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com/1007-9327office World J Gastroenterol 2011 November 7; 17(41): 4545-4553

[email protected] ISSN 1007-9327 (print) ISSN 2219-2840 (online)
doi:10.3748/wjg.v17.i41.4545 © 2011 Baishideng. All rights reserved.

EDITORIAL

Pathophysiology and prevention of postoperative peritoneal

adhesions

Willy Arung, Michel Meurisse, Olivier Detry

Willy Arung, Department of General Surgery, Cliniques Univer- wound surfaces. Their results are encouraging but
sitaires de Lubumbashi, University of Lubumbashi, Lubumbashi most of them are contradictory and achieved mostly
1825, Katanga Province, Congo in animal model. Until additional findings from future
Michel Meurisse, Olivier Detry, Department of Abdominal Sur- clinical researches, only a meticulous surgery can be
gery and Transplantation, CHU de Liège, University of Liege,
recommended to reduce unnecessary morbidity and
Liège B4000, Belgium
mortality rates from these untoward effects of surgery.
Author contributions: Arung W performed the review and
wrote the manuscript; Meurisse M and Detry O supervised the In the current state of knowledge, pre-clinical or clini-
review and corrected the manuscript. cal studies are still necessary to evaluate the effective-
Correspondence to: Olivier Detry, Professor, Department of ness of the several proposed prevention strategies of
Abdominal Surgery and Transplantation, CHU de Liège, Univer- postoperative peritoneal adhesions.
sity of Liege, Liège B4000, Belgium. [email protected]
Telephone: +32-4-3667645 Fax: +32-4-3664069 © 2011 Baishideng. All rights reserved.
Received: May 4, 2011  Revised: August 26, 2011
Accepted: September 3, 2011 Key words: Abdominal surgery; Laparoscopy; Complica-
Published online: November 7, 2011 tion; Occlusion; Abdominal pain

Peer reviewers: Eric S Hungness, MD, FACS, Assistant Pro­

fessor, Division of Gastrointestinal and Oncologic Surgery,
Abstract Northwestern University Feinberg School of Medicine, 676 N.
St. Clair St., Suite 650, Chicago, IL 60611-2908, United States;
Peritoneal adhesions represent an important clinical Beat Schnüriger, MD, University of Southern California, Keck
challenge in gastrointestinal surgery. Peritoneal adhe- School of Medicine, Department of Surgery, Division of Acute
sions are a consequence of peritoneal irritation by Care Surgery, Trauma, Emergency Surgery and Surgical Critical
infection or surgical trauma, and may be considered as Care, 1200 North State Street, Inpatient Tower (C), 5th Floor,
the pathological part of healing following any perito- Room C5L100, Los Angeles, CA 90033-4525, United States
neal injury, particularly due to abdominal surgery. The
balance between fibrin deposition and degradation is Arung W, Meurisse M, Detry O. Pathophysiology and preven-
critical in determining normal peritoneal healing or ad- tion of postoperative peritoneal adhesions. World J Gastroenter-
hesion formation. Postoperative peritoneal adhesions ol 2011; 17(41): 4545-4553 Available from: URL: http://www.
are a major cause of morbidity resulting in multiple wjgnet.com/1007-9327/full/v17/i41/4545.htm DOI: http://
complications, many of which may manifest several dx.doi.org/10.3748/wjg.v17.i41.4545
years after the initial surgical procedure. In addition
to acute small bowel obstruction, peritoneal adhesions
may cause pelvic or abdominal pain, and infertility.
In this paper, the authors reviewed the epidemiology, INTRODUCTION
pathogenesis and various prevention strategies of ad-
hesion formation, using Medline and PubMed search. Peritoneal adhesions represent an important clinical chal-
Several preventive agents against postoperative peri- lenge in gastrointestinal surgery. Peritoneal adhesions are
toneal adhesions have been investigated. Their role a consequence of peritoneal irritation by infection or sur-
aims in activating fibrinolysis, hampering coagulation, gical trauma. They are a major cause of morbidity, result-
diminishing the inflammatory response, inhibiting col- ing in multiple complications, many of which may mani-
lagen synthesis or creating a barrier between adjacent fest several years after the initial surgical procedure[1,2].

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 Arung W et al . Postoperative peritoneal adhesions

