reconstr Surg Glob
13. Cierny GI. A clinical staging system for adult osteo- Open. 2021;9(3)
myelitis. Contemp Orthop. 1985;10:17–37. 24. McLean DH, Buncke HJ Jr. Autotransplant of omen-
14. Mader JT, Cripps MW, Calhoun JH. Adult posttrau- tum to a large scalp defect, with microsurgical revas-
matic osteomyelitis of the tibia. Clin Orthop Relat cularization. Plast Reconstr Surg. 1972;49(3):268–74.
Res. 1999;360:14–21. 25. Cho EH, et al. Muscle versus fasciocutaneous free
15. Rod-Fleury T, et al. Duration of post-surgical antibi- flaps in lower extremity traumatic reconstruction: a
otic therapy for adult chronic osteomyelitis: a single- multicenter outcomes analysis. Plast Reconstr Surg.
centre experience. Int Orthop. 2011;35:1725–31. 2018;141(1):191–9.
16. Farzaliyev F, et al. Long-term oncological and func- 26. Haddock NT, et al. Applications of the medial femo-
tional outcome after multimodal treatment for sarco- ral condyle free flap for foot and ankle reconstruction.
mas of the hand and wrist of 168 patients. Orthoplast Foot Ankle Int. 2013;34(10):1395–402.
Surg. 2020;1:3–10. 27. Bürger HK, et al. Vascularized medial femoral troch-
17. Brennan MF, et al. Lessons learned from the study of lea osteocartilaginous flap reconstruction of proxi-
10,000 patients with soft tissue sarcoma. Ann Surg. mal pole scaphoid nonunions. J Hand Surg Am.
2014;260(3):416. 2013;38(4):690–700.
18. Henderson M, Neumeister MW, Bueno RA Jr. Hand 28. Bürger HK, et al. Vascularized medial femo-
tumors: II. Benign and malignant bone tumors of the ral trochlea osteochondral flap reconstruction of
hand. Plast Reconstr Surg. 2014;133(6):814e–21e. advanced Kienböck disease. J Hand Surg Am.
19. Majno G. The healing hand: man and wound in the 2014;39(7):1313–22.
ancient world, vol. 57. Harvard University Press; 29. Stranix JT, et al. Medial femoral condyle free flap
1975. p. 230. reconstruction of complex foot and ankle pathology.
20. Boriani F, et al. Orthoplastic surgical collaboration is Foot Ankle Orthop. 2019;4(4):2473011419884269.
required to optimise the treatment of severe limb inju- 30. Nelson JA, et al. Striving for normalcy after lower
ries: a multi-Centre, prospective cohort study. J Plast extremity reconstruction with free tissue: the role of
Reconstr Aesthet Surg. 2017;70(6):715–22. secondary esthetic refinements. J Reconstr Microsurg.
21. Azoury SC, et al. Principles of orthoplastic surgery 2015;32:101–8.
for lower extremity reconstruction: why is this impor-
tant? J Reconstr Microsurg. 2021;37(01):042–50.
Evolution of Diabetic Foot
Reconstruction
29
Joon Pio Hong
Abstract larization. Plast Reconstr Surg.

Despite the long existence of diabetes and its 2006;1117:261s–93s.
most dreaded complication, diabetic foot, the 3. Attinger C, Brown BJ. Amputation and ambu-
treatment for diabetic foot remains difficult. lation in diabetic patients: function is the goal.
The multiple factors involved, and the wide Diabetes Metab Res Rev. 2012;28(Suppl
spectrum of treatment makes it difficult for 1):93–6.
one surgeon to manage. Nevertheless, with a 4. Oh TS, Lee HS, Hong JP. Diabetic foot recon-
team approach, plastic surgeons can play a struction using free flaps increases 5-year-sur-
crucial role in managing the diabetic foot. In vival rate. J Plast Reconstr Aesth Surg.
this chapter, critical studies that have shaped 2013;66:243–50.
the roles for plastic surgeons and studies that
have provided fundamental concepts for
reconstruction will be discussed in detail. 29.1 Introduction
The topic of diabetic reconstruction has always

Keywords been synonymous with difficulty. Treatment for
the diabetic foot is multifactorial, involving
Diabetic foot reconstruction · Angiosomes ·
blood sugar, nutrition, walking habits, wound
Free flaps · Diabetic foot biomechanics
management, vascular supply, infection, and sur-
gical management [1]. This is why it makes it
Key Landmark Papers very difficult to treat without a good multidisci-
1. Robson MC, Edstrom LE. The diabetic foot: plinary team. One of the most dreaded complica-
an alternative approach to major amputation. tions of the diabetic foot is loss of limb, which
Surg Clin North Am. 1977;57(3):1089–102. leads to a sedentary life and ultimately to
2. Attinger CE, et al. Angiosomes of the foot and increased risk for mortality.
ankle and clinical implications for limb sal- In the mid-nineteenth century, scientists
vage: Reconstruction, incisions, and revascu- suspected an association between diabetes and
gangrene of the foot. Amputation was one of
the main modalities to treat gangrene but even
J. P. Hong (*) with the introduction of penicillin, the mortal-
Department of Plastic Surgery, Asan Medical Center,
Seoul, Korea (Republic of)
https://doi.org/10.1007/978-3-031-57132-9_29
304 J. P. Hong
ity rate after amputation was still high. 29.2 Principle of Diabetic Foot
Although introduction of insulin did improve Management
the mortality directly from diabetes, it didn’t
control the outcome for complications such as Robson MC and Edstrom LE were one of the pio-
diabetic foot. It was in 1964, with the introduc- neers advocating conservative surgery combined
tion of angioplasty, diminished circulation with infection control and debridement as an
from sclerosed arteries was able to be improved, alternative to major amputation for the diabetic
opening the possibilities of revascularization foot. In 1977, their study The diabetic foot: an
[2]. alternative approach to major amputation advo-
When the limb has reasonable circulation, cated treatment based on pathophysiology of vas-
the plastic surgeon can play a crucial role in cular insufficiency, neurotrophic changes, and
providing wound care and reconstruction as an infection [3]. This study set forth the basis of the
alternative to amputation. However, due to the modern approach addressing each of the major
wide spectrum of treatment and multiple vari- components leading to the diabetic foot. Today,
ables involved, it remains difficult to accu- managing the systemic condition, good wound
rately access the indication for reconstruction. care principles (infection control, debridement,
The number of impact papers are still scarce maintaining good circulation, and off-loading)
due to the difficulties involved in diabetic advanced wound management (negative wound
reconstruction. Nevertheless, increased reports pressure therapy, growth factors, stem cell ther-
are favoring limb salvage, as the technique of apy, cell therapy, dermal allografts, dermal substi-
vascular imaging and revascularization are tutes), wound preparation, and definitive surgery
evolving. by means of reconstruction or amputation are the
main components for diabetic foot management.
Robson MC, Edstrom LE. The diabetic foot: an alternative approach to major amputation. Surg Clin North Am.
1977;57(3):1089–102
Strengths • Clearly addressing the major factors involved in diabetic foot pathology
• Delivering the early concept of wound preparation
Limitations • Conceptual study with lack of clinical experience
Impact This study was one of the pioneering works to show good management focused on pathophysiology
can improve wound status and also prepare the wound for successful reconstruction. This was the
inception of modern wound care and management for diabetic foot
29.3 Angiosome of the Foot— expose tissue with better circulation. The work
Crucial Anatomy from Attinger C.E. et al. in 2006 Angiosomes of
for Reconstruction the foot and clinical implications for limb sal-
for Diabetic Foot vage: Reconstruction, incision, and revascular-
ization was a revolutionary study which changed
The angiosome principle was defined by Ian the concept of debridement for diabetic foot and
Taylor, where a source artery supplies a corre- sequential reconstruction [5]. Understanding
sponding three dimensional block of tissue [4]. the six different angiosomes of the foot will
This work provided the knowledge and theoreti- allow you to debride the ischemic tissue while
cal background for flaps to evolve, ultimately obtaining well-vascularized surrounding tissue,
resulting in the use of perforator flaps. The select incision lines that will not hinder the cir-
angiosome concept was used from a different culation of the foot, target the revascularization,
aspect to predict ischemic territories from a and design viable flaps. This is an essential
sclerosed end artery which clinically led to bet- paper that surgeons need to understand prior to
ter debridement of the ischemic tissue and to committing to diabetic foot reconstruction.
29 Evolution of Diabetic Foot Reconstruction 305
Attinger CE, et al. Angiosomes of the foot and ankle and clinical implications for limb salvage: Reconstruction,
incisions, and revascularization. Plast Reconstr Surg. 2006;1117:261s–93s
Strengths • Providing clear understanding for the angiosome anatomy through cadaver studies and clinical
experience
• Expanded the angiosome application to debridement, targeted angioplasty, and selection of flaps
• Provided the basis for angiosome-based reconstruction
Limitations 50 Cadaver dissections combined with clinical evaluation
Impact This study provided new anatomical knowledge and better understanding for circulation in the
diabetic foot. This revolutionized the thinking process for debridement especially for ischemic
diabetic feet. The idea and concepts from this paper now represent the standard approach and thinking
in diabetic foot reconstruction
29.4 It’s All About the Function biomechanics of the foot is crucial to obtaining a
of the Foot highly functioning limb as well as minimizing
post-reconstruction complications. Often with
The reconstructive surgeon, along with the trans-metatarsal amputation and reconstruction,
patient’s strong will to preserve the limb, often frequent re-ulceration of the forefoot side of the
tried to salvage the limb at all costs. Without clear reconstruction can be seen. This is most likely due
understanding of long-term outcome, the patient to the fact of faulty biomechanics in not releasing
may undergo challenging rehabilitation, repetitive the tight Achilles tendon shifting the weight
operations, and increased economic burden trying toward the forefoot during gait [6]. Although
to achieve a reasonable functioning limb. The role selection of different flaps may play a role in
of amputation in limb salvage is often poorly recurrence of ulceration, the most important fac-
defined and the difficulty lies in selecting limb tor is biomechanics. The 20-year study presented
salvage versus early amputation. For the seden- by Attinger et al. Amputation and ambulation in
tary patient, even a suboptimal functioning limb diabetic patients: Function is the goal discusses
still can provide a higher quality of life than an these factors and advocates the correct solution to
amputation. However, active patients may benefit the patients’ lifestyle and their medical, physical,
from amputation that leads to earlier ambulation and psychological conditions so they can achieve
and better quality of gait. The focus of any limb their desired level of activity as quickly as p ossible
salvage needs to be functional. Understanding [7].
Attinger C, Brown BJ. Amputation and ambulation in diabetic patients: function is the goal. Diabetes Metab Res
Rev. 2012;28(Suppl 1):93–6
Strengths Well conducted study
• Addresses the importance of biomechanics
• Provided long-term follow-up of 20 years
Impact Advocated that amputation needs to be seen from the greater picture of reconstruction. When
considering reconstruction, the surgeons need to consider the functional outcome at the time of
reconstruction and weigh the benefits over amputation. Understanding biomechanics will lead to
minimized complication for diabetic foot reconstruction
29.5 The Significance diabetes patients in 18 studies showed that flap

of Reconstruction survival was 92% and limb salvage of 83.4%,
for Diabetic Foot thus proving that with the pathophysiology-based
approach to the diabetic foot reconstruction can
It is known that mortality rate after major ampu- have substantial results [9]. The significance of
tation from diabetic foot can be as high as 50% reconstruction for the diabetic foot was presented
within 5 years [8]. In a meta-analysis review, 528 by Oh et al. in the study Diabetic foot reconstruc-
306 J. P. Hong
tion using free flaps increases 5-year survival risk factors related to complication in patients
rate. The overall limb salvage rate was 84.9% who underwent lower extremity angioplasties,
and the 5-year survival was 86.8%, doubling the with peripheral artery disease and taking immu-
life quantity in patients who salvaged their limbs nosuppressive agents after kidney
by free flap. The study also identified significant transplantation.
Oh TS, Lee HS, Hong JP. Diabetic foot reconstruction using free flaps increases 5-year-survival rate. J Plast
Reconstr Aesth Surg. 2013;66:243–50
Strengths Well-conducted study
• Identified the risk factors involved in failures for flap reconstruction
• Long-term follow study looking at 5-year survival
Limitations • Low impact journal
Impact The benefits for microsurgical reconstruction for diabetic foot was established in terms of quantity of
life. Risk factors for failure was introduced providing insight related to patient selection for
reconstruction leading to higher success
29.6 Expert Concluding with the concept of “orthoplastic surgery.” After

Commentary all, the foot is all about the function.
The field of diabetic foot reconstruction still

remains one of the most challenging fields of References
reconstruction. A large portion of diabetic foot
patients may undergo amputations that could 1. Hong JP, Oh TS. An algorithm for limb sal-
vage for diabetic foot ulcers. Clin Plast Surg.
have been salvaged or some patients may undergo 2012;39(3):341–52.
reconstruction despite amputation being a better 2. Sanders LJ, Robbins JM, Edmonds ME. History of the
functional outcome. team approach to amputation prevention: pioneers and
To minimize unnecessary amputations, the milestones. J Vasc Surg. 2010;52(3 Suppl):3S–16S.
3. Robson MC, Edstrom LE. The diabetic foot: an alter-
plastic and reconstructive surgeons need to be native approach to major amputation. Surg Clin North
actively involved from the beginning of the Am. 1977;57(5):1089–102.
patient’s journey. The treatment for diabetic foot 4. Taylor GI, Palmer JH. The vascular territories (angio-
is not easy to provide alone, but rather requires a somes) of the body: experimental study and clinical
applications. Br J Plast Surg. 1987;40(2):113–41.
team effort and many resources, often intimidat- 5. Attinger CE, Evans KK, Bulan E, Blume P, Cooper
ing the reconstructive surgeon. This may be one P. Angiosomes of the foot and ankle and clinical
of the reasons why, diabetic foot reconstruction, implications for limb salvage: reconstruction, inci-
despite a huge population of patients, is still sions, and revascularization. Plast Reconstr Surg.
2006;117(7 Suppl):261S–93S.
being underserved by plastic surgeons. Much 6. Lumley ES, Kwon JG, Kushida-Conteras BH, Brown
more research and studies need to be done, as E, Viste J, Aulia I, et al. Free tissue transfer after open
landmark papers in this field are very scarce, as transmetatarsal amputation in diabetic patients. J
shown in this chapter. Reconstr Microsurg. 2021;37(9):728–34.
7. Attinger CE, Brown BJ. Amputation and ambulation
When performing reconstruction, it is crucial in diabetic patients: function is the goal. Diabetes
that we understand the biomechanics of the foot Metab Res Rev. 2012;28(Suppl 1):93–6.
predicting the outcome after salvage and recon- 8. Ecker ML, Jacobs BS. Lower extremity amputation in
struction, helping the patient to go through a diabetic patients. Diabetes. 1970;19(3):189–95.
9. Fitzgerald O’Connor EJ, Vesely M, Holt PJ, Jones KG,
meaningful treatment and recovery. The biome- Thompson MM, Hinchliffe RJ. A systematic review of
chanics of the foot is the key to gaining function free tissue transfer in the management of non-traumatic
and also crucial to minimize complication after lower extremity wounds in patients with diabetes. Eur
reconstruction. This principle is synonymous J Vasc Endovasc Surg. 2011;41(3):391–9.
Part XI
Genitourinary Reconstruction
Evolution of Genitourinary
Reconstruction
30
Brooke L. Moore, Alan Yang, and Curtis Cetrulo

We identified and described five landmark papers 1. Bürger RA, Müller SC, El-Damanhoury H,
that have been paramount in the development of Tschakaloff A, Riedmiller H, Hohenfellner
surgical techniques in the field of genito-urinary R. The buccal mucosal graft for urethral
perineal reconstruction. Rather than approach the reconstruction: a preliminary report. J Urol.
discipline as a single entity, we identified five 1992;147(3):662–4.
revolutionary procedures and highlighted the 2. Chang TS, Hwang WY. Forearm flap in one-
investigations that provided breakthrough stage reconstruction of the penis. Plast
advances for each. By incorporating additional Reconstr Surg. 1984;74(2):251–8.
references, we sought to describe the advance- 3. Cetrulo CL Jr, Li K, Salinas HM, Treiser
ments made since the initial landmark study. MD, Schol I, Barrisford GW, et al. Penis
Additionally, we hope to provide readers with a transplantation: first US experience. Ann
direction for future works by illuminating areas Surg. 2018;267(5):983–8.
that may benefit from more robust investigation. 4. Hage JJ, Bouman FG, Bloem JJ. Constructing
a scrotum in female-to-male transsexuals.
Keywords 5. Wee JT, Joseph VT. A new technique of vagi-
nal reconstruction using neurovascular
Landmark · Buccal graft mucosa ·
pudendal-thigh flaps: a preliminary report.
Scrotoplasty · Singapore flap · Gender-
affirming surgery · Phalloplasty · Penile
transplantation · Immunosuppression
30.1 Introduction
Financial Disclosures: None.
Genitourinary reconstructive surgery is a
B. L. Moore (*) dynamic discipline that is constantly evolving to
Department of Urology, Massachusetts General optimize the management of diverse pathologies.
Hospital, Boston, MA, USA Subsequently, the utility of genitourinary recon-
A. Yang · C. Cetrulo struction is quite broad. Significant defects may
Division of Plastic and Reconstructive Surgery, result from oncologic management, infectious
etiologies, traumatic injuries, or congenital
anomalies. Gender affirming surgery also com-
https://doi.org/10.1007/978-3-031-57132-9_30
310 B. L. Moore et al.
prises a large volume of the field, requiring a In 1992, Burger et al. popularized the buccal
multidisciplinary approach with specialists from mucosal graft (BMG) as a means of repairing
the field of plastic, urologic, and gynecologic long, anterior urethral strictures where additional
surgery. length is required to form a tension-free anasto-
In addition to its many indications, genitouri- mosis. Their investigation explored the efficacy
nary reconstruction encompasses a variety of sur- of the BMG in six patients who required urethral
gical procedures, including urethroplasty, revision secondary to multiple failed reconstruc-
phalloplasty, penile transplantation, scrotoplasty, tions. A full thickness mucosal graft was har-
and vulvar reconstruction. Through a review of vested from the inner cheek and placed in the
literature published over the last 50 years, we urethral bed as either a pre-formed tube (four
aimed to identify the hallmark studies that were patients) or a patch (two patients). The authors
fundamental to the development of modern-day emphasized that, in order to prevent disruption of
surgical techniques used in each of the aforemen- the facial nerve or buccinator muscle, dissection
tioned surgeries. deeper than the submucosa should be avoided. Of
their six patients, two developed small distal fis-
tulas and one developed both meatal stenosis and
30.2 Urethral Reconstruction a small distal fistula. These complications were,
in part, attributed to the impaired vascularity of
Urethral stricture disease is a common, costly the graft bed, which resulted from their prior ure-
pathology that often requires urethral reconstruc- thral repairs. However, given the good cosmetic
tion. Patients affected by strictures frequently results as well as the inherent elasticity and hair-
complain of lower urinary tract symptoms, less surface of the BMG, the investigators con-
including a weak, intermittent stream and urinary cluded that the buccal mucosa graft was a
retention, though recurrent infections, stone dis- reasonable alternative for urethral reconstruction,
ease, and upper tract deterioration have also been particularly in cases of inadequate penile or pre-
described [1]. The etiologies of stricture disease putial skin [6].
are extensive, including infection, inflammation, Barbagali et al. echoed these findings in their
trauma, and iatrogenic injury, and the pathogen- investigation, which compared efficacy of buccal
esis is well described. Insult to the urethral or mucosa to preputial skin grafts for management
corporal epithelium causes healthy pseudostrati- of anterior urethral strictures. Of their six patients
fied columnar cells to be replaced with squamous who underwent 1-stage stricture repair with
metaplasia. Disruption of the native cell barrier incorporation of a BMG, none required addi-
results in urinary extravasation into the neighbor- tional procedures at time of follow-up [7].
ing corporal tissue. This process stimulates a Although alternative methods of urethral
local inflammatory reaction characterized by reconstruction exist, such as the use of penile
deposition of dense, fibrotic tissue, which ulti- skin flaps or excision and primary anastomosis
mately leads to stricture formation [2]. (EPA), the buccal mucosa graft has evolved as
Most urethral strictures are identified in the the gold standard for repair of long strictures in
anterior urethra, which is further divided into the both the anterior and posterior urethra [8, 9].
bulbar and penile urethra [2]. Management of Nonetheless, controversy still exists surround-
short (<2 cm) strictures is typically endoscopic, ing the optimal approach for graft onlay.
including cold knife incision as well as laser ure- Proponents of the dorsal approach argue the
throtomy [3–5]. However, due to variable success mechanical support provided by the corpus
rates of endoscopic stricture management, par- spongiosum results in a more stable graft,
ticularly for longer strictures, alternative treat- thereby preventing folding and subsequent
ment options have been explored. reduction in the caliber of the urethral lumen
30 Evolution of Genitourinary Reconstruction 311
[10]. The ventral approach, however, requires function or overall complications between the
less urethral mobilization, and, subsequently, two approaches [13]. Surgeon preference and
less dissection [11, 12]. Notably, there does not comfort with one technique over the other
appear to be any difference in voiding/erectile should dictate the chosen approach.
Bürger RA, Müller SC, El-Damanhoury H, Tschakaloff A, Riedmiller H, Hohenfellner R. The buccal mucosal graft
for urethral reconstruction: a preliminary report. J Urol. 1992;147(3):662–4
Strengths • This was one of the first published case series describing the use of buccal mucosal grafts in
urethral reconstruction, which ultimately led to the universal incorporation of this technique for
management of long urethral strictures
Limitations • The study included a very small sample size, short follow-up period (6–13 months), and did not
include patients undergoing primary stricture repair
Impact This investigation demonstrated the value of buccal mucosa for repair/revision of congenital or
acquired urethral defects, leading to the development of the buccal mucosa graft as the gold standard
for repair of long strictures in both the anterior and posterior urethra
30.3 Penile Shaft Reconstruction In 1984, Chang et al. combined the prior work
of Puckett et al. and Biemer in their design of the
Penile reconstructive surgery is a continuously radial forearm flap phalloplasty. The investiga-
evolving field that aims to construct a cosmeti- tors published a case series that included seven
cally appealing phallus capable of both func- patients who underwent tube-within-a-tube phal-
tional voiding and penetrative intercourse. loplasty using this technique [18]. To obtain
Reconstruction is often indicated following appropriate tissue, they first harvested a RFFF
trauma or management of malignancy; however, that was 11–12 cm long and 14–15 cm wide. The
iatrogenic injury, infection, and congenital anom- flap was then transected into a larger, ~11 cm sec-
alies may also warrant penile reconstruction. tion, which was ultimately constructed into the
Various approaches to penile reconstruction penile shaft, as swell as a smaller, ~3 cm section,
have been described. In cases where sufficient which was revised into a neourethra. The sec-
viable tissue is present, primary repair may be tions relied on the radial artery and cephalic vein
possible [14]. Split thickness skin grafts may also as the predominant vascular supply to the flaps.
be used for smaller defects, though some sur- Once the segments were isolated, they were tubu-
geons prefer full thickness grafts due to their larized around a 14 Fr or 16 Fr Foley catheter
superior elasticity and decreased risk of contrac- thereby creating a tube-within-a-tube design
ture [15]. For larger defects, where primary repair (Figs. 30.1 and 30.2).
or skin grafting is not possible, flap construction Both the neophallus and a graft of costal carti-
may be necessary. lage were then transferred to the heterotopic site.
The development of the radial forearm free The donor vessels were anastomosed to either the
flap (RFFF) marked a major advancement in the saphenous vein or a nearby tributary and a branch
field of penile reconstructive surgery. The advan- of the femoral artery system, often the circumflex
tages of the radial forearm free flap were femoris lateralis or the profunda femoris. The
described in 1983 by Dr. Edgar Biemer, who costal cartilage graft was sutured to the corpus
developed an osteocutaneous variant of the spongiosum and the neourethra was anastomosed
RFFF. His approach, which included a portion of with the native urethra. Of the seven patients
the radial bone, produced good functional and enrolled in their study, only one developed a
cosmetic results for thumb reconstruction [16]. urethral fistula that required reoperation.

Simultaneously, Puckett et al. were exploring the Otherwise, there were no major complications
free flap phalloplasty as an alternative approach reported, confirming the efficacy of the radial
to penile reconstruction [17]. forearm flap for single-stage phalloplasties. Their
Fig. 30.1 De-

epithelialized flap with
two segments, one small
and one large, that will
be constructed into an
inner and outer tube,
respectively [18]
Fig. 30.2 Using a

catheter as a stent, the
smaller section of the
flap is tubularized to
form a neourethra [18]
success was recognized globally and, ultimately, tube-within-a-tube design with similar recognized
popularized the radial forearm flap. success [19]. Although alternative techniques—
Shortly thereafter, Kao et al. described a fas- including the anterolateral thigh flap, latissimus
ciocutaneous version of the RFFF that relied on a dorsi flaps, and ulnar flaps—have been described,
the radial forearm flap remains the gold standard tures and fistulas. As the field of penile recon-
for all fields of penile reconstruction, including struction progresses, we anticipate further
gender-affirming surgery [20–23]. Notably, the modifications in surgical technique that will con-
aforementioned techniques are all associated with tinue to improve sexual and voiding functions and
frequent complications, including urethral stric- minimize postoperative complication rates.
Chang TS, Hwang WY. Forearm flap in one-stage reconstruction of the penis. Plast Reconstr Surg.
1984;74(2):251–8
Strengths • This study demonstrated the efficacy of the RFFF for construction of a neophallus, which allows
for micturition and sexual penetration with a low associated complication rate despite the newness
of the procedure
Limitations • Successful implementation of this technique requires an autologous graft of costal cartilage. The
investigation also incorporated a small sample size
Impact These findings ultimately popularized the tube-within-a-tube approach for phalloplasty using a radial
forearm flap—an approach that is still widely used today
30.4 Penile Transplant Soon after, Cetrulo et al. championed penile

transplantation in the US. Preoperatively, the
Transplant surgery is an evolving discipline that investigators relied heavily on CTA/MRI to eval-
affords patients a treatment for a diverse array of uate both donor anatomy and recipient candidacy
pathologies. First described in the 1500s by the for transplant. Donor procurement included bilat-
Italian surgeon Gasparo Tagliacozzi, who used a eral fasciocutaneous flaps to preserve blood sup-
skin transplant for a reconstructive surgery, vari- ply via the external pudendal vessels as well as
ous organ transplants are now routinely proximal amputation at the pubic bone to maxi-
performed [24]. Interestingly, transplantation mize both corporal and urethral length. Surgeons
was only recently considered for the manage- approached the reconstructive transplantation in
ment of perineal pathologies. a stepwise manner, beginning with a spatulated
The devastating psychosocial effects of urethral anastomosis. They then reapproximated
impaired penile structure and function are well the corporal bodies, which served as a scaffold-
described [25, 26]. Although many flap and grafting for the neurovascular anastomoses (Fig. 30.3).
based reconstructive options exist, patients con- Various nerve and vascular grafts were also
tinue to report impaired erectile function and employed to achieve adequate length for a
abnormal voiding patterns post procedurally [27, tension- free anastomosis between donor and
28]. Further, there is no exact replacement for recipient tissue. In the postoperative period,
penile tissue and its distinct qualities. To improve broad spectrum antibiotics, anticoagulation, and
outcomes, transplantation is currently being immunosuppression were initiated to minimize
explored as a management option for patients risk of infection and graft rejection. Despite vari-
suffering from large penile defects. ous complications, including hematoma forma-
The first attempted penile transplant occurred tion and acute allograft rejection, managed with
in 2006 following a traumatic accident that steroids and antithymocyte globulin, the patient
resulted in a near total penectomy. Unfortunately, recovered sensation in the proximal shaft and
the patient experienced severe psychological dis- was voiding without difficulty by 6 months post-
tress requiring explant on day 14; therefore, long- operatively [31].
term voiding and erectile function could not be At present, five penile transplants have been
elucidated [29]. In 2014, the first successful performed globally with variable successes, as
penile transplant was described. This recipient two recipients have ultimately required explant
was noted to have satisfactory urinary and sexual [29–33]. Given the limited sample size and lack
functions without need for explant [30]. of long-term data, there is still much uncertainty
Fig. 30.3 Corporal body anastomosis formed between donor (left) and recipient (right) [31]
about best practices surrounding penile trans- sue perfusion of the allograft. However, many
plantation. To improve patient and donor selec- questions remain about how to optimize penile
tion, surgical technique, and immunosuppressive transplantation from a preoperative, intraopera-
regimens, investigators have attempted to con- tive, and postoperative standpoint. Despite much
struct guidelines based on prior successes and uncertainty, current experience demonstrates
challenges [34]. Inclusion of the external puden- that, from a cosmetic and functional perspective,
dal artery, for instance, is deemed critical for tis- penile transplant harbors unrivaled potential.
Cetrulo CL Jr, Li K, Salinas HM, Treiser MD, Schol I, Barrisford GW, et al. Penis transplantation: first US
experience. Ann Surg. 2018;267(5):983–8
Strengths • This investigation described a novel, single-staged technique for management of large penile
defects that ultimately creates an aesthetic, functional phallus with organic erectile function and
sensation
Limitations • As is required for any transplant recipient, patients need ongoing immunosuppression. Further, only
a single patient was included in their report
Impact Investigators described the first successful penile transplant in the United States, thereby highlighting
the potential of penile transplantation for management of large penile defects
30.5 Scrotoplasty indications for scrotoplasties are vast. Life-

threatening infections, such as Fournier’s, often
Scrotal reconstruction is a specialized form of warrant scrotal reconstruction to address signifi-
perineal surgery that aims to recreate either a por- cant tissue defects, and congenital anomalies,
tion of or an entirely new scrotum [35]. Similar to such as penoscrotal webbing, also constitute a
other forms of genital reconstructive surgery, the significant portion of scrotoplasty patients. At
A B C D E F
Fig. 30.4 V-Y technique which involves an initial prosthetic testicle, after which the skin is closed in a Y-like
V-shaped incision in the labia majora followed by blunt manner to allow for greater caudal length of the labia
dissection of the underlying dartos to form a cavity for the majora [38]
present, scrotoplasties are routinely performed required to perform 13 reoperations. Despite

for transgender patients undergoing gender- these revisions, the authors concluded that the
affirming bottom surgery. V-Y approach provided both adequate cosmetic
Surgical technique is variable and is dictated and sensory results without needing additional
by a multitude of factors, including indication tissue through graft or flap procurement—alter-
and defect size. Depending on the aforemen- native methods that may result in further compli-
tioned characteristics, some surgeons may opt for cations, including greater scar burden [38].
a simple scrotoplasty with primary repair, while Their results popularized the V-Y technique,
others may employ grafts or flaps—including though various refinements to the approach have
perineal and anterior lateral thigh flaps—for been reported over the last few decades [39, 40].
scrotal reconstruction [36, 37]. However, the V-Y In the field of gender-affirming surgery, for
scrotoplasty is frequently regarded as the optimal instance, Selvaggi et al. medially rotated the
approach, particularly for gender-affirming superior aspect of the labia majora prior to sutur-
surgery. ing the flap edges together. This modification
First detailed in 1993, Hage and colleagues resulted in improved cosmesis and overall
constructed a bifid scrotum in 50 female-to-male patient satisfaction compared to that described
patients using the V-Y technique. This technique by their predecessors [40]. Chang et al. imple-
involved an initial V-shaped incision in the labia mented a tailored approach to the V-Y scroto-
majora followed by a central incision in the plasty, known as the V-Y advancement technique,
underlying dartos fascia through which a cavity for correction of penoscrotal webbing in pediat-
was formed. Testicular implants were then ric patients [41]. Their approach ultimately pro-
placed, though not fixed, in the newly formed vided patients with greater scrotal skin length
cavity and the labia majora were closed in a affording investigators with a safe and effective
Y-like manner thereby attributing greater length technique for correction of the webbed penis.
to the already elastic skin (Fig. 30.4). Modified versions have also been performed for
The bifid quality of the scrotum was created management of large scrotal skin defects, includ-
after the medial aspect of the labia was excised ing those resulting from infectious etiologies
and the raw surfaces were sutured together. like Fournier’s [42]. Despite refinements to the
Although complications were considered V-Y scrotoplasty, the fundamental technique
minor—such as prosthesis migration or expul- described by Hage et al. is still employed glob-
sion of the prosthetic testicle secondary to ally for management of many different scrotal
impaired wound healing—the investigators were pathologies.
Hage JJ, Bouman FG, Bloem JJ. Constructing a scrotum in female-to-male transsexuals. Plast Reconstr Surg.
1993;91(5):914–21
Strengths • The described approach is easily understood and implemented and does not require additional
tissue via graft or flap procurement. Further, select study patients had a >10-year follow-up period,
allowing for complications to be well elucidated
Limitations • Investigators included a small sample size and a moderately high (~20%) complication rate was
described
Impact This was the first study to describe the utility of the V-Y technique for scrotoplasty in female-to-male
patients—a technique that is still commonly used and modified for scrotal reconstruction
30.6 Vulvar Reconstruction vulva that allowed for coitus in three women.
Their successes ultimately popularized the
Similar to penile reconstruction, the indications Singapore flap, thereby affording plastic sur-
for vulvar reconstruction include gender- geons with an accessible fasciocutaneous flap
affirming surgery, congenital anomalies, and that could be easily manipulated to cover large
reconstruction following malignant resection. vulvar defects [44].
The importance of vulvar reconstruction goes far Since 1989, many variations of the Singapore
beyond the restoration of appearance; indeed, flap have been illustrated. For example, Yi and
critical bodily functions such as micturition, def- Niranjan designed the Lotus Petal flap [45].
ecation, and coitus are all dependent on suitable Similar to the Singapore flap, the Lotus Petal
reconstruction. However, as women are diag- flap also relied on branches of the internal
nosed with gynecological malignancy at progres- pudendal artery the associated anastomotic net-
sively younger ages, the value of reconstructing work. However, it differs in that it is not located
an aesthetically-pleasing, sexually functional at the femoral triangle. The full-wing flap is
vulva is heightened [43]. another variant of the Singapore flap, which also
Many methods have been proposed for vulvar relies on branches of the internal pudendal artery
reconstruction, ranging from local advancement for its vascular supply; however, it is located
or transposition flaps to fasciocutaneous flaps more anterior in the perineum than the Singapore
and myocutaneous flaps. Despite significant flap [46].
diversity in approach, the Singapore flap is still Despite being one of the most revolutionary
widely employed for vulvar reconstruction. advances in the field of vulvar and perineal
The axial fasciocutaneous flap, otherwise reconstruction, the Singapore flap is not the only
known as the Singapore flap, was first described effective technique. Local advancement flaps
by Wee and Joseph in 1989 as a novel technique (e.g., rhomboid, V-Y), perforator flaps (e.g., ALT,
for vulvar reconstruction. Using two cadavers, SGAP, SCIP), and muscle or myocutaneous flaps
the investigators demarcated the perineal vascu- (e.g., gracilis, VRAM) have proved successful in
lature in an effort to delineate a viable tissue flap select patients [47, 48]. Designating the optimal
for vulvoplasties. They identified the posterior technique is often challenging. Therefore, vari-
labial artery, a terminal branch of the internal ous algorithms have been described to assist sur-
pudendal artery, as a critical structure for perineal geons in selecting the most appropriate approach
blood supply as it forms an anastomosis with [43, 47]. Surgeons often base their flap selections
branches of the deep external pudendal artery at off the anatomic region encompassing the defect
the femoral triangle. This discovery led to the and the degree of the deficit [43, 49]. However,
creation of the Singapore flap: a ~15 × 6 cm flap given the technical versatility required for vulvar
that is supplied by the posterior labial artery and reconstruction, it is critical that reconstructive
its rich anastomotic network (Fig. 30.5). surgeons are well-versed in the many described
Using the Singapore flap, Wee and Joseph techniques in order to construct a cosmetic, func-
were able to recreate a cosmetically-appealing tional vulva for their patients.
Internal iliac artery Femoral artery
Anterior branch of
Deep external pudendal
obturator artery
artery
Medial circumflex femoral
artery
Posterior labial artery
Fig. 30.5 Arterial blood supply to the female perineum [44]
Wee JT, Joseph VT. A new technique of vaginal reconstruction using neurovascular pudendal-thigh flaps: a
preliminary report. Plast Reconstr Surg. 1989;83(4):701–9
Strengths • This investigation identified a novel axial flap with a reliable blood supply that could be easily
isolated for the reconstruction of vulvovaginal defects
Limitations • Despite described successes, the Singapore flap is not appropriate for management of
vulvovaginal defects with large volumes of dead space
Impact To this day, the Singapore flap is widely cited as one of the fundamental reconstructive techniques
for management of vulvar defects. Is creation has inspired several variants that are also commonly
implemented
30.7 Expert Concluding flap and graft selection and viability, may also
Commentary mandate that surgeons tailor their approaches.
Conversely, penile transplantation is a modern
Perineal reconstruction is an ever-changing field, management option for large penile defects, only
evolving to meet the diverse and growing array of effectively introduced in the last decade. Despite
indications. The advent of gender-affirming sur- well-described successes, this approach requires
gery in particular has influenced the discipline, attention to many additional factors, including
presenting surgeons with unique challenges that the psychological well-being of the recipient,
require innovation and refinement of existing sur- assembly of a multidisciplinary surgical team,
gical practices. and the need for lifelong immunosuppression.
Techniques such as the buccal mucosa graft, These considerations have limited its global
radial forearm flap, V-Y scrotoplasty, and adoption. From a cosmetic and functional per-
Singapore flap have been subjected to various spective, however, penile transplant provides
modifications since their introductions in the paramount results. As investigators continue to
twentieth century. To minimize complication clarify optimal perioperative care, particularly
rates and promote patient satisfaction, we antici- regarding intraoperative technique and postoper-
pate further refinements to these methods. The ative immunosuppressive regimens, the wide-
rising prevalence of various comorbidities, such spread implementation of penile transplantation
as obesity and diabetes, which strongly influence may become more feasible.
Irrespective of technique or indication, it is 14. Garcia KS, Becker GW, Gretzer MB. Successful
replantation of self-amputated penis using microvas-
critical for reconstructive surgeons to understand cular repair resulting in restoration of voiding and
the five aforementioned techniques, as they are erectile function. Urol Case Rep. 2023;46:102319.
fundamental to the field. Further, they serve as 15. Garaffa G, et al. Penile reconstruction in the male.
the foundation for many of the adaptations cur- Arab J Urol. 2013;11:267–72.
16. Biemer E, Stock W. Total thumb reconstruction: a
rently being implemented in perineal reconstruc- one-stage reconstruction using an osteo-cutaneous
tive surgery. To optimize outcomes, consideration forearm flap. Br J Plast Surg. 1983;36:52–44.
of patient-specific characteristics and an up-to- 17. Puckett CL, Reinisch JF, Montie JE. Free flap phal-
date understanding of the current literature is loplasty. J Urol. 1982;128:294–7.
18. Chang TS, Hwang WY. Forearm flap in one-stage
crucial. reconstruction of the penis. Plast Reconstr Surg.
1984;74:251–8.
19. Kao XS, et al. One-stage reconstruction of the penis
References with free skin flap: report of three cases. J Reconstr
Microsurg. 1984;1:149–53.
20. Zhe Y, et al. The pedicled anterolateral thigh flap for
1. Mundy AR, Andrich DE. Urethral strictures. BJU Int.
penile reconstruction. Zhonghua Zheng Xing wai ke
2011;107:6–26.
za zhi=Zhonghua Zhengxing Waike Zazhi=Chin J
2. Hampson LA, McAnich JW, Breyer BN. Male ure-
Plast Surg. 2015;31:406–10.
thral strictures and their management. Nat Rev Urol.
21. Rashid M, Tamimy MS. Phalloplasty: the dream and
2014;11:43–50.
the reality. Indian J Plast Surg. 2013;46:283.
3. Pansadoro V, Emiliozzi P. Internal urethrotomy in the
22. Hetson AL, et al. Phalloplasty: techniques and out-
management of anterior urethral strictures: long-term
comes. Transl Androl Urol. 2019;8:254.
followup. J Urol. 1996;156:73–5.
23. Bencic M, et al. Musculocutaneous latissimus Dorsi
4. Dutkiewicz SA, Wroblewski M. Comparison of treat-
Phalloplasty. Indian J Plast Surg. 2022;
ment results between holmium laser endourethrotomy
24. Bezinover D, Saner F. Organ transplantation in the
and optical internal urethrotomy for urethral stricture.
modern era. BMC Anesthesiol. 2019;19:1–4.
Int Urol Nephrol. 2012;44:717–24.
25. Ficarra V, et al. Comparison of the quality of life of
5. Jin T, et al. Safety and efficacy of laser and cold
patients treated by surgery or radiotherapy in epider-
knife urethrotomy for urethral stricture. Chin Med J.
moid cancer of the penis. Progres en urologie: journal
2010;123:1589–95.
de l’Association francaise d’urologie et de la Societe
6. Burger RA, et al. The buccal mucosal graft for ure-
francaise d’urologie. 1999;9:715–20.
thral reconstruction: a preliminary report. J Urol.
26. Opjordsmoen S, Fosså SD. Quality of life in patients
1992;147:662–4.
treated for penile cancer. A follow-up study. Br J Urol.
7. Barbagli G, Palminteri E, Rizzo M. Dorsal onlay
1994;74:652–7.
graft urethroplasty using penile skin or buccal
27. Jun MS, Santucci RA. Urethral stricture after pahl-
mucosa in adult bulbarurethral strictures. J Urol.
loplasty. Transl Androl Urol. 2019;8:266.
1998;160:1307–9.
28. Garaffa G, Raheem AA, Ralph DJ. Penile frac-
8. Angulo JC, Gómez RG, Nikolavasky
ture and penile reconstruction. Curr Urol Rep.
D. Reconstruction of membranous urethral strictures.
2011;12:427–31.
Curr Urol Rep. 2018;19:1–10.
29. Hu W, et al. A preliminary report of penile transplan-
9. Hoy NY, Chapman DW, Rourke KF. Better defining
tation. Eur Urol. 2006;50:851–3.
the optimal management of penile urethral strictures:
30. Batemen C. World’s first successful penis transplant
a retrospective comparison of single-stage vs. two-
at Tygerberg Hospital. S Afr Med J. 2015;105:251–2.
stage urethroplasty. Can Urol Assoc J. 2019;13:414.
31. Cetrulo CL Jr, et al. Penis transplantation: first US
10. Barbagli G, et al. Bulbar urethroplasty using the dor-
experience. Ann Surg. 2018;267:983–8.
sal approach: current techniques. Int Braz J Urol.
32. Van der Merwe A, et al. Penile allotransplantation
2003;29:155–61.
for penis amputation following ritual circumcision:
11. Kulkarni S, Joshi PM, Bhadranavar S. Advances in
a case report with 24 months of follow-up. Lancet.
urethroplasty. Med J Armed Forces India. 2022;
2017;390:1038–47.
12. Kellner DS, Fracchia JA, Armenakas NA. Ventral
33. Redett RJ III, et al. Total penis, scrotum, and lower
onlay buccal mucosal grafts for anterior urethral stric-
abdominal wall transplantation. N Engl J Med.
tures: long-term followup. J Urol. 2004;171:726–9.
2019;381:1876–8.
13. Shalkamy O, et al. Erectile and voiding function
34. Lopez CD, Girard AO, Lake IV, Oh BC, Brandacher
outcomes after buccal mucosa graft urethroplasty
G, Cooney DS, et al. Lessons learned from the first
for long-segment bulbar urethral stricture: ven-
15 years of penile transplantation and updates to the
tral versus dorsal onlay technique. World J Urol.
Baltimore Criteria. Nat Rev Urol. 2023;20:1–14.
2023;41:205–10.
35. Fahmy MAB. Scrotoplasty. In: Normal and abnormal 43. Tan BK, et al. Subunit principle of vulvar recon-
scrotum; 2022, pp. 435–447. struction: algorithm and outcomes. Arch Plast Surg.
36. Lucas JW, Higgins AM, Simhan J. Scrotal reconstruc- 2014;41:379–86.
tion and testicular prosthetics. In: Textbook of male 44. Wee JT, Joseph VT. A new technique of vaginal
genitourethral reconstruction; 2019, pp. 751–763. reconstruction using neurovascular pudendal-thigh
37. Dolen UC. Flap based reconstruction for the defects flaps: a preliminary report. Plast Reconstr Surg.
of Fournier’s Gangrene. Turk J Plast Surg. 2019; 1989;83:701–9.
27:56. 45. Yii NW, Niranjan NS. Lotus petal flaps in
38. Hage JJ, Bouman FG, Bloem JJ. Constructing a scro- vulvo-vaginal reconstruction. Br J Plast Surg.
tum in female-to-male transsexuals. Plast Reconstr 1996;49:547–54.
Surg. 1993;91:914–21. 46. Han HH, et al. Internal pudendal perforator artery-
39. Miller TJ, et al. Transgender scrotoplasty and peri- based gull wing flap for vulvovaginal 3D reconstruc-
neal reconstruction with labia majora flaps. Ann Plast tion after tumour excision: a new flap. Int Wound J.
Surg. 2021;87:324–30. 2016;13:920–6.
40. Selvaggi G, et al. Scrotal reconstruction in female-to- 47. Wesborn CM, Talbot SG. An algorithmic approach
male transsexuals: a novel scrotoplasty. Plast Reconstr to perineal reconstruction. Plast Reconstr Surg Glob
Surg. 2009;123:1710–8. Open. 2019;7:e2572.
41. Chang SJ, Liu SP, Hsieh JT. Correcting penoscrotal 48. Shridharani SM, Wang HD, Sacks JM. Pedicled
web with the V-Y advancement technique. J Sex Med. anterolateral thigh flap for vaginal and perineal recon-
2008;5:249–50. struction. Eplasty. 2013;13:ic46.
42. Rapp DE, et al. Use of tissue expansion for scro- 49. Pusic AL, Mehrara BJ. Vaginal reconstruction: an
tal sac reconstruction after scrotal skin loss. J Urol. algorithm approach to defect classification and flap
2006;175:1764. reconstruction. J Surg Oncol. 2006;94:515–21.
Part XII
Perineal and Pelvic Reconstruction
Evolution of Perineal and Pelvic
Reconstruction
31
Raymund E. Horch, Andreas Arkudas,
and Alexander Geierlehner
Abstract size, location, and complexity of the defects,

