Influence of transurethral enucleation with bipolar of the prostate on erectile function: Prospective analysis of 51 patients at 12-month follow-up.

BACKGROUND: Transurethral enucleation with bipolar (TUEB) is a safe and effective surgery for benign prostatic obstruction (BPO). However, few data exist concerning the influence of TUEB on erectile function (EF) in patients with BPO.
OBJECTIVE: To evaluate the influence of TUEB on EF in patients with BPO at 3- and 12-month follow-up.
MATERIAL AND METHODS: We prospectively enrolled 51 patients who underwent TUEB from June 2016 to April 2020. We evaluated maximum urinary flow rate (Qmax), postvoid residual urine (PVR), International Prostate Symptom Score (IPSS), quality of life (QoL), and International Index of Erectile Function-5 (IIEF-5) preoperatively and at 3- and 12-month follow-up. We classified the patients according to their preoperative IIEF-5 score into group 1 (IIEF-5 ≥10; n = 24) and group 2 (IIEF-5 <10; n = 27), and for further evaluation of EF, into subgroups a: severe (IIEF-5 5-7), b: moderate (8-11), c: mild to moderate (12-16), d: mild (17-21), and e: no erectile dysfunction (22-25). Data are displayed as median or median (interquartile range).
RESULTS: The study comprised 51 patients with a median age of 75 (70.5-79.5) years. Median prostate and transition zone volumes were 69.5 (46.5-78.8) mL and 30.5 (19-43) mL, respectively. Urinary function improved significantly when comparing respective preoperative, 3-month, and 12-month follow-up values: Qmax (7.6, 12.9, 15.2 mL/s), PVR (50, 0, 0 mL), IPSS (20.5, 9, 6), and QoL (5, 2, 2), respectively. There was no significant change in IIEF-5 score across the three time points: 9, 7, 8. The IIEF-5 score slightly but significantly increased between the preoperative and 12-month follow-up values in group 2 (5, 5, 6) and subgroup a (5, 5, 5).
CONCLUSION: TUEB was effective and safe surgery for patients with BPO and showed no significant influence on EF at 12-month follow-up after TUEB in patients with BPO.

Introduction

Benign prostatic hyperplasia (BPH) is a histological diagnosis regarding the proliferation of glandular epithelial tissue, connective tissue, and smooth muscle in the prostate transition zone (TZ) [1]. This condition can progress through benign prostatic enlargement to benign prostatic obstruction (BPO) [2]. BPO is a subset of bladder outlet obstruction and is diagnosed when the cause of obstruction is thought to be benign prostatic enlargement [2]. Monopolar transurethral resection of the prostate (TURP) has been considered the gold standard surgical treatment for BPO [3]. In recent years, a variety of transurethral surgical treatments have been developed to achieve comparable surgical outcomes and to reduce complications. In addition to monopolar TURP, bipolar TURP, holmium laser enucleation of the prostate (HoLEP), and photoselective vaporization of the prostate (PVP) have become the main surgical procedures for patients with BPO [4-6]. Recently, transurethral enucleation with bipolar (TUEB) surgery has been developed, which is a transurethral bipolar enucleation method using a specially designed loop for enucleation and coagulation (TUEB loop) [7]. Although the benefits of TUEB have not been established against TURP, previous studies reported high efficacy and safety and a low perioperative morbidity rate with TUEB [7-11]. When surgery is considered for patients with BPO, erectile function (EF) is one of the considerable surgical factors [12]. There were several reports that TURP (monopolar or bipolar), HoLEP, and PVP had no significant influence on EF [13-15]. Although a majority of studies showed that transurethral surgery for BPO has no significant influence on EF, few data exist concerning the influence of TUEB on EF [12]. Therefore, we conducted a single-center, prospective study to evaluate the influence of TUEB on EF in 51 patients with BPO.

Material and methods

This prospective study investigated patients with BPO who underwent TUEB from June 2016 to April 2020. The Ethics Committee of our institution approved this study on 23 May 2016 (approval no. 290) and 29 October 2018 (approval no. 363). This study complied with the Declaration of Taipei on Ethical Considerations regarding Health Databases and Biobanks [16]. We obtained written informed consent from all patients who participated in this study. The authors ascertain the availability of all original data reported in this study.

Eligible patients were aged 20 years or older and required surgery for BPO. We consider TUEB to be the standard surgery in patients with BPO refractory to medical therapy (including urinary retention) in our institution. We excluded patients with severe urethral stricture requiring urethrotomy, previous prostate surgery, or a history of bladder cancer or prostate cancer. We prospectively enrolled 51 BPO patients who underwent TUEB from June 2016 to April 2020 and were followed up at 3 and 12 months postoperatively. We preoperatively performed a general clinical evaluation with digital rectal examination, urinalysis, maximum urinary flow rate (Qmax), postvoid residual urine (PVR), International Prostate Symptom Score (IPSS), quality of life (QoL) and International Index of Erectile Function-5 (IIEF-5) scores, serum prostate-specific antigen (PSA), transabdominal ultrasonography, cystoscopy, and pelvic magnetic resonance imaging (MRI). Only one patient who was unable to undergo MRI due to contraindications to MRI was excluded from the prostate volume analysis. We collected preoperative and postoperative data including operation time and length of time catheterized. At the 3- and 12-month follow-ups, we collected questionnaires (IPSS, QoL, and IIEF-5) and measured Qmax and PVR.

We measured prostate volume and TZ preoperatively with pelvic MRI. We performed transverse measurements in the axial plane, which shows the maximal diameter and allows best visualization of the surgical capsule and enlarged TZ boundaries for transverse measurement. We also performed sagittal length measurement in the sagittal plane, which shows the urethra most clearly [17]. We calculated the volume by using the maximal height and width in the axial plane, and the length of the prostate and TZ in the sagittal plane, applying the formula for a geometric model of an oblong ellipsoid [17].