Development of peritoneal adhesions has been studied obstruction (ASBO)[1,10-13]. Colorectal surgery has proved
extensively, but to date, there has been no definitive strat- to be the most important type of surgery that may cause
egy to prevent their formation, as controversies concern- intra-abdominal adhesions[14]. This surgery has the high-
ing the effectiveness of available preventive agents still est total number of inpatient episodes, inpatient days,
exist. In addition, most of the available clinical literature operating time, theater time, and costs due to peritoneal
concern gynecological patients; for patients undergoing adhesion-related intestinal obstruction[14]. Among open
general and/or abdominal surgery, no recommendations gynecological procedures, ovarian surgery had the highest
or guidelines exist[3]. The aim of this review is to present rate of readmissions directly related to adhesions (7.5/100
the epidemiology, pathogenesis and various prevention initial operations)[13].
strategies of adhesion formation. We performed a litera- Small bowel obstructions (SBO) is the most common
ture search for this review in Medline and PubMed, using complication of peritoneal adhesions[1,2,8,9]. At Westmin-
the key words: “adhesions”, “intraperitoneal adhesions”, ster Hospital (London, United Kingdom), intestinal ob-
“intra-abdominal adhesions”, “adhesion reduction”, struction accounted for 0.9% of all admissions, 3.3% of
“adhesion prevention”, “adhesion formation”, “adhe- major laparotomies, and 28.8% of cases of large or SBO
sion pathophysiology”. We also reviewed the reference over 24 years[5]. A 1992 British survey has reported an an-
lists in all articles retrieved in the search, as well as those nual total of 12 000-14 400 cases of adhesive intestinal
of major texts regarding peritoneal adhesion formation. obstruction. Barmparas et al[15] have studied the incidence
Both clinical and experimental studies upon adhesion for- and risk factors for ASBO following laparotomy. The
mation were retained. There was no restriction regarding overall incidence of ASBO was 4.6% and the risk of
publication language. ASBO was highly influenced by the type of procedure,
with ileal pouch-anal anastomosis being associated with
Definition, epidemiology and consequences of perito- the highest incidence of SBO[15]. In 1988 in the United
neal adhesions States, admissions for adhesiolysis accounted for nearly
Peritoneal adhesions are pathological bonds usually be- 950 000 d of inpatient care[5]. All these studies have dem-
tween omentum, loops of bowel and the abdominal wall. onstrated that ASBO is a significant health issue both in
These bonds may be a thin film of connective tissue, a the developed and developing world. However, ASBO
thick fibrous bridge containing blood vessels and nerve risk factors, such as the type of past surgical procedure,
tissue, or a direct contact between two organ surfaces[4]. the site of adhesions, as well as the timing and recurrence
According to their etiology, peritoneal adhesions may rate of adhesive obstruction, remain unpredictable or
be classified as congenital or acquired, which can be poorly understood[5].
postinflammatory or postoperative (the most frequent)[5]. In addition to ASBO, peritoneal adhesions may cause
Among postoperative adhesion formation, three pro- pelvic or abdominal pain, and infertility[1,2,16]. Peritoneal ad-
cesses may be distinguished: adhesion formation (adhesions hesions may also prolong the time needed to gain access
formed at operative sites); de novo adhesion formation (adhe- to the abdominal cavity at subsequent surgery[17,18], and
sions formed at non-operative sites); and adhesion reforma- may increase the risk of bowel injury during subsequent
tion (adhesions formed after the lysis of previous adhe- surgery[19]. Controversy remains on the role of peritoneal
sions)[6] . Diamond et al[7] have distinguished type 1 and adhesions on abdominal pain. Adhesions have been im-
type 2 formation of postoperative peritoneal adhesions. plicated as a significant cause of chronic pelvic pain, and
Type 1 or de novo adhesion formation concerns adhesions their surgical lysis has been proposed as the therapeutic
formed at sites that did not have previous adhesions, modality of choice[20,21]. However, chronic pelvic pain
including type 1A (no previous operative procedure at is one of most common gynecological complaints and
the site of adhesions) and type 1B (previous operative yet remains an enigma. A comparison of chronic pelvic
procedures at the site of adhesions). Type 2 involves ad- pain patients and asymptomatic infertility patients has
hesion reformation, with two separate subtypes: type 2A not revealed a significant difference in the density or the
(no operative procedure at the site of adhesions besides location of adhesions[22]. Thus, it is possible that a com-
adhesiolysis) and type 2B (other operative procedures at mon mechanism for pelvic pain exists and that adhesions
the site of adhesions besides adhesiolysis)[7]. are only associated features. Bradykinin, histamine and
Peritoneal adhesions are mostly induced by surgical other autocoids are able to stimulate pain receptors. For
procedures in the peritoneal cavity, and their prevalence Rapkin et al[22], these findings question the role of pelvic
after major abdominal procedures has been evaluated at adhesions as a cause of chronic pelvic pain. According to
63%-97%[8,9]. Overall, approximately one-third of patients other authors, although adhesions are thought to cause
who underwent open abdominal or pelvic surgery were pain indirectly by restricting organ motion, thus stretch-
readmitted an average of two times over the subsequent ing and pulling smooth muscle of adjacent viscera or
10 years for conditions directly or possibly related to ad- the abdominal wall, adhesions themselves are capable of
hesions, or for further surgery that could potentially be generating pain stimuli. Sulaiman et al[23] have studied the
complicated by adhesions; > 20% of all such readmis- distribution, location, size and type of nerve fibers pres-
sions occurred during the first year after initial surgery, ent in human peritoneal adhesions, associated or not with
and 4.5% of readmissions were for adhesive small bowel chronic pelvic pain. They have found that nerve fibers,

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 Arung W et al . Postoperative peritoneal adhesions

identified histologically, ultrastructurally, and immuno- incompletely degraded fibrin may serve as a scaffold for
histochemically, were present in all examined peritoneal fibroblasts and capillary in growth to form peritoneal ad-
adhesions. Furthermore, fibers expressing the sensory hesions.
neuronal markers calcitonin gene-related protein and Peritoneal injury, due to surgery, infection or irritation,
substance P were present in all adhesions irrespective of initiates inflammation with fibrinous exudate and fibrin
reports of chronic abdominopelvic pain. That study has formation[32]. Fibrin results from coagulation cascade ac-
suggested that these structures may be capable of con- tivation that is activated in the peritoneal cavity, resulting
ducting pain after appropriate stimulation, and peritoneal in the formation of thrombin that triggers conversion
adhesions are implicated as a cause of chronic abdomi- of fibrinogen into fibrin. However, owing to activation
nopelvic pain. In addition, many patients are relieved of of the fibrinolytic system, any intra-abdominal fibrin de-
their symptoms after adhesiolysis[23]. posits must be lysed. After abdominal surgery, however,
As consequence, peritoneal adhesions have a signifi- the equilibrium between coagulation and fibrinolysis is
cant economic impact. Their direct costs in Sweden can disturbed, in favor of the coagulation system. Thus, fibrin
be estimated to be $13 million annually[24]. It has been esti- forms deposits are a matrix for ingrowth of fibrocol-
mated that in the United States, there are 117 hospitaliza- lagenous tissue. Indeed, fibroblasts invade the fibrin ma-
tions for adhesion-related problems per 100 000 people, trix and the extracellular matrix (ECM) is produced and
and the total cost for hospital and surgical expenditure is deposited. This ECM can still be completely degraded
about $1.3 billion[25]. In some European countries, the di- by the proenzymes of matrix metalloprotease (MMP),
rect medical costs for adhesion-related problems are more leading to normal healing. However, if this process is
than the surgical expenditure for gastric cancer and almost inhibited by tissue inhibitors of MMPs, peritoneal adhe-
as much as for rectal cancer[3,26,27]. Indeed, postoperative sions may be formed[33]. Generally, if fibrinolysis does not
adhesions have a profound economic impact, including occur within 5-7 d of the peritoneal injury, the temporary
the surgical procedure itself, hospitalization, recuperation fibrin matrix persists and gradually becomes organized
and lost productivity[25]. During 1988, excluding patient with collagen-secreting fibroblasts. This process leads to
and indirect costs, hospitalization in the United States, ac- peritoneal adhesion formation[34,35] and growth of new
counting for 948 727 d of inpatient care, was responsible blood vessels mediated by angiogenic factors[13].
for an estimated $1179.9 million in expenditure, of which Activation of the fibrinolytic system results in the
$925 million was associated with hospital costs and $254.9 conversion of plasminogen into plasmin that is highly ef-
million with surgeons’ fees[25]. The study of Ray et al[28] fective in the degradation of fibrin into fibrin degradation
has demonstrated substantial costs associated with surgi- products. Tissue-type plasminogen activator (tPA) and
cal procedures and hospitalization for adhesiolysis. Dur- urokinase-type plasminogen (uPA) are both plasminogen
ing 1996, the total annual cost of adhesions management activators. They are expressed in endothelial cells, meso-
exceeded $2 billion, excluding recuperation and lost thelial cells and macrophages. tPA, a serine protease, is
productivity[28]. Hospitalization for adhesiolysis alone cost the main plasminogen activator and has a high affinity
> $700 million. Furthermore, > 300 000 patients are esti- for fibrin. It binds to a specific receptor, which exposes
mated to undergo surgery to treat adhesion-induced SBO a strong plasminogen-binding site on the surface of the
in the United States annually[25]. Thus, developing effec- fibrin molecule. Therefore, in the presence of fibrin, the
tive strategies for adhesion prevention may help to reduce activation rate of plasminogen is strikingly enhanced,
adhesions management costs and unnecessary morbidity whereas in the absence of fibrin, tPA is a poor activator
and mortality rates. of plasminogen[36,37]. This results in higher plasminogen
activation at the sites where it is required, whereas system-
Postoperative peritoneal adhesion pathophysiology ic activation is prevented. In the peritoneal cavity, tPA is
The first peritoneal adhesions were described at post- responsible for 95% of plasminogen-activating activity[38].
mortem examination of a patient with peritoneal tuber- uPA is equally effective in the degradation of fibrin[39], but
culosis in 1836. To explain this finding, it was suggested its much lower affinity for fibrin results in a significantly
in 1849 that coagulated lymphatic vessels may turn into lower plasminogen-activating activity. Besides activation
fibrinous adhesions[29,30]. Until now, the exact pathophysi- of plasminogen, uPA may play an important role in tissue
ology of peritoneal adhesions has remained elusive. De- remodeling[40].
spite many clinical and experimental studies, peritoneal Plasminogen activation is hampered by plasminogen-
adhesions pathophysiology remains controversial. activating inhibitor (PAI)-1 and 2 throughformation of
Aside from the normal peritoneal regeneration, the inactive complexes. The most potent inhibitor of tPA
process of postoperative peritoneal adhesion formation and uPA is the glycoprotein PAI-1. PAI-2 is less effec-
may be considered as the pathological part of healing fol- tive in counteracting plasminogen activators. It probably
lowing any peritoneal injury, particularly due to abdominal plays a role in peritoneal tissue repair[41]. Both PA-1 and
surgery[5,31]. The balance between fibrin deposition and PAI-2 are produced by endothelial cells, mesothelial cells,
degradation is crucial in determining normal peritoneal monocytes, macrophages and fibroblasts. Other plas-
healing or adhesion formation. If fibrin is completely de- minogen activator inhibitors have been identified: PAI-3
graded, normal peritoneal healing may occur. In contrast, and protease nexin 1. Several protease inhibitors, such as

