PLOS ONE

RESEARCH ARTICLE

Bipolar Transurethral Enucleation of the

Prostate: Is it a size-independent endoscopic
treatment option for symptomatic benign
prostatic hyperplasia?
Carolina Bebi1, Matteo Turetti1, Elena Lievore1, Francesco Ripa1, Lorenzo Rocchini1,
Matteo Giulio Spinelli1, Elisa De Lorenzis1,2, Giancarlo Albo1,2, Fabrizio Longo1,
Franco Gadda1, Paolo Guido Dell’Orto1, Andrea Salonia ID3, Emanuele Montanari1,2,
Luca Boeri ID1*
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1 Department of Urology, Foundation IRCCS Ca’ Granda–Ospedale Maggiore Policlinico, University of Milan,
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Milan, Italy, 2 Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy,
a1111111111 3 Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
a1111111111
a1111111111 * [email protected]

Abstract
OPEN ACCESS

Citation: Bebi C, Turetti M, Lievore E, Ripa F, Background

Rocchini L, Spinelli MG, et al. (2021) Bipolar
Transurethral Enucleation of the Prostate: Is it a
Bipolar Transurethral Enucleation of the Prostate (B-TUEP) is recommended as a first-
size-independent endoscopic treatment option for choice treatment for benign prostatic obstruction in prostates >80 ml. Differently, B-TUEP is
symptomatic benign prostatic hyperplasia? PLoS only considered as an alternative option after TURP for smaller prostates (30–80 ml). The
ONE 16(6): e0253083. https://doi.org/10.1371/
aim of our study is to assess the relation between prostate size and surgical outcomes after
journal.pone.0253083
B-TUEP.
Editor: Henry Woo, University of Sydney,
AUSTRALIA
Methods
Received: February 17, 2021
We performed a retrospective analysis of data collected from 172 patients submitted to B-
Accepted: May 27, 2021 TUEP. Patients were segregated according to tertiles of prostate volume (PV) (�60 ml, 61–
Published: June 9, 2021 110 ml, >110 ml). For each group we evaluated enucleation efficacy (enucleated weight/
Peer Review History: PLOS recognizes the enucleation time), complication rates, urinary and sexual function parameters. Functional
benefits of transparency in the peer review and sexual parameters were compared between groups at baseline, 1 and 3 months follow
process; therefore, we enable the publication of up. Descriptive statistics and linear and logistic regression models tested the association
all of the content of peer review and author
between PV and postoperative complications/outcomes.
responses alongside final, published articles. The
editorial history of this article is available here:
https://doi.org/10.1371/journal.pone.0253083 Results
Copyright: © 2021 Bebi et al. This is an open Operative time and weight of enucleated adenomas increased along with prostate volumes
access article distributed under the terms of the (all p�0.01). Enucleation efficacy was higher in men with PV >110 ml compared to other
Creative Commons Attribution License, which
groups (p�0.001). Length of hospital stay, catheterization time and rates of postoperative
permits unrestricted use, distribution, and
reproduction in any medium, provided the original complications, such as transfusion and clot evacuation rates and bladder neck/urethral stric-
author and source are credited. tures, were comparable between groups. Urinary symptoms improved at 1-and 3-months in
Data Availability Statement: All relevant data are each group as compared to baseline evaluation (all p<0.01) but they did not differ according
within the paper. to PV. In each group maximum urinary flow and post-void residual volume significantly

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PLOS ONE B-TUEP is a size independent procedure for BPH

Funding: The authors received no specific funding improved at 3 months compared to baseline (all p�0.01), without differences according to
for this work. PV. Sexual symptoms were similar between groups at each follow up assessment. At multi-
Competing interests: The authors have declared variable linear and logistic regression analysis, prostate volume was not associated with
that no competing interests exist. postoperative functional outcomes and complications. Conversely, patient’s comorbid sta-
tus and antiplatelet/anticoagulation use were independently associated with postoperative
complications.

Conclusion
According to our findings, B-TUEP should be considered a “size independent procedure” as
it can provide symptom relief in men with prostates of all sizes with the same efficacy and
safety profile.

