Gain of Chromosome 5q Predicts a Favorable Prognosis in Localized Renal Cell Carcinoma.

Approximately 65% of renal cell carcinomas (RCC) are diagnosed at a localized stage. We investigated the chromosome 5q gain impact on disease-free survival (DFS) in RCC patients. Overall, 676 patients with stages 1-2 RCC and having cytogenetic analysis were included. Gain of 5q was observed in 108 patients, more frequently in clear cell (ccRCC) than non-clear cell tumors. Gain of 5q is likely an independent prognostic factor since the concerned patients had a decreased recurrence risk in stages 1-2 RCC, confirmed in multivariable analysis. Detecting 5q gain could enhance recurrence risk assessment, allowing tailored post-surgery surveillance, and reducing unnecessary treatments.

The association between N-methylnaltrexone, a peripherally acting mu-opioid receptor antagonist, and clinical outcomes in patients undergoing robotic-assisted radical cystectomy.

PURPOSE: To assess the impact of N-methylnaltrexone, a peripherally acting mu-opioid receptor antagonist, on the post-operative recovery of patients undergoing robotic-assisted radical cystectomy for bladder cancer. METHODS: We retrospectively reviewed patients undergoing robotic-assisted radical cystectomy by a single surgeon (KC) prior to (control group) and after (treatment group) the routine use of N-methylnaltrexone. Kaplan-Meier curves and the log-rank test were used to quantify time to flatus, bowel movement, and discharge. Daily mean opioid use, daily pain assessment rating, and episodes of severe pain (7-10/10) were compared. Gastrointestinal-related complications, including ileus, emesis, and/or need for post-op nasogastric tube placement, and 30-day readmissions were also compared between groups. Charge capture data were compared between groups to analyze cost impact. RESULTS: 29 patients each in the control and treatment group met inclusion criteria. Patients receiving N-methylnaltrexone had reduced length of stay compared with no N-methylnaltrexone (median 4 vs. 7 days, p < 0.01). Time to flatus and bowel movement, however, were similar. In a multivariable analysis controlling for possible confounders, however, the improvement in length of stay associated with N-methylnaltrexone use did not reach statistical significance (p = 0.11). Episodes of severe pain and composite gastrointestinal-related complications were reduced in the N-methylnaltrexone group (44.8% vs. 10.3%, p < 0.01). The reduction in length of stay was associated with approximately $10,500 in cost savings per patient. CONCLUSIONS: In this study, N-methylnaltrexone was associated with reduced length of stay, fewer episodes of severe pain, and reduced costs. These results provide the impetus for further study.

Melanoma-associated antigen-A and programmed death-ligand 1 expression are associated with advanced urothelial carcinoma.

BACKGROUND: Melanoma-associated antigen-A (MAGE-A) and programmed-death ligand 1 (PD-L1) are present in urothelial carcinoma (UC). We assessed survival outcomes in patients with MAGE-A and PD-L1 expression. METHODS: MAGE-A and PD-L1 expression on neoplastic cells was analyzed using tissue microarrays from patients with UC. We compared differential expression between disease stage and grade. MAGE-A and PD-L1 co-expression was subcategorized. Fisher's exact test was done for categorical variables followed by univariable and multivariable analysis of recurrence-free survival (RFS) and progression-free survival (PFS). RESULTS: Co-expression of MAGE+/PD-L1+ was higher in advanced disease; however, only MAGE+/PD-L1- was associated with shorter RFS [hazard ratio (HR) 1.89; 95% confidence interval (CI) 1.19-2.99; p = .006]. MAGE+/PD-L1+ was associated with the worst PFS (HR 17.1; 95% CI 5.96-49.4; p ≤ .001). MAGE-A expression was more prevalent with high-grade (p = .015), and higher-stage ≥ pT2 (p = .001) disease. The 5-year RFS was 44% for MAGE+ versus 58% for MAGE- patients. On multivariable analysis, MAGE+ was also associated with shorter RFS (HR 1.55; 95% CI 1.05-2.30; p = .03). Similarly, MAGE+ was associated with shorter PFS (HR 3.12; 95% CI 1.12-8.68; p = .03). CONCLUSION: MAGE-A and PD-L1 expression is increased in advanced disease and associated with shorter PFS. Furthermore, MAGE-A expression was significantly associated with higher-grade and -stage disease and associated with shorter RFS and PFS. The worse prognosis associated with MAGE-A+/PD-L1+ provides evidence that a combinatorial treatment strategy co-targeting MAGE/PD-L1 might be feasible. Further studies are needed to validate these findings.

