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To determine the effectiveness of 2 different continuous quality improvement interventions in an integrated community urology practice. We specifically assessed the impact of audited physician feedback on improving physicians' adoption of active surveillance for low-risk prostate cancer (CaP) and adherence to a prostate biopsy time-out intervention.The electronic medical records of Genesis Healthcare Partners were analyzed between August 24, 2011 and September 30, 2020 to evaluate the performance of 2 quality interventions: audited physician feedback to improve active surveillance adoption in low-risk CaP patients, and audited physician feedback to promote adherence to an electronic medical records embedded prostate biopsy time-out template. Physician and Genesis Healthcare Partners group adherence to each quality initiative was compared before and after each intervention type using ANOVA testing.For active surveillance, we consistently saw an increase in active surveillance adoption for low risk CaP patients in association with continuous audited feedback (P.001). Adherence to the prostate biopsy time-out template improved when audited feedback was provided (P.001).The implementation of clinical guidelines into routine clinical practice remains challenging and poses an obstacle to the improvement of United States healthcare quality. Continuous quality improvement should be a dynamic process, and in our experience, audited feedback coupled with education is most effective.

560 Background: Active Wnt signaling via WNT5A through ROR1 and its partner, ROR2, or WNT5A/frizzled 2 (FZD2) is linked to processes driving tumorigenesis, disease progression and therapy resistance. The role of this pathway in the pathogenesis of urothelial carcinoma (UC) is not fully elucidated. In adult tissue, ROR1 is largely absent, which makes it ideal for targeted therapies, with several ROR1 targeting agents in early clinical development. We utilized a large dataset of molecularly characterized UC tumors to investigate the significance of Wnt5a/ ROR1, ROR2 or FZD2 transcriptional expression. Methods: NextGen Sequencing of DNA (592 genes or WES)/RNA (WTS) was performed for 4743 UC tumors submitted to Caris Life Sciences (Phoenix, AZ). PD-L1 expression (SP142; Positive (+): ³2+, ³%5) was tested by IHC. Gene expression profiles were analyzed for a transcriptional signature predictive of response to immunotherapy (T cell-inflamed; Bao, 2020). WNT5a, ROR1, ROR2, and FZD2-high and -low expression were defined as ³ top and < bottom quartile of transcripts per million (TPM), respectively. Mann-Whitney U and X2/Fisher-Exact tests were applied where appropriate, with P-values adjusted for multiple comparisons ( q < .05). Real-world overall survival (OS) information was obtained from insurance claims data and Kaplan Meier estimates were calculated for molecularly defined cohorts. Results: We observed similar expression of these WNT5A signaling pathway genes between upper (N=795) and lower tract UC (N=3,204): WNT5A (22.7 v. 22.2 median TMP (mTPM), q = .18), FZD2 (3.4 v 3.5, q = .93), ROR1 (2.0 v. 1.7, q = .05), and ROR2 (2.1 v 2.5, q < .01). WNT family gene expression varied significantly between primary (N=2,756) and metastatic sites (N=1,361): WTN5A (25.2 v 16.8 mTPM), FZD2 (3.2 v 4.05), ROR1 (1.7 v 2.1), and ROR2 (2.4 v 2.6) for primary vs. metastatic sites respectively ( q < .05 for all). Comparison of high- and low-expression subgroups revealed variation in the prevalence of TP53, FGFR3 and RB1 mutations, as well as PDL1+ staining and T cell-inflamed scores (Table). High gene expression for ROR2 (HR 0.66, 95% CI 0.56-0.78, p < .001) and FZD2 (HR 0.75, 95% CI 0.63-0.89, p < .001) was associated with worse OS compared to low gene expression. No significant difference in OS was observed for WNT5A (HR 0.97, 95% CI 0.82-1.15, p < .76) and ROR1 (HR 0.86, 95% CI 0.72-1.01, p < .068). Conclusions: Distinct genomic and immune landscapes for the four investigated WNT pathway components were observed and should be leveraged to identify combination therapies that complement the current pipeline of WNT pathway-targeting drugs. [Table: see text]