Introduction
Transurethral resection of the prostate (TURP) has been considered the gold standard surgical
treatment of benign prostatic obstruction (BPO) for decades. This technique, however, is asso-
ciated with cumulative short-term morbidity rates as high as 11.1% [1], which prompted clini-
cal researchers to focus on equally effective, but safer alternatives. Among new surgical
options, Bipolar Transurethral Enucleation of the Prostate (B-TUEP) has been proposed to
exploit the advantages of bipolar electrocautery and the superiority of enucleation over resec-
tion [2]. Studies have shown its safety and efficacy in comparison to other forms of BPO sur-
gery [3–6]. However, the majority of studies on B-TUEP focus on larger prostate sizes [7, 8].
As a matter of fact, according to the European Urological Association (EAU) guidelines treat-
ment algorithms, B-TUEP is recommended, together with TURP and laser enucleation, as first
choice in case of prostate volumes >80 ml, but it is only considered as an alternative option
after TURP for smaller prostates (30–80 ml) [9]. To the best of our knowledge, there is a lack
of studies comparing surgical outcomes after B-TUEP in patients with a wide range of prostate
volume (from small to range volume). Nevertheless, the same principle has extensively been
applied for enucleative techniques employing Holmium and Thulium laser energies [10–15]
and laser enucleation is currently considered a size independent treatment option for BPH.
Because prostate size at baseline has been shown to correlate with both perioperative and post-
operative outcomes after BPO surgery, it is important to determine whether B-TUEP out-
comes are also dependent on prostate volumes when we offer this technique as a treatment
option for BPO relief.
The aim of our study is to comprehensively assess the relation between prostate size and
surgical outcomes after B-TUEP in terms of complication rates, and modifications of urinary
and sexual parameters on the basis of our 3 years single centre experience.

Materials and methods

Between 01/11/2016 and 01/05/2019 a total of 172 consecutive white-European patients
suffering from LUTS/BPO underwent B-TUEP in our institution. Clinical data, perioperative
characteristics and surgical outcomes were prospectively collected for all patients and retro-
spectively analysed for the purpose of this study. For each subject we considered measured
Body Mass Index (BMI), rates of preoperative urethral catheterization (POC), BPO-related
drug use (alpha-blockers, 5-alpha reductase inhibitors or combination therapy) and significant
comorbid conditions, which were scored with the Charlson Comorbidity Index (CCI;

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PLOS ONE B-TUEP is a size independent procedure for BPH

categorized 0 vs. �1) [16]. The routine pre-operative assessment included measurement of
prostate specific antigen (PSA), and evaluation of prostate volume (PV) and maximum urinary
flow rate respectively by means of trans-rectal ultrasonography and uroflowmetry. Patients
were also invited to complete the International Prostate Symptoms Score (IPSS) questionnaire
in order to objectively quantify baseline LUTS severity [17]. The International Index of Erectile
Function- Erectile Function (IIEF-EF) domain and the Male Sexual Health Questionnaire-
Ejaculatory function (MSHQ-EJ) questionnaires were used to record erectile function and
ejaculation characteristics [18, 19], whereas urinary incontinence was investigated by means of
the International Consultation of Incontinence–Short Form questionnaire (ICIQ-SF) [20]. As
recommended by current European Association of Urology Guidelines, we offered B-TUEP as
a surgical option to relieve LUTS/BPO in men with prostate volumes >30 ml [9]. There was
no predetermined upper limit on prostate size that could be treated by B-TUEP. Before sur-
gery, urine culture was required for each patient and those positive to the test were treated on
the basis of the antibiogram. All patients received a preoperative wide-spectrum antibiotic pro-
phylaxis (second generation cephalosporin if not contraindicated).
All surgeries were performed in the same tertiary referral centre skin-to-skin by a single
expert surgeon (P.D.) (>100 cases).

Surgical technique
All surgeries were carried out with the Olympus UES-40 SurgMaster TUR system (Olympus
Europa Holding GmbH, Hamburg, Germany). To perform enucleation, the surgeon employed
either the standard tungsten wire loop or the B-TUEP loop, which consists of a spatula
attached to the standard wire and is specifically designed to apply the required pressure to enu-
cleate the adenoma and achieve haemostasis (Fig 1). The B-TUEP procedure was carried out

Fig 1. The Bipolar Transurethral Enucleation of the Prostate (B-TUEP) loop.

https://doi.org/10.1371/journal.pone.0253083.g001

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PLOS ONE B-TUEP is a size independent procedure for BPH

