Skip to main content
PLOS One logoLink to PLOS One
. 2021 Jun 9;16(6):e0253083. doi: 10.1371/journal.pone.0253083

Bipolar Transurethral Enucleation of the Prostate: Is it a size-independent endoscopic treatment option for symptomatic benign prostatic hyperplasia?

Carolina Bebi 1, Matteo Turetti 1, Elena Lievore 1, Francesco Ripa 1, Lorenzo Rocchini 1, Matteo Giulio Spinelli 1, Elisa De Lorenzis 1,2, Giancarlo Albo 1,2, Fabrizio Longo 1, Franco Gadda 1, Paolo Guido Dell’Orto 1, Andrea Salonia 3, Emanuele Montanari 1,2, Luca Boeri 1,*
Editor: Henry Woo4
PMCID: PMC8189479  PMID: 34106986

Abstract

Background

Bipolar Transurethral Enucleation of the Prostate (B-TUEP) is recommended as a first-choice treatment for benign prostatic obstruction in prostates >80 ml. Differently, B-TUEP is only considered as an alternative option after TURP for smaller prostates (30–80 ml). The aim of our study is to assess the relation between prostate size and surgical outcomes after B-TUEP.

Methods

We performed a retrospective analysis of data collected from 172 patients submitted to B-TUEP. Patients were segregated according to tertiles of prostate volume (PV) (≤60 ml, 61–110 ml, >110 ml). For each group we evaluated enucleation efficacy (enucleated weight/enucleation time), complication rates, urinary and sexual function parameters. Functional and sexual parameters were compared between groups at baseline, 1 and 3 months follow up. Descriptive statistics and linear and logistic regression models tested the association between PV and postoperative complications/outcomes.

Results

Operative time and weight of enucleated adenomas increased along with prostate volumes (all p≤0.01). Enucleation efficacy was higher in men with PV >110 ml compared to other groups (p≤0.001). Length of hospital stay, catheterization time and rates of postoperative complications, such as transfusion and clot evacuation rates and bladder neck/urethral strictures, were comparable between groups. Urinary symptoms improved at 1-and 3-months in each group as compared to baseline evaluation (all p<0.01) but they did not differ according to PV. 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. Sexual symptoms were similar between groups at each follow up assessment. At multivariable linear and logistic regression analysis, prostate volume was not associated with postoperative functional outcomes and complications. Conversely, patient’s comorbid status 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 associated with cumulative short-term morbidity rates as high as 11.1% [1], which prompted clinical 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 resection [2]. Studies have shown its safety and efficacy in comparison to other forms of BPO surgery [36]. 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 treatment 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 [1015] 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 postoperative outcomes after BPO surgery, it is important to determine whether B-TUEP outcomes 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 retrospectively 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; 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 surgery, 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 prophylaxis (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 enucleate the adenoma and achieve haemostasis (Fig 1). The B-TUEP procedure was carried out 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, followed by two additional grooves at the 5 and 7 o’clock positions, laterally to the veru montanum (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 capsule. 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, electrocautery 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.

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

Fig 1

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.

Fig 2

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.

Fig 3

After the tissue is released into the bladder, tissue morcellation is performed (Lumenis VersaCut Tissue Morcellator). After the procedure, a 22 Fr 3-way catheter is positioned for continuous 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.

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 questionnaires 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 strictures). 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 prostate or bladder cancer (N = 1); neurogenic disorders or history of bladder disease or other urologic conditions likely to affect micturition (e.g. urethral stenosis, urinary incontinence, chronic bacterial prostatitis) (N = 8); concomitant antidepressant therapy (N = 3); and previous surgical treatment for LUTS/BPO (N = 5).

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 information for future studies. The study was approved by the IRCCS Foundation Ca’ Granda–Maggiore 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 variables 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. Univariable (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 postoperative 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 determined 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 comparable 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 medications was similar among groups.

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

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 reduction 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 strictures) was similar among groups.

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

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 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.

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

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.

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.

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).

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

Discussion

In this study we found that B-TUEP is an excellent surgical option for BPO treatment. According 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 efficacy 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 [2730].

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 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 corresponding 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-operative 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 experience 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 measurement of operative time, due to the impact of the surgeon’s learning curve on velocity. However, 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 categorized 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-randomised 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 volumes 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)

Data Availability

All relevant data are within the paper.

Funding Statement

The authors received no specific funding for this work.