457 Background: Plasma cell-free DNA (pcfDNA) has shown great promise for non-invasive, multi-cancer early detection (MCED), but has lower sensitivity for early-stage urological cancers due to low tumor fraction in plasma. Urine cfDNA (ucfDNA) has the potential to improve detection and monitoring of early-stage urological cancers due to its proximity to the affected organs and ease of collection. We conducted an exploratory study to assess the utility of methylation patterns in ucfDNA to detect BC in patients with suspicious bladder lesions, and compare to detection using matched pcfDNA. Methods: Urine and blood were collected from patients with suspicion of new (N=17) or recurrent (N=20) non-muscle invasive BC (NMIBC), and from non-cancer (NC) patients with urological conditions (N=16). Patients with suspicion of NMIBC were diagnosed and staged by transurethral resection of bladder tumor (TURBT) and conventional imaging. Tumor allele fraction (TAF) estimates from ucfDNA were inferred using a method trained on methylation patterns enriched in BC tissue (N=49) relative to an external reference dataset of NC ucfDNA (N=176). We set a detection threshold, using a maximum TAF value from a separate set of NC urine samples (N=50), to determine ucfDNA sensitivity for detecting BC in our study. Sensitivity in pcfDNA was determined using a validated MCED test classifier at 99% specificity. Results: Of 17 patients with suspicion of new NMIBC, 12 were diagnosed with BC after TURBT (Stage 0: N=6, I: N=5, II: N=1), and 10/12 were high grade (HG). Among patients with confirmed BC, ucfDNA sensitivity was 91.7% overall (11/12; 95% CI 61.5-99.8%) and 90% for HG (9/10). Whereas, pcfDNA sensitivity was 16.7% overall (2/12) and 10.0% for HG (1/10). Of 20 patients with suspicion of recurrent NMIBC, 14 were confirmed as BC (Stage 0: N=10, I: N=2, II: N=2) and 11/14 were HG. Sensitivity of ucfDNA for recurrence detection was 78.6% overall (11/14; 95% CI 49.2-95.3%), and 100% for HG (11/11), while pcfDNA sensitivity was 14.3% (2/14) overall and 18.2% (2/11) for HG. Notably, TAF in urine from NC patients (N=16) and patients with suspicion of new NMIBC found to be benign by TURBT (N=5) were all below the detection threshold. Among patients with suspicion of recurrent NMIBC but not found to have BC by TURBT, TAF estimates for 4/6 (66.7%) were above the detection threshold. Conclusions: We observed increased sensitivity in urine compared to matched plasma in patients with NMIBC, consistent with local shedding of bladder tumors into stored urine. A urine-based cfDNA assay with high sensitivity at high specificity, combined with non-invasive sampling, could be an ideal tool to use alongside the standard of care (e.g., cystoscopy) for clinical diagnosis and monitoring of BC. Further studies are needed to validate these findings and determine the clinical utility of ucfDNA in the diagnosis and surveillance of BC.

INTRODUCTION AND OBJECTIVE:Upper urinary tract urothelial carcinoma (UTUC) affects both men and women and accounts for approximately 5% of urothelial malignancies and 5 to 10% of renal cancers. Alt...

Multiparametric magnetic resonance imaging (mpMRI) has transformed the management of localized prostate cancer by improving identification of clinically significant disease at diagnosis. Approximately 20% of primary prostate tumors are invisible to mpMRI, and we hypothesize that this invisibility reflects fundamental molecular properties of the tumor. We therefore profiled the genomes and transcriptomes of 40 International Society of Urological Pathology grade 2 tumors: 20 mpMRI-invisible (Prostate Imaging-Reporting and Data System [PI-RADS] v2

Background: Despite extensive research to identify biomarkers of response in patients with non–muscle-invasive bladder cancer (NMIBC), there is no biomarker to date that can serve this purpose. Herein, we report how we leveraged serial urine samples to query a panel of cytokines at varying time points in an attempt to identify predictive biomarkers of response in NMIBC. Methods: Serial urine samples were collected from 50 patients with intermediate- or high-risk NMIBC enrolled in a phase II study, evaluating intravesical BCG ± intradermal HS-410 therapy. Samples were collected at baseline, week 7, week 13, week 28, and at end of treatment. A total of 105 cytokines were analyzed in each sample. To predict outcome of time-to-event (recurrence or progression), univariate and multivariable Cox analyses were performed. Results: Fifteen patients developed recurrence and 4 patients progressed during the follow-up period. Among clinicopathologic variables, ever-smoker versus nonsmoker status was associated with an improved response rate (HR 0.38; 95% confidence interval (CI), 0.14–0.99; P = 0.04). In the most clinically relevant model, the percent change (for 100 units) of IL18-binding protein-a (HR 1.995; 95% CI, 1.16–3.44; P = 0.01), IL23 (HR 1.12; 95% CI, 1.01–1.23; P = 0.03), IL8 (HR 0.27; 95% CI, 0.07–1.08; P = 0.06), and IFNγ-induced protein-10 (HR 0.95; 95% CI, 0.91–0.99; P = 0.04) at week 13 from baseline best predicted time to event. Conclusions: Urinary cytokines provided additional value to clinicopathologic features to predict response to immune-modulating agents in patients with NMIBC. Impact: This study serves as a hypothesis-generating report for future studies to evaluate the role of urine cytokines as a predictive biomarker of response to immune treatments.