Surgical repair of defects in the perineal have been developed over the last few
region, which can be caused by trauma, decades. The necessity for flap reconstruc-
infection, or cancer, has been a challenging tion in colorectal radical surgery has a high
issue from the very beginning. The history of morbidity rate of up to 66%, with the cre-
perineal, vaginal, and pelvic reconstruction ation of a surgical dead space in the pelvis
is closely related to the development of onco- and pelvic floor created by a wide resection,
logical surgery for rectal, anal, and vulvar followed by potential fluid and hematoma
tumors with the invention of multimodal neo- accumulation, risk of wound infection, pel-
adjuvant therapies, creating central perineal vic abscess, anastomotic dehiscence, adhe-
and pelvic defects from the resection for sions, and the development of fistulae and
oncological clearance of these cancers. sinus tracts and perineal herniae.
Adjacent perineal defects mostly stem from
extensive metastases to the regional lymph
Keywords
pathways from these tumors. Necrotizing
fasciitis (such as Fournier’s gangrene), injury Pelvic reconstruction · VRAM-flap · Gracilis
from radiation, thermal, and combat-related flap · Pudendal flap · Gluteal thigh flap ·
trauma, as well as congenital abnormalities Omentum flap · Vaginal reconstruction ·
or the consequences of gender reassignment Perineal reconstruction
surgeries are less frequent causes for perineal
reconstruction and do not always involve flap
surgery. A number of various surgical tech- The Five Most Impactful Papers
niques, such as local flaps, free flaps, and 1. McCraw JB, Massey FM, Shanklin KD,
grafts, that can be used for perineal, vaginal, Horton CE. Vaginal reconstruction with graci-
and pelvic reconstruction, depending on the lis myocutaneous flaps. Plast Reconstr Surg.
1976;58(2):176–83.
2. Hurwitz DJ, Swartz WM, Mathes SJ. The glu-
R. E. Horch (*) · A. Arkudas · A. Geierlehner teal thigh flap: a reliable, sensate flap for the
Department of Plastic and Hand Surgery, University closure of buttock and perineal wounds. Plast
Hospital Erlangen, Friedrich Alexander University Reconstr Surg. 1981;68(4):521–32.
Erlangen Nuernberg FAU, Erlangen, Germany
https://doi.org/10.1007/978-3-031-57132-9_31
324 R. E. Horch et al.
3. Moreaux J, Horiot A, Barrat F, Mabille J. with the creation of a surgical dead space in the
Obliteration of the pelvic space with pedicled pelvis and pelvic floor created by a wide resec-
omentum after excision of the rectum for can- tion, followed by potential fluid and hematoma
cer. Am J Surg. 1984;148(5):640–4. accumulation, risk of wound infection, pelvic
4. Wee JT, Joseph VT. A new technique of vagi- abscess, anastomotic dehiscence, adhesions,
nal reconstruction using neurovascular puden- and the development of fistulae and sinus tracts
dal-thigh flaps: a preliminary report. Plast and perineal herniae.
Reconstr Surg. Apr 1989;83(4):701–9. Surgical flaps in pelvic, vaginal, and perineal
5. Horch RE, Hohenberger W, Eweida A, et al. A reconstruction do not only reduce the dead space
hundred patients with vertical rectus abdomi- in the pelvic floor, but also facilitate wound clo-
nis myocutaneous (VRAM) flap for pelvic sure, quality of life, and aesthetic appearance;
reconstruction after total pelvic exenteration. they provide structural support and enhance the
Int J Colorectal Dis. 2014;29(7):813–23. process of postoperative healing [1]. In addition,
they can prevent adhesions of organs and viscera
in the pelvis and pelvic side walls and floor [3, 4].
31.1 Introduction Five special landmark papers of classical peri-
neal, vaginal, and pelvic reconstruction tech-
Surgical repair of defects in the perineal region, niques are discussed.
which can be caused by trauma, infection, or
cancer, has been a challenging issue from the
very beginning. The history of perineal, vagi- 31.2 Gracilis Flap
nal, and pelvic reconstruction is closely related
to the development of oncological surgery for The manuscript discusses the reconstruction of a
rectal, anal, and vulvar tumors with the inven- functional vagina after vaginectomy, a challeng-
tion of multimodal neoadjuvant therapies, cre- ing surgical problem. Back in the 1970s, other
ating central perineal and pelvic defects from existing methods had significant limitations lead-
the resection for oncological clearance of these ing to suboptimal surgical outcomes. A few years
cancers [1]. Adjacent perineal defects mostly after the introduction of the gracilis myocutane-
stem from extensive metastases to the regional ous flap by Orticochea [5], this paper proposes a
lymph pathways from these tumors. Necrotizing new reconstructive approach for functional vagi-
fasciitis (such as Fournier’s gangrene), injury nal reconstruction. The study is based on experi-
from radiation, thermal, and combat-related mental studies in dogs that led to the development
trauma, as well as congenital abnormalities or of this technique. The gracilis island myocutane-
the consequences of gender reassignment sur- ous flap was initially used out of necessity for the
geries are less frequent causes for perineal coverage of perineal radiation ulcers. Throughout
reconstruction and do not always involve flap the process, after gaining further experience
surgery. A number of various surgical tech- McCraw et al. switched from secondary to pri-
niques, such as local flaps, free flaps, and grafts, mary vaginal reconstruction at the time of total
that can be used for perineal, vaginal, and pel- pelvic exenteration. Although this work strictly
vic reconstruction, depending on the size, loca- used the gracilis flap for vaginal reconstruction, it
tion, and complexity of the defects, have been is nevertheless considered the basis for perineal
developed over the last decades [2]. The neces- reconstruction and is therefore regarded by us as
sity for flap reconstruction in colorectal radical a landmark paper.
surgery is the high morbidity rate of up to 66%
31 Evolution of Perineal and Pelvic Reconstruction 325
McCraw JB, Massey FM, Shanklin KD, Horton CE. Vaginal reconstruction with gracilis myocutaneous flaps. Plast
Reconstr Surg. 1976;58(2):176–83
Strengths • The technique is based on experimental studies, providing a scientific foundation
• The approach is applicable not only for vaginal reconstruction but also for other perineal defects
Limitations • The manuscript lacks detailed statistical data, such as success rates, complications, and long-term
outcomes
• The manuscript does not discuss potential limitations, risks, or challenges of the proposed
technique
Impact The proposed technique addresses a significant clinical problem and provides a potential solution for
functional vaginal reconstruction. Immediate primary healing and reduced morbidity are highlighted
as significant advantages of this approach. The manuscript suggests that this technique can have
applications beyond vaginal reconstruction, making it a valuable contribution to perineal
reconstruction surgery
31.3 Gluteal Thigh Flap consists of the gluteus maximus muscle and its
overlying skin. Back in the 1980s this technique
In 1981, Hurwitz et al. were the first to describe was considered revolutionary to perineal and but-
the use of the gluteal thigh flap for reconstructing tock reconstruction, addressing the challenges
complex wounds in the buttock and perineal associated with wound closure in this complex
regions. The technique involves the use of a flap anatomical region. Further research and broader
that receives its blood supply from the inferior clinical experiences solidified its position as a
gluteal artery and sensory innervation from the valuable tool in the field of perineal reconstruc-
posterior cutaneous nerve of the thigh. The flap tive surgery.
Hurwitz DJ, Swartz WM, Mathes SJ. The gluteal thigh flap: a reliable, sensate flap for the closure of buttock and
perineal wounds. Plast Reconstr Surg. 1981;68(4):521–32
Strengths • The technique’s versatility is highlighted through its application in various clinical scenarios,
including chronic pressure sores, post-traumatic wounds, and carcinoma metastasis
• The study reports a successful closure of 18 out of 21 problematic wounds using this flap
technique, indicating its effectiveness in wound healing
Limitations • The study is based on a relatively small sample size of 21 patients. Larger and more diverse patient
cohorts would have provided a stronger basis for evaluating the technique’s effectiveness
• The study does not extensively provide detailed outcome comparisons
Impact The technique offers potential advantages in terms of wound healing, low morbidity, and versatility
in addressing different types of perineal wounds. While the study’s sample size is limited, its
successful application in challenging clinical cases highlights the impact this paper has had on
perineal reconstruction in recent decades
31.4 Pedicled Omentum Flap The rationale behind this new procedure at the
time was to improve postoperative outcomes, par-
At the time of the publication from Moreaux ticularly in cases where healing is challenging,
et al. in 1984, the omentum flap had already such as in patients who have received preoperative
been used for the repair of vesicovaginal fistulas radiation treatment. Therefore, the pedicled omen-
or for the protection of low rectal anastomoses tum flap, based on the left gastroepiploic artery,
[6–8]. However, the authors were the first to was intended to obliterate the dead space in the
describe its application for perineal reconstruc- pelvis and promote better wound healing. With the
tion using it as pelvic filling after abdominoper- advancement of medical practice and surgical
ineal resection (54 patients) or the extended techniques in the last few years, recent studies
Hartmann procedure (12 patients) in rectal can- have been able to evaluate and demonstrate the
cer patients. timeliness and applicability of this technique.
Moreaux J, Horiot A, Barrat F, Mabille J. Obliteration of the pelvic space with pedicled omentum after excision of
the rectum for cancer. Am J Surg. 1984;148(5):640–4.
Strengths • The manuscript presents positive results with a high rate of wound healing by primary intention, a
low incidence of complications and reduced hospital stays
• The technique is particularly relevant for patients who have received preoperative radiotherapy, as
it enhances the healing process in irradiated tissues
Limitations • The manuscript does not provide a direct comparison with other techniques or methods, making it
challenging to assess the relative effectiveness of the described approach
• The manuscript does not provide long-term follow-up data, which is essential to evaluate the
durability and potential late complications of the surgical technique
Impact The authors introduced a surgical technique that was novel at the time of the study. The use of pedicled
omentum flaps for pelvic reconstruction had a significant impact on the field of perineal reconstruction.
The positive outcomes reported in the study led to further exploration and refinement of the technique in
the last decades, potentially influencing subsequent approaches to perineal reconstruction
31.5 Pudendal Thigh Flap innervation from branches of the pudendal nerve,
the posterior cutaneous nerve of the thigh.
At first, the authors conducted cadaveric studies Transposing and meeting the corresponding flap
to further understand the blood supply and inner- from the opposite, it forms a cul-de-sac in the
vation of the medial groin, upper thigh, and the midline. In this study, this technique has been
perineum. The flap was designed as horn shaped, successfully used in one adult undergoing total
measuring 15 × 6 cm with its posterior skin mar- pelvic exenteration for malignancy and two chil-
gin at the posterior end of the introitus. The flap dren with congenital vaginal anomalies.
was raised with the deep fascia of the thigh, the Wee et al. are the first to describe the neuro-
epimysium of the adductor muscles, and a skin vascular pudendal thigh flap procedure, which
island supplied by the posterior labial arteries. over the years has proven to be a viable and reli-
The pudendal thigh flap receives its sensitive able method for perineal reconstruction.
Wee JT, Joseph VT. A new technique of vaginal reconstruction using neurovascular pudendal-thigh flaps: a
preliminary report. Plast Reconstr Surg. Apr 1989;83(4):701–9.
Strengths • Flap has a robust and reliable blood supply, leading to successful healing
• Simple and reliable method for perineal reconstruction
• Surgery does not require additional thigh wounds or skin grafts, reducing donor site morbidity
Limitations • Short follow-up period for the cases
• Limited sample size, with only three cases reported
• Flap may not be suitable for certain cases, such as squamous cancers with a high possibility of
lymphatic spread to the groin
• The study lacks comparative data with other perineal reconstruction techniques
Impact The authors present their results on a very small patient population. Nevertheless, the careful
anatomical workup and the fact that this method is described as safe and technically simple makes
this study a significant paper for perineal reconstruction
31.6 Vertical Rectus Abdominis perineal cylindrical resections for advanced and
Myocutaneous (VRAM) Flap neoadjuvant irradiated situations. Pelvic exenter-
ation is a curative treatment for locally advanced
In this paper, Horch et al. discuss the standard- primary or recurrent rectal cancer. The VRAM
ized use of vertical rectus abdominis myocutane- flap was used to cure fistulae, ureter, and urethral
ous (VRAM) transpelvic flaps for the lesions, to fill up the pelvic space and to reduce
reconstruction of pelvic, vaginal, and perineal wound complications after extensive pelvic
defects after extended colorectal abdomino- resection, offering better wound healing and
31 Evolution of Perineal and Pelvic Reconstruction 327
lower morbidity rates. The study analyzed 100 11% in this study. The percentage of flap necrosis
consecutive patients who underwent pelvic and was 2%. The expertise of Horch et al. with a case
perineal reconstruction using VRAM flaps from series of over 160 VRAM flap reconstructions at
2003 to 2012. The patients’ age, sex, general the time of publication and over more than two
health, tumor stage, and preoperative radiation decades distinguishes this study from previous
dose were recorded, and postoperative complica- flap descriptions performed by different surgeons
tions were documented and analyzed. The com- as a landmark paper for pelvic /perineal
plication rate of partial wound dehiscence was reconstruction.
Horch RE, Hohenberger W, Eweida A, et al. A hundred patients with vertical rectus abdominis myocutaneous
(VRAM) flap for pelvic reconstruction after total pelvic exenteration. Int J Colorectal Dis. 2014;29(7):813–23
Strengths • Large patient sample size (100 consecutive patients)
• Prospectively collected data, which adds to the reliability of previous retrospective observations
and standardization of synchronous tumor and reconstructive surgery
• Emphasis on the importance of the VRAM flap technique in pelvic reconstruction in irradiated
patients
Limitations • The study lacks a control group for direct comparison and relies on historic patient data
• The study does not consider the long-term functional outcomes and all aspects of quality of life for
patients in detail
Impact The authors provide valuable insights into the programmed use of VRAM flap reconstruction for
pelvic-perineal-vaginal defects after extensive pelvic resection. It highlights the advantages of this
technique in reducing wound complications and improving wound healing in patients undergoing
pelvic exenteration. The study’s findings did influence surgical practices and contributed to better
postoperative outcomes in patients with locally advanced pelvic malignancies
31.7 Expert Concluding wound healing outcomes after abdominoperineal

Commentary resection (APR). Another hot topic in this context
is the use of plastic and biological meshes or
This chapter provides the reader with a concise acellular allogeneic matrices for pelvic floor
overview of five crucial surgical procedures for sealing and perineal hernia prophylaxis [10, 11].
the reconstruction of the perineal, vaginal, and Although this is possible in principle, it carries
pelvic region. In addition, it aims to highlight the the risk of lack of healing and biofilm coloniza-
challenges posed by such complex defects often tion due to the lack of vascularization in the irra-
caused by radical multivisceral resection with an diated recipient area with often significant
additional neoadjuvant therapy. These include bacterial contamination [12]. The choice of the
adequate sealing of the pelvic cavity using well- reconstruction procedure is not only determined
vascularized tissue, avoidance of bacterial con- by the resection defect and the extent of the irra-
tamination, rapid wound healing, and prevention diated area, but also by any previous operations
of chronic fistulae and cavity formation. For this (laparotomy scars, scar hernias, stomas, etc.) and
purpose, different fascio- and myocutaneous the resulting tissue availability. For this reason,
flaps have been developed and successively the choice of one of the above flaps for perineal
refined over the last 50 years. These surgical pro- reconstruction should be selected and applied
cedures made the previously common treatment individually for each patient in a considered
of the open wound with tamponade of the cavity manner. From an expert point of view and as a
by bandages unnecessary. Such conservative leading high-volume center for perineal recon-
wound treatments often required months of heal- struction especially after pelvic exenteration, we
ing and in some cases even showed failure of prefer the use of VRAM flap for various different
wound healing after more than 1 year [9]. The reasons. First, it has become a reliable and safe
use of myocutaneous flaps for perineal recon- procedure due to their constant anatomy and vas-
struction showed significant improvement in cularity. Second, the flap volume allows suffi-
cient obliteration of the created cavity and thus cal surgery of the pelvic region : combined oncosur-
gical and plastic reconstruction measures. Chirurg.
prevents the small bowel from sinking into the 2015;86(3):242–50.
pelvic floor. And third, the composition of this 5. Orticochea M. A new method of total reconstruction
flap allows for additional complete anterior and of the penis. Br J Plast Surg. 1972;25(4):347–66.
posterior vaginal reconstruction if needed [3, 13]. 6. Kiricuta I, Goldstein AM. The repair of extensive ves-
icovaginal fistulas with pedicled omentum: a review
It is our hope that this chapter not only serves as of 27 cases. J Urol. 1972;108(5):724–7.
a focused historical review of perineal recon- 7. Goldsmith HS. Protection of low rectal anasto-
struction procedures over the past several mosis with intact omentum. Surg Gynecol Obstet.
decades, but also as an overview of the most 1977;144(4):584–6.
8. Turner-Warwick R. The use of the omental ped-
diverse possibilities of perineal reconstruction. icle graft in urinary tract reconstruction. J Urol.
This chapter should also serve to expand one’s 1976;116(3):341–7.
own armamentarium, especially in complex cases 9. Artioukh DY, Smith RA, Gokul K. Risk factors for
where one or the other procedure can no longer impaired healing of the perineal wound after abdomi-
noperineal resection of rectum for carcinoma. Color
be applied. Dis. 2007;9(4):362–7.
10. Dijkstra EA, Kahmann NLE, Hemmer PHJ, Havenga
K, van Etten B. A low incidence of perineal her-
References nia when using a biological mesh after extralevator
abdominoperineal excision with or without pel-
vic exenteration or distal sacral resection in locally
1. Devulapalli C, Jia Wei AT, DiBiagio JR, Baez ML,
advanced rectal cancer patients. Tech Coloproctol.
Baltodano PA, Seal SM, et al. Primary versus flap
2020;24(8):855–61.
closure of perineal defects following oncologic resec-
11. Wille-Jorgensen P, Pilsgaard B, Moller
tion: a systematic review and meta-analysis. Plast
P. Reconstruction of the pelvic floor with a biologi-
Reconstr Surg. 2016;137(5):1602–13.
cal mesh after abdominoperineal excision for rectal
2. Butler CE, Gündeslioglu ÖA, Rodriguez-Bigas
cancer. Int J Color Dis. 2009;24(3):323–5.
MA. Outcomes of immediate vertical rectus abdomi-
12. Nyame TT, Lemon KP, Kolter R, Liao EC. High-
nis myocutaneous flap reconstruction for irradiated
throughput assay for bacterial adhesion on acellular
abdominoperineal resection defects. J Am Coll Surg.
dermal matrices and synthetic surgical materials.
2008;206(4):694–703.
3. Horch RE, Ludolph I, Cai A, Weber K, Grutzmann
13. Horch RE, Gitsch G, Schultze-Seemann W. Bilateral
R, Arkudas A. Interdisciplinary surgical approaches
pedicled myocutaneous vertical rectus abdominus
in vaginal and perineal reconstruction of advanced
muscle flaps to close vesicovaginal and pouch-vaginal
rectal and anal female cancer patients. Front Oncol.
fistulas with simultaneous vaginal and perineal
2020;10:719.
reconstruction in irradiated pelvic wounds. Urology.
4. Beier JP, Croner RS, Lang W, Arkudas A, Schmitz M,
2002;60(3):502–7.
Göhl J, et al. Avoidance of complications in oncologi-
Part XIII
Aesthetic Surgery
Evolution of Facelift Surgery
32
Katherine B. Santosa and Foad Nahai

The goal of this chapter is to trace the evolu- 1. Skoog T. Plastic surgery: new methods and
tion of facelift surgery through the discussion refinements. Philadelphia: Saunders; 1974.
of five key landmark articles spanning several 2. Mitz V, Peyronie M. The superficial mus-
decades. These landmark papers provide a culo-aponeurotic system (SMAS) in the
comprehensive overview of facelift surgery parotid and cheek area. Plast Reconstr Surg.
and offer valuable insights into the anatomy, 1976;58(1):80–8.
techniques, and outcomes of various 3. Hamra ST. Composite rhytidectomy. Plast
approaches to surgically rejuvenate the face. Reconstr Surg. 1992;90(1):1–13.
In addition, we cite other supporting articles 4. Connell BF, Shamoun JM. The significance
contributing to our understanding of the mod- of digastric muscle contouring for rejuvena-
ern facelift. We believe that these five key tion of the submental area of the face. Plast
articles are essential reading for all perform- Reconstr Surg. 1997;99(6):1586–90.
ing facelifts, whether a young trainee or an 5. Alpert BS, Baker DC, Hamra ST, et al.
experienced master plastic surgeon. Identical twin face lifts with differing tech-
niques: a 10-year follow-up. Plast Reconstr
Surg. 2009;123(3):1025–33.
Keywords
Rhytidectomy · Facelift · Rhytidoplasties · 32.1 Introduction

Platysmaplasty · Face · Anatomy
Since its early days well over 100 years ago,
facelift surgery has been drastically transformed
and continues to evolve. Refinements in our
K. B. Santosa understanding of facial anatomy, aging process,
Center for Plastic Surgery at MetroDerm,
surgical techniques, and addition of ancillary
Atlanta, GA, USA
procedures have undoubtedly improved the
Artisan Plastic Surgery, Atlanta, GA, USA
safety and outcomes of patients undergoing facial
F. Nahai (*) rejuvenation. Moreover, facial aesthetic surgery
Center for Plastic Surgery at MetroDerm,
remains one of the most performed aesthetic sur-
Atlanta, GA, USA
gical procedures [1] and is the gold standard for
Emory University, Atlanta, GA, USA
rejuvenating the aging face. We briefly describe
https://doi.org/10.1007/978-3-031-57132-9_32
332 K. B. Santosa and F. Nahai
here the evolution of the modern facelift through Moreover, Suzanne Noel, the first female aes-
the review of five key landmark publications and thetic surgeon, described the facelifts and other
other our selection of other significant aesthetic surgery procedures in her book pub-
contributions. lished in 1926, in which she also emphasized the
social role of aesthetic surgery [8, 9].
From the early 1900s, ellipse excision evolved
32.2 Early Days of Facelift Surgery to skin undermining and excision and ultimately,
the subcutaneous facelift became the most per-
Although aesthetic surgery was being performed formed procedure to rejuvenate the face until the
in the early twentieth century, it was largely con- 1970s [2, 4]. After dissecting a skin flap in the
sidered to be socially unacceptable and was per- face and neck, excess skin was excised and inci-
formed surreptitiously [2–4]. In fact, various sions were closed, whereby relying on skin ten-
members of the American medical community sion for the lift. Perhaps one of the greatest
attempted to propose a law outlawing facelifting advances that resulted in a major paradigm shift
in the 1920s [5]. This overwhelming sentiment in facelift surgery was the realization by Skoog
forced surgeons to perform aesthetic procedures that manipulating deeper structures of the face
in secrecy, mislabel operative case logs, and avoid (besides the skin only) led to longer lasting
any publication of surgical techniques related to results [10].
aesthetic surgery [2]. As a result, our knowledge
of the origins of the facelift is somewhat vague.
There remains some debate over whom and 32.3 Era of the SMAS
where the first facelift was described. Historically,
most have credited Eugene von Hollander with Tord Skoog is traditionally credited with being
the first facelift, which he reportedly performed the first to describe dissecting not only the skin
on a Polish aristocrat in 1912 [6]. However, and subcutneous tissues, but also the deeper fas-
recently Denkler and Hudson argue that the ori- cial layers [10]. Up to that point, the subcutane-
gins of facial cosmetic surgery are due to the ous facelift was the most commonly performed
work of a self-reported American Dermatologist, procedure for rejuvenating the aging face and it
John H. Woodbury [3]. Review of his self- had its limitations. Termed “buccal fascia,”
published beauty booklet and advertisements Skoog described elevating this fascial layer that
suggest that he described an early version of the was continuous from the cheek to the platysma in
lower facelift via posterior auricular neck exci- the neck. In addition to dissecting the overlying
sion to address “flabbiness of the skin” in 1901 skin, Skoog felt that advancing the “buccal fas-
[3]. Other surgeons such as Miller, Passot, and cia” (later termed superficial musculoaponeu-
Bourget have also been credited with describing rotic system, SMAS by Mitz and Peyronie) led to
elliptical excisions to rejuvenate the face and improved facial contours and longer-lasting
periorbital area at around the same time [2, 7]. results [10].
Skoog T. Plastic surgery: new methods and refinements. Philadelphia: Saunders; 1974
Strengths • First description of manipulating deeper fascial layer of the face termed “buccal fascia” for
improved outcomes after rhytidectomy
Limitations • Description of anatomy and technique only
• No clinical outcomes
Impact In this textbook, Tord Skoog shared methods and refinements based on his own personal surgical
experience, one of which was the use of a subfascial dissection to improve results after a facelift. In
the 1960s, it is believed that surgeons began addressing deeper tissues to improve upon results from
the subcutaneous facelift; however, Skoog is widely credited for the first description of facelift
surgery that encompassed the use of the deeper fascial layers in the face, which he termed “buccal
fascia” and was later referred to as the superficial musculoaponeurotic system (SMAS) by Mitz and
Peyronie
32 Evolution of Facelift Surgery 333
Several years after Skoog’s description of this cadaver dissections, imaging, and histologic sec-
deeper fascial layer, Vladimir Mitz and Martine tioning [11]. In addition to defining the SMAS
Peyrone presented their work at the French and its relationship to nearby structures such as
Society of Plastic Surgeons in October 1974, vessels, facial muscles, sensory nerves, facial
describing the anatomy and surgical implications nerve braches, and the parotid gland, Mitz and
of the superficial musculoaponeurotic system Peyronie describe a safe approach to undermin-
(SMAS) [11]. This study published in 1976 is ing and mobilizing the SMAS. They go on to
regarded as the “anatomic basis of the modern argue that mobilization of the SMAS results in a
facelift”. The paper described the SMAS in the more effective lift compared to only underming
cheek and parotidomasseteric area based on 15 the skin [11].
Mitz V, Peyronie M. The superficial musculo-aponeurotic system (SMAS) in the parotid and cheek area. Plast
Reconstr Surg. 1976;58(1):80–8
Strengths • Anatomical description of the superficial musculoaponeurotic system (SMAS)
• Provides relationship of SMAS to nearby structures such as facial nerve
• Argues more effective lifting during facelift with mobilization of SMAS compared to skin-only
undermining
Limitations • No clinical outcomes
Impact This study describes the SMAS and its relation to other nearby structures by using 15 cadaveric
dissections, X-ray imaging, and histologic studies. Although the term ‘SMAS’ was coined by their
mentor, Dr. Paul Tessier, this study by Mitz and Peyronie is considered to be the “anatomical basis of
the modern facelift,” and has facilitated the use of the SMAS for longer-lasting results after facelift
surgery
32.4 Era of the Deep-Plane 403 patients he has performed this procedure on.
Overall, four (1.0%) patients developed hema-
Following the description of the SMAS, many toms requiring evacuation, four (1.0%) patients
modifications for SMAS management were pub- had temporary neuropraxia, and two (0.05%)
lished, including a paper by Mark Lemon and patients suffered from pseudomonal infection
Sam Hamra [12]. Recognizing the limtiations of [13]. Based on his experience, he argues that the
SMAS techniques to effectively correct the laxity deep-plane facelift results in improved apper-
of the nasolabial folds, Sam Hamra first described ances of the nasolabial fold, jawline, and neck-
the deep-plane facelift (he started performing in line compared to other techniques with relatively
1979) in 1990 [13]. In this very impactful publi- few complications [13], which has been corrobo-
cation, Dr. Hamra first describes the operative rated by others as well [14].
steps of this technique in which he describes a Shortly after Hamra published his technique
“Skoog-type sub-SMAS dissection” that is and outcomes of the deep-plane facelift, he pub-
extended superiorly over the zygomaticus muscle lished his work on composite facelift in 1992,
and medially beyond the nasolabial folds [13]. which we have identified as a key landmark arti-
By releasing all the SMAS attachments, he is cle [15]. In addition to repositioning the cheek fat
able to create a thick musculocutaneous flap and platysma muscle, Dr. Hamra recognized that
composed of skin, subcutaneous fat, and the pla- his traditional deep-plane facelift technique left
tysma muscle. Inclusion of the malar fat pads the ptotic orbicularis muscle unaddressed. As a
into this dissection he argues, results in an result, he modified his deep-plane facelift to
improved appearance of the nasolabial folds after reposition and fixate the orbicularis oculi muscle
deep-plane facelift. In addition to describing his while also repositioning the SMAS, cheek fat,
technique in very clear step-by-step instructions, and platysma with the overlying skin as a com-
he also presents complication data among the posite musculocutaneous flap [15]. He argues
that with this technique he is able to address all other and with the overlying skin. In addition to
three elements of the aging face: (1) reposition- providing step-by-step instructions and accom-
ing the orbicularis oculi improves the upper face; panying figures describing how he performs this
(2) repositioning the cheek fat improves the mid- technique, he also shares his outcomes of 167
face; and (3) repositioning the platysma improves patients who underwent a composite facelift.
the lower face and jawline. Additionally, he Overall, one (0.6%) patient required evacuation
emphasizes the importance of addressing these of a hematoma and no patients suffered any nerve
three deep components of aging without disrupt- injuries or alteration of their orbicularis oculi
ing their normal anatomy relationship with each muscle function [15].
Hamra ST. Composite rhytidectomy. Plast Reconstr Surg. 1992;90(1):1–13