References

  • 1.Reich O, Gratzke C, Bachmann A, Seitz M, Schlenker B, Hermanek P, et al. Morbidity, mortality and early outcome of transurethral resection of the prostate: a prospective multicenter evaluation of 10,654 patients. J Urol. 2008. Jul;180(1):246–9. doi: 10.1016/j.juro.2008.03.058 [DOI] [PubMed] [Google Scholar]
  • 2.Giulianelli R, Gentile B, Albanesi L, Tariciotti P, Mirabile G. Bipolar Button Transurethral Enucleation of Prostate in Benign Prostate Hypertrophy Treatment: A New Surgical Technique. Urology. 2015. Aug 1;86(2):407–14. doi: 10.1016/j.urology.2015.03.045 [DOI] [PubMed] [Google Scholar]
  • 3.Geavlete B, Stanescu F, Iacoboaie C, Geavlete P. Bipolar plasma enucleation of the prostate vs open prostatectomy in large benign prostatic hyperplasia cases—a medium term, prospective, randomized comparison. BJU Int. 2013. May;111(5):793–803. doi: 10.1111/j.1464-410X.2012.11730.x [DOI] [PubMed] [Google Scholar]
  • 4.Chen S, Zhu L, Cai J, Zheng Z, Ge R, Wu M, et al. Plasmakinetic enucleation of the prostate compared with open prostatectomy for prostates larger than 100 grams: a randomized noninferiority controlled trial with long-term results at 6 years. Eur Urol. 2014. Aug;66(2):284–91. doi: 10.1016/j.eururo.2014.01.010 [DOI] [PubMed] [Google Scholar]
  • 5.Lingfeng Zhu, Shushang Chen, Shunliang Yang, Meijing Wu, Rong Ge, Weizhen Wu, et al. Electrosurgical Enucleation Versus Bipolar Transurethral Resection for Prostates Larger than 70 ml: A Prospective, Randomized Trial with 5-Year Followup. Journal of Urology. 2013. Apr 1;189(4):1427–31. [DOI] [PubMed] [Google Scholar]
  • 6.Mu X-N, Wang S-J, Chen J, Jin X-B, Huang Z-X, Zhang L-Y. Bipolar transurethral enucleation of prostate versus photoselective vaporization for symptomatic benign prostatic hyperplasia (>70 ml). Asian J Androl. 2017;19(5):608–12. doi: 10.4103/1008-682X.178484 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Mallikarjuna C, Nayak P, Ghouse SM, Reddy PC, Ragoori D, Bendigeri MT, et al. Transurethral enucleation with bipolar energy for surgical management of benign prostatic hyperplasia: Our initial experience. Indian J Urol. 2018;34(3):219–22. doi: 10.4103/iju.IJU_71_16 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Giulianelli R, Gentile BC, Mirabile G, Albanesi L, Tariciotti P, Rizzo G, et al. Bipolar Plasma Enucleation of the Prostate (B-TUEP) in Benign Prostate Hypertrophy Treatment: 3-Year Results. Urology. 2017. Sep 1;107:190–5. doi: 10.1016/j.urology.2017.05.021 [DOI] [PubMed] [Google Scholar]
  • 9.Professionals S-O. EAU Guidelines: Management of Non-neurogenic Male LUTS [Internet]. Uroweb. [cited 2020 Apr 19]. Available from: https://uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/#note_354
  • 10.Seki N, Tatsugami K, Naito S. Holmium laser enucleation of the prostate: comparison of outcomes according to prostate size in 97 Japanese patients. J Endourol. 2007. Feb;21(2):192–6. doi: 10.1089/end.2006.0123 [DOI] [PubMed] [Google Scholar]
  • 11.Shah HN, Sodha HS, Kharodawala SJ, Khandkar AA, Hegde SS, Bansal MB. Influence of prostate size on the outcome of holmium laser enucleation of the prostate. BJU Int. 2008. Jun;101(12):1536–41. doi: 10.1111/j.1464-410X.2007.07434.x [DOI] [PubMed] [Google Scholar]
  • 12.Department of Urology, Gulhane Training and Research Hospital, Ankara, Turkey, Yalcin S, Yilmaz S, Department of Urology, Gulhane Training and Research Hospital, Ankara, Turkey, Gazel E, Clinic of Urology, Acibadem Ankara Hospital, Ankara, Turkey, et al. Holmium laser enucleation of the prostate for the treatment of size-independent BPH: A single-center experience of 600 cases. Turkish Journal of Urology. 2020. May 8;46(3):219–25. doi: 10.5152/tud.2020.19235 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Kuntz RM, Lehrich K, Ahyai S. Does perioperative outcome of transurethral holmium laser enucleation of the prostate depend on prostate size? J Endourol. 2004. Mar;18(2):183–8. doi: 10.1089/089277904322959842 [DOI] [PubMed] [Google Scholar]
  • 14.Humphreys MR, Miller NL, Handa SE, Terry C, Munch LC, Lingeman JE. Holmium Laser Enucleation of the Prostate—Outcomes Independent of Prostate Size? The Journal of Urology. 2008. Dec 1;180(6):2431–5. doi: 10.1016/j.juro.2008.08.019 [DOI] [PubMed] [Google Scholar]
  • 15.Netsch C, Tiburtius C, Bach T, Knipper S, Gross AJ. Association of prostate size and perioperative morbidity in thulium: YAG vapoenucleation of the prostate. Urol Int. 2014;93(1):22–8. doi: 10.1159/000355105 [DOI] [PubMed] [Google Scholar]
  • 16.Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83. doi: 10.1016/0021-9681(87)90171-8 [DOI] [PubMed] [Google Scholar]