Fig 2. After creating a groove at the 12 o’clock position, two additional grooves are performed at the 5 and 7 o’clock positions, laterally to the veru montanum.
https://doi.org/10.1371/journal.pone.0253083.g002

in the same fashion for all cases, regardless of prostate size, presence of prominent middle
lobes or asymmetry. The first step of surgery is to create a groove at the 12 o’clock position, fol-
lowed by two additional grooves at the 5 and 7 o’clock positions, laterally to the veru monta-
num (Fig 2). Next, the lateral lobes and the middle lobe, when present, are bluntly dissected
circumferentially from the prostate apex towards the bladder following the plane of the cap-
sule. This allows for the enucleation of the adenoma, which is gently torn-away by repeatedly
pushing the loop against the adenoma with a circular motion (Fig 3). During this process, elec-
trocautery is not in use, but it is solely applied for precise coagulation of crossing vessel that
may bleed when the adenoma is separated from the rest of the prostate. After the process of
enucleation is completed, the button electrode may be employed to limit bleeding, based on
surgeon’s preference.
After the tissue is released into the bladder, tissue morcellation is performed (Lumenis Ver-
saCut Tissue Morcellator). After the procedure, a 22 Fr 3-way catheter is positioned for contin-
uous bladder irrigation, which is continued overnight and weaned gradually as needed.

Postoperative care
The indwelling catheter is most commonly removed on post-operative day 1 or 2 and patients
are discharged after spontaneous voiding of urine. In case of significant gross haematuria,
catheter removal was postponed on the basis of the treating physician’s decision.

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PLOS ONE B-TUEP is a size independent procedure for BPH

Fig 3. Next, the lateral lobes of the prostate are bluntly dissected circumferentially from the prostate apex towards the bladder following the plane of the capsule.
https://doi.org/10.1371/journal.pone.0253083.g003

All patients were instructed to access the hospital emergency department in the event of
post-surgical complications. Surgical complications were classified according to Dindo et al.
[21]. As per standard clinical protocol, follow-up office/based visits were routinely scheduled
1, 3 and 12 months after surgery. Patients were asked to complete the psychometric question-
naires at all follow-up assessments, whereas uroflowmetry and PSA were only repeated 3 and
12 months after surgery. The primary objective of the study was to investigate the relationship
between prostate volume and surgical outcomes after B-TUEP. For the specific purpose of the
study, patients were segregated according to tertiles of prostate volume (namely, �60 ml, 61–
110 ml, and >110 ml). Perioperative outcomes included weight of the enucleated adenoma
and calculation of the enucleation efficacy, expressed as enucleated weight/enucleation time.
Among postoperative outcomes we recorded length of hospital stay, catheterization time and
complication rates (i.e. incidence of transfusions, clot evacuation rates, development of stric-
tures). Evaluated urinary parameters included the IPSS and ICIQ-SF scores, maximum urinary
flow and post-void residual volume, whereas IIEF-EF scores were used to document changes
in sexual parameters from baseline to follow-up.
Exclusion criteria were: patients older than 80 years old (N = 10); presence of a known pros-
tate or bladder cancer (N = 1); neurogenic disorders or history of bladder disease or other uro-
logic conditions likely to affect micturition (e.g. urethral stenosis, urinary incontinence,
chronic bacterial prostatitis) (N = 8); concomitant antidepressant therapy (N = 3); and previ-
ous surgical treatment for LUTS/BPO (N = 5).

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PLOS ONE B-TUEP is a size independent procedure for BPH

Data were collected following the principles outlined in the Declaration of Helsinki. All
patients signed an informed consent form agreeing to share their own anonymous informa-
tion for future studies. The study was approved by the IRCCS Foundation Ca’ Granda–Mag-
giore Policlinico Hospital Ethical Committee (Prot. 25508).