TUEB was performed by two surgeons (Y.K. and H.A.) in our department with the patient under general anesthesia in a lithotomy position. We used a bipolar generator (Olympus SurgMaster UES-40), TUEB loop, standard wire loop, and 26 Fr resectoscope (all from Olympus, Tokyo, Japan). The TUEB loop comprised two parts, a front-end polytetrafluoroethylene loop designed for blunt enucleation (spatula) and a standard wire loop for coagulation. The generator for TUEB was set at 280 W for cutting and 100 W for coagulation. We used normal saline (0.9%) as irrigation fluid. After confirming the bilateral ureter orifice, bladder, verumontanum, and sphincter, we marked the resection borders at the proximal part of verumontanum from the 5 to 7 o’clock position to gain the enucleation plane. Then, we marked the resection borders circumferentially. We found the smooth plane with clear vessels between the adenoma and the capsule at 5 to 7 o’clock and enucleated the adenoma from the capsule with the TUEB loop. If bleeding occurred, we immediately coagulated it with the TUEB loop. If the middle lobe existed, we enucleated the adenoma from the capsule retrogradely toward the bladder neck. We sequentially enucleated the adenoma bilaterally and anteriorly. After performing subtotal enucleation of the adenoma and leaving a bridge of tissue at the bladder neck at the 6 o’clock position, we resected the adenoma layer by layer with a standard wire loop with little to no bleeding. After we resected the bridge of tissue and any residual adenoma, we evacuated the prostate tips with a bladder syringe and ensured complete hemostasis. We performed lithotripsy at the same time in the patients with bladder stones. At the end of surgery, we inserted a 22 Fr 3-way Foley catheter with continuous irrigation. We discontinued irritation on the morning after surgery. The catheter was removed 4 to 6 days after TUEB according to the study protocol. We checked hemoglobin before and the day after surgery. We noted all surgical complications until the 12-month follow-up and classified them according to the Clavien-Dindo classification system [18].

According to preoperative IIEF-5 scores, we classified the patients into group 1 (IIEF-5 ≥10, n = 24) and group 2 (IIEF-5 <10, n = 27). For the further evaluation of EF, we also classified the patients according to their preoperative IIEF-5 score into subgroups a: severe (IIEF-5 5–7, n = 23); b: moderate (IIEF-5 8–11, n = 13); c: mild to moderate (IIEF-5 12–16, n = 9); d: mild (IIEF-5 17–21, n = 5); and e: no erectile dysfunction (IIEF-5 22–25, n = 1) [19].

Data are reported as the median or median (interquartile range). We compared the categorical variables using Fisher’s exact test and calculated the differences between each group using the Mann-Whitney U test and Kruskal-Wallis test. We calculated the changes of the parameters in each group preoperatively and at the 3- and 12-month follow-ups using the Wilcoxon signed rank test. We assessed the factors that influence the IIEF-5 score using logistic regression. The data were analyzed as of 1 June 2021. All statistical analyses were performed using the open-source software EZR version 1.27 (Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface of R (The R Foundation for Statistical Computing, Vienna, Austria). P-values are two-sided, and a value of <0.05 was considered statistically significant.

Results

We registered 51 patients with BPO in the study and performed TUEB on all of them. Their characteristics are listed in Table 1. The median age was 75 (70.5–79.5) years, and that of group 1 was significantly younger than that of group 2 (72 vs 76 years). Median prostate volume and TZ volume were 69.5 (46.5–78.8) mL and 30.5 (19–43) mL, respectively, with no significant differences between the two groups. Nine (17.6%) patients on an alpha-blocker had urinary retention and could not void without catheterization when we performed TUEB. Twenty-four (47.1%) patients had hypertension, 12 (23.5%) had diabetes mellitus, and 10 (19.6%) had cardiovascular disease. The patients with cardiovascular disease were all in group 2.

Table 1

Patient characteristics.

	All men		Patients		Patients		p Value
	(n = 51)		with IIEF-5 ≥10		with IIEF-5 <10
			(Group 1; n = 24)		(Group 2; n = 27)
Age (y)	75	(70.5–79.5)	72	(68.5–75)	76	(72–80.5)	0.0357
PSA (ng/mL)	5.8	(2.6–10.1)	7.4	(3.9–10.6)	3.7	(2.0–7.6)	0.0713
Prostate volume (mL)
Total	69.5	(46.5–78.8)	70.5	(63.8–78)	53	(38.2–95.5)	0.356
Transition zone	30.5	(19–43)	31	(25.3–40)	27.5	(14.8–44.5)	0.443
Urinary retention before TUEB, n (%)	9	(17.6)	4	(16.7)	5	(18.5)	1
IPSS	20.5	(16.8–28)	18.5	(14.2–22)	24	(18.3–30)	0.0266
QoL	5	(4–6)	5	(4–6)	5	(4–6)	0.991
Qmax (mL/s)	7.6	(5.8–10.9)	6.9	(5.4–10.6)	8.4	(6.5–11.2)	0.174
PVR (mL)	50	(3–107.8)	53	(22.5–94.8)	42	(3–107.8)	0.98
IIEF-5	9	(5–12.5)	13.5	(10.8–15.5)	5	(5–6)	<0.001
Prostate morphology, n (%)
Bilateral lobes enlarged	42	(82.4)	18	(75)	24	(88.9)	0.276
Bilateral and middle lobes enlarged	9	(17.6)	6	(25)	3	(11.1)	0.276
Bladder stone, n (%)	3	(5.9)	2	(8.3)	1	(3.7)	0.595
Alpha-blocker therapy, n (%)	50	(98)	24	(100)	26	(96.2)	1
Alpha-reductase inhibitor therapy, n (%)	5	(9.8)	2	(8.3)	3	(11.1)	1
ASA score	2	(2–2)	2	(2–2)	2	(2–2)	0.215
Past history n (%)
Hypertension	24	(47.1)	8	(33.3)	16	(59.3)	0.093
Diabetes mellitus	12	(23.5)	4	(16.7)	8	(29.6)	0.335
Cardiovascular disease	10	(19.6)	0	(0)	10	(37)	<0.001

IIEF-5: International Index of Erectile Function-5, IQR: interquartile range, PSA: prostate-specific antigen, TUEB: transurethral enucleation with bipolar, IPSS: International Prostate Symptom Score, QoL: quality of life, Qmax: maximum urinary flow rate, PVR: postvoid residual urine.