PI-RADS Version 2 Category on 3 Tesla Multiparametric Prostate Magnetic Resonance Imaging Predicts Oncologic Outcomes in Gleason 3 + 4 Prostate Cancer on Biopsy.

PURPOSE: Three Tesla multiparametric magnetic resonance imaging with PI-RADS™ (Prostate Imaging Reporting and Data System) version 2 scoring is a common tool in prostate cancer diagnosis which informs the likelihood of a cancerous lesion. We investigated whether PI-RADS version 2 also predicts adverse pathology features mainly in patients with biopsy Gleason score 3 + 4 disease. MATERIALS AND METHODS: We reviewed the records of 326 consecutive men with a preoperative template and/or magnetic resonance imaging-ultrasound fusion biopsy Gleason score of 6-7 from a prospectively maintained database of men who underwent robotic radical prostatectomy. The primary analysis was done in patients with biopsy Gleason score 3 + 4 to assess the primary outcome of adverse pathology features on univariate and multivariate logistic regression. The secondary outcome was biochemical recurrence-free survival using the Kaplan-Meier method. Similar analysis was done in patients with a biopsy Gleason score of 6-7. RESULTS: Of men with Gleason score 3 + 4 findings 27%, 15%, 36% and 23% showed a PI-RADS version 2 score of 0-2, 3, 4 and 5, respectively. On univariate analysis PI-RADS version 2 category 5 predicted adverse pathology features vs categories 0-2 (OR 10.7, 95% CI 3.7-31, p ≤0.001). On multivariate analysis the PI-RADS version 2 category 5 was associated with adverse pathology when adjusting for preoperative magnetic resonance imaging targeted biopsy (OR 11.4, 95% CI 3.7-35, p ≤0.0001). In men with a targeted biopsy Gleason score of 3 + 4 prostate cancer PI-RADS version 2 category 5 was associated with adverse pathology (OR 14.7, 95% CI 1.5-146.9, p = 0.02). Of men with biopsy Gleason score 3 + 4 disease 92% and 58% with a PI-RADS version 2 score of 4 and 5, respectively, had 2-year biochemical recurrence-free survival. CONCLUSIONS: A PI-RADS version 2 category 5 lesion in patients with a biopsy Gleason score 3 + 4 lesion predicted adverse pathology features and biochemical recurrence-free survival. These findings suggest that preoperative 3 Tesla multiparametric magnetic resonance imaging may serve as a prognostic marker of treatment outcomes independently of biopsy Gleason score or biopsy type.

PI-RADS Version 2 Category on 3 Tesla Multiparametric Prostate Magnetic Resonance Imaging Predicts Oncologic Outcomes in Gleason 3 + 4 Prostate Cancer on Biopsy.

PURPOSE: Three Tesla multiparametric magnetic resonance imaging with PI-RADS™ (Prostate Imaging Reporting and Data System) version 2 scoring is a common tool in prostate cancer diagnosis which informs the likelihood of a cancerous lesion. We investigated whether PI-RADS version 2 also predicts adverse pathology features mainly in patients with biopsy Gleason score 3 + 4 disease. MATERIALS AND METHODS: We reviewed the records of 326 consecutive men with a preoperative template and/or magnetic resonance imaging-ultrasound fusion biopsy Gleason score of 6-7 from a prospectively maintained database of men who underwent robotic radical prostatectomy. The primary analysis was done in patients with biopsy Gleason score 3 + 4 to assess the primary outcome of adverse pathology features on univariate and multivariate logistic regression. The secondary outcome was biochemical recurrence-free survival using the Kaplan-Meier method. Similar analysis was done in patients with a biopsy Gleason score of 6-7. RESULTS: Of men with Gleason score 3 + 4 findings 27%, 15%, 36% and 23% showed a PI-RADS version 2 score of 0-2, 3, 4 and 5, respectively. On univariate analysis PI-RADS version 2 category 5 predicted adverse pathology features vs categories 0-2 (OR 10.7, 95% CI 3.7-31, p ≤0.001). On multivariate analysis the PI-RADS version 2 category 5 was associated with adverse pathology when adjusting for preoperative magnetic resonance imaging targeted biopsy (OR 11.4, 95% CI 3.7-35, p ≤0.0001). In men with a targeted biopsy Gleason score of 3 + 4 prostate cancer PI-RADS version 2 category 5 was associated with adverse pathology (OR 14.7, 95% CI 1.5-146.9, p = 0.02). Of men with biopsy Gleason score 3 + 4 disease 92% and 58% with a PI-RADS version 2 score of 4 and 5, respectively, had 2-year biochemical recurrence-free survival. CONCLUSIONS: A PI-RADS version 2 category 5 lesion in patients with a biopsy Gleason score 3 + 4 lesion predicted adverse pathology features and biochemical recurrence-free survival. These findings suggest that preoperative 3 Tesla multiparametric magnetic resonance imaging may serve as a prognostic marker of treatment outcomes independently of biopsy Gleason score or biopsy type.

