Author's Accepted Manuscript Bipolar versus monopolar transurethral resection of the prostate: A prospective randomized trial focussing on bleeding complications P. Stucki , L. Marini , A. Mattei , K. Xafis , M. Boldini , H. Danuser

PII: DOI: Reference:

S0022-5347(14)04936-2 10.1016/j.juro.2014.08.137 JURO 12023

To appear in: The Journal of Urology Accepted Date: 27 August 2014 Please cite this article as: Stucki P, Marini L, Mattei A, Xafis K, Boldini M, Danuser H, Bipolar versus monopolar transurethral resection of the prostate: A prospective randomized trial focussing on bleeding complications, The Journal of Urology® (2014), doi: 10.1016/j.juro.2014.08.137. DISCLAIMER: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our subscribers we are providing this early version of the article. The paper will be copy edited and typeset, and proof will be reviewed before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to The Journal pertain.

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Klinik für Urologie, Luzerner Kantonsspital, Luzern, Switzerland

Bipolar versus monopolar transurethral resection of the prostate:

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A prospective randomized trial focussing on bleeding complications.

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Stucki P*, Marini L*, Mattei A, Xafis K, Boldini M, Danuser H

and the draft of the manuscript.

Word count (Abstract): 248

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* P. Stucki and L. Marini contributed equally to the realisation of the study

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Word count (Manuscript): 2230

Key Words: monopolar transurethral resection of the prostate, bipolar transurethral resection of the prostate, randomized study, outcome,

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bleeding complications

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Corresponding author: Patrick Stucki, MD

Klinik für Urologie, Luzerner Kantonsspital CH-6000 Luzern, Switzerland Tel. +41 41 205 45 12 / Fax. +41 41 205 45 31 Email: [email protected]

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Abstract

Purpose: To compare monopolar versus bipolar transurethral resection of the

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prostate (TURP) in patients with benign prostatic hyperplasia (BPH)

focussing on functional outcome, and rates of bleeding complications

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and TURP syndrome.

Material and Methods:

One-hundred and thirty-seven BPH patients (mean age 67 yrs, range 47-

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91 yrs) were prospectively randomly assigned to undergo monopolar TURP (M-TURP) (n=67) or bipolar TURP (B-TURP) (n=70). Patient characteristics of the 2 groups were similar. Haemoglobin (as a marker of blood loss) was measured pre- and perioperatively; the international prostate symptom score (IPSS), IPSS-quality of life (IPSS-QoL) score,

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maximal flow rate, and postvoid residual urine volume were assessed preoperatively, and 3 and 12 months postoperatively. Duration of surgery, indwelling catheter and hospitalisation were also documented, as were postoperative clot retention requiring removal by catheterization

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Results:

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or surgery, and rates of bladder neck and/or urethral strictures.

No significant perioperative differences were found in duration of surgery, catheterisation or hospitalisation, or in blood loss or blood transfusion and TURP-syndrome rates. Postoperatively there were no significant differences in IPSS or IPSS-QoL scores, or rates of rehospitalisation, clot retention, blood transfusions, reoperation or

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urethral strictures. Bladder neck strictures, however, occurred significantly more often in the bipolar group (8.5% vs 0%; p=0.02). Three and 12-month follow-ups showed significant and equal improvement in

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micturition in the 2 groups.

Conclusions:

Both B- and M-TURP are effective and safe techniques for surgical

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treatment of BPH. The only significant difference between them was a

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significantly higher rate of bladder neck strictures with B-TURP.

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Introduction

In aging men benign prostatic hyperplasia (BPH)-related lower urinary

quality of life and may lead to serious outcomes. (1)

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tract symptoms (LUTS) are common. They can impact daily activity and

According to the European Association for Urology guidelines,

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monopolar transurethral resection of the prostate (M-TURP) remains the treatment of choice for BPH-related moderate to severe LUTS in men with enlarged prostates (30-80 ml) refractory to medical therapy. Its high

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success rate is reflected in the reported substantial improvements in symptom scores, urinary flow rates, postvoid residual urine volume (PVR), and its low retreatment rate on long-term follow-up. (2-5) M-TURP, however, is still associated with a risk of haemorrhage particularly in patients with larger prostates, bleeding disorders, or who

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are undergoing anticoagulation therapy and TURP syndrome, a rare but potentially life threatening complication due to the resorption of nonconductive hypoosmolar irrigation fluid resulting in water toxicity and electrolyte abnormalities. (2-5)

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Since its introduction, bipolar TURP (B-TURP) has gained increasing popularity among urologists and is advocated by some to replace M-

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TURP as the treatment of choice. (6) With bipolar technologies, such as the Gyrus PlasmaKinetic SuperPulse System, the electric current completes the circuit without passing through the patient. This allows saline solution to be used for irrigation during resection instead of electrolyte-free solutions. Use of isotonic saline as irrigant effectively eliminates the risk of the dreaded TURP syndrome with severe hyponatraemia. A meta-analysis of 4

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all randomized controlled studies by Mamoulakis et al. disclosed not a single instance of TURP syndrome among all the B-TURP groups. (7) Recent laboratory investigations showed a lower bleeding rate and deeper coagulation capacity with the bipolar armamentarium. (8, 9) This

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could lead to lower blood loss and a reduced risk of clot retention in the clinical setting.