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 Arung W et al . Postoperative peritoneal adhesions

Peritoneal injury principles” (W.S. Halsted 1852-1922), the first surgeon

who recognized the importance of these measures[45].
Inflammation Blood vessel Peritoneal damage should be avoided by careful tissue
wall and mesothelium cells damages handling, meticulous hemostasis, continuous irrigation
and avoiding unnecessary drying, ineffective use of for-
-Increases proteins, cytokines Prothrombin
eign bodies, and suturing or clamping of tissue. The use
-Increases cells
of fine and biocompatible suture materials, atraumatic
Fibrinogen instruments and starch-free gloves is also recommended.
(macrophages, platelets
Starched gloves are a significant risk factor for postopera-
lymphocytes, mesothelials) Thrombin tive adhesions. Several experimental studies have shown
that the use of starch-powdered gloves during laparotomy
Fibrin
is associated with an increased risk of extensive post-
operative peritoneal adhesions[46]. Foreign bodies most
tPA
Plasminogen PAI-1 frequently found in postoperative adhesions are: surface
uPA
PAI-2 powders from surgical gloves; lint from packs, drapes, or
PAI-1 gowns; wood fibers from disposable paper items; and su-
tPA
PAI-2 ture materials. However, recent data have suggested that,
uPA
Fibrin in growth in the absence of an additional peritoneal injury, foreign
(Fibroblasts, collagen synthesis) bodies are an infrequent cause of adhesion induction[9,47].
TIMPs Plasmin Ordonez et al[48] have evaluated the effect of training on
(-) postoperative adhesion formation in a rabbit model. The
Pr-MMPs MMPs training effect was evaluated by duration of surgery and
ECM Fibrin degradation
amount of bleeding. This study has shown that there
products is a significant effect of experience on duration of sur-
gery. With experience, duration of surgery progressively
Degradation Capillaires
products ingrowth
decreases, and postoperative adhesions also decrease in
extent, tenacity, type and total score. According to these
Normal healing findings, surgical training and the respect of some basic
Normal Adhesion (Peritoneal repair)
healing
principles (“Halstedian principles”) are important for ad-
hesion prevention.
Figure 1 Balance between plasminogen activators and plasminogen in- Some intraoperative techniques, such as avoiding un-
hibitors. TIMP: Tissue inhibitors of metalloproteinases; MMP: Matrix metallopro- necessary peritoneal dissection or avoiding closure of the
tease; ECM: Extracellular matrix; tPA: Tissue-type plasminogen activator; uPA: peritoneum, should be applied. Many experimental studies
Urokinase-type plasminogen; PAI: Plasminogen-activating inhibitor. have shown that non-closure of the peritoneum is associ-
ated with decreased peritoneal adhesion formation[49-51].
However, some studies have reported no difference[52,53]
α2-macroglobulin, α1-antitrypsin and α2-antiplasmin,
or even decreased peritoneal adhesion[54] with peritoneal
inhibit plasmin directly. However, their roles in peritoneal
closure. However, grafting or suturing peritoneal defects
fibrinolysis are not well defined[42]. The balance between
may increase peritoneal ischemia, devascularization, and
plasminogen activators and plasminogen inhibitors is cru-
necrosis, predisposing the site to decreased fibrinolytic
cial in determining normal healing or adhesion formation
activity and increased adhesion formation[55].
(Figure 1). Therefore, PAI-1 is considered to be an im-
Furthermore, surgical trauma should be reduced as
portant factor in the development of adhesions and high much as possible. The surgical approach (open vs lapa-
PAI concentrations are found in adhesions and peritoneal roscopic) could play an important role in the develop-
tissue of patients with extensive adhesions[43,44]. ment of adhesions. In most abdominal procedures, the
laparoscopic approach is associated with a significantly
Prevention lower incidence of postoperative peritoneal adhesions or
Several preventive agents against postoperative peritoneal adhesion-related re-admissions. Brokelman et al[56] have
adhesions have been investigated. Their roles are in ac- shown in a prospective trial that there is no difference in
tivating fibrinolysis, hampering coagulation, diminishing tPA antigen, tPA-activity, uPA antigen, or PAI-1 antigen
the inflammatory response, inhibiting collagen synthesis, concentrations in peritoneal biopsies taken at the begin-
or creating a barrier between adjacent wound surfaces. ning compared to the end of the laparoscopic procedure,
These prevention strategies can be grouped into four cat- irrespective of the intra-abdominal pressure or light activ-
egories: general principles, surgical techniques, mechanical ity. In contrast, some studies have reported no difference
barriers, and chemical agents[3]. between both surgical approaches. A role for CO2 pneu-
moperitoneum in adhesion formation after laparoscopic
General principles and surgical techniques: Some basic surgery has been reported[48,57].
principles should be respected during all abdominal surgical During laparoscopic surgery, CO2 pneumoperitoneum
procedures. These principles are close to the “Halstedian by itself has a real impact on abdominal adhesions. It has