Diagnostic biomarkers in non-muscle invasive bladder cancer.

Successful treatment of non-muscle invasive bladder cancer (NMIBC) relies heavily on our ability to accurately detect disease typically in the presence of hematuria as well as to detect the early recurrent tumors in patients with a history of NMIBC. Unfortunately, the current biomarker landscape for NMIBC is a work in progress. Cystoscopy continues to be the gold standard, but can still miss 10% of tumors. Therefore, physicians frequently use additional tools to aid in the diagnosis of bladder cancer, such as urinary cytology. The urinary cytology is a good option for high-grade disease; however, it is limited by low sensitivity in detecting low-grade disease, as well as variable interpretation among cytopathologists. Thus, the limitations of cystoscopy and urinary cytology have brought to light the need for more robust diagnostic assays. In this non-systematic review, we discuss the performance, potential advantages or disadvantages of these tests, and the future direction of biomarkers in NMIBC.

Treatment utilization and overall survival in patients receiving radical nephroureterectomy versus endoscopic management for upper tract urothelial carcinoma: evaluation of updated treatment guidelines.

PURPOSE: While radical nephroureterectomy (RNU) is the gold standard treatment for upper tract urothelial carcinoma (UTUC), select patients may benefit from endoscopic treatment (ET). European Association of Urology guidelines recommend ET for patients with low-risk (LR) disease: unifocal, < 2 cm, low-grade lesions without local invasion. To inform the utility of ET, we compare the overall survival (OS) of patients receiving ET and RNU using current and previous guidelines of LR disease. MATERIALS AND METHODS: Patients with non-metastatic, cT1 or less UTUC diagnosed in 2004-2012 were collected from the National Cancer Database. OS was analyzed with inverse probability of treatment weighted Cox proportional hazard regression. Analyses were conducted for LR disease under updated (size < 2 cm) and previous guidelines (size < 1 cm). RESULTS: Patients who were older, healthier, and treated at an academic facility had higher odds of receiving ET. In 851 identified patients with LR disease, RNU was associated with increased OS compared with ET (p = 0.006); however, there was no difference between ET and RNU (p = 0.79, n = 202) under the previous guidelines (size < 1 cm). In, otherwise, LR patients, the largest tumor size with no difference between ET and RNU was ≤ 1.5 cm (p = 0.07). CONCLUSIONS: RNU is associated with improved survival when compared with ET in the management of LR UTUC using current guidelines with a size threshold of < 2 cm. In appropriately selected LR patients, we find no difference between RNU and ET up to a tumor size of ≤ 1.5 cm. However, in the absence of prospective studies, the usage of ET is best left up to clinician discretion.

Comparative effectiveness of radical prostatectomy with adjuvant radiotherapy versus radiotherapy plus androgen deprivation therapy for men with advanced prostate cancer.