Data are shown as the median (interquartile range).

The perioperative data of this study are listed in Table 2. TUEB surgery was completed successfully in all patients. There were no statistically significant differences in the perioperative data between groups 1 and 2. The complications (according to the Clavien-Dindo classification) associated with TUEB are shown in Table 3.

Table 2

Perioperative data.

	All men		Patients		Patients		p Value
	(n = 51)		with IIEF-5 ≥10		with IIEF-5 <10
			(n = 24)		(n = 27)
Operative time (min)	61	(50–90)	62.5	(52.3–84)	61	(46–90)	0.917
Resection weight (g)	29	(20–50)	34	(25.5–50.5)	26	(14.5–46)	0.253
Hemoglobin decrease (g/dL)	1	(0.4–1.65)	1.15	(0.5–1.8)	1	(0.3–1.4)	0.186
Indwelling catheter (days)	5	(4–6)	5	(4–6)	5	(4–6)	0.574

IIEF-5: International Index of Erectile Function-5.

Data are shown as the median (IQR).

Table 3

Complications (Clavien-Dindo classification).

			All men		Patients		Patients
			(n = 51)		with IIEF-5 ≥10		with IIEF-5 <10
Grade	Complication	Treatment			(n = 24)		(n = 27)
I	Capsular perforation	None	3	(5.9)	2	(8.3)	1	(3.7)
	Urinary retention	Recatheterization	4	(7.8)	2	(8.3)	2	(7.4)
	Hematuria	Prolonged bladder irrigation and hematoma evacuation	3	(5.9)	1	(4.2)	2	(7.4)
	Urinary incontinence
	Stress	Oral administration	1	(2)	1	(4.2)	0	(0)
	Urge	Oral administration	1	(2)	0	(0)	1	(3.7)
II	Urinary tract infection	Antibiotics	5	(9.8)	2	(8.3)	3	(11.1)
IIIa	Urethral stricture	Dilation (bougie)	3	(5.9)	0	(0)	3	(11.1)
IIb	Bladder neck sclerosis	Bladder neck incision	1	(2)	0	(0)	1	(3.7)

IIEF-5: International Index of Erectile Function-5.

Data are shown as n (%).

The follow-up data of this study are listed in Table 4. There was a significant improvement in urinary function in the comparison of preoperative, 3-, and 12-month follow-up data (median): Qmax (7.6, 12.9, 15.2 mL/s), PVR (50, 0, 0 mL), IPSS (20.5, 9, 6), and QoL (5, 2, 2). There were no significant differences in these parameters between groups 1 and 2 except for preoperative IPSS. PSA levels decreased from 5.8 (2.6–10.1) to 0.6 (0.4–1.3) ng/mL (89.2% decrease) at the 12-month follow-up. There was no significant change in the IIEF-5 scores in the comparison of preoperative, 3-, and 12-month follow-up data (median): (9, 7, 8). There was a slight but nonsignificant decrease in the IIEF-5 score in the comparison of preoperative, 3-, and 12-month follow-up in group 1 (13.5, 12.5, 13) and subgroup c (14, 13, 11). In contrast, there was a slight but significant increase in the IIEF-5 score in the comparison of preoperative and 12-month follow-up data in group 2 (5, 5, 6) and subgroup a (5, 5, 5). We also show in Fig 1 the proportion of patients who improved, remained unchanged, and worsened for each IIEF-5 score with reference to a previous study [20]. In group 1 and subgroup c, there were more patients with worsening IIEF-5 score than those with an improved score. Conversely, in group 2 and subgroup a, there were more patients with an improved IIEF-5 score than those with worsening score. We could not find a correlation between worsening of IIEF-5 scores (≥1 and ≥4) and urinary retention before TUEB, 5α reductase inhibitor therapy before TUEB, past history of hypertension, diabetes mellitus, cardiovascular disease, capsular perforation, operation time (≥61 or <61 minutes), and hemoglobin decrease (≥1.1 or <1.1 g/dL).

Table 4

Preoperative and follow-up data.

