Optilume drug-coated balloon for anterior urethral stricture: 2-year results of the ROBUST III trial.

Objective: The aim of this study is to report the updated 2-year results of the intervention arm of the ROBUST III randomized trial evaluating the safety and efficacy of the Optilume drug-coated balloon (DCB) versus standard endoscopic management of recurrent male anterior urethral stricture. Materials and Methods: Eligible patients included men with recurrent anterior urethral stricture ≤3 cm in length and ≤12Fr in diameter, International Prostate Symptom Score (IPSS) ≥11 and peak flow rate (Qmax) <15 mL/s. Patients were randomized to treatment with the Optilume DCB or standard-of-care endoscopic management. Primary efficacy endpoints measured at 2 years included freedom from re-intervention and changes in IPSS, Qmax and post-void residual (PVR). Secondary endpoint was impact on sexual function using the International Index of Erectile Function (IIEF). Primary safety endpoint was freedom from serious procedure- or device-related adverse events (AEs). Results: A total of 127 patients enrolled at 22 sites in the United States and Canada (48 randomized to standard-of-care dilation and 79 to DCB dilation). Seventy-five patients in the DCB arm entered the open-label phase after 6 months. Participants averaged 3.2 prior endoscopic interventions (range 2-10); most (89.9%) had bulbar strictures with an average stricture length of 1.63 cm (SD 0.76). Significant improvements in IPSS, average Qmax and PVR were maintained at 2 years. Freedom from repeat intervention was significantly higher in the Optilume DCB arm at 2 years versus the Control arm at 1 year (77.8% vs. 23.6%, p < 0.001). During the follow-up period, there were 15 treatment failures and two non-study-related deaths. Treatment-related AEs were rare and generally self-limited (haematuria, dysuria and urinary tract infection). Conclusion: The Optilume DCB shows sustained improvement in both objective and subjective voiding parameters at 2-year follow-up. Optilume appears to provide a safe and effective endoscopic treatment alternative for short recurrent anterior urethral strictures among men who wish to avoid or delay formal urethroplasty.

A Drug-Coated Balloon Treatment for Urethral Stricture Disease: Three-Year Results from the ROBUST I Study.

Introduction: Endoscopic management of male anterior urethral stricture disease is common; however, repeat treatment is associated with high recurrence rates. Here, we report the 3-year results of the ROBUST I trial, which evaluated the safety and efficacy of the Optilume® drug coated balloon (DCB) in men with recurrent urethral strictures. Methods: Adult men with recurrent bulbar urethral strictures ≤2 cm in length and 1-4 prior endoscopic interventions were treated with the Optilume DCB. Functional success was defined as ≥50% reduction in International Prostate Symptom Score (IPSS) without need for retreatment. Other outcomes included quality of life, maximum flow rate, post-void residual urine volume, erectile function, and freedom from repeat intervention. Results: Of the 53 enrolled and treated men, 33 completed the 3-year visit, with 10 patients experiencing clinical failures at previous visits, giving a total of 43 subjects evaluable for the functional success endpoint. Functional success was achieved in 67% (29/43) and freedom from retreatment in 77% (33/43). Average IPSS improved from 25.2 at baseline to 5.5 at 3 years (p<0.0001). Significant improvements were observed in quality of life, flow rate, and post-void residual urine volume. Erectile function was not affected by treatment. Device-related adverse events were mild or moderate in nature and resolved quickly after onset. There were no serious treatment-related adverse events. Conclusion: Symptomatic improvement after treatment with the Optilume DCB was maintained through 3 years in a population highly susceptible to recurrent urethral stricture disease. This minimally invasive therapy is safe with no negative impact on sexual function.

One-Year Results for the ROBUST III Randomized Controlled Trial Evaluating the Optilume® Drug-Coated Balloon for Anterior Urethral Strictures.

