Urethroplasty for Failed Hypospadias Repair Related Strictures in Adults: A Retrospective Analysis With Long-term Follow-up.

OBJECTIVE: To report long-term surgical outcomes after urethroplasty for failed hypospadias repair (FHR) related strictures in adults. MATERIALS AND METHODS: A database of all adult (≥18 years) men who underwent urethroplasty since 2000 at Ghent University Hospital was created (prospective data since 2008). Patients with a follow-up <1 year or non-FHR related strictures were excluded. Postoperative complications were categorized according to Clavien-Dindo (<90 days), high-grade being ≥ grade 3. Failure was defined as stricture recurrence at the site of reconstruction requiring additional urethral manipulation. For penile strictures, outcomes were stratified per surgical technique. RESULTS: In total, 85 patients were included with a median (IQR) follow-up of 89 (57-165) months. Respectively 76, 6 and 3 patients had a penile, bulbar and penobulbar stricture. Postoperative complication rate was 27%. High-grade complications were seen in 7 of 85 (8.2%) patients and in 4 of 85 (4.7%) patients this involved fistula formation. Failure occurred in 29 of 85 (34%) patients, corresponding with a failure-free survival estimate (SD) of 82% (4.1), 73% (5.0) and 57% (6.7) after respectively 1, 5 and 10 years. For penile strictures, anastomotic repair had the highest failure rate (5/7, 71%) and a first stage Johanson procedure only had the lowest failure rate (1/10, 10%), followed by definitive perineal urethrostomy (1/4, 25%), pedicled flap urethroplasty (2/8, 25%) and free graft urethroplasty (7/23, 30%). CONCLUSION: FHR related strictures are predominantly seen in the penile urethra. Failure rate after urethroplasty for FHR related strictures increases steadily over time suggesting prolonged follow-up in these patients. For penile FHR related strictures, anastomotic repair should be discouraged.

Perineal Urethrostomy for Complicated Anterior Urethral Strictures: Indications and Patient's Choice. An Analysis at a Single Institution.

OBJECTIVES: To explore indications for a definitive perineal urethrostomy (PU). To objectify the proportion of patients not completing the final stage procedure in an intended multi-stage urethroplasty. To analyze the incentives for both of these scenarios. MATERIALS AND METHODS: Since 2000, data of all men undergoing urethroplasty at our center have been collected in a database. This study included patients with a definitive PU and patients after ≥1 stages of an intended multi-stage urethroplasty. Patients <18 years or with a follow-up <3 m were excluded. Descriptive statistics were used and groups were compared with nonparametric statistical tests. RESULTS: Among 1015 urethroplasties, 34 patients underwent a definitive PU and 63 underwent ≥1 stages of an intended multi-stage urethroplasty with a median (IQR) follow-up of respectively 57 (31-120) and 32 (14-101) months. In the definitive PU group, patients were significantly older (P < .001) and had more cardiovascular comorbidity (P = .01), panurethral stricture disease (P = .02) and longer strictures (P = .02) than patients in the multi-stage urethroplasty group. Half of the definitive PUs were surgeon driven and 33% were patient driven. Final stage procedures were completed by 35/63 (56%) patients. Patients not completing the final stage were significantly older (P = .001). CONCLUSION: Definitive PU is particularly performed in older patients with worse cardiovascular condition, panurethral stricture disease and longer strictures. PU is often explicitly chosen by well informed patients and as nearly half of the patients refuse closure of the urethrostomy after the first stage, a definitive PU should be proposed as reasonable alternative to complicated urethral reconstruction from the start, especially in older patients.

Primary versus Redo Urethroplasty: Results from a Single-Center Comparative Analysis.