	Preoperative		Follow-up (3 mo)		Follow-up (12 mo)		p Value
	(n = 51)		(n = 51)		(n = 51)		vs 3 mo**	vs 12 mo**
Qmax (mL/s)*	7.6	(5.8–10.9)	12.9	(9.1–17.6)	15.2	(10.5–19.9)	<0.001	<0.001
Group 1	6.9	(5.4–10.6)	12.5	(10.1–21.35)	16.4	(12.7–22.4)	<0.001	<0.001
Group 2	8.4	(6.5–11.2)	13.3	(8.6–16.9)	14.8	(10.2–18.2)	0.0175	<0.001
p value (1 vs 2)	0.174		0.228		0.549
PVR (mL)*	50	(3–107.8)	0	(0–10)	0	(0–7)	<0.001	<0.001
Group 1	53	(22.5–94.8)	0	(0–5.5)	0	(0–1.5)	<0.001	<0.001
Group 2	42	(3–107.8)	0	(0–16)	4	(0–9)	<0.001	<0.001
p value (1 vs 2)	0.98		0.409		0.0967
IPSS	20.5	(16.8–28)	9	(6–13)	6	(4–11)	<0.001	<0.001
Group 1	18.5	(14.3–22)	8.5	(4.5–11.5)	6.5	(2–10.5)	<0.001	<0.001
Group 2	24	(18.3–30)	9	(7.5–15)	6	(5–11)	<0.001	<0.001
p value (1 vs 2)	0.0266		0.188		0.421
QoL	5	(4–6)	2	(1–3)	2	(1–3)	<0.001	<0.001
Group 1	5	(4–6)	2	(1–3.25)	2	(1–2)	<0.001	<0.001
Group 2	5	(4–6)	2	(1–3)	2	(1–3)	<0.001	<0.001
p value (1 vs 2)	0.991		0.454		0.121
PSA	5.8	(2.6–10.1)			0.6	(0.4–1.3)		<0.001
Group 1	7.4	(3.9–10.6)			0.6	(0.4–1.2)		<0.001
Group 2	3.7	(2–7.6)			0.6	(0.4–1.3)		<0.001
p value (1 vs 2)	0.0713				0.659
IIEF-5	9	(5–12.5)	7	(5–14)	8	(5–14)	0.647	0.956
Group 1 (n = 24)	13.5	(10.8–15.5)	12.5	(7–15.3)	13	(8.8–16)	0.0784	0.0851
Group 2 (n = 27)	5	(5–6)	5	(5–6.5)	6	(5–7.5)	0.105	0.0306
p value (1 vs 2)	<0.001		<0.001		<0.001
IIEF-5	9	(5–12.5)	7	(5–14)	8	(5–14)	0.647	0.956
Subgroup a (n = 23)	5	(5–5)	5	(5–6)	5	(5–7)	0.0534	0.0122
Subgroup b (n = 13)	10	(9–10)	9	(7–15)	10	(6–14)	0.723	1
Subgroup c (n = 9)	14	(13–15)	13	(10–14)	11	(8–14)	0.172	0.159
Subgroup d (n = 5)	18	(17–19)	16	(12–18)	18	(16–18)	0.104	0.134
Subgroup e (n = 1)	23	(23–23)	23	(23–23)	23	(23–23)	NaN	NaN
p value	<0.001		<0.001		<0.001

Group 1: Patients with IIEF-5 ≥10 (n = 24), Group 2: Patients with IIEF-5 <10 (n = 27), Subgroup a: Patients with IIEF-5 Severe (5–7) (n = 23), Subgroup b: Patients with IIEF-5 Moderate (8–11) (n = 13), Subgroup c: Patients with IIEF-5 Mild to moderate (12–16) (n = 9), Subgroup d: Patients with IIEF-5 Mild (17–21) (n = 5), Subgroup e: Patients with IIEF-5 No erectile dysfunction (22–25) (n = 1), NaN: not a number. Other abbreviations as in Table 1.

Data are shown as median (interquartile range).

* Expect patients with urinary retention before operation.

** Compared with preoperative data.

Fig 1

Outcomes according to IIEF-5 score at 3- and 12-month follow-up after TUEB in patients with BPO.

(a) Outcomes based on changes in the IIEF-5 score ≥1. (b) Outcomes based on changes in the IIEF-5 score ≥4. (c) Outcomes based on changes in the IIEF-5 score ≥1 in patients with an IIEF-5 score ≥10 (group 1, left side of chart) and IIEF-5 score <10 (group 2, right side of chart). (d) Outcomes based on changes in the IIEF-5 score ≥4 in patients with an IIEF-5 score ≥10 (group 1, left side of chart) and an IIEF-5 score <10 (group 2, right side of chart). (e) Outcomes based on changes in the IIEF-5 score ≥1 in patients with an IIEF-5 score 5–7 (subgroup a), IIEF-5 score 8–11 (subgroup b), IIEF-5 score 12–16 (subgroup c), IIEF-5 score 17–21 (subgroup d), and IIEF-5 score 22–25 (subgroup e). (f) Outcomes based on changes in the IIEF-5 score ≥4 in patients with IIEF-5 scores as defined in panel (e). BPO: benign prostatic obstruction, IIEF: International Index of Erectile Function, TUEB: transurethral enucleation with bipolar.

Discussion

HoLEP and thulium laser transurethral enucleation of the prostate (ThuLEP) are well-established enucleation procedures for patients with BPO [21]. However, in our experience, TUEB is relatively easy to learn and has almost equivalent safety and efficacy compared with laser enucleation surgeries such as HoLEP and ThuLEP [7, 21]. Because there are few data on how TUEB influences EF, unlike data on major transurethral surgery for BPO, we performed this prospective study to evaluate the influence of TUEB on EF.

In the present study, we found significant improvements of Qmax, PVR, IPSS, and QoL, and a decrease of PSA. Although Qmax at 12-month follow-up was slightly low, these results were almost comparable with previously reported results of transurethral enucleation surgeries such as HoLEP and ThuLEP (S1 Table) [22-28] and also almost equivalent with those of a prospective randomized trial between TUEB and TURP (S1 Table) [11]. One of the reasons for this slightly low Qmax might be that we did not exclude patients with neurogenic bladder, but we were unable to determine an exact reason because we did not perform pressure flow studies. Total rates of complications according to the Clavien-Dindo classification were 41.1% (23.5% [grade I], 9.8% [grade II], 5.9% [grade IIIa], and 2% [grade IIIb]) (Table 3). According to a recent review, complications in the transurethral enucleation surgeries showed the respective rates of stress and urge incontinence to be 0.7–28.6% and 0.6–48.1% and those of urethral stricture and bladder neck sclerosis to be 0.6–8.7% and 0.5–3.6% [29-31]. Although the rates of urethral stricture and bladder neck sclerosis might be relatively high (5.9% and 2%), we thought that the incidences of these complications were comparable with these previous studies [29-31].

We decided to assess EF with the IIEF-5 score because it is easy to use and understand compared with the original IIEF [19]. In addition, the IIEF-5 questionnaire has the advantage of being previously validated in Japanese, the language used by this study population. This study provided a prospective analysis of 51 patients who received TUEB and showed no significant influence on the IIEF-5 score in comparison with preoperative versus 3- and 12-month follow-up considering the entire population. In the groups, there was a slight but nonsignificant decrease in the IIEF-5 score in the comparison of preoperative, 3-, and 12-month follow-up data in group 1 and subgroup c. In contrast, there was a slight but significant increase in the IIEF-5 score in the comparison of preoperative and 12-month follow-up data in group 2 and subgroup a (Table 4).