Strengths • First to describe an approach to address orbicularis oculi ptosis that results in the malar crescent
• Provides step-by-step instructions with accompanying figures on how to perform this procedure
• Addresses three elements that contribute to signs of aging of the upper face (orbicularis oculi),
midface (cheek fat) and lower face/jawline (platysma)
• Relatively large number of patients included in retrospective review (n = 167)
Limitations • Only complication data provided: 0.5% hematoma, 0 nerve injury, 0 dysfunction of orbicularis
oculi
• No patient-reported outcomes
Impact Known as the second most highly cited article in the facelift literature (CITE), Hamra describes his
composite facelift technique and shares complication data of 167 patients who underwent this
procedure. The hallmark of the composite facelift is the repositioning and fixation of the orbicularis
oculi, SMAS, cheek fat pads, and platysma with the overlying skin as a thick musculocutaneous flap.
In this study, Hamra expands on his work from 1990, in which he describes the deep-plane facelift to
include repositioning and fixation of the ptotic orbicularis oculi muscle found in patient who present
with facial aging
Following the work of Hamra, the evolution and der, cervicomental angle, sternocleidomastoid-
modifications of the SMAS Facelift continued submental line angle, and visibility of a
through the work of Bruce Connell, Fritz Barton, subhyoid depression, thyroid cartilage bulge,
Tim Marten, and Andrew Jacono [16–18]. and/or anterior border of the sternocleidomas-
toid muscle [19]. Traditionally, necklift surgery
includes skin flap elevation with or without pla-
32.5 Necklift tysma plication. To further improve results, sur-
geons have delved into addressing deeper
Although this chapter is dedicated to describing structures of the neck.
the evolution of the facelift through landmark Nahai elucidated the anatomy of the neck by
publications, we would be remiss not to include describing his layered approach with three dis-
important contributions with respect to the neck. tinct layers of the neck. These consist of (1) the
Almost all patients who present with facial aging, superficial layer (skin and subcutaneous fat), (2)
will show changes of the neck below the man- the intermediate layer (platysma muscle and
dibular line. The changes involve the skin, subcu- interplatysmal fat), and (3) the deep layer (sub-
taneous, and deeper tissues. Rather than lifting of platysmal fat, digastric muscles, submandibular
the neck, we consider neck rejuvenation as neck glands, mandible, hyoid bone, and cervical verte-
contouring through volume modification and brae) [20]. This comprehensive understanding of
skin management. neck anatomy has allowed surgeons to safely
In 1980, Ellenbogen and Karlin provided a excise or manipulate deeper structures of the
comprehensive description of the youthful neck neck and achieve a more youthful contoured
by characterizing the inferior mandibular bor- appearance of the neck after surgery.
The works of Connell introduced the deep digastric muscles that were left unaddressed
neck procedures below the platysma. We have resulted in suboptimal outcomes after face and
selected one of his papers as a key landmark necklift surgery. In addition to describing the
publication, which addresses the importance of anatomy of this region, the authors also thor-
the digastric muscles, a deep plane structure of oughly describe their technique and selection of
the neck, in rejuvenating the submental region appropriate candidates for this procedure, as
[21]. In 1997, Connell and Shamoun described patients who present with fullness in the sub-
their surgical technique of partial resection of mental region, poorly defined cervicomental
the anterior belly of the digastric muscle. They angle, and a poorly defined anterolateral sub-
argue that previous to their publication, correct- mental border [21]. Of the 21 patients evaluated,
ing the submental contour only addressed the none had complications although the authors
skin, subcutaneous tissue, platysma, subplatys- present potential complications such as hemato-
mal fat, submaxillary glands, thyroid cartilage, mas and excess concavity in the submental
and hyoid bone. Moreover, they felt that bulky region.
Connell BF, Shamoun JM. The significance of digastric muscle contouring for rejuvenation of the submental area of
the face. Plast Reconstr Surg. 1997;99(6):1586–90
Strengths • Anatomical description of the submental region
• Provides surgical technique to tangentially excise the anterior belly of the digastric muscle
• Introduces the influence of deeper structures of the neck on aging of the face and neck
Limitations • Relatively smaller cohort (n = 21), no complications reported
Impact This technique article describes the anatomy of the submental region and highlights the importance
of the digastric muscle on facial aging. Review of 21 patients who underwent this procedure
demonstrated no complications, although the authors present possible risks
There has been continued evolution in deep plane 32.7 Autologous Fat Grafting
procedures with recently renewed interest
through the works of Nahai, Marten, Mendelson, Although autologous fat grafting was first
O’Daniel, and Auerswald [22–26]. described in the late nineteenth century [33],
Sydney Coleman is widely credited for standard-
izing techniques for harvesting, processing, and
32.6 Short Scar or Long Scar reinjecting fat via his sentinel publications on
“lipostructure” in the 1990s [34, 35]. In 1997,
As facelifts gained in popularity and younger Coleman described his method for fat grafting in
patients with normal skin elasticity considered the face, including the use of low-pressure
facelifts, the original short scar facelift, described syringes and placement of fat in small aliquots to
at the turn of the last century by the Frenchman improve survival, and ultimately, facilitating the
Virenque [27], was popularized by Baker [28, ability to obtain more reliable results [34]. Since
29] and later by Tonnard et al. [30, 31] and these initial descriptions by Coleman, fat grafting
Tonnard and Verpaele [32] with their MACS lift. has become increasingly popular as an adjunct to
There has always been a debate on patient selec- facial aesthetic procedures such as facelift sur-
tion for short scars. Nahai has described the verti- gery [36] and blepharoplasty [37] in addition to
cal simulation test for selecting patients suitable being used independently to improve signs of
for the short scar approach [20]. volume deflation that occurs with facial aging
[36]. Future studies determining the ideal tech- differences in these procedures at postoperative
nique for harvest, processing, and re-injection of follow-up times [41]. Moreover, Becker and
fat in conjunction with facelift surgery are Bassichis compared these two groups and found
warranted. that deep-plane techniques offered slightly
improved results over SMAS facelifts among
older patients 70–80 years old but authors con-
32.8 Evaluating Outcomes cluded that deep-plane facelifts were not superior
among patients younger than 70 [42]. However in
32.8.1 Subcutaneous Versus SMAS 2007, Adamson and colleagues evaluated 25
Facelift patients who underwent SMAS plication facelift
and 25 patients who underwent a deep-plane
Although the subcutaneous facelift has fallen out facelift at 6 months postoperatively [40]. Three
of favor due to its limitations, there have been facial plastic surgeons were blinded to the proce-
historic publications that compare outcomes of dure performed for the patient and used postop-
these two approaches. For example, in the 1970s, erative photographs to evaluate the degree of
two separate groups evaluated outcomes by per- improvement in the malar eminence, melolabial
forming a skin only lift on one side and a SMAS fold, jowling, neck banding, and cervicomental
facelift on the other side [38, 39]. In 1974, Tipton angle. The authors found that there was signifi-
performed this mixed facelift approach on 33 cant improvement in all aspects evaluated except
patients and evaluated outcomes based on post- neck banding among the cohort who underwent
operative photos [38]. Additionally, Rees and deep-plane facelifts versus SMAS plication face-
Aston conducted a very similar study on 25 lift [40]. Overall, results comparing SMAS to
patients, had three observers evaluate for any dif- deep-plane facelifts have been mixed, resulting in
ferences, and concluded that there were no appre- no clear consensus as to which approach may be
ciable differences between the two sides as well superior.
[39]. However, it is worth noting that these stud-
ies lacked standardization, objectivity, and long-
term follow-up. Conceivably, there likely could 32.8.3 Twin Studies
have been differences between the two sides if
patients were evaluated several years after their Despite the many options described to surgically
initial surgical date. improve the appearance and longevity of the
aging face, there has been a paucity of evidence-
based studies to determine which techniques
32.8.2 SMAS Facelift Versus Deep- offer superior results after facelift surgery. As a
Plane Facelift result, a few notable authors have compared
results after different facelift approaches on iden-
There have been several studies comparing the tical twins to find the most ideal technique
results between SMAS facelifts and deep-plane [43–45].
facelifts [40–42]. Through a prospective cohort Perhaps the most notable and one that we
study performed in 1997, Ivy and co-authors ran- identified as a key landmark publication is the
domized to undergo split facelift surgeries with twin study that was initiated in 1995 and included
either a SMAS facelift on one side and an long-term follow-up at 10 years after surgery
extended SMAS or composite facelift on the [44]. Led by Dr. Alpert, the study recruited two
other side. By evaluating patients intraopera- sets of identical twins who underwent different
tively and postoperatively, the authors found that types of facelifts with either Dr. Dan Baker
patients demonstrated significant reversal of mid- (Twin Set A), Dr. Sam Hamra (Twin Set A), Dr.
face ptosis intraoperatively with the more exten- John Owsley (Twin Set B), or Dr. Oscar Ramirez
sive procedures but did not appreciate significant (Twin Set B). These patients were followed up
for the first 10 weeks postoperatively by another Owsley, who performed a SMAS facelift, or Dr.
plastic surgeon and then seen and photographed Ramirez, who performed a subperiosteal lift.
at 1, 6, and 10 years postoperatively [44]. The Photographs at 1, 6, and 10 years were discussed
first set of twins (Twin Set A) underwent surgery at the annual meetings of the American Society
with either Dr. Baker, who performed a lateral for Aesthetic Plastic Surgery (ASAPS) by a
SMAS-ectomy, or Dr. Hamra, who performed a panel consisting of the four operating surgeons,
composite facelift. The subsequent set of twins who critiqued their own and their colleagues’
(Twin Set B) underwent surgery with either Dr. results [44].
Alpert BS, Baker DC, Hamra ST, et al. Identical twin face lifts with differing techniques: a 10-year follow-up. Plast
Reconstr Surg. 2009;123(3):1025–33
Strengths • Two sets of identical twins were recruited and evaluated
• Everyone underwent a different type of facelift technique (e.g., SMAS-ectomy, composite facelift,
SMAS facelift, or subperiosteal facelift)
• Postoperative photographs and results discussed among 4 surgeons who participated in the study
• Long-term follow-up at 1, 6, and 10 years
Limitations • No objective clinical outcome data
Impact This impactful study recruited two sets of identical twins in 1995. Every individual underwent a
different type of facelift with a different surgeon and was followed for 10 weeks perioperatively, then
at 1, 6, and 10 years after surgery. The publication includes direct quotes from the panelists and
moderators to highlight surgeon critiques of their own work and that of their colleagues. Additionally,
remarks from surgeons about how their practice patterns have changed provide valuable insight to the
reader. Although no objective clinical outcome data are presented, clinical photographs of all
participants help to illustrate that no one technique may be superior to the other
In addition, Dr. Antell and his team have also 32.9 Current Trends
made great contributions to our understanding of
patient outcomes after different types of facelifts We feel this is such an exciting time to be an aes-
through identical twin studies [43, 45]. Between thetic surgeon with advances and innovations
1997 and 1999, Antell and Orseck recruited eight continuing in the field. In addition to the intro-
sets of identical twins who underwent facelift duction of minimally invasive collagen stimulat-
surgery. Four different types of facelift were per- ing devices and technology to our field, thought
formed including: (1) skin only, no SMAS; (2) leaders have challenged conventionally accepted
SMAS flap; (3) SMAS-ectomy; and (4) SMAS wisdom and have made important refinements on
plication. The authors evaluated photographs of older techniques that have been described in this
all participants from 1 to 5 years after surgery review chapter. For example, the corset platys-
and concluded that there was no difference maplasty has drawn some discussion as to its
between facelift techniques and patient outcomes effectiveness. While it provides tightening of the
[45]. Recently in 2016, Antell and colleagues neck, it also limits the upward and lateral pull on
also sought to compare outcomes between identi- the neck. Some believe that this “tug-of-war”
cal twins who underwent short-scar incision ver- between the downward and medial pull of the
sus classic facelift procedures [43]. Authors platysma and the upward and lateral pull of the
concluded that while both approaches have simi- SMAS compromises surgical results after face
lar efficacy in the short-term, full facelift proce- and neck lift [2]. As a result, Jacono and Parikh
dures had longer-term results at 5 years compared have described the extended deep-plane facelift
to short-scar techniques [43]. in which the sub-SMAS dissection is carried
down below the mandibular angle allowing for included patient-reported outcomes (PROs) and
more movement of the deeper tissues of the neck none of the articles included the use of vali-
[46]. Additional modifications to Hamra’s origi- dated patient- reported outcome measures
nal description of the deep-plane facelift have (PROMs) [51]. Moreover, at our national and
been advocated by other surgeons to further international scientific meetings, panels con-
improve correction of the midface, jawline, and sisting of facelift surgery experts have and will
neck [47, 48]. continue to debate which technique results in
Another current debate in facial rejuvenation superior outcomes. Recognizing that there are
surgery is whether to address deeper structures of various approaches to surgically rejuvenate the
the neck. Current proponents of manipulating fact, it is imperative to conduct prospective,
deeper structures of the neck argue that a keen multi-center cohort studies to evaluate out-
understanding of the layers of the neck and comes (i.e., complication data and PROs) of
nearby structures allows the surgeon to be safe patients undergoing different types of facelifts
and to achieve superior outcomes than only with various surgeons. These large, multicenter
addressing the superficial layers of the neck alone studies, which require intentional collaboration
[23, 49]. Despite the rising popularity of these and funding support, have been successfully
procedures, concerns about their safety remain. executed in other fields of plastic surgery and
In 2006 for example, Baker shared his opinions significantly improve our understanding of the
of the procedure citing the “radical neck appear- impact of various surgical approaches on
ance” as an undesired outcome after deep proce- patient outcomes [52, 53].
dures in the neck [50]. Additionally, in 2015,
Mendelson and Tutino shared their experience
after submandibular gland resection noting that 32.10.2 Improving Our
one patient suffered a potentially life-threatening Understanding of Adjunct
subplatysmal hematoma [24]. Future compara- Technology and Procedures
tive studies evaluating the safety and outcomes of
manipulating deeper structures of the neck versus In addition to performing higher quality and
only addressing superficial layers are warranted. greater powered studies evaluating facelift out-
Based on our 25 years of experience operating comes, improving our understanding of patient
deep to the platysma, we firmly believe that in outcomes with the use of new technology will be
selected patients subplatysmal procedures are paramount. With the surge of new technology
safe and result in superior contouring of the neck. used as adjuncts to facelift surgery or used
entirely on their own, we anticipate that the next
decade of literature on facelift surgery will
32.10 Future Directions examine the effectiveness of these minimally
invasive devices and procedures. While partner-
32.10.1 Inclusion of Patient- ship with industry is vital for the future of our
Reported Outcomes specialty, it is our duty as surgeons and scientists
in Facelift Studies to critically evaluate the implementation of this
newer technology on patient safety and
Although these landmark and other important outcomes.
publications have greatly contributed to our Utilizing adjunct procedures such as lipofill-
understanding of the modern facelift, they also ing, resurfacing procedures (e.g., chemical peels,
emphasize the need for concerted efforts to lasers), and use of energy-based devices is com-
improve the quality of the current studies we monplace for many aesthetic surgeons who per-
use to evaluate outcomes after facelift surgery. form facelifts today, which makes it more
For example, in a robust review of 100 of the challenging to compare outcomes of different
most highly cited articles on facelift, only 10 techniques of facelift surgeries. However, as we
continue to leverage these adjunct procedures, it 2. Barrett DM, Casanueva FJ, Wang TD. Evolution of
the rhytidectomy. World J Otorhinolaryngol-Head
will be imperative for us to share our outcomes Neck Surg. 2016;2(1):38–44.
and to conduct comparative effectiveness studies 3. Denkler KA, Hudson RF. The 19th century origins
to help determine how to optimize results with of facial cosmetic surgery and John H. Woodbury.
the use of these procedures. Aesthet Surg J. 2015;35(7):878–89.
4. Luu NN, Friedman O. Facelift surgery: history,
anatomy, and recent innovations. Facial Plast Surg.
2021;37(5):556–63.
32.11 Expert Concluding 5. Ryan RF. A 1927 view of cosmetic surgery. Plast
Commentary Reconstr Surg. 2000;106(5)
6. Hollander E. Plastische (kosmetische) Operation: kri-
tische Darstellung ihres gegenwärtigen Standes. Neue
Since the conception of our understanding of Deutsche Klinik. 1932;9:1–17.
facelift surgery, countless publications have 7. Vrebos J. The contributions of Julien Bourguet
described the anatomy, introduced refinements to (1876–1952) to frontocervicofacial lifting. Historical
aspects of the first face lift. Ann Chir Plast Esthet.
the procedure, discussed complications and 1990;35(2):160–6.
methods by which to avoid them, and evaluated 8. Regnault P, Stephenson KL. Dr. Suzanne Noel. The
patient outcomes, all of which have improved our first woman to do esthetic surgery. Plast Reconstr
knowledge about this commonly performed sur- Surg. 1971;48(2):133–9.
9. Noël S. La chirurgie esthetique. Imprimerie Thiron &
gical procedure. In this chapter, we gratefully Cie; 1928.
acknowledge the opportunity to summarize the 10. Skoog T. Plastic surgery: new methods and refine-
impact of five key landmark publications that we ments. Philadelphia: Saunders; 1974.
believe have significantly contributed to the evo- 11. Mitz V, Peyronie M. The superficial musculo-
aponeurotic system (SMAS) in the parotid and cheek
lution of facelift surgery across several decades. area. Plast Reconstr Surg. 1976;58(1):80–8.
In reviewing these publications, however, we also 12. Lemmon ML, Hamra ST. Skoog rhytidectomy: a
recognize the shortcomings of many publications five-year experience with 577 patients. Plast Reconstr
surrounding facelift surgery and other aesthetic Surg. 1980;65(3):283–97.
13. Hamra ST. The deep-plane rhytidectomy. Plast
surgery procedures. To ensure that we continue to Reconstr Surg. 1990;86(1)
propel innovation within our craft and to opti- 14. Kamer FM. One hundred consecutive deep plane
mize patient outcomes, it is imperative that surface-lifts. Arch Otolaryngol Head Neck Surg.
geons and researchers alike collaborate to 1996;122(1):17–22.
15. Hamra ST. Composite rhytidectomy. Plast Reconstr
conduct more robust, multicenter, and multi- Surg. 1992;90(1):1–13.
surgeon studies that evaluate the outcomes of 16. Connell BF, Marten TJ. The trifurcated SMAS flap:
patients undergoing different types of facelifts three-part segmentation of the conventional flap for
with and without adjunct procedures. Surgical improved results in the midface, cheek, and neck.
Aesthetic Plast Surg. 1995;19(5):415–20.
rejuvenation of the face will remain a commonly 17. Barton FE Jr. Rhytidectomy and the nasolabial fold.
performed procedure and we look forward to Plast Reconstr Surg. 1992;90(4):601–7.
critically reviewing future impactful publications 18. Jacono AA, Parikh SS, Kennedy WA. Anatomical
in this space that will ultimately help us to comparison of platysmal tightening using superficial
musculoaponeurotic system plication vs deep-plane
improve outcomes of the many patients undergo- rhytidectomy techniques. Arch Facial Plast Surg.
ing these procedures. 2011;13(6):395–7.
19. Ellenbogen R, Karlin JV. Visual criteria for success
in restoring the youthful neck. Plast Reconstr Surg.
1980;66(6):826–37.
References 20. F. N. Art of aesthetic surgery. 1st ed. St. Louis, MO,
2003.
1. Society TA. Aesthetic Plastic Surgery National 21. Connell BF, Shamoun JM. The significance of
Databank Statistics 2020–2021 February 13, 2023, digastric muscle contouring for rejuvenation of the
2021. Available at: chrome-extension://bdfcnmeidp- submental area of the face. Plast Reconstr Surg.
pjeaggnmidamkiddifkdib/viewer.html?file=https:// 1997;99(6):1586–90.
cdn.theaestheticsociety.org/media/statistics/2021- 22. Weinstein AL, Nahai F. A layered approach to neck
TheAestheticSocietyStatistics.pdf. lift. Plastic Aesthet Res. 2021;8:11.
23. O'Daniel TG. Optimizing outcomes in neck lift sur- system plication face-lift. Arch Facial Plast Surg.
gery. Aesthet Surg J. 2021;41(8):871–92. 2007;9(1):9–11.
24. Mendelson BC, Tutino R. Submandibular gland 41. Ivy EJ, Lorenc ZP, Aston SJ. Is there a difference?
reduction in aesthetic surgery of the neck: review A prospective study comparing lateral and stan-
of 112 consecutive cases. Plast Reconstr Surg. dard SMAS face lifts with extended SMAS and
2015;136(3):463–71. composite rhytidectomies. Plast Reconstr Surg.
25. Auersvald A, Auersvald LA, Oscar UC. Subplatysmal 1996;98(7):1135–43. discussion 1144–7
necklift: a retrospective analysis of 504 patients. 42. Becker FF, Bassichis BA. Deep-plane face-lift vs
Aesthet Surg J. 2017;37(1):1–11. superficial musculoaponeurotic system plication
26. Nahai FRaN, F. Partial resection of the submandibular face-lift: a comparative study. Arch Facial Plast Surg.
gland. In: Panfilov DE, editor. Aesthetic surgery of the 2004;6(1):8–13.
facial mosaic. Berlin, Heidelberg: Springer-Verlag; 43. Antell DE, May JM, Bonnano MJ, et al. A comparison
2007. of the full and short-scar face-lift incision techniques
27. Virenque M, Georges-Charles-Maurice D. Traitement in multiple sets of identical twins. Plast Reconstr
chirurgical des rides de la face et du cou. In: Pauchet Surg. 2016;137(6):1707–14.
V, editor. La Pratique Chirugicale Ilustree. Paris: 44. Alpert BS, Baker DC, Hamra ST, et al. Identical twin
Gaston Don et Cie; 1927. face lifts with differing techniques: a 10-year follow-
28. Baker DC. Lateral SMASectomy. Plast Reconstr up. Plast Reconstr Surg. 2009;123(3):1025–33.
Surg. 1997;100(2):509–13. 45. Antell DE, Orseck MJ. A comparison of face lift tech-
29. Baker DC. Minimal incision rhytidectomy (short scar niques in eight consecutive sets of identical twins.
face lift) with lateral SMASectomy: evolution and Plast Reconstr Surg. 2007;120(6):1667–73.
application. Aesthet Surg J. 2001;21(1):14–26. 46. Jacono AA, Parikh SS. The minimal access deep
30. Tonnard P, Verpaele A, Monstrey S, et al. Minimal plane extended vertical facelift. Aesthet Surg J.
access cranial suspension lift: a modified S-lift. Plast 2011;31(8):874–90.
Reconstr Surg. 2002;109(6):2074–86. 47. Jacono A, Bryant LM. Extended deep plane face-
31. Tonnard PL, Verpaele A, Gaia S. Optimising lift: incorporating facial retaining ligament release
results from minimal access cranial suspen- and composite flap shifts to maximize midface,
sion lifting (MACS-lift). Aesthetic Plast Surg. jawline and neck rejuvenation. Clin Plast Surg.
2005;29(4):213–20. discussion 221 2018;45(4):527–54.
32. Tonnard PL, Verpaele AM. The MACS-lift: short-scar 48. Jacono AA, Bryant LM, Ahmedli NN. A novel
rhytidectomy. Thieme; 2004. extended deep plane facelift technique for jaw-
33. Costanzo D, Romeo A, Marena F. Autologous fat line rejuvenation and volumization. Aesthet Surg J.
grafting in plastic and reconstructive surgery: an his- 2019;39(12):1265–81.
torical perspective. Eplasty. 2022;22:e4. 49. Marten T, Elyassnia D. Deep neck lift: defining ana-
34. Coleman SR. Facial recontouring with lipostructure. tomical problems and choosing appropriate treatment
Clin Plast Surg. 1997;24(2):347–67. strategies. Facial Plast Surg. 2022;38(6):630–49.
35. Coleman SR. Structural fat grafting. Aesthet Surg J. 50. Baker DC. Face lift with submandibular gland and
1998;18(5):386:388. digastric muscle resection: radical neck rhytidectomy.
36. Marten TJ, Elyassnia D. Fat grafting in facial rejuve- Aesthet Surg J. 2006;26(1):85–92.
nation. Clin Plast Surg. 2015;42(2):219–52. 51. Dutt A, Dutt AP, Reddy RK, Charles WN, Khademi
37. Marten T, Elyassnia D. Periorbital fat grafting: a new Mansour HR, Nahai F, Khajuria A, et al. A biblio-
paradigm for rejuvenation of the eyelids. Facial Plast metric analysis of the highest cited rhytidectomy lit-
Surg Clin North Am. 2021;29(2):243–73. erature. Aesthet Surg J Open Forum. 2023;5:ojad099.
38. Tipton JB. Should the subcutaneous tissue be pli- PMID: 38075298; PMCID: PMC10702622.
cated in a face lift? Plast Reconstr Surg. 1974;54(1): 52. Santosa KB, Qi J, Kim HM, et al. Long-term patient-
1–12. reported outcomes in postmastectomy breast recon-
39. Rees TD, Aston SJ. A clinical evaluation of the results struction. JAMA Surg. 2018;153(10):891–9.
of submusculo-aponeurotic dissection and fixation in 53. Bennett KG, Qi J, Kim HM, et al. Comparison of
face lifts. Plast Reconstr Surg. 1977;60(6) 2-year complication rates among common techniques
40. Adamson PA, Dahiya R, Litner J. Midface effects of for postmastectomy breast reconstruction. JAMA
the deep-plane vs the superficial musculoaponeurotic Surg. 2018;153(10):901–8.
Evolution of Rhinoplasty Surgery
33
Bahman Guyuron and Anthony DeLeonibus

The goal of this chapter is to review the evolu- 1. Anderson JR, Johnson CM, Adamson P.
tion of rhinoplasty through the discussion of Open rhinoplasty: an assessment. Otolaryngol
five seminal articles in rhinoplasty. These Head Neck Surg. 1982;90:272–4.
papers account for significant paradigm shift 2. Sheen JH. Spreader graft: a method of recon-
in how rhinoplasty surgeons prepare, structing the roof of the middle nasal vault
approach, and execute the contemporary nasal following rhinoplasty. Plast Reconstr Surg.
surgery. These selected articles detail several 1984;73:230–7.
decades of rhinoplasty history, but we addi- 3. Gunter JP, Friedman RM. Lateral crural strut
tionally support these articles with references graft: technique and clinical applications in
that further augment the modern rhinoplasty rhinoplasty. Plast Reconstr Surg.
surgeon’s understanding of aesthetic and func- 1997;99(4):943–52.
tional nasal surgery. These articles cannot and 4. Troell RJ, Powell NB, Riley RW, Li KK.
will not reflect all the evolution that this sur- Evaluation of a new procedure for nasal alar
gery has undergone. Simply, these articles are rim and valve collapse: nasal alar rim recon-
selected on the important role they play in cur- struction. Otolaryngol Head Neck Surg.
rent rhinoplasty and are indeed five of many. 2000;122(2):204–11.
5. Guyuron B, Behmand RA. Nasal tip sutures
Keywords Part II: the interplays. Plast Reconstr Surg.
2003;112(4):1130–45.
Rhinoplasty · Nasal surgery · Dynamics ·
Spreader graft · Open technique · Lateral
crural strut · Piezoelectric surgery · 33.1 Introduction
Preservation rhinoplasty
Since the inception of nasal surgery centuries
ago, the techniques, and approach to rhinoplasty
B. Guyuron (*) have continued to evolve. Nasal surgery is a
Zeeba Clinic, Lyndhurst, OH, USA highly technical and demanding aesthetic surgery
Case Western Reserve University, that requires diligent attention to details to pro-
Cleveland, OH, USA vide optimal results while not compromising
A. DeLeonibus functionality.
Cleveland Clinic Foundation, Cleveland, OH, USA
https://doi.org/10.1007/978-3-031-57132-9_33
342 B. Guyuron and A. DeLeonibus
Throughout the course of recorded history, the “Italian Method,” became a fixture in nasal sur-
nose had a paramount role in identifying an indi- gery [1].
vidual’s beauty, harmony, and honor. Classically, Rhinoplasty rapidly progressed in nine-
the nose was often disfigured and amputated as a teenth century thanks to the work of many
means of punishing individuals who debased Western society nasal surgeons. In 1845,
ancient societal norms through various impetuous Johann Friedrich Dieffenbach discussed his
acts [1]. It was through this punitive repercussion work in his book titled Operative Surgery
along with war and infectious and traumatic eti- where he described nasal surgery through the
ologies that reconstructive rhinoplasty was lens of anesthetic agents and most significantly
started. As far back as the BCE 1500s, both the through an endonasal or subcutaneous approach
Egyptians and Indian communities recognized the [3, 4]. In 1887, Dr. John Orlando Roe pub-
impact of nasal deformities and need for subse- lished his work on treatment for large lower
quent surgery. However in the fifth century BCE, lateral cartilages coined “pug nose.” [5] Dr.
Sushruta, an Ayurvedic physician, classically Roe’s sole intention from the surgery via an
described nasal reconstruction of amputated noses intranasal approach was for aesthetic benefits
through pedicled forehead and cheek flap transfer and is regarded as the first documented aes-
[1, 2]. Sushruta is often considered the creator of thetic rhinoplasty surgery performed [1]. In
the “Indian Method” for nasal reconstruction with 1891, Dr. Roe published additional work on
the forehead flap. Although despite his rather correcting nasal angular deformities via a sub-
ingenious use of local anatomy for surgical repair, cutaneous approach [1]. Concurrently, in the
the technique was largely lost by geographical late nineteenth century Dr. Robert Weir incor-
and etymological barriers. porated the use of osteotomes in manipulating
As centuries passed, advances in rhinoplasty the nasal dorsum, detailing in-fractures, and
were abandoned as many pious and influential correcting interalar width discrepancies
political figures in Western cultures viewed sur- through wedge resection of the ala, coined the
gery and especially nasal surgery as an obstruc- Weir excision [1].
tion of God’s will. Fast forward hundreds of Dr. Jacques Lewin Joseph, regarded as one of
years to the Middle Ages, much of rhinoplasty the forefathers of rhinoplasty, who significantly
focused on purely nasal reconstruction for advanced the field by expounding on the work of
acquired defects. In 1442 AD, at the hands of Dieffenbach, Roe, and Weir. Joseph incorporated
Sicilian surgeons Branca D’Branca and his son the use of photographs, anatomic restoration as
Antonius, nasal reconstruction with arm flaps the basis for rhinoplasty maneuvers, and devel-
gained wide locoregional recognition [1]. oped reduction and augmentation procedures [1,
However, their advances went largely unrecog- 6]. Many rhinoplasty surgeons regard Dr.
nized as their findings were lost to history through Joseph’s contributions as the turning point in our
secrecy and failure to document their techniques. conceptualization of twentieth century rhino-
It was not until the late sixteenth century, when plasty. Despite all these advances, rhinoplasty
Gaspare Tagliacozzi of Bologna recorded his was being performed almost exclusively in a
work on the arm flap for nasal reconstruction had closed manner. The yearning for better results
nasal surgery been discussed. Nevertheless, the spawned the most influential advancement in rhi-
use of the arm for nasal reconstruction coined the noplasty, the open approach.
33 Evolution of Rhinoplasty Surgery 343
33.2 Emergence of Open

Rhinoplasty
Anderson JR, Johnson CM, Adamson P. Open rhinoplasty: an assessment. Otolaryngol Head Neck Surg.
1982;90:272–4
Strengths • First detailed account of open rhinoplasty in an era where closed rhinoplasty was predominant
approach
• Widely accepted as inception study for open rhinoplasty
• Details 17 indications for performing open approach over closed
Limitations • Technique paper, retrospective study
• No control group, inability to perform internal control analysis
Impact This study introduced the concept of open rhinoplasty in a large cohort of patients. The study
detailed the benefits of the open approach in seasoned surgeons’ hands as well as addressed the
various criticisms of the open approach. This study is classically described as a paradigm
shifting article in how rhinoplasty exposure is approached
The first landmark article that brought forth one In 1982, Anderson’s paper was published in a
of the most pivotal changes in rhinoplasty was time where almost all North American surgeons
introduction of the open rhinoplasty technique. were performing closed rhinoplasty. The article
Throughout the early and mid-twentieth century, prefaces this fact by stating that Anderson him-
rhinoplasty was exclusively performed through a self had been performing endonasal rhinoplasty
closed approach. The endonasal or closed for 25 years and sought to investigate the open
approach was widely accepted and taught, how- approach after hearing about Padovan and
ever, the closed approach lacked sufficient visual- Goodman’s experience. Despite Anderson’s
ization of the nasal morphological incongruences understanding that open approach allows for bet-
and precise anatomical control of the cartilagi- ter visualization, many surgeons felt an external
nous components. Surgeons became keen to the columellar scar should be met with fervent oppo-
idea that if you cannot visualize a problem then sition [7]. Anderson goes on to list 17 indications
you cannot as effectively correct it. as to why open approach was beneficial in their
In 1966, the first extended experience of open practice at the time treating over 700 patients.
approach was reported by a rhinoplasty surgeon Anderson states that the open approach’s biggest
from Yugoslavia, Ivo Padovan, who reported on reward is that it provides better control of the
his “external approach” to rhinoplasty in his cohort operation over closed rhinoplasty.
of 400 patients and 500 of his mentor Ante Sercer’s While the open technique remained contro-
patients [8]. Padovan and Sercer’s motivation for versial for several years and even decades, there
open technique came from the work of Aurel Rethi is no question about its major impact in rhino-
of Budapest [9]. Most surgeons were apprehensive plasty today. Those of us who have been inter-
about adapting their style and were cautiously ested in rhinoplasty for a long time witnessed
optimistic. However, in Canada, William Goodman heated debates between Jack Sheen and Jack
who had attended Padovan’s lecture and returned Gunter, two giants of rhinoplasty field, on numer-
to Toronto was enthused to perform this own open ous panel discussions. Although there are still
approach. Subsequently, Peter Adamson, who was many who perform closed rhinoplasty, majority
a fellow Canadian rhinoplasty contemporary, left of the rhinoplasties are done through open tech-
for New Orleans to complete a fellowship with nique today.
Jack Anderson and his colleague Calvin Johnson. The cardinal advantages of the open technique
It was through the work and teachings of Adamson, include direct visualization of the anatomy and
Anderson, and Johnson that the open approach the pathology, ability to detect minor asymme-
took fire and created a paradigm shift in perform- tries, which may not be readily detectable with-
ing and teaching rhinoplasty [7, 10]. out opening the nose, empowering the rhinoplasty
surgeons to demonstrate the technique to the stu- vantages of this technique. Today, these claims
dents of this technique, and more controlled remain largely anecdotal. Although there are
alteration of the structures. The opponents of the occasional suboptimal scars caused by poorly
technique cite more postoperative swelling, the repaired incisions on patients with unusually
columellar incisional scar, and requirement of thick skin, the open rhinoplasty scar is seldom
more time to complete the surgery as the disad- discernable in majority of the cases.
33.3 Middle Vault Reconstruction

With Spreader Grafts
Sheen JH. Spreader graft: a method of reconstructing the roof of the middle nasal vault following rhinoplasty. Plast
Reconstr Surg. 1984;73:230–7 [11]
Strengths • Detailed description of the etiology and outcome of failure to address the middle vault
• Surgical description of how to construct the spreader graft, in vivo graft placement and pearls on
how to improve aesthetic and functional outcomes in middle vault reconstruction
Limitations • Retrospective review on surgeon technique and experience
• No control comparison group
• Small cohort of clinical examples (n = 3)
Impact This report detailed the various reasons as to why inadequate aesthetic and functional outcomes result
from lack of middle vault reconstruction. This study introduced the first account of the spreader
grafts, their design, construction, and placement in order to open the internal nasal valve and prevent
“inverted v” deformity
Another article that had enormous impact in the He noted that in thin skinned patients with ade-
aesthetic and functional outcomes of rhinoplasty quate nasal bone length without roof reconstruc-
was the introduction of the spreader graft reported tion, the thin skinned revealed the confluence of
by Jack Sheen. He noticed that there were obvi- the nasal bones with the upper lateral cartilages
ous aesthetic and functional shortcomings in (ULCs) and created an obvious “inverted-v”
both native noses and traditional rhinoplasty out- deformity [11]. Lastly, he determined that weak
comes when the middle vault was improperly ULCs predisposed patients to mid-vault collapse
addressed. Sheen concluded that post-operative due to the fact that when the roof is reduced the
airway obstruction with obvious narrowing of broad nasal dorsum is no longer in continuity
middle vault resulted from the visible falling-in with the ULCs, forcing the ULCs to fall into the
of the lateral walls and nasal valve abnormalities face medially [11]. Aside from the spreader grafts
on inspiration [11]. bolstering the INV angle functionally, the aes-
The middle vault contains the internal nasal thetics of the mid-vault reconstructed nose
valve (INV) that controls the majority of airway improved the dorsal aesthetic lines by preventing
transmittance and breathing patterns. Sheen mid nose external concavities..
noticed that patients with naturally acute INV There was no controversy about this article,
angles or post rhinoplasty with mid vault col- and essentially every rhinoplasty surgeon
lapse had obvious obstructive issues. He observed embraced this technique unconditionally. Today,
that abnormal valving occurred when the upper rarely a rhinoplasty is performed without the use
lateral cartilages collapsed on inspiration, nar- of spreader graft or spreader flap, a variation that
rowing the INV angle further and creating an is optimal for a patient with a large hump. While
obstruction in the ingress and egress of nasal air. the initial article was introduced for the closed
Sheen appropriately recognized that patients rhinoplasty technique, it is currently used widely
with short nasal bones lacked the ability to sup- during the open rhinoplasty as well to establish
port the upper lateral cartilages in the mid vault. optimal dorsal aesthetic lines and maintain or
improve the internal valve function. Prior to sion for nasal elongation or gain of projection,
introduction of spreader graft many noses devel- which is called extended spreader grafts [12].
oped the tell-tale sign of post-surgical “inverted- Guyuron used extended spreader grafts and a
V” deformity. This deformity, however, was often columella strut to optimally aligned with the
not apparent shortly after surgery but it marred septum to create a stable frame to elongate the
the aesthetic dorsal lines 6 months, a year, or nose or suspend the medial crura to gain more
years later. tip projection and prevent hiding the upper inci-
Unlike many techniques that have had numer- sor teeth on patients with borderline or inade-
ous variations and refinements, the only major quate upper incisor show. Otherwise,
variation of the technique was introduced by the deterioration of this condition could occur as a
senior author for elongation of the nose or cre- result of a columella strut displacing the upper
ation of a reliable and symmetric septal exten- lip caudally [12].
33.4 Lateral Crural Strut
Gunter JP, Friedman RM. Lateral crural strut graft: technique and clinical applications in rhinoplasty. Plast Reconstr
Surg. 1997;99(4):943–52 [13]
Strengths • Large cohort of patients (n = 118)
• Detailed how to design, construct, and place grafts in vivo
• Reports on specific clinical applications in which the lateral crural strut plays a pivotal role, boxy
nasal tip, malpositioned lateral crura, alar rim retraction, alar rim collapse, and concave lateral crura
Limitations • Retrospective review on surgeon technique and experience
• No control comparison group
• Mean follow up was 8.5 months
Impact This report details the first use of the lateral crural strut in providing structure and support to
deficient lower lateral cartilage lateral crura. This study outlines specific clinical indications to aid
rhinoplasty surgeons to add this technique to their armamentarium when addressing inadequate
lateral crura
A uniformly accepted technique that was another septal cartilage graft. He would first perform a lat-
milestone in the progress of rhinoplasty was the eral crural cephalic trim and then contour the
introduction of the lateral crural strut by Jack grafts 3–4 mm wide by 15–25 mm long. Gunter
Gunter. This is in our view, Jack Gunter’s biggest released the vestibular skin/mucoperichondrium
contribution to rhinoplasty amongst his many from the native lateral crura and positioned the
other contributions. strut underneath the lateral crura. He stated that
Gunter identified that tip control and appear- longer lateral crural struts were necessary for mal-
ance relied heavily on the stability of the lateral positioned, alar retraction, and alar collapse [13].
crura and the medial crura. When the lateral crura The lateral crural strut has considerable value
is weakened, misshapened, malpositioned, or defi- when treating the boxy tip, malpositioned lateral
cient, tip support is diminished [13]. Gunter pro- crura, alar rim retraction, and concave lateral
posed the lateral crural strut, strips of autologous crura. Horizontal mattress transdomal suture
cartilage fixated to the undersurface of the lateral approximation first described by McCollough
crus to fortify the tip support and to eliminate the helps create ideal tip definition but has a tendency
convexity of the lower lateral cartilages [13]. to medialize the lateral margin of the lateral crura
Gunter initially reported the use of the lateral [13, 14]. Gunter used the combination of the
crural strut in an open approach. He most com- transdomal suture with lateral crura strut to define
monly used septal cartilage followed by costal car- the tip and contour the lateral extent of the lateral
tilage for the creation of the strut, in the absence of crus and alar margin [13].
The lateral crural strut graft is used frequently lateral cartilage is repositioned caudally. After
in primary or secondary rhinoplasty, unilaterally hydrodissection, the lower lateral cartilage is
or bilaterally and whenever the lateral crus of the separated from the underling mucoperichon-
lower lateral cartilage is weak, disrupted, or drium, and the strut is sutured to the lower later
cephalically oriented. Another common indica- cartilage and repositioned in a new pocket
tion for the use of this strut is when the lower caudally.
33.5 Use of Alar Rim Graft
Troell RJ, Powell NB, Riley RW, Li KK. Evaluation of a new procedure for nasal alar rim and valve collapse: nasal
alar rim reconstruction. Otolaryngol Head Neck Surg. 2000;122(2):204–11 [15]
Strengths • Large cohort of patients (n = 79)
• Consecutive patient series
• Long-term follow up at 16.89 months
• Detailed how to design, construct, and place alar grafts in vivo
• Comparison control group of nasal valve cartilage graft vs. nasal alar rim reconstruction groups
Limitations • Retrospective review on technique and experience
• Subjective patient directed non-validated evaluation of nasal obstruction as primary outcome
measure
Impact This report details the first use alar rim graft coined as the nasal alar rim reconstruction graft. The
graft was placed in the subcutaneous plane as a means to reconstruct and support the alar rim for
external valve deficits. The study focused almost exclusively on the functional results and did not
appreciate the impact that this graft grew to have on the aesthetic outcomes of the alar rim margin
Troell is credited with describing the first use of cartilages (LLCs) [16]. It is for this reason inser-
alar rim grafts called nasal alar rim reconstruction of the alar rim grafts becomes mandatory in
tion (NARR) [15]. He primarily focused on most cases.
opening the external valve to help with breathing. Variations and importance in this technique
He inserted the graft through an incision in the was demonstrated through the work of Guyuron,
vestibular skin at the junction of the nares and Rohrich and Davis [16–21]. A version of alar rim
nasal lobule, undermined skin to create a subcu- graft, described by Davis, called an “Articulated
taneous pocket from the piriform aperture, just Alar Rim Graft” has become very popular [17].
shy of the nasal tip and placed a 3–4 mm wide Davis introduced the idea of the articulated alar
25–30 mm long beveled cartilage graft in the rim graft to provide the alar rim with a structur-
pocket [15]. He noticed that in addition to aug- ally integrated support to the lateral crus and/or
menting the nasal valve it strengthened the nasal septal extension graft [17]. Guyuron has advo-
alar margin. cated the use of the alar rim graft not only in revi-
The initial goal of the alar rim graft was to sionary alar rim reconstruction but more
treat the valve dysfunction but has been demon- importantly as prophylaxis against alar rim dis-
strated to provide considerably more benefits crepancies in primary rhinoplasties [16, 18].
[16]. Many sutures that adjust the tip shape, espe- Introduction of the alar rim graft has enabled
cially interruption of the domes, result in concav- us to produce more graceful, and often elegant
ity of the lateral crura of the lower lateral transition from the alar base to the nasal tip. In
cartilages and thus medial curving of the alar rim most practices focused on rhinoplasty, this graft
[16]. These maneuvers include transdomal is used almost routinely in primary rhinoplas-
sutures, lateral crura spanning suture, and exci- ties and in majority of the secondary
sion of the cephalic portion of the lower lateral rhinoplasties.
33.6 Use of Suture Techniques
Guyuron B, Behmand RA. Nasal tip sutures Part II: the interplays. Plast Reconstr Surg. 2003;112(4):
1130–45 [22]
Strengths • Part 2 report on tip sutures and associated interplay based on extended senior surgeon experience
• Details the purpose of each suture technique, indications, how to execute the maneuver, and pitfalls
if the suture was placed incorrectly
Limitations • Narrative review study on suture techniques
• Not an experimental study without any cases or control for comparisons
Impact This report details the most ubiquitously performed and powerful tip suture techniques in a concise
manner. The report explains how to place each suture and describes how alterations in placement
influences the dynamics of the nose and neighboring structures
Another milestone in rhinoplasty progress was suture is a powerful suture technique that involves
introduction of suture techniques and articles that a horizontal mattress spanning the domal arch
reviewed and described these sutures, their use anterior to the vestibular lining [14]. The purpose
and their dynamics. Guyuron and Behmand com- of the transdomal suture is to narrow the tip,
prehensively discussed the most important tip however, this suture reduces the domal angle,
suture techniques paramount to a rhinoplasty sur- increases lobular fullness, increases tip projec-
geon’s armamentarium including the medial crura tion, and marginally reduce interdomal distance.
suture, middle crura suture, interdomal suture, Understanding the nuances of cranial or caudal
transdomal suture, lateral crura suture, medial positioning of the transdomal suture is important
crura-septal suture, tip rotation suture, medial as this can cranially or caudally rotate the lateral
crura footplate suture, and the lateral crura con- crus, respectively. Tebbetts described the use of
vexity control suture [22, 23]. Additionally, the lateral crura suture in detail as a horizontal
Guyuron described septal rotation suture to over- mattress suture on the middle two-thirds of both
come the challenge of the anterior deviation of the LLCs spanning the nasal dorsum [25]. This
septum over the distal half of the dorsum and suture can elongate the nose as well as help
warping prevention suture to minimize the carti- reduce lateral crural convexity depending on the
lage graft related complications [24]. tension of the suture. The medial crura-septal tip
The medial crura suture is used to bring suspension suture is placed between the medial
together the medial crura and narrow the colu- crus or footplate and the caudal septum. This
mella. Placement of the medial crura suture is suture is used to help control tip projection and
important since caudal or cranial positioning can can also create columella retraction based on
create caudal or cranial rotation of the lower lat- placement of the suture along the septum. The tip
eral cartilages inadvertently. The middle crura rotation suture is placed between genu of the
suture is placed along the medial aspect of both LLCs and fixated to the anterocaudal septum
LLC genu with the overarching goal to reduce helping to rotate the tip cephalically [26]. The
the interdomal distance. The middle crura suture medial crura suture is a u-shaped stitch placed
helps strengthen the columella and aids in between the medial crura after excision of a tri-
improving tip support. The interdomal suture is angle piece of caudal septum based anteriorly
placed on the most anterior aspect of the domes and the proportional amount of membranous sep-
and helps narrow the tip, increase tip projection, tum to help approximate the medial crura to the
and helps volumize the lobule. The placement of septum and thus rotate the tip cephalically in a
the interdomal suture controls the distance secure manner. The lateral crura convexity con-
between and equalizes the domes. Ideally, the trol suture described by Gruber is placed as a
interdomal suture is of great utility when the horizontal suture along lateral crus and based on
domal angles are satisfactory but the interdomal the tension the crus is flattened [27–29]. This is a
distance remains too far apart. The transdomal powerful suture that is used to stabilize the lateral
crura in a planar orientation by reducing the con- tures in situ. Setting the tip in the correct position
vexity but over tightening can inadvertently cre- requires three-dimensional maneuvers and atten-
ate lateral crura concavity and narrowing the tion to detail in order not to compromise adjacent
external nasal valve. nasal tip components.
A septal rotation suture is a mattress suture The three principal components in tip aesthet-
that is started cephalically on the side to which ics include length, projection, and rotation [33].
the anterior septum and spreader grafts are being In 1969, Anderson introduced a simplified ver-
shifted and cephalically on the side to which the sion of tip architecture through the nasal tip tri-
anterior septum and the spreader grafts are shifted pod concept [33, 34]. Anderson explained the tip
currently. The suture is tied incrementally to as being an integrated structural culmination of a
align the dorsum perfectly with the intercanthal central leg composed by conjoined medial crura
and upper lip midlines [24]. and two side legs being the lateral crura [33, 34].
The warping prevention suture is a running The location where the three legs meet defines
suture which is started on the convex surface of the tip defining points. Manipulation of the leg
the cartilage that had been place in saline for length by shortening or elongation influences the
10–15 min to reveal the direction of warpage. tip projection and invariably rotation and length.
The suture is ended on the convex surface and The tripod concept has stood the test of time in
tied incrementally enough to straighten the understanding the nature of the tip. The tripod
warped cartilage [30]. This suture has replaced theory has been expounded to the M-arch model
the use of k-wire. by breaking down the tripod into paired arches of
the medial crura, intermediate crura, and lateral
crura bilaterally [33].
33.6.1 Key Publications Helping
Understanding Rhinoplasty
33.8 Understanding Dynamics
While the previously mentioned articles consti- of Rhinoplasty
tute some of the most important articles in rhino-
plasty, attributing the rhinoplasty progress strictly In mid-1980s, Guyuron discovered that one of
to these articles could be misjustice to others that the major factors making rhinoplasty so complex
had substantial impact in rhinoplasty progress is its dynamic interplays. He observed that each
culminating in the current state of the art. The given maneuver delivered the objective goal, but
authors take liberty of mentioning some other it also resulted in several unintended changes that
articles with salient impact in rhinoplasty. were not part of the aesthetic plan. It was clear
that understanding these changes was crucial to
planning and delivery of more predictable
33.7 Tripod Concept to Tip outcomes.
Aesthetics Guyuron concluded that the true challenge is
predicting not only the targeted outcome but the
Surgical management of the nasal tip dysmor- cascading effect of the maneuver in intended
phology is widely considered the most challeng- structure and adjacent, communicating nasal
ing and prodigious aspect of rhinoplasty. The components, and harmony of the face [18,
majority of residual flaws following rhinoplasty 35–38]. For example, he described the illusion of
are within the lower 1/third of the nose and dis- the intercanthal distance change after dorsal
satisfaction about the tip shape is one of the most hump reduction or augmentation. He reported
common reasons for revision rhinoplasty [17, 31, that in dorsal reduction the intercanthal distance
32]. Optimizing tip aesthetics requires a thorough appears wider while in augmentation the inter-
understanding of the anatomical components and canthal distance appears smaller albeit no actual
the ideal orientation of the cartilaginous struc- change in true intercanthal distances [36]. His in-
depth study outlines such a change, essentially, tric instruments give surgeons immediate feed-
related to every common maneuver in each zone back, better control, and the ability to evaluate
of the nose. He subsequently has studied the bony composition [40].
dynamic interplays of many recent maneuvers
and the impact that each has on the overall nose
and face congruity [35–39]. 33.10 Columella Strut
The columella strut is a cartilaginous graft placed