  • 17.Badía X, García-Losa M, Dal-Ré R. Ten-language translation and harmonization of the International Prostate Symptom Score: developing a methodology for multinational clinical trials. Eur Urol. 1997;31(2):129–40. doi: 10.1159/000474438 [DOI] [PubMed] [Google Scholar]
  • 18.D’Elia C, Cerruto MA, Cavicchioli FM, Cardarelli S, Molinari A, Artibani W. Critical points in understanding the Italian version of the IIEF 5 questionnaire. Arch Ital Urol Androl. 2012. Dec;84(4):197–201. [PubMed] [Google Scholar]
  • 19.Ugolini V, Pescatori ES. Presentazione della versione italiana del Male Sexual Health Questionnaire (MSHQ). GIMSeR 2005;12:215–216. Available at: http://www.andrologiaitaliana.it/upload/content/docs/gimser_4_05.pdf. [Google Scholar]
  • 20.Tubaro A, Zattoni F, Prezioso D, Scarpa RM, Pesce F, Rizzi CA, et al. Italian validation of the International Consultation on Incontinence Questionnaires. BJU Int. 2006. Jan;97(1):101–8. doi: 10.1111/j.1464-410X.2006.05885.x [DOI] [PubMed] [Google Scholar]
  • 21.Dindo D, Demartines N, Clavien P-A. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004. Aug;240(2):205–13. doi: 10.1097/01.sla.0000133083.54934.ae [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Giulianelli R, Gentile BC, Mirabile G, Tema G, Nacchia A, Albanesi L, et al. Bipolar Plasma Enucleation of the Prostate: 5 Years Outcomes. Journal of Endourology. 2019. May;33(5):396–9. doi: 10.1089/end.2019.0050 [DOI] [PubMed] [Google Scholar]
  • 23.Hirasawa Y, Kato Y, Fujita K. Transurethral Enucleation with Bipolar for Benign Prostatic Hyperplasia: 2-Year Outcomes and the Learning Curve of a Single Surgeon’s Experience of 603 Consecutive Patients. J Endourol. 2017;31(7):679–85. doi: 10.1089/end.2017.0092 [DOI] [PubMed] [Google Scholar]
  • 24.Boeri L, Capogrosso P, Ventimiglia E, Fontana M, Sampogna G, Zanetti SP, et al. Clinical Comparison of Holmium Laser Enucleation of the Prostate and Bipolar Transurethral Enucleation of the Prostate in Patients Under Either Anticoagulation or Antiplatelet Therapy. Eur Urol Focus. 2020. 15;6(4):720–8. doi: 10.1016/j.euf.2019.03.002 [DOI] [PubMed] [Google Scholar]
  • 25.Uchida T, Ohori M, Soh S, Sato T, Iwamura M, Ao T, et al. Factors influencing morbidity in patients undergoing transurethral resection of the prostate. Urology. 1999. Jan;53(1):98–105. doi: 10.1016/s0090-4295(98)00524-x [DOI] [PubMed] [Google Scholar]
  • 26.Chen S-S, Lin M-J, Weng M-F, Zhu L-F, Deng Z, Wu C-Y, et al. Influence of prostate size on the perioperative and postoperative outcome of transurethral plasmakinetic enucleation of the prostate: Results of 892 patients with 3 years of follow-up. The Kaohsiung Journal of Medical Sciences. 2018. Oct 1;34(10):576–82. doi: 10.1016/j.kjms.2018.03.001 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Bebi C, Turetti M, Lievore E, Ripa F, Bilato M, Rocchini L, et al. Sexual and ejaculatory function after holmium laser enucleation of the prostate and bipolar transurethral enucleation of the prostate: a single-center experience. Int J Impot Res. 2020. Oct 20. doi: 10.1038/s41443-020-00366-8 [DOI] [PubMed] [Google Scholar]
  • 28.Briganti A, Naspro R, Gallina A, Salonia A, Vavassori I, Hurle R, et al. Impact on Sexual Function of Holmium Laser Enucleation Versus Transurethral Resection of the Prostate: Results of a Prospective, 2-Center, Randomized Trial. The Journal of Urology. 2006. May 1;175(5):1817–21. doi: 10.1016/S0022-5347(05)00983-3 [DOI] [PubMed] [Google Scholar]
  • 29.Carmignani L, Bozzini G, Macchi A, Maruccia S, Picozzi S, Casellato S. Sexual outcome of patients undergoing thulium laser enucleation of the prostate for benign prostatic hyperplasia. Asian J Androl. 2015;17(5):802–6. doi: 10.4103/1008-682X.139255 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Capogrosso P, Ventimiglia E, Ferrari M, Serino A, Boeri L, Capitanio U, et al. Long-term sexual outcomes after holmium laser enucleation of the prostate: which patients could benefit the most? Int J Impot Res. 2016. Sep;28(5):189–93. doi: 10.1038/ijir.2016.29 [DOI] [PubMed] [Google Scholar]
  • 31.Jeong CW, Oh JK, Cho MC, Bae J-B, Oh S-J. Enucleation ratio efficacy might be a better predictor to assess learning curve of holmium laser enucleation of the prostate. Int braz j urol. 2012. Jun;38(3):362–72. doi: 10.1590/s1677-55382012000300009 [DOI] [PubMed] [Google Scholar]
  • 32.Kim M, Lee H-E, Oh S-J. Technical Aspects of Holmium Laser Enucleation of the Prostate for Benign Prostatic Hyperplasia. Korean J Urol. 2013. Sep;54(9):570–9. doi: 10.4111/kju.2013.54.9.570 [DOI] [PMC free article] [PubMed] [Google Scholar]