BACKGROUND: Men with locally advanced prostate cancer (LAPCa) or regionally advanced prostate cancer (RAPCa) are at high risk for death from their disease. Clinical guidelines support multimodal approaches, which include radical prostatectomy (RP) followed by radiotherapy (XRT) and XRT plus androgen deprivation therapy (ADT). However, there are limited data comparing these substantially different treatment approaches. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, this study compared survival outcomes and adverse effects associated with RP plus XRT versus XRT plus ADT in these men. METHODS: SEER-Medicare data were queried for men with cT3-T4N0M0 (LAPCa) or cT3-T4N1M0 (RAPCa) prostate cancer. Propensity score methods were used to balance cohort characteristics between the treatment arms. Survival analyses were analyzed with the Kaplan-Meier method and Cox proportional hazards models. RESULTS: From 1992 to 2009, 13,856 men (≥65 years old) were diagnosed with LAPCa or RAPCa: 6.1% received RP plus XRT, and 23.6% received XRT plus ADT. At a median follow-up of 14.6 years, there were 2189 deaths in the cohort, of which 702 were secondary to prostate cancer. Regardless of the tumor stage or the Gleason score, the adjusted 10-year prostate cancer-specific survival and 10-year overall survival favored men who underwent RP plus XRT over men who underwent XRT plus ADT. However, RP plus XRT versus XRT plus ADT was associated with higher rates of erectile dysfunction (28% vs 20%; P = .0212) and urinary incontinence (49% vs 19%; P < .001). CONCLUSIONS: Men with LAPCa or RAPCa treated initially with RP plus XRT had a lower risk of prostate cancer-specific death and improved overall survival in comparison with those men treated with XRT plus ADT, but they experienced higher rates of erectile dysfunction and urinary incontinence.

Adjuvant Therapy for High Risk Localized Kidney Cancer: Emerging Evidence and Future Clinical Trials.

PURPOSE: We reviewed the literature on adjuvant therapies for patients with high risk localized kidney cancer following surgical resection. In this analysis we merge 2 recently published prospective trials with conflicting results within the context of their respective designs. In addition, we spotlight upcoming trials that use novel immunotherapy based checkpoint inhibitors and have the potential to establish a new standard of care. MATERIALS AND METHODS: We searched PubMed® for English language articles published through January 2017 using the keywords "renal cell carcinoma," "kidney cancer," "immunotherapy," "targeted therapy" and "adjuvant therapy." ClinicalTrials.gov was queried for ongoing studies. Relevant data recently presented at major urology and medical oncology meetings are also included. RESULTS: Adjuvant therapies for high risk localized kidney cancer can be grouped into the categories of 1) traditional immunotherapy, 2) inhibitors of the vascular endothelial growth factor and mTOR (mammalian target of rapamycin) pathways, 3) vaccines and antibody dependent cytotoxic agents, and 4) immune checkpoint inhibitors. Several trials of traditional immunotherapy, such as interferon-α and high dose interleukin-2, failed to demonstrate benefit as adjuvant treatment and were associated with significant adverse events. Vascular endothelial growth factor and mTOR inhibitors have less severe toxicity in metastatic disease and, therefore, are natural considerations for adjuvant trials. However, current data are conflicting. The ASSURE (Sunitinib Malate or Sorafenib Tosylate in Treating Patients with Kidney Cancer that was Removed by Surgery, NCT00326898) trial found no recurrence-free survival benefit of sorafenib or sunitinib over placebo, while S-TRAC (Clinical Trial Comparing Efficacy and Safety of Sunitinib versus Placebo for the Treatment of Patients at High Risk of Recurrent Renal Cell Cancer, NCT00375674) revealed that 1 year of sunitinib improved recurrence-free survival by 1.2 years. Vaccine based treatments and antibody dependent cytotoxic agents have had mixed results. New trials evaluating immune checkpoint inhibitors are planned, given the impressive efficacy and tolerability as second line agents in metastatic disease. Future adjuvant trials are likely to be guided by molecular signatures to treat patients most likely to benefit. CONCLUSIONS: Based on the available data, there appears to be no role for traditional immunotherapy as adjuvant treatment in patients with high risk localized kidney cancer following surgical resection. S-TRAC provides evidence that 1 year of adjuvant sunitinib in patients with higher risk locoregional disease increases the median time to recurrence. However, the data on overall survival are immature and adverse effects are common. Results from trials investigating immune checkpoint inhibitors are highly anticipated.