OBJECTIVES: To explore the differences between primary and redo urethroplasty and to directly compare according stricture-free survival (SFS). Materials and Methods. Data of all male patients who underwent urethroplasty at Ghent University Hospital were collected between 2000 and 2018. Exclusion criteria for this analysis were age <18 years and follow-up <1 year. Two patient groups were created for further comparison: the primary urethroplasty (PU) group (no previous urethroplasty) and redo urethroplasty (RU) group (≥1 previous urethroplasty), irrespective of prior endoscopic treatments. A comparison between groups was performed using the Mann-Whitney U test and Fisher's Exact test. SFS was calculated using Kaplan-Meier statistics. A functional definition of failure, being the need for further urethral manipulation, was used. Uni- and multivariate Cox regression analyses were performed on the entire patient cohort. RESULTS: 805 patients were included. Median (IQR) follow-up of the PU (n = 556) and RU (n = 556) and RU (p=0.1). The RU group involved more penile strictures (p=0.1). The RU group involved more penile strictures (p=0.1). The RU group involved more penile strictures (p=0.1). The RU group involved more penile strictures (p=0.1). The RU group involved more penile strictures (p=0.1). The RU group involved more penile strictures (p=0.1). The RU group involved more penile strictures (p=0.1). The RU group involved more penile strictures (p=0.1). The RU group involved more penile strictures (. CONCLUSIONS: Several differences between primary and redo urethroplasties exist. Redo urethroplasty entails a distinct patient population to treat and is, in general, associated with lower stricture-free survival than primary urethroplasty, although more homogeneous series are required to corroborate these results. Prior urethroplasty and diabetes are independent risk factors for urethroplasty failure.

Independent risk factors for failure after anterior urethroplasty: a multivariate analysis on prospective data.

PURPOSE: To identify independent risk factors for urethroplasty failure in a prospective dataset. METHODS: Since 2008, data of all male patients undergoing urethroplasty at Ghent University Hospital have been prospectively recorded and maintained. This analysis excluded: posterior strictures, strictures of the perineostomy, urethral malignancy-related strictures, age < 18 years and follow-up < 1 year. Postoperatively, a voiding cysto-urethrography (VCUG) was performed after 2 weeks and in absence of significant contrast extravasation, the transurethral catheter was removed. Patients were followed after 3 m, 12 m and annually thereafter. Failure was defined as stricture recurrence requiring additional urethral intervention(s). Uni- and multivariate Cox regression analyses were performed on the entire patient cohort and for one-stage urethroplasty (OSU) at specific locations. RESULTS: In total, 474 patients were included. Median follow-up was 62 m (IQR 35-91). Significant extravasation was present in 6.9%. Bulbar stricture location was identified as independent protective factor for urethroplasty failure (HR 0.44; p = 0.046) and significant extravasation at first VCUG was identified as independent risk factor for urethroplasty failure (HR 2.86; p = 0.005). Cox regression analyses for OSU at specific locations could not identify other risk factors. All but one (89%) of the failures preceded by significant extravasation at first VCUG occurred within 2 years of follow-up whereas 44% of the failures with no or insignificant extravasation at first VCUG occurred after 2 years of follow-up (p = 0.03). CONCLUSIONS: Bulbar stricture location is an independent protective factor for urethroplasty failure. Significant extravasation at first urethrography is an independent risk factor for urethroplasty failure and is associated with earlier stricture recurrence than other failed cases.

A Comprehensive Review Emphasizing Anatomy, Etiology, Diagnosis, and Treatment of Male Urethral Stricture Disease.

To date, urethral stricture disease in men, though relatively common, represents an often poorly managed condition. Therefore, this article is dedicated to encompassing the currently existing data upon anatomy, etiology, symptoms, diagnosis, and treatment of the disease, based on more than 40 years of experience at a tertiary referral center and a PubMed literature review enclosing publications until September 2018.

Vessel-sparing Excision and Primary Anastomosis.