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 Arung W et al . Postoperative peritoneal adhesions

been demonstrated that adhesion formation increases Adept is a safe and effective adhesion reduction agent in
with the duration of CO2 pneumoperitoneum and in- laparoscopy.
sufflation pressure[48,57]. Indeed, prolonged laparoscopic There are non-absorbable and bio-absorbable films,
surgery requires long duration and large volume gas insuf- gels or solid membranes. The most commonly used me-
flations, which raise concerns about the adverse effects of chanical barriers are oxidized regenerated cellulose (Inter-
prolonged gas insufflations[58]. The standard CO2 used in ceed®; Johnson & Johnson Medical, Arlington, TX, United
current laparoscopic practice is cold dry CO2, which is not States), expanded polytetrafluoroethylene (Preclude Peri-
physiological to the normal conditions of the peritoneal toneal Membrane®; W.L. Gore and Associates Inc., Flag-
cavity[57]. Many studies have shown that short-duration staff, AZ, United States), hyaluronic acid-carboxymethyl-
laparoscopy, < 3 h, with cold dry CO2 insufflation can cellulose (Seprafilm®; Genzyme Biosurgery, Cambridge,
cause peritoneal alterations and result in numerous detri- MA, United States) and polyethylenglycol (SprayGel®;
mental outcomes, including postoperative peritoneal ad- Confluent Surgical Inc., Waltham, MA, United States).
hesion formation[48,58]. The benefits of heated humidified Preclude is non-degradable and requires a second opera-
CO2 insufflation (37 ℃ and 95% relative humidity, physi- tion for removal. The most extensively studied bioab-
ological conditions) have been reported to include less sorbable films are Seprafilm and Interceed. Seprafilm is
hypothermia, less postoperative pains, shortened recovery absorbed within 7 d and excreted from the body within
room stay, better convalescence, less tumor spread and 28 d[63,64]. Prospective randomized controlled trials have
growth[48,58], and less adhesion formation[35]. Furthermore, shown the efficacy of Seprafilm in reducing the incidence
Molinas et al[59] have demonstrated that CO2 pneumoperi- and extent of postoperative adhesions[65-68]. However,
toneum increases postoperative peritoneal adhesions in a Seprafilm may cause a significant impairment of anasto-
time- and pressure-dependent relationship, and that this moses, and should not be applied to anastomosis cases[69].
increase is reduced by the addition of 2%-4% oxygen, Other experimental studies have demonstrated that cover-
suggesting peritoneal hypoxia as the driving mechanism. ing lesions of the parietal peritoneum with microsurgically
It supposes that when fibrinolytic activity decreases, the applied autologous peritoneal transplants can completely
process of adhesion formation does not depend anymore prevent severe peritoneal adhesion formation. However,
on the surgical approach, but evolves on its own account. the advantage of a synthetic barrier is that the material
does not need to be obtained surgically and can be cut to
Mechanical barriers: Liquid or solid mechanical barriers size outside of the abdomen and then applied without
may prevent postoperative peritoneal adhesion formation sutures[70].
by keeping peritoneal surfaces separate during the 5-7 d
required for peritoneal re-epithelialization. They prevent Chemical agents: Chemical agents generally prevent
contact between the damaged serosal surfaces for the first the organization of the persisting fibrin, by fibroblastic
few critical days. An ideal barrier should be biodegrad- proliferation inhibition. Many agents are used to inhibit
able, safe, non-inflammatory, non-immunogenic, persist this proliferation such as, non-steroidal anti-inflammatory
during the critical re- mesothelialization phase, stay in drugs (NSAIDs), corticosteroids, calcium channel block-
place without sutures or staples, remain active in the pres- ers, histamine antagonists, antibiotics, fibrinolytic agents,
ence of blood, and be rapidly and easily applied[60,61]. Also, anticoagulants, antioxidants, hormones, vitamins, colchi-
it should not interfere with healing, promote infection, cines and selective immunosuppressors[60].
or cause adhesions. Barriers are currently considered the NSAIDs reduce peritoneal adhesions in some animal
most useful adjuncts that may reduce postoperative peri- models by prostaglandin and thromboxane synthesis inhi-
toneal adhesion formation. Various solid or fluid barrier bition[9]. They decrease vascular permeability, plasmin in-
agents have been tested experimentally and in clinical trials. hibitors, platelet aggregation, and coagulation and also en-
Liquids such as crystalloids, dextran, hyaluronic acid, hance macrophage function[9]. Rodgers et al[71] have shown
cross-linked hyaluronic acid and icodextrin have been that postoperative administration of anti-inflammatory
used to prevent adhesion. They separate injured surfaces drugs to the site of injury reduced the formation of post-
by “hydroflatation” but their effectiveness is controversial. operative adhesions in two animal models. A rat model
Crystalloids, such as saline and Ringer’s lactate, are used has been used to investigate the efficacy of nimesulide, a
in large amounts but they are rapidly absorbed. The most selective cyclooxygenase-2 inhibitor, in the prevention of
commonly used hypertonic solution was 32% dextran 70, adhesion formation. This study has shown that preopera-
but it was abandoned because of serious complications[61]. tive intramuscular or postoperative intraperitoneal admin-
Other liquid barriers that have the advantage of a longer istration of nimesulide to the site of injury reduced the
residence time in the abdominal cavity, such as hyaluronic formation of postoperative adhesion in this rat model[72].
acid (Sepracoat®, Genzyme Corporation, Cambridge, MA, Generally, some anti-inflammatory drugs may be effective
United States), cross-linked hyaluronic acid (Intergel® Hy- in preventing adhesions, but there is no clinical significant
alobarrier gel; Baxter, Pisa, Italy), and icodextrin (Adept®, evidence from any published study to recommend their
Baxter Healthcare Corporation, Deerfield, IL, United use in humans for this purpose, and several side effects
States) have shown promising results in experimental and still have to be ascertained[73].
clinical studies[61]. Brown et al[62] have demonstrated that Corticosteroid therapy reduces vascular permeability