Overall survival in patients with residual disease after radical cystectomy and neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been shown to improve survival in patients with urothelial carcinoma (UC). However, there are a subset of patients who do not respond or progress despite systemic treatment. METHODS: Data from the National Cancer Database on patients who underwent a radical cystectomy (RC) with or without NAC from 2006 to 2013 were abstracted. Covariates were balanced using inverse probability weighting methods. The primary outcome of overall survival in patients with residual disease by stage was evaluated using 90-day conditional landmark analysis and Cox proportional hazards modeling. Secondary outcome of predictors of residual disease was evaluated using multivariable logistic regression analysis. RESULTS: A total of 20,128 patients met our inclusion criteria; 16,058 patients underwent RC only (80%) and 4070 underwent RC with NAC (20%). Patients who received NAC were younger and healthier, treated at an academic center, and presented with higher stage. NAC was associated with improved overall survival amongst patients with cT3-4aN0 (HR 0.84 95% CI 0.73-0.97; p = 0.02) and cN+ (HR 0.70, 95% CI 0.58-0.86; p = 0.001). Predictors of no residual disease were NAC (OR 0.17, 95% CI 0.14-0.21; p < 0.001) and treatment at an academic facility (OR 0.47, 95% CI 0.37-0.60; p < 0.001). Patients with cT3-4a or cN+ had increased odds of having residual UC (OR 2.01, 95% CI 1.53-2.64; p < 0.001, and OR 2.14, 95% CI 1.43-3.21; p < 0.001, respectively) compared with cT2. CONCLUSION: In patients with residual UC, NAC is associated with a significant survival benefit in higher stage disease only. Furthermore, those treated with NAC or at an academic center were less likely to have residual disease. Given the toxicity of NAC, more prudent patient selection for NAC is warranted and requires further study.

Trends in urinary diversion after radical cystectomy for urothelial carcinoma.

PURPOSE: To assess how trends in urinary diversion (UD) type following radical cystectomy (RC) have changed in recent years and investigate pre-operative predictors of UD type. METHODS: Data were abstracted from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) from 2011 to 2015. We quantified the percentages of continent diversions (CD) versus incontinent diversions (ID) completed over this time frame. Using univariate and multivariable logistic regression analyses, we compared UD type across year of operation as well as predictors of type of diversion. RESULTS: We identified 4790 patients in the cohort, of which 81% underwent an incontinent diversion. Patients undergoing incontinent diversions were older (p < 0.001), more likely to be female (p < 0.001), had higher American Society of Anesthesiologists (ASA) classification (p < 0.001) and had more comorbidities with worse preoperative lab values. On multivariable analysis, the odds of incontinent diversion increased per year (OR 1.16, 95% CI 1.06-1.26; p = 0.001). Neoadjuvant chemotherapy (NAC) was associated with lower odds of receiving an ID (OR 0.33, 95% CI 0.17-0.64; p = 0.001). Being male, healthy and young were associated with higher odds of CD. CONCLUSION: We demonstrate that there has been a decrease in continent diversion use in recent years. Neoadjuvant chemotherapy, proxies of life expectancy and gender are significant predictors of continent diversion. Further investigation to determine the underlying cause of decreased utilization of CD is warranted.

Intracrine androgen biosynthesis in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is one of the most lethal genitourinary cancers. The presence of androgen receptor (AR) in RCC has recently been shown to be associated with higher tumour stage irrespective of gender. Because the clinical context of androgens in female RCC patients is similar to that of prostate cancer patients undergoing androgen-deprivation therapy, mechanisms underlying the emergence of castration-resistant prostate cancer (CRPC) may be at play in AR-positive RCC cells. Therefore, we hypothesized that AR-positive RCC has intratumoral steroidogenesis and that anti-androgen therapy may result in tumour suppression. METHODS: Mice were injected with an AR-positive RCC cell line. When tumours became palpable, surgical castration was performed and tumour volume was measured. Using ELISA, the levels of intracellular testosterone and dihydrotesterone were measured in AR-positive human RCC cell lines. Lastly, male mice containing xenografts were treated with enzalutamide or abiraterone acetate (AA) for 3 weeks to measure tumour volume. RESULTS: We first observed in vivo that castration retards the growth of AR-positive RCC tumour xenograft in mice. Next, AR-positive human RCC cell lines and tissues were found to have elevated levels of testosterone and dihydrotestosterone and express key enzymes required for intracellular androgen biosynthesis. A mouse xenograft study with AR-positive RCC cell line using the commonly used anti-androgen therapies showed significant tumour suppression (P<0.01). CONCLUSIONS: Intracrine androgen biosynthesis is a potential source of androgen in AR-positive RCC and that the androgen signaling axis is a potential target of intervention in RCC.