Multiparametric magnetic resonance imaging and biopsy based molecular tests such as the 17-gene Oncotype DX® Genomic Prostate Score™ assay are increasingly performed to improve risk stratification in men with clinically localized prostate cancer. The prostate score assay was previously shown to be a significant independent predictor of adverse pathology findings at radical prostatectomy in men diagnosed by systematic biopsies only. Therefore, we investigated the ability of the prostate score assay to predict adverse pathology findings in the setting of magnetic resonance imaging guided prostate biopsy.We identified men diagnosed with NCCN® (National Comprehensive Cancer Network®) very low, low or intermediate risk prostate cancer who underwent simultaneous multiparametric magnetic resonance imaging fusion targeted and systematic prostate biopsy with subsequent radical prostatectomy within 6 months. Prostate score assay testing was performed on biopsy tissue with the highest Gleason score. The primary outcome of the study was adverse pathology findings, defined as Gleason score 4 + 3 or greater disease and/or pT3+ at radical prostatectomy. Independent predictors of adverse pathology findings were determined in a multivariable model to adjust for clinical parameters.A total of 134 men were eligible for primary analysis. On univariable analysis the UCLA score, magnetic resonance imaging, prostate score assay results and biopsy Gleason score were significant predictors of adverse pathology findings. After multivariable adjustment prostate score assay values remained a significant predictor of adverse pathology results (prostate score assay per 20 U OR 3.28, 95% CI 1.74-6.62, p0.001). A wide and overlapping distribution of prostate score assay results was seen across PI-RADS® (Prostate Imaging Reporting and Data System) version 2 scores.The prostate score assay result is an independent predictor of adverse pathology findings in patients who were diagnosed with very low, low or intermediate risk prostate cancer in the setting of multiparametric magnetic resonance imaging fusion prostate biopsy. This assay can be useful as an independent technology or an adjunct technology to multiparametric magnetic resonance imaging to individualize risk stratification of low and intermediate risk prostate cancer.

// Izak Faiena 1, * , Sinae Kim 2, 3, * , Nicholas Farber 1 , Young Suk Kwon 1 , Brian Shinder 1 , Neal Patel 1 , Amirali H. Salmasi 1 , Thomas Jang 1 , Eric A. Singer 1 , Wun-Jae Kim 4 and Isaac Y. Kim 1 1 Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey and Division of Urology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA 2 Department of Biostatistics, Rutgers School of Public Health, Piscataway, NJ, USA 3 Divison of Biometrics, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA 4 Department of Urology, Chungbuk National University College of Medicine, Cheonju, Korea * These authors have contributed equally to this work Correspondence to: Isaac Y. Kim, email: kimiy@cinj.rutgers.edu Keywords: prostate cancer, biomarkers, prostate acid phosphatase Received: July 29, 2017 Accepted: September 08, 2017 Published: September 28, 2017 ABSTRACT Previous studies have reported association of multiple preoperative factors predicting clinically significant prostate cancer with varying results. We assessed the predictive model using a combination of hormone profile, serum biomarkers, and patient characteristics in order to improve the accuracy of risk stratification of patients with prostate cancer. Data on 224 patients from our prostatectomy database were queried. Demographic characteristics, including age, body mass index (BMI), clinical stage, clinical Gleason score (GS) as well as serum biomarkers, such as prostate-specific antigen (PSA), parathyroid hormone (PTH), calcium (Ca), prostate acid phosphatase (PAP), testosterone, and chromogranin A (CgA), were used to build a predictive model of clinically significant prostate cancer using logistic regression methods. We assessed the utility and validity of prediction models using multiple 10-fold cross-validation. Bias-corrected area under the receiver operating characteristics (ROC) curve (bAUC) over 200 runs was reported as the predictive performance of the models. On univariate analyses, covariates most predictive of clinically significant prostate cancer were clinical GS (OR 5.8, 95% CI 3.1–10.8; P < 0.0001; bAUC = 0.635), total PSA (OR 1.1, 95% CI 1.06–1.2; P = 0.0003; bAUC = 0.656), PAP (OR 1.5, 95% CI 1.1–2.1; P = 0.016; bAUC = 0.583), and BMI (OR 1.064, 95% C.I. 0.998, 1.134; P < 0.056; bAUC = 0.575). On multivariate analyses, the most predictive model included the combination of preoperative PSA, prostate weight, clinical GS, BMI and PAP with bAUC 0.771 ([2.5, 97.5] percentiles = [0.76, 0.78]). Our model using preoperative PSA, clinical GS, BMI, PAP, and prostate weight may be a tool to identify individuals with adverse oncologic characteristics and classify patients according to their risk profiles.

Introduction The presence of extracapsular extension (ECE) in prostate cancer (PCa) can influence a surgeon's decision to perform a nerve-sparing approach during radical prostatectomy (RP). Preoperatively, multiparametric MRI (mp-MRI) is often used to stage PCa. More recently, the use of mp-MRI has gained wide acceptance in fusion biopsy of the prostate. In this framework, the reported accuracy of mp-MRI has been highly variable, with data often originating from large referral centers with experienced radiologists. We sought to determine the sensitivity and specificity of mp-MRI for detecting ECE in the community. Materials and Methods We reviewed a prospectively maintained database of men with PCa who had undergone RP. We recorded the prevalence of ECE at RP and determined the sensitivity, specificity, positive predictive value, and negative predictive value of MRI for detecting ECE. We assessed these values according to the D'Amico risk groups and compared the predictive value of MRI to that of the Partin tables. Results The prevalence of ECE was 11.5%, 28.1%, and 47.1% in the low-, intermediate, and high-risk groups, respectively, with an overall prevalence of 24.1%. The overall sensitivity, specificity, positive predictive value, and negative predictive value of MRI was 12.5%, 93.1%, 36.4%, and 77.0%, respectively. Conclusion The reduction in the sensitivity of preoperative mp-MRI to determine ECE in the community setting is significant. Even with stratification using the D'Amico criteria and Partin tables, the performance of mp-MRI was not significantly improved. Because most cases of PCa are diagnosed and treated in the community, it is questionable whether mp-MRI is a suitable staging modality in the community.