Bruyere et al. reported that capsular perforation and a past history of cardiovascular disease were significant risk factors associated with EF after TURP [32]. In the present study, there were 3 (5.9%) capsular perforations, which was higher than that of the previous study [7]. Contrary to the previous study, the IIEF-5 scores in all of the present patients did not worsen in the comparison of preoperative, 3-, and 12-month follow-up data: (5, 6, 6), (11, 7, 14), and (10, 15, 16), respectively. Because the number of cases in the present study was small, it is difficult to evaluate the effect of capsular perforation on EF. Capsular perforation occurred in the first 30 cases, which likely reflected the learning curve, and it will decrease with experience. There was a significant difference in the past history of cardiovascular disease between group 1 (IIEF-5 ≥10; n = 0) and group 2 (IIEF-5<10; n = 10). However compared to a previous study, the results showed a slight but nonsignificant decrease in the IIEF-5 score in group 1 and a slight but significant increase in the IIEF-5 score in group 2 [32]. We assessed whether cardiovascular disease influenced the IIEF-5 score, but it was not a significant factor worsening the IIEF-5 score in the present study. Unfortunately, we did not evaluate the severity of cardiovascular disease before TUEB in the present study.

Although the effect of the mechanism of transurethral surgery on EF is controversial, Akman et al. proposed that direct thermal injury to the erectile nerves leads to the worsening of EF [33]. Previous studies reported that the depth of coagulation was 0.14 mm with a wire loop for TURP, and the depths of penetration (i.e., the coagulation zone) were 0.4 mm with the holmium YAG laser used for HoLEP and 0.8 mm with the 532-nm (i.e., greenlight) laser used for PVP [20, 34, 35]. Considering the depth of coagulation, the coagulation effect of TUEB on EF might be similar to that of HoLEP. In recent years, several reports have been published regarding transurethral bipolar enucleation with a button electrode using it to coagulate bleeding vessels during the enucleation of prostate lobes [34, 36, 37]. However, the depth of coagulation was 2.4 mm with the button electrode for this surgery [20]. Although these reports mentioned that this surgery had no significant effect on EF, the coagulation effect of TUEB on EF might be smaller compared with this surgery because the depth of coagulation was considered to be shallow.

Akman et al. also proposed that thermal injury might have more impact at the apex than at the base [33]. They mentioned that the depth of erectile nerves was 1.5 mm at the apex and 3 mm at the base [33]. We could not evaluate the thermal effect on the procedure at the apex because we did not record the energy used such as that of laser energy. However, the basic procedure for HoLEP and TUEB is enucleation, which mechanically removes prostate adenoma between the adenoma and the capsule [7, 38]. These processes might result in a lower effect of thermal damage on EF compared with resection (TURP) or vaporization (PVP) [20].

The present study showed a slight but significant increase in the IIEF-5 score between preoperative and 12-month follow-up values in group 2 and subgroup a. A randomized controlled study comparing the influences of sexual function after HoLEP and TURP reported nonsignificant improvement in EF [38]. Several studies in which preoperative oral therapy including alpha-blocker or 5 alpha-reductase inhibitor was discontinued showed a slight contribution to the improvement of EF [11, 39]. However, we found no significant relationship between the change in IIEF-5 score and discontinuance of 5 alpha-reductase inhibitor following TUEB in the present study. Li et al. noted that the benefit of relief from BPO could counteract the negative effect of surgery on EF, leading to unchanged EF postoperatively [14]. Further studies are needed to investigate the effects of the discontinuance of preoperative oral therapy and surgery on EF.

Soans et al. found that patients with good preoperative EF may have worsened EF, and patients with severe preoperative EF may have improved EF [12]. The present study showed no significant influences on EF considering the overall population. In the groups, however, there was a slight but nonsignificant worsening of EF in group 1 and subgroup c and a slight but significant improvement in EF in group 2 and subgroup a. The nonsignificant worsening of EF in subgroup c might be derived from not only the surgery itself but also aging or comorbidities, but we could not speculate as to the exact reason because the number or patients was small. We infer that the influence of TUEB on EF is minor in subgroups d and e, but again, the number of patients was too small. When patients with BPO are counseled prior to surgery, these findings might be an important factor.

This study has some limitations. Our sample size was rather small, and we could not find significant factors for a worsening IIEF-5 after TUEB. Second, an indwelling catheter was used for a relatively long time. We kept the urethral catheter in place for a longer period than usual to rest the bladder after TUEB to avoid temporary urinary retention or hemorrhage [7]. As well, a previous study reported that in a case series, TUEB required a shorter catheterization time (44.9 hours) [10]. Third, we could not compare this study cohort with randomized studies of other surgery such as monopolar or bipolar TURP. Fourth, most of the patients in this study had severe to moderate erectile dysfunction, and it was difficult for us to assess the influence on patients with mild to no erectile dysfunction. Indeed, because we have to consider the possibility of worsening of EF in subgroup c, we infer that the influence of TUEB on EF is minor in subgroups d and e. Fifth, the follow-up period of this study was only 12 months after TUEB. However, a previous study mentioned that changes in EF more than one year after surgery were derived from aging and comorbidities rather than the surgery itself [40]. Sixth, this study was a single-center non-randomized study. However, we think TUEB is an almost equally effective and safe surgery compared to transurethral laser enucleation surgeries such as HoLEP and ThuLEP [21]. Finally, this study includes relatively smaller-sized prostates, even though the great advantage of enucleation surgery is achieved in large prostates of over 100 mL [5]. A prospective multicenter study will be appropriate to assess the influence of other forms of transurethral surgery and TUEB on EF in patients with BPO.

Conclusion

TUEB was effective and safe surgery for patients with BPO. The present study showed no significant influence of TUEB on EF in patients with BPO.

Prospective randomized trials of enucleation surgery of the prostate.

(XLSX)

Click here for additional data file.

Supporting information data set.

(XLSX)

Click here for additional data file.