Statistical analysis
Distribution of data was tested with the Shapiro-Wilk test. Data are presented as medians
(interquartile range; IQR) or frequencies (proportions). Pre-, intra-, and post-operative vari-
ables were compared between the three groups (i.e. PV� 60 ml, PV 61–110 ml and PV>110
ml) with the Fisher exact test and the Kruskal-Wallis test with multiple comparisons. In each
group, potential differences in functional and sexual parameters at each follow-up assessment
(baseline, 1 and 3 months) were evaluated with the paired t-test. Functional and sexual
outcomes were compared between groups at each follow-up with the Kruskal-Wallis test.
Spearman’s correlation tested the association between clinical variables and prostate size. Uni-
variable (UVA) and multivariable (MVA) linear regression analyses tested the associations
between clinical predictors and 1-3-months post-surgery IPSS in the whole cohort. Similarly,
UVA and MVA logistic regression analysis were used to identify potential predictors of post-
operative complications (any). Statistical analyses were performed using SPSS v.26 (IBM
Corp., Armonk, NY, USA). All tests were two sided and statistical significance level was deter-
mined at p<0.05.

Results
Table 1 details preoperative characteristics of patients submitted to B-TUEP and categorized
according to tertiles of prostate volume. Overall, 49 (28.4%), 74 (43.2%) and 49 (28.4%) men
had a preoperative PV of �60 ml, 61–110 ml and >110 ml, respectively. Groups were compa-
rable in terms of age, BMI, CCI and anticoagulation/antiplatelet (AC/AP) use. Serum PSA
increased with increasing prostate size (p�0.001). A higher rate of men with PV >110 ml had
POC as compared to those in the other groups (p = 0.01). The lowest preoperative maximum
flow was reported in men with PV >110 ml (p�0.001). The distribution of BPH-related medi-
cations was similar among groups.

Perioperative outcomes among B-TUEP patients according to prostate size

Operative time and the weight of the enucleated adenoma increased along with the categories
of prostate volumes (all p�0.01) (Table 2). The enucleation efficacy was higher in men with
PV >110 ml compared to those in the other groups (p�0.001). The percentage of PSA reduc-
tion was significantly correlated with enucleated adenoma (Spearman’s Rho = 0.5, p�0.001).
Length of hospital stay, catheterization time and rates of postoperative complications were
comparable between groups (Table 2). In particular, transfusion and clot evacuation rates were
independent of PV (S1 Table). The rate of late complications (bladder neck and urethral stric-
tures) was similar among groups.

Functional outcomes among B-TUEP patients

Preoperative total IPSS score was similar between groups (Table 3). After surgery, total IPSS
score improved at 1-and 3-months in each group as compared to baseline evaluation (all
p<0.01). However, at each follow up assessment, total IPSS score did not differ according to
prostate volume. Both storage and voiding symptoms significantly improved after surgery,
irrespective of PV (all p<0.01) (Table 3). The ICIQ-SF score was higher at 1 months after

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PLOS ONE B-TUEP is a size independent procedure for BPH

Table 1. Preoperative characteristics of the whole cohort of patients submitted to B-TUEP as segregated according to prostate volume (no. = 172).
� 60 ml 61–110 ml > 110 ml p value�
No. of patients [No. (%)] 49 (28.4) 74 (43.2) 49 (28.4)
Age (years) 0.9
Median (IQR) 71 (65–74) 71 (66–76) 71 (64–76)
Range 55–80 51–83 51–85
BMI (kg/m2) 0.8
Median (IQR) 25.8 (23.8–27.8) 25.0 (23.1–27.4) 24.9 (23.8–27.8)
Range 20.3–39.6 17.6–38.1 19.3–35.0
CCI > = 1 [No. (%)] 28 (57.1) 42 (56.8) 23 (46.9) 0.5
AP/AC therapy [No. (%)] 21 (42.9) 23 (31.1) 13 (26.5) 0.2
Year of surgery [No. (%)] 0.7
2017 15 (30.6) 29 (39.2) 18 (36.7)
2018 16 (32.7) 25 (33.8) 20 (27.0)
2019 18 (36.7) 20 (27.0) 14 (28.6)
PSA (ng/mL) �0.001
Median (IQR) 1.6 (0.8–3.6) 3.8 (1.8–5.9) § 4.6 (2.7–6.7) §
Range 0.2–12.5 0.1–15.3 0.9–21.5
POC [No. (%)] 6 (12.2) 22 (30.6) § 18 (36.2) § 0.01
Duration of POC (months) 0.9
Median (IQR) 7.0 (5.0–8.0) 7.0 (4.0–9.0) 7.0 (4.0–13.0)
Range 0.0–12 3.0–16 6.0–20
BPH-related drugs [No. (%)] 0.8
Alpha-blockers 21 (44.4) 27 (37.1) 20 (40.9)
5-ARI 6 (13.4) 14 (18.5) 4 (9.1)
Combination 22 (42.2) 33 (44.3) 25 (50.0)
Prostate Volume (ml) �0.001
Median (IQR) 60 (50–60) 80 (70–90) § 130 (120–146) §, #
Range 30–60 65–110 115–260
Flow Max (mL/sec) �0.01
Median (IQR) 9.2 (7.9–13.0) 7.3 (4.6–8.4) § 5.1 (4.4–11.3) §,#
Range 3.5–20.0 2.9–11.9 1.9–20.2
Post-void residual volume (ml) 0.01
Median (IQR) 80 (30–100) 100 (30–140) § 115 (60–170) §
Range 0–800 0–900 0–800
Preoperative Hemoglobin (g/dL) 0.8
Median (IQR) 14.5 (13.8–15.5) 14.5 (13.7–15.3) 14.9 (13.6–15.5)
Range 11.3–18.1 10.9–17.1 10.0–16.6