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.

INTRODUCTION AND OBJECTIVES:Multiparametric MRI (mpMRI) has transformed prostate cancer (PCa) management by improving identification of clinically significant disease. However, ∼20% of primary pros...

We evaluated the complications, mortality, hospital length of stay (LOS), and cost for patients with diabetes undergoing radical cystectomy (RC).Data were extracted from the National (Nationwide) Inpatient Sample for 2001 to 2012 using the "International Classification of Diseases, Ninth Revision, Clinical Modification" codes for patients with uncontrolled diabetes (UD) (patients with diabetes receiving treatment that did not keep the blood glucose at acceptable levels) and controlled diabetes (CD) (patients with diabetes not otherwise stated as uncontrolled) who had undergone RC. χIn the present study, 989 patients had UD, 15,693 CD, and 73,603 had no diabetes (ND). Postoperative complications were significantly more common in the UD group (73%) than in the CD (51%) and ND (52%) groups (P .0001). On multivariable analysis, the UD group were more likely than the CD group to have any complication (odds ratio [OR], 2.3; 95% confidence interval [CI], 2.0-2.7), including renal (OR, 2.1; 95% CI, 1.8-2.4) and infectious (OR, 2.7; 95% CI, 2.3-3.1) complications. Patients with UD were also 4.3 times (95% CI, 3.1-5.8) more likely to die after surgery than were patients with CD. The ND group was slightly more likely than the CD group to experience any complication (OR, 1.13; 95% CI, 1.09-1.17) and death (OR, 1.6; 95% CI, 1.4-1.8). The LOS and cost for UD patients were greater than for CD patients. On multivariable analysis, UD patients had a 30% increase in LOS and 23% increase in cost (P .0001).The findings from the present study have demonstrated an increase in post-RC complications rates, hospital mortality, and hospital resource usage for patients with UD undergoing RC. UD might be a modifiable preoperative risk factor for post-RC morbidity and mortality. Further studies are needed to validate this association.

Positive surgical margins (PSMs) are associated with treatment failure after radical prostatectomy (RP) for patients with prostate cancer (CaP). We investigated institutional variations in PSM after RP, as well as clinical and demographic factors predicting PSM.Patients undergoing RP for clinically localized CaP were identified in the National Cancer Database in 2010 to 2013 and clinicodemographics were recorded. Treating institution was defined as academic (AMC) or nonacademic medical centers (nAMC). The primary outcome was the PSM rate. Multivariable logistic regression and propensity matching with inverse probability treatment weighing were used to both compare outcomes between AMC and nAMC and to identify predictors of PSM following RP.A total of 167,260 patients met our inclusion criteria. PSM rate was significantly lower in patients treated at AMC (13,435, 18.9%) compared with 22,145 (23.0%) in those treated at nAMC (P0.01). The difference between PSM rate in AMC and nAMC was more pronounced in lower volume centers while it was not significant in higher volume centers. On multivariable analysis, age, race, prostate-specific antigen (PSA), biopsy Gleason score, comorbidity profile, insurance type, income, and treatment facility were significantly associated with PSM rate.PSM rates appear to be lower at AMC and higher volume facilities, which can potentially reflect institutional differences in surgical quality. In addition, we identified several socioeconomic and demographic factors that contribute to the likelihood of PSM following RP for localized CaP, suggesting potential systematic variation in the quality of surgical care. The cause of this variation warrants further investigation and evaluation.

PurposeWhile 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

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.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.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.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.

Introduction With prostate cancer (CaP) screening, overtreatment of low-risk CaP remains a concern. We investigated the patterns of radical prostatectomy (RP) for pathologic insignificant (iCaP) and significant CaP (sCaP) as well as variations between academic and nonacademic hospitals. Patients and methods Patients undergoing RP for clinical T1c CaP were identified in the National Cancer Database between 2006 and 2013. The primary outcome was the trend of RP for insignificant prostate cancer (iCaP) and significant prostate cancer (sCaP) over the study period. The secondary outcome was to compare the RP rate in academic vs. nonacademic institutions. Univariable and multivariable analysis were utilized to evaluate the association between overtreatment and practice type. iCaP was defined as organ confined CaP with Gleason Score ≤6. Results The total number of RP increased from 17,970 cases in 2006 to 25,324 in 2013. The RP rate decreased for iCaP from 39.9% to 19.8%, while increasing for sCaP from 18% to 27% over the study period. Patients undergoing RP in academic settings were less likely to have iCaP (odds ratio 0.88, 95% confidence interval 0.80–0.97). Caucasian race, private insurance, younger age, and treatment in the Eastern United States were associated with higher rates of iCaP at RP. Conclusion The rate of iCaP has declined over time in the United States for patients undergoing RP. Although RP in nonacademic setting was more likely to have iCaP on surgical pathology, this trend has been downward among practice types. Treatment appropriateness is an underrecognized, undermeasured, but increasingly important component of the high-value care discussion that warrants greater attention.