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In this prospective randomized trial we compare standard M-TURP with B-TURP using the Gyrus PlasmaKinetic system with regard to their

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TURP syndrome rates.

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clinical efficacy, safety profiles (focussing on bleeding complications) and

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Material and Methods

All consecutive BPH patients scheduled to undergo TURP were considered for this study. The indications for TURP included presence of

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LUTS and relevant reduction in IPSS-QoL and/or significant PVR >100 ml refractory to medical therapy with alpha-blockers and/or 5-alpha

reductase inhibitors. BPH patients with acute urinary retention and a

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failed trial of voiding after catheter removal were also eligible.

Exclusion criteria were neurogenic bladder, prostate cancer, previous

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prostatic or urethral surgery, and bleeding disorders.

The 137 patients (mean age 67 yrs, range 47-91 yrs) enrolled in the study were computer randomized at a 1:1 ratio to undergo either MTURP (n=67; mean age 66 yrs, range 49-91 yrs) or B-TURP (n=70;

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mean age 67 yrs, range 47-86 yrs). (Table 1)

Informed, written consent was obtained from all patients. The study was performed in accordance with the Declaration of Helsinki, and was

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approved by the local ethics committee (Submission File 12051).

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Before surgery, voiding symptoms were evaluated with the international prostate symptom score (IPSS), IPSS quality of life (IPSS-QoL) score, maximal uroflow (Qmax) and PVR. Baseline blood investigations included serum prostate-specific antigen (PSA), sodium (Na+), creatinine, and haemoglobin (Hb). (Table2)

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All endoscopic resections were performed by 3 experienced urologists and 7 urology residents in spinal or general anaesthesia at different points in their respective learning curves. The 7 urology residents were always under the supervision of a staff member.

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A standard Storz resectoscope (24 Fr) (Karl Storz Co., Tuttlingen, Germany) and an Erbe electrical current generator (ERBE

Elektromedizin GmbH, Tuebingen, Germany) were used for M-TURP

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and the Gyrus PK SuperPulse Generator (Olympus, Shinjuku, Japan) for the B-TURP. M-TURP was done with standard loops using 230 W cutting power and 60 W coagulation power with sorbitol / mannitol as

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irrigation fluid. Bipolar resection was performed using the bipolar "Super Loop" set at 160 W for cutting and 80 W for coagulation with saline 0.9% as irrigation fluid.

Both irrigating solutions contained 1% ethanol and intraoperative fluid

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absorption during both M-TURP and B-TURP was monitored every 10 minutes by concurrent measurement of expiratory alcohol levels using an Alcomed 3010 alcometer (Biotest Co., Frankfurt, Germany). The

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absorbed irrigation fluid was calculated using the Widmark formula. (10)

An expiratory alcohol concentration between 0.01‰ and 0.2 ‰ means a

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fluid absorption of 50ml to 1000 ml, an expiratory alcohol concentration between 0.2‰ and 0.4‰ means a fluid absorption of 1000ml to 2000 ml, and a fluid absorption >0.4‰ means a fluid absorption >2000 ml. An expiratory alcohol concentration >0.2‰ is the limit for us to stop TURP.

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At completion of the procedure, a 20F 3-way Foley’s catheter was inserted for continuous bladder irrigation. The catheter was removed from the first postoperative day onwards if the urine stayed clear 4 hours after stopping the irrigation. "Clear" means that a newspaper headline

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could be read through the drainage tube.

After surgery, patient serum Na+ and Hb were monitored at 6h and 24h.

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Any complications, such as TURP syndrome, clot retention, or need for recatheterization, were documented. The catheterization time and

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duration of hospitalization were also noted.

After discharge, patients were reassessed at 3 and 12-month follow-ups for complications and treatment efficacy as measured by IPSS, IPSSQoL, Qmax and PVR.

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The primary end point was the occurrence of bleeding complications (clot retention); secondary end points were resection time, weight of resected prostate tissue, blood transfusion, TURP syndrome and changes in preoperative and postoperative Hb

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levels, days of indwelling catheter placement and bladder irrigation, days of hospital stay, and improvement in IPSS and IPSS-QoL

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scores, Qmax, and PVR at 3 and12 months.

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Statistical analysis was performed using the two-tailed t-test and Fisher's exact test. Statistical significance was defined as p0.2‰) indicating a risk of TURP syndrome, the procedure was interrupted in 6/67 of the MTURP patients, and in 2/70 of the B-TURP patients (p= 0.15). However, clinical TURP syndrome occurred in only one M-TURP patient versus 0

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B-TURP patients (p=0.48). (Table 2) Among the patients whose procedure was stopped, additional procedures were required in 2/6 of the

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M-TURP group and in 2/2 of the B-TURP group. The instances of breath alcohol >0.2‰ may have been due to our residents’ relative lack of experience: 7 of the 8 procedures that had to be stopped were performed by residents.