PURPOSE: The Optilume® drug-coated balloon (DCB) is a urethral dilation balloon with a paclitaxel coating that combines mechanical dilation for immediate symptomatic relief with local drug delivery to maintain urethral patency. The ROBUST III study is a randomized, single-blind trial evaluating the safety and efficacy of the Optilume DCB against endoscopic management of recurrent anterior urethral strictures. MATERIALS AND METHODS: Eligible patients were adult males with anterior strictures ≤12Fr in diameter and ≤3 cm in length, at least 2 prior endoscopic treatments, International Prostate Symptom Score ≥11 and maximum flow rate <15 ml per second. A total of 127 subjects were enrolled at 22 sites. The primary study end point was anatomical success (≥14Fr by cystoscopy or calibration) at 6 months. Key secondary end points included freedom from repeat treatment, International Prostatic Symptom Score and peak flow rate. The primary safety end point included freedom from serious device- or procedure-related complications. RESULTS: Baseline characteristics were similar between groups, with subjects having an average of 3.6 prior treatments and average length of 1.7 cm. Anatomical success for Optilume DCB was significantly higher than control at 6 months (75% vs 27%, p <0.001). Freedom from repeat intervention was significantly higher in the Optilume DCB arm. Immediate symptom and urinary flow rate improvement was significant in both groups, with the benefit being more durable in the Optilume DCB group. The most frequent adverse events included urinary tract infection, post-procedural hematuria and dysuria. CONCLUSIONS: The results of this randomized controlled trial support that Optilume is safe and superior to standard direct vision internal urethrotomy/dilation for the treatment of recurrent anterior urethral strictures <3 cm in length. The Optilume DCB may serve as an important alternative for men who have had an unsuccessful direct vision internal urethrotomy/dilation but want to avoid or delay urethroplasty.

A drug-coated balloon treatment for urethral stricture disease: Two-year results from the ROBUST I study.

INTRODUCTION: Mechanical balloon dilation and direct visualization internal urethrotomy (DVIU) are the most widely used treatments for urethral stricture disease in the U.S., but recurrence rates are high, especially after re-treatment. This study investigates the safety and efficacy of the Optilume™ paclitaxel-coated balloon for the treatment of recurrent strictures. METHODS: Men with recurrent bulbar strictures ≤2 cm with 1-4 prior endoscopic treatments were treated with the Optilume™ drug-coated balloon. Patients were evaluated within 14 days, three, six, 12, and 24 months post-treatment. The primary safety endpoint was serious urinary adverse events. The primary efficacy endpoint was ≥50% improvement in International Prostate Symptom Score (IPSS) at 24 months. Secondary outcomes included quality of life, erectile function, flow rate, and post-void residual urine volume. RESULTS: A total of 53 subjects were enrolled and treated; 46 completed the 24-month followup. Forty-three percent of men had undergone >1 previous dilations, with a mean of 1.7 prior dilations. There were no serious adverse events related to treatment at two years. Success was achieved in 32/46 (70%), and baseline IPSS improved from a mean of 25.2 to 6.9 at 24 months (p<0.0001). Quality of life, flow rate, and post-void residual urine volumes improved significantly from baseline. There was no impact on erectile function. CONCLUSIONS: Two-year data indicates the Optilume™ paclitaxel-coated balloon is safe for the treatment of recurrent bulbar urethral strictures. Early efficacy results are encouraging and support further followup of these men through five years, as well as further investigation with a randomized trial.

Liposomal Bupivacaine Local Infiltration for Buccal Mucosal Graft Harvest Site Pain Control: A Single-blinded Randomized Controlled Trial.