Background Multiparametric magnetic resonance imaging (mpMRI) undoubtedly affects the diagnosis and treatment of localized prostate cancer (CaP). However, clinicians need a better understanding of its accuracy and limitations in detecting individual CaP foci to optimize management. Objective To determine the per-lesion detection rate for CaP foci by mpMRI and identify predictors of tumor detection. Design, setting, and participants We carried out a retrospective analysis of a prospectively managed database correlating lesion-specific results from mpMRI co-registered with whole-mount pathology (WMP) prostatectomy specimens from June 2010 to February 2018. Participants include 588 consecutive patients with biopsy-proven CaP undergoing 3-T mpMRI before radical prostatectomy at a single tertiary institution. Outcome measurements and statistical analysis We measured mpMRI sensitivity in detecting individual CaP and clinically significant (any Gleason score ≥7) CaP foci and predictors of tumor detection using multivariate analysis. Results and limitations The final analysis included 1213 pathologically confirmed tumor foci in 588 patients with primarily intermediate- (75%) or high-risk (12%) CaP. mpMRI detected 45% of all lesions (95% confidence interval [CI] 42–47%), including 65% of clinically significant lesions (95% CI 61–69%) and nearly 80% of high-grade tumors. Some 74% and 31% of missed solitary and multifocal tumors, respectively, were clinically significant. The majority of missed lesions were small (61.1% ≤1 cm); 28.3% were between 1 and 2 cm, and 10.4% were >2 cm. mpMRI missed at least one clinically significant focus in 34% of patients overall, and in 45% of men with multifocal lesions. On multivariate analysis, smaller, low-grade, multifocal, nonindex tumors with lower prostate-specific antigen density were more likely to be missed. Limitations include selection bias in a prostatectomy cohort, lack of specificity data, an imperfect co-registration process, and uncertain clinical significance for undetected lesions. Conclusions mpMRI detects less than half of all and less than two-thirds of clinically significant CaP foci. The moderate per-lesion sensitivity and significant proportion of men with undetected tumor foci demonstrate the current limitations of mpMRI. Patient summary Magnetic resonance imaging of the prostate before surgical removal for prostate cancer finds less than half of all individual prostate cancer tumors. Large, solitary, aggressive tumors are more likely to be visualized on imaging.

Although tumor tract seeding from renal mass biopsy (RMB) is exceedingly rare, the possibility of tumor capsule violation from RMB leading to perinephric fat invasion has not been quantified. We evaluated the association between RMB and perinephric fat invasion in patients with clinical T1a renal cell carcinoma who underwent partial or radical nephrectomy.We reviewed the National Cancer Database from 2010-2013 and identified patients who underwent surgery for clinical T1a tumors. Patients were classified as upstaged only if final pathology demonstrated perinephric invasion only (pT3a). Mixed-effect logistic regression analysis was performed on inverse probability weighted matched groups to identify predictors of perinephric fat invasion. Multivariable Cox proportional hazards models and Kaplan-Meier survival curves were used to evaluate overall survival (OS).A total of 24,548 patients met our inclusion criteria. Pathologic upstaging to pT3a perinephric fat involvement occurred in 1.2% of patients. This rate of upstaging was 1.1% in the no biopsy group compared with 2.1% in patients who underwent RMB (P0.01). In multivariable logistic model, RMB was associated with pT3a perinephric fat upstaging (OR 1.69, 95% CI 1.17-2.44, P0.01). Upstaging to pT3a was also associated with worse OS (HR 1.71, 95% CI 1.13-2.60, P = 0.01). Kaplan-Meier survival curves demonstrated similar OS estimates in patients upstaged to pT3a disease, irrespective of undergoing RMB or not (Log-Rank = 0.87).RMB was associated with increased rate of upstaging to pT3a perinephric fat involvement in clinical T1a RCC. This effect is small with unclear clinical significance. This is perhaps balanced by the importance of the information acquired from biopsies. Future studies are needed to elucidate clinical significance of this finding.