33.9 Implementation in a pocket between the nasal footplates to help
of Piezoelectric Instruments support the medial crura and central limb of the
in Rhinoplasty nasal tip tripod. The utility of columellar strut has
proven invaluable since its early descriptions by
The manipulation of the cartilage is fundamen- Dibbel [44]. Since its inception for the cleft lip
tally controlled through trimming, sutures, and rhinoplasty, many have described variations in
grafting techniques. The manipulation of bony surgical technique, alterations in columellar cau-
structures is much more challenging and requires dal septal relationships, and columellar medial
finesse. Classically, osteotomies and ostectomies crura interplay [45, 46]. Columellar strut pro-
of the nasal bones were performed by handheld vides stability to the tip but also provides a back-
osteotomes and rasps first introduced by Joseph bone in which other corrective tip maneuvers can
[6]. However, there is considerably less control be accomplished.
and ability to contour the nasal bones particularly A columella strut can be fixed or floated and
in inexperienced hands using these tools [40]. then approximated to the medial crura when defi-
Piezoelectric surgery was introduced to create cient to provide robust structure to the columella.
a less traumatic and precise means of surgical Columella strut grafts have been weighed against
osteotomies, with minimal soft tissue damage. the septal extension graft in terms of superiority
Ultrasonic instrumentation is produced by con- but both grafts have specific roles and indications
verting electrical current into ultrasonic waves that should be used in designated roles.
through a transducer. The ultrasonic waves are
then conveyed through a handpiece with an inter-
changeable cutting tip scalpel [41]. The vibration 33.11 Septal Extension Graft
is unique in that it only cuts mineralized struc-
tures at a frequency of 25–29 Hz and theoreti- Byrd described fixation of oversized columellar
cally stops when it encounters soft tissue [42]. strut to one side of the caudal septum as a way to
Gerbault has propelled the use of piezoelectric stabilize the tip and maintain projection which
ultrasonic instruments in rhinoplasty surgery but led to his inception of the septal extension graft
the initial description was by Robiony in 2005 and [47]. However, since this graft is fixed to one side
published in 2007 [40–43]. Robiony demon- of the septum it carries the potential tip asymme-
strated the first use of ultrasonic technology in try proportional to thickness of the septal carti-
rhinoplasty and showed that piezoelectric creates lage. To prevent this asymmetry Guyuron
less nasal and mucosal injury in a more controlled proposed alignment of the columella strut as an
manner and reduces post-operative ecchymosis extension graft with variety of widths and shapes,
and edema [41]. Subsequently Robiony published depending on the caudal nose morphology. He
on piezoelectric use in bony vault control, medial, introduced using extended spreader grafts that
lateral osteotomies, and cephalic to keystone are sutured to the caudal septum and unified with
junction en-block bony hump reduction [43]. the columella strut with additional sutures to pro-
The advent of the piezoelectric instruments vide reliable stability and dependable alignment
profoundly changed the rhinoplasty surgeon’s for control of projection and the length of the
view on how we treat nasal bones. The piezoelec- nose, serving as a septal extension graft [48].
33.12 Preservation Rhinoplasty Nevertheless, at the present time the technique

remains somewhat controversial and not every-
Preservation rhinoplasty (PR) has garnered one has incorporated a form of this technique in
increasing attention globally as a philosophical their rhinoplasty practice.
approach to rhinoplasty with the goal to preserve
and maintain as much of the natural ligamentous
and structural components of the nose as possi- 33.13 Expert Concluding
ble. Although many view PR as a competing Commentary
methodology to structural rhinoplasty, they both
originate from the closed rhinoplasty school of The long and tenured history of rhinoplasty has
thought. taken many turns along its evolutionary tale.
PR focuses on three pillars: (1) soft tissue However, the aforementioned articles detailing
envelop preservation through subperichondrieal- the introduction of the open approach, treatment
subperiosteal dissection, (2) dorsal preservation of middle vault collapse, lateral crural instability,
(DP) without creating an open roof, and (3) alar alar rim deficiency, and use of sutures provides a
cartilage preservation with suture/grafting tech- modest glimpse into rhinoplasty’s evolution.
niques over excision [49–51]. The idea of preser- Although there is substantially more to discuss,
vation rhinoplasty is not new or novel and is a the overarching goal of this chapter was to pres-
continuation of work done by Cottle in the mid ent key aspects of the nasal surgery progression
twentieth century [52]. Preservation rhinoplasty to the point where we reside today.
was met with opposition and never took hold in
rhinoplasty circles especially as open rhinoplasty
became popular. Surgeons elected to perform dor- References
sal hump reductions as Joseph described due to
ease, predictability, and teachability. Hesitancy in 1. Belinfante LS. History of rhinoplasty. Oral Maxillofac
performing preservation rhinoplasty lingered in Surg Clin North Am. 2012;24(1):1–9.
twentieth century as open approach gave surgeons 2. Breasted J. The Edwin Smith surgical Papyrus, vol. 1.
University of Chicago; 1930.
direct visualization and access to dorsal and tip 3. Whitaker IS, Karoo RO, Spyrou G, Fenton OM. The
issues. In the late twentieth century, Yves Saban birth of plastic surgery: the story of nasal reconstruc-
of France actively performed preservation rhino- tion from the Edwin Smith Papyrus to the twenty-first
plasty and is noted as the catalyst to the modern century. Plast Reconstr Surg. 2007;120(1):327–36.
4. Eisenberg I. A history of rhinoplasty. S Afr Med J.
movement across Europe in the early twenty-first 1982;62(9):286–92.
century [50]. Preservation rhinoplasty was con- 5. Roe JO. The deformity termed “pug nose” and its
sidered an approach centered around use in the correction by a simple operation. By John Orlando
closed approach, but subsequently PR has been Roe, 1887. Arch Otolaryngol Head Neck Surg.
1989;115(2):156–7.
incorporated in the open approach. 6. Joseph J. Nasenplastik und sonstige Gesichtsplastik,
The vast majority of preservation rhinoplasty nebst einem Anhang über Mammaplastik und einige
in practice and in the literature deals with dorsal weitere Operationen aus dem Gebiete der äußeren
preservation by maintaining the natural architec- Körperplastik. Ein Atlas und Lehrbuch. Published
online 1931.
ture of the nasal dorsum while lowering the 7. Anderson JR, Johnson CM, Adamson P. Open rhino-
osseocartilaginous structure into the face. DP plasty: an assessment. Otolaryngol Head Neck Surg.
employs various techniques in handling of the 1982;90(2):272–4.
boney nasal bones and cartilaginous septum. 8. Sercer A, Mundnich K. Plastiche Operationen an Der
Ohrmuschel. Stuttgart (Germany): Georg Thieme
Boney work is accomplished either by a push- Verlag; 1962.
down or let-down technique. Cartilaginous work 9. Rethi A. Operation to shorten an excessively long
has more variation in approach and technique but nose. Rev Chir Plast. 1934;2:85–7.
all rely on excisional patterns to allow septal 10. Anderson J, Ries W. Rhinoplasty: emphasizing the
external approach. Thieme, Inc; 1986.
descent along with boney descent [50, 52–57].
11. Sheen JH. Spreader graft: a method of reconstruct- 30. Guyuron B, Wang DZ, Kurlander DE. The car-
ing the roof of the middle nasal vault following tilage warp prevention suture. Aesth Plast Surg.
rhinoplasty. Plast Reconstr Surg. 1984;73(2): 2018;42(3):854–8.
230–9. 31. Gillman GS, Simons RL, Lee DJ. Nasal tip bossae
12. Bahman G, Xia TY. Evolution and versatility of the in rhinoplasty. Etiology, predisposing factors, and
bilateral extended spreader graft: a review and an management techniques. Arch Facial Plast Surg.
update to the tongue-and-Groove technique. Aesth 1999;1(2):83–9.
Plast Surg. 2022; Published online June 7 32. Yu K, Kim A, Pearlman SJ. Functional and aesthetic
13. Gunter JP, Friedman RM. Lateral crural strut graft: concerns of patients seeking revision rhinoplasty.
technique and clinical applications in rhinoplasty. Arch Facial Plast Surg. 2010;12(5):291–7.
Plast Reconstr Surg. 1997;99(4):943–52. discussion 33. Sands NB, Adamson PA. Nasal tip deprojection with
953–955 crural cartilage overlap: the M-arch model. Facial
14. McCollough EG, English JL. A new twist in nasal Plast Surg Clin North Am. 2015;23(1):93–104.
tip surgery. An alternative to the Goldman tip for 34. Anderson J. The dynamics of rhinoplasty. In:
the wide or bulbous lobule. Arch Otolaryngol. Presented at: Ninth international congress of otorhi-
1985;111(8):524–9. nolaryngology; 1969. Mexico City, Mexico.
15. Troell RJ, Powell NB, Riley RW, Li KK. Evaluation 35. Guyuron B. Dynamics of rhinoplasty. Aesth Plast
of a new procedure for nasal alar rim and valve col- Surg. 2002;26(Suppl. 1):S10.
lapse: nasal alar rim reconstruction. Otolaryngol Head 36. Guyuron B. Dynamics in rhinoplasty. Plast Reconstr
Neck Surg. 2000;122(2):204–11. Surg. 2000;105(6):2257–9.
16. Guyuron B, Bigdeli Y, Sajjadian A. Dynamics of the 37. Guyuron B. Dynamics of rhinoplasty. Plast Reconstr
alar rim graft. Plast Reconstr Surg. 2015;135(4):981–6. Surg 1991;88(6):970–978. discussion 979.
17. Ballin AC, Kim H, Chance E, Davis RE. The articu- 38. Xia TY, Punjabi A, Oh JH, Wee C, Guyuron
lated alar rim graft: reengineering the conventional B. Updated dynamics of rhinoplasty: a review of
alar rim graft for improved contour and support. the literature and comprehensive list of the findings.
Facial Plast Surg. 2016;32(4):384–97. Aesth Plast Surg. 2020;44(3):904–9.
18. Guyuron B. Alar rim deformities. Plast Reconstr 39. Guyuron B. Dynamic interplays during rhinoplasty.
Surg. 2001;107(3):856–63. Clin Plast Surg. 1996;23(2):223–31.
19. Rohrich RJ, Raniere J, Ha RY. The alar con- 40. Gerbault O. Ultrasonic rhinoplasty and septoplasty
tour graft: correction and prevention of alar rim for Dorsum preservation and for dorsum structural
deformities in rhinoplasty. Plast Reconstr Surg. reconstruction. Facial Plast Surg Clin North Am.
2002;109(7):2495–505.; discussion 2506–2508. 2023;31(1):143–54.
20. Rohrich RJ, Durand PD. Expanded role of alar con- 41. Robiony M, Polini F, Costa F, Toro C, Politi
tour grafts. Plast Reconstr Surg. 2021;148(4):780–5. M. Ultrasound piezoelectric vibrations to perform
21. Unger JG, Roostaeian J, Small KH, et al. Alar con- osteotomies in rhinoplasty. J Oral Maxillofac Surg.
tour grafts in rhinoplasty: a safe and reproducible way 2007;65(5):1035–8.
to refine alar contour aesthetics. Plast Reconstr Surg. 42. Gerbault O, Daniel RK, Kosins AM. The role of
2016;137(1):52–61. piezoelectric instrumentation in rhinoplasty surgery.
22. Guyuron B, Behmand RA. Nasal tip sutures Aesthet Surg J. 2016;36(1):21–34.
part II: the interplays. Plast Reconstr Surg. 43. Robiony M, Toro C, Costa F, Sembronio S,
2003;112(4):1130–45.; discussion 1146–1149. Polini F, Politi M. Piezosurgery: a new method
23. Behmand RA, Ghavami A, Guyuron B. Nasal tip for osteotomies in rhinoplasty. J Craniofac Surg.
sutures part I: the evolution. Plast Reconstr Surg. 2007;18(5):1098–100.
2003;112(4):1125–9.; discussion 1146-1149. 44. Dibbell DG. A cartilaginous columellar strut in cleft
24. Guyuron B, Behmand RA. Caudal nasal deviation. lip rhinoplasties. Br J Plast Surg. 1976;29(3):247–50.
Plast Reconstr Surg. 2003;111(7):2449–57; discus- 45. Rohrich RJ, Kurkjian TJ, Hoxworth RE, Stephan PJ,
sion 2458–2459. Mojallal A. The effect of the columellar strut graft
25. Tebbetts JB. Shaping and positioning the nasal tip on nasal tip position in primary rhinoplasty. Plast
without structural disruption: a new, systematic Reconstr Surg. 2012;130(4):926–32.
approach. Plast Reconstr Surg. 1994;94(1):61–77. 46. Rohrich RJ, Hoxworth RE, Kurkjian TJ. The role of
26. Baker SR. Suture contouring of the nasal tip. Arch the columellar strut in rhinoplasty: indications and
Facial Plast Surg. 2000;2(1):34–42. rationale. Plast Reconstr Surg. 2012;129(1):118e–25e.
27. Gruber RP. Suture correction of nasal tip cartilage con- 47. Byrd HS, Andochick S, Copit S, Walton KG. Septal
cavities. Plast Reconstr Surg. 1997;100(6):1616–7. extension grafts: a method of controlling tip projection
28. Gruber RP, Friedman GD. Suture algorithm for shape. Plast Reconstr Surg. 1997;100(4):999–1010.
the broad or bulbous nasal tip. Plast Reconstr Surg. 48. Ponsky DC, Harvey DJ, Khan SW, Guyuron B. Nose
2002;110(7):1752–64. discussion 1765–1768 elongation: a review and description of the septal
29. Gruber RP, Weintraub J, Pomerantz J. Suture extension tongue-and-groove technique. Aesthet Surg
techniques for the nasal tip. Aesthet Surg J. J. 2010;30(3):335–46.
2008;28(1):92–100.
49. Daniel RK, Kosins AM. Current trends in preser- 54. Patel PN, Abdelwahab M, Most SP. A review and mod-
vation rhinoplasty. Aesthet Surg J Open Forum. ification of dorsal preservation rhinoplasty techniques.
2020;2(1):ojaa003. Facial Plast Surg Aesthet Med. 2020;22(2):71–9.
50. Saban Y, Daniel RK, Polselli R, Trapasso M, Palhazi 55. Ishida LC, Ishida J, Ishida LH, Tartare A, Fernandes
P. Dorsal preservation: the push down technique reas- RK, Gemperli R. Nasal hump treatment with carti-
sessed. Aesthet Surg J. 2018;38(2):117–31. laginous push-down and preservation of the bony cap.
51. Daniel RK. The preservation rhinoplasty: a new rhino- Aesthet Surg J. 2020;40(11):1168–78.
plasty revolution. Aesthet Surg J. 2018;38(2):228–9. 56. Ishida J, Ishida LC, Ishida LH, Vieira JC, Ferreira
52. Cottle MH, Loring RM. Corrective surgery of MC. Treatment of the nasal hump with preservation
the external nasal pyramid and the nasal septum of the cartilaginous framework. Plast Reconstr Surg.
for restoration of normal physiology. Ill Med J. 1999;103(6):1729–33. discussion 1734–1735
1946;90:119–35. 57. Gonçalves Ferreira M, Ishida LC, Ishida LH,
53. Saban Y, Braccini F, Polselli R. Rhinoplasty: morpho- Santos M. Ferreira-Ishida Technique: spare roof
dynamic anatomy of rhinoplasty. Interest of conser- technique B. Step-by-step guide to preserving the
vative rhinoplasty. Rev Laryngol Otol Rhinol (Bord). bony cap while dehumping. Plast Reconstr Surg.
2006;127(1–2):15–22. 2022;149(5):901e–4e.
Evolution of Post Massive Weight
Loss Surgery
34
Francesco M. Egro, Mario Alessandri Bonetti,
and J. Peter Rubin
Abstract 2. Song AY, Jean RD, Hurwitz DJ, Fernstrom

Massive weight loss following bariatric sur- MH, Scott JA, Rubin JP. A classification of
gery has led to the evolution of a new field: contour deformities after bariatric weight
postbariatric body contouring. This chapter loss: the Pittsburgh Rating Scale. Plast
discusses body contouring surgery after mas- Reconstr Surg. 2005;116(5):1535–44. dis-
sive weight loss narrated through the five cussion 1545–6.
most cited landmark papers in the literature. 3. Song AY, Rubin JP, Thomas V, Dudas JR,
Each of the selected articles had a unique Marra KG, Fernstrom MH. Body image and
impact on the anatomy, classification, presen- quality of life in post massive weight loss
tation, and clinical approach to post-bariatric body contouring patients. Obesity (Silver
patients. Other important references are used Spring). 2006;14(9):1626–36.
to provide a better comprehensive overview 4. Coon D, Gusenoff JA, Kannan N, El
of the topic. Khoudary SR, Naghshineh N, Rubin JP.
Body mass and surgical complications in
Keywords the postbariatric reconstructive patient:
analysis of 511 cases. Ann Surg. 2009;
Massive weight loss · Body contouring · 249(3):397–401.
Postbariatric · Obesity · Abdominoplasty 5. Nemerofsky RB, Oliak DA, Capella JF.
Body lift: an account of 200 consecutive
The Five Most Impactful Papers cases in the massive weight loss patient.
1. Lockwood TE. Superficial fascial system Plast Reconstr Surg. 2006;117(2):414–30.
(SFS) of the trunk and extremities: a new
concept. Plast Reconstr Surg.
1991;87(6):1009–18. 34.1 Introduction
Obesity in the United States is a major problem

with an age-adjusted prevalence among adults of
F. M. Egro (*) · M. A. Bonetti · J. P. Rubin
Department of Plastic Surgery, University of 42.4% in 2017–2018 and 44.8% among middle-
Pittsburgh, Pittsburgh, PA, USA aged adults aged 40–59 [1]. Bariatric surgery is
widely accepted as the best treatment for obesity,
https://doi.org/10.1007/978-3-031-57132-9_34
354 F. M. Egro et al.
with sleeve gastrectomy overcoming Roux-en-Y its function [9]. At that time, many anatomists
gastric bypass as the most common bariatric pro- doubted the true existence of this fascia as a dis-
cedure in the United States [2, 3]. In recent years, tinct entity. The SFS corresponds to a connective
body contouring surgery after massive weight tissue network that extends from the subdermal
loss has emerged due to the increasing preva- plane to the muscle fascia. It is a horizontal mem-
lence of obesity and the growing popularity of branous sheet separated by varying amounts of
bariatric weight loss operations. According to a fat with interconnecting vertical or oblique
5-Year prospective study, 80% of bariatric sur- fibrous septa. Vertical extensions of the SFS con-
gery patients either underwent body contouring nect with the overlying dermis encasing the
surgery or is considering it [4]. These trends are superficial fat in vertically oriented compart-
reflected by data published in 2020 by the ments. Similar extensions connect the SFS to the
American Society of Plastic Surgery, showing underlying muscle fascia. It is the scaffold of the
that a total of 46,577 body contouring proce- subcutaneous fat and it varies in both density and
dures after massive weight loss were performed quality. In some areas (called zones of adher-
in the United States during that year, with ence) the superficial fat is tightly adherent to the
abdominoplasty being the most common one musculoskeletal fascia, creating creases and val-
(over 40%) [5]. The likely reason is that patients leys. In other parts, their interconnection is loose,
tend to lose up to 50% of their weight in a short and it creates bulges over deep fat deposits. Areas
period following bariatric surgery. This often of greatest adherence include vertical anterior
leads to soft tissue deflation, loose skin, and and posterior midlines, horizontal inguinal, and
unexpected folds [6]. In addition to contributing lateral gluteal depressions expanded the identifi-
to the perception of an unattractive body, the cation of zones of adherence to mid medial thigh,
excess skin results in physical and functional inferolateral iliotibial tract, and distal posterior
symptoms such as pain and itching, skin infec- thigh [10].
tions, mobility limitations, and hindrances in The likely reason why surgeons and anato-
daily life activities [7]. Body contouring after mists could not recognize the SFS was due to
massive weight loss has emerged a safe and reli- the dilution of the connective tissue in obese
able option to improve self-esteem, social life, individuals. Indeed, fat deposits separate the
work ability, physical activity, and sexual activ- layers of the SFS until they can barely be recog-
ity [8]. This book chapter aims to discuss body nized. Another confusing feature of the SFS is
contouring surgery after massive weight loss the inconsistent anatomy from one body region
narrated through the five most cited landmark to another. SFS is usually well-defined in the
papers in the literature. Each of the selected arti- lower trunk (Scarpa’s) and the perineum
cles had a unique impact on the anatomy, classi- (Colles’), but not in other areas. The SFS is
fication, presentation, and clinical approach to interestingly more prominent on the posterior
post-bariatric patients. half of the trunk and thigh compared to the ante-
rior half. Also, in the epigastric area and the
extremities, the SFS becomes less noticeable
34.2 Principle of Body Contouring and it is difficult to separate the superficial fat
in Massive Weight Loss (above the horizontal fascial layer) from the fat
Patients: The Superficial within the SFS.
Fascial System Inter-sex variability is significant in the breast,
where the SFS splits to form the anterior and pos-
Lockwood conducted a mixed study on cadavers terior lamellae of the breast. In turn, the posterior
and body contouring patients to describe the lamella fixes the breast to the pectoralis muscle
superficial fascial system (SFS) of the body and fascia. Another difference can also be observed in
34 Evolution of Post Massive Weight Loss Surgery 355
the region of the iliac crest, where in males, the and to transmit tension distally to improve the
SFS is tightly adherent to the periosteum of the contour.
crest. In women, the SFS is relatively adherent to After the documentation of the role of the SFS
the muscle fascia of the gluteal depression (sev- in body shaping, Lockwood applied these new
eral centimeters inferior to the iliac crest) and it findings to body contouring surgery. SFS suspen-
forms the roof of the localized fat deposit that sion replaced de-epithelialized dermal flap sus-
overlies the crest. This difference in SFS explains pension in lifting techniques of the back, flank,
variability in flank contour between males and buttock, and thighs [11–13]. Advantages of SFS
females. suspension and repair includes reduction of late
The basic function of the SFS is to support the scar depression and maintenance of the excursion
skin and fat of the body. The skin, superficial fat, of the skin, superficial fat, and SFS unit on the
and SFS should be considered as a supportive muscles during dynamic activities as bending or
functional unit for trunk and extremities. As we walking, avoiding the suture of the dermal flap to
age, the skin, superficial fat, and SFS unit relaxes the muscle fascia or periosteum. Before
and loosens, enhancing skin laxity especially in Lockwood’s paper, the repair of the Scarpa’s fas-
areas of minor adherence such as periumbilical cia in abdominoplasty closures was usually
and flanks areas. This ptosis is accentuated by the ignored. The repair of the SFS (Scarpa’s fascia)
SFS adherence deep to fat deposits, producing prior to skin closure allowed resolution of com-
bulges or pseudo-fat deposit deformity. mon problems in abdominoplasty including
The understanding of the anatomic principles avoidance of superior displacement of the pubic
of the SFS had profound implications in post- hair, reduction of tension on the skin flap (in turn
bariatric body contouring surgery. Since the SFS reducing the risk of necrosis and abnormal scar-
provides support to the skin and fat deposits of ring), and reduction of suprapubic scar depres-
the body, lifting procedures of the trunk and sions (due to retraction of the separated SFS)
extremities should utilize the SFS for suspension [14]. A similar concept was applied to breast sur-
and to provide longer-lasting support. Some of gery with the resuspension of the SFS for infra-
these zones can limit the skin excursion and need mammary fold reconstruction instead of
to be released when performing body contouring de-epithelialized dermal flap suspension [15].
surgery to allow skin advancement for excision
Lockwood TE. Superficial fascial system (SFS) of the trunk and extremities: a new concept. Plast Reconstr Surg.
1991;87(6):1009–18
Strengths • Anatomic study conducted on both cadavers and clinical patients, prospective, innovative concept,
and reasoned approach to the development of a new technique
Limitations • Small sample (32 patients), incomplete description of material and methods
Impact Critical advancement in body contouring surgery and its aesthetic outcome. The first study to
highlight the role of the superficial fascial system as a support for skin and subcutaneous tissue in
massive weight loss surgery
34.3 Classification of Contour amount of adipose tissue, and previously

Deformities: The Pittsburgh smooth contours now appear deflated and
Rating Scale wrinkled (Fig. 34.1). These transformations
can take place anywhere on the body and can
Weight loss surgery leads to multiples changes be unpredictable based on the patient. However,
to the body aesthetics. Unexpected folds and the abdomen is cited as the location with the
creases can appear where there used to be large most severe deformities after massive weight
Fig. 34.1 57 year-old female status post massive weight stage included circumferential lower body lift with gluteal
loss who underwent staged body contouring surgery. First flap shaping. Preoperative and 1 year post fist stage photo-
stage included mastopexy and upper body lift; second graphs are shown
loss [6]. Massive weight loss patients can have Moreover, for the first time it provides guidance
a considerable overhanging pannus that dis- on the appropriate surgical interventions for each
rupts the silhouette while having completely level of deformities. Song et al. identified 10
normal-looking buttocks, hips, and legs. Not anatomical areas: arms, breasts, abdomen, flank,
infrequently, you can observe patients who pubis, back, buttocks, medial thighs, hips/lateral
have a pleasing upper body contour including thighs, and lower thighs/knees. For each region of
arms, breasts, and abdomen, but have ptotic the body, a 4-point grading scale (range from 0 to
and pleated buttocks and thighs, with residual 3) was designed to describe the common deformi-
excess adiposity. This varied presentation ties: grade 0 indicates a normal appearance, grade
depends on many factors such as age, gender, 1 indicates a mild deformity, grade 2 indicates
and degree of weight loss. moderate deformity, and grade 3 indicates severe
The plethora of body types and severity makes deformity. The rating scale was customized for
the decision-making challenging. Song et al. from each region of the body to account for the variety
the University of Pittsburgh developed in 2005 of deformities. The best surgical approach was
the Pittsburgh Rating Scale (PRS) to help classify associated to each grade. In general, a deformity
body contouring deformities resulting after mas- considered as mild would require non-excisional
sive weight loss and to guide appropriate surgical or a minimally invasive procedure for correction
treatment [16]. Before publication of the PRS, no (i.e., liposuction). A moderate deformity would
single rating system existed to help with a compre- require an excisional procedure. A severe defor-
hensive assessment of post–bariatric weight loss mity would require combinations of excisional,
patients. The PRS classification system overcame lifting, and noninvasive procedures and would
the drawbacks of prior classification systems that frequently involve large areas of undermining.
limited the description to a single region of the The PRS was validated by the authors after a ret-
body, and lacked a category for more complex rospective analysis of full body photographs of
deformities (such as multiple rolls in the pannus). 300 patients.
The PRS allows the description of preoperative comparing preoperative to postoperative scores.
deformities in a standardized, graded approach The rapid worldwide spread of the PRS as a stan-
and allows the correlation of deformity to sur- dardized method for analysis of massive weight
gical strategy. In addition, this system is useful loss patients is justified by the ease of adminis-
for quantifying the benefit of body contouring tration, appropriateness, validity, reliability, and
surgery in improvement of patient’s appearance, ability to measure the surgical impact on the body.
Song AY, Jean RD, Hurwitz DJ, Fernstrom MH, Scott JA, Rubin JP. A classification of contour deformities after
bariatric weight loss: the Pittsburgh Rating Scale. Plast Reconstr Surg. 2005;116(5):1535–44. discussion 1545–6
Strengths • Well-designed methodology, large sample, well documented, innovative classification, validated
Limitations • Female patients only
Impact This study provided the first standardized assessment tool of the severity of body contouring
deformities after massive weight loss. In addition, appropriate treatment was correlated to each type
of deformity. The Pittsburgh Rating Scale is now adopted worldwide
34.4 Impact of Body Contouring body contouring procedures on quality of life

Procedures to Body Image using a standardized methodology. The authors
and Quality of Life prospectively investigated 18 patients to deter-
mine whether body contouring surgery resulted
As an increasing number of bariatric surgery in a quantifiable difference in self-perception of
patients are successful in losing weight, many are appearance and if surgery changed their body
unfortunately left with contour irregularities and ideals. All included patients underwent the
deformities consisting of loose and ptotic skin abdominal contouring procedure of panniculec-
envelopes and residual localized adipose depos- tomy or cosmetic abdominoplasty. Among the 18
its. In turn this may lead to intertriginous rashes, patients enrolled, 11 patients underwent addi-
hygiene struggles, difficulties with mobility, and tional body contouring procedures, including
emotional distress. Although the relationship lower body lift, breast reduction, and brachio-
between post-bariatric weight loss and improve- plasty. Patients’ self-perception of their current
ment in quality of life had been proven in various appearance significantly improved after body
studies [17, 18], quality of life and psychological contouring procedures and remained stable
impact after body contouring surgery had 6 months postoperatively. The three most fre-
remained largely unexplored before Song et al.’s quent anatomical areas of concern at initial con-
[19] landmark paper. sultation were the abdomen (69%), flanks (56%),
Prior to Song et al.’s paper, research focused and hips/outer thighs (44%). The top three ana-
predominantly on the understanding of the physi- tomical areas of distress 3 months following
ologic effects of bariatric surgery on the body and body contouring were the hips/outer thighs
the successful strategies to tackle morbid obesity. (46%), medial thighs (38%), and flanks (31%).
Body contouring following massive weight loss There was an increase in frequency of arms,
represented an interesting intersection between back, and buttocks being named as areas of dis-
cosmetic and functional surgery, and it was not tress. At 6 months, medial thigh (54%), flanks
originally considered as a key step of the weight (36%), and hips/outer thighs (27%) remained the
loss journey. top three named areas of distress.
Song et al. were pioneers in highlighting the Despite the small sample size, this study was
importance of quality of life in post-bariatric able to demonstrate that body contouring after
patients and to scientifically assess the impact of post-bariatric weight loss improves quality of life
and body image with statistical significance. As deformity that were previously hidden from
expected, body image satisfaction improved in view; for example, after resection of a hanging
areas that underwent a body contouring opera- pannus, the medial thighs become more notice-
tion, but this change also resulted in increased able and a frequently mentioned area of distress.
overall body satisfaction. Interestingly, patients Song et al. were the first group to demonstrate
who underwent body contouring tended to choose the importance of including reconstructive body
a leaner silhouette as their ideal shape, indicating contouring surgery as an essential step in the
a shift in beauty standard towards a thinner sil- multidisciplinary approach and algorithm of the
houette belonging to the general society ideal. surgical treatment of morbid obesity. This was
The authors further demonstrated that treating the first study to investigate quality of life after
one area of distress has the potential to reveal body contouring and it served as a steppingstone
additional areas of dissatisfaction. This could to further research in this topic [20]. Long-term
occur for several reasons. Firstly, contouring one results on self-perception and quality of life after
area of the body may turn the other areas into body contouring procedures in massive weight
relative disproportion, making them more notice- loss patients confirmed improvement in patient’s
able to the patient. Additionally, removing large appearance and enhanced physical, psychologi-
amounts of skin frequently revealed areas of cal, and social health and well-being [21, 22].
Song AY, Rubin JP, Thomas V, Dudas JR, Marra KG, Fernstrom MH. Body image and quality of life in post massive
weight loss body contouring patients. Obesity (Silver Spring). 2006;14(9):1626–36
Strengths • Well-designed, prospective, patient reported outcomes
Limitations • Small sample (18 patients), short follow up (9 months)
Impact This was the first study to demonstrate beneficial effects of body contouring surgery on
postbariatric patients’ quality of life and provided a scientific understanding of the
psychological aspects related to massive weight loss and redundant skin correction
34.5 The Impact of BMI in Patient patients who underwent multiple/concomitant

Selection and Outcomes procedures. As expected, Group II reported sig-
nificantly longer operative time and more com-
The surge in post-bariatric procedures raised sev- plications (any complication, dehiscence, seroma,
eral questions about patient selection, complica- and necrosis) in comparison to Group I. The most
tion rate, and predictive factors of complications. frequently reported complications among both
Small case series and retrospective studies pro- groups were dehiscence (22.4%), seroma
vided some insight, but Coon et al. conducted the (13.1%), cellulitis (7.7%), necrosis (6.8%), and
largest prospective study examining the impact hematoma (4.7%). Both Max BMI and Delta
of BMI as a predictor of postoperative complica- BMI were found to be significantly associated
tions in post-bariatric massive weight loss with the development of any complication, with
patients. [23] The study included 449 prospec- OR of 1.17 and 1.24 respectively. Also, Max BMI
tively enrolled post-bariatric patients represent- and Delta BMI were predictors of wound dehis-
ing 511 separate surgical cases. The authors cence, the most common complication in body
identified Current BMI (BMI at the time of sur- contouring surgery. In addition, Current BMI
gery), Max BMI (maximum BMI prior to weight >35 was not more significantly associated with
loss), and Delta BMI (calculated by subtracting complications than Current BMI <35. However,
Current BMI from Max BMI). The cohort was Current BMI (BMI at the time of surgery) was
divided in two groups: Group I consisted of not associated to the development of complica-
patients who underwent only one procedure (e.g., tions. When Group I and Group II were analyzed
panniculectomy), while Group II consisted of separately, Group I was found to have Max BMI
and Current BMI as predictors for complications, in multiple procedures. In contrast, wound infec-
and Current BMI as predictor for wound dehis- tions were substantially more common in patients
cence; Group II was found to have Delta BMI as with greater Max BMI. This finding is likely
predictor for any complications and the need for related to the fact that deformities in these
a blood transfusion. patients may be more extensive, thereby requir-
With successful weight loss, a patient who ing longer incisions which increases the risk of
starts out with a higher BMI and loses more infection. As confirmed by another landmark
weight is likely to have greater deformities, thus article by Nemerofsky et al. [24], the most fre-
requiring more extensive operations with longer quent complication in this study was wound
incisions, prolonged operative time, and conse- dehiscence, most often on the buttocks of the
quently higher risk of complications. Current body lift patients. Of note, the authors excluded
BMI was a predictor of complications only in active smokers from surgery, requesting cessa-
single-procedure cases, meaning that the impor- tion for 4–6 weeks and using urine nicotine tests
tance of Current BMI decreases as the extent of to verify compliance.
the operation grows. Despite the overall higher This study reliably assessed the risk of com-
risk of complications in Group II compared to plications according to Max BMI, Delta BMI,
Group I, the authors conclude that the overall and BMI at the time of intervention and it repre-
morbidity was still low, suggesting that concur- sents a landmark paper for patients’ selection and
rent procedures can be justified in well selected preparation to body contouring surgery after
patients. massive weight loss. A comprehensive preopera-
The study by Coon et al. suggested that obe- tive evaluation of the patient (general health,
sity increases the risk of different complications change in BMI, and extent of the surgery) is
at varying rates. Hematoma incidence did not essential to ensure patient optimization and a
correlate with a higher BMI or occur more often reduction of complications.
Coon D, Gusenoff JA, Kannan N, El Khoudary SR, Naghshineh N, Rubin JP. Body mass and surgical complications
in the postbariatric reconstructive patient: analysis of 511 cases. Ann Surg. 2009;249(3):397–401
Strengths • Large sample, prospective, well documented
Limitations • No data on smokers
Impact This study is a landmark reference for the assessment of the predictive value of Max BMI, Delta
BMI, and Current BMI on complications rate. It provides reliable incidence estimates for each
complication
34.6 The Body Lift procedure after Lockwood [12], Aly [26], and
Hurwitz’s [27] outstanding contributions. The
The body lift is a major surgical procedure in authors provided insight on the indications, com-
body contouring that incorporates simultaneous plications rates, poor predictors, and patients’
abdominoplasty, thigh, and buttock lift (Fig. 34.2). selection criteria. They classified the patients into
It has also been named as belt lipectomy, lower three types depending on the preoperative BMI:
body lift, and circumferential torsoplasty based type I, less than 28; type II, between 28 and 32;
on the incision pattern, and it was first described and type III, greater than 32. The overall com-
by Mario Gonzolez-Ulloa in 1960 [25]. The fifth plication rate was 50%. The most frequent com-
most cited paper in the post-bariatric massive plication was dehiscence (32.5%), followed by
weight loss body contouring literature is a paper seromas (16.5%), skin necrosis (9.5%), infection
by Nemerofsky et al. [24]. The authors published (3.5%), and hematoma (3%). Deep vein thrombo-
in 2006, a landmark study on 200 body lifts that sis occurred in only 1% of the patients, which lead
further advanced our understanding about this to pulmonary embolism in only 1 case.
Fig. 34.2 49 year old female who is status post massive lower body lift; second stage included mastopexy and
weight loss and underwent staged body contouring sur- upper body lift. Preoperative and 14 months post second
gery. First stage included fleur-de-lis abdominoplasty and stage photographs are shown
Consistently with the paper by Coon et al. [23], Some of the technical contributions of
the authors observed that patients with higher Max Nemerofsky et al.’s body lift paper include descrip-
BMI (body mass index before massive weight tion of the intraoperative patient’s positioning and
loss) had more complications. An individual with draping to allow a shorter operative time and the
a BMI of 70 before massive weight loss had a importance of undermining the gluteal region, in
15-times greater chance of having complications order to achieve optimal traction, tension-free clo-
following a body lift than a patient with a BMI of sure, and satisfactory aesthetic results. Nemerofsky
40. Likewise, patients with larger changes in BMI et al. identified the ideal candidate for a body lift in
before and after massive weight loss had a signifi- those post-bariatric patients who have a more cen-
cantly greater chance of having complications. tral fat distribution or android body habitus and a
BMI at the time of the body lift was not found to BMI less than 35. On the hand, patients with gyne-
have a significant association with complications. coid body habitus are more likely to have excess
Type III patients had a complication rate of 61.7% skin and cellulite along the distal thighs following a
versus 47.7% for type I patients. Type III patients body lift. Indeed, as the contour deformity of the
had more complications than type I and II patients. massive weight loss patient extends farther from the
No difference was observed between type I and II, waistline, the impact of the procedures diminishes.
when the analysis was adjusted for smoking habit. According to the authors, patients with a BMI
Unlike Coon et al. [23], Nemerofsky et al. [24] greater than 35 have a more difficult and protracted
included patients with a history of smoking and recovery, as well as minor benefits from the lifting
they found that smokers had a higher complication procedure because traction from the waistline often
rate of 69.4% versus 45.7% for nonsmokers. has only a minimal effect on skin excess and cellu-
Moreover, smokers had a significantly higher rate lite along the lower buttocks and distal thighs.
of dehiscence and skin necrosis than nonsmokers. This study demonstrates that body lift pro-
When looking at the final cosmetic outcomes, vides excellent aesthetic and functional out-
patient’s BMI at the time of surgery, max BMI, comes. However, due to the high risk of
and age were all associated with worse aesthetic complications, careful patient selection and edu-
outcomes. cation are critical to optimize outcomes.
Nemerofsky RB, Oliak DA, Capella JF. Body lift: an account of 200 consecutive cases in the massive weight loss
patient. Plast Reconstr Surg. 2006;117(2):414–30
Strengths • Detailed description of the technique, large sample
Limitations • Retrospective
Impact This paper provides large data on complications of the body lift in massive weight loss and it
describes a new method for draping and preparation of the patients, which has been widely adopted

Commentary
1. Hales CM, Carroll MD, Fryar CD, Ogden
CL. Prevalence of obesity and severe obesity among
Body contouring has greatly evolved over the
adults: United States, 2017-2018. NCHS Data Brief.
past couple of decades and the above-men- 2020;360:1–8.
tioned studies have significantly impacted 2. Verhoeff K, Mocanu V, Dang J, et al. Effect of the
various aspects of our knowledge on post mas- COVID-19 pandemic on bariatric surgery in North
America: a retrospective analysis of 834,647 patients.
sive weight loss surgery including the patient
Surg Obes Relat Dis. 2022;18(6):803–11.
selection, description of the incidence and 3. Kizy S, Jahansouz C, Downey MC, Hevelone
predictive factors of complications, strategies N, Ikramuddin S, Leslie D. National Trends in
to improve surgical outcomes, and demonstra- Bariatric Surgery 2012–2015: demographics, proce-
dure selection, readmissions, and cost. Obes Surg.
tion of the beneficial effects of body contour-
2017;27(11):2933–9.
ing surgery on post- bariatric patients’ 4. Buer L, Kvalem IL, Bårdstu S, Mala T. Comparing
emotional-health and quality of life. These bariatric surgery patients who desire, have under-
studies proved that body contouring surgery is gone, or have no desire for body contouring surgery:
a 5-year prospective study of body image and mental
a fundamental step in the journey of the mor-
health. Obes Surg. 2022;32(9):2952–9.
bidly obese patient. 5. 2020 Plastic Surgery Statistics Report. Plastic
Despite the widespread diffusion of post mas- Surgery. Published online 2020.
sive weight loss body contouring procedures, the 6. Zammerilla LL, Zou RH, Dong ZM, Winger DG,
Rubin JP, Gusenoff JA. Classifying severity of
greatest part of the available literature is level III
abdominal contour deformities after weight loss to aid
or IV evidence, with only few prospective cohort in patient counseling: a review of 1006 cases. Plast
studies and randomized clinical trials. Improving Reconstr Surg. 2014;134(6):888e–94e.
the level of evidence on this topic is critical to 7. Danilla S, Cuevas P, Aedo S, et al. Introducing
the body-QoL®: a new patient-reported outcome
achieve better predictability of surgical
instrument for measuring body satisfaction-related
outcomes. quality of life in aesthetic and post-bariatric body
Patient reported outcomes have become contouring patients. Aesth Plast Surg. 2016;40(1):
increasingly important in the surgical world and 19–29.
8. Hurwitz DJ, Ayeni O. Body contouring surgery in
various measures have been introduced such as
the massive weight loss patient. Surg Clin North Am.
the BODY-Q [28]. Future research should focus 2016;96(4):875–85.
on the routine implementation of such measures 9. Lockwood TE. Superficial fascial system (SFS) of the
to better guide the decision-making, better under- trunk and extremities: a new concept. Plast Reconstr
Surg. 1991;87(6):1009–18.
stand the weaknesses of the currently available
10. Rohrich RJ, Smith PD, Marcantonio DR, Kenkel
procedures, and stimulate innovation and evolu- JM. The zones of adherence: role in minimizing and
tion of surgical options trying to fulfill the preventing contour deformities in liposuction. Plast
patients’ needs. Reconstr Surg. 2001;107(6):1562–9.
11. Lockwood T. Brachioplasty with superficial fas-
Also, in the field of postbariatric surgery, most
cial system suspension. Plast Reconstr Surg.
of the studies describe a single-center experience. 1995;96(4):912–20.
To improve generalizability, cooperation between 12. Lockwood T. Lower body lift with superficial
institutions is needed to obtain multicenter fascial system suspension. Plast Reconstr Surg
1993;92(6):1112-1122; discussion 1123-1125.
studies.
13. Lockwood TE. Transverse flank-thigh-buttock lift 21. van der Beek ESJ, Geenen R, de Heer FAG, van der
with superficial fascial suspension. Plast Reconstr Molen ABM, van Ramshorst B. Quality of life long-
Surg. 1991;87(6):1019–27. term after body contouring surgery following bariat-
14. Lockwood T. High-lateral-tension abdominoplasty ric surgery: sustained improvement after 7 years. Plast
with superficial fascial system suspension. Plast Reconstr Surg. 2012;130(5):1133–9.
Reconstr Surg. 1995;96(3):603–15. 22. Klassen AF, Cano SJ, Scott A, Johnson J, Pusic
15. Lockwood T. Reduction mammaplasty and masto- AL. Satisfaction and quality-of-life issues in body
pexy with superficial fascial system suspension. Plast contouring surgery patients: a qualitative study. Obes
Reconstr Surg. 1999;103(5):1411–20. Surg. 2012;22(10):1527–34.
16. Song AY, Jean RD, Hurwitz DJ, Fernstrom MH, Scott 23. Coon D, Gusenoff JA, Kannan N, El Khoudary
JA, Rubin JP. A classification of contour deformities SR, Naghshineh N, Rubin JP. Body mass and sur-
after bariatric weight loss: the Pittsburgh rating scale. gical complications in the postbariatric recon-
Plast Reconstr Surg 2005;116(5):1535-1544; discus- structive patient: analysis of 511 cases. Ann Surg.
sion 1545-1546. 2009;249(3):397–401.
17. Kolotkin RL, Crosby RD, Pendleton R, Strong 24. Nemerofsky RB, Oliak DA, Capella JF. Body lift:
M, Gress RE, Adams T. Health-related quality an account of 200 consecutive cases in the mas-
of life in patients seeking gastric bypass surgery sive weight loss patient. Plast Reconstr Surg.
vs non- treatment-seeking controls. Obes Surg. 2006;117(2):414–30.
2003;13(3):371–7. 25. Gonzalez-Ulloa M. Belt lipectomy. Br J Plast Surg.
18. de Zwaan M, Lancaster KL, Mitchell JE, et al. 1960;13:179–86.
Health-related quality of life in morbidly obese 26. Aly AS, Cram AE, Chao M, Pang J, McKeon M. Belt
patients: effect of gastric bypass surgery. Obes Surg. lipectomy for circumferential truncal excess: the
2002;12(6):773–80. University of Iowa experience. Plast Reconstr Surg
19. Song AY, Rubin JP, Thomas V, Dudas JR, Marra 2003;111(1):398-413.
KG, Fernstrom MH. Body image and quality of 27. Hurwitz DJ, Rubin JP, Risin M, Sajjadian A,
life in post massive weight loss body contour- Sereika S. Correcting the saddlebag deformity in
ing patients. Obesity (Silver Spring). 2006;14(9): the massive weight loss patient. Plast Reconstr Surg.
1626–36. 2004;114(5):1313–25.
20. Toma T, Harling L, Athanasiou T, Darzi A, Ashrafian 28. Klassen AF, Cano SJ, Alderman A, et al. The body-Q:
H. Does body contouring after bariatric weight loss a patient-reported outcome instrument for weight loss
enhance quality of life? A systematic review of QOL and body contouring treatments. Plast Reconstr Surg
studies. Obes Surg. 2018;28(10):3333–41. Glob Open. 2016;4(4):e679.
Evolution of Fat Grafting
35
Shawn J. Loder, Roy Kazan, Francesco M. Egro,
and J. Peter Rubin