OBJECTIVE: To assess efficacy and safety of liposomal bupivacaine (LB) infiltration of the buccal mucosal graft (BMG) harvest site in alleviating pain by evaluating the postoperative narcotic usage, pain score, and morbidities. PATIENTS AND METHODS: Single-blinded randomized controlled trial of 43 adult patients for BMG substitution urethroplasty between January 2015 to June 2017 (Clinicaltrials.gov: NCT03720223). A computer-generated allocation scheme randomized patients to control group (n = 22) no further local anesthetic infiltration aside from that of used in the hydrodissection for BMG harvest, and to intervention group with additional infiltration of LB to BMG harvest site (n = 21). We assessed postoperative cumulative narcotic use on post-op day 1 and 2 (24- and 48-hour total intravenous [IV] morphine equivalents in milligrams). A self-reported 10-point numeric rating scale survey was administered to assess postprocedural oral pain, oral conditions, and morbidity on days 1-3, and at 1-month follow-up. Fisher's exact test and independent T test were performed to assess differences between treatment groups. Linear regression was used to determine adjusted effect estimates of intervention. RESULTS: Compared to controls, a significantly lower narcotic use was noticed among the LB treatment group on post-op day 1 (IV morphine equivalent mean difference 8.58 mg; 95% confidence interval 1.59, 15.56, P =.017), while no significant difference was noticed on post-op day 2. There was no significant difference between treatment groups with regards to postprocedural oral pain score or oral morbidities. CONCLUSION: Our study showed that LB infiltration of the BMG harvest site is safe and associated with lower 24-hour narcotic use only at post-op day 1.

Surgical management and outcomes of adult acquired buried penis with and without lichen sclerosus: a comparative analysis.

PURPOSE: Adult acquired buried penis (AABP) can present with concomitant Lichen Sclerosus (LS), a chronic dermatosis that may affect surgical outcomes. Our aim was to evaluate outcomes of patients undergoing AABP repair with and without LS. METHODS: A retrospective cohort study was performed for AABP repair patients at a single institution from 1/1991 to 12/2017. Patient characteristics and surgical and peri-operative outcomes, including success, erectile function, and complications, were collected. RESULTS: Sixty-seven AABP patients with mean follow-up of 16.1 ± 20.4 months were identified. Overall surgical success was 91%. Overall surgical complication rate was 50.7% (23.9% Clavien-Dindo ≥ 3). Forty-two (62.7%) patients had concomitant LS. A higher proportion of patients with LS required a STSG (90% vs 60%, p = 0.005). There was no difference in surgical success (90.5% vs 92.0%, p = 0.999), overall complication rate (57.1% vs 40.0%, p = 0.212), Clavien-Dindo ≥ 3 complications (23.8% vs 24.0%, p = 0.999) or early complications (35.7% vs 32.0%, p = 0.797) between patients with and without LS, respectively. However, a higher proportion of patients with LS experienced late complications (33.3% vs 8.0%, p = 0.020), which were mainly related to wound healing. Satisfaction with erectile function was higher among patients with LS (59.5% vs 320%, p = 0.043). CONCLUSION: AABP patients with LS behave somewhat differently than their non LS counterparts. They are more likely to require skin graft during surgical treatment. Though surgical success and complications are similar, they do experience a higher rate of late complications from impaired wound healing. Work on improving wound healing in this population should be considered.

A drug-coated balloon treatment for urethral stricture disease: Interim results from the ROBUST I study.

INTRODUCTION: We aimed to investigate the safety and preliminary efficacy of the Optilume™ paclitaxel-coated balloon for the treatment of recurrent urethral stricture. METHODS: Men with bulbar urethral strictures ≤2 cm with 1-4 prior endoscopic treatments were enrolled at four study sites after ethics committee approvals. All subjects were treated with mechanical balloon dilation or direct visualization internal urethrotomy prior to drug-coated balloon treatment. Patients were evaluated at 2-5 days, 14 days, three, six, and 12-months post-treatment. The primary safety endpoint was serious complications through 90 days post-procedure. The preliminary efficacy endpoint was anatomic success, defined as urethral lumen ≥14 Fr at 12 months. RESULTS: A total of 53 subjects were enrolled and treated; 46 completed the 12-month followup. Forty-three percent of men had undergone >1 previous dilation; the mean for the overall study population was 1.7 prior dilations. There were no serious adverse events related to the treatment within 90 days. Anatomic success was achieved in 32/46 (70%; 95% confidence interval [CI] 54-82%) at 12 months. The 14 failures included seven cystoscopic recurrences, five retreatments, and two patients who exited the study early due to symptom recurrence. CONCLUSIONS: One-year data indicates the Optilume paclitaxel-coated balloon is safe for the treatment of recurrent bulbar urethral strictures. Early efficacy results are encouraging and support further followup of these men through five years, as well as further investigation with a randomized trial.