Adrenalectomy for benign and malignant disease: utilization and outcomes by surgeon specialty and surgical approach from 2003-2013.

INTRODUCTION: Data on the utilization of open, laparoscopic and robotic adrenalectomy on a national level is limited. MATERIALS AND METHODS: Data on patients who underwent open, laparoscopic, or robotic adrenalectomy for benign or malignant disease in the US from 2003-2013 were extracted using ICD-9 codes from the Premier Hospital Database. Surgeon specialty, patient demographics, hospital characteristics, and complications were compared. Data were analyzed using univariate and multivariable logistic regression analyses. RESULTS: A total of 8,831 adrenalectomies were performed for benign and malignant tumors. There was no significant difference in rate of adrenalectomy with regards to comorbidities, insurance status, or hospital characteristics. Non-urologists performed adrenalectomy more often for both benign (57% versus 43%; p = 0.011) and malignant disease (66% versus 34%; p = 0.011). Across all indications, non-urologists performed open surgery most often followed by laparoscopic and robotic approaches (56.3% versus 37.4% versus 6.4%, respectively), compared to urologists (48.8% versus 38.4% versus 12.9%, respectively). Overall, urologists were more likely to use laparoscopic or robotic approaches (p = 0.001). There was no difference in complication rates or operative times between surgical specialties or by surgeon/hospital case volume. On multivariable regression analysis, the best predictor of major complication was a Charlson Comorbidity Index (CCI) ≥ 2 (OR 3.9, 95%CI 2.1-7.1; p = < 0.001). Compared to open surgery, laparoscopy had significantly reduced odds of major complication (OR 0.6, 95%CI 0.3-0.9; p = 0.03). Patients undergoing robotic procedures had the shortest length of stay. CONCLUSION: In this retrospective study, adrenalectomy was more commonly performed by non-urologists via an open approach. Patients with CCI ≥ 2 were more likely to have postoperative complications while surgeon volume, hospital volume, and surgical approach did not influence complication rates.

Female Urethral Reconstruction.

PURPOSE: Female urethral reconstruction can be used successfully to treat a heterogeneous group of urethral disorders through an expanding number of unique approaches. Understanding the diverse etiologies of female urethral stricture and loss is essential in evaluating and diagnosing patients. Although there is an appreciable body of literature addressing female urethral reconstruction individually, there is a paucity of resources that approach this issue holistically. We discuss the relevant female urethral anatomy, pathophysiology, diagnosis and evaluation of female urethral disorders, and current reconstructive techniques, as well as published outcomes data and potential future directions for female urethral reconstruction. MATERIALS AND METHODS: We reviewed articles published in English and indexed in the PubMed®, Embase® and Google Scholar™ databases, and consulted textbooks. Key search terms used were female, urethra, urethral reconstruction, urethroplasty, pathology, stricture, vaginal flap, bladder flap, graft, dilation, pubovaginal sling, catheterization, imaging, tissue engineering and bioscaffold. We created a synopsis of relevant articles, including original research studies and reviews. RESULTS: Urethral tissue loss and strictures are caused by traumatic injuries, iatrogenic injuries and, rarely, infections and malignancies. A comprehensive patient history and physical examination are critical for diagnosis. Flexible cystoscopy, voiding cystourethrography and endovaginal magnetic resonance imaging can help to determine the surgical method of repair. Minimally invasive approaches to female urethral reconstruction are associated with poor outcomes. Definitive treatment options for repair of female urethral stricture include vaginal flap/wall urethroplasty, graft urethroplasty and distal urethrectomy with advancement meatoplasty. Repair techniques for urethral loss include primary closure, vaginal flap/wall urethroplasty and bladder flap urethroplasty. Vaginal flap approaches with well vascularized grafts and buccal mucosal grafts have high success rates. Tissue engineered grafts are being investigated as a novel treatment modality. CONCLUSIONS: Female urethral reconstruction is complex, and one must carefully evaluate patients afflicted with urethral disorders. Urethral stricture and urethral loss have different etiologies. Variations of a standard approach might best address the condition of an individual patient. Long-term outcomes data are not available for contemporary techniques of female urethral reconstruction. The highest success rates have been reported with vaginal flap and buccal mucosal graft urethroplasty. Further studies focusing on newer reconstruction techniques and long-term outcomes are warranted.