Fat grafting, now a cornerstone in aesthetic 1. Coleman SR. Long-term survival of fat
and reconstructive surgery, has spurred sig- transplants: controlled demonstrations.
nificant innovation and research. This chapter Aesthetic Plast Surg. 1995;19:421–5.
elucidates the science and technique of fat 2. Rohrich RJ, Sorokin ES, Brown SA. In
grafting, as informed by the five most seminal search of improved fat transfer viability: a
papers in the field. Each work adds distinctive quantitative analysis of the role of centrifu-
insights into adipose tissue physiology, graft- gation and harvest site. Plast Reconstr Surg.
ing techniques, patient outcomes, and 2004;113(1):391–5. discussion 396–7.
enhancement of graft survival. Complemented 3. Khouri RK Jr, Khouri RE, Lujan-Hernandez
by additional vital references, this analysis JR, Khouri KR, Lancerotto L, Orgill DP.
provides an enriched understanding of this Diffusion and perfusion: the keys to fat graft-
prevalent procedure. The goal of this chapter ing. Plast Reconstr Surg Glob Open.
is to offer an incisive and insightful overview 2014;2(9):e220.
of fat grafting, encapsulating its intricacies 4. Gutowski KA, ASPS Fat Graft Task Force.
and potential within contemporary surgical Current applications and safety of autolo-
practice. gous fat grafts: a report of the ASPS fat graft
task force. Plast Reconstr Surg.
Keywords 2009;124:272–80.
5. Bourne DA, Bliley J, James I, Donnenberg
Fat graft · Lipografting · Autologous fat ·
AD, Donnenberg VS, Branstetter BF 4th,
Adipose · Landmark
Haas GL, Radomsky E, Meyer EM, Pfeifer
ME, Brown SA, Marra KG, Coleman S,
Rubin JP. Changing the paradigm of cranio-
facial reconstruction: a prospective clinical
trial of autologous fat transfer for craniofa-
cial deformities. Ann Surg.
S. J. Loder · R. Kazan · F. M. Egro (*) · J. P. Rubin 2021;273(5):1004–11.
Department of Plastic Surgery, University of
Pittsburgh, Pittsburgh, PA, USA
https://doi.org/10.1007/978-3-031-57132-9_35
364 S. J. Loder et al.
35.1 Introduction technique resulted in rapid distribution and

inclusion of fat grafting as an accepted tool
The introduction of autologous fat grafting to within the aesthetic and reconstructive surgeons’
modern aesthetic and reconstructive surgery has armamentarium [13–16].
been a paradigm shift in management and correc- Now, data from the American Society of
tion of soft tissue deficits. Thanks to its adapt- Plastic Surgeons reveal that an impressive 63,013
ability, wide applicability, efficacy, and procedures were conducted in the United States
availability, fat graft is now ubiquitous across the alone in 2022, testifying to the technique’s bur-
field of plastic surgery and has been rapidly geoning acceptance among patients [17]. The
adopted across the breadth of surgical care. Until appeal of utilizing one’s own body fat as a natural
recently, however, adipose autotransplantation alternative to synthetic implants or fillers ampli-
has developed slowly with scattered descriptions fies the procedure’s popularity. Subsequent to the
as far back as 1889 with Dr. Van der Meulen’s procedure, approximately 70% of patients
attempted used of free omental fat to treat dia- reported enhanced satisfaction with their physi-
phragmatic hernia [1–3]. Similar attempts were cal appearance, and a remarkable 75% noted
made by contemporaries including Dr. Czery improvements in their daily lives due to elevated
who attempted reconstruction of surgical breast confidence and self-esteem. The success of fat
defect with autologous lipoma and Dr. Neuber grafting is attributable to its advantageous char-
who attempted lipofilling of a depressed facial acteristics such as availability, biocompatibility,
scar with adipose of the forearm [4–6]. While cost-effectiveness, and minimal donor site mor-
early results were variable, their efforts let the bidity. Despite its proliferating application and
development of en bloc and dermal fat grafts trends, a universally accepted practice methodol-
which are still utilized today. Use of a lipocan- ogy, encompassing harvest, processing, and
nula for adipose harvest and collection was first injection remains elusive. This can be ascribed to
proposed by Dr. Brunning in 1911 and was uti- an extensive body of literature which has not
lized with variable success throughout the decidedly favored one approach over another.
1910s–1970s [1, 2, 7]. The work of Dr. Peer Consequently, the field of fat grafting and
regarding the resorption rates and volume loss research into adipose autograft continues to
with fat grafts at that time described as high as expand. In this chapter, we perform a compre-
50% resorption of tissue within a year—ulti- hensive exploration into the science and applica-
mately limiting the general interest in the tech- tion of fat grafting is conducted, showcasing a
nique [8]. critical analysis of the five most influential papers
In the 1970s, a series of major advances set in the field.
the stage for the modern boom in popularity of
adipose allograft. First, liposuction via blunt
cannula as it is currently described by Dr. Arbad 35.2 Coleman’s Long-Term Fat
and Giorgio Fischer was developed in 1975 and Graft Survival Study
then subsequently refined by Drs. Illouz and
Toledo [9–12]. Second, the development and It would be challenging to identify a surgeon–sci-
success of lipofilling by Drs. Fournier, Bircoll entist more associated with modern fat grafting
and Coleman demonstrated that predictable than Dr. Sydney Coleman and a list of the most
results could be achieved and in 1995, the publi- influential studies in the field of fat grafting could
cation of Dr. Sydney Coleman’s eponymous easily be dominated by his works [16, 18–23].
35 Evolution of Fat Grafting 365
Here we turn to his seminal paper on the longev- cance of appropriate surgical techniques to main-
ity and success rate of autologous fat tissue trans- tain graft longevity.
plants for correcting nasolabial folds [16]. Dr. Furthermore, Coleman suggested that inade-
Coleman’s key innovation stems from the devel- quate initial correction primarily leads to long-
opment of his eponymous technique in 1986, term failure. Thus, he preferred multiple surgeries
aimed at safeguarding fragile adipose from for deeper nasolabial folds rather than risking
potential hazards and contamination, such as air overcorrection in a single operation. This
exposure and barotrauma. This practice builds approach aligns with earlier studies by
upon earlier studies advocating for careful han- Ellenbogen, suggesting that overfilled grafts may
dling of adipose tissue during transplantation, compromise their survival [26]. Consequently,
like Peer’s work in 1956, which suggested that Coleman’s work contributed to the system of
graft survival depends on delicate fat manipula- structural fat grafting, involving precise, low-
tion [8, 24]. Coleman’s fat grafting approach pressure injection of small fat aliquots into differ-
involves three steps: harvesting, processing, and ent tissue planes [16, 18–23]. This technique
re-injecting the adipose tissue [18]. He empha- replaced the traditional method of larger-volume
sizes the gentle handling of fat to maintain adipo- fat injection, which often yielded unpredictable
cyte viability and minimizes exposure to and less durable results due to inconsistent
atmospheric air and pressure changes, protecting resorption. The ability to deposit small quantities
the fat graft, which aligns with Peer’s 1956 study, of fat with greater precision improved control
but Coleman’s methodology offers further refine- over shape and volume, resulting in more predict-
ment [16, 24]. able and aesthetically pleasing outcomes.
To evaluate the procedure’s effectiveness, While Dr. Coleman’s technique for autologous
Coleman’s study employed a 6 year photographic fat tissue transplantation offered a promising
comparison method. Illouz also proposed a simi- solution for long-term correction of nasolabial
lar technique in 1988, advocating for systematic folds, its potential was best demonstrated in the
photographic documentation to assess graft lon- proof-of-concept of successful fat grafting and the
gevity [25]. Interestingly, Coleman used an eponymous technique. This work reaffirmed the
untreated crease as a control in his study, provid- need for rigorous adherence to the transplantation
ing an innovative methodology for direct com- technique to achieve successful results, enhancing
parison and control over individual variability predictability and durability, a concept under-
[16]. Over the 6 year duration, no signs of re- scored in previous and ultimately helped establish
absorption or recurrence were observed in the fat grafting as a reliable and lasting procedure for
treated fold, indicating the technique’s potential soft tissue augmentation and facial rejuvenation,
for long-term correction. This finding concurs increasing acceptance of autologous fat transplan-
with earlier research emphasizing the signifi- tation in plastic and aesthetic surgery [27].
Coleman SR. Long-term survival of fat transplants: controlled demonstrations. Aesthetic Plast Surg. 1995;19:
421–5
Strengths • Early standardization of fat grafting technique.
• Application of long-term outcomes in a controlled environment.
• Discussion of how to safely and effectively apply autologous fat to a challenging recipient site to
minimize resorption and redistribution of tissue
Limitations • Case series of two patients.
• Outcome metrics limited to photographic evaluation
Impact This seminal paper by Sydney R. Coleman is often credited as the first to describe the process of
structural fat grafting. Coleman found that with the proper extraction, processing, and injection
methods, transplanted fat could survive long-term in a new location. This study opened the door for
surgeons to view adipose tissue as a valuable tool for reconstructive and cosmetic surgery
35.3 Impact of Centrifugation and cess, a commonly used technique for processing
Harvest Site on Fat Graft fat grafts [31]. Their methodology involved com-
Viability prehensive quantitative analysis using a colori-
metric assay of cell proliferation, comparing
Minimizing resorption, and consequently graft adipocytes harvested from usual liposuction sites
loss, is in part dependent on the viability of the such as the abdomen, thigh, flank, and knee. The
transferred adipocytes, which in turn is influenced findings revealed that neither the donor site nor
by the process through which the adipose tissue is the centrifugation process significantly affected
harvested, processed, and transplanted. Processing the viability of fat cells. No matter if the samples
is seen as a critical and involves both the removal were obtained and untreated or harvested and
of unwanted components, such as blood, oil, and centrifuged, the adipocyte viability remained sta-
local anesthetic, which could impair the survival tistically indistinguishable, regardless of whether
of the grafted adipose tissue [28], and the concen- the fat was derived from the abdomen, thigh,
tration of desired cellular and structural element flank, or knee.
within the lipoaspirate. Several techniques are uti- Ultimately their results had significant impli-
lized including decanting [29], centrifugation cations for clinical practice, suggesting that fat
[27], Telfa rolling [30], and filtration [31]. Being tissue transfers from these common donor sites
derived from the original Coleman technique, could be treated as equivalent in terms of viabil-
centrifugation is one of the more popular and ity. Also, it seemed that centrifugation, a popular
widespread of the options; however, optimal char- method for cleaning fat, doesn’t confer any
acteristics were not immediately available. The immediate viability advantage to the fat tissue
2004 study “In Search of Improved Fat Transfer before implantation [27].
Viability: A Quantitative Analysis of the Role of Regrettably, a consensus has yet to be
Centrifugation and Harvest Site” by Rohrich, reached regarding the optimal technique for
Sorokin, and Brown sought to fill that void and any of the essential steps in fat transfer and the
give new insights into the unpredictable nature of authors rightfully underscored the necessity
fat grafting. They examined the effect of the donor for more research, particularly involving
site and centrifugation process on the longevity of in vivo animal models to further explore long-
fat grafts, a critical aspect considering the high term cell viability. They also highlighted the
reported resorption rates, which can vary from 20 need for examining other factors that might
to 90% [27]. affect cell growth or differentiation among
The resorption process of implanted fat grafts subjects, such as smoking, nutritional status,
is a complex process, which further complicates and drug use. Lastly, the study underscored the
the task. Therefore, the main goal of the study need for ongoing research into identifying the
was to discover a specific group of adipocytes optimal technique for fat cleaning, opening
that could inherently possess greater resilience, doors for considering other methods like
thereby enhancing the viability of fat grafts. The decanting or even exploring newer, innovative
research also scrutinized the centrifugation pro- techniques.
Rohrich RJ, Sorokin ES, Brown SA. In search of improved fat transfer viability: a quantitative analysis of the role of
centrifugation and harvest site. Plast Reconstr Surg. 2004;113(1):391–5. discussion 396–7
Strengths • First in kind study comparing adipocytes from distinct anatomic sites alongside the role of
centrifugation in fat cell survival
Limitations • Limited to evaluation of five patients
• No evaluation of long-term outcomes
Impact This paper examined factors affecting fat graft viability. While the authors were not able to identify
differences in viability based on the site of harvest or processing method this work set a framework
and metrics by which future studies could better evaluate success rate of fat grafting and optimize
technique moving forward
35.4 Keys to Fat Graft Success: gen being unable to meet the metabolic demands
Diffusion and Perfusion of the tissue [35]. Additionally, when the distance
from the oxygen source doubles, the diffusion
In similar vein to the above work by Dr. Rohrich rate of oxygen is reduced by a factor of 4 [36].
regarding the importance of fat graft harvest and According to the Microribbon Model, the max-
processing to graft survival, many have pursued a imum radius of a fat graft that can exist without a
better understanding of the key steps involved in necrotic (dead tissue) zone is 0.16 cm. Beyond this
placement of the adipose autograft. This is of radius, the necrotic zone increases rapidly [32, 36,
particular interest for progressively larger fat 37]. This model is supported by experimental data
graft volumes (small-volume (<100 mL, face, and the findings from several other studies.
hands, superficial sites), large-volume Another determinant of fat graft survival men-
(100–200 mL, for breast and body contouring), tioned in the study is the capability of nearby cap-
and mega-volume (>300 mL, breast and buttock illaries to supply oxygen-rich blood to the graft.
augmentation)). As volumes grew beyond what Overstuffing a small recipient site could lead to a
was originally recommended in the Coleman rise in interstitial fluid pressure (IFP), resulting in
technique, a greater understanding of fat survival capillary constriction and causing ischemia in the
in the recipient site became necessary. Khouri grafted tissues [32, 36, 37]. The paper also delves
et al. (2014) explored this in a combination litera- into the concept of pre-expanding the recipient site
ture review and study highlighting the depen- for fat grafting with a device like the BRAVA,
dency of oxygen supply on graft survival [32]. A which is a suction-based external volume expan-
key theory discussed is that the concentration of sion (EVE) device [38]. If the volume of the fat to
oxygen at any given point within the graft be grafted is significantly larger than the recipient
depends on factors including the concentration of site, pre-expansion could prevent overcrowding,
oxygen in the adjacent capillaries, the diffusion graft coalescence, increased IFP, reduced perfu-
rate of oxygen, the distance from the source of sion and oxygen delivery, and substantial volume
oxygen, and the metabolic rate of cells within the loss [39]. The utilization of a device like the
graft [33]. The metabolic rate of a particular por- BRAVA also augments the vascular density and
tion of adipose tissue (AT) has been shown to be diameter at the recipient site, hastening graft
directly proportional to its volume (V), and the revascularization, which plays a crucial role in
diffusion rate of a substance such as oxygen is volume retention [38].
directly related to the surface area (SA) through In conclusion, the study emphasizes the sig-
which it diffuses [34]. As the radius of a cylindri- nificance of factors such as oxygen delivery, graft
cal injection of AT enlarges, the SA:V ratio size, and recipient site pre-expansion for the lon-
diminishes, leading to the diffusion rate of oxy- gevity of fat grafts. It further provides new mod-
els for understanding and optimizing these stage for successful large and mega-volume fat
variables to enhance graft survival and long-term grafts expanding the safe use of adipose into a
results [32]. These results have helped to set the wider range of aesthetic and reconstructive areas.
Khouri RK Jr, Khouri RE, Lujan-Hernandez JR, Khouri KR, Lancerotto L, Orgill DP. Diffusion and perfusion: the
keys to fat grafting. Plast Reconstr Surg Glob Open. 2014;2(9):e220
Strengths • Consolidated a theoretical framework for how fat survives in vivo tying together prior work
regarding the success and failure of fat grafting by site, volume, and technique
Limitations • This was primarily a review at time of publication with the proposal of several models for the
survival of transplanted adipose
• Experimental data utilizing these models not presented in this initial manuscript
Impact This paper emphasized the importance of diffusion and perfusion in the success of fat grafting. The
authors proposed a ‘mega-volume’ fat grafting technique that optimizes the ratio of grafted fat to
recipient site volume, allowing for better perfusion. It also introduces the concept of pre-expansion of
the recipient site to improve graft take
by high-quality studies received grade A or B,

35.5 ASPS Task Force on Fat Graft while those with low or inconsistent evidence
Safety and Applications were given grade C or D. Summarized their rec-
ommendations included an expectation of satis-
As critical as the survival of the fat graft is, of factory results for breast augmentation and
equal or greater importance is the safety of the correction of defects with no recommendation/
process itself. And while the safety of modern fat need for further research in the areas of gluteal,
grafting is now well-documented, there continues facial, and lip augmentation, penis enlargement,
to be ongoing scrutiny across three main dimen- and hand rejuvenation. No specific outcome of
sions: surgical, biological, and oncologic safety. harvest technique or site, graft preparation,
Evaluation of these domains was the goal of the injection technique or site was favored, however,
American Society of Plastic Surgeons (ASPS) Fat recommendations to minimize exposure to air,
Graft Task Force in their 2009 report [40]. In their minimize time from harvest to delivery, and
report they sought to systematically identify and minimize mechanical damage were recom-
assess available literature on autologous fat graft- mended. The summary of risks and complica-
ing (PubMed, Cochrane) using a comprehensive tions including infection, bleeding, and
list of terms related to autologous fat grafting. interference with breast cancer detection favored
After initial search and exclusion of articles by rel- fat as a relatively safe method of augmentation
evance they were left with 110 articles within this with lower risks than other types of surgery.
review which included clinical trials, randomized Those with high-risk, including patients at ele-
controlled trials, systematic reviews, case series, vated risk for breast cancer were to be consid-
and reports. All articles were categorized by study ered with caution and baseline mammography
type and critically assessed for their quality, with was recommended. Ultimately, the field was
each being assigned a level of evidence as per the determined to be in need of further research and
ASPS Evidence Rating Scales [41]. recommendations were made regarding in vitro
Based on this critical appraisal, clinical prac- and animal studies indicate potential efficacy of
tice recommendations were developed. These techniques like co-injection additives, pretreat-
were formed through a consensus of the ment of graft site, and cell-culture techniques,
American Society of Plastic Surgeons Fat Graft which could impact future methods of autolo-
Task Force. Recommendations were based on gous fat grafting.
the strength of the supporting evidence and were These conclusions reflect the uncertainty
graded accordingly. Recommendations backed regarding the clinical use of fat grafts based on
the literature of the time. The task force acknowl- coverage and reimbursement. The task force rec-
edged the many potential applications and the ognizes autologous fat grafting as a promising
general safety of the approach, however, noted area for research, but the existing literature is pre-
that lack of standardized techniques for graft har- dominantly composed of case studies and lacks
vesting, preparation, and injection may lead to robust clinical trials. Therefore, it put forth a call
variable outcomes. Importantly, there appears to for more research in the form of high-quality
be an absence of evidence pointing towards an clinical studies to validate current methods or
increased risk of malignancy with fat grafting to innovate new ones. The ultimate influence of
the breast. these recommendations continues to evolve as
Ultimately, these recommendations helped to clinical and research interest in fat grafting has
set the stage for current clinical indications for fat expanded since the guidelines’ issuance.
grafting affecting not only physician use but also
Gutowski KA, ASPS Fat Graft Task Force. Current applications and safety of autologous fat grafts: a report of the
ASPS fat graft task force. Plast Reconstr Surg. 2009;124:272–80.
Strengths • Critical and formulaic review of the available evidence around autologous fat grafting safety
• Provided clear clinical recommendations for safe practice where available and highlighted areas
lacking in data where further study was needed
Limitations • No new data explored in this manuscript
• At time of recommendations secondary to a lack of strong data the task force was limited in its
ability to make specific recommendations for the clinical use of fat grafts
Impact This paper provided a comprehensive review of the applications and safety of fat grafting at the
time. The authors concluded that fat grafting was a safe and valuable tool for reconstructive and
cosmetic surgery. They also emphasized the importance of surgeon training, patient education, and
ongoing research in the field
35.6 Prospective Trial on Fat of fat grafting resorted positive outcomes and high
Grafting for Craniofacial patient satisfaction, the early data on retention was
Reconstruction unpredictable and is worsened when grafts are
placed in scarred and fibrotic tissue beds as might
While Dr. Coleman’s technique certainly opened up be found in these defects. At that time fat grafting
the opportunity for fat grafting for use in aesthetic lacked specific data on volume retention, cellular
recontouring, more work remained necessary for its characteristics, and validated quality of life metrics
utilization in reconstruction of hostile and highly limited advancement of the field [47]. These limita-
aesthetic areas post-trauma. As described above, tions were particularly apparent in specialized areas
modern fat grafting is defined by its retention and of fat grafting and bridging this gap was the goal of
long-term graft survival is paramount to ensuring Bourne et al. (2021) in the application of autolo-
stable and replicable results. While fat grafting pos- gous fat to reconstruction of craniofacial deformi-
sesses several elements of an ideal soft-tissue filler ties [48].
for reconstruction [41], its early descriptions Their team conducted a prospective cohort
focused on aesthetic and congenital deformities study assessing the safety and efficacy of autolo-
[42–46]. Trauma, particularly in highly aesthetic gous fat transfer for treatment of post-traumatic
areas such as craniofacial trauma, has more typi- and postsurgical craniofacial deformities. These
cally involved prosthetic, microsurgical, or com- post-traumatic defects represent a challenging
plex flap reconstruction. Further, while early reports niche for reconstruction with autologous fat trans-
fer given the presence of fibrotic scar tissue, poor Ultimately, patients reported increased satisfac-
soft-tissue compliance, and deficient microvascu- tion with physical appearance and perceived
lature. Bourne et al. demonstrated that these impact on others from baseline to 9 months. The
defects could reliably be treated with autologous authors additionally used this opportunity to cor-
fat in a manner both safe and effective. They dem- relate the cellular and patient characteristics to
onstrated an average retention rate of 63% at better understand predictors or retention. They
9-months within the described range at the time of noted that SVF viability and smoking cessation at
25–80% across all recipient sites. Importantly, least 1 month prior to surgery were predictive of
they found that 3-month retention was predictive higher graft retention. Interestingly, and counter
of long-term results which allowed for improved to their hypothesis at the time, the mean retention
planning and shortened time to regrafting as nec- rate of second-stage grafting was similar to initial
essary. These data inform the clinical conversa- engraftment when compared internally to the
tion both the in pre- and post-operative period as a same individual. Differences between individuals
physician could reliably council patients to expect in terms of retention, however, were significant,
an average resorption rate around 37% and to plan suggestive of inherent differences in host factors
accordingly either for repeat procedures or for such that the results of first engraftment may be
overfilling at time of initial engraftment. able to predict results of future grafting.
Bourne DA, Bliley J, James I, Donnenberg AD, Donnenberg VS, Branstetter BF 4th, Haas GL, Radomsky E, Meyer
EM, Pfeifer ME, Brown SA, Marra KG, Coleman S, Rubin JP. Changing the paradigm of craniofacial
reconstruction: a prospective clinical trial of autologous fat transfer for craniofacial deformities. Ann Surg.
2021;273(5):1004–11
Strengths • Prospective cohort study on safety and efficacy of autologous fat in difficult to reconstruct defects
• Demonstrated clinical success in treating these defects with long-term follow-up
• Identified success factors for both initial and repeat grafting
Limitations • Aggregate of post-surgical and post-trauma patients
• Limited cohort of 20 patients for initial treatment, only 5/20 patients proceeded to second stage
treatment
Impact Ultimately, these results have had significant implication for clinical practice and serve as a bridge
for the transition from fat grafting for aesthetic and congenital reconstruction of the face towards
reconstruction of complex and hostile craniofacial defects. Given the challenges inherent to
reconstruction of these defects, having a simple, reliable alternative to complex microsurgical and
staged reconstruction
35.7 Expert Concluding These papers detail the progressive refine-

Commentary ment in method, technology, and used in fat
grafting. Rohrich and colleagues enhanced our
The field of fat grafting in plastic surgery has understanding of the process, setting out a stan-
undergone significant evolution, both in under- dard framework with which to evaluate the role
standing and in application. From the renaissance of graft viability during harvest and processing.
of structural fat graft survival attributed to the Khouri et al. further expanded this understand-
Coleman technique, the field has expanded expo- ing by emphasizing the importance of diffusion
nentially to recognize not only the inherent value and perfusion for graft survival, proposing a
of adipose tissue as a grafting medium, but also “mega-volume” grafting approach and introduc-
as a rich source of multipotent stem cells with ing the concept of pre-expansion to increase
vast potential in regenerative medicine. graft take.
The work of the ASPS Fat Graft Task Force 11. Fischer A, Fischer G. First surgical treatment for
molding body’s cellulite with three 5 mm incisions.
has served to consolidate the field’s understand- Bull Int Acad Cosmet Surg. 1976;3:35.
ing of fat grafting and its safety, establishing it as 12. Illouz YG. Une nouvelle technique pour less lipodys-
a widely accepted and integral part of plastic and trophies localizes. La Revue de Chirurgie Esthetique
reconstructive surgery. Bourne et al. have de Langue Francaise. 1980;6:19–23.
13. Egro FM, Roy E, Rubin JP, Coleman SR. Evolution of
expanded this horizon even further, illuminating the Coleman Technique. Plastic Reconstruct Surgery.
the potential of fat grafting for the reconstruction 2022;150(2):329e–36e.
of traditionally challenging defects such as the 14. Fournier PF. Fat grafting: my technique. Dermatologic
scarred face where fat can be successfully used as Surg. 2000;26(12):1117–28.
15. Bircoll M. Autologous fat transplantation. Plast
a powerful alternative to more complex recon- Reconstr Surg. 1987;79(3):492–3.
structive options. 16. Coleman SR. Long-term survival of fat trans-
In conclusion, these cumulative contributions plants: controlled demonstrations. Aesth Plast Surg.
represent major milestones in the journey of fat 1995;19(5):421–5.
17. American Society of Plastic Surgeons (ASPS). Plastic
grafting in plastic surgery. They have not only surgery statistics report. Arlington Heights, IL: ASPS;
honed the technical aspects and safety of this pro- 2023.
cedure but also vastly expanded its potential appli- 18. Coleman SR. Facial recontouring with lipostructure.
cations. Today, fat grafting represents a crossroads Clin Plast Surg. 1997;24:347–67.
19. Coleman SR. Structural fat grafts: the ideal filler?
of surgical reconstruction, aesthetic refinement, Clin Plast Surg. 2001;28:111–9.
and regenerative medicine. Yet, as these papers 20. Coleman SR. Hand rejuvenation with structural fat
suggest, this field remains dynamic, with ample grafting. Plast Reconstr Surg. 2002;110:1731–44;
room for future research and innovation. discussion 1745–1747.
21. Coleman SR. Structural fat grafting: more than a
permanent filler. Plast Reconstr Surg. 2006;118(3
Suppl):108S–20S.
References 22. Coleman SR. Facial augmentation with structural fat
grafting. Clin Plast Surg. 2006;28:111–9.
1. Billings E Jr, May JW Jr. Historical review and pres- 23. Coleman SR, Saboeiro AP. Fat grafting to the breast
ent status of free fat graft autotransplantation in plas- revisited: safety and efficacy. Plast Reconstr Surg.
tic and reconstructive surgery. Plast Reconstr Surg. 2007;119:775–85; discussion 786–787.
1989;83(2):368–81. 24. Peer LA. The neglected free fat graft, its behavior and
2. Bellini E, Grieco MP, Raposio E. The science behind clinical use. Am J Surg. 1956;92(1):40–7.
autologous fat grafting. Ann Med Surg (Lond). 25. Illouz YG. Present results of fat injection. Aesth Plast
2017;24:65–73. Surg. 1988;12(3):175–81.
3. Van der Meulen. Considérations générales sur les 26. Ellenbogen R. Free autogenous pearl fat grafts in the
greffes graisseuses et séro-graisseuses épiplöiques et face—a preliminary report of a rediscovered tech-
leurs principals applications [these medicine]. Paris; nique. Ann Plast Surg. 1986;16(3):179–94.
1919. 27. Rohrich RJ, Sorokin ES, Brown SA. In search of
4. Champaneria MC, Wong WW, Hill ME, Gupta improved fat transfer viability: a quantitative analy-
SC. The evolution of breast reconstruction: a histori- sis of the role of centrifugation and harvest site. Plast
cal perspective. World J Surg. 2012;36(4):730–42. Reconstr Surg. 2004;113(1):391–5; discussion 396–7.
5. Czerny V. Plastischer ersatz der brustdruse durch ein 28. Pu LLQ, Coleman SR, Cui X, Ferguson REH Jr,
lipom. Zentralbl Chir. 1895;27:72. Vasconez HC. Autologous fat grafts harvested and
6. Neuber GA. Fett transplantation. Verl Dtsch Ges Chir. refined by the Coleman technique: a comparative
1893;22:66. study. Plast Reconstr Surg. 2008;122(3):932–7.
7. Brunning P. Contribution à l’étude des greffes adipeu- 29. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz
ses. Bull Mem Acad R Med Belg. 1919;28:440. AJ, Benhaim P, Lorenz HP, Hedrick MH. Multilineage
8. Peer LA. Loss of weight and volume in human fat cells from human adipose tissue: implications for cell-
graft, with postulation of a “cell survival theory”. based therapies. Tissue Eng. 2001;7(2):211–28.
Plast Reconstr Surg. 1950;5:217. 30. Smith P, Adams WP Jr, Lipschitz AH, Chau B,
9. O’Toole JP, Song A, Rubin JP. The history of body Sorokin E, Rohrich RJ, Brown SA. Autologous
contouring surgery. Semin Plast Surg. 2006;20(1):5–8. human fat grafting: effect of harvesting and prepa-
10. Flynn TC, Coleman WP 2nd, Field LM, Klein JA, ration techniques on adipocyte graft survival. Plast
Hanke CW. History of liposuction. Dermatologic Reconstr Surg. 2006;117(6):1836–44.
Surg. 2000;26:515–20. 31. Gir P, Brown SA, Oni G, Kashefi N, Mojallal A,
Rohrich RJ. Fat grafting: evidence-based review on
autologous fat harvesting, processing, reinjection, and report of the ASPS fat graft task force. Plast Reconstr
storage. Plast Reconstr Surg. 2012;130(1):249–58. Surg. 2009;124(1):272–80.
32. Khouri RK, Smit JM, Cardoso E, Pallua N, Lantieri 41. American Society of Plastic Surgeons (ASPS).
L, Mathijssen IM, Khouri R, Rigotti G. Percutaneous Evidence rating scales. 2007. https://www.plas-
aponeurotomy and lipofilling: a regenerative alter- ticsurgery.org/Documents/medical-professionals/
native to flap reconstruction? Plast Reconstr Surg. health-policy/e.
2014;134(5):668–79. 42. Bucky LP, Percec I. The science of autologous fat graft-
33. Eto H, Kato H, Suga H, Aoi N, Doi K, Kuno S, ing: views on current and future approaches to neoadi-
Yoshimura K. The fate of adipocytes after nonvas- pogenesis. Aesthet Surg J. 2008;28(3):313–321; quiz
cularized fat grafting: evidence of early death and 322–4.
replacement of adipocytes. Plast Reconstr Surg. 43. Gupta V, Winocour J, Shi H, Shack RB, Grotting
2012;129(5):1081–92. JC, Higdon KK. Autologous fat grafting: a system-
34. Pires Fraga MF, Nishio RT, Ishikawa RS, Perin LF, atic review of patient satisfaction. Aesthet Surg J.
Helene A Jr, Malheiros CA. Increased survival of free 2023;43(3):349–57.
fat grafts with platelet-rich plasma in rabbits. J Plast 44. Ramos R, Silva JD, Di Martino M, Lago J, Correia
Reconstr Aesthet Surg. 2010;63(12):e818–22. A. Autologous fat grafting for facial rejuvenation: a
35. Butler CE, Yannas IV, Compton CC, Correia CA, systematic review. Aesthet Surg J. 2023;43(1):77–91.
Orgill DP. Comparison of cultured and uncultured 45. Johnson M, Summers SH. A systematic review
keratinocytes seeded into a collagen-GAG matrix for of the safety and efficacy of autologous fat graft-
skin replacements. Br J Plast Surg. 1998;51(1):39–44. ing in facial reconstructive surgery. Ann Plast Surg.
36. Khouri RK, Rigotti G, Cardoso E, Khouri RK, 2022;89(2):185–9.
Biggs TM. Megavolume autologous fat transfer: 46. Lee J, Kim S, Choi TH, Kim HY, Kim SH. Patient
part II. Practice and techniques. Plast Reconstr Surg. satisfaction and clinical outcomes following fat graft-
2014;133(6):1369–77. ing for facial rejuvenation. Arch Aesthet Plast Surg.
37. Chang Q, Li J, Dong Z, Liu L, Lu F. Survival of fat 2022;28(1):1–7.
grafts after grafting with different volumes and its 47. Herold C, Ueberreiter K, Busche MN, Vogt
effect on the overlying skin in a murine model. Aesth PM. Autologous fat transplantation: volumetric
Plast Surg. 2017;41(5):1098–106. tools for estimation of volume survival. A systematic
38. Khouri RK, Rigotti G, Marchi A, Cardoso E, review. Aesthet Plast Surg. 2023;41(1):134–43.
Rotemberg SC, Khouri RK. Tissue-engineered breast 48. Bourne DA, Bliley J, James I, Donnenberg AD,
reconstruction with Brava-assisted fat grafting: a Donnenberg VS, Branstetter BF 4th, Haas GL,
7-year, 488-patient, multicenter experience. Plast Radomsky E, Meyer EM, Pfeifer ME, Brown SA,
Reconstr Surg. 2015;135(3):643–58. Marra KG, Coleman S, Rubin JP. Changing the para-
39. Del Vecchio D, Rohrich RJ. A classification of clini- digm of craniofacial reconstruction: a prospective
cal fat grafting: different problems, different solu- clinical trial of autologous fat transfer for craniofacial
tions. Plast Reconstr Surg. 2012;130(3):511–22. deformities. Ann Surg. 2021;273(5):1004–11.
40. Gutowski KA, Fat Graft Task ASPS, Force. Current
applications and safety of autologous fat grafts: a
Evolution of Body Contouring
Surgery
36
Alfredo Hoyos and Mauricio Perez
Abstract Keywords
The history of liposuction can be traced back High definition lipo · Liposculpture · Body
to the early twentieth century, with several key contouring · Research · Fat grafting
developments along the way. In fact, body
contouring surgery has emerged as the top
aesthetic procedure in most countries world- The Five Most Impactful Papers
wide, surpassing even breast surgeries. 1. Illouz YG. Body contouring by lipolysis: a
Techniques have evolved, ranging from sim- 5-year experience with over 3000 cases.
ple adipose tissue removal (also known as Plast Reconstr Surg. 1983;72(5):591–7.
liposuction) to body sculpting (liposculpture), 2. Rao RB, Ely SF, Hoffman RS. Deaths related
and to the current standard of care: High to liposuction. N Engl J Med.
Definition Lipoplasty (HDL), which involves 1999;340(19):1471–5.
fat grafting and 360° liposculpture as the cor- 3. Grazer FM, Goldwyn RM. Abdominoplasty
nerstones for body contouring surgery. assessed by survey, with emphasis on com-
Research in liposuction in the 1980s was pri- plications. Plast Reconstr Surg.
marily focused on describing techniques and 1977;59(4):513–7.
assessing their reliability. After its evident 4. González-Ortiz M, Robles-Cervantes JA,
success, the evolution of surgical techniques Cárdenas-Camarena L, Bustos-Saldaña R,
and technologies in the field of aesthetic lipo- Martínez-Abundis E. The effects of surgi-
plasty has led to the investigation of safer and cally removing subcutaneous fat on the met-
more effective ways to address unwanted body abolic profile and insulin sensitivity in obese
fat and improve an individual’s appearance. In women after large-volume liposuction treat-
this chapter, we will provide our expert ment. Horm Metab Res. 2002;34(8):446–9.
insights and engage in a brief discussion about 5. Klein JA. Tumescent technique for regional
the most remarkable papers in body contour- anesthesia permits lidocaine doses of 35 mg/
ing surgery. kg for liposuction. J Dermatol Surg Oncol.
1990;16(3):248–63.
A. Hoyos (*)
Dhara Clinic, Bogota, Colombia
M. Perez
Total Definer, Rochester, MN, USA
https://doi.org/10.1007/978-3-031-57132-9_36
374 A. Hoyos and M. Perez
36.1 Background which refinements can be done. Nowadays, most

research centers/teams devote their resources and
Beauty is a complex but at the same time intan- efforts to design different processes to improve
gible concept that could be considered as an safety and decrease the likelihood of complica-
appreciation of a certain beholder, based on expe- tions, even those described as minor. As of today,
riences of reward and satisfaction throughout liposuction remains as the number 1 aesthetic
their life. Almost 2 million years have passed by procedure worldwide, with about 491,000 proce-
since the conception of a human being on earth, dures performed in 2021. In effect, safety and
yet behavior, costumes, preferences, beliefs, and efficacy remain consolidated as top priority
many other rational perceptions have changed in among most plastic surgeons [7–13].
the recent decades more than ever before [1, 2]. High-Definition Liposuction (HDL) has
Such drastic shifts within population may be due emerged as the standard of care for patients who
to easy access to information and current overlap seek aesthetic improvement of their body con-
between cultures in social media, almost- tour [14–18]. Since the first description of the
immediate spreading of information, migration technique, authors worldwide have adopted
opportunities and of course, influencers. The era artistic, aesthetic, and safety premises to deliver
of interactive networks and platforms has a consistent and generalizable procedure. In
impacted both positively and negatively the con- effect, growing interest in this technique is prob-
ception of beauty and consequently the tendency ably due to new trends and social standards of
of the masses towards certain physical stereo- becoming athletic with a fitness lifestyle, and
types. To some extent, it might be considered a also, as techniques based on an individual’s own
public health problem or even a matter of interna- anatomy and phenotype are destined to success.
tional concern [3–6]. Comparatively, cosmetic HDL has incorporated different upgrades includ-
surgeries involving the body contour went from ing new artistic and anatomic concepts, addition
being a simple fat removal procedure, to a tech- of ancillary techniques and intermingle between
nique completely dedicated to sculpting the other procedures [18–22]. In fact, the name
underlying anatomy of the individual [7, 8]. After shifted to Dynamic Definition Liposuction
the description, popularization, and subsequent (HD2) due to the incorporation of motion and
improvements to the original technique, liposuc- muscular dynamics to the original concept of
tion and liposculpture remain procedures in HDL (Fig. 36.1). As a consequence, multiple
Fig. 36.1 High a b

definition liposculpture
in a female patient. This
is a 29-year-old woman
who underwent HD2
with moderate to
extreme muscular
definition. Note the new
athletic slim contour of
the abdomen, with
defined arms and legs
from the 6-month
postoperative (b)
picture, compared to the
preoperative one (a)
36 Evolution of Body Contouring Surgery 375
other authors have postulated either improve- mation with high fidelity and reliable informa-
ments or new techniques to overcome the plau- tion of outcomes. In the present chapter, we have
sible flaws derived from superficial liposuction selected five of those we consider the most influ-
[13, 23–26]. However, research quality in aes- ential papers in body contouring surgery, based
thetic plastic surgery has always been a chal- on high-quality evidence, proper description of
lenge due to funds limitations, poor follow-up, the outcomes, and the number of citations among
lack of trustworthy information, patients’ little plastic surgery papers. After each manuscript’s
compliance, and, above all, deficient research summary box, we will give our expert opinion
team skills. In any case, what is extremely about the subject and will try to broaden the per-
important is a proper analysis and design of spective of the reader about the topic in
studies which bring about evidence-based infor- discussion.
36.2 Papers
Illouz YG. Body contouring by lipolysis: a 5-year experience with over 3000 cases. Plast Reconstr Surg.
1983;72(5):591–7.
Strengths • Large cohort of patients (1326 with 3000+ procedures)
• Describes the tunneling technique as a way to decrease the adipose tissue in certain areas of the
body
• Blunt tip cannulas for liposuction
Limitations • No statistical analysis
• Concept of the tunneling technique and the invention liposuction is somehow divided by Illouz and
Fischer
Impact Retrospective study reporting a large cohort of patients (n = 1326) who underwent 3447 procedures
of liposuction. The author is exposing his technique for liposuction by removing localized deposits
of adipose tissue accumulated throughout different regions of the body. Surgical technique is based
on the creation of numerous subdermal “tunnels” that will result in homogeneous contractions of the
overlying skin
Throughout history, surgeons and other physi- body contouring. Suction Assisted Liposuction
cians have improved the liposuction technique by (SAL) has continued to grow over the years and
adding new devices, new anatomical consider- has become the most frequent procedure in aes-
ations, and numerous procedural details that have thetic surgery. As of today, liposuction could be
elevated such procedure to higher and higher considered just the starting point of a body con-
standards over time. Unfortunately, Dr. Fischer tour makeover, since there are many other ancil-
and his father probably experienced the down- lary procedures that aid for the impressive
side of rejection by the time they described lipo- outcomes that we all see in social media.
suction and the well-known tunneling technique, Evidence continues to support the safety profile
which was popularized by Dr. Illouz in this and the minimal risk of complications derived
remarkable paper [27]. Almost 10 years later, Dr. from this procedure. The authors from this paper
Fischer published “the correct history of liposuc- also mention how important it has been to include
tion” in which he states how he created the tun- new technologies and safety practices to over-
neling technique and designed specific come the potential complications derived from
non-traumatic cannulas for such purpose [28]. liposuction. Even so, we usually struggle to get
More than 900 citations make this paper from Dr. either enough data or homogenize/standardize
Illouz a landmark in Plastic Surgery and an out- protocols for surgery, which usually end up in
standing paper in body contouring surgery. A bias when performing clinical studies. In that
recent study from Stein et al. [29] reports an early sense, collaboration and friendly discussions
(n = 1150) and a recent cohort (n = 1660 RC) of have become pillars to deliver the safest practices
patients who underwent liposuction and its new for our patients.
trends despite multiple emerging technologies in
It would be unforgivable to write a book High Definition Liposculpture is considered the