Keys: B-TUEP = bipolar transurethral enucleation of the prostate; BMI = body mass index; CCI = Charlson Comorbidity Index
AP/AG = Antiplatelet/Anticoagulation; PSA = Prostate specific antigen; POC = pre-operative catheterization
BPH = benign prostatic hyperplasia; 5-ARI = 5-alpha reductase inhibitors
�
P value according to unpaired Kruskal Wallis test for continuous data and Fisher Exact test for categorical variables, as indicated.
§ p < 0.01 vs. � 60 ml group
# p < 0.01 vs. 60–110 ml group

https://doi.org/10.1371/journal.pone.0253083.t001

surgery in each group as compared to baseline (all p�0.01), but it returned to preoperative
value at 3 months. No differences were found in terms of ICIQ-SF scores at each follow up
assessment according to prostate size.

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PLOS ONE B-TUEP is a size independent procedure for BPH

Table 2. Perioperative characteristics of the whole cohort of patients submitted to B-TUEP as segregated according to prostate volume (no. = 172).
� 60 ml (N = 49) 61–110 ml (N = 74) > 110 ml (N = 49) p value�
Operative time (min) � 0.01
Median (IQR) 85 (64–115) 105 (90–126) § 150 (123–167) §, #
Range 45–190 45–320 57–240
Enucleation time (min) � 0.001
Median (IQR) 56 (40–71) 70 (60–83) § 90 (76–106) §, #
Range 20–120 30–213 40–140
Enucleated adenoma (ml) � 0.001
Median (IQR) 30 (20–40) 70 (45–90) § 110 (90–150) §, #
Range 20–60 55–140 70–180
Enucleation efficacy (ml/min) � 0.001
Median (IQR) 0.4 (0.3–0.7) 0.6 (0.5–0.9) §, # 0.8 (0.6–1.0) §, #
Range 0.1–1.1 0.2–1.5 0.4–2.1
Catheterization time (days) 0.1
Median (IQR) 2.0 (1.0–3.0) 2.0 (1.0–3.0) 2.0 (2.0–3.0)
Range 1.0–10.0 1.0–9.0 1–7
Length of stay (days) 0.6
Median (IQR) 3.0 (3.0–4.0) 3.0 (3.0–4.0) 4.0 (3.0–4.0)
Range 2.0–19.0 2.0–9.0 2–9
Hemoglobin drop (g/dL) 0.1
Median (IQR) 1.0 (0.5–1.9) 1.0 (0.7–2.2) 1.2 (0.9–2.3)
Range 0.0–5.5 0.0–4.8 0.0–5.5
PSA reduction from baseline (%) 0.001
Median (IQR) 38.0 (20–65) 60.0 (45–81) § 84 (54–90) §, #
Range 10.0–93.0 11.0–97.0 15.0–98.1
Overall Complications [No. (%)] 10 (20.4) 12 (16.2) 10 (20) 0.8
Complication severity [No. (%)] 0.5
Clavien Dindo I 1 (2.0) 5 (6.8) 2 (4.1)
Clavien Dindo II 3 (6.1) 5 (6.8) 5 (10.2)
Clavien Dindo IIIa 6 (12.2) 3 (4.1) 3 (6.1)
Transfusion rate [No. (%)] 1 (2.0) 0 (0.0) 1 (2.0) 0.6