Off-Target Effect of Sildenafil on Postsurgical Erectile Dysfunction: Alternate Pathways and Localized Delivery System.

INTRODUCTION: There is no consensus on the best oral phosphodiesterase type 5 inhibitor (PDE5I) for patients undergoing penile rehabilitation after surgical nerve injury. AIM: To determine the mechanism of PDE5I on cultured neuronal cells and the effectiveness of local drug delivery using nanospheres (NSPs) to sites of nerve injury in a rat model of bilateral cavernous nerve injury (BCNI). METHODS: The effects of sildenafil, tadalafil, and vardenafil on cyclic adenosine monophosphate, cyclic guanosine monophosphate, and cell survival after exposure to hypoxia and H2O2 were measured in PC12, SH-SY5Y, and NTERA-2 (NT2) cell cultures. The effects of phosphodiesterase type 4 inhibitor (PDE4I) and PDE5I on neuronal cell survival were evaluated. Male rats underwent BCNI and were untreated (BCNI), immediately treated with application of empty NSPs (BCNI + NSP), NSPs containing sildenafil (Sild + NSP), or NSPs containing rolipram (Rol + NSP). MAIN OUTCOME MEASURES: Viability of neuronal cells was measured. Intracavernous pressure changes after cavernous nerve electrostimulation and expression of neurofilament, nitric oxide synthase, and actin in mid-shaft of penis were analyzed 14 days after injury. RESULTS: Sildenafil and rolipram significantly decreased cell death after exposure to H2O2 and hypoxia in PC12, SH-SY5Y, and NT2 cells. PC12 cells did not express PDE5 and knockdown of PDE4 significantly increased cell viability in PC12, SH-SY5Y, and NT2 cells exposed to hypoxia. The ratio of intracavernous pressure to mean arterial pressure and expression of penile neurofilament, nitric oxide synthase, and actin were significantly higher in the Sild + NSP and Rol + NSP groups than in the BCNI and BCNI + NSP groups. Limitations included analysis in only two PDE families using only a single dose. CONCLUSION: Sildenafil showed the most profound neuroprotective effect compared with tadalafil and vardenafil. Sildenafil- or rolipram-loaded NSP delivery to the site of nerve injury prevented erectile dysfunction and led to increased neurofilament, nitric oxide synthase, smooth muscle content in rat penile tissue after BCNI.

Bullying has a potential role in pediatric lower urinary tract symptoms.

PURPOSE: National statistics estimate that a quarter of American school children are regularly bullied, making this issue the main parental concern and the leading form of school violence. To our knowledge no study in the literature has examined the association of bullying with lower urinary tract symptoms. We evaluated the relationship between being bullied and lower urinary tract symptoms in the pediatric population. MATERIALS AND METHODS: We accrued 100 patients from a pediatric urology practice in prospective case-control fashion. The degree of lower urinary tract symptoms was determined by the voiding severity score obtained by a single pediatric urologist. Using the Peer Relations Questionnaire and a thermometer scale we surveyed participants for evidence of victimization from bullying and school related anxiety. We then correlated voiding symptom severity with the degree of bullying. RESULTS: After applying our study exclusion criteria we examined and analyzed data on 38 control children without lower urinary tract symptoms and on 38 children with lower urinary tract symptoms. Mean age was similar in the 2 groups. There were more females in the group with lower urinary tract symptoms (22 vs 13). Mean case voiding severity score was 3.82 (range 2 to 5). As measured by Bullied Index Score the degree of being bullied was significantly higher in the case group (4.76 vs 1.95, p <0.001), as was the anxiety level estimated by the thermometer score (3.68 vs 0.97, p <0.001). We also found that physical forms of bullying accounted for worse voiding severity scores (4.56 vs 3.67, p <0.01). CONCLUSIONS: To our knowledge our study is the first to show that 1) bullying is significantly associated with pediatric lower urinary tract symptoms and 2) physical forms of bullying accompany worsened symptoms.

Oncologic outcomes in men with metastasis to the prostatic anterior fat pad lymph nodes: a multi-institution international study.