chapter about body contouring and avoid bring- standard of care for patients who undergo lipo-
ing up High Definition Liposculpture. This tech- suction procedures. Although risk for asymme-
nique for detailed body contouring was published tries, unnatural results, and overall contour
in 2007 by Hoyos [14] and then popularized by deformities decrease after the surgeon’s learning
many other authors around the world, most of curve, that is usually not the case for complica-
whom were trained by Dr. Hoyos himself. The tions derived from adverse effects either from
technique was first mentioned during a plastic medications, defective equipment, inherent cir-
surgery conference in 2003, in which the senior cumstances, among others [9, 13, 31–35]. Drug-
author shared his 2-year experience and a small related complications are the ones to fear the
cohort of patients. Recently, Hoyos et al. [30] most during and after elective surgeries. Hence,
reported a retrospective cohort of patients who prevention and proper planning are crucial to
underwent High definition liposculpture proce- avoid them. Complication rates in liposuction
dures including suction assisted lipoplasty, are among the lowest for elective surgical proce-
VASER-assisted high definition liposculpture, dures and HDL is not the exception, contrarily to
and dynamic definition liposculpture. It com- what some people think. Another recent update
prises an 18-year experience of the senior author of HD2 is the applicability of an algorithm to
with HDL technique. Authors report a cohort of suit the best liposculpture procedure to a certain
5052 patients who underwent HDL. What is patient. Basically, the paper reports different
most interesting about this study is the detailed degrees of muscular definition (Basic, Moderate,
description of the technique’s evolution during and Xtreme) depending on the individual’s phe-
an 18-year time lapse. The authors also analyze notype, body habitus, and underlying muscular
the differences in outcomes, complication rates, anatomy [18]. In addition, many other proce-
and surgical highlights. Conclusions broaden the dures added to the original technique have
reader’s perspective about how large volume boosted up the results, including fat grafting,
liposuction procedures have become safe, reli- excisional procedures, new technologies for
able, and generalizable for different populations. additional skin retraction, among others.
Rao RB, Ely SF, Hoffman RS. Deaths related to liposuction. N Engl J Med. 1999;340(19):1471–5
Strengths • Post-mortem analysis of five patients who underwent liposuction
• Important clinical data related to procedure specifics
• Awareness of lidocaine toxicity within the infiltration fluid
• Focused on safety
Limitations • Case series study
• Selection bias due to area-restriction report (New York, USA)
• Only two patients had certainty of death
• Cannot establish association due to study design
• Further studies strongly recommended to support the authors’ statements
• Single center experience
Impact Authors present a retrospective review of autopsy reports from January 1, 1993, through December
31, 1996, and death-notification records from January 1, 1993, through March 1, 1998, at the Office
of Chief Medical Examiner of the City of New York that had been identified by a computer search
using the key words “liposuction,” “cosmetic,” “lipoplasty,” “plastic,” “lipectomy,” “abdominoplasty,”
and “therapeutic complication.” Five cases were found and four analyzed completely by post-mortem
autopsy. Two of them had unexplained causes of death and were discussed in terms of lidocaine
toxicity due to recent awareness of tumescent fluid overdosing. Authors conclude that tumescent
liposuction can be fatal, perhaps in part because of lidocaine toxicity or lidocaine-related drug
interactions
Advent of liposuction and techniques derived from 35 mg of lidocaine per kilogram, and “at least”
it had their boom in the late 1980s and the early 55 mg/kg, toxic ranges are still somehow not calcu-
1990s. Tumescent technique was one of those great lated by some surgeons intraoperatively. The actual
improvements of Liposuction procedure that still risk does not occur during surgery or immediate
happens to be widely used today. Klein et al. postop period, but during the early hours after sur-
described tumescent solution in order to make lipo- gery. Plasma lidocaine concentrations have been
suction not only less painful but also safer for the found to rise for 16 h or even 23 h postop depend-
patient [36]. An interesting paper from Hanke et al. ing on the saturability of CYP3A4 by this type of
[37] reported extensive data from a nationwide sur- anesthetic.
vey answered by 66 dermatologic surgeons in Some press anecdotes and case reports sug-
order to track the overall complication rate and gest that deaths after tumescent liposuction
demographical data from more than 15,000 might not be truly isolated events but actually
patients. Most complications were listed as minor, underreported. Social media and other press
and no serious complications were reported. Most statements have blamed “tumescent anesthe-
recent paper from Cardenas-Camarena et al. dis- sia,” epinephrine or lidocaine toxicity, hypo-
cussed [38] the evolution of their practice in light thermia, and fluid overload as possible causes
of safety, reproducibility, and technical data about of isolated deaths after liposuction. Medical
the conceptualization of Liposculpture as a differ- rationalization includes cardiac “depression,”
ent approach to body contouring than liposuction. pulmonary edema, and lidocaine toxicity, but
Paper under discussion by Rao et al. [39] addresses such cases have not been formally reported
an alarming situation after lidocaine overdosing [39]. In comparison, complications after
and drug-to-drug interactions during liposuction liposuction and morbidity associated with the
procedures back in the late 1990s. In effect, deaths procedure are usually associated to prior medi-
associated with earlier liposuction methods resulted cal conditions and/or unnoticed preoperative
primarily from pulmonary thromboembolism or fat considerations that could be subject to optimi-
emboli. However, emergence of “wet technique” zation (Fig. 36.2). In that sense, Cardenas-
involved the subcutaneous infusion an epinephrine- Camarena et al., Bayter et al., and Hoyos et al.
anesthetic rich solution to reduce both capillary [9, 11, 40] have all tried to improve the preop-
bleeding and postoperative pain. Despite the max- erative planning and have dedicated their
dosing advice from the guidelines of the American efforts to make HDL and HD2 safer procedures
Academy of Dermatologists for tumescent fluid of for all patients.
Grazer FM, Goldwyn RM. Abdominoplasty assessed by survey, with emphasis on complications. Plast Reconstr
Surg. 1977;59(4):513–7
Strengths • First description of complications after abdominoplasty procedures
• States modifications to Pitanguy’s technique for a safer approach
• Most cited article in abdominoplasty
Limitations • No statistical analysis
• Lack of association
• Data relies on self-report from surgeons which can lead to reporting bias
• Satisfaction index is not measured by a validated scale
Impact A survey was responded by 958 surgeons to determine the complications of abdominoplasties. The
authors conclude that patients contemplating abdominoplasty and surgeons who plan to perform it
should be both aware of the unpleasant reality of complications after such procedure. Complications
range from the minor asymmetries and scars to even death. Regardless, nearly all patients were quite
satisfied with their results
a b
Fig. 36.2 High definition liposculpture in a male patient. the 2-month postoperative photo (b) shows a new shred-
This is a 34-year-old man who underwent HD2 with ded and muscular appearance of the torso, with a better
extreme muscular definition. There is a significant accu- muscle projection of the arms, the chest, and abdomen,
mulation of adipose tissue over the anterior and posterior thanks to intramuscular fat grafting
torso (a) with an overweight appearance. Comparatively,
The United States is among the top three coun- mainstream of body contouring surgery, though
tries preforming aesthetic surgical procedures they are not quite the solution for a certain group
worldwide [41]. As a matter of fact, surgeons of patients. Hyperlaxity and loss of normal skin
from all over the world keep continuous track of recoil are common concerns for patients after
the latest trends and recommendations from the delivery and/or massive weight loss. The rapid
American Associations that watch over data from decrease of intra- and extra-abdominal adipose
board certified plastic surgeons. Although Grazer content in the latter and the sudden reduction of
FM published his study on abdominoplasty in intra-abdominal volume from the former are both
1973, addressing the changes he introduced to the main causes of such lack of tissue strength [16].
classic abdominal lipectomy from Dr. Pitanguy Indeed, collagen fibers and overall connective tis-
[42, 43], it was this second study that changed the sue structure progressively change their confor-
paradigms from abdominal lipectomy to new mation to adjust for such specific conditions. In
safer procedures focused on both reducing com- these cases, the aid of excisional procedures came
plications and improving aesthetic outcomes. up to restore the normal structure of the abdomi-
Evolution of abdominoplasty has been influenced nal wall and ultimately, the body contour.
by multiple authors including the introduction of Abdominoplasty was described even before
High Definition Lipoabdominoplasty by Hoyos liposculpture by Demars and Marx in France in
and Perez [15, 16, 44]. It is worth mentioning and 1890, then Kelly in the US in 1899. Surgeons
discussing, the swapping paradigm from just used transverse abdominal lipectomy to remove
removing fat to aspirating and relocating adipose excess skin and to improve the abdominal sup-
tissue to improve the body contouring surgery port after herniorrhaphy [46]. By today, many
stated by Cardenas-Camarena in the late 1990s papers have addressed different techniques and
[45]. Liposculpture procedures then became approaches to restore the abdominal wall
a b
Fig. 36.3 Flap ischemia and necrosis in a patient who neo-vascularization over the ischemic flap and further
underwent Dynamic Definition Miniabdominoplasty. The delimitate the ischemic zone (b). After 3 weeks, the
early postoperative picture (a) shows a congestive distal patient underwent scar revision and a small z-plasty to
flap with scar necrosis and delimitation. We implemented correct the defect (c)
Negative Pressure Wound Therapy (NPWT) to improve
strength and aesthetic contour; however, it was tasis of the rectus abdominis muscle [49]. We
Matarasso et al. [47] who reported the first large also did our part and reported our experience
data from multiple surgeons, different patient with TULUA technique and High- Definition
features, demographics, and backgrounds to Liposuction for males [23].
make lipoabdominoplasty generalizable thereaf- In terms of abdominoplasty, the span of possibili-
ter by analyzing complications and safety meth- ties is innumerable when developing excisional
ods to achieve such procedure (Fig. 36.3). We procedures for body contouring. Considerations
also reported our experience with procedures for patients after massive weight loss are substan-
combining excisional surgeries and High tially different from those for patients with local-
Definition Liposculpture [15, 16, 44]. Recently, ized skin excess and those after pregnancy. In
we published a manuscript addressing an algo- fact, each plastic surgeon must focus on design-
rithm to ease the decision- making for those ing a certain procedure that fits the patient’s spe-
patients requiring full abdominoplasty, miniab- cific needs [8, 46, 50–52]. Currently, the addition
dominoplasty, sliding abdominoplasty, umbili- of new technologies for skin retraction and neo-
cus relocation, and Full- and bridge-reverse collagen synthesis have reduced the need of exci-
abdominoplasties [48]. Likewise, Villegas sional surgeries and have allowed surgeons to
described in 2014 a technique merging trans- move into more conservative procedures. In
verse muscular plication, limited abdominal flap effect, the future might be brightened by robotic
undermining, liposuction, and neoumbilico- surgeries and less invasive procedures to achieve
plasty (TULUA) for those patients without dias- better results.
González-Ortiz M, Robles-Cervantes JA, Cárdenas-Camarena L, Bustos-Saldaña R, Martínez-Abundis E. The

effects of surgically removing subcutaneous fat on the metabolic profile and insulin sensitivity in obese women after
large-volume liposuction treatment. Horm Metab Res. 2002;34(8):446–9.
Strengths • Clinical trial
• Multidisciplinary research
• Well-designed intervention/methods
• Addressed both metabolic profile and clinical effect
• Set a base for future research
• Short follow up
• Medium-impact journal
• Short discussion
Impact Authors studied the metabolic profile and insulin sensitivity in 12 obese women after large-volume
liposuction by means of an open clinical trial. After randomization, six volunteers were enrolled to the
treatment group, while the remaining six were considered as the non-intervention group. Metabolic
profiles and insulin tolerance were assessed before and 21–28 days afterwards. Authors demonstrated
a significant decrease in glucose and uric acid levels after liposuction; insulin sensitivity improved as
well. No complications were reported in the authors’ trial
Drawing conclusions and giving recommenda- Similarly, Kelley [57] further questions
tions based on papers with Level III–IV of evi- Klein’s et al.’s conclusions by simply explain-
dence is always hard and controversial in the ing how thermodynamics and adipose tissue
medical environment. Especially in aesthetic metabolism play a significant role in meta-
plastic surgery, the lack of funds and/or volun- bolic syndromes. Therefore, any low-risk pro-
teers, limitations due to patient-surgeon eco- cedure, even surgical, which might decrease
nomic binding, and the increasing pressure the risk of someone progressing into meta-
from social media are all determinants when bolic syndromes and pathologies affecting the
designing and carrying out clinical studies. It cardiovascular system would be beneficial.
is the paper by Gonzalez-Ortiz et al. of those Maintaining a normal body weight can be
that opened up [53] new potential research and very challenging and difficult not only for
clinical applications for liposuction surgery as patients experiencing metabolic pathologies but
an adjuvant for metabolic syndromes. for the average individual. Several studies have
Although controversial, this topic has been shown the benefits from liposculpture in patients
addressed by many other authors in higher who were overweight and now follow a healthy
impact journals, yet study design, quality, and lifestyle [2, 58]. Currently, there is a high demand
conclusions are far more debatable. Klein and a significant increase in surgical subcutane-
et al. [54] concluded that abdominal liposuc- ous fat remoal (SSFR) to improve physical
tion did not significantly improve obesity- appearance. Liposuction is an elective procedure
associated metabolic abnormalities and would that has reigned as the fast track to both lose
not achieve the metabolic benefits of weight weight and improve the physical appearance.
loss; however, such paper received several Moreover, adipose tissue has been recognized as
comments and replies due to the lack of a a vital endocrine organ that produces several bio-
proper design, a very small sample size, and, active proteins, hence liposuction might have a
as a result, conclusions were criticized as they potential benefit on regulating them. In short, a
were not supported by the data on their manu- recent study from Badran et al. [59] focused on
script whatsoever [55–57]. As a matter of fact, reviewing the metabolic sequelae after SSFR
Giuliano et al. [55] reported the great benefits interventions for dealing with cosmetic body
of liposuction by ameliorating insulin resis- appearance. Data were extracted from prior sys-
tance and decreasing markers of vascular tematic reviews and organized accordingly.
inflammation, which could help obese sub- The authors concluded that there is a gap in
jects to reduce their cardiovascular risk. terms of the probability of weight gain or accu-
mulation of fat post-SSFR, but data regarding harm. We do agree with the authors that there is
the short term shows a likely metabolic benefit a strong need for properly designed dose-
of excess abdominal subcutaneous fat removal. response prospective clinical studies to unravel
However, long-term data is required to deter- these changes and once and for all demonstrate
mine if this benefit is sustained over time. their benefit or none. In turn, this will help us
Additionally, patients undergoing liposuction/ not only to confirm the safety of these proce-
lipectomy (SSFR) represent a unique popula- dures but also to define if they can be used for
tion with a sudden removal of their adipose tis- metabolic benefit and to broaden our knowl-
sue. Hence, metabolic changes after these edge about the mechanisms underpinning
procedures are still unclear, and existing stud- excess adipose tissue and its association with
ies suggest a trend toward benefit rather than metabolic consequences.
Klein JA. Tumescent technique for regional anesthesia permits lidocaine doses of 35 mg/kg for liposuction. J
Dermatol Surg Oncol. 1990;16(3):248–63
Strengths • First detailed description of tumescent technique
• Pharmacokinetic specifics to determine peak concentration for lidocaine after infiltration
• Estimation of maximum safe dose for lidocaine during liposuction
Limitations • Small sample of patients
• Lack of sample demographics and/or clinical data
• No details on selection strategies nor long-term follow up
• Single center experience
Impact Authors carried out an interventional study which scientifically asserted the safety of using elevated
concentrations of lidocaine during liposuction. They reported a variety of procedures in eight
patients, in order to predict lidocaine maximal safe dose using the tumescent technique (35 mg/kg).
They also found that the speed of infiltration, lidocaine dilution, and liposuction, all delayed the
absorption and reduced the peak plasma concentrations. Their findings suggest that the tumescent
technique is useful in the removing of significant volumes of fat, with minimal blood loss without
patient discomfort
Liposuction might be considered under the ent flaws or weaknesses from the thousands of
umbrella of dermatologic surgeries. However, techniques and procedures that exist in aesthetic
plastic surgeons are currently the ones who lead surgery, and how to improve or overcome them.
these type of procedures. The broad spectrum of To name one of the most recent and outstanding
body contouring procedures, including flap research in aesthetic plastic surgery, we would
resection surgeries, is probably the reason why like to refer to the clinical trial conducted by
there is only a small proportion of dermatologists Hoyos et al. [61], regarding the use of tranexamic
performing them. The paper in discussion by acid in liposuction. The authors conducted a mul-
KLEIN [60] explained for the first time how to ticenter, double-blind, randomized, controlled
improve the infiltration process in order to reduce clinical trial in patients who were scheduled for
the risk of bleeding and postoperative discomfort liposculpture in three plastic surgery centers
from patients undergoing liposuction. They not between January 2019 and February 2020. One
only asserted the safe dose of lidocaine as per hundred forty-one patients were randomly
patient weight, but also described the tumescent assigned into three groups (each one 47): intrave-
technique itself. We believe this is one of the first nous (1 g of tranexamic acid = TXA), subcutane-
papers that was truly dedicated to improve the ous (1 g), and placebo (normal saline). Pre and
patient experience during liposuction, and also postoperative hemoglobin analysis was listed as
portrayed a new point of view on how to improve the main outcome. Group IV showed a higher
what was considered already safe enough (i.e., hemoglobin level compared to that from the other
liposuction). In the recent decades, multiple two groups on both day 1 and day 5 postop
authors have dedicated their efforts to find differ- (p < 0.0001).
High quality studies in aesthetic plastic sur- Even more since societies are drifting rapidly
gery have always been a challenge due to limited towards different perspectives of human behavior,
patient compliance, lack of reliable data, poor identity, and self-recognition. In that sense, trans-
statistical analyzes, patient-surgeon rapport gender and non-binary patients who seek different
affected by financial-bonds, and the overall lack standards of muscularization or body structure
of interest in such medical community. require suitable procedures for body contouring
Tranexamic acid has been studied before as a that usually do not follow the usual aesthetics for
potential agent to reduce blood loss in aesthetic either male or female techniques. Similarly, sev-
plastic surgery [62–64]. However, this ground- eral new technologies happen to aid for a fast
breaking paper has taken patient safety to a new recovery and optimal preoperative preparation of
level and has demonstrated the effectiveness of patients undergoing body contouring procedures.
TXA in the reduction of blood loss after Plastic surgeons should be aware of the specifics
HDL. Moreover, the multicenter approach of such technologies to provide a certain patient
involving different surgeons allows the authors with the latest and safest approach to reach the
to infer interesting conclusions and ensure the desired outcomes.
generalizability of the results. Although the Safety is paramount for us and seems to be
paper [61] was released just a couple of months the current trend among most research groups.
before the preparation of this document, it has Moreover, the further increase of liposculpture
been widely spread with a considerable number demand is probably associated with the global
of citations in a short period of time. We do rise in the number of bariatric surgeries, which
expect that with wider dissemination of the is currently the single most durable intervention
study’s findings, more surgeons will begin to for mitigating obesity. A recent literature review
adopt TXA as a modulator for blood loss after from Willet et al. [13] brings up interesting con-
liposuction. We strongly believe that TXA has clusions about the increasing demand of HDL
substantially improved the intraoperative effec- among males (56%), and the broad age spec-
tiveness of the coagulation cascade and has trum of patients undergoing surgery
reduced postoperative blood loss, for patients (Avg = 38 years; range 15–76). Moreover, satis-
undergoing aesthetic procedures. Since elective faction rates are considered high (93%) despite
surgeries are commonly recognized as both flaw- the fact that patients with grade I and even grade
less and bloodless, it is our obligation to adopt II obesity were included in the review (BMI was
the safest conducts for ensuring the best periop- 25 kg/m2 in avg.; range 18–38). In comparison,
erative scenario for our patients based on top- the overall complication rate was reported as
quality medical evidence. The aforementioned 14.4% (n = 994) with only 0.2% (n = 13)
paper is one of the few well-designed double accounting as major ones. Transient hyperpig-
blind randomized clinical trials which might mentation, seroma, and soft tissue fibrosis were
change the course of body contouring surgery. In reported as the most common complications.
effect, we do expect more surgeons and institu- Comparatively, we have reported a lower com-
tions to be inspired and make their best efforts to plication rate in our cohort studies compared to
design and carry out studies with high level of that from the present study, probably due to our
evidence. specific protocols about safety, perioperative
optimization of patients’ health status, and
many other methods that are usually overseen
36.3 Future Directions by other colleagues (postoperative therapy,
blood loss prevention, normothermia, zero-
As any other surgical procedure, techniques for infection strategy, hyperbaric oxygen therapy,
body contouring including High Definition (HDL) etc.) [61, 63, 65].
and Dynamic Definition Liposculptures (HD2) Our next purpose in aesthetic body contour-
are all subject to improvement and evolution. ing surgery is the modification of the individu-
al’s bone structure to further improve the 8. Khajuria A, Charles WN, Dutt A, Hoyos A. The
100 most-cited articles in abdominoplasty: a bib-
patient’s overall shape. In fact, we are currently liometric analysis. Plast Reconstr Surg Glob Open.
running an international collaboration to report 2021;9(3):e3426.
the new trends for patients who lack a proper sil- 9. Cárdenas-Camarena L, Andrés Gerardo LP, Durán H,
houette or those who want to transform their Bayter-Marin JE. Strategies for reducing fatal com-
plications in liposuction. Plast Reconstr Surg Glob
body due to sexual/gender identification prefer- Open. 2017;5(10):e1539.
ences. These studies include floating rib removal 10. Thomas AB, Shammas RL, Orr J, et al. An assessment
and remodeling, collar bone shortenings, scapula of bleeding complications necessitating blood trans-
smoothing surgery, among others. fusion across inpatient plastic surgery procedures.
Plast Reconstr Surg. 2019;143(5):1109e–17e.
Body contouring surgery is rapidly evolving 11. Enrique Bayter-Marin J, Cárdenas-Camarena L,
to new methods and techniques to provide the Peña WE, et al. Patient blood management strate-
patient with ultimate technologies, safest surgi- gies to avoid transfusions in body contouring opera-
cal environment possible, and individualized tions: controlled clinical trial. Plast Reconstr Surg.
2021;147(2):355–63.
procedures. The low rate of complications, the 12. Chia CT, Neinstein RM, Theodorou SJ. Evidence-
high satisfaction index, and the increasing based medicine. Plast Reconstr Surg.
demand of High Definition liposculpture makes 2017;139(1):267e–74e.
it the current standard for body contouring sur- 13. Willet JW, Alvaro AI, Ibrahim AK, Javed MU. A
systematic review of efficacy and complications
gery. Ancillary procedures improve the results of high definition liposuction. Plast Reconstr Surg.
after HDL for those patients whom liposuction is 2023;152:1.
usually not enough. 14. Hoyos A, Millard J. VASER-assisted high-definition
liposculpture. Aesthet Surg J. 2007;27(6):594–604.
15. Hoyos Ariza AE, Perez Pachon ME. High-definition
excisional body contouring: mini lipoabdominoplasty
References (FIT mommy) and enhanced viability abdomino-
plasty. Clin Plast Surg. 2020;47(3):415.
1. Rogers AR, Harris NS, Achenbach AA. Neanderthal- 16. Hoyos A, Perez ME, Guarin DE, Montenegro A. A
Denisovan ancestors interbred with a distantly related report of 736 high-definition lipoabdominoplasties
hominin. Sci Adv. 2020;6(8):eaay5483. performed in conjunction with circumferential VASER
2. Swami V, Frederick DA, Aavik T, et al. The attractive liposuction. Plast Reconstr Surg. 2018;142(3):662.
female body weight and female body dissatisfaction 17. Hoyos AE, Prendergast P. High definition body
in 26 countries across 10 world regions: results of the sculpting. Art and advanced Lipoplasty techniques,
international body project I. Personal Soc Psychol vol. 1. 1st ed. Springer; 2014.
Bull. 2010;36(3):309–25. 18. Hoyos AE, Perez ME, Domínguez-Millán R.
3. Homan K. Athletic-ideal and thin-ideal internaliza- Variable sculpting in dynamic definition body con-
tion as prospective predictors of body dissatisfac- touring: procedure selection and management algo-
tion, dieting, and compulsive exercise. Body Image. rithm. Aesthet Surg J. 2021;41(3):318.
2010;7(3):240–5. 19. Hoyos AE, Stefanelli M, Perez ME, Brenes-Leñero
4. Bell HS, Donovan CL, Ramme R. Is athletic really E, Padilla M. Adipose tissue transfer in dynamic
ideal? An examination of the mediating role of definition liposculpture—PART I. Back: latissimus
body dissatisfaction in predicting disordered eat- Dorsi and trapezius muscles. Plast Reconstr Surg
ing and compulsive exercise. Eat Behav. 2016;21: Glob Open. 2023;11(1):e4587.
24–9. 20. Hoyos AE, Stefanelli M, Perez ME, Padilla
5. Thompson JK, Heinberg LJ. The media’s influence on M. Adipose tissue transfer in dynamic defini-
body image disturbance and eating disorders: we’ve tion liposculpture PART III. The arms: biceps, tri-
reviled them, now can we rehabilitate them? J Soc ceps, and deltoids. Plast Reconstr Surg Glob Open.
Issues. 1999;55(2):339–53. 2023;11(1):e4651.
6. Cheung YTD, Lee AM, Ho SY, et al. Who wants a 21. Hoyos AE, Stefanelli M, Perez ME, Padilla M,
slimmer body? The relationship between body weight Dominguez-Millan R. Adipose tissue transfer
status, education level and body shape dissatisfac- in dynamic definition Liposculpture part II. The
tion among young adults in Hong Kong. BMC Public lower limb: gastrocnemius, vastus Medialis, vastus
Health. 2011;11(1):835. Lateralis, and rectus Femoris muscles. Plast Reconstr
7. Reddy RK, Dutt A, Charles WN, Hoyos A, Khajuria Surg Glob Open. 2023;11(1):e4765.
A. The 100 Most-cited articles in liposuction. Ann 22. Hoyos AE. TOTAL DEFINER: atlas of advanced
Plast Surg. 2021;87(6):615–22. body sculpting, vol. 1. Thieme; 2023. p. 1st ed.
23. Babaitis R, Villegas FJ, Hoyos AE, Perez M, Mogollon 40. Bayter-Marin JE, Cárdenas-Camarena L, Durán H,
IR. TULUA male high-definition abdominoplasty. Valedon A, Rubio J, Macias AA. Effects of thermal
Plast Reconstr Surg. 2022;149(1):96. protection in patients undergoing body contouring
24. Del Vecchio DA, Wall SJ, Mendieta CG, et al. Safety procedures: a controlled clinical trial. Aesthet Surg J.
comparison of abdominoplasty and Brazilian butt 2018;38(4):448–56.
lift: what the literature tells us. Plast Reconstr Surg. 41. The Aesthetic Society. Procedural statistics. The
2021;148(6):1270–7. Aesthetic Society. Procedural statistics 2020-2021.
25. Danilla S. Rectus abdominis fat transfer (RAFT) in 2022. https://www.theaestheticsociety.org/media/
lipoabdominoplasty: a new technique to achieve fit- procedural-statistics. Accessed 1 Nov 2022.
ness body contour in patients that require tummy tuck. 42. Pitanguy V. Abdominal lipectomy. Clin Plast Surg.
Aesth Plast Surg. 2017;41(6):1389–99. 1975;2(3):401–10.
26. Flores González EA, Viaro MSS, Duran Vega HC, 43. Grazer FM. ABDOMINOPLASTY. Plast Reconstr
et al. Incorporation of the UGRAFT technique to Surg. 1973;51(6):617–23.
high-definition liposuction. Plast Reconstr Surg Glob 44. Hoyos AE, Perez ME, Castillo L. Dynamic definition
Open. 2022;10(7):e4447. mini-lipoabdominoplasty combining multilayer lipos-
27. Illouz YG, Illouz YG. Body contouring by lipolysis. culpture, fat grafting, and muscular plication. Aesthet
Plast Reconstr Surg. 1983;72(5):591–7. Surg J. 2013;33(4):545.
28. Fischer G. Liposculpture: the “correct” history 45. Cárdenas-Camarena L, Lacouture AM, Tobar-Losada
of liposuction. Part I. J Dermatol Surg Oncol. A. Combined gluteoplasty: liposuction and lipoinjec-
1990;16(12):1087–9. tion. Plast Reconstr Surg. 1999;104(5):1524–31; dis-
29. Stein MJ, Sasson DC, Harrast J, Alderman A, cussion 1532–3.
Matarasso A, Gosain AK. A sixteen-year review of 46. Mirrafati S. Abdominoplasty history and techniques.
clinical practice patterns in liposuction based on con- In: Aesthetic surgery of the abdominal wall, vol. 1.
tinuous certification by the American Board of Plastic Springer-Verlag; 2005. p. 62–6.
Surgery. Plast Reconstr Surg. 2023;1(1):523. 47. Matarasso A, Swift RW, Rankin M. Abdominoplasty
30. Hoyos AE, Cala LC, Perez ME, Mogollon IR, and abdominal contour surgery: a National
Dominguez-Millan R. High-definition liposculpture Plastic Surgery Survey. Plast Reconstr Surg.
18-year evolution: patient safety and aesthetic out- 2006;117(6):1797–808.
comes. Plast Reconstr Surg. 2023;151(4):737–47. 48. Hoyos AE, Perez ME, Mogollon IR, Arcila
31. Dolsky L, Newman MDJ, Fetzek DOJR, Anderson A. Decision-making algorithm for advanced
MDRW. Liposuction, history, techniques and compli- excisional body contouring: dynamic defini-
cations. Adv Dermatologic Surg. 1987;5(2):313–33. tion solutions for skin laxity. Plast Reconstr Surg.
32. Katz BE, Bruck MC, Felsenfeld L, Frew KE. Power 2022;150(6):1248–59.
liposuction: a report on complications. Dermatologic 49. Villegas FJ. A novel approach to abdominoplasty:
Surg. 2003;29(9):925–7. TULUA modifications (Transverse plication, no
33. Kokosis G, Coon D. Safety in body contouring to avoid undermining, full liposuction, Neoumbilicoplasty,
complications. Clin Plast Surg. 2019;46(1):25–32. and low transverse abdominal scar). Aesth Plast Surg.
34. Harrison B, Khansa I, Janis JE. Evidence-based 2014;38(3):511–20.
strategies to reduce postoperative complica- 50. Lockwood T. High-lateral-tension abdominoplasty
tions in plastic surgery. Plast Reconstr Surg. with superficial fascial system suspension. Plast
2016;137(1):351–60. Reconstr Surg. 1995;96(3):603–15.
35. Hoyos AE, Perez ME. Invited discussion on: post- 51. Dabb RW, Hall WW, Baroody M, Saba
operative complications and patient satisfaction AA. Circumferential suction lipectomy of the trunk
after abdominal etching—prospective case series with anterior rectus fascia plication through a perium-
of 25 patients: abdominal definition liposuction or bilical incision: an alternative to conventional abdom-
high definition Liposculpture? Aesth Plast Surg. inoplasty. Plast Reconstr Surg. 2004;113(2):727–32.
2020;44(3):836. 52. Hoyos A. Excisional body sculpting. In: Perez M, edi-
36. Flynn TC, Coleman WP, Field LM, Klein JA, Hanke tor. Total definer: atlas of advanced body sculpting,
WC. History of liposuction. Dermatologic Surg. vol. 1. 1st ed. Thieme; 2022. p. 389–438.
2000;26(6):515–20. 53. Gonzalez-Ortiz M, Robles-Cervantes JA, Cardenas-
37. Hanke WC, Bernstein G, Bullock S. Safety of tumes- Camarena L, Bustos-Saldaña R, Martinez-Abundis
cent liposuction in 15,336 patients. Dermatologic E. The effects of surgically removing subcutaneous
Surg. 1995;21(5):459–62. fat on the metabolic profile and insulin sensitivity in
38. Cárdenas-Camarena L, Reyes-Herrera MF, Vargas- obese women after large-volume liposuction treat-
Flores E, López-Fabila DA, Robles-Cervantes ment. Horm Metab Res. 2002;34(8):446–9.
JA. Lipoabdominoplasty: what we have implemented 54. Klein S, Fontana L, Young VL, et al. Absence of
and what we have modified over 26 years. Plast an effect of liposuction on insulin action and risk
Reconstr Surg Glob Open. 2023;11(2):e4805. factors for coronary heart disease. N Engl J Med.
39. Rao RB, Ely SF, Hoffman RS. Deaths related to lipo- 2004;350(25):2549–57.
suction. N Engl J Med. 1999;340(19):1471–5.
55. Giugliano G, Nicoletti G, Grella E, et al. Effect of 61. Hoyos AE, Duran H, Cardenas-Camarena L, et al.
liposuction on insulin resistance and vascular inflam- Use of tranexamic acid in liposculpture: a double-
matory markers in obese women. Br J Plast Surg. blind, multicenter, randomized clinical trial. Plast
2004;57(3):190–4. Reconstr Surg. 2022;150(3):569.
56. Esposito K, Giuliano G, Giuliano D. Metabolic 62. Elena SE. A systematic review of tranexamic acid in
effects of liposuction—yes or no? N Engl J Med. plastic surgery: what’s new? Plast Reconstr Surg Glob
2004;351(13):1354–7. Open. 2021;9(3):e3172.
57. Kelley DE. Thermodynamics, liposuction, and metab- 63. Cansancao AL, Condé-Green A, David JA,
olism. N Engl J Med. 2004;350(25):2542–4. Cansancao B, Vidigal RA. Use of tranexamic acid to
58. Sorice SC, Li AY, Gilstrap J, Canales FL, Furnas reduce blood loss in liposuction. Plast Reconstr Surg.
HJ. Social media and the plastic surgery patient. Plast 2018;141(5):1132–5.
Reconstr Surg. 2017;140(5):1047–56. 64. Rohrich RJ, Cho MJ. The role of tranexamic
59. Badran S, Doi SA, Hamdi M, et al. Metabolic aspects acid in plastic surgery. Plast Reconstr Surg.
of surgical subcutaneous fat removal: an umbrella 2018;141(2):507–15.
review and implications for future research. Bosn J 65. Hoyos A. Safety. In: Perez M, editor. Total definer: atlas
Basic Med Sci. 2022. of body sculpting, vol. 1. 1st ed. Thieme; 2023. p. 49–87.
60. KLEIN JA. Tumescent technique for regional anes-
thesia permits lidocaine doses of 35 mg/kg for lipo-
suction. J Dermatol Surg Oncol. 1990;16(3):248–63.
Evolution of Hair Transplantation
37
Jae Hyun Park
Abstract Keywords
Hair transplant surgery has undergone remark- Hair follicle · Hair transplantation · Follicular
able developments during the past 20–30 years. unit · Follicular unit transplantation ·
Since establishment of the concept of modern Follicular unit extraction · Follicular unit
hair transplantation in the mid to late 1990s, excision
novel surgical methods have been introduced
in the order of follicular unit excision (FUE),
follicular unit transplantation megasessions, The Five Most Impactful Papers
FUE megasessions, non-shaven FUE, and 1. Unger W, Solish N, Giguere D, et al. Delineat-
long-hair FUE. Instruments and devices for ing the “safe” donor area for hair transplant-
FUE procedures have also made tremendous ing. Am J Cosmet Surg. 1994;11(4):239–43.
progress, potentiating the harvest of high- 2. Limmer BL. Elliptical donor stereoscopi-
quality grafts with minimal follicular injury. cally assisted micrografting as an approach
The field of female hairline correction surgery to further refinement in hair transplantation.
has progressed beyond the concept of simple J Dermatol Surg Oncol. 1994;20(12):789–93.
reconstruction in alopecic areas and now 3. Rassman WR, Bernstein RM, McClellan R,
proudly takes its place as facial aesthetic sur- Jones R, Worton E, Uyttendaele H. Follicular
gery that changes the facial contour and com- unit extraction: minimally invasive surgery for
pletes the harmony of the entire face. hair transplantation. Dermatol Surg. 2002;
The present chapter introduces and reviews 28(8):720–8.
five landmark papers in the field of hair trans- 4. Park JH, Na YC, Moh JS, Lee SY, You SH.
plant surgery from the 1990s to the present Predicting the permanent safe donor area for
with the aim of discussing the developments hair transplantation in Koreans with male pat-
in this field. tern baldness according to the position of the
parietal whorl. Arch Plast Surg. 2014;
41(3):277–84.
5. Jung JH, Rah DK, Yun IS. Classification of
the female hairline and refined hairline cor-
J. H. Park (*) rection techniques for Asian women.
Dana Plastic Surgery Clinic, Seoul, South Korea Dermatol Surg. 2011;37(4):495–500.
https://doi.org/10.1007/978-3-031-57132-9_37
388 J. H. Park
37.1 Introduction mendous amounts of innovation to facilitate the

process of acquiring donor grafts [3]. Additionally,
During the past 20–30 years, hair transplant sur- FUE techniques are applied not only to the scalp
gery has undergone tremendous changes and but also other body parts to broaden the range and
remarkable developments, incomparable to any selection of donor hairs and enable body hair
other field in medicine. The follicular unit excision transfer of the beard and hairs from the chest and
(FUE) method has now surpassed follicular unit abdomen [4]. Moreover, hair transplant surgery is
transplantation (FUT) and has become the most not limited to restoring alopecic areas but has
adopted harvesting method in hair restoration extended beyond such a conventional concept to
worldwide, with even non-shaven FUE and long- encompass aesthetic properties [5]. This chapter
hair FUE considered actively practiced procedures explores the evolution of hair transplant surgery
[1, 2]. Robotic systems are also used to assist sur- and the present stance along with a review of the
gery, and surgical instruments have undergone tre- five landmark papers in the field.
37.2 Safe Donor Area (SDA)
Unger W, Solish N, Giguere D, et al. Delineating the “safe” donor area for hair transplanting. Am J Cosmet Surg.
1994;11(4):239–43
Strengths • Well-conducted study
• Reasoned approach to define the SDA for hair transplantation of patients with male pattern
baldness
Limitations • The SDA is suggested based on probabilistic possibility rather than an absolute definition
• The paper was published in 1994, and the authors’ suggestion is still accepted as the most standard
definition of the SDA. However, 30 years have passed since its publication, and the data may not
be uniformly applicable because of the increase in life expectancy, development of novel medical
or surgical treatment methods, and other changes that have occurred over time
Impact By suggesting the definition of the SDA in patients with male pattern baldness, this paper provided
an important milestone in hair restoration surgery that transfers hair follicles from the donor to the
recipient area.
The authors’ definition is still accepted as the most standard definition of the SDA
The theoretical roots of modern hair transplanta- In this paper published in 1994, Unger et al.
tion are based on the above-mentioned definition classified 328 patients with male pattern baldness
of the SDA established by Unger et al. along with aged ≥65 years into Norwood classification I to
the donor dominance theory established by VII hair loss, then classified the area containing
Orentreich [6]. at least eight hairs per 4-mm circle as a potential
Hair transplant surgery basically involves SDA. This is still acknowledged as an established
extraction of hair follicles from the back of the theory, and hair transplantation surgery in
head, which is predicted to be permanently safe patients with male pattern baldness is being
from hair loss, and transfer of the donor hairs to implemented based on this definition of the
the recipient area in need of restoration. safety zone.
Therefore, the definition of the SDA can be con- However, we must not overlook the fact that
sidered as the most fundamental concept in the such a definition of the SDA is not an absolute
field of hair transplant surgery. concept but a potential SDA based on probabil-
37 Evolution of Hair Transplantation 389
ity. This is because Unger et al. defined alope- When it comes to the prediction of hair loss
cia as a continuous progressive condition and progression, our crystal balls are always cloudy.
proposed the most reasonable standard by cal- Therefore, the SDA should never be taken as
culating the probability of the worst-case absolute. Judicious and flexible interpretation is
scenario. needed by comprehensively considering various
Under the following two assumptions, Unger clinical circumstances. For example, in some
et al. defined the SDA as an area that remains developed countries, the average life expectancy
intact when the alopecia does not progress to has already exceeded 80 years [7]. At the time
Norwood stage VII: this paper was published, FUE surgery had not
yet been introduced. FUE surgery uses a very
1. The global mean life expectancy was wide donor area, and there is a tendency to apply
≤80 years. a more liberal interpretation of the SDA. Of
2. More than 80% of men aged 70–79 years had course, the excellent hair loss prevention effects
less than Norwood type VII hair loss. of drugs such as finasteride, dutasteride, and min-
oxidil are also taken into account [8].
By contrast, if hair loss progresses to Norwood Despite some ambiguity in interpretation, it
stage VII, the defined SDA is unsafe and the cannot be denied that the definition of the SDA
donor scar will be exposed, even affecting the by Unger et al. has remained the most fundamen-
transplanted grafts. tal theoretical basis in hair transplant surgery.
37.3 FUT
Limmer BL. Elliptical donor stereoscopically assisted micrografting as an approach to further refinement in hair
transplantation. J Dermatol Surg Oncol. 1994;20(12):789–93
Strengths • Provided a thorough description of the micrograft procedure, in which an elliptical linear excision
of the scalp was followed by microscopic dissection and FUT
• Included a relatively large number of cases (presented a review of the surgical experience of 330
patients during a 6-year period)
Limitations • Because of the lack of advances in technology, the number of donor grafts was limited to only
1200–2400 hairs
Impact This is the first paper to introduce the modern and standardized concept of transplantation by
individual follicular units along with microscopic dissection. Early transplants involved insertion of
larger sections of hair-bearing skin into the recipient area, creating results that are too unnatural to be
aesthetically acceptable. Evolving from such a precursor, FUT of one to four hairs creates a much
more even and natural look of the transplanted hair. This method remains the standard for FUT hair
transplant surgery
This paper served as a touchstone for transition author performed an elliptical linear strip exci-
of hair transplantation from punch graft or mini- sion on the patient’s occipital region and then
graft procedures, which resulted in unsightly dissected individual hair follicles under a
grafts that were unnaturally spread apart, to microscope. Slit incisions were then made
micrograft transplantation for the achievement of using a 16-, 18-, or 20-guage needle followed
natural and aesthetically pleasing results. by individual graft insertion of harvested hair
FUT refers to the method of transplanting follicles by forceps. This method remains the
follicular units consisting of one to four hairs standard for FUT hair transplant surgery. The
and perifollicular tissue. In this paper, the advantages of the micrograft method are a nat-
390 J. H. Park
ural-looking grafted area without tufting or a ergonomic equipment and devices as well as
“corn row” appearance and rapid healing of the conceptual innovations [9, 10].
donor site. However, it is a labor-intensive sur- From the 1990s to the early 2000s, the FUT
gery and necessitates additional equipment and technique introduced in the present paper has
a well-trained workforce. Such shortcomings become the standard technique for hair restor-
are unavoidable from the viewpoint of the ative surgery worldwide. It was a decisive factor
recent trend of performing megasessions and the starting point for the rapid expansion of
involving 3–4000 grafts within a day and are the field and facilitated a dramatic transition to a
continuously being overcome through various natural surgical result.
37.4 FUE (Previously Known

as Follicular Unit Extraction)
Rassman WR, Bernstein RM, McClellan R, Jones R, Worton E, Uyttendaele H. Follicular unit extraction: minimally
invasive surgery for hair transplantation. Dermatol Surg. 2002;28(8):720–8
• First paper to introduce surgical techniques and histological aspects of FUE and to suggest standards
for the method
• It is the most-cited scientific article in the field of hair transplant surgery to date
Limitations • As the very first paper to report the FUE method, more technicality is desired in the reality of
contemporary standards owing to tremendous advances of the technique. At that time, there was no
understanding of the anchoring system that supports the hair, such as the erector pili muscle; the
varied difficulty upon extraction was explained by the thickness of the dermis. The rate of
contraindication for FUE was as high as 26% because of the technical limitations of the time
Impact This is the most-cited paper in the literature and a monument in the field of hair transplantation
because it first reported the FUE method, a harvesting method that is now most often adopted beyond
FUT
Worldwide, FUE has now surpassed FUT to In this paper, the authors advised partial inci-
become the most commonly performed surgical sion of the skin (only to the dermis level) because
method with the present article as a starting of the splay phenomenon. However, they
point. reported that such a technique was still insuffi-
In the introduction of this paper, the authors cient for preventing follicular damage. The
counted the donor scar as the only drawback of authors termed FUE the “FOX procedure” and
the strip surgery. They also suggested that FUT is categorized it into five classes: In class 1, all fol-
not adequate in patients with very tight scalps licular units were intact; in class 2, there was
and explained the necessity of the FUE method. loss of <20% of the surrounding fat, with most
In general, however, the disadvantages of hair follicles harvested intact; class 3 was neu-
the strip method not only include a linear donor tral; in class 4, most of the surrounding fat was
scar but also postoperative pain, which was avulsed with a significant number of distal folli-
ameliorated to a great degree by implementing cles amputated; and in class 5, most of the folli-
FUE [11]. cles were damaged. Classes 1 and 2 after the
FOX test were considered good indications for the key to successful FUE is to acknowledge that
FUE, while classes 4 and 5 were not proper can- the acquired hair follicles may be slender rather
didates for FUE. than plump as in FUT and to obtain a clean and
According to the authors’ study, 26% of the healthy intact follicle without follicular injury.
study participants (10% from FOX class 4 and The increased understanding of the physics and
16% from FOX class 5) were not proper candi- dynamics of FUE and related instruments has
dates for FUE; in other words, FUE was not indi- enabled the harvest of a large amount of high-
cated for about a quarter of the study quality hair follicles in a short period of time,
participants. thus contributing to the explosive development of
This high percentage is attributed to the lack the method.
of advances in FUE devices and instruments as A representative disadvantage of the FUE
well as limited information and understanding of method is that the donor area must be shaved. To
the physics and dynamics of the procedure. overcome this problem, the non-shaven FUE
Nowadays, many fewer patients have technical method was introduced to help patients who
contraindications for FUE. wish to undergo FUE surgery but cannot shave
Notably, the FUE method has changed many their hair for various reasons. Because the back
aspects of hair transplant surgery to the extent of the head is not shaved, evidence of having
that modern hair transplant surgery is divided undergone the procedure is not noticeable imme-
into pre-FUE and post-FUE eras, with this paper diately after treatment, allowing a quick return to
playing an important touchstone role. daily life [1].
As a method that overcomes postoperative Non-shaven FUE does not necessitate donor
pain and linear donor strip scars, which are the shaving, but the hair shaft of the harvested donor
representative disadvantages of the FUT hairs is as short as 0.5–1.0 mm in length.
method, FUE is being increasingly spotlighted Tremendous progress has recently been made in
and has developed to the extent that thousands the field, and long-hair FUE was introduced to
of follicular units are transplanted in a single complement the short hair shaft [14].
session. FUE devices and instruments have under-
In the past, the reliability of the surgical results gone remarkable advances as well, starting from
of FUE compared with FUT was questioned. The performing the procedure with a manual punch
main concern was whether the survival rate of in the early 2000s to the subsequent use of
FUE was comparable to that of FUT. Researchers motorized FUE devices, robotic FUE machines,
pointed out that a smaller amount of perifollicu- multiphasic operating systems, motorized fore-
lar tissue than FUT hair follicles was the cause, head-supporting FUE chair systems, punch
and efforts were accordingly made to obtain machines operated by Bluetooth and fingertip
plump hair follicles similar to those in touch sensors, and various punch tips including
FUT. However, Park and You [12] compared FUE flared punches [10, 15–17].
and FUT hair follicles and reported that grafts With respect to terminology, “follicular unit
harvested by FUE may have minor injuries such extraction” was long accepted as the standard
as paring, fracture, and dermal papilla injury that term, but it has since been changed to “follicular
were rarely seen in FUT hair follicles. FUE grafts unit excision” by the International Society of
with minor injuries were transplanted in nude Hair Restoration Surgery. Thus, the term “exci-
mice to prove that such minor injuries had a neg- sion” instead of “extraction” is now mainly in
ative effect on the survival rate [13]. Therefore, use.
392 J. H. Park
37.5 Relationship Between