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 Arung W et al . Postoperative peritoneal adhesions

and liberation of cytokines and chemotactic factors and Some antibiotics are commonly used for prophylaxis
has reduced peritoneal adhesion formation in some ani- against postoperative infections and adhesion formation.
mal models[70]. However, corticosteroids have side effects, Less peritoneal infection may lead to less peritoneal adhe-
such as immunosuppression and delayed wound heal- sion formation. Linezolid (Zyvox®; Pfizer, New York, NY,
ing[60,74]. Kirdak et al[75] have investigated the effectiveness United States) has been found to reduce intraperitoneal
of different doses of methylprednisolone in preventing adhesion formation in a rat uterine horn model[83]. How-
experimentally induced peritoneal adhesions in rats. They ever, other studies have shown that intra-abdominal appli-
have found that there was no difference in the effective- cation itself causes adhesion formation[73]. Sortini et al[84]
ness of different methylprednisolone doses, administered have shown that antibiotics led to greater adhesion forma-
topically, in preventing peritoneal adhesion formation, tion by Zühlke score as compared to saline, whereas no
and furthermore, steroids did not prevent peritoneal ad- difference was observed between antiseptics and saline.
hesion development[75]. Indeed, antibiotics in intraperitoneal irrigation solutions
In animal models, these hormones may prevent adhe- have been demonstrated to increase peritoneal adhesion
sion formation, but some studies have not confirmed this formation in rat models, and thus, are not recommended
effectiveness in humans[74]. Progesterone has been report- as a single agent for adhesion prevention[79].
ed to have an anti-inflammatory as well as immunosup- Vitamin E is the most studied vitamin in adhesion
pressive effect, and may prevent adhesion formation[73]. prevention. In vitro studies have demonstrated that vitamin
However, Confino et al[76] have shown that there was no E has antioxidant, anti-inflammatory, anticoagulant and
significant difference overall in the incidence of adhesion antifibroblastic effects, and decreases collagen production.
formation between progesterone-treated and control rab- It has been found to be effective for reducing adhesion
bits. They have revealed a beneficial effect of progester- formation by some authors[85]. Corrales et al[86] have shown
one in the reduction of only minor adhesion formation that vitamin E, administered intraperitoneally, is as effec-
formed after minor peritoneal damage[76]. Furthermore, it tive as carboxymethylcellulose membrane in preventing
has been shown that neither estrogen nor gonadotropin- postoperative adhesions. By contrast, the same effect has
releasing hormone prevented adhesion formation, but not been achieved after intramuscular administration[87]. A
there were fewer adhesions formed in estrogen-treated significant difference has been found between intraperito-
than untreated animals[77]. neal and intramuscular vitamin E administration[87]. Thus,
The use of anticoagulants to prevent the formation intraperitoneal administration of vitamin E might be
of peritoneal adhesions has been enthusiastically reported recommended to prevent adhesion formation. However,
in the literature[78]. Many molecules have been used, such according to our literature review, there have been no hu-
as heparin or dicumarol, which prevents adhesion by in- man studies that have recommended the use of vitamin E
creasing the fibrinolysis due to serine esterase activity[79]. for postoperative adhesion prevention.
Heparin is the most widely investigated anticoagulant One study has been carried out to elucidate the effects
used for prevention of adhesions. However, its efficacy in of different concentrations of methylene blue on the pro-
reducing adhesion formation whether administered alone cess of peritoneal adhesion formation and to define its
or in combination with interceed barrier has not been minimum dose that can effectively prevent the formation
demonstrated in clinical trials[78]. of such adhesions in a rat model[88]. It could be concluded
Fibrinolytic agents such as recombinant tPA, when ap- that 1% methylene blue had the best anti-adhesion poten-
plied locally, have reduced adhesions in animal models[73]. tial[88]. If methylene blue prevents peritoneal adhesions, it
However, these fibrinolytic agents may cause hemorrhagic can cause significant impairment of anastomotic bursting
complications[73]. Three different drugs, tPA (Actilyse®; pressure during the early phase of the wound healing pro-
Boehringer Ingelheim International GmbH, Ingelheim cess by its transient inhibitory effect on the nitric oxide
am Rhein, Germany), fondaparinux (Arixtra®; GlaxoS- pathway[89].
mithKline, France), and activated drotrecogin alfa (Xigris®; Adhesions are a result of the inflammatory response
Elli Lilly and Co., DSM Pharmaceuticals, Inc. Greenville, to tissue injury in the peritoneal space. Although the
NC, United States), which affect the coagulation process mechanism is unclear, local anesthetics are reported to
at various stages, have been studied for their effective- have some anti-inflammatory effects, as shown in some
ness in preventing intraperitoneal adhesion formation in animal studies[90]. These anti-inflammatory effects are
rats[80]. All three agents were effective in preventing adhe- related to the inhibition of neutrophils. It has also been
sions when compared to the control group. Nevertheless, shown that local anesthetics activate the fibrinolytic sys-
activated drotrecogin alfa seemed the most effective ex- tem, reduce factor Ⅷ, plasminogen and α2-antiplasmin
cept when considering clinical applicability, in which case concentration, and inhibit platelet aggregation[91,92]. Thus,
fondaparinux seemed to offer the greatest advantage[80]. besides the accelerative effect of a mixture of 2.5% lido-
However, further studies have suggested that all these caine and 2.5% prilocaine in the wound healing process,
approaches may have only limited success, impeded lack some studies have demonstrated that intraperitoneal lido-
of safety, efficacy and many adverse effects without elimi- caine and prilocaine inhibit the formation of postopera-
nating the problem of postoperative peritoneal adhesion tive peritoneal adhesions without compromising wound
formation[81,82]. healing in a bacterial peritonitis rat model[93].

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 Arung W et al . Postoperative peritoneal adhesions