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. 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. 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

The purpose of the study was to evaluate the cost differences between robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP) in various census regions of the United States because RARP has been reported to be more expensive than ORP with significant regional cost variations in radical prostatectomy (RP) cost across the United States.International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify patients with prostate cancer who underwent RARP or ORP from the Nationwide Inpatient Sample (NIS) database from 2009 to 2011. Hospital costs were compared using the Wilcoxon rank sum test and multivariable linear regression analysis adjusting for age, sex, race, comorbidities, and hospital characteristics.From the NIS database, 24,636 RARP and 13,590 ORP procedures were identified and evaluated. The lowest cost overall was in the South; the highest cost RARP was in the West and for ORP in the Northeast. In multivariable analysis, adjusted according to patient and hospital characteristics, RARP was 43.3% more costly in the Midwest, 37.2% more costly in the South, and 39.1% more costly in the West (P.0001 for all). In contrast, the cost for RARP in the Northeast was 12.8% less than for ORP (P.0001).Cost for RP significantly varies within the nation and in most regions it is significantly greater for RARP than for ORP. ORP in the Northeast is more costly than RARP. Further research is needed to delineate the reason for these differences and to optimize the cost of RP.

Early studies describing robot-assisted radical prostatectomy (RARP) reported the use of pneumoperitoneum at a pressure of 15 mm Hg. While higher insufflation pressures (20 mm Hg) may reduce venous oozing and improve visualization, the safety of this method has not been confirmed. This study evaluates the short-term perioperative outcomes of patients undergoing RARP with insufflation pressures of 20 mm Hg.A single-surgeon, prospectively maintained database of patients undergoing RARP was retrospectively analyzed. Patients who underwent RARP with a pneumoperitoneum pressure of 15 and 20 mm Hg for the entire procedure were analyzed. Preoperative and postoperative hemoglobin levels and estimated glomerular filtration rate (eGFR) were compared. Complications, operative time, and estimated blood loss were also examined.The number of patients in the experimental (20 mm Hg) and control (15 mm Hg) groups were 550 and 201, respectively. The groups were well matched with respect to age and operative time. The experimental group had a significantly smaller decrease in mean hemoglobin levels after surgery (-1.18 vs-2.13 mg/dL, P0.0001). There was no significant difference in the eGFR on the first day after surgery (postoperative day [POD]1) (88.4 vs 85.0 mL/min/1.73m(2), P=0.11) or in the change in eGFR from preoperative to POD1 levels (-0.49 vs 1.54 mL/min/1.73m(2), P=0.18). The complication rate in the experimental group was 8.55% vs 8.46% in the control group.Pneumoperitoneum using a pressure of 20 mm Hg for RARP is safe and has no significant short-term effects on renal function and hemoglobin. Increased insufflation pressure was not associated with a higher complication rate.

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. 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. We identified 4790 patients in the cohort, of which 81% underwent an incontinent diversion. Patients undergoing incontinent diversions were older (p

With increasing utilization of robot-assisted surgery in urologic oncology, robotic nephroureterectomy (RNU) is becoming the surgical modality of choice for patients with upper tract urothelial carcinoma (UTUC). The role of surgical approach on lymph node dissection (LND) and lymph node (LN) yield is unclear, and potential therapeutic effects are unknown. Here we analyze the effects of surgical approach on LN yield, performance of LND, and overall survival (OS).Patients with UTUC who underwent nephroureterectomy from 2010 to 2013 were identified in the National Cancer Database. Outcomes of interest included rate of LND, LN yield, and OS. Logistic regression analyses were used to predict performance of LND. Negative binomial regression was used to derive incidence rate ratios for LN yield. Cox proportional hazards models were used to quantify survival outcomes.A total of 3,116 patients met inclusion criteria. LND was performed in 41% (314/762) of RNU, 27% (380/1385) of LNU cases, and 35% (340/969) of ONU (P0.001). Compared with an ONU, patients who underwent a LNU had significantly lower odds of receiving a LND (OR = 0.70, 95% CI: 0.55-0.87) and had fewer LNs removed (IRR = 0.69, 95% CI: 0.60-0.80), while RNU trended toward increased LN yield (IRR = 1.14, 95% CI: 0.98-1.33). In a Cox proportional hazards model, increasing LN yield was associated with improved OS in patients with pN0 disease (HR = 0.97 per 1 unit increase in LN yield, 95% CI: 0.95-0.99).Compared with an ONU, RNU does not compromise performance of a LND and may be associated with improved LN yield. LNU is associated with the lowest rates of LND and LN yield. Increasing LN yield is associated with improved OS in patients with pN0 disease. Despite differential rates of LND and LN yield, surgical approach did not independently affect OS.

PurposeWe 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 methodsWe 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.ResultsAdjuvant 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.ConclusionsBased 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.