22 Mar 2022

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Reviewer #1: I read the manuscript entitled:" Influence of transurethral enucleation with bipolar of the prostate on erectile function: Prospective analysis of 51 patients at 12-month follow-up"

All parts were written well but there is a concern about selection bias. All patients had erectile dysfunction before surgery (moderate as a whole or mild to moderate in group a and even severe in group b).

It is probable if the authors select patients with good erectile function maybe they could find any effect on erectile function.

Reviewer #2: The authors must be congratulated for their intent to evaluate the influence of TUEB on EF in patients with BPO.

However, the study shows all the results of a prospective database. Therefore, either the objective must be changed, or the results have to be adjusted, focusing in the proposed objective.

That being said, I would recommend to devide the patients according to the previously described ED classification based on the IIEF-5 score: severe (5-7), moderate (8-11), mild to moderate (12-16), mild (17-21), and no ED (22-25).

Reviewer #3: 1. Are you comparing your data to HoLEP and enucleation techniques or all prostate reducing procedures?

2. Advantages of using Bipolar enucleation versus well established enucleation techniques such as HoLEP and ThuLEP?

3. The data needs to be evaluated against TURP and thus a randomized prospective trial between the two would be necessary since the size of the gland appears to be in TURP category.

4. Many limitations to your study including one institution, size limitation, no comparison to other modalities, and too many patients with ED before the surgery.

5. Bipolar enucleation has not been established against TURP or other enucleation procedure.

6. Long catheterizations post op is concerning. By the way, in the discussion, ureteral catheterization should be changed to urethral catheterization.

7. The big advantage of enucleation techniques are for large glands usually over 100 grams, all the prostates in this study were less. What was the impetus for bipolar enucleation in this study?

8 I would suggest a re-write and compare your data only to enucleation procedures from a previously published randomized prospective trial. The flow the paper should be better and more concise. Your goal appears to suggest Bipolar enucleation can be performed with minimal effects on ED and with good outlet outcomes.

**********

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Reviewer #1: Yes: Farzad Allameh

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5 May 2022

Replies to the Editor and Reviewers

Dear Dr. Kobayashi,

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.

ACADEMIC EDITOR:

I hope you can adapt your manuscript as the reviewers requested. My advice is also to write your conclusin in a more modest way.

1→Thank you very much for your suggestion. I changed the sentence to make it easier to understand. We revised the text to reflect this change (Conclusion section, page 29, line 398).

Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming.

2→Thank you very much for your advice.

I change the file name as follows:

Fig. 1→Fig1

We combined 6 figures into 1 figure in Fig. 2 and added panels e and f to panels a-d.

Although not pointed out, is it possible to make the following corrections?

3→We deleted the abbreviation “n.s.: not significant” in Table 2 and now show the actual p values.

Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files

4→Thank you very much for your advice.

I upload our study’s minimal underlying data set as a Supporting Information file (file name: S2_Table).

Your ethics statement should only appear in the Methods section of your manuscript.

5→Thank you very much for your advice.

I deleted the “Ethics approval and consent to participate” section.

Reviewer #1: I read the manuscript entitled:" Influence of transurethral enucleation with bipolar of the prostate on erectile function: Prospective analysis of 51 patients at 12-month follow-up" All parts were written well but there is a concern about selection bias. All patients had erectile dysfunction before surgery (moderate as a whole or mild to moderate in group a and even severe in group b). It is probable if the authors select patients with good erectile function maybe they could find any effect on erectile function.

6→Thank you very much for your comments and suggestion. We classified the patients according to their preoperative IIEF-5 score into subgroup a: severe (IIEF-5 5-7, n=23), subgroup b: moderate (IIEF-5 8-11, n=13), subgroup c: mild to moderate (IIEF-5 12-16, n=9), subgroup d: mild (IIEF-5 17-21, n=5), and subgroup e: no ED (IIEF-5 22-25, n=1). There was a slight but nonsignificant decrease in the IIEF-5 score in the comparison of preoperative, 3-, and 12-month follow-up data in subgroup c (14, 13, 11) but no remarkable changes in subgroups d (18, 16, 18) and e (23, 23, 23). Although we cannot say for sure because of the small number of patients, we have to consider the possibility of worsening of EF in subgroup c but we infer that the influence of TUEB on EF is minor in subgroups d and e. We revised the text to reflect these results (Abstract section, page 2, line 31; Material and methods section, page 9, lines 146, 152; Results section, page 15, line 203/page 16, lines 209, 225; and Discussion section, page 23, line 292/page 27, lines 356, 358/page 28, line 376) and revised Fig 2 and Table 4.

Reviewer #2: The authors must be congratulated for their intent to evaluate the influence of TUEB on EF in patients with BPO. However, the study shows all the results of a prospective database. Therefore, either the objective must be changed, or the results have to be adjusted, focusing in the proposed objective. That being said, I would recommend to devide the patients according to the previously described ED classification based on the IIEF-5 score: severe (5-7), moderate (8-11), mild to moderate (12-16), mild (17-21), and no ED (22-25).

7→Thank you very much for your suggestion. We classified the patients according to your valuable advice as follows: subgroup a: severe (IIEF-5 5-7, n=23), subgroup b: moderate (IIEF-5 8-11, n=13), subgroup c: mild to moderate (IIEF-5 12-16, n=9), subgroup d: mild (IIEF-5 17-21, n=5), and subgroup e: no ED (IIEF-5 22-25, n=1). There was a slight but significant increase in the IIEF-5 score in the comparison of preoperative and 12-month follow-up data in subgroup a. There was a slight but nonsignificant decrease in the IIEF-5 score in the comparison of preoperative, 3-, and 12-month follow-up data in subgroup c (14, 13, 11) but no remarkable changes in subgroups d (18, 16, 18) and e (23, 23, 23). Although we cannot say for sure because of the small number of patients, we have to consider the possibility of worsening of EF in subgroup c but we infer that the influence of TUEB on EF is minor in subgroups d and e. We revised the text to reflect these results (Abstract section, page 2, line 31/page 3, line 45; Material and methods section, page 9, lines 146, 152; Results section, page 15, lines 203, 206/page 16, lines 209, 210; and Discussion section, page 23, lines 292, 294/page 26, line 341/page 27, lines 356, 357, 358/page 28, line 376) and revised Fig 2 and Table 4.