Urethroplasty is considered to be the standard treatment for urethral strictures since it provides excellent long-term success rates. For isolated short bulbar or posterior urethral strictures, urethroplasty by excision and primary anastomosis (EPA) is recommended. As EPA only requires the excision of the narrowed segment and the surrounding spongiofibrosis, a full-thickness transection of the corpus spongiosum, as performed in the traditional transecting EPA (tEPA), is usually unnecessary. Jordan et al. introduced the idea of a vessel-sparing approach in 2007, aiming to reduce surgical trauma, especially to the dual arterial blood supply of the urethra, and, thus, potentially reducing the risk of postoperative erectile dysfunction or glans ischemia. This approach could also be beneficial for subsequent urethral interventions such as redo urethroplasty using a free graft, in which a well-vascularized graft bed is imperative. Nevertheless, these potential benefits are only assumptions as prospective studies comparing the functional outcome of both techniques with validated questionnaires are currently lacking. Moreover, vessel-sparing EPA (vsEPA) should at least be able to provide similar surgical outcomes as tEPA. The aim of this paper is to give an elaborate, step-by-step overview of how to manage patients with isolated short bulbar or posterior urethral strictures with vsEPA. The main objective of this manuscript is to outline the surgical technique and to report the representative surgical outcome. A total of 117 patients were managed according to the described protocol. The analysis was performed on the entire patient cohort and on the bulbar (n = 91) and posterior (n = 26) vsEPA group separately. Success rates were 93.4% and 88.5% for the bulbar and posterior vsEPA, respectively. To conclude, vsEPA, as outlined in the protocol, provides excellent success rates with low complication rates for isolated short bulbar and posterior urethral strictures.

Update on early instillation of chemotherapy after transurethral resection of non-muscle-invasive bladder cancer.

INTRODUCTION: Non-muscle-invasive bladder cancer (NMIBC) is a highly recurrent disease. Early bladder chemotherapy instillation (EBCI) after transurethral resection (TURB) is an efficient way to diminish recurrence. However, this method is often challenged. Areas covered: There was a recent publication of a large meta-analysis with the original patient data and the largest study ever on EBCI. Both brought new evidence on EBCI. Also the results of the 2 trials of EBCI with apaziquone appeared. EBCI is discussed among other methods to decrease recurrence. Expert commentary: EBCI obtains a 35% relative reduction of recurrence with the best results in low risk tumors. However, tumors with an EORTC recurrence score of 5 or more do not respond. It should be given within a few hours after TURB. Mitomycin C and epirubicin have been most widely used with no difference in response. Intensive rinsing of the bladder is also able to reduce recurrence rates by about 21%. A rare, but major problem and reason for not using EBCI is the possible extravasation of the drug after TURB. Apaziquone is rapidly inactivated in tissue and blood and is therefore ideal for local use. Two phase III trials however obtained only a modest result.

Single ablative intravesical electromotive mitomycin C administration for small non-muscle-invasive bladder cancer: a prospective study.

Objectives To explore the effect of electromotive drug administration of mitomycin C (EMDA-MMC) using a single dose of intravesical mitomycin C (MMC) to avoid transurethral resection (TURBT) for small non-muscle-invasive bladder cancer. Material and methods All patients presenting small (<2 cm), single or multiple papillary bladder tumors were proposed to undergo a single EMDA-MMC instillation with 60 mg MMC before planning TURBT. The end point is complete disappearance of all papillary tumors at 2-4 weeks after EMDA-MMC. Results Thirty-six instillations were given to 32 patients. In general the treatment was well supported, except for two patients who had severe bladder spasms, resulting in early evacuation of the MMC. Complete response occurred in 28% (10/36 instillations). In 4 EMDA-MMCs with multiple tumors some tumors disappeared while others remained. In 61% (22/36) the tumors remained unchanged. Conclusion A single EMDA-MMC in l papillary bladder tumors <2 cm gives insufficient ablative effect.

Perspective on cytoreduction and metastasis-directed therapy in node positive and metastatic urothelial carcinoma of the bladder.

The outcome of node positive or metastatic urothelial carcinoma of the bladder (mUCB) is poor and palliative chemotherapy has long been considered the only treatment option for this patient group. Cytoreduction and metastasis-directed therapy, either by surgery or radiotherapy, has been successfully applied in other metastatic solid tumors in order to increase survival. In this article, we explore the literature supporting cytoreduction and metastasis-directed therapy in node positive and mUCB and try to define a patient cohort that could benefit from these treatments. From these data, it is clear that a selected group of patients survive a long time or could even be cured, however the data are scarce and the level of evidence is low. The criteria of a randomized clinical trial, to deliver the necessary evidence, are proposed.