Objective To investigate the impact of prostate-specific antigen density (PSAD) on existing prostate cancer (PCa) active surveillance (AS) protocols. Methods Prospectively maintained database on men with PCa who underwent radical prostatectomy was reviewed retrospectively. Demographic data and pathologic characteristics of patients who fulfilled the AS inclusion criteria under the National Comprehensive Cancer Network (NCCN), Prostate Cancer Research International Active Surveillance (PRIAS), and University of California, San Francisco (UCSF) guidelines were examined. Results Of 930 patients, 231, 280, and 325 fulfilled the NCCN, PRIAS, and UCSF AS criteria, respectively. The frequencies of advanced disease on surgical pathology (upstaging and/or upgrading) were 31.6% (NCCN), 35.4% (PRIAS), and 34.2% (UCSF) of the study cohorts. PSAD was significantly higher in patients with advanced disease compared with that in patients with nonadvanced disease in all 3 AS schemas. Modifying the PRIAS and UCSF criteria using the NCCN's lower PSAD cutoff of 0.15 ng/mL 2 decreased the rates of the advanced disease significantly to 33.5% and 31.4%, respectively. Using the receiver operating characteristic curve analysis, the optimal PSAD cutoff level for the prediction of advanced disease was 0.085 ng/mL 2 (sensitivity/specificity of 76.7%/50.6% in NCCN and 75.6%/49.7% in PRIAS). Conclusion Among patients with low-risk PCa who underwent radical prostatectomy, PSAD is a predictor of advanced disease at the time of surgery. Adopting a lower PSAD threshold of 0.085 ng/mL 2 decreased the risk of the advanced disease to 17.5%-21.7%. Therefore, PSAD should be part of all AS guidelines.

The recovery of potency following radical prostatectomy is complex and has a very wide range. In this study, we analyzed in detail the precise pattern of recovery of potency following robot-assisted radical prostatectomy (RARP).Prospectively collected database of patients with a minimum follow-up of 1 year after RARP were evaluated retrospectively. Of 503 patients identified, 483 patients completed the sexual health inventory for men (SHIM) preoperatively and postoperatively every 3 months for the first 12 months. Overall potency, usage of phosphodiesterase type-5 (PDE-5) inhibitors, and return to baseline erectile function were evaluated. Potency was defined as having erection that is sufficient for sexual intercourse more than 50% of attempts, while quality potency was defined as being potent without the use of PDE-5 inhibitors.Preoperatively, the overall potency and quality potency rate were 67.1% and 48.1%, respectively. Postoperatively, the overall potency rate was 61.4%, while the quality potency rate was 37.2%. In multivariate regression analysis, independent predictors of potency recovery were young age (60), preoperative potency status, and bilateral preservation of neurovascular bundles (NVBs). In men with SHIM21, the overall potency and quality potency rate were 79.7% and 41.2%, respectively. More importantly, only 21.4% of the men with normal erection preoperatively (SHIM21) returned to baseline erectile function (SHIM21) 12 months after surgery.This study indicates that young age (60), preoperative potency, and bilateral preservation of NVBs were positive predictors of potency recovery following RARP. However, an overwhelming majority of men experience a deterioration in the overall quality of erection after RARP.

PURPOSE: Patients with metastatic renal cell carcinoma (mRCC) commonly present with tumor thrombi in the renal vein and inferior vena cava (IVC). The benefit of cytoreductive nephrectomy (CN) in this population is unclear and the effect on overall survival (OS) has been incompletely evaluated. MATERIALS AND METHODS: We queried the National Cancer Database from 2010 to 2013 for patients diagnosed with mRCC and tumor thrombi, which was defined as renal vein, infradiaphragmatic IVC, or supradiaphragmatic IVC. Descriptive statistics were performed and associations between clinicopathologic variables and utilization of CN were analyzed. Patients were matched on the receipt of CN and Kaplan Meier analyses and multivariable Cox proportional hazards models were used to estimate survival. RESULTS: In total, 8,629 patients were found to have mRCC during the study period. Approximately 27% (n=2,376) had tumor thrombus. Tumor thrombus was associated with increased rates of CN utilization, however rates decreased as thrombus level increased. In a matched Kaplan Meier analysis, CN was associated with improved OS in patients without thrombus, and with renal vein or infradiaphragmatic thrombus (all p

Objective To review the urological management and outcomes of patients with the OEIS (omphalocele, exstrophy of the bladder, imperforate anus, spinal abnormalities) complex. Patients and methods 80 patients with the OEIS complex managed at a single institution between 1974 and 2009 were reviewed. Results 37 had initial closure at our institution (2 failed – 5%); 22 with successful closure were referred for incontinence; 15 failed closure at an outside institution (2 of whom are awaiting closure); 6 are skin-covered variants. Osteotomy was performed in 39/43 (91%) with successful closure versus 8/17 (47%) who failed initial bladder closure. 40 were dry (56%), but most needed additional urinary reconstruction: 2 had small bowel neobladders; 32 (84%) had augmentation cystoplasty; 30 (79%) had a continent catheterizable channel; only 9 (24%) were continent with an intact urethra. Bladder neck reconstruction allowed dryness in 7 (18%). 45 patients had XY genotype – 19 had female gender assignment at birth. All patients with XX genotype had female gender assignment. Conclusions Osteotomy improves success of initial bladder closure. A bladder neck procedure, catheterizable channel, and augmentation cystoplasty will be required in the majority of patients to attain urinary dryness.