Keys: B-TUEP = bipolar transurethral enucleation of the prostate; PSA = Prostate specific antigen � P value according to unpaired Kruskal Wallis test for continuous data
and Fisher Exact test for categorical variables, as indicated.
§ p < 0.01 vs. � 60 ml group
# p < 0.01 vs. 60–110 ml group

https://doi.org/10.1371/journal.pone.0253083.t002

In each group maximum urinary flow and post-void residual volume significantly
improved at 3 months compared to baseline (all p�0.01), without differences according to PV.
Preoperative IIEF-EF scores were similar between groups. After surgery, IIEF-EF scores
were comparable to baseline values at each follow-up assessment irrespective of the study
group (Table 3).

Clinical predictors of postoperative IPSS and complications

Table 4 reports UVA and MVA liner regression analyses showing the associations between
study variables and 1-3-months post-surgery IPSS in the whole cohort. Prostate volume was
not associated with postoperative IPSS in men submitted to B-TUEP. This was also the case
for patient’s age, CCI, rates of POC and AC/AP use and preoperative IPSS scores.

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PLOS ONE B-TUEP is a size independent procedure for BPH

Table 3. Functional and sexual characteristics of the whole cohort of patients as segregated according to prostate size [median (IQR)].
� 60 ml 61–110 ml > 110 ml p value�
Functional outcomes
Total IPSS score
Preoperative n = 49 18.0 (15–27) n = 74 18.0 (14–24) n = 49 20.0 (10–30) 0.8
1 month n = 48 6.0 (3–15) § n = 74 7.0 (2–10) § n = 49 8.0 (4–15) § 0.4
3 months n = 48 6.0 (3–13) § n = 72 5.0 (3–10) § n = 48 7.0 (5–16) § 0.2
IPSS-storage score
Preoperative 8.0 (6–9) 7.0 (5–11) 7.0 (4–11) 0.8
1 month 5.0 (2–8) § 5.0 (4–8) § 5.0 (3–9) § 0.7
3 months 4.0 (3–7) § 4.0 (2–7) § 4.0 (3–11) § 0.4
IPSS-voiding score
Preoperative 10.0 (6–12) 10.0 (5–12) 8.0 (5–14) 0.9
1 month 4.0 (1–8) § 1.0 (0–4) § 2.0 (1–6) § 0.3
3 months 3.0 (1–6) § 1.0 (0–2) § 2.0 (0–4) § 0.2
ICIQ-SF
Preoperative 1.0 (0–7) 0.0 (0–4) 0.0 (0–5) 0.4
1 month 3.0 (0–9) § 2.0 (0–7) § 3.0 (0–9) § 0.3
3 months 0.0 (0–6) # 0.0 (0–5) # 0.0 (0–5) # 0.6
Flow Max (mL/sec)
3 months n = 48 24.0 (14–35) § n = 71 25.0 (11–30) § n = 48 23.0 (10–29) § 0.1
Post-void residual volume (ml)
3 months 0.0 (0–30) § 0.0 (0–23) § 0.0 (0–26) § 0.7
Sexual outcomes
IIEF-EF score
Preoperative 23.0 (5–29) 23.0 (5–28) 22.0 (5–28) 0.5
1 month 20.0 (4–28) 20.0 (6–29) 21.0 (4–28) 0.7
3 months 20.0 (5–29) 19.0 (5–27) 20.0 (4–27) 0.7

Keys: IPSS = International Prostatic Symptoms Score; ICIQ-SF = The International Consultation of Incontinence–Short Form
IIEF-EF = International Index of Erectile Function- Erectile Function domain
�
P value according to unpaired Kruskal Wallis test
§ p < 0.01 vs. baseline. P value according to paired t-test