BACKGROUND: The presence of lymph nodes (LN) within the prostatic anterior fat pad (PAFP) has been reported in several recent reports. These PAFP LNs rarely harbor metastatic disease, and the characteristics of patients with PAFP LN metastasis are not well-described in the literature. Our previous study suggested that metastatic disease to the PAFP LN was associated with less severe oncologic outcomes than those that involve the pelvic lymph node (PLN). Therefore, the objective of this study is to assess the oncologic outcome of prostate cancer (PCa) patients with PAFP LN metastasis in a larger patient population. METHODS: Data were analyzed on 8800 patients from eleven international centers in three countries. Eighty-eight patients were found to have metastatic disease to the PAFP LNs (PAFP+) and 206 men had isolated metastasis to the pelvic LNs (PLN+). Clinicopathologic features were compared using ANOVA and Chi square tests. The Kaplan-Meier method was used to calculate the time to biochemical recurrence (BCR). RESULTS: Of the eighty-eight patients with PAFP LN metastasis, sixty-three (71.6%) were up-staged based on the pathologic analysis of PAFP and eight (9.1%) had a low-risk disease. Patients with LNs present in the PAFP had a higher incidence of biopsy Gleason score (GS) 8-10, pathologic N1 disease, and positive surgical margin in prostatectomy specimens than those with no LNs detected in the PAFP. Men who were PAFP+ with or without PLN involvement had more aggressive pathologic features than those with PLN disease only. However, there was no significant difference in BCR-free survival regardless of adjuvant therapy. In 300 patients who underwent PAFP LN mapping, 65 LNs were detected. It was also found that 44 out of 65 (67.7%) nodes were located in the middle portion of the PAFP. CONCLUSIONS: There was no significant difference in the rate of BCR between the PAFP LN+ and PLN+ groups. The PAFP likely represents a landing zone that is different from the PLNs for PCa metastasis. Therefore, the removal and pathologic analysis of PAFP should be adopted as a standard procedure in all patients undergoing radical prostatectomy.

Large cell differentiation of metastatic prostate cancer after androgen deprivation therapy.

We present a case of a 75-year-old male with a history of high risk prostate cancer who underwent androgen deprivation therapy and palliative radiation treatments for his disease. Subsequently, he presented with gross hematuria and severe lower urinary tract symptoms. A palliative transurethral resection of the prostate (TURP) at that time, demonstrated large cell differentiated neuroendocrine carcinoma with metastasis to the lung. We review the limited literature on this rare form of disease and present current treatment strategies.

Performance of partial cystectomy in the United States from 2001 to 2010: trends and comparative outcomes.

INTRODUCTION: To investigate the trends in the performance of radical cystectomy (RC) versus partial cystectomy (PC) in the United States over the past 10 years and compare postoperative outcomes between two procedures. MATERIALS AND METHODS: The data was captured from the Nationwide Inpatient Sample (NIS) 2001-2010 using the appropriate ICD-9-CM diagnosis and procedure codes. Patient sociodemographics, comorbidities and in-hospital complications after PC and RC were compared, taking into account some hospital characteristics. A chi-square analysis including a Cochran-Armitage trend test and a multivariable logistic regression analysis were employed. RESULTS: RC rate increased from 84.8% in 2001 to 90.3% in 2010, while PC decreased from 15.2% to 9.7% (p < 0.0001). PC patients were older than their RC counterparts (72.1 ± 11.3 versus 68.6 ± 10.1 years; p < 0.0001), had higher prevalence of major comorbidities, but decreased rate of postoperative complications overall (21.3% versus 38.6%; p < 0.001). The greatest rates of PC utilization were found in the Northeast and South (12.8% and 12.7%). The frequency of PC was 18.9% in non-teaching hospitals compared to 9.0% in teaching hospitals (p < 0.0001). In multivariate analysis, females, octogenarians, patients with hypertension and obesity, and patients in non-teaching and rural hospitals were more likely to receive PC. CONCLUSIONS: Despite the potential advantages in cancer control offered by RC, PC is being performed more frequently on the elderly, female patients, patients with hypertension and obesity, in non-teaching and rural hospitals, and in certain United States geographic regions, which can be partially explained by disparities in access to high volume cancer centers.