Hepatocyte growth factor (HGF) can inhibit collagen 10 Ergul E, Korukluoglu B. Peritoneal adhesions: facing the en-
deposition and has fibrinolytic capacity[94,95]. Liu et al[96] emy. Int J Surg 2008; 6: 253-260
11 Menzies D. Peritoneal adhesions. Incidence, cause, and pre-
have demonstrated that local application of recombinant vention. Surg Annu 1992; 24 Pt 1: 27-45
adenovirus carrying the HGF gene reduced adhesion 12 Wilkins BM, Spitz L. Incidence of postoperative adhesion
formation in a rat model. Other studies have investigated obstruction following neonatal laparotomy. Br J Surg 1986;
the use of gene therapy to manage postoperative adhe- 73: 762-764
13 Ellis H, Moran BJ, Thompson JN, Parker MC, Wilson MS,
sions. Smad7, a protein that occupies a strategic position
Menzies D, McGuire A, Lower AM, Hawthorn RJ, O’Brien
in fibrinogenesis, inhibits transforming growth factor-β F, Buchan S, Crowe AM. Adhesion-related hospital readmis-
and has the potential to attenuate postoperative adhesion. sions after abdominal and pelvic surgery: a retrospective
Guo et al[97] have investigated in an experimental model cohort study. Lancet 1999; 353: 1476-1480
the therapeutic potential of exogenous Smad7 to prevent 14 Lower AM, Hawthorn RJ, Ellis H, O’Brien F, Buchan S,
Crowe AM. The impact of adhesions on hospital readmis-
fibrinogenesis in postoperative intra-abdominal adhe- sions over ten years after 8849 open gynaecological opera-
sion. In this rat model, ultrasound-microbubble-mediated tions: an assessment from the Surgical and Clinical Adhe-
Smad7 transfection significantly decreased the incidence sions Research Study. BJOG 2000; 107: 855-862
and severity of peritoneal adhesions, but the use of tar- 15 Barmparas G, Branco BC, Schnüriger B, Lam L, Inaba K,
geted gene therapy as a preventive agent against ASBO Demetriades D. The incidence and risk factors of post-lapa-
rotomy adhesive small bowel obstruction. J Gastrointest Surg
still needs extensive evaluation before any clinical trial. 2010; 14: 1619-1628
16 Marana R, Rizzi M, Muzii L, Catalano GF, Caruana P, Man-
cuso S. Correlation between the American Fertility Society
CONCLUSION classifications of adnexal adhesions and distal tubal occlu-
Postoperative peritoneal adhesions are a major health sion, salpingoscopy, and reproductive outcome in tubal sur-
gery. Fertil Steril 1995; 64: 924-929
problem with a significant economic impact. Fibrinolysis 17 Beck DE, Ferguson MA, Opelka FG, Fleshman JW, Gervaz P,
seems to be a key factor in determining the pathogenesis Wexner SD. Effect of previous surgery on abdominal open-
of adhesion formation and in its prevention. Several stud- ing time. Dis Colon Rectum 2000; 43: 1749-1753
ies on this problem have been conducted. Their results 18 Coleman MG, McLain AD, Moran BJ. Impact of previous
surgery on time taken for incision and division of adhesions
are encouraging, but most of them are contradictory and
during laparotomy. Dis Colon Rectum 2000; 43: 1297-1299
have been conducted in animal models. Until additional 19 Van Der Krabben AA, Dijkstra FR, Nieuwenhuijzen M,
findings from future clinical studies, only meticulous Reijnen MM, Schaapveld M, Van Goor H. Morbidity and
surgery can be recommended to reduce unnecessary mor- mortality of inadvertent enterotomy during adhesiotomy. Br
bidity and mortality rates from these untoward effects of J Surg 2000; 87: 467-471
20 Goldstein DP, deCholnoky C, Emans SJ, Leventhal JM. Lap-
surgery. In the current state of knowledge, preclinical or aroscopy in the diagnosis and management of pelvic pain in
clinical studies are still necessary to evaluate the effective- adolescents. J Reprod Med 1980; 24: 251-256
ness of the several proposed prevention strategies for 21 Kresch AJ, Seifer DB, Sachs LB, Barrese I. Laparoscopy in
postoperative peritoneal adhesions. 100 women with chronic pelvic pain. Obstet Gynecol 1984; 64:
672-674
22 Rapkin AJ. Adhesions and pelvic pain: a retrospective
REFERENCES study. Obstet Gynecol 1986; 68: 13-15
23 Sulaiman H, Gabella G, Davis MSc C, Mutsaers SE, Boulos P,
1 Parker MC. Epidemiology of adhesions: the burden. Hosp Laurent GJ, Herrick SE. Presence and distribution of sensory
Med 2004; 65: 330-336 nerve fibers in human peritoneal adhesions. Ann Surg 2001;
2 Boland GM, Weigel RJ. Formation and prevention of post- 234: 256-261
operative abdominal adhesions. J Surg Res 2006; 132: 3-12 24 Ivarsson ML, Holmdahl L, Franzén G, Risberg B. Cost of
3 Schnüriger B, Barmparas G, Branco BC, Lustenberger T, bowel obstruction resulting from adhesions. Eur J Surg 1997;
Inaba K, Demetriades D. Prevention of postoperative peri- 163: 679-684
toneal adhesions: a review of the literature. Am J Surg 2011; 25 Ray NF, Denton WG, Thamer M, Henderson SC, Perry S.
201: 111-121 Abdominal adhesiolysis: inpatient care and expenditures in
4 Diamond MP, Freeman ML. Clinical implications of post- the United States in 1994. J Am Coll Surg 1998; 186: 1-9
surgical adhesions. Hum Reprod Update 2001; 7: 567-576 26 Tingstedt B, Johansson J, Nehez L, Andersson R. Late ab-
5 Ellis H. The clinical significance of adhesions: focus on intes- dominal complaints after appendectomy--readmissions dur-
tinal obstruction. Eur J Surg Suppl 1997; (577): 5-9 ing long-term follow-up. Dig Surg 2004; 21: 23-27
6 Pouly JL, Seak-San S. Adhesions: laparoscopy versus lapa- 27 Diamond MP, Nezhat F. Adhesions after resection of ovar-
rotomy. In: DiZerega GS, editor. Peritoneal surgery. New ian endometriomas. Fertil Steril 1993; 59: 934-935; author
York: Springer-Verlag, 2000: 183-192 reply 935-936
7 Diamond MP. Reduction of de novo postsurgical adhesions 28 Ray NF, Larsen JW, Stillman RJ, Jacobs RJ. Economic impact
by intraoperative precoating with Sepracoat (HAL-C) solu- of hospitalizations for lower abdominal adhesiolysis in the
tion: a prospective, randomized, blinded, placebo-controlled United States in 1988. Surg Gynecol Obstet 1993; 176: 271-276
multicenter study. The Sepracoat Adhesion Study Group. 29 Hodgkin T. Lectures on the morbid anatomy of the serous
Fertil Steril 1998; 69: 1067-1074 and mucous membranes, Vol 1. London: Simpkin Marshall
8 Kössi J, Salminen P, Rantala A, Laato M. Population-based and Co, 1836: 141
study of the surgical workload and economic impact of bow- 30 Rokitansky C. A Manual of pathological anatomy, Vol 2,
el obstruction caused by postoperative adhesions. Br J Surg The abdominal viscera. London: Sydenham Society, 1849: 39
2003; 90: 1441-1444 31 Duron JJ. Postoperative intraperitoneal adhesion patho-
9 Menzies D, Ellis H. Intestinal obstruction from adhesions-- physiology. Colorectal Dis 2007; 9 Suppl 2: 14-24
how big is the problem? Ann R Coll Surg Engl 1990; 72: 60-63 32 Holmdahl L. The role of fibrinolysis in adhesion formation.