Decision Letter 0

Henry Woo

9 Apr 2021

PONE-D-21-05323

Bipolar Transurethral Enucleation of the Prostate: is it a size-independent endoscopic treatment option for symptomatic benign prostatic hyperplasia?

PLOS ONE

Dear Dr. Boeri,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by May 24 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Henry Woo

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2.  Please provide the full name of the institution that participants were recruited from."

3. Thank you for providing the date(s) when patient medical information was initially recorded. Please also include the date(s) on which your research team accessed the databases/records to obtain the retrospective data used in your study

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This study aimed to assess the relation between prostate size and surgical outcomes after Bipolar Transurethral Enucleation of the Prostate (B-TUEP). According to the conclusions of the authors, prostate volume was not associated with postoperative functional outcomes and complication rates. Thus, the current study may extend the current knowledge regarding the surgical outcomes of B-TUEP based on baseline prostatic volumes. However, there are still some major problems which need to be addressed.

1. In the Abstract, there is no description about comparison of efficacies of B-TUEP according to the baseline prostatic volumes. Please, add it in the Result section of the Abstract.

2. The introduction section of this manuscript needs to be clearer and more focused. Thus, the introduction section of this manuscript needs to be improved.

3. Also, the Discussion section needs to be further improved and summarized, focusing on the major findings of the study.

Reviewer #2: Bipolar Transurethral Enucleation of the Prostate: is it a size-independent endoscopic treatment option for symptomatic benign prostatic hyperplasia?

Abstract:

Retrospective study of 172 patients undergoing bipolar transurethral enucleation of the prostate (B-TUEP), aim of the study was to assess relationship between prostatic size and surgical outcomes following this technique.

Should change classification from quartiles to tertiles give that there’s only 3 groups (<60, 61-110, >110)

Outcomes of interest – efficiency (weight/time), complication rates, urinary/sexual function, LOS

Introduction:

I’d specify which laser energies (holmium, thulium etc) have been previously demonstrated as size-independent and I’d include Humpreys et al - Holmium Laser Enucleation of the Prostate—Outcomes Independent of Prostate Size? (2008) as another study for size independence.

Materials and Methods:

Small spelling error – ultrasonography and uroflowmetry (line 86)

Utilization of standardized metrics is helpful for cross study comparisons

Would specify which antibiotic was commonly used

Surgical Technique:

Intra-operative images or illustrations would be very helpful

I’d include a new header for postoperative care and data analysis to separate from the surgical technique section.

Again groups are better described as tertiles

Results:

Table 1 could be presented more cleanly if not across 2 pages (same for Table 2)

Discussion

Agree that part of the difficulty with small gland enucleation is probably represents a more challenging operation from an efficacy standpoint.