Reviewer #3: 1. Are you comparing your data to HoLEP and enucleation techniques or all prostate reducing procedures?

8→Thank you very much for your question. We compared our data with previously reported results of transurethral enucleation surgery such as HoLEP and ThuLEP. Although Qmax at 12-month follow-up was slightly low and the rate of urinary tract infection was relatively high, we think our data were almost comparable with those of previous studies. We revised the text to reflect these results (Discussion section, page 21, lines 252, 258/page 22, lines 264, 268, 269) and added Supplementary Table 1.

2. Advantages of using Bipolar enucleation versus well established enucleation techniques such as HoLEP and ThuLEP?

9→Thank you very much for your question. We think TUEB is relatively easy to learn, and we are able to control intraoperative bleeding with ease. We also think that we can precisely enucleate the adenoma from the capsule, which might reduce injury to the sphincter. We revised the text to reflect your suggestion (Discussion section, page 20, line 241).

3. The data needs to be evaluated against TURP and thus a randomized prospective trial between the two would be necessary since the size of the gland appears to be in TURP category.

10→Thank you very much for your suggestion. We compared our data with a prospective study between TUEB and TURP. Although Qmax at 12-month follow-up was slightly low, we think our data were almost comparable with those of this study. We revised the text to reflect this result (Discussion section, page 21, lines 255, 258) and added Supplementary Table 1.

4. Many limitations to your study including one institution, size limitation, no comparison to other modalities, and too many patients with ED before the surgery.

11→Thank you very much for your comment. We revised the limitations to reflect your suggestion (Discussion section, page 28, lines 376, 381, 384).

5. Bipolar enucleation has not been established against TURP or other enucleation procedure.

12→Thank you very much for your comment. We revised the text to reflect your suggestion (Introduction section, page 4, line 65).

6. Long catheterizations post op is concerning.

13→Thank you very much for your comment. We think that we might be able to remove the catheter earlier. A previous study reported that TUEB required a shorter catheterization time. We revised the text to reflect your suggestion (Discussion section, page 27, line 368).

By the way, in the discussion, ureteral catheterization should be changed to urethral catheterization.

14→Thank you very much for pointing out our mistake. We corrected this error (Discussion section, page 28. line 370).

7. The big advantage of enucleation techniques are for large glands usually over 100 grams, all the prostates in this study were less. What was the impetus for bipolar enucleation in this study?

15→Thank you very much for your comment and question. This study included 10 patients with prostate size over 100 mL, and we were able to perform surgery without any problems using the same procedure. We revised the text to reflect your suggestion (Discussion section, page 28, line 384).

8 I would suggest a re-write and compare your data only to enucleation procedures from a previously published randomized prospective trial. The flow the paper should be better and more concise. Your goal appears to suggest Bipolar enucleation can be performed with minimal effects on ED and with good outlet outcomes.

16→Thank you very much for your comment. As mentioned, we compared our data with a randomized prospective trial of transurethral enucleation surgery. Although Qmax at 12-month follow-up was slightly low and the rate of urinary tract infection was relatively high, we think our data were almost comparable with these studies. We might be able to suggest that TUEB can be performed with minimal effects on ED and with good outlet outcomes. We revised the text to reflect this result (Discussion section, page 21, lines 252/258; page 22, lines 264/268, 269) and added Supplementary Table 1.

Word limit in the Abstract section

17→Dear editor,

I revised the Abstract section according to the comments of Reviewers #1 and #2. As a result, the word count now exceeds 300 words (304 words). I hope this will not be a problem.

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool

→Thank you very much for your advice. I checked the figure files with PACE.

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

9 Jun 2022

26 Jun 2022

Replies to the Editor and Reviewers

Dear Dr. Kobayashi,

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.

ACADEMIC EDITOR:

Can you revise again, with help of the reviewers comments?

→We are grateful for this additional opportunity to revise our paper. We thank you and the reviewers for the time and effort spent providing fine feedback to strengthen our paper. We have revised and submitted our updated manuscript.

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

→Thank you very much for your suggestion. We have checked all articles cited in the references, and none show any indication that they have been retracted.

Reviewers' comments:

Reviewer's Responses to Questions

Reviewer #2: Thanks for addressing all the raised questions.

Some minor issues:

Abstract:

Material and methods:

The groups identification is quite complex. There is initially a GROUP A and GROUP B. Then, there are subgroups a, b, c, d and e. This leads to misunderstandings and is hard to interpretate. Maybe you could use groups 1 and 2 and subgroups a to e.

1→Thank you very much for your valuable advice, which has made the results easier to understand. We revised the two main group names to Group 1 and Group 2 throughout the manuscript and in Tables 1 and 4.

I could not understand the following sentence: “Data are displayed as median or median (interquartile range) or (preoperative, at 3-month follow-up, at 12-month follow-up).”. In the abstract and in the method section.

2→Thank you very much for your advice. We deleted the confusing second half of the sentence to make it easier to understand. We revised the text to reflect this change in the Abstract, page 2, line 33, and the Material and Methods section, page 9, line 149.

Methods

Line 142: Please describe the groups in a new paragraph

3→Thank you very much for your suggestion. We revised the text to reflect your suggestion (Material and Methods section, page 8, line 143).

Line 138: statistical analysis description should be the last paragraph of the methods section.

4→Thank you very much for your suggestion. All text related to statistical analysis is included in the last paragraph of the Material and Methods section (page 9, lines 149-161).

Results/ Objectives:

Once again, I believe the results and discussion deal with a lot of things that are not mentioned in the objective of the study!