https://doi.org/10.1371/journal.pone.0253083.t003

Table 4. Univariable and multivariable linear regression models (beta; p value [95%CI]) predicting IPSS at 1 and 3 months after surgery.
1-month IPSS 3-months IPSS
UVA model MVA model UVA model MVA model
Age 0.21; 0.89 [-0.24–0.21] 0.12; 0.37 [-0.14–0.38] 0.14; 0.22 [-0.10–0.37] 0.11; 0.49 [-0.21–0.43]
CCI �1 -0.92; 0.51 [-3.74–1.89] -0.96; 0.53 [-4.06–2.13]
POC 0.03; 0.98 [-3.73–3.47] -2.61; 0.26 [-7.29–2.07] -1.34; 0.45 [-4.93–2.25] -3.13; 0.22 [-8.33–2.06]
Prostate size
� 60 ml Ref Ref Ref Ref
61–110 ml 0.31; 0.38 [-1.54–1.91] 0.26; 0.22 [-2.97–1.41] 0.82; 0.31 [-1.37–1.73] 0.51; 0.27 [-1.09–2.06]
> 110 ml 0.65; 0.73 [-2.19–2.49] 0.69; 0.42 [-1.55–2.93] 0.87; 0.14 [-1.98–3.73] 0.53; 0.55 [-1.71–2.79]
AP/AC 1.34; 0.36 [-1.61–4.29] 1.93; 0.24 [-1.33–5.19]
Preoperative IPSS -0.18; 0.11 [-0.41–0.05] -0.14; 0.23 [-0.36–0.09] -0.17; 0.21 [-0.44–0.11] -0.11; 0.51 [-0.43–0.22]

Keys: UVA = Univariate model; MVA = Multivariate model, CCI = Charlson Comorbidity Index
AP/AG = Antiplatelet/Anticoagulation; POC = pre-operative catheterization; IPSS = International Prostatic Symptoms Score.

https://doi.org/10.1371/journal.pone.0253083.t004

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Table 5. Univariable and multivariable logistic regression models predicting postoperative complications (any) after surgery.
Odds Ratio 95% CI p value Odds Ratio 95% CI p value
UVA MVA
Age 1.03 0.97; 1.11 0.21 1.02 0.95; 1.08 0.59
CCI �1 3.78 1.53; 9.31 <0.01 2.78 1.05; 7.45 0.04
Operative time 1.01 0.99; 1.01 0.67 1.01 0.99; 1.02 0.15
Prostate size
� 60 ml Ref Ref
61–110 ml 0.75 0.69; 1.91 0.53 0.66 0.52; 1.99 0.46
> 110 ml 0.81 0.58; 2.18 0.9 0.76 0.61; 2.91 0.69
AP/AC 2.83 1.29; 6.21 <0.01 2.69 1.08; 6.76 0.03

Keys: UVA = Univariate model; MVA = Multivariate model, CCI = Charlson Comorbidity Index
AP/AG = Antiplatelet/Anticoagulation

https://doi.org/10.1371/journal.pone.0253083.t005

On the contrary, multivariable analysis revealed that CCI�1 (OR 2.78; p = 0.04) and AC/
AP use (OR 2.69; p = 0.03) were independently associated with postoperative complications,
after accounting for age, operative time and prostate volume (Table 5).

Discussion
In this study we found that B-TUEP is an excellent surgical option for BPO treatment. Accord-
ing to our findings, this technique can be considered as a “size independent procedure” since
it is able to provide symptom relief in men with prostates of all sizes with the same efficacy and
safety profile. Transurethral enucleation of the prostate with bipolar energy is well known to
be effective in larger prostate sizes [4, 3, 6, 7], whereas only a few studies documented its effi-
cacy in smaller prostates [22, 23].
Our study, however, was motivated by the complete lack of studies that aimed to directly
compare outcomes of B-TUEP according to prostate volume.
In terms of complication rates, our findings are comparable to results reported for other
enucleative techniques [8, 23]. Rates of perioperative complications, such as transfusion and
clot evacuation were low, as only 2 patients in the whole cohort required transfusions and 4
patients required clot evacuation. The incidence of late complications such as bladder neck
and urethral strictures was also limited, 4.1% in the �60 ml group, 4% in the 61–110 ml group,
4.1% in the >110ml group). As already reported, B-TUEP is safe in patients under AC/AP
therapy [24], however, current results reported that AC/AP use and patients with comorbid
conditions (as depicted by the CCI score) were at higher risk of postoperative complications,
yet irrespective of prostate size. Notably, according to our analysis, complication rates, length
of hospital stay, and catheterization time after surgery were comparable in all groups. While
for trans-urethral resection of the prostate rates of complications have long been known to
increase with higher prostate volumes [1, 25], more recent findings on enucleative techniques
found no direct relation between complication rates and prostate volumes [10, 13, 26], which
is consistent with our findings.
Additionally, in our cohort, urinary parameters such as IPSS score, maximum urinary flow
and post-void residual volume also appeared to improve independently form prostate size.
Erectile function, as expressed by changes in the IIEF-EF scores, did not change after surgery,
which is consistent with previously reported findings for most studies on BPO surgery [27–30].
One of the most prominent aspects of our findings is that the enucleation efficacy increased
along with prostate volume categories. This parameter is expressed as a simple fraction

