Jessica DeLong

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

To determine patient‐perceived and clinical outcomes of the AdVance sling at 3 years follow‐up in men with post‐prostatectomy incontinence (PPI).

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.

Urinary Diversion/Reconstruction for Cases of Catheter Intolerant Secondary Progressive Multiple Sclerosis With Refractory Urinary Symptoms

PURPOSE We assessed surgical outcomes for patients intolerant of catheters with secondary progressive multiple sclerosis undergoing urinary diversion/reconstruction for refractory urinary symptoms. MATERIALS AND METHODS Patients with secondary progressive multiple sclerosis treated with ileovesicostomy, enterocystoplasty and ileal loop surgeries were reviewed for demographic, operative and postoperative data. All patients had attempted maximal conservative therapy, including catheterization options. Evaluated outcome measures included incidence of postoperative urinary incontinence, urinary tract infections and Clavien grade 3 or higher complications. RESULTS A total of 26 patients (22 female) with secondary progressive multiple sclerosis underwent 15 ileovesicostomy, 7 enterocystoplasty and 4 ileal loop procedures. All patients had significant neurological impairment (mean Expanded Disability Status Scale 7), and the most common indications for surgery were chronic urinary tract infection (77%) and refractory incontinence (77%). Maximum preoperative bladder capacity was 185 cc and mean bladder compliance was 5.7 cc/cm H(2)O. After a mean followup of 16 months 63% of patients were continent (p = 0.01) and 58% had no further urinary tract infections (p = 0.03). The type of diversion/reconstruction was not associated with significantly improved continence or urinary tract infection reduction. No new upper tract changes developed in any patients. There were 11 high grade complications, and patients with a preoperative indwelling catheter (HR 5.89, p = 0.024), diabetes (HR 5.60, p = 0.009) and increasing blood loss during surgery (HR 1.09, p = 0.014) were at greatest risk for significant complications. CONCLUSIONS Patients with secondary progressive multiple sclerosis treated with urinary diversion/reconstruction who cannot tolerate catheters had improved continence and fewer urinary tract infections. However, patients with secondary progressive multiple sclerosis with preoperative indwelling catheters, diabetes, increased body mass index and increasing operative blood loss were at greatest risk for postoperative morbidity.

Interstitial Cystitis and the Overlap with Overactive Bladder

There has been significant interest and discussion in the literature regarding overactive bladder and interstitial cystitis/painful bladder syndrome. Contemporary studies have estimated a much higher prevalence of both syndromes compared with earlier figures. The two syndromes have many symptoms in common, and recent research suggests that they have significant overlap, not only in presentation but also potentially in etiology and consequently in treatment. This review aims to summarize the latest findings in the literature regarding epidemiology, proposed pathophysiology, methods of evaluation, and treatment algorithms.

MP79-11 COMPARISON OF OUTCOMES BETWEEN ULNAR AND RADIAL FREE FLAPS FOR NEOPHALLUS CONSTRUCTION

METHODS: 15 transgender patients who were already living as females presented to our institution from 1/2016 to 10/2016, and underwent our previously defined RAPiV. Briefly, the RAPiv is performed in the low lithotomy position and the penis is degloved through a circumcision incision. An additional perineal incision is made to the bulbar urethra. The dissected penis, urethra, neurovascular bundle, glans and corpora are delivered through the perineal incision (Figure 1a). We spare the dorsal aspect of the tunica of the corpora cavernosa to reduce risk of glans necrosis. Four robotic ports were placed and the abdomen was insufflated (1b) and robot docked. Denonviller’s fascia is opened (1c) and the abdominal dissection is continued to the peritoneal one (1d), the neovagina is passed into robotic field (1e) and pexed to the anterior reflection of the posterior peritoneum (1f). The peritoneal reflection is then closed (1g). We then complete the labioplasty and clitoroplasty. RESULTS: The average operative time for RAPiV was 5.8 hours (5-7), 8/15 (53%) required mobilization of additional tissue flaps (4/15, 27%) or underwent concomitant abdominoplasty and skin graft harvest (4/15 27%) to supplement penile skin. EBL was 386cc (100600) and LOS was 3.7 (2-6). Average postoperative vaginal depth was 11.3cm (10.2-12.7). Two patients had complications, 1 dehiscence of labioplasty treated with conservative therapy and 1 had loss of neovagina depth and distal urethral stenosis secondary to wound infection requiring debridement. CONCLUSIONS: We have performed 15 cases utilizing our novel method for robot assisted penile inversion vaginoplasty. Under direct visualization the neovaginal canal is created. This technique achieves maximal vaginal length in a reproducible manner.