Postoperative clot retention, blood transfusion, reoperation and urethral stricture rates did not differ between the 2 groups. There was no 10

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significant difference in rehospitalisation, and postoperative bleeding rates. However, bladder neck strictures occurred significantly more often in the bipolar group (0% vs. 9%; p = 0.02).

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Overall, 5/67 patients in the M-TURP group and 8/70 patients in the BTURP group required reoperation, 4/67 and 1/70 due to clot retention

(p=0. 2), 0/67 and 6/70 due to bladder neck stricture (p=0.02), and1/67

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and 1/70 due to urethral strictures (p=1). (Table 3)

The 3 and 12 month follow-up data are shown in Fig. 1. The preoperative

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to postoperative improvements in IPSS, flow rate (Qmax), and PVR (Fig 1) were highly significant (p < 0.001) in both groups at 3-month follow-up, with no significant differences between the 2 groups. These results

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remained stable at the 12-month follow-up.

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Discussion:

TURP is considered to be the reference surgical treatment for benign prostatic obstruction. (4) However, the morbidity of the procedure,

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notably TURP syndrome, bleeding and urethral stricture, remains

substantial at 11% based on a prospective, multicentre study of 10 654 men. (3) TURP syndrome affects 1.4% of patients undergoing TURP,

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requiring blood transfusion in 2.9% of these patients. (3) The urethral stricture rate is 2.2% to 9.8%, while 0.3% to 9.2% of patients may

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experience bladder neck stricture over the longer term. (17)

Laboratory studies (8, 9) and a meta-analysis of randomized controlled studies (7) suggest that B-TURP can reduce or eliminate TURP syndrome and bleeding complications in BPH patients undergoing TURP. Does B-TURP fulfil this promise? The principal advantage of

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bipolar technology is its use of isotonic irrigating fluid, which does eliminate the risk of the TURP syndrome (7). It does not, however, prevent fluid absorption, which can cause severe cardiopulmonary failure

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in cases of large volume uptake. (11)

In our series only one TURP syndrome occurred in the M-TURP group

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and none in the B-TURP too few to reach statistical significance; there were also 6 interruptions of surgery in the M-TURP group and 2 in the BTURP group due to an alcohol breath level >0.2% (p = 0.15). B-TURP should result in less bleeding because of the cut-and-seal effect of plasma created by bipolar energy. (12) Intraoperative monopolar coagulation zones were reported to be lower than bipolar ones, signifying that B-TURP might have better haemostatic efficacy. (9) In the present 12

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study, the decrease in Hb did not differ significantly between the 2 groups, and there was no significant difference in days of catheterization or hospitalisation, or in the rates of blood transfusions or clot retentions. Our data therefore do not show a substantial benefit from the bipolar

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resection technique with regard to bleeding complications. Our clot

retention and rehospitalisation rates, however, were higher than those of a meta-analysis (13) showing rates of 4.9% and 1%, respectively, for the

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monopolar technique and 4.3% and 0% for the bipolar technique. These higher rates may be attributable to the relative lack of experience of our

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residents, who accounted for 80% of clot retentions.

Blood transfusions were required in one patient in each group due to clot retention after hospital discharge. This finding is in agreement with the recent meta-analysis of Ahyai et al. (13) showing that the risk of blood transfusion is comparable for both techniques, suggesting a similar blood

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loss for M-TURP and B-TURP.

Our findings show no significant difference in operative time between the 2 procedures. The mean catheterization times in B-TURP patients

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versus the M-TURP patients did not differ significantly. Consequently, the average hospital stays were similar for the 2 groups and were

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consistent with a meta-analysis. (7) Recently, Ahyai, et al. (13) reported in their meta-analysis that the length of catheter time (mean: 2.7 d) after B-TURP was slightly shorter than after M-TURP; this finding however may depend on differences in the criteria for catheter removal.

TURP is associated with proven durability of improved micturition. Our present results show significant and equal improvements in terms of 13

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IPSS, IPSS-QoL, PVR, and Qmax for both M-TURP and B-TURP at both 3-month and 12-month follow-up.

These results agree with those of the first randomised controlled trial to

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compare B-TURP (Gyrus PlasmaKinetic system) with M-TURP (14): the trial involved 70 patients and showed a significant and equal

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improvement in functional outcome.

The two major late complications of M-TURP are bladder neck strictures (0.3-9.2%) and urethral strictures (2.2-9.8%). (15) It has been suggested

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that B-TURP is associated with a higher incidence of urethral strictures (16), which our finding of a urethral stricture in one patient in each group (3.6%) could not confirm. Our finding is consistent with that of other studies. (17, 18) Urethral strictures might not be specifically associated with bipolar technique. Bladder neck stricture occurred in 0 patients in

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out M-TURP group and in 6 patients in our B-TURP group (8.5%) (p=0.02), which is unexpectedly high compared with meta-analysis (13) showing a rate of 2% (range 0%-21%) with the monopolar technique and

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a rate of 0.5% (range 0%-4%) with the bipolar technique.

The incidence of bladder neck strictures varies from 0.3% to 9.2%, and

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they usually occur after smaller glands (