Non-transecting bulbar urethroplasty is favored over transecting techniques.

PURPOSE: To present current evidence supporting the vessel sparing technique to reconstruct bulbar urethral strictures via primary anastomosis. METHODS: English literature review of presented series of transecting and non-transecting bulbar urethroplasty from 2000 to 2018. RESULTS: Since its introduction in 2007, vessel-sparing excision and primary anastomosis (VS-EPA) has been utilized in multiple centers across the world. Success rates range from 90 to 98%, comparable to traditional transecting EPA. Complication rates and erectile function outcomes are similar or better in VS-EPA, according to recent publications. CONCLUSIONS: Non-transection excision and primary anastomosis is a well-tolerated, highly successful reconstructive option for short bulbar urethral strictures in appropriately selected patients. Results are comparable with traditional transecting anastomosis and mid-term multinational follow-up has proven efficacy and safety of the technique. Further well-designed multi-institutional studies are necessary to determine superiority to traditional EPA in terms of surgical outcomes and erectile function preservation.

International multi-institutional experience with the vessel-sparing technique to reconstruct the proximal bulbar urethra: mid-term results.

OBJECTIVE: To present mid-term outcomes from an international, multi-institutional cohort of patients undergoing vessel-sparing excision and primary anastomosis urethroplasty for the reconstruction of the anterior urethra. MATERIALS AND METHODS: From June 2003 to December 2011, 68 patients underwent vessel-sparing anterior urethral reconstruction at five different international institutions using the vessel-sparing technique described by Jordan et al. (J Urol 177(5):1799-1802, 2007). RESULTS: Patients' age range was from 3 to 82 years (mean 51.2). Stricture length ranged from 1 to 3 cm (mean 1.78). After a mean follow-up of 17.6 months, 95.6 % of patients had a widely patent urethral lumen. Three patients failed the procedure, requiring either direct vision internal urethrotomy or urethral dilation, after which all were free of symptoms and did not require further instrumentation. Complications were minimal and as expected following open urethroplasty. CONCLUSION: Preservation of blood supply is a noble pursuit in surgery; however, it can be technically difficult and often requires more time and effort. This vessel-sparing technique for anterior urethral reconstruction is reproducible and appears to be reliable in this international cohort. Larger studies and longer follow-up are needed to support these encouraging results.

The advance transobturator male sling for post-prostatectomy incontinence: subjective and objective outcomes with 3 years follow up.

AIMS: To determine patient-perceived and clinical outcomes of the AdVance sling at 3 years follow-up in men with post-prostatectomy incontinence (PPI). METHODS: Data was prospectively collected of men with PPI treated with the AdVance male sling between February 2008 and March 2010. Twenty-four-hour pad counts and weights and patient completed validated questionnaires were obtained pre-operatively and at 3 years. The primary outcome was improvement in pad count with secondary outcomes of questionnaire scores and patient perception of success. RESULTS: At a median follow-up of 39 months (IQR: 36-44), we identified 30 men meeting inclusion criteria who had the AdVance male sling placed for mild to severe PPI. Eighteen (60%) patients were cured (no pad usage or one pad for security) and an additional 4 (13%) showed improvement (≥50% reduction in pad usage). Eight (27%) patients failed: six patients underwent seven salvage procedures including urethral bulking with collagen (n = 1), Virtue perineal sling (n = 1), and artificial urinary sphincter (n = 5). There were 16 post-operative complications: 13 Clavien I, 2 Clavien II, and 1 Clavien IIIb. CONCLUSIONS: AdVance male sling is an effective treatment option for PPI evidenced by objective improvements in 24-hr pad count and pad weight and patient perceived success via validated questionnaires.