Duration of urethral catheterization after urethroplasty: how long is enough?

BACKGROUND: To report the impact of duration of urethral catheterization (DUC) on the rate of extravasation on voiding cysto-urethrography (VCUG) and the subsequent need of catheter replacement in urethroplasty. METHODS: Two hundred nineteen consecutive patients undergoing urethroplasty between October 2010 and November 2014 were evaluated for the impact of DUC. Patients were divided into 2 groups, based on the scheduled DUC≤10 days (group 1, N.=86) or >10 days (group 2, N.=133). RESULTS: Fourteen patients (6.4%) had extravasation on VCUG with an additional period of catheter usage. In 10 of the 14 patients (71.4%) clinical signs of impaired wound healing were present. In group 1 (median DUC 8 days) 3 patients (3.5%) needed an additional period of urethral catheterization, compared to 11 patients (8.3%) in group 2 (median DUC 14 days). Strictures in group 2 were longer (4 vs. 2 cm, P<0.001) and more complex. Redo urethroplasty was needed in 9 of the 14 patients with extravasation. CONCLUSIONS: In uncomplicated cases of urethroplasty, the urethral catheter can be safely removed after 8 to 10 days postoperatively. Extravasation on VCUG occurs in around 6% of urethroplasties and is a prognostic factor for stricture recurrence and reoperation.

Nontransecting Anastomotic Repair in Urethral Reconstruction: Surgical and Functional Outcomes.

PURPOSE: We evaluated the surgical and functional outcomes, and the effect of the learning curve of nontransecting anastomotic repair for short bulbar and posterior urethral strictures. MATERIALS AND METHODS: A total of 75 patients were treated with nontransecting anastomotic repair for short bulbar strictures in 55 and for posterior strictures in 20. Surgical morbidity was scored using the Clavien-Dindo classification at 3 months. Sexual function was measured using SHIM (Sexual Health Inventory for Men) scoring preoperatively and postoperatively. Post-void dribbling before and after nontransecting anastomotic repair was also determined. To evaluate the learning curve outcomes were evaluated in patients 1 to 25, 26 to 50 and 51 to 75. RESULTS: Median followup was 30 months. Stricture recurred in 6 patients (8%), all diagnosed within 7 months after nontransecting anastomotic repair. Median operative time was 95 minutes and median hospital stay was 2 days. In 61 patients (81.3%) no surgical morbidity was recorded. Five (6.7%), 6 (8%) and 3 patients (4%) experienced a grade 1, 2 and 3b complication, respectively. Seven of 32 (21.9%) and 2 of 42 evaluable patients (4.7%) reported de novo erectile dysfunction and post-void dribbling, respectively, 3 months after nontransecting anastomotic repair. No difference in outcomes was observed among the 3 patient groups. CONCLUSIONS: Nontransecting anastomotic repair appears to be safe without a substantial learning curve effect. Patient counseling about possible surgical complications and transient erectile dysfunction is important.

Increasing age is not associated with toxicity leading to discontinuation of treatment in patients with urothelial non-muscle-invasive bladder cancer randomised to receive 3 years of maintenance bacille Calmette-Guérin: results from European Organisation for Research and Treatment of Cancer Genito-Urinary Group study 30911.

OBJECTIVE: To determine the relationship of age to side-effects leading to discontinuation of treatment in patients with stage Ta-T1 non-muscle-invasive bladder cancer (NMIBC) treated with maintenance bacille Calmette-Guérin (BCG). PATIENTS AND METHODS: We evaluated toxicity for 487 eligible patients with intermediate- or high-risk Ta-T1 (without carcinoma in situ) NMIBC randomised to receive 3 years of maintenance BCG therapy (247 BCG alone and 240 BCG + isoniazid) in European Organisation for Research and Treatment of Cancer Genito-Urinary Group trial 30911. The percentage of patients who stopped for toxicity and the number of treatment cycles that they received were compared in four age groups, ≤60, 61-70, 71-75 and >75 years, using the Mantel-Haenszel chi-square test for trend. RESULTS: The percentage of patients stopping BCG for toxicity was 17.9% in patients aged ≤60 years, 21.9% in patients aged 61-70 years, 22.9% in patients aged 71-75 years, and 16.4% in patients aged >75 years (P = 0.90). For both systemic and local side-effects, there was likewise no significant difference. CONCLUSION: In patients with intermediate- and high-risk Ta-T1 NMIBC treated with BCG, no differences in toxicity as a reason for stopping treatment were detected based on patient age.