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PLOS ONE B-TUEP is a size independent procedure for BPH

consisting of a numerator (enucleated weight) and a denominator (enucleation time) and this
ratio was found to increase in larger prostates. If the enucleation is performed correctly, the
increase in enucleated weight, i.e. the numerator, is expected to be proportional to the increase
in volume. Interestingly, according to our findings, when prostates become larger, the corre-
sponding increase in enucleation time, i.e. the denominator, must be smaller in proportion to
the increase in volume. As a consequence, we may deduce that smaller adenomas take more
time to be enucleated if compared to bigger ones. In other words, smaller prostates appear to
be more difficult to enucleate. This concept corroborates a notion that has already been
reported in previous studies [31], and is also often reported by surgeons as a mere intra-opera-
tive perception. A study by Hirasawa et al. [23] demonstrated that enucleation efficacy not
only increased as prostate size increased, but also improved markedly when the surgeons expe-
rience level exceeded 50 cases. This implies that technical proficiency is paramount in order to
perform B-TUEP.
Of note, as often recommended [32], surgeons tend to tackle larger prostates after having
experience with smaller glands, which may represent a confounding factor for the measure-
ment of operative time, due to the impact of the surgeon’s learning curve on velocity. How-
ever, in our cohort, the number of small, intermediate and large prostates was evenly
distributed throughout the years, therefore enucleation time could not be influenced by the
surgeon’s experience.
The clinical implications of our study are several. First, we conducted the first thorough
investigation of functional and sexual outcomes following B-TUEP performed in men catego-
rized according to different prostate volume. Indeed, our findings showed that B-TUEP is a
size independent procedure. Second, we showed, for the first time, that enucleation efficacy
during B-TUEP was higher in larger prostates as compared to smaller ones. These findings
corroborate the difficulties of enucleating small adenomas that surgeons experience in the
everyday clinical practice, thus potentially suggesting that the beginning of the learning curve
of B-TUEP should be focused on large prostates.
Our study is not devoid of limitations. First, it was designed as a retrospective, non-rando-
mised study, with the intrinsic limitations of its nature. Likewise, clinical homogeneity of the
population might have influenced our results. Moreover, it describes the experience of a single
surgeon in a single centre, therefore larger studies across different centres are needed in order
to confirm our findings.

Conclusions
B-TUEP is a “size independent procedure” since it can be performed in prostates of all vol-
umes with comparable safety profile and functional results. The enucleation efficacy is higher
for larger prostates with no effect on surgical outcomes. Prostate volume was not associated
with postoperative functional outcomes and complication rates, while CCI�1 and AC/AP
therapy emerged as the only independent predictors of complications after B-TUEP. Future
studies should also stratify their results on the basis of prostate size in order to determine if
and how changes in volume may affect BPO surgery and whether prostate volume represents a
parameter to be taken into account for adequate patient selection.

Supporting information
S1 Table. Descriptive characteristics of postoperative complications according to prostate
size (N = 172).
(DOCX)

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PLOS ONE B-TUEP is a size independent procedure for BPH

Author Contributions
Conceptualization: Carolina Bebi, Luca Boeri.
Data curation: Carolina Bebi, Matteo Turetti, Elena Lievore, Francesco Ripa, Lorenzo Roc-
chini, Matteo Giulio Spinelli, Elisa De Lorenzis, Giancarlo Albo, Fabrizio Longo, Franco
Gadda, Paolo Guido Dell’Orto, Andrea Salonia, Emanuele Montanari, Luca Boeri.
Methodology: Andrea Salonia, Emanuele Montanari, Luca Boeri.
Supervision: Carolina Bebi, Andrea Salonia, Emanuele Montanari, Luca Boeri.
Writing – original draft: Carolina Bebi.
Writing – review & editing: Carolina Bebi.

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