Location of Parietal Whorl
(PW) and SDA
Park JH, Na YC, Moh JS, Lee SY, You SH. Predicting the permanent safe donor area for hair transplantation in
Koreans with male pattern baldness according to the position of the parietal whorl. Arch Plast Surg.
2014;41(3):277–84
• Reasoned approach to defining the SDA in relation to the location of the PW for hair transplantation
in patients with male pattern baldness
• Large number of study subjects
• Very logical approach
Limitations • This paper states that vertex alopecia mostly progresses within 6 cm of the PW toward the occipital
side. In clinical practice, however, it is difficult to establish this as a general rule because of possible
exceptional circumstances
Impact This article is the only publication to date that revised and complemented the definition of the SDA
established by Unger et al., which was the fundamental definition used in hair transplant surgery for
male pattern baldness. The location of the PW was studied in 952 volunteers, and its influence on
vertex alopecia was proven. The study findings suggested that patients in whom the PW was located
very posteriorly may develop Norwood stage VII hair loss as soon as vertex alopecia starts to
progress, leaving a much narrower SDA than the conventional SDA. That is, the SDA differs by the
location of the PW, and its location therefore has a very significant impact by influencing the selection
of the surgical method, decision of the treatment method, and prognosis
The modern concept of hair transplant surgery to a degree as severe as Norwood stage VII. This
has its roots in the donor dominance theory estab- paper holds some clues to the answer. The logical
lished by Orentreich [6] and the definition of the reasoning demonstrated in this article is as
SDA in patients with male pattern baldness. This follows.
paper states that although the theory proposed by First, vertex alopecia in patients with male
Unger et al. is the most standard definition of the pattern baldness progresses in a radial pattern
SDA, it is based on probability and not an abso- starting from the center of the PW. Second, the
lute definition. Unger et al. presented this SDA position of the PW (anterior or posterior) greatly
theory under the following two assumptions: varies on an individual-patient basis. Third, the
starting point of vertex alopecia will therefore
1. The global mean life expectancy was also be affected by the location of the PW. Fourth,
≤80 years. posterior progression of vertex alopecia will be
2. More than 80% of men aged 70–79 years delayed in patients with the PW at a very anterior
have less than Norwood type VII hair loss. position. (However, there is no certainty pertain-
ing to the exact time or speed at which this delay
In actual clinical practice, we meet patients occurs). By contrast, when the PW is very poste-
whose SDA does not match the definition estab- riorly positioned, alopecia will progress to the
lished by Unger et al., and we sometimes even area corresponding to Norwood stage VII as soon
encounter very young patients. What are the as vertex alopecia begins to advance. Such a sign
exceptions to the rule suggested by Unger et al.? may be a red flag for hair transplant surgery or
Are there any factors that predict the possibility may simply inform the surgeon of the narrower
of progressing to Norwood stage VII in advance? vertical height of the SDA and serve as a possible
The greatest concern when encountering a indication for FUT over FUE.
relatively young patient with early-stage hair loss Detailed surgical planning in terms of the
who has a father with advanced-stage alopecia is donor area, harvesting method, and timing of sur-
whether the patient’s condition will also progress gery differ by the effectiveness of drugs such as
finasteride and dutasteride, the degree of patient 1.5–11 cm). The PW was located at 1–4 cm in
compliance, the density of the occipital donor 8.4% of the subjects (anteriorly positioned PW),
area, and other factors. However, the very funda- 4–9 cm in 85.8% (normally positioned PW), and
mental concept of hair transplantation, namely 9–11 cm in 5.8% (posteriorly positioned PW).
the SDA, varies by the location of the PW. This That is, in the 5.8% of subjects with a posteriorly
theory of PW location is the only one to date that positioned PW, vertex alopecia, as soon as it
has supplemented the conventional definition of starts to advance, will invade the area correspond-
the SDA. ing to Norwood stage VII. These individuals may
Therefore, what is the difference between an not be indicated for hair transplantation, or only
anteriorly positioned PW, normally positioned follicular unit strip surgery may be recom-
PW, and posteriorly positioned PW? The authors mended. Even with surgery, these patients require
found that the mean distance from the vertical thorough management of hair loss, including
bimeatal line to the PW was 6.25 ± 1.7 cm (range, medical treatment prior to and after surgery.
37.6 Female Hairline Correction

Surgery
Jung JH, Rah DK, Yun IS. Classification of the female hairline and refined hairline correction techniques for Asian
women. Dermatol Surg. 2011;37(4):495–500
• Delineated the morphological classification of the female hairline and provided a general
description of basic surgical techniques
Limitations • As described in this paper, there are various hairline shapes (round, M-shaped, rectangular,
bell-shaped, and triangular). The authors only focused on correction of the M-shaped
frontotemporal recess area. Notably, the M-shaped hairline is the most frequent chief complaint and
operative indication in the field of female hairline correction
Impact It is a landmark paper of female hairline surgery which evolved into a more sophisticated form from
the established hair restorative surgery; main purpose of which is merely restoring the recipient area
with hair loss. With this paper serving as a catalyst for further development, various research results
and papers on female hairline correction surgery have since been published
Hair transplant surgery, which has been actively A total of 350 women with an M-shaped hair-
performed for patients with hair loss during the line, which is characterized by a deep frontotem-
past two decades, has recently evolved into a cos- poral recess area, underwent hairline correction
metic surgery that changes the outline of the face surgery, and the basic surgical method and loca-
and creates a small and slim facial shape. Hairline tion of the main hairline structures were mea-
correction surgery is continuously in the spot- sured and reported.
light and actively performed especially in The upper 45–55% of the facial contour is
women. defined by the hairline. The lower contour is
The present paper is the touchstone article in mainly composed of the zygoma and mandible.
the field of hairline correction surgery. The Therefore, hairline correction surgery should be
authors classified the shape of the hairline of 234 designed in harmony with the overall facial
female volunteers into five types and found that contour.
27.4% had a round hairline, 28.2% had an Hairline correction surgery has made great
M-shaped hairline, 27.4% had a rectangular hair- leaps and is now performed as a supplement or
line, 10.3% had a bell-shaped hairline, and 3.0% alternative to facial aesthetic surgery. It helps
had a triangular hairline. correct the appearance of the eyes, such as close-
394 J. H. Park
set eyes; complements the insufficient part of The development of the field of hair transplan-
facial bone surgery; and corrects the deformation tation in the next 10–20 years is looked forward
caused by various surgeries, such as facial lifting with excitement.
surgery [18–20]. Therefore, the importance of Many publications have led to the remarkable
hairline correction surgery in the field of facial development of hair transplant surgery. In this
aesthetic surgery should not be overlooked. chapter, five papers that have had the greatest
Acquiring a basic understanding of hairline cor- impact in this field were selected, and the overall
rection surgery will allow aesthetic surgeons to development of hair transplant surgery was
proceed with better surgical planning and thus reviewed through these papers. Because hair
expect much better surgical outcomes. transplant surgery has undergone such innovative
Likewise, because of the exponential expan- and dramatic advances, it is impossible to explain
sion of the field of hair transplant surgery, every detail of the development of hair transplant
advanced techniques such as non-shaven FUE surgery with merely five papers. In particular,
and long-hair FUE have been introduced. These many papers would have been ideal to discuss
procedures have established their position as very when it comes to subdivisions of the field, but
advanced-level aesthetic surgeries that create a such papers are too numerous. However, through
beautiful facial contour. these five papers, the general direction and trend
of the development and innovation of hair trans-
plant surgery can be summarized along with the
37.7 Up-to-Date Commentary current state of the field.
The field of hair transplantation is changing at
Now, hair transplant surgery is becoming incred- a rapid pace, and its future looks promising.
ibly popular all over the world. The speed of
development in the field is accelerating due to the
rise in patient standard. Surgery that was unimag- References
inable 10–20 years ago is now a reality and has
become an everyday routine surgery. 1. Park JH, You SH, Kim NR. Nonshaven follicular
unit extraction: personal experience. Ann Plast Surg.
Looking at the development process, it has 2019;82(3):262–8.
developed in the order of FUT, FUT megases- 2. Trivellini R, Perez-Meza D, Renaud HJ, Gupta
sion, FUE, FUE megasession, Non-Shaven FUE, AK. Preview long hair follicular unit excision: an
and Long hair FUE. Deeper knowledge and up-and-coming technique. J Cosmet Dermatol.
2021;20(11):3422–6. Epub 2021 Mar 9
understanding of physics, dynamics, and ergo- 3. Rose PT, Nusbaum B. Robotic hair restoration.
nomics of FUE surgery led to remarkable prog- Dermatol Clin. 2014;32(1):97–107.
ress in the advances of FUE devices and 4. Umar S. Use of body hair and beard hair in hair
instruments. As a result, surgeons can produce restoration. Facial Plast Surg Clin North Am.
2013;21(3):469–77.
more natural and satisfactory surgical results by 5. Park JH. Novel principles and techniques to create a
swiftly and accurately acquiring high-quality natural design in female hairline correction surgery.
grafts. It is undeniable that the previously delin- Plast Reconstr Surg Glob Open. 2016;3(12):e589.
eated five landmark papers have become crucial 6. Orentreich N. Autografts in alopecias and other
selected dermatological conditions. Ann N Y Acad
stepping stones to the growth. Sci. 1959;83:463–79.
The future definitely holds some other good 7. Kontis V, Bennett JE, Mathers CD, Li G, Foreman
excellent surgical method and brilliant papers to K, Ezzati M. Future life expectancy in 35 industri-
make our hearts beat and contribute to bringing alised countries: projections with a Bayesian model
ensemble. Lancet. 2017;389(10076):1323–35. Epub
better surgical results and happiness to patients. 2017 Feb 22
Science has always advanced beyond human pre- 8. Adil A, Godwin M. The effectiveness of treatments for
dictions, and the same goes for hair androgenetic alopecia: a systematic review and meta-
transplantation. analysis. J Am Acad Dermatol. 2017;77(1):136–141.
e5. Epub 2017 Apr 7
9. Gan YY, Du LJ, Hong WJ, Hu ZQ, Miao 15. Gupta AK, Bruce A, Trivellini R, et al. Innovations
Y. Theoretical basis and clinical practice for FUE hair restoration surgeons have made to adapt to the
megasession hair transplantation in the treatment of challenges of follicular unit excision. J Cosmet
large area androgenic alopecia. J Cosmet Dermatol. Dermatol. 2020;19(8):1883–91. Epub 2020 Jun 9.
2021;20(1):210–7. Epub 2020 Apr 28. 16. Park JH, You SH, Kim N. Forehead-supporting chair
10. Park JH, Kim NR, Manonukul K. Ergonomics in system for follicular unit extraction hair transplanta-
follicular unit excision surgery. J Cosmet Dermatol. tion. Arch Aesthetic Plast Surg. 2019;25(1):42–4.
2022;21(5):2146–52. Epub 2021 Aug 11. 17. Umar S, Lohlun B, Ogozuglu T, Carter MJ. A novel
11. Kim YS, Na YC, Park JH. Comparison of postop- follicular unit excision device for all-purpose hair
erative pain according to the harvesting method graft harvesting. Clin Cosmet Investig Dermatol.
used in hair restorative surgery. Arch Plast Surg. 2021;14:1657–74.
2019;46(3):241–7. Epub 2019 May 15. 18. Park JH. Masking the close eye appearance in the
12. Park JH, You SH. Various types of minor trauma to east Asian female population: infratemporal hair-
hair follicles during follicular unit extraction for line reduction with hair grafting. Aesth Plast Surg.
hair transplantation. Plast Reconstr Surg Glob Open. 2016;40(6):921–5. Epub 2016 Sep 8.
2017;5(3):e1260. 19. Park JH. Side-hairline correction in Korean
13. Kwack MH, Kim MK, You SH, Kim N, Park female patients. Plast Reconstr Surg Glob Open.
JH. Comparative graft survival study of follicular 2015;3(3):e336.
unit excision grafts with or without minor injury. 20. Kim YS, Na YC, Park JH. Hair transplantation in
Dermatologic Surg. 2021;47(5):e191–4. patients with hair loss or scar deformity in the side
14. Park JH, You SH, Kim NR, Ho YH. Long hair follicu- hairline after midfacelifting surgery. Arch Plast Surg.
lar unit excision: personal experience. Int J Dermatol. 2019;46(2):147–51. Epub 2019 Mar 31.
2021;60(10):1288–95. Epub 2021 May 24.
Evolution of Non-surgical/
Minimally Invasive Treatments
38
Neil M. Vranis, Erez Dyan, and Spero Theodorou

The number of non-invasive or minimally 1. Carruthers J, Carruthers J. Treatment of gla-
invasive procedures continues to increase as bellar frown lines with C. Botulinum-A
patients request less expensive treatment Exotoxin. J Dermatol Surg Oncol.
modalities with minimal downtime and risk 1992;18(1):17–21.
profile. 2. Duranti F, Salti G, Bovani B, Calandra M,
Additionally, patients tend to seek these Rosati ML. Injectable hyaluronic acid gel for
rejuvenating or “preventative” treatments at soft tissue augmentation: a clinical and histo-
younger ages. While most of the devices and logical study. Dermatologic Surg.
treatments focus on facial rejuvenation, many 1998;24(12):1317–25.
of these technologies have been applied on 3. Bassichis B, Dayan S, Thomas R. Use of a
various other anatomic areas. Non-invasive nonablative radiofrequency device to rejuve-
and minimally invasive rejuvenation treat- nate the upper one-third of the face.
ments target neuromuscular paralysis for rhy- Otolaryngol Head Neck Surg. 2004;
tid effacement, filler for soft tissue volume 130(4):397–406.
restoration, and skin tightening and adipolysis 4. Rittes PG. The use of phosphatidylcholine
for contour improvements. for correction of localized fat deposits.
Aesthetic Plast Surg. 2003;27(4):315–8.
5. Manstein D, Laubach H, Watanabe K,
Keywords Farinelli W, Zurakowski D, Anderson RR.
Selective cryolysis: a novel method of non-
Minimally invasive facial rejuvenation · invasive fat removal. Lasers Surg Med.
Radiofrequency skin tightening · Fillers and 2008;40(9):595–604.
neurotoxins · Minimally invasive fat reduc-
tion and contouring · Non-surgical aesthetics
38.1 Introduction
N. M. Vranis (*) Non-invasive cosmetic procedures consistently
Ghavami Plastic Surgery, Beverly Hills, CA, USA
outperform cosmetic and reconstructive surgeries
E. Dyan in terms of volume and revenue as tracked by the
Avance Plastic Surgery, Reno, NV, USA
American Society of Plastic Surgeons (ASPS)
S. Theodorou [1]. A sample of volumes determined on an
BodySculpt, New York, NY, USA
https://doi.org/10.1007/978-3-031-57132-9_38
398 N. M. Vranis et al.
Table 38.1 Non-invasive cosmetic procedures consistently outperformed cosmetic surgical volume, despite both sec-
tors showing positive annual growth over the past decade in the United States. Procedural volumes are presented includ-
ing the top-five most common non-invasive treatment sub-categories per year (ASPS Published Data)
2010 2015 2020
Surgical cosmetic procedures 1,600,000 1,700,000 2,300,000
Non-invasive cosmetic procedures 11,600,000 14,200,000 13,200,000
Neurotoxins 5,300,000 6,700,000 4,400,000
Soft tissue fillers 1,700,000 2,400,000 3,400,000
Chemical peel 1,100,000 1,300,000 930,000
Laser resurfacing – – 1,000,000
Intense pulsed light treatment – – 800,000
Laser hair removal 900,000 1,100,000 –
Microdermabrasion 800,000 800,000 –
annual basis show that 13.2 million cosmetic research, and development focus on these
non-invasive procedures compared to 2.3 million modalities. These non-invasive treatments fall
cosmetic surgical procedures were performed in in the purview of plastic surgeons and medical
2020. Both sectors have experienced growth as providers such as cosmetic dermatologists, den-
11.6 million and 1.6 million cosmetic procedures tists, family medicine, and non-physician pro-
were performed in 2010, respectively. The top viders. Lastly, demand is driven by patients who
five most common non-invasive procedures are: will often prefer a series of office-based treat-
Neurotoxins (4.4 million), Soft Tissue Fillers ments with minimal downtime compared to lon-
(3.4 million), Chemical Peels (931,473), Laser ger, invasive surgical procedures that require
Resurfacing (997,245), and Intense Pulsed Light significant scar burden and/or general
(IPL) Treatments (827,409) (Table 38.1) [1]. anesthesia.
Neurotoxins, soft tissue fillers, and chemical Paralleling the high volume of non-invasive
peels have been consistently the most frequently cosmetic procedures, research on each of these
performed non-invasive procedures. More topics is abundant. Publications span safety,
recently, national trends show that laser resurfac- patient satisfaction/outcomes, indications for
ing and IPL procedures have surpassed laser hair treatments, comparative studies, treatment set-
removal and microdermabrasion procedures. tings/protocols, the physics behind the technol-
Also, during this time period, novel devices and ogy, and review articles (systematic reviews and
technologies have emerged to compete for mar- continued medical education reviews).
ket share. These include injectables and devices Therefore, selecting five landmark papers in the
indicated for fat reduction and non-surgical skin non-surgical/minimally invasive space is quite
tightening which were not even reported in ASPS challenging. This paper highlights five publica-
census data until 2016. tions in the non-invasive/minimally-invasive
The number of minimally invasive and non- space that have sparked paradigm shifts in
invasive treatments available are rapidly grow- patient care and aesthetic outcomes. Each of
ing for several reasons. Medications, these studies has led to downstream investiga-
pharmaceuticals, and device-based treatments tions in their respective topics and is subse-
are potentially quite profitable for industry. quently referenced numerous times in the
Thus, it is not surprising that investment, literature.
38 Evolution of Non-surgical/Minimally Invasive Treatments 399
38.2 Injectable Neurotoxins for the

Treatment of Dynamic and
Static Rhytids
Carruthers J, Carruthers J. Treatment of glabellar frown lines with C. Botulinum-A Exotoxin. J Dermatol Surg
Oncol. 1992;18(1):17–21 [2]
Strengths • Meticulous administration of same dosage and location for all subjects (medial corrugator).
Excellent and frequent patient follow-up to establish duration of treatment effects
Limitations • Low n (n = 18), lacking a real-time control group. Subjective rhytid severity grading scale
Impact Initial observation that botulinum toxin can be utilized for an aesthetic purpose. First to identify and
correlate that underlying muscle relaxation leads to effacement of surface rhytids. Revolutionized the
practice of treating facial rhytids
Deep rhytids of the face and neck are associated neck. While the number of patients in this study is
with advancing age in addition to a misperception low, the known mechanism of action—presynap-
of emotions. Patients with exaggerated static and tic inhibition of acetylcholine neurotransmitter
dynamic rhytids in the upper third of the face release in skeletal muscles—correlates with the
acknowledge that others assume they are angry, observed clinical findings. For over a decade, neu-
sad, or tired. Prior to the seminal paper by rotoxin was used off-label. They were studied
Carruthers and Carruthers [2], attempts to fill in extensively in two large randomized control stud-
the lines with collagen, silicone, or autologous ies before the United States Food and Drug
fat was the standard of care. The husband-wife Administration (FDA) approved its use for the
team had familiarity with the power of neurotox- treatment of glabellar rhytids (corrugators, pro-
ins when treating benign essential blepharo- cerus, and depressor supercilii) for cosmetic pur-
spasm, strabismus and hemifacial spasm with poses [3].
botulinum toxin. Incidentally, they astutely The continuous cycle of expanding indica-
observed that the patients injected for the treat- tions for cosmetic purposes is fueled by patient
ment of benign essential blepharospasm would demand, mastery of facial muscle anatomy,
return to their follow-up appointments without injector creativity, and tolerance to inject in off-
glabellar rhytids. They proceeded to explore label areas. As certain areas gain popularity and
these observations in a formal study. safety is demonstrated, the FDA eventually
Eighteen patients (17 female, 1 male) were expands cosmetic indications. FDA approved
injected with 10–12 units of botulinum toxin in cosmetic indications now including the treatment
the medial belly of each corrugator. Other than of crow’s feet (orbicularis oculi) since 2013 and
the one patient lost to follow-up, one patient was forehead lines (frontalis) since 2017 [4]. Popular
a non-responder. Improvement in glabellar off-label areas of injection include the depressor
rhytids for the remainder of the patients ranged septi nasi, nasalis, levator labii superioris alaeque
from “completely smooth” (n = 6), “minimal nasi, orbicularis oris, depressor anguli oris, men-
residual line” (n = 2) to “discernable brow crease talis, platysma, and masseter [5]. Expert practi-
but less deep” (n = 8). They demonstrated that tioners also utilize neurotoxins to manipulate
these treatments are safe and effective since all eyebrow shape, amount of visible upper lip ver-
complications noted were transient and minor in milion at rest, the angulation of the lateral lips/
nature. They also observed that the rhytids would commissure, and the amount of incisor shown
recur at approximately 3 to 4 months after injec- with smile animation.
tion and patients would return requesting an Until recently, there were three FDA-approved
additional injection. formulations, Botox (Allergan, Irvine, CA),
Prior to this study, botulinum toxin had been Dysport (Ipsen, Paris, France), and Xeomin
approved and utilized to treat various medical con- (Merz, Frankfurt, Germany), all of which have
ditions of muscular dysfunction of the head and unique formulations and dosing instructions.
However, all exhibited paralytic effects for able neurotoxins for targeted muscle paralysis for
3–4 months [6]. In 2021, DaxibotulinumtoxinA aesthetic purposes. Since that pivotal observa-
(DAXI), a similar neurotoxin with a proprietary tion, there has also been an inversely proportional
non-albumin complexing protein gained FDA decline in the practice of filling lines with col-
approval. Published results endorse a longer last- lage, silicone, and autologous fat.
ing clinical effect, up to 6 months due to the sta- Even though that particular indication for fill-
bility of the complexing protein [7]. ers has decreased, the utility of soft tissue fillers
Neurotoxins have revolutionized office-based in facial volume augmentation has grown expo-
cosmetic procedures given their overall safety nentially. After injectable neurotoxin procedures,
profile, ease of injection, and intermediate-lasting soft tissue fillers have consistently ranked as the
results. The serendipitous observation by second most performed procedure in the United
Carruthers and Carruthers propelled use inject- States in the recent years [1].
38.3 Soft Tissue Fillers: The Rise

of Hyaluronic Acid Fillers
Duranti F, Salti G, Bovani B, Calandra M, Rosati ML. Injectable hyaluronic acid gel for soft tissue augmentation: a
clinical and histological study. Dermatologic Surg. 1998;24(12):1317–25 [8]
Strengths • Serial clinical and histologic evaluations of implanted hyaluronic acid filler in the face were
performed to determine safety, efficacy, and duration of treatment effect. The histology portion of
the study included a comparative control, the standard of care at the time, and injectable collagen
implant
Limitations • Only the pathologist, during the histology portion of the study, was blinded. Inclusion of a control
group, i.e., collagen injections in the same anatomic locations, for the clinical arm of the study
would have further validated the findings
Impact This study was the first to assess the safety and efficacy of hyaluronic acid fillers in the United States.
Since then, this class of fillers has become the industry standard given the biocompatibility, ease of
use, manufacturing/production scalability, and capacity to enzymatically dissolve when clinically
indicated
Various products have been utilized as soft tissue the intradermal matrix that decreases with age,
fillers throughout the years. While we are most contributing to dermal dehydration and
familiar with hyaluronic acid (HA) products substance.
nowadays, this has not always been the case. Non-animal, synthetic HA fillers that obviate
Bovine collagen (the gold standard since the the need for pre-treatment skin testing were ini-
1970s), silicone, and autologous fat have histori- tially approved for use in Europe but not in the
cally been the preferred materials for injection. United States. Although available worldwide
However, of all fillers, the bio-characteristics of since the 1990s, HA fillers were not approved by
HA fillers most closely resemble the ideal filler the FDA until 2003, after numerous studies
properties that practitioners desire [9]. Safe and affirmed safety [9, 10] and efficacy [11].
effective ideal characteristics include: biocom- Duranti and colleagues were pioneers in bring-
patibility, non-antigenic, nonpyrogenic, nonin- ing HA fillers to the United States. They injected
flammatory, nontoxic, easy to use, stable after Restylane (Q-Med, Uppsala, Sweden) into 273
injection, non-migratory, long-lasting, resorb- facial areas (acne scars, glabellar lines, oral com-
able, affordable, and reversible. HA is a natu- missure folds, nasolabial folds, and lips) for 158
rally occurring hydrophilic structure found in consecutive patients. Subjective ratings were
recorded for the patient and physician (in-person been reported in addition to the minor, transient
and photographs) at various time points. In gen- complications observed in the early studies.
eral, a high percentage, greater than 70% of These include angioedema, malar edema, and
patients and physicians noted “marked” to “mod- vascular occlusion leading to downstream tissue
erate” improvements that lasted until the final necrosis or blindness [12]. Anatomic danger
time point of 8 months post injection. Adverse areas have been identified for injectors to refer-
events were transient and mild in terms of sever- ence along with published safety principles to
ity. Discomfort, edema, erythema, and tenderness minimize the risk of these devastating complica-
localized to the treatment site were observed. Five tions [13, 14]. Injecting filler into the nose was
volunteers were injected with both HA and colla- originally avoided and thought to be extremely
gen in the forearms. The histology portion of the high risk for vascular compromise given the
study confirmed longevity, presence of HA filler highly vascular nature of the nose. Current stud-
at the 52-week biopsy, and the favorable safety ies have affirmed that it can be performed safely
profile given that a minimal amount of surround- by keeping the injection deep and midline with
ing inflammation with very few inflammatory manual massage to push the filler laterally when
cells were identified on microscopy. Unlike col- needed [15]. Most importantly, clinicians per-
lagen implantation, the high biocompatibility of forming filler augmentation procedures, espe-
HA eliminates the need for preliminary skin test- cially when in off-label areas, must have a robust
ing [8]. Years later, a randomized controlled, dou- understanding of three-dimensional facial
ble-blind, split face, multi-center study comparing anatomy.
HA filler (Restylane, Q-Med, Uppsala, Sweden) As the demand for non-surgical facial rejuve-
to Bovine collagen (Zyplast, McGhan Medical, nation continues to grow worldwide, HA prod-
Santa Barbara, CA) found that less volume of HA ucts have become the gold standard for injectable
was used to achieve an “optimal cosmetic result” fillers [11]. Practitioners can curate treatment
making it the more effective and durable treat- plans leveraging the benefits of particular fillers
ment option [10] In addition to providing level I based on rheologic properties, anatomic loca-
evidence, this study implemented objective mea- tion, and depth of injection to optimize the
sures—The Wrinkle Severity Rating Scale and patient experience and attain the best aesthetic
the Global Aesthetic Improvement Scale to gauge results.
the degree of their findings. Mild degrees of skin laxity can be improved
Manufacturers of HA fillers have been able to by restoring volume to the underlying soft tis-
alter rheology creating a host of products by sues with filler. However, it is important to
altering various physical properties: degree of refrain from injecting disproportionate
crosslinking, molecular weight, and concentra- amounts of volume in hopes of treating excess
tion of HA chains. Also, the ability to mass pro- skin laxity. Achieving aesthetic harmony relies
duce non-animal derived synthetic product, on the practitioner making the correct diagno-
through bacterial fermentation lab techniques, sis and using multiple modalities when
has contributed to the large scalability for this addressing volume deficiency and skin laxity.
class of facial dermal fillers. This will avoid complications such as an over-
Consequently, since the widespread use of HA filled face colloquially referred to as “filler
fillers, certain significant complications have face.”
38.4 Non-excisional
Improvements in Skin Laxity
Bassichis B, Dayan S, Thomas R. Use of a nonablative radiofrequency device to rejuvenate the upper one-third of
the face. Otolaryngol Head Neck Surg. 2004;130(4):397–406 [16]
Strengths • Objectively measured contractile effect via degree of brow elevation. Compared results to a control
group that did not undergo treatment
Limitations • Limited sample size (n = 24). Attempted to objectively measure degree of skin tightening indirectly
via brow elevation
Impact First generation non-invasive radiofrequency devices showed promising skin tightening results by
creating controlled thermal damage to the dermis without the need for damaging the epidermal layer.
Next generation, bipolar radiofrequency devices have been subsequently developed to more safely
address the disparity in temperature thresholds—achieving a controlled thermal injury to the dermis
inducing neocollagenesis and fat reduction without irreversibly damaging the epidermis
Dermabrasion, laser resurfacing, and chemical The first FDA approved device in this space,
peels have all been utilized to improve skin qual- Thermage™ (Solta Medical, Hayward, CA), was
ity and treat skin laxity. Skin excision has been designed to generate a controlled thermal injury
the gold standard for the treatment of skin laxity; to the dermis without removing or harming the
however, the associated scars can be quite exten- epidermis. It harnessed benefits from radiofre-
sive. Thus, patients and practitioners have quency energy (heating of the dermis) along with
recently turned to non-invasive/minimally inva- simultaneous conductive cooling (preventing
sive treatments to prevent the need for excisional epidermal thermal injury) [16]. The sequence of
procedures or even just to minimize scar burden. action for the first-generation devices involved a
Skin rejuvenating treatments create a small, full cycle of pre-cooling, radiofrequency heating, and
thickness injury to the skin relying on subsequent post-cooling. This allowed for heating the dermis
wound healing mechanisms (re-epithelialization to 65 °C while the epidermal temperature would
and dermal remodeling). Consequently, repairing not exceed 45 °C. In order to achieve thermally
the inciting damage leads to dermal thickening induced denaturing of collagen in the dermis, a
through neocollagenesis. Clinically this trans- temperature of 60 °C must be reached. However,
lates to skin resurfacing, effacement of irregulari- temperatures greater than 45 °C on the epidermis
ties, and the treatment of fine rhytids. However, generate an irreversible injury.
excessive inadvertent epithelial damage may Prior to this landmark study, the first-
result in suboptimal healing and scaring in addi- generation radiofrequency wave devices
tion to prolonged recovery “downtime.” Dark described above were used on abdominal skin
skin patients with a higher Fitzpatrick skin type specimens after abdominoplasty to evaluate
are too high risk and therefore not indicated for treatment settings as well as histologic evaluation
these treatments. New frontiers in the non- to identify skin changes. However, the results of
invasive and minimally invasive space were con- this experiment were not published at that time.
quered with the application of radiofrequency Bassichis and colleagues were the first to publish
waves for skin tightening. It involves a safe the utility of this device to treat forehead rhytids
method to indirectly deliver thermal energy (con- of 24 patients. Precise measurements of the eye-
verted from electrical current rather than a light brow position relative to the pupil were taken to
source) to the dermis without damaging the epi- indirectly measure skin contraction. At 1-month
dermis. This is critical to the efficacy and safety post treatment, a statistically significant increase
of these treatments [17]. Additionally, these in brow elevation (uniform at all points along the
devices are considered extremely versatile in eyebrow) was observed in the majority of
terms of the number of devices that exist and the patients. Although patient satisfaction did not
breadth of aesthetic indications [18]. improve, the significance of these findings was
that this technology could generate skin contrac-
tion and tightening [16]. Shortly after their publi- Some non-invasive treatments combine mul-
cation a second study confirmed these tiple modalities. A recently popularized device
observations. The authors utilized the same combines radiofrequency, for fat reduction,
device to demonstrate improvement in skin laxity along with high-intensity focused electromag-
of the neck and cheek without any significant netic energy, for improvements in muscle tone.
complications [19]. An ultrasound-based sham-controlled study
The introduction of radiofrequency-based demonstrated clinically significant fat reduction
devices into the clinical setting for skin/mucosal and muscle gain after three treatments. Patient
tightening and neocollagenesis has extended the satisfaction with regard to body contouring
frontier of minimally invasive office-based proce- improvements in the treatment group was also
dures. The initial tightening benefit is attributed to significantly higher without evidence of compli-
coagulation, while downstream neocollagenesis cations [22].
and dermal remodeling offer additional tightening/ As the sophistication of these devices contin-
contraction at the 2–3 month time period. ues to improve, the ability to compare outcomes
Subsequent generations of the devices integrated in the literature becomes more challenging.
cooling systems within the tip to maintain more Practitioners can modulate numerous variables
consistent temperatures and avoid temperature including: maximal temperature achieved, time
peaks. Nowadays, even more sophisticated monop- spent at goal temperature, energy delivered,
olar, bipolar, multipolar, and microneedling devices energy delivered at a specific depth, number of
based on the number of electrodes have been devel- pulses, number of passes at various depths, num-
oped to deliver controlled amounts of radiofre- ber of treatments, etc. Additionally, the over-
quency energy to precise location of the skin and whelming majority of the studies use patient
subcutaneous tissues. The real-time internal and/or surveys to assess outcomes. Albeit these mea-
external temperature monitoring provides an addi- sures are not standardized, patient reported satis-
tional layer of safety. Thermal energy delivered to faction, improvements in quality of life or
the subcutaneous layer can reduce adipose tissue in symptomatic improvement considered represent
addition to previously identified skin tightening the ultimate endpoint of patient care. What
benefits [17, 18]. Initially indicated for the face and patients perceive or how much improvement they
body, more recently, studies have shown improve- endorse from these treatments is more clinically
ments in the following symptoms: dry eyes, vulvo- relevant than the amount of tightening or percent-
vaginal irritation, and vaginal dryness or age of collagen produced in animal or ex vivo
vulvovaginal atrophy [20]. In 2022, Rohrich et al. studies. Ultimately, the rapidly growing trajec-
re-evaluated the literature on radiofrequency treat- tory of minimally invasive radiofrequency-based
ments, affirming that both monopolar and bipolar treatments that can be performed in the office set-
radiofrequency platforms lead to skin and soft tis- ting reflects the high demand for these proce-
sue contraction with an acceptable risk profile. dures coupled with the nuanced modulation of
Aligning with previous findings, the authors note settings by the practitioner to achieve excellent
that adverse effects were mild and transient [21]. outcomes.
38.5 Targeted Injectable Lipolysis

for Submental Contouring
Rittes PG. The use of phosphatidylcholine for correction of localized fat deposits. Aesthetic Plast Surg.
2003;27(4):315–8 [23]
Strengths • A long, 2-year, follow-up of the patients is commendable. Authors describe the importance of
systematic delivery of “medication” to achieve an even distribution in the target area
Limitations • The study lacks a control group even though they monitor weight fluctuations to control for the
most important confounding variable
Impact Introduced the possibility of using injectable adipolytics in the office setting to reduce subcutaneous
fat and affect contours
Patients and practitioners appreciate the ease, 101 suggesting a dose-dependent relationship
simplicity, reduced financial burden, and high even though this study was not designed to com-
satisfaction rates with injectables. The growth of pare dosing regimens. Overall, the treatment was
the industry is also reflected by the rise in number well tolerated with minimal adverse effects even
of medical spas providing comfortable and con- though a statistically significant number of
venient access to such treatments. While neuro- patients, 10% from each of the ATX-101 arms (1
toxins and soft tissue fillers dominate the and 2 mg/cm−2), withdrew from the study com-
injectable space for the treatment of facial rhytids pared to placebo [24]. A separate multi-center,
and soft tissue deficiency, respectively, a novel phase III, randomized controlled study, found
class of injectable medication was introduced in that the 66.5% compared to 22.2% of adults
the early 2000. treated with ATX-101 versus placebo achieved
Injectable adipolytic therapies have been improvement in patient reported submental fat
attempted since 1950; however, many were impact scale of at least 1 grade, while 18.6% ver-
banned from clinical use due to lack of scientific sus 3.0% had improvements of 2 or more grades.
evidence demonstrating safety and efficacy. In addition to patient satisfaction ratings, mag-
Phosphatidylcholine is a component of bile netic resonance imaging confirmed fat reduction
responsible for emulsification of lipids from in the submental area while patient surveys dem-
ingested food. In this pivotal study, phosphatidyl- onstrate the psychological benefit and high
choline was isolated and serially injected subcu- patient satisfaction after AXT-101 injection treat-
taneously in a systematic manner to the abdomen, ments [25]. Scientific validation and widespread
neck, arms, or thighs depending on patient use has essentially created a new class of non-
desires. Ideal candidates for this study included invasive treatments in the realm of aesthetic plas-
patients at their ideal body weight that presented tic surgery. The submental region is an
with modest amounts of localized adiposity. anatomically well-defined region framed by the
Contour improvements were observed and docu- inferior mandibular border down to the level of
ment with photography for all patients [23]. the hyoid. This particular area is often highly
Subsequently, ATX-101, a synthetically troublesome to patients. It also provides a con-
derived formulation of deoxycholic acid, was tained area amenable to studying the efficacy of
designed to disrupt adipocyte cell membranes, such treatments.
induce apoptosis with downstream inflammation Determining the quality of aesthetic outcomes
and phagocytosis. It also results in a clinical is subjective often times. Caution must be
reduction in fat and affecting overlying contours. employed when measuring and analyzing the
ATX-101 was the first in its class of injectable cervicomental angle of pre- and post-treatment
medication for targeting localized subcutaneous photographs as an attempt to create objective out-
adiposity to be studied as a medication undergo- comes. However, this is extremely unreliable.
ing rigorous phase I, II, and III trials. Phase 1 and Neck aesthetics on a lateral photograph can be
2 studies introduced this injectable medication to easily manipulated by translating the head in the
the world while assessing safety and dosing. It anterior-posterior (AP) direction, tilting the head
was not until a large volume phase 3 study from (looking up or down), translating the mandible in
multiple centers in Europe that encourages FDA the AP direction and instructing the patient to
approval for its use in the United States. place the tongue against the hard palate raising
Compared to placebo, patients treated with ATX- the entire tongue musculature complex.
101 (1 and 2 mg cm−2 groups) were significantly Overall, in the appropriately selected
more satisfied with their submental fat appear- patient—patients with minimal submental focal
ance. Also, clinicians reported improved sub- adiposity and no evidence of banding—the
mental fat severity in both treatment arm groups. results of serial ATX-101 injections can be satis-
Greater improvements in all outcomes were fying for both the clinician and patient. In 2019,
observed with the higher administration of ATX- a different group conducted a study using
3-dimentional Vectra imaging to assess the effi- minimally invasive procedures that have gained
cacy of this injectable medication. They found popularity recently target neck contouring by
improved patient satisfaction scores and a statis- liposuction coupled with bipolar radiofrequency
tically significant volume reduction in 13 energy devices [21] and light guided, percutane-
patients [26]. Awareness of ATX-101, how to ous suture suspension techniques [27].
administer it with the appropriate dosing, is Unfortunately, no studies to date directly com-
valuable to maintain in a surgeon’s armamentar- pare the efficacy of these minimally invasive/
ium for non-invasive neck contouring. Other non-invasive treatment modalities.
38.6 Targeted Transcutaneous