Varicocele: the origin of benign prostatic hypertrophy? Testosterone dosages in the periprostatic plexus.

OBJECTIVES: In 2008, Gat et al. wrote the hypothesis that benign prostatic hypertrophy (BPH) was caused by reflux from high free testosterone containing blood from varicocele. The purpose of this study is to measure testosterone at the prostatic veins in patients operated for large BPH, confirming Gat's theory. MATERIAL AND METHODS: In 13 patients, operated by Millin technique, the periprostatic plexus was punctured in 45° tilted position in order to the measure total and free testosterone and dihydrotestosterone. Brachial blood was taken simultaneously for similar measurements. Seven patients had a clinical varicocele. RESULTS: High testosterone levels, in comparison with the brachial blood, were detected in only two patients. Dihydrotestosterone was at least doubled in all cases, demonstrating that the puncture was done in prostatic drainage area. CONCLUSION: Gat's theory, concerning the role of varicocele in the origin of BPH, could not be confirmed in this study. Technical limitations can be responsible for this.

Systematic Review and Individual Patient Data Meta-analysis of Randomized Trials Comparing a Single Immediate Instillation of Chemotherapy After Transurethral Resection with Transurethral Resection Alone in Patients with Stage pTa-pT1 Urothelial Carcinoma of the Bladder: Which Patients Benefit from the Instillation?

CONTEXT: The European Association of Urology non-muscle-invasive bladder cancer (NMIBC) guidelines recommend that all low- and intermediate-risk patients receive a single immediate instillation of chemotherapy after transurethral resection of the bladder (TURB), but its use remains controversial. OBJECTIVE: To identify which NMIBC patients benefit from a single immediate instillation. EVIDENCE ACQUISITION: A systematic review and individual patient data (IPD) meta-analysis of randomized trials comparing the efficacy of a single instillation after TURB with TURB alone in NMIBC patients was carried out. EVIDENCE SYNTHESIS: A total of 13 eligible studies were identified. IPD were obtained for 11 studies randomizing 2278 eligible patients, 1161 to TURB and 1117 to a single instillation of epirubicin, mitomycin C, pirarubicin, or thiotepa. A total of 1128 recurrences, 108 progressions, and 460 deaths (59 due to bladder cancer [BCa]) occurred. A single instillation reduced the risk of recurrence by 35% (hazard ratio [HR]: 0.65; 95% confidence interval [CI], 0.58-0.74; p<0.001) and the 5-yr recurrence rate from 58.8% to 44.8%. The instillation did not reduce recurrences in patients with a prior recurrence rate of more than one recurrence per year or in patients with an European Organization for Research and Treatment of Cancer (EORTC) recurrence score ≥5. The instillation did not prolong either the time to progression or death from BCa, but it resulted in an increase in the overall risk of death (HR: 1.26; 95% CI, 1.05-1.51; p=0.015; 5-yr death rates 12.0% vs 11.2%), with the difference appearing in patients with an EORTC recurrence score ≥5. CONCLUSIONS: A single immediate instillation reduced the risk of recurrence, except in patients with a prior recurrence rate of more than one recurrence per year or an EORTC recurrence score ≥5. It does not prolong either time to progression or death from BCa. The instillation may be associated with an increase in the risk of death in patients at high risk of recurrence in whom the instillation is not effective or recommended. PATIENT SUMMARY: A single instillation of chemotherapy immediately after resection reduces the risk of recurrence in non-muscle-invasive bladder cancer; however, it should not be given to patients at high risk of recurrence due to its lack of efficacy in this subgroup.