MP46-17 ASSOCIATION BETWEEN EARLY POSTOPERATIVE URINARY RETENTION AND OUTCOMES AFTER TRANSOBTURATOR SLING INSERTION FOR TREATMENT OF MALE STRESS URINARY INCONTINENCE

INTRODUCTION AND OBJECTIVES: Male stress urinary incontinence (SUI) is a common sequela of radical prostatectomy and occasionally benign prostatic hyperplasia surgery, causing significant impact on quality of life. The AdVance transobturator sling has been described as a safe and effective minimally invasive treatment for male SUI, but early postoperative urinary retention (EPUR) is not uncommon. This study evaluates the outcomes of patients who have EPUR after insertion of an AdVance transobturator male sling for treatment of SUI. Our hypothesis is that although EPUR can be concerning, it is usually transient and may be associated with favorable continence outcomes. METHODS: A review of all men with SUI treated with an AdVance transobturator sling by a single surgeon during the period of January 1, 2006 through August 1, 2016, was performed. Perioperative, continence and complication outcomes (including urinary retention, mesh erosion and reoperation) were assessed. Outcomes of men who experienced EPUR were compared with men who did not experience EPUR. Statistical analyses such as Chi Square test were performed in Microsoft Excel 2016. RESULTS: 257 men (mean age 68 years) underwent insertion of a transobturator sling for SUI during the study period. Mean follow up was 25 months; 5 men were lost to follow up. Overall, success rate was 84%, with 45% (114/252) of men reporting complete continence and 39% (98/252) reporting improvement only. Overall, the mean number of pads used per patient per day improved from 3.7 pre-sling to 1.3 post-sling insertion. 16% (41/252) of patients experienced EPUR which was treated with reinsertion of indwelling Foley urethral catheter and repeat void trial. Most cases of urinary retention resolved within weeks; one patient required explantation of the sling due to ongoing urinary retention beyond 3 months. In the group of patients who had EPUR, success rate was 98%, with 61% of men achieving complete continence and 37% reporting improvement only. By comparison, in the group of patients who did not have EPUR, success rate was 82%, with 42% of men reporting complete continence and 39% of men stating improvement only. The difference in continence success rate between the EPUR and no EPUR groups was statistically significant (p<0.05). CONCLUSIONS: Insertion of an AdVance transobturator sling for treatment of male SUI was complicated by EPUR in 16% of men. Most cases of EPUR were transient. The continence success rate in the group of men who experienced EPUR was significantly better than in the group of men without EPUR.

Abstract 1161: Detection and identification of a miRNA expression profile from cell-free urine: Potential utility in bladder cancer

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Introduction/Objective: MicroRNAs are small, non-coding RNAs that have been shown to play an important role in tumorigenesis. There is differential expression of miRNA in cancer progression, and profiling of miRNA is promising for both diagnosis and treatment of malignant tumors. In this study we isolated RNA from cell-free urine in an attempt to characterize miRNA profiles indicating the presence of urothelial carcinoma and its potential use as a non-invasive assay to identify patients with cancer progression. Methods: Urine was collected from patients diagnosed with bladder cancer and control patients with no history of cancer under an IRB-approved protocol. Urine was centrifuged and total RNA was isolated from the supernatants using the mirVana Paris™ kit. A total of 178 samples were grouped according to grade and stage (healthy controls (35), TaG1 (19), T1G3 (16), ≥T2 (30), carcinoma in situ (CIS; 28) and no evidence of disease following therapy (50). Seven hundred and thirty miRNAs were profiled by qRT-PCR on pooled samples within each group. Validation of selected miRNAs was performed on individual samples using qRT-PCR. Results: Cell-free RNA was isolated from urine of 35 healthy controls and 143 patients with bladder cancer. Of the 730 miRNAs tested, 236 were detected in at least one of the pooled samples using a Ct cutoff of 35. The number of miRNAs detected in the pooled samples correlated with disease progression where the healthy control group and the ≥T2 group expressed 8 and 228 miRNAs, respectively. qRT-PCR of individual samples revealed a gradual increase of some miRNAs with disease progression. Statistical analysis adjusted for multiple comparisons demonstrated differences between groups based on miRNA expression levels. In addition, a panel of miRNAs was identified which discriminated between cancer and cancer-free patients. Conclusion: This study demonstrates the successful isolation of miRNAs from cell-free urine. Utilizing non-invasive urine based assays, we identified a miRNA panel that can discriminate between cancer-free patients and patients with urinary carcinoma of the bladder. These findings provide evidence that profiling of miRNAs from cell-free urine holds the promise for the development of valuable clinical tools. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1161. doi:10.1158/1538-7445.AM2011-1161