WJG|www.wjgnet.com 4551 November 7, 2011|Volume 17|Issue 41|

 Arung W et al . Postoperative peritoneal adhesions

Eur J Surg Suppl 1997; (577): 24-31 55 Gomel V, Urman B, Gurgan T. Pathophysiology of adhesion
33 Cheong YC, Laird SM, Li TC, Shelton JB, Ledger WL, Cooke formation and strategies for prevention. J Reprod Med 1996;
ID. Peritoneal healing and adhesion formation/reformation. 41: 35-41
Hum Reprod Update 2001; 7: 556-566 56 Brokelman WJ, Holmdahl L, Bergström M, Falk P, Klinken-
34 Holmdahl L, Ivarsson ML. The role of cytokines, coagula- bijl JH, Reijnen MM. Peritoneal fibrinolytic response to vari-
tion, and fibrinolysis in peritoneal tissue repair. Eur J Surg ous aspects of laparoscopic surgery: a randomized trial. J
1999; 165: 1012-1019 Surg Res 2006; 136: 309-313
35 Rout UK, Diamond MP. Role of plasminogen activators dur- 57 Yesildaglar N, Koninckx PR. Adhesion formation in intubat-
ing healing after uterine serosal lesioning in the rat. Fertil ed rabbits increases with high insufflation pressure during
Steril 2003; 79: 138-145 endoscopic surgery. Hum Reprod 2000; 15: 687-691
36 Ichinose A, Takio K, Fujikawa K. Localization of the bind- 58 DiZerega GS. Peritoneum, peritoneal healing and adhesions
ing site of tissue-type plasminogen activator to fibrin. J Clin formation. In: diZerega GS,editor. Peritoneal surgery. New
Invest 1986; 78: 163-169 York: Springer-Verlag, 2000: 3-38
37 Norrman B, Wallén P, Rånby M. Fibrinolysis mediated by 59 Molinas CR, Mynbaev O, Pauwels A, Novak P, Koninckx
tissue plasminogen activator. Disclosure of a kinetic transi- PR. Peritoneal mesothelial hypoxia during pneumoperito-
tion. Eur J Biochem 1985; 149: 193-200 neum is a cofactor in adhesion formation in a laparoscopic
38 Holmdahl L, Eriksson E, al-Jabreen M, Risberg B. Fibrino- mouse model. Fertil Steril 2001; 76: 560-567
lysis in human peritoneum during operation. Surgery 1996; 60 Risberg B. Adhesions: preventive strategies. Eur J Surg Suppl
119: 701-705 1997; (577): 32-39
39 Lu HR, Wu Z, Pauwels P, Lijnen HR, Collen D. Comparative 61 DiZerega GS. Use of adhesion prevention barriers in pelvic
thrombolytic properties of tissue-type plasminogen activator reconstructive and gynecologic surgery. In : DiZerega GS,
(t-PA), single-chain urokinase-type plasminogen activator editor. Peritoneal surgery. New York: Springer-Verlag, 2000:
(u-PA) and K1K2Pu (a t-PA/u-PA chimera) in a combined 379-399
arterial and venous thrombosis model in the dog. J Am Coll 62 Brown CB, Luciano AA, Martin D, Peers E, Scrimgeour A,
Cardiol 1992; 19: 1350-1359 diZerega GS. Adept (icodextrin 4% solution) reduces adhe-
40 Vassalli JD, Pepper MS. Tumour biology. Membrane prote- sions after laparoscopic surgery for adhesiolysis: a double-
ases in focus. Nature 1994; 370: 14-15 blind, randomized, controlled study. Fertil Steril 2007; 88:
41 Andreasen PA, Georg B, Lund LR, Riccio A, Stacey SN. Plas- 1413-1426
minogen activator inhibitors: hormonally regulated serpins. 63 Belluco C, Meggiolaro F, Pressato D, Pavesio A, Bigon E,
Mol Cell Endocrinol 1990; 68: 1-19 Donà M, Forlin M, Nitti D, Lise M. Prevention of postsurgi-
42 Holmdahl L. The plasmin system, a marker of the propen- cal adhesions with an autocrosslinked hyaluronan derivative
sity to develop adhesions. In: DiZerega GS, editor. Peritoneal gel. J Surg Res 2001; 100: 217-221
surgery. New York: Springer-Verlag, 2000: 117-131 64 Carta G, Cerrone L, Iovenitti P. Postoperative adhesion pre-
43 Ivarsson ML, Bergström M, Eriksson E, Risberg B, Holmdahl vention in gynecologic surgery with hyaluronic acid. Clin
L. Tissue markers as predictors of postoperative adhesions. Exp Obstet Gynecol 2004; 31: 39-41
Br J Surg 1998; 85: 1549-1554 65 Becker JM, Dayton MT, Fazio VW, Beck DE, Stryker SJ,
44 Munireddy S, Kavalukas SL, Barbul A. Intra-abdominal Wexner SD, Wolff BG, Roberts PL, Smith LE, Sweeney SA,
healing: gastrointestinal tract and adhesions. Surg Clin North Moore M. Prevention of postoperative abdominal adhesions
Am 2010; 90: 1227-1236 by a sodium hyaluronate-based bioresorbable membrane: a
45 Heuer GJ, Miller RT, Matas R. In memoriam William Stew- prospective, randomized, double-blind multicenter study. J
ard Halsted : 1852- 1922. Arch Surg 1925; 10: 293-305 Am Coll Surg 1996; 183: 297-306
46 Falk K, Holmadhl L. Foreign materials. In : DiZerega GS, 66 Lim R, Morrill JM, Lynch RC, Reed KL, Gower AC, Leeman
editor. Peritoneal surgery. New York: Springer-Verlag, 2000: SE, Stucchi AF, Becker JM. Practical limitations of bioresorb-
153-174 able membranes in the prevention of intra-abdominal adhe-
47 Holtz G. Prevention and management of peritoneal adhe- sions. J Gastrointest Surg 2009; 13: 35-41; discussion 41-42
sions. Fertil Steril 1984; 41: 497-507 67 Ersoy E, Ozturk V, Yazgan A, Ozdogan M, Gundogdu H.
48 Ordoñez JL, Domínguez J, Evrard V, Koninckx PR. The ef- Comparison of the two types of bioresorbable barriers to
fect of training and duration of surgery on adhesion forma- prevent intra-abdominal adhesions in rats. J Gastrointest Surg
tion in the rabbit model. Hum Reprod 1997; 12: 2654-2657 2009; 13: 282-286
49 O'Leary DP, Coakley JB. The influence of suturing and 68 Irkorucu O, Ferahköşe Z, Memiş L, Ekinci O, Akin M. Re-
sepsis on the development of postoperative peritoneal adhe- duction of postsurgical adhesions in a rat model: a compara-
sions. Ann R Coll Surg Engl 1992; 74: 134-137 tive study. Clinics (Sao Paulo) 2009; 64: 143-148
50 Elkins TE, Stovall TG, Warren J, Ling FW, Meyer NL. A his- 69 Beck DE, Cohen Z, Fleshman JW, Kaufman HS, van Goor
tologic evaluation of peritoneal injury and repair: implica- H, Wolff BG. A prospective, randomized, multicenter, con-
tions for adhesion formation. Obstet Gynecol 1987; 70: 225-228 trolled study of the safety of Seprafilm adhesion barrier in
51 Milewczyk M. [Experimental studies on the development of abdominopelvic surgery of the intestine. Dis Colon Rectum
peritoneal adhesions in cases of suturing and non-suturing 2003; 46: 1310-1319
of the parietal peritoneum in rabbits]. Ginekol Pol 1989; 60: 70 Liakakos T, Thomakos N, Fine PM, Dervenis C, Young RL.
1-6 Peritoneal adhesions: etiology, pathophysiology, and clinical
52 Viana Ade T, Daud FV, Bonizzia A, Barros PH, Gouvêa ES. significance. Recent advances in prevention and manage-
Comparative study between parietal peritoneum suture and ment. Dig Surg 2001; 18: 260-273
nonsuture in midline laparotomies in rats. Acta Cir Bras 2008; 71 Rodgers KE, Girgis W, Campeau JD, diZerega GS. Reduc-
23: 348-351 tion of adhesion formation by intraperitoneal administration
53 Leon CJ, Gomez NA, Iñiguez SA. Suturing of the peritone- of anti-inflammatory peptide 2. J Invest Surg 1997; 10: 31-36
um during abdominal wall closure after laparotomy. World J 72 Guvenal T, Cetin A, Ozdemir H, Yanar O, Kaya T. Preven-
Surg 1994; 18: 292 tion of postoperative adhesion formation in rat uterine horn
54 Whitfield RR, Stills HF, Huls HR, Crouch JM, Hurd WW. model by nimesulide: a selective COX-2 inhibitor. Hum Re-
Effects of peritoneal closure and suture material on adhesion prod 2001; 16: 1732-1735
formation in a rabbit model. Am J Obstet Gynecol 2007; 197: 73 Nappi C, Di Spiezio Sardo A, Greco E, Guida M, Bettocchi S,
644.e1-644.e5 Bifulco G. Prevention of adhesions in gynaecological endos-