MicroRNA Profile to Predict Gemcitabine Resistance in Bladder Carcinoma Cell Lines.

MicroRNAs (miRNA) are small, noncoding RNAs with important regulatory roles in development, differentiation, cell proliferation, and death as well as the complex process of acquired drug resistance. The goal of this study was to identify specific miRNAs and their potential protein targets that confer acquired resistance to gemcitabine in urothelial carcinoma of the bladder (UCB) cell lines. Gemcitabine-resistant cells were established from 6 cell lines following exposure to escalating concentrations of the drug and by passaging cells in the presence of the drug over a 2- to 3-month period. Differential miRNA expression was identified in a microarray format comparing untreated controls with resistant cell lines, representing the maximum tolerated concentration, and results were validated via qRT-PCR. The involvement of specific miRNAs in chemoresistance was confirmed with transfection experiments, followed by clonogenic assays and Western blot analysis. Gemcitabine resistance was generated in 6 UCB cell lines. Microarray analysis comparing miRNA expression between gemcitabine-resistant and parental cells identified the differential expression of 66 miRNAs. Confirmation of differential expression was recorded via qRT-PCR in a subset of these miRNAs. Within this group, let-7b and let-7i exhibited decreased expression, while miR-1290 and miR-138 displayed increased expression levels in gemcitabine-resistant cells. Transfection of pre-miR-138 and pre-miR-1290 into parental cells attenuated cell death after exposure to gemcitabine, while transfection of pre-miR-let-7b and pre-miR-let-7i into the resistant cells augmented cell death. Mucin-4 was up-regulated in gemcitabine-resistant cells. Ectopic expression of let-7i and let-7b in the resistant cells resulted in the down-regulation of mucin-4. These results suggest a role for miRNAs 1290, 138, let-7i, and let-7b in imparting resistance to gemcitabine in UCB cell lines in part through the modulation of mucin-4. Alterations in these miRNAs and/or mucin-4 may constitute a potential therapeutic strategy for improving the efficacy of gemcitabine in UCB.

Comparison of laparoscopic versus robotic assisted partial nephrectomy: one surgeon's initial experience.

INTRODUCTION/OBJECTIVE: Partial nephrectomy is an effective surgical treatment for small renal masses. We compare a single surgeon's experience with consecutive laparoscopic and robotic partial nephrectomy to assess potential perioperative outcomes. A review of the literature is provided. MATERIALS AND METHODS: A retrospective review was performed comparing 15 consecutive patients undergoing laparoscopic partial nephrectomy to the subsequent consecutive 13 patients undergoing robotic assisted partial nephrectomy for small renal tumors. All patients had normal contralateral kidney appearance on cross sectional imaging. A similar transperitoneal technique was employed for both cohorts. A 4-arm technique was used for the robotic cases using the da Vinci (Intuitive Surgical, Sunnyvale, USA) surgical system. Patient demographics, tumor characteristics, intraoperative, and postoperative data including tumor size, warm ischemia time, and estimated blood loss (EBL) were compared using Student t-test, Wilcoxon rank-sum, or Chi square test as appropriate. RESULTS: All cases were completed laparoscopically or with robotic assistance without conversion to open surgery. Demographic data were not statistically different between the two groups. Warm ischemia time (WIT) was shorter in the robotic group: 29.7 minutes versus 39.9 minutes for the laparoscopic group (p < 0.0001). Operative time was longer in the robotic group: 253 versus 352 minutes (p < 0.0001). Mean hospital stay and postoperative complication rates were not statistically different. Two (13%) of patients in the laparoscopic group required conversion of partial nephrectomy to radical nephrectomy while none did in the robotic group. Final pathology revealed negative margins in all cases. CONCLUSIONS: Robotic partial nephrectomy resulted in decreased WIT as compared to the conventional laparoscopic approach. Total operating time was increased in the robotic group.