Non-injectable
Cryo-adipolysis
Manstein D, Laubach H, Watanabe K, Farinelli W, Zurakowski D, Anderson RR. Selective cryolysis: a novel method
of non-invasive fat removal. Lasers Surg Med. 2008;40(9):595–604 [28]
Strengths • Findings affirm safety and efficacy of a novel technology by objectively demonstrating a decrease
in adipocytes without damaging overlying skin in the porcine model
Limitations • Study utilizing an animal model (n = 4). Study was sponsored by Zeltiq aesthetics (manufactured
the CoolSculpt device). Generalizability to human application of these findings was initially
questioned
Impact First to coin the term “selective cryolysis” by using a device to deliver a controlled cold temperature
to target focal areas of adiposity. After success in the porcine model, this technology was
subsequently translated to the clinical setting for humans adding an additional modality for fat
reduction and body contouring in the non-invasive space
Cold panniculitis is a form of traumatic fat necro- demonstrated notable concave external contours
sis initially described in 1902. It is a phenomenon that matched the shape and size of the applicator.
that mostly affects infants and children; seen in Forty percent fat reduction was observed which
critical care units after the application of cold was contained to the superficial adipose layer
packs, in countries with extreme cold outdoor with minimal or no change to the deep fat com-
temperatures and even a case report of “popsicle partment. Histologically, adipose cell apoptosis
panniculitis” of the buccal fat pad, the thermal with the presence of macrophages indicated the
exposure triggers fat necrosis with subsequent post cryo-lipolysis inflammatory effect—peaked
hardening of the soft tissues [29]. between day 14 and 30—on a cellular level.
The demand for non-invasive body contouring Overall, this pivotal but preliminary study dem-
continues to challenge surgeons and industry to onstrated that cold-induced apoptosis of adipo-
develop technologies that can efficiently target cytes in the superficial fat layer triggered an
adipose tissue without damaging adjacent sur- inflammatory reaction. Most importantly, there
rounding tissue or confer significant risk to the was no evidence of skin injury on gross or histo-
patient. One type of technology that has recently logic evaluation. These findings were repeated
gained popularity takes advantage of fat cells and expanded upon in a subsequent study the fol-
being more sensitive to cold temperatures than lowing year [30].
other cells. After treatment, adipocyte cell lysis Numerous clinical investigations have since
triggers an internal processing sequence to been performed to expand upon the significant
Non-invasive cold exposure was applied to implication of the initial porcine findings. The
porcine animals. The investigators examined the reduction of fat has been demonstrated on gross
effects (gross and microscopic) at various time inspection, photographic analysis, ultrasound,
points after modulating the degree of cold expo- and histologic assessments [31, 32]. The FDA
sure. Three-month evaluations after treatment approved cryo-lipolysis technology for clinical
use in 2010. While, initially approved for the customizing treatment plans for patients. We
flanks, indications have expanded to include the have seen over the years, the power of utilizing
abdomen (2012), thighs (2014), bra fat (2016), multi-modality treatments in order to optimize
back (2016), submental (2017), banana roll outcomes and to meet the increasingly high
(2018), and upper arms (2019). patient expectations. This trend will continue in
Many studies have demonstrated a level of the plastic surgery/cosmetic dermatology arena
clinical efficacy and safety associated with these and providers will be obligated to stay current on
treatments [33, 34]. Patient compliance with available non-surgical options with a deep under-
multiple treatment sessions and patients is often standing of their associated limitations/benefits.
required [32]. Erythema, bruising, discomfort,
and temporary pain/neuralgia are the more com- Financial Disclosure Statement Dr. Vranis does not
mon side effects. However, the risk of paroxys- have any financial disclosures. Dr. Dyan receives royalties
from Thieme and is a consultant/investigator for InMode.
mal adipose hyperplasia (PAH), albeit a small Dr. Theodorou has financial interest in InMode and
percentage of treated patients develop PAH, may receives royalties from Thieme.
deter some practitioners from recommending it
to patients. PAH is treated with liposuction and
depending on the skin quality, a skin tightening References
treatment may also be warranted. Each fat reduc-
tion treatment modality ranging from maximally 1. American Society of Plastic Surgery. Annual plastic
invasive (excisional procedures and/or liposuc- surgery statistics report. https://www.plasticsurgery.
org/news/plastic-surgery-statistics. Accessed 30 Jan
tion) to non-invasive procedures have their own 2023.
unique set of risks and benefits. While suction 2. Carruthers J, Carruthers J. Treatment of glabel-
assisted lipectomy remains the gold standard, lar frown lines with C. Botulinum—a exotoxin. J
other modalities can be used for a more modest Dermatol Surg Oncol. 1992;18(1):17–21.
3. Frampton JE, Easthope SE. Botulinum toxin a
transformation. Together with patients, one can (Botox® cosmetic): a review of its use in the treat-
select the most appropriate or combination of ment of glabellar frown lines. Am J Clin Dermatol.
treatments when formulating a comprehensive 2003;4(10):709–25.
body contouring plan. 4. de Boulle K, Carruthers A, Solish N, et al.
Onabotulinumtoxina treatment for moderate to severe
forehead lines: a review. Plast Reconstr Surg Glob
Open. 2020;8(3):e2669.
38.7 Expert Concluding 5. Small R. Botulinum toxin for facial wrinkles. Am
Commentary Fam Physician. 2014;90(3):168–75.
6. Frevert J. Pharmaceutical, biological, and clinical
properties of botulinum neurotoxin type a products.
The non-invasive and minimally invasive space Drugs R D. 2015;15(1):1–9.
compliments and may even augment surgical 7. Solish N, Carruthers J, Kaufman J, Rubio RG, Gross
practice. Over the last 50 years, we have seen TM, Gallagher CJ. Overview of DaxibotulinumtoxinA
for injection: a novel formulation of botulinum toxin
notable discoveries with profound advancements type a. Drugs. 2021;81(18):2091–101.
in the application of neurotoxins, fillers, radiofre- 8. Duranti F, Salti G, Bovani B, Calandra M, Rosati
quency, and adipolytics in aesthetic medicine. ML. Injectable hyaluronic acid gel for soft tis-
These powerful treatments can have significant sue augmentation: a clinical and histological study.
Dermatologic Surg. 1998;24(12):1317–25.
effects in facial or body contours, skin tightening, 9. Friedman PM, Mafong EA, Kauvar ANB, Geronemus
and overall rejuvenation. Typically, patient will RG. Safety data of injectable nonanimal stabilized
require a series of treatments; however, the ease hyaluronic acid gel for soft tissue augmentation.
to perform, smaller financial burden, and mini- Dermatologic Surg. 2002;28(6):491–4.
10. Narins RS, Brandt F, Leyden J, Lorenc ZP, Rubin
mal downtime make them worthwhile for both M, Smith S. A randomized, double-blind, multi-
patients and providers. As technology continues center comparison of the efficacy and tolerability of
to evolve, we anticipate that the practitioner will Restylane versus Zyplast for the correction of naso-
have even more modalities to choose from when labial folds. Dermatologic Surg. 2003;29(6):588–95.
11. Rohrich RJ, Bartlett EL, Dayan E. Practical approach 24. Rzany B, Griffiths T, Walker P, Lippert S, McDiarmid
and safety of hyaluronic acid fillers. Plast Reconstr J, Havlickova B. Reduction of unwanted submental
Surg Glob Open. 2019;7(6):e2172. fat with ATX-101 (deoxycholic acid), an adipocyto-
12. Funt D, Pavicic T. Dermal fillers in aesthetics: an lytic injectable treatment: results from a phase III,
overview of adverse events and treatment approaches. randomized, placebo-controlled study. Br J Dermatol.
Clin Cosmet Investig Dermatol. 2013;6:295–316. 2014;170(2):445–53.
13. Scheuer JF, Sieber DA, Pezeshk RA, Gassman AA, 25. Humphrey S, Sykes J, Kantor J, et al. ATX-101
Campbell CF, Rohrich RJ. Facial danger zones: tech- for reduction of submental fat: a phase III ran-
niques to maximize safety during soft-tissue filler domized controlled trial. J Am Acad Dermatol.
injections. Plast Reconstr Surg. 2017a;139(5):1103–8. 2016;75(4):788–797.e7.
14. Scheuer JF, Sieber DA, Pezeshk RA, Campbell CF, 26. Grow JN, Holding J, Korentager R. Assessing the
Gassman AA, Rohrich RJ. Anatomy of the facial dan- efficacy of deoxycholic acid for the treatment of sub-
ger zones: maximizing safety during soft-tissue filler mental fat: a three-dimensional study. Aesthetic Surg
injections. Plast Reconstr Surg. 2017b;139(1):50e–8e. J. 2019;39(12):1400–11.
15. Rohrich RJ, Agrawal N, Avashia Y, Savetsky 27. Gomez DA, James IB, Turer DM, et al. Light-guided
IL. Safety in the use of fillers in nasal augmenta- percutaneous neck rejuvenation with division of pla-
tion—the liquid rhinoplasty. Plast Reconstr Surg Glob tysma bands and suture suspension: a multicenter ret-
Open. 2020;8:1–2. rospective study. Aesthetic Surg J 2022;00(0):1–12.
16. Bassichis B, Dayan S, Thomas R. Use of a nonab- 28. Manstein D, Laubach H, Watanabe K, Farinelli W,
lative radiofrequency device to rejuvenate the upper Zurakowski D, Anderson RR. Selective cryolysis:
one-third of the face. Otolaryngol Head Neck Surg. a novel method of non-invasive fat removal. Lasers
2004;130(4):397–406. Surg Med. 2008;40(9):595–604.
17. Schavelzon D, Paul MD. A safety and feasibility study 29. Quesada-Cortés A, Campos-Muñoz L, Díaz-Díaz
of a novel radiofrequency-assisted liposuction tech- RM, Casado-Jiménez M. Cold panniculitis. Dermatol
nique. Plast Reconstr Surg. 2008;125(3):998–1006. Clin. 2008;26(4):485–9.
18. Sadick N, Rothaus KO. Aesthetic applica- 30. Zelickson B, Egbert BM, Preciado J, et al.
tions of radiofrequency devices. Clin Plast Surg. Cryolipolysis for noninvasive fat cell destruction:
2016;43(3):557–65. initial results from a pig model. Dermatologic Surg.
19. Alster TS, Tanzi E. Improvement of neck and 2009;35(10):1462–70.
cheek laxity with a non-ablative radiofrequency 31. Bernstein EF, Bloom JD, Basilavecchio LD,
device: a lifting experience. Dermatologic Surg. Plugis JM. Non-invasive fat reduction of the flanks
2004;30(4):503–7. using a new cryolipolysis applicator and over-
20. Ward S, Iglesia CB. Energy-based therapies in female lapping, two-cycle treatments. Lasers Surg Med.
genital cosmetic surgery: hype, hope and a way for- 2014;46(10):731–5.
ward. OBG Manag. 2019;31(5):SS9–SS15. 32. Mulholland RS, Paul MD, Chalfoun C. Noninvasive
21. Rohrich RJ, Schultz KP, Chamata ES, Bellamy JL, body contouring with radiofrequency, ultrasound,
Alleyne B. Minimally invasive approach to skin cryolipolysis and low-level laser therapy. Clin Plast
tightening of the face and body: systematic review of Surg. 2011;38(3):503–20.
monopolar and bipolar radiofrequency devices. Plast 33. Grant Stevens W, Pietrzak LK, Spring MA. Broad
Reconstr Surg. 2022;150(4):171–80. overview of a clinical and commercial experience with
22. Samuels JB, Katz B, Weiss RA. Radiofrequency coolsculpting. Aesthetic Surg J. 2013;33(6):835–46.
heating and high-intensity focused electromagnetic 34. Ingargiola MJ, Motakef S, Chung MT, Vasconez
treatment delivered simultaneously: the first sham- HC, Sasaki GH. Cryolipolysis for fat reduction
controlled randomized trial. Plast Reconstr Surg. and body contouring: safety and efficacy of cur-
2022;149(5):893–900. rent treatment paradigms. Plast Reconstr Surg.
23. Rittes PG. The use of phosphatidylcholine for cor- 2015;135(6):1581–90.
rection of localized fat deposits. Aesth Plast Surg.
2003;27(4):315–8.
Part XIV
Evolution of Patient-Reported
Outcomes (PROs)
The Evolution of Patient-Reported
Outcome Measures (PROMs)
39
in Plastic Surgery
Colby J. Hyland, Anne F. Klassen,

and Andrea L. Pusic
Abstract Keywords
Patient-reported outcomes (PROs) are health Patient-reported outcomes · Patient-reported
outcomes that are only known to, and can be outcome measures · PROs · PROMs · Quality
reported by, patients, such as physical, psy- of life
chosocial, and sexual wellbeing after surgery.
Patient-reported outcome measures (PROMs)
are questionnaires that enable rigorous and The Five Most Impactful Papers
quantifiable measurement of PROs. Improving 1. Pusic AL, Klassen AF, Scott AM, Klok JA,
the health-related quality-of-life (HRQL) of Cordeiro PG, Cano SJ. Development of a
patients is central to performing the vast new patient-reported outcome measure for
majority of plastic and reconstructive surgery breast surgery: the BREAST-Q. Plast Recon-
procedures. As such, PROMs are useful and str Surg. 2009;124(2):345–53.
important metrics for patient-centered care, 2. Santosa KB, Qi J, Kim HM, Hamill JB,
innovation, and quality improvement. Here, Wilkins EG, Pusic AL. Long-term Patient-
we review five landmark papers to demon- Reported Outcomes in Postmastectomy
strate the evolution of PROMs in plastic sur- Breast Reconstruction. JAMA Surg.
gery. Specifically, we highlight key studies in 2018;153(10):891–9.
the development, utility, impact, and imple- 3. Klassen AF, Cano SJ, Scott A, Snell L,
mentation of PROMs in plastic surgery. Pusic AL. Measuring patient-reported out-
comes in facial aesthetic patients: develop-
ment of the FACE-Q. Facial Plast Surg.
2010;26(4):303–9.
4. Chung KC, Kim HM, Malay S, Shauver MJ.
Comparison of 24-month outcomes after treat-
ment for distal radius fracture: the WRIST ran-
C. J. Hyland · A. L. Pusic (*) domized clinical trial. JAMA Netw Open.
Division of Plastic and Reconstructive Surgery, 2021;4(6):e2112710.
Brigham and Women’s Hospital, Boston, MA, USA 5. Nelson JA, Chu JJ, Dabic S, et al. Moving
Patient-Reported Outcomes, Value & Experience towards patient-reported outcomes in routine
(PROVE) Center, Boston, MA, USA clinical practice: implementation lessons
A. F. Klassen from the BREAST-Q. Qual Life Res. 2023;
McMaster University, Hamilton, ON, Canada 32(1):115–25.
https://doi.org/10.1007/978-3-031-57132-9_39
412 C. J. Hyland et al.
39.1 Introduction cal research, Pusic et al. first described the

range of generic, ad hoc, oncologic, and educa-
Measuring meaningful health outcomes has long tion questionnaires that had been used to mea-
been a critical component of healthcare delivery sure outcomes in breast surgery studies. Of 227
[1]. Originating in the 1980s, the “outcomes questionnaires, only seven were breast-spe-
movement” was borne out of an increasing need cific, and of these, six had undergone limited
for standardized metrics to address geographic development and psychometric validation [6].
variability in care delivery, competition among The authors noted that valid, reliable, and
insurers, and to drive cost containment [1, 2]. responsive instruments to measure patient-
Since that time, the definition of meaningful reported outcomes in cosmetic and reconstruc-
health outcomes has evolved from more tradi- tive breast surgery were lacking. To address
tional metrics of mortality and readmission rates this deficit, Pusic et al. subsequently described
to patient-centered outcomes, such as physical, the development of the BREAST-Q, a vali-
emotional, and social well-being [1]. dated PROM for breast surgery, which fol-
Increasing interest in patient-centered out- lowed international standards for psychometric
comes coincided with scientific advances in mea- questionnaire development and satisfied crite-
surement theory and psychometrics. In particular, ria set forth by the Food and Drug
advances such as Item Response Theory (IRT) Administration (FDA) [7].
and Rasch Measurement Theory (RMT) have Their seminal work, which incorporated
enabled more scientific and quantitative measure- patient interviews, expert panels, focus groups,
ments of qualitative data, for both groups and and extensive literature reviews not only
individuals [3]. In turn, patient-reported outcomes resulted in a new PROM that could be used
(PROs)—or reports made directly by patients preoperatively and postoperatively in both cos-
about their health-related quality of life (HRQL)— metic and reconstructive settings, but also set
could be developed into rigorous patient-reported the standard for high-quality PROM develop-
outcome measures (PROMs) [4, 5]. ment in plastic surgery [7]. Specifically, with
In plastic and reconstructive surgery, where data from a large field-test study, the authors
constant innovation presents patients and sur- documented adherence to key psychometric
geons with many different options, and where properties, such as acceptability, reliability
improving HRQL from the patient’s perspective (e.g., internal consistency, test-retest reproduc-
is often the indication for performing surgery, ibility), and validity (e.g., content validity,
PROMs are particularly relevant and important. construct validity) [7]. They also utilized
Here, we describe five landmark papers to high- Rasch analysis, which enabled detection of
light the evolution of PROMs in plastic surgery. meaningful clinical changes in PROM scoring
Specifically, we describe key studies in PROM for individual patients—creating potential for
development, how PROMs have been used to the use of the BREAST-Q not only in clinical
generate meaningful comparisons for clinical research but also in routine clinical care [7]. In
decision-making, and the application of PROMs sum, the BREAST-Q enabled rigorous and sci-
across plastic surgery sub-specialties in both entific measurement of breast surgery out-
research and routine clinical care. comes from the unique perspective of the
patient and created a framework for future
PROM development across plastic surgery
39.2 Establishing a Standard disciplines.
for Rigorous Development
of PROMs in Plastic Surgery
Amidst increasing interest in the use of patient-

reported outcome measures (PROMs) in clini-
39 The Evolution of Patient-Reported Outcome Measures (PROMs) in Plastic Surgery 413
Pusic AL, Klassen AF, Scott AM, Klok JA, Cordeiro PG, Cano SJ. Development of a new patient-reported outcome
measure for breast surgery: the BREAST-Q. Plast Reconstr Surg. 2009;124(2):345–53 [7]
Strengths • Use of rigorous psychometric methods that followed international standards for PROM
development
• Application across different types of breast surgery (i.e., reconstructive and cosmetic)
• Modular design which makes it possible to add new scales in the future to keep pace with
innovation (e.g., breast sensation)
Limitations • Developed within a population of North American women, which may limit generalizability to
other populations
• Initially developed for a limited set of procedures (e.g., did not include a breast conserving therapy
module)
Impact As the first PROM for breast surgery, the BREAST-Q has enabled scientific comparison of surgical
procedures and techniques from the perspective of patients. The BREAST-Q established a high-
quality standard for patient-centered outcome measurement that would facilitate quality improvement
and innovation in plastic surgery
39.3 The Utility of PROMs tion [8]. Importantly, they also showed that
in Clinical Decision-Making patients who underwent autologous reconstruc-
tion experienced worse abdominal well-being
Development of the BREAST-Q offered much [8]. These findings offered long-term, patient-
clinical potential, particularly by enabling com- centered outcomes, concerning both advantages
parison of patient-centered outcomes between and disadvantages of different breast reconstruc-
reconstructive options for breast surgery. In their tion options, that can inform shared decision-
multicenter, prospective study, Santosa et al. making between patients and plastic surgeons.
examined BREAST-Q outcomes of 2013 patients As many reconstructive options are available for
who had received either implant-based or autolo- a given patient presentation across plastic sur-
gous reconstruction at 3–4 years postoperatively gery sub-specialties, this study also highlights
[8]. They showed that patients who underwent the utility of PROMs as comparative metrics for
autologous reconstruction experienced signifi- surgical options in plastic surgery. Many other
cantly greater satisfaction with breasts as well as studies have used PROMs to prospectively com-
better psychosocial and sexual well-being than pare outcomes in breast [9] and hand surgery
those who underwent implant-based reconstruc- [10], among other fields.
Santosa KB, Qi J, Kim HM, Hamill JB, Wilkins EG, Pusic AL. Long-term Patient-Reported Outcomes in
Postmastectomy Breast Reconstruction. JAMA Surg. 2018;153(10):891–9 [8]
Strengths • Multi-center, prospective study of 2013 women that used PROMs to compare different
reconstructive modalities
• Long-term follow up of 3–4 years post-operative
Limitations • Lower response rates at long-term follow up timepoints
• Non-randomized design, which may have introduced confounds for patients who opted for
implant-based versus autologous reconstruction
• Inclusive of patients who successfully completed reconstruction only
Impact This was the first study that prospectively assessed patient-centered outcomes using a rigorously
validated PROM for different breast reconstruction surgical modalities. This study showed that
patients who undergo autologous reconstruction may have greater satisfaction and HRQL
compared with patients who undergo implant-based reconstruction. This study provides
information that plastic surgeons can use to help patients make more informed choices for types of
breast reconstruction
39.4 Widespread Applications be asked to complete the appearance that mea-

of PROMs in Plastic Surgery sures satisfaction with the nose, and relevant
HRQL scales (e.g., Psychological and Social
Given the diverse range of disease types, organ Function) [12].
systems, and patient populations implicated in Since the development of the BREAST-Q and
plastic surgical care, it was important to ensure FACE-Q, many other PROMs have been devel-
all areas of plastic surgery have PROMs to use to oped and validated for use across plastic surgery
evaluate outcomes from the patient perspective. sub-specialties. Some examples include the
In their landmark work, Klassen et al. describe CLEFT-Q for cleft lip and/or palate surgery,
the development of FACE-Q Aesthetics, which which was carefully designed for use with chil-
addressed a key deficit in patient-centered out- dren aged 8 years to young adults aged up to
come measurement for patients undergoing both 29 years [13], the WOUND-Q for chronic wounds
surgical and nonsurgical facial aesthetic proce- [14], and the brief Michigan Hand Questionnaire
dures [11]. The modular approach taken to [15], among others. Ongoing PROM develop-
develop FACE-Q Aesthetics provides 40 inde- ment will be important to assess patient-centered
pendently functioning scales that measure outcomes as surgical techniques and patient pop-
appearance, HRQL, and adverse effects of treat- ulations evolve. At the same time, validating
ment. This approach to measurement reduces existing PROMs for new languages and/or cul-
patient burden and maximizes clinical relevance tural contexts—beyond the populations in which
for different patient presentations [12]. For they were initially developed—will be critical for
example, depending on the research question or ensuring equitable access and representation
clinical relevance, a rhinoplasty candidate could moving forward.
Klassen AF, Cano SJ, Scott A, Snell L, Pusic AL. Measuring patient-reported outcomes in facial aesthetic patients:
development of the FACE-Q. Facial Plast Surg. 2010;26(4):303–9 [12]
Strengths • Inclusion of multiple scales for both surgical and nonsurgical facial aesthetic procedures that can
be used according to clinical relevance
• Development of an overall scale (satisfaction with face) that can be used for all patients, regardless
of the type and number of procedures undergone
Limitations • Developed within a North American population, which may limit generalizability to other
populations
• Concerns only item generation, without subsequently generated data on scale development and
psychometric testing, which is available in subsequent publications
Impact The FACE-Q enabled rigorous, psychometric measurement of patient-centered outcomes in aesthetic
facial procedures. The availability of multiple scales enabled efficient and clinically relevant outcome
capture for patients having different procedures (e.g., facelifts, blepharoplasty, minimally invasive
procedures). Together with the BREAST-Q, FACE-Q aesthetics established the important role of
psychometrics and PROM development in the field of plastic surgery across diverse procedure types
39.5 PROMs as Key Patient- randomized clinical trials. In their landmark

Centered Outcome Metrics study, Chung et al. conducted a multicenter,
in Clinical Trials international, randomized study assessing long-
term (24-month) outcomes using PROMs after
As many plastic surgery interventions target surgical or non-surgical treatment of unstable
improvements in patient-centered endpoints distal radius fracture [16]. Their study demon-
(e.g., return of function, HRQL), PROMs have strated no significant difference in outcomes at
proven useful not only in non-randomized, pro- the long-term follow-up timepoint, suggesting
spective studies but also as primary endpoints in that surgeons and patients could consider non-
operative management in some cases, without showed that PROMs can serve as a valuable end-
sacrificing long-term benefits [16]. Importantly, point in randomized clinical trials, especially in
this study helped to better inform patient expecta- plastic surgery where there are often many rea-
tions in the preoperative setting and provided sonable operative and non-operative options
reassuring long-term results for those patients available for a given condition that warrant mean-
who may not be operative candidates. This study ingful head-to-head comparison.
Chung KC, Kim HM, Malay S, Shauver MJ. Comparison of 24-month outcomes after treatment for distal radius
fracture: the WRIST randomized clinical trial. JAMA Netw Open. 2021;4(6):e2112710 [16]
Strengths • Randomized, international, multicenter clinical trial that used a PROM as the primary outcome
measure.
• Long-term (24 month) outcome measures between multiple different treatment options for unstable
distal radius fractures
Limitations • Attrition of older, less active, and less healthy patients in the study may have overestimated
long-term outcome improvement
• Patients lost to long-term follow-up may have been satisfied with outcomes and contribute to
underestimation of long-term outcome improvement
Impact Given no differences in outcomes at 24 months among the four treatment groups following unstable
distal radius fracture, older patients can consider non-operative management and expect similar
long-term outcomes as patients undergoing other types of operative management. PROMs have
applicability across multiple plastic surgery sub-specialties and can aid discussion of long-term,
patient-centered expectations when considering surgical versus non-surgical options
tion with electronic medical records, and inade-

39.6 The Application of PROMs quate staffing and resources [21–24]. In their
in Routine Clinical Care work documenting a nearly 10 year quality
improvement initiative for routine collection of
In addition to serving as powerful metrics when BREAST-Q data in clinical care, Nelson et al.
used in research and clinical trials, there is also identified key facilitators and barriers toward
much value and opportunity for the use of achieving over 80% response rates [25].
PROMs in routine clinical care. Many benefits Specifically, the authors highlight the impor-
have been shown and proposed for routine clini- tance of shifting the culture and language around
cal PROM use, including improvements in PROMs use—from mere research tools to vital
patient symptom control, increased access to aspects of the clinical encounter, akin to vital
supportive care measures, reduction in unneces- signs [25]. They also underscored the necessity
sary healthcare utilization, and improved patient for seamless integration with the electronic med-
satisfaction and health outcomes [17–20]. ical record, routine feedback to patients and pro-
However, collecting, analyzing, and acting on viders, and active engagement on PROM data in
PROMs in routine clinical care is not without its clinical encounters [25]. Their study provides an
challenges. As such, a range of barriers have essential framework for clinical PROM collec-
been cited, including difficulty in selecting tion that can be adapted by institutions in the
appropriate and relevant PROMs, non-integra- future.
Nelson JA, Chu JJ, Dabic S, et al. Moving towards patient-reported outcomes in routine clinical practice:
implementation lessons from the BREAST-Q. Qual Life Res. 2023;32(1):115–25 [25]
Strengths • Evaluated facilitators to successful implementation of a clinical PROMs program in plastic surgery
practice
• Informed by nearly 10 years of clinical insights and quality improvement
Limitations • Findings limited to a single academic institution, which may not be generalizable to other
institutions or less resourced settings
• Involved implementation of a single PROM within a highly specialized practice setting
Impact With increasing interest in using PROMs in routine clinical care, this study demonstrated how
institutions may develop, implement, and achieve a successful clinical PROM program in plastic
surgery. Specifically, re-framing PROMs as a clinical—rather than simply research—tool and
incorporating new technologies into clinical workflows may enable institutions to scale-up clinical
PROM programs
39.7 Expert Concluding Financial Disclosures CJH has no relevant financial dis-
closures. ALP and AFK are co-developer of the QPROMS
Commentary which are owned by Memorial Sloan-Kettering Cancer
Center, McMaster University, Brigham and Women’s
PROMs serve a relevant, unique, and important Hospital and the University of British Columbia and
role in plastic surgery, for both research and rou- receives a portion of licensing fees (royalty payments)
when the QPROMS are used in industry sponsored clini-
tine clinical care. Importantly, given constant cal trials.
innovation and shifting patient demands in plas-
tic surgery, adaptability and ongoing optimiza-
tion of PROMs will be important. For example, References
surgical innovation led to neurotization tech-
niques and improvements in breast sensation fol- 1. Epstein AM. The outcomes movement—will
lowing mastectomy and reconstruction, it get us where we want to go? N Engl J Med.
warranting the development of new breast sensa- 1990;323(4):266–70.
2. Laikhter E, Manstein SM, Pusic AL, Chung KC,
tion scales for the BREAST-Q [26]. Similarly, Lin SJ. The impact of outcomes research in plas-
evolving techniques and increasing access to tic and reconstructive surgery. Plast Reconstr Surg.
gender affirming care merits ongoing develop- 2021;148(4):921–6.
ment of PROMs specific to this burgeoning 3. Stemler SE, Naples A. Rasch Measurement v. Item
response theory: knowing when to cross the line.
patient population [27]. At the same time, there is Pract Assess Res Eval 2021;26(11).
increasing interest in using PROMs as metrics to 4. Nguyen H, Butow P, Dhillon H, Sundaresan P. A
benchmark provider performance, as drivers of review of the barriers to using patient-reported out-
quality improvement, and as indicators for reim- comes (PROs) and patient-reported outcome measures
(PROMs) in routine cancer care. J Med Radiat Sci.
bursement in value-based healthcare models 2021;68(2):186–95.
[18]. As such, optimizing the use of PROMs in 5. Weldring T, Smith SMS. Patient-reported outcomes
routine clinical care—beyond just the research (PROs) and patient-reported outcome measures
setting—will be essential. However, given that (PROMs). Heal Serv Insights. 2013;6:61–8.
6. Pusic AL, Chen CM, Cano S, et al. Measuring quality
certain demographics and populations may have of life in cosmetic and reconstructive breast surgery: a
disparate PROM outcomes, and owing to exist- systematic review of patient-reported outcomes instru-
ing disparities in PROM collection among cer- ments. Plast Reconstr Surg. 2007;120(4):823–37.
tain patient groups, it will be critical to ensure 7. Pusic AL, Klassen AF, Scott AM, Klok JA,
Cordeiro PG, Cano SJ. Development of a new
equitable and representative collection of PROMs patient-reported outcome measure for breast
in routine clinical care moving forward in order surgery: the BREAST-Q. Plast Reconstr Surg.
to promote health equity. 2009;124(2):345–53.
8. Santosa KB, Qi J, Kim HM, Hamill JB, Wilkins EG, reform. Value Heal J Int Soc Pharm Outcomes Res.
Pusic AL. Long-term patient-reported outcomes in 2017;20(6):834–6.
postmastectomy breast reconstruction. JAMA Surg. 19. Hildon Z, Neuburger J, Allwood D, van der Meulen J,
2018;153(10):891–9. Black N. Clinicians’ and patients’ views of metrics of
9. Cohen WA, Mundy LR, Ballard TNS, et al. The change derived from patient reported outcome mea-
BREAST-Q in surgical research: a review of the sures (PROMs) for comparing providers’ performance
literature 2009-2015. J Plast Reconstr Aesthet Surg. of surgery. BMC Health Serv Res. 2012;12:171.
2016;69(2):149–62. 20. Basch E, Deal AM, Kris MG, et al. Symptom moni-
10. Notermans BJW, van der Oest MJW, Selles RW, de toring with patient-reported outcomes during routine
Boer LHL, van der Heijden BEPA. Patient-reported cancer treatment: a randomized controlled trial. J Clin
outcomes 1 year after proximal interphalangeal joint Oncol Off J Am Soc Clin Oncol. 2016;34(6):557–65.
arthroplasty for osteoarthritis. J Hand Surg Am. 21. Snyder CF, Aaronson NK, Choucair AK, et al.
2022;47(7):603–10. Implementing patient-reported outcomes assessment
11. Kosowski TR, McCarthy C, Reavey PL, et al. A in clinical practice: a review of the options and con-
systematic review of patient-reported outcome siderations. Qual Life Res Int J Qual Life Asp Treat
measures after facial cosmetic surgery and/or non- Care Rehabil. 2012;21(8):1305–14.
surgical facial rejuvenation. Plast Reconstr Surg. 22. Zhang B, Lloyd W, Jahanzeb M, Hassett MJ. Use of
2009;123(6):1819–27. patient-reported outcome measures in quality oncol-
12. Klassen AF, Cano SJ, Scott A, Snell L, Pusic ogy practice initiative-registered practices: results of a
AL. Measuring patient-reported outcomes in facial National Survey. J Oncol Pract. 2018;14(10):e602–11.
aesthetic patients: development of the FACE-Q. Facial 23. Philpot LM, Barnes SA, Brown RM, et al. Barriers
Plast Surg. 2010;26(4):303–9. and benefits to the use of patient-reported out-
13. Klassen AF, Riff KWW, Longmire NM, et al. come measures in routine clinical care: a qualitative
Psychometric findings and normative values for the study. Am J Med Qual Off J Am Coll Med Qual.
CLEFT-Q based on 2434 children and young adult 2018;33(4):359–64.
patients with cleft lip and/or palate from 12 countries. 24. NEJM. Patient engagement buzz survey: PROMs use
C Can Med Assoc J. 2018;190(15):E455–62. is growing, but implementation takes effort. NEJM
14. Klassen AF, van Haren ELWG, van Alphen TC, Catal. 2019.
et al. International study to develop the WOUND-Q 25. Nelson JA, Chu JJ, Dabic S, et al. Moving towards
patient-reported outcome measure for all types of patient-reported outcomes in routine clinical practice:
chronic wounds. Int Wound J. 2021;18(4):487–509. implementation lessons from the BREAST-Q. Qual
15. Waljee JF, Kim HM, Burns PB, Chung life Res an Int J Qual life Asp Treat care Rehabil.
KC. Development of a brief, 12-item version of the 2022;32:115.
Michigan hand questionnaire. Plast Reconstr Surg. 26. Tsangaris E, Klassen AF, Kaur MN, et al.
2011;128(1):208–20. Development and psychometric validation of the
16. Chung KC, Kim HM, Malay S, Shauver BREAST-Q sensation module for women undergo-
MJ. Comparison of 24-month outcomes after treating post-mastectomy breast reconstruction. Ann Surg
ment for distal radius fracture: the WRIST randomized Oncol. 2021;28(12):7842–53.
clinical trial. JAMA Netw Open. 2021;4(6):e2112710. 27. Klassen AF, Kaur M, Johnson N, et al. International
17. Sisodia RC, Dewdney SB, Fader AN, et al. Patient phase I study protocol to develop a patient-reported
reported outcomes measures in gynecologic oncol- outcome measure for adolescents and adults receiving
ogy: a primer for clinical use, part I. Gynecol Oncol. gender-affirming treatments (the GENDER-Q). BMJ
2020;158(1):194–200. Open. 2018;8(10):e025435.
18. Squitieri L, Bozic KJ, Pusic AL. The role of patient-
reported outcome measures in value-based payment

Landmark Papers in Plastic Surgery-1stkhajuria2024

Uploaded by

Copyright:

Available Formats

Landmark Papers in Plastic Surgery-1stkhajuria2024

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Landmark Papers in Plastic Surgery-1stkhajuria2024

Uploaded by

Copyright:

Available Formats

Landmark

Foreword by Rod J. Rohrich

Foreword by Rod J. Rohrich

Department of Surgery and Cancer

ISBN 978-3-031-57131-2 ISBN 978-3-031-57132-9 (eBook)

If disposing of this product, please recycle the paper.

In the ever-evolving realm of medicine, a few disciplines have seen as much

Defining Landmark Papers

The Journey Through Landmark Papers

As you embark on this journey through Landmark Papers in Plastic Surgery,

Expert Commentary: Navigating the Future

In addition to presenting these seminal studies, Landmark Papers in Plastic

Expert Concluding Commentary

In conclusion, Landmark Papers in Plastic Surgery is more than just a collec-

Oxford, UK Ankur Khajuria

Part I Basic Science

Part II Head and Neck

Part III Breast Surgery

Part IV Hand and Upper Extremity

Part V Nerve Surgery

Part VI Skin Cancer Management

Part VII Burn Surgery

Part VIII Trunk Reconstruction

26 Evolution of Trunk Reconstruction������������������������������������������������ 273

Part IX Abdominal Wall Reconstruction

27 Evolution of Abdominal Wall Reconstruction������������������������������ 285

Part X Lower Extremity

Part XI Genitourinary Reconstruction

Part XII Perineal and Pelvic Reconstruction

Part XIII Aesthetic Surgery

Part XIV Evolution of Patient-Reported Outcomes (PROs)

Angelica Hernandez Alvarez Division of Plastic and Reconstructive

Mark Clemens MD Anderson Cancer Center, The University of Texas,

Ryoko Hamaguchi Division of Plastic and Reconstructive Surgery, Brigham

Jonathan Lans Hand and Upper Extremity Service, Department of

Mauricio Perez Total Definer, Rochester, MN, USA

Krystle R. Tuaño Hand and Upper Extremity Service, Department of

Abstract The Five Most Impactful Papers

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024 3

1.1 Expert Concluding high-definition 3D cameras provides the oppor-

Abstract 3. Behan FC. The keystone design perforator

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024 9

Hyakusoku H, et al. The propeller flap method. Br J Plast Surg. 1991;44(1):53–4

DIEP flap provided the bulk of tissue while spar-

2.7 Expert Concluding I am excited to be part of the rapid evolution

Abstract and presenting hereon the highlights as well as

Vascularized composite allotransplantation (VCA)

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024 15

Pre-Transplant 18 months post-Transplant Five years post-Transplant

Fig. 3.3 To map the

no sufficient treatment is available, preventing same techniques as described in the landmark

9. Sollinger HW. Mycophenolates in transplantation. 28. de la Garza M, Sauerbier M, Günter G, et al.

Abstract The Five Most Impactful Papers

R. Hamaguchi · D. P. Orgill (*)

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024 29

4.1 Introduction of wound care, but to guide future efforts to max-

4.1.2 Negative Pressure Wound medical-grade reticulated polyurethane ether

4.1.4 Cell-Based Therapies: sheets that can be clipped onto petroleum-

Table 4.1 Determinants of success for wound healing innovations

Defining Landmark Papers

The Journey Through Landmark Papers

Expert Commentary: Navigating the Future

Expert Concluding Commentary

Oxford, UK Ankur Khajuria

Part I Basic Science

Part II Head and Neck

Part III Breast Surgery

Part IV Hand and Upper Extremity

Part V Nerve Surgery

Part VI Skin Cancer Management

Part VII Burn Surgery

Part VIII Trunk Reconstruction

26 Evolution of Trunk Reconstruction�� 273

Part IX Abdominal Wall Reconstruction

27 Evolution of Abdominal Wall Reconstruction�� 285

Part X Lower Extremity

Part XI Genitourinary Reconstruction

Part XII Perineal and Pelvic Reconstruction

Part XIII Aesthetic Surgery

Part XIV Evolution of Patient-Reported Outcomes (PROs)

1.1 Expert Concluding high-definition 3D cameras provides the oppor-

2.7 Expert Concluding I am excited to be part of the rapid evolution

4.1 Introduction of wound care, but to guide future efforts to max-

4.1.2 Negative Pressure Wound medical-grade reticulated polyurethane ether

4.1.4 Cell-Based Therapies: sheets that can be clipped onto petroleum-

4.2 Expert Concluding (2) biophysical effects of mechanical forces, (3)

5.3 Physiologic Procedures formed lymphaticovenous anastomosis or

5.4 Expert Concluding 6. Brorson H, Svensson H. Complete reduction of

6.5 Expert Concluding creative approaches are changing the paradigm

7.1 Introduction safety of breast implants was controversial [1].

7.3 Assessing Fat-Grafting imaged the patients with mammography before

7.4 Volumetric Assessment mean error of 54.63 ± 46.30 and a correlation

7.6 Evaluating Skin-Flap concepts: (1) the decreasing distal perfusion of

8.2 Duplex Ultrasound

between CTA and ICG-A in pre-operative imag- 8.8 Expert Concluding

9.3 Development ing. He perfected a roentgenographic technique

9.4 Invention of Computed involved combining X-ray data from multiple

9.5 Beginning of 3D Imaging Additionally, they developed a surgical simula-

9.7 Expert Concluding patients’ unique craniofacial structures, enabling

10.2 Blow-Out Fracture of Orbit

10.3 Complex Maxillary Fractures

10.4 LeFort Fractures

10.5 Nasoethmoid Orbital (NOE)

10.6 Mandible Fracture

10.7 Expert Concluding References

11.4 Cleft Palate Repair magnification through an operating microscope