WJG|www.wjgnet.com 4552 November 7, 2011|Volume 17|Issue 41|

 Arung W et al . Postoperative peritoneal adhesions

copy. Hum Reprod Update 2007; 13: 379-394 Bras 2008; 23: 36-41
74 Sarr MG, Tito WA. Intestinal obstruction. In: Zuidema GD, 87 de la Portilla F, Ynfante I, Bejarano D, Conde J, Fernández A,
editor. Shackelford’s surgery of the alimentary tract. 4th ed, Ortega JM, Carranza G. Prevention of peritoneal adhesions
Vol 5. Philadelphia: WB Saunders Company, 1996: 387-389 by intraperitoneal administration of vitamin E: an experi-
75 Kirdak T, Uysal E, Korun N. [Assessment of effectiveness mental study in rats. Dis Colon Rectum 2004; 47: 2157-2161
of different doses of methylprednisolone on intraabdominal 88 Mahdy T, Mohamed G, Elhawary A. Effect of methylene
adhesion prevention]. Ulus Travma Acil Cerrahi Derg 2008; 14: blue on intra-abdominal adhesion formation in rats. Int J
188-191 Surg 2008; 6: 452-455
76 Confino E, Friberg J, Vermesh M, Thomas W, Gleicher N. Ef- 89 Dinc S, Ozaslan C, Kuru B, Karaca S, Ustun H, Alagol H,
fects of progesterone on postoperative adhesion formation in Renda N, Oz M. Methylene blue prevents surgery-induced
hysterectomized rabbits. Int J Fertil 1998; 33: 139-142 peritoneal adhesions but impairs the early phase of anasto-
77 Blauer KL, Collins RL. The effect of intraperitoneal proges- motic wound healing. Can J Surg 2006; 49: 321-328
terone on postoperative adhesion formation in rabbits. Fertil 90 Hollmann MW, Durieux ME. Local anesthetics and the in-
Steril 1988; 49: 144-149 flammatory response: a new therapeutic indication? Anesthe-
78 Türkçapar AG, Ozarslan C, Erdem E, Bumin C, Erverdi N, siology 2000; 93: 858-875
Kutlay J. The effectiveness of low molecular weight heparin 91 Borg T, Modig J. Potential anti-thrombotic effects of local an-
on adhesion formation in experimental rat model. Int Surg aesthetics due to their inhibition of platelet aggregation. Acta
1995; 80: 92-94 Anaesthesiol Scand 1985; 29: 739-742
79 Gutmann JN, Penzias AS, Diamond MP. Adhesions in 92 Bredbacka S, Blombäck M, Hägnevik K, Irestedt L, Raabe
reproductive surgery. In: Wallach EE, Zaccur HA, editors. N. Per- and postoperative changes in coagulation and fi-
Reproductive medicine and surgery. St. Louis: Mosby, 1995: brinolytic variables during abdominal hysterectomy under
681-193 epidural or general anaesthesia. Acta Anaesthesiol Scand 1986;
80 Topal E, Ozturk E, Sen G, Yerci O, Yilmazlar T. A compari- 30: 204-210
son of three fibrinolytic agents in prevention of intra-abdom- 93 Yuzbasioglu MF, Ezberci F, Senoglu N, Ciragil P, Tolun
inal adhesions. Acta Chir Belg 2010; 110: 71-75 FI, Oksuz H, Cetinkaya A, Atli Y, Kale IT. Intraperitoneal
81 Menzies D. Postoperative adhesions: their treatment and EMLA (lidocaine/prilocaine) to prevent abdominal adhesion
relevance in clinical practice. Ann R Coll Surg Engl 1993; 75: formation in a rat peritonitis model. Bratisl Lek Listy 2008;
147-153 109: 537-543
82 Doody KJ, Dunn RC, Buttram VC. Recombinant tissue plas- 94 Warn R, Harvey P, Warn A, Foley-Comer A, Heldin P, Ver-
minogen activator reduces adhesion formation in a rabbit snel M, Arakaki N, Daikuhara Y, Laurent GJ, Herrick SE,
uterine horn model. Fertil Steril 1989; 51: 509-512 Mutsaers SE. HGF/SF induces mesothelial cell migration
83 Aytan H, Caliskan AC, Yener T, Demirturk F, Aytan P, and proliferation by autocrine and paracrine pathways. Exp
Yenisehirli A. A novel antibiotic, linezolid, reduces intra- Cell Res 2001; 267: 258-266
peritoneal adhesion formation in the rat uterine horn model. 95 Yang J, Dai C, Liu Y. Systemic administration of naked plas-
Acta Obstet Gynecol Scand 2009; 88: 781-786 mid encoding hepatocyte growth factor ameliorates chronic
84 Sortini D, Feo CV, Maravegias K, Carcoforo P, Pozza E, renal fibrosis in mice. Gene Ther 2001; 8: 1470-1479
Liboni A, Sortini A. Role of peritoneal lavage in adhesion 96 Liu HJ, Wu CT, Duan HF, Wu B, Lu ZZ, Wang L. Adenovi-
formation and survival rate in rats: an experimental study. J ral-mediated gene expression of hepatocyte growth factor
Invest Surg 2006; 19: 291-297 prevents postoperative peritoneal adhesion in a rat model.
85 Sanfilippo JS, Booth RJ, Burns CD. Effect of vitamin E on Surgery 2006; 140: 441-447
adhesion formation. J Reprod Med 1995; 40: 278-282 97 Guo H, Leung JC, Cheung JS, Chan LY, Wu EX, Lai KN.
86 Corrales F, Corrales M, Schirmer CC. Preventing intraperito- Non-viral Smad7 gene delivery and attenuation of postop-
neal adhesions with vitamin E and sodium hyaluronate/car- erative peritoneal adhesion in an experimental model. Br J
boxymethylcellulose: a comparative study in rats. Acta Cir Surg 2009; 96: 1323-1335

S- Editor Lv S L- Editor Kerr C E- Editor Xiong L

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