The aim of the study was: “Therefore, we conducted a single-center, prospective study to evaluate the influence of TUEB on EF in 51 patients with BPO.”

The following topics have nothing to do with the aim of the study, unless you evaluate if theses complications could interfere with the post-operative erectile function.

Line 172: correlation between TZ volume and resection weight

5→Thank you very much for your advice, which has improved the flow of this paper and made it more concise. We deleted the sentence you pointed out and another related sentence (Material and Methods section, page 9, line 152 and Results section, page 13, line 179).

Line 175: patients with transient urinary retention after catheter removal, urinary retention resolved spontaneously without oral administration of medication

6→We deleted the sentence you pointed out (Results section, page 13, line 181).

Line: 177: patients with hematuria

7→We deleted the sentence you pointed out (Results section, page 13, line 183).

Line 179: urethral structure and bladder neck sclerosis

8→We deleted the sentence you pointed out (Results section, page 13, line 185).

Table 3 is enough to show the complications due to the procedure.

Figure 1 is not necessary.

9→Thank you. We deleted Figure 1. Previous Figure 2 is now Figure 1.

Discussion:

Regarding complications, instead of citing 7 studies, I would cite

1) for incontinence (line 254):

- Castellani D, Rubilotta E, Fabiani A, Maggi M, Wroclawski M, Teoh JYC, Pirola GM, Gubbioti M, Pavia MP, Gomez Sancha F, Galosi AB, Gauhar V. Correlation between transurethral interventions and their influence on type and duration of postoperative urinary incontinence: results from a systematic review and meta-analysis of comparative studies. J Endourol. 2022 May 19. doi: 10.1089/end.2022.0222.

10→Thank you for alerting us to these three very useful papers. We revised the text to reflect your suggestions (Discussion section, page 22, line 279).

2) For urethral stricture (line 255):

- Pirola GM, Castellani D, Lim EJ, Wroclawski ML, Le Quy Nguyen D, Gubbiotti M, Rubilotta E, Chan VW, Corrales M, Rojo EG, Herrmann TRW, Teoh JY, Gauhar V. Urethral stricture following endoscopic prostate surgery: a systematic review and meta-analysis of prospective, randomized trials. World J Urol. 2022 Feb 13. doi: 10.1007/s00345-022-03946-z.

11→We revised the text to reflect your suggestion (Discussion section, page 22, line 281).

3) For bladder neck sclerosis (line 255):

- Castellani D, Wroclawski ML, Pirola GM, Gauhar V, Rubilotta E, Chan VW, Cheng BK, Gubbiotti M, Galosi AB, Herrmann TRW, Teoh JY. Bladder neck stenosis after transurethral prostate surgery: a systematic review and meta-analysis. World J Urol. 2021 Nov;39(11):4073-4083. doi: 10.1007/s00345-021-03718-1.

12→We revised the text to reflect your suggestion (Discussion section, page 23, line 282).

Lines 259 – 268 (TZ volume and MRI) does not correlate to the topic of the study. In my opinion, it should be deleted.

13→We deleted the related sentences you pointed out (Discussion section, page 23, lines 286-295).

Line 365: Regarding the safety and efficacy of TUEB, I would cite the metanalysis that compared laser versus non-laser enucleation procedures and did not find any significant differences between the techniques (Wroclawski ML, Teles SB, Amaral BS, Kayano PP, Cha JD, Carneiro A, Alfer W Jr, Monteiro J Jr, Gil AO, Lemos GC. A systematic review and meta-analysis of the safety and efficacy of endoscopic enucleation and non-enucleation procedures for benign prostatic enlargement. World J Urol. 2020 Jul;38(7):1663-1684. doi: 10.1007/s00345-019-02968-4.)

14→Thank you for telling us about this very useful paper. We revised the text to reflect your suggestion (Discussion section, page 29, lines 394-396).

Line 375: Enucleation is a procedure indicated for prostates of any size according to the AUA guidelines and for prostates over 30g according to the EAU guidelines. So, no need to justify your approach.

15→Thank you very much for your advice. We deleted the sentences to reflect your suggestion (Discussion section, page 29, lines 398-400).

Reviewer #3: This is one section that should be revised.

"HoLEP is a well-established enucleation surgery in patients with BOO

233 [5]. However, HoLEP requires much experience and appropriate endoscopic

234 skills to avoid complications [21], whereas TUEB is relatively easy to learn

235 [7]. We can coagulate any bleeding immediately during adenoma enucleation

236 because the TUEB loop is equipped with a standard wire loop. In addition, we

237 can precisely enucleate the adenoma from the capsule with the TUEB loop,

238 which might reduce injury to the sphincter at the apex [11]."

This section should be re-written. This is truly an opinion from the surgeons doing bipolar enucleations. Learning curve has been defined with other procedures over longer time period at different institutions. Reproducibility is an important part of learning curve and multi-institutional trials need to be done to appropriately comment on this.

Phrasing should be not so presumptive. Accuracy with Holmium and Thulium of bleeders are also easily accomplished with experience. I realize your enthusiasm of this technique, however, you need to tone it down throughout the discussion and introduction. Maybe try the phrase, "In our experience,..." to phrase some the presumptive statements. In addition, please focus on erectile function as the title would suggest.

16→Thank you very much for your advice. We used the phrase "In our experience" to focus on the ease of learning TUEB and reduced any presumptiveness on our part. We also focused on erectile function in this paragraph (Discussion section, page 21, lines 251-259).

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

25 Jul 2022

Influence of transurethral enucleation with bipolar of the prostate on erectile function: Prospective analysis of 51 patients at 12-month follow-up

PONE-D-21-39626R2

Dear Dr. Kobayashi,

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.

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Academic Editor

PLOS ONE

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Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

2. 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 #2: Yes

Reviewer #3: Yes

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

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #2: No

Reviewer #3: No

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2 Aug 2022

PONE-D-21-39626R2

Influence of transurethral enucleation with bipolar of the prostate on erectile function: Prospective analysis of 51 patients at 12-month follow-up

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