Clinical homogeneity of the patient population should be included as a potential weakness in the discussion.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Ryan Dobbs

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2021 Jun 9;16(6):e0253083. doi: 10.1371/journal.pone.0253083.r002

Author response to Decision Letter 0


10 Apr 2021

Dr Emily Chenette

Deputy Editor-in-Chief, PLOS ONE

Dr Henry Woo

Academic Editor

PLOS ONE

Milan, April 10th, 2021

Dear Dr Emily Chenette,

Dear Dr Henry Woo,

please find enclosed the revised version of the manuscript titled “Bipolar Transurethral Enucleation of the Prostate: is it a size-independent endoscopic treatment option for symptomatic benign prostatic hyperplasia?” (PONE-D-21-05323- Authors: Carolina Bebi, et al) to be considered for publication in PLOS ONE.

We are very grateful to the Reviewers for their insightful comments to our paper.

List of the changes made in the manuscript:

REVIEWER #1

COMMENT#1.

In the Abstract, there is no description about comparison of efficacies of B-TUEP according to the baseline prostatic volumes. Please, add it in the Result section of the Abstract.

A1. We thank the Reviewer#1 for this important comment. We have revised the Abstract accordingly.

COMMENT#2. The introduction section of this manuscript needs to be clearer and more focused. Thus, the introduction section of this manuscript needs to be improved

A2. We thank the Reviewer#1 for this comment. We have revised the Introduction section of the manuscript accordingly.

COMMENT#3. Also, the Discussion section needs to be further improved and summarized, focusing on the major findings of the study

A3. We thank the Reviewer#1 for this comment. We have revised the Discussion section of the manuscript accordingly.

REVIEWER #2

COMMENT#1.

Should change classification from quartiles to tertiles give that there’s only 3 groups (<60, 61-110, >110)

A1. We thank the Reviewer#2 for this important comment. We have revised the text accordingly.

COMMENT#2.

I’d specify which laser energies (holmium, thulium etc) have been previously demonstrated as size-independent and I’d include Humpreys et al - Holmium Laser Enucleation of the Prostate—Outcomes Independent of Prostate Size? (2008) as another study for size independence.

A2. We thank the Reviewer#2 for this important comment. The Introduction section of the manuscript has been revised accordingly.

COMMENT#3.

Small spelling error – ultrasonography and uroflowmetry (line 86)

Utilization of standardized metrics is helpful for cross study comparisons

Would specify which antibiotic was commonly used

A3. We thank the Reviewer#2 for this comment. We have revised the Methods section as suggested.

COMMENT#4.

Surgical Technique:

Intra-operative images or illustrations would be very helpful

A4. We thank the Reviewer#2 for this comment. We have included Figures 1 to 3 in the new version of the manuscript

COMMENT#5.

I’d include a new header for postoperative care and data analysis to separate from the surgical technique section.

Again groups are better described as tertiles

A5. We thank the Reviewer#2 for this comment. We have revised the Methods section as suggested.

COMMENT#6.

Table 1 could be presented more cleanly if not across 2 pages (same for Table 2)

A6. We thank the Reviewer#2 for this comment. We have revised the Results section as suggested.

COMMENT#7.

Agree that part of the difficulty with small gland enucleation is probably represents a more challenging operation from an efficacy standpoint.

Clinical homogeneity of the patient population should be included as a potential weakness in the discussion.

A7. We thank the Reviewer#2 for this comment. We have revised the Discussion section as suggested.

We hope that the paper is now suitable to be considered for publication in the Original Articles section of PLOS ONE.

Sincerely yours,

Luca Boeri on behalf of all the authors

Luca Boeri, M.D.,

IRCCS Foundation Ca’ Granda, Ospedale Maggiore Policlinico, Department of Urology

University of Milan

Via della Commenda 15, 20122 Milan, Italy

Tel. +39 02 55034501; Fax +39 02 50320584

Email: dr.lucaboeri@gmail.com

Decision Letter 1

Henry Woo

28 May 2021

Bipolar Transurethral Enucleation of the Prostate: is it a size-independent endoscopic treatment option for symptomatic benign prostatic hyperplasia?

PONE-D-21-05323R1

Dear Dr. Boeri,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Henry Woo

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Henry Woo

1 Jun 2021

PONE-D-21-05323R1

Bipolar Transurethral Enucleation of the Prostate: is it a size-independent endoscopic treatment option for symptomatic benign prostatic hyperplasia?

Dear Dr. Boeri:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Henry Woo

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

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

    (DOCX)

    Data Availability Statement

    All relevant data are within the paper.


    Articles from PLoS ONE are provided here courtesy of PLOS

    RESOURCES