EORTC Nomograms and Risk Groups for Predicting Recurrence, Progression, and Disease-specific and Overall Survival in Non-Muscle-invasive Stage Ta-T1 Urothelial Bladder Cancer Patients Treated with 1-3 Years of Maintenance Bacillus Calmette-Guérin.

BACKGROUND: There are no prognostic factor publications on stage Ta-T1 non-muscle-invasive bladder cancer (NMIBC) treated with 1-3 yr of maintenance bacillus Calmette-Guérin (BCG). OBJECTIVE: To determine prognostic factors in NMIBC patients treated with 1-3 yr of BCG after transurethral resection of the bladder (TURB), to derive nomograms and risk groups, and to identify high-risk patients who should be considered for early cystectomy. DESIGN, SETTING, AND PARTICIPANTS: Data for 1812 patients were merged from two European Organization for Research and Treatment of Cancer randomized phase 3 trials in intermediate- and high-risk NMIBC. INTERVENTION: Patients received 1-3 yr of maintenance BCG after TURB and induction BCG. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Prognostic factors for risk of early recurrence and times to late recurrence, progression, and death were identified in a training data set using multivariable models and applied to a validation data set. RESULTS AND LIMITATIONS: With a median follow-up of 7.4 yr, 762 patients recurred; 173 progressed; and 520 died, 83 due to bladder cancer (BCa). Statistically significant prognostic factors identified by multivariable analyses were prior recurrence rate and number of tumors for recurrence, and tumor stage and grade for progression and death due to BCa. T1G3 patients do poorly, with 1- and 5-yr disease-progression rates of 11.4% and 19.8%, respectively, and 1- and 5-yr disease-specific death rates of 4.8% and 11.3%. Limitations include lack of repeat transurethral resection in high-risk patients and exclusion of patients with carcinoma in situ. CONCLUSIONS: NMIBC patients treated with 1-3 yr of maintenance BCG have a heterogeneous prognosis. Patients at high risk of recurrence and/or progression do poorly on currently recommended maintenance schedules. Alternative treatments are urgently required. PATIENT SUMMARY: Non-muscle-invasive bladder cancer patients at high risk of recurrence and/or progression do poorly on currently recommended bacillus Calmette-Guérin maintenance schedules, and alternative treatments are urgently required. TRIAL REGISTRATION: Study 30911 was registered with the US National Cancer Institute clinical trials database (protocol ID: EORTC 30911). Study 30962 was registered at ClinicalTrials.gov, number NCT00002990; http://clinicaltrials.gov/ct2/show/record/NCT00002990.

Ablative Intravesical Chemotherapy for Small Recurrent Non-Muscle-Invasive Bladder Cancer: A Prospective Study.

OBJECTIVE: The efficacy of intravesical chemotherapy in abolishing small papillary recurrences of non-muscle-invasive bladder cancer (NMIBC), the disease-free interval in responders and patients' preferences were explored. METHODS: When a small (≤1 cm) papillary recurrence of a NMIBC was diagnosed, the patient could choose between immediate transurethral resection of the bladder (TURB) or four weekly intravesical instillations with mitomycin C (MMC) or epirubicin (ERC). Control cystoscopy was scheduled 2-3 weeks after the last instillation. Complete remission was defined as total disappearance of all papillary tumours and negative cytology. RESULTS: 25 patients with 47 recurrence episodes were recruited from February 2003 until August 2011. The median follow-up was 35 months. After exclusion of 2 patients with intolerance to the instillations, 45 study episodes could be analysed. All patients to whom this was proposed preferred the instillations over immediate TURB. Complete, partial and no response was seen in 23 (51%), 6 (13%) and 16 (36%) out of 45 episodes, respectively. The median disease-free interval after complete remission was 16 months (95% confidence interval 9-24). CONCLUSIONS: Small papillary recurrences of NMIBC completely disappear in about half of the cases receiving four weekly bladder instillations with MMC or ERC. This is followed by a disease-free interval. Intravesical chemotherapy was preferred by all patients over immediate TURB.