Leiomyosarcoma of the kidney is a rare entity, and our understanding of this type of renal sarcomas is limited. A 46-year-old Caucasian male presented with a chief complaint of right flank pain for 1 month. He came to our facility for an additional opinion regarding the management of his renal mass. Computed tomography (CT) of the abdomen showed an enhancing, heterogeneous right renal mass, consistent with the features of renal cell carcinoma (RCC). Robotic-assisted total nephrectomy of the right kidney revealed a tan mass with central necrosis that involved the upper pole of the kidney. Based on gross specimen observation and immunochemical analysis, the patient was diagnosed with high-grade leiomyosarcoma. While the prognosis is poor, radical nephrectomy remains the treatment of choice. The potential benefits of adjuvant therapy should be discussed with selected patients. World J Nephrol Urol. 2015;4(2):213-217 doi: http://dx.doi.org/10.14740/wjnu214w

Androgen deprivation therapy (ADT) still remains the foundation of high-risk and metastatic prostate cancer treatment. Since the discovery of the androgen-dependent nature of prostate cancer, ADT has been used in various treatment settings. ADT is used as an adjuvant treatment with radical prostatectomy, in combination with radiation, or as a palliative option for metastatic disease. Based on the clinical context, the optimal timing of ADT varies. More recently the role of intermittent ADT has also been shown to improve quality of life while reducing cost of treatment. However, ADT is associated many significant complications that affects many organ systems. These range from cardiovascular and metabolic abnormalities to decreased bone density and cognitive and emotional disturbances. It is important to understand not only the role and appropriate timing of ADT use in the treatment of prostate cancer but also the need to counsel patients regarding potential complications and side effects of this treatment.

In the era of increasing scrutiny of delivery of quality care, efforts to decrease surgical overtreatment of insignificant prostate cancer (iCaP) continue.To quantify the incidence of surgical overtreatment over time among a contemporary series of men diagnosed with CaP.We retrospectively reviewed the medical records and pathologic specimens for men with CaP who underwent radical prostatectomy between January 2009 and December 2016 at a tertiary referral center. Overtreatment, defined as presence of iCaP in radical prostatectomy specimens, was the primary endpoint. iCaP was defined as a tumor of Gleason score no more than 6 and a tumor diameter ≤10mm (volume0.5 cc). Independent predictors of iCaP were determined using a multivariable model.A total of 1,283 men were eligible for analysis. Overtreatment was found in 86 (6.7%) patients. The frequency of overtreatment significantly decreased from 15% (24/165) in 2009 to 3% (4/134) of patients in 2016 (P0.001). In the multivariable analysis, prostate-specific antigen density ≥0.15 vs.0.15 (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.15-0.64, P0.01), biopsy Gleason score 3+4 vs. 3+3 (OR 0.15, 95% CI 0.08-0.29, P0.01), African American vs. White ethnicity (OR 0.13, 95% CI 0.02-0.96, P = 0.045), and year of surgery (OR 0.88, 95% CI 0.77-0.99, P = 0.03) remained significant predictors of iCaP at surgery. Over the years of study, the odds of overtreatment decreased by 12% annually (OR 0.88, 95 CI 0.77-0.99, P = 0.03). At the same time, the pathological evidence of advanced disease at surgery (≥T3a with/without lymph node involvement) remained unchanged.Surgical overtreatment of CaP has declined to a rate of approximately 3% at this tertiary referral center; further decline is likely. The decline probably has a multifactorial explanation: decreased rate of overdiagnosis, better patient selection for surgery, or change in the referral pattern.

TPS544 Background: BCG unresponsive NMIBC includes patients with persistent high-grade disease or recurrence within 6 months of receiving at least two courses of BCG; or T1 high-grade disease at the first evaluation following BCG induction alone. The recommendation after failing BCG in patients suitable for surgery is cystectomy or for unwilling/unfit patients, salvage chemotherapy or immunotherapy (administered with limited success). This highlights a critical need for novel preservation therapies to facilitate a better quality of life and reduce health-care costs for patients who are unresponsive to BCG (Correa 2015, Dalbagni 2006, Dinney 2013, Kamat 2017). Altor BioScience has initiated a phase II clinical study in BCG unresponsive patients to expand on promising data collected from a compassionate use patient who remains disease free more than 2.5 years after ALT-803 plus BCG treatment for refractory NMIBC (Huang 2017). Methods: This is a Phase II, open-label, single-arm, multicenter study of intravesical BCG plus ALT-803 in patients with BCG unresponsive high grade NMIBC. Group A will enroll patients who have histologically confirmed presence of CIS [with or without Ta or T1 disease]. Group B will enroll patients who have histologically confirmed high-grade Ta or T1 disease (in the absence of CIS). All patients will receive BCG plus ALT-803 weekly for 6 consecutive weeks. A cystoscopy will be performed at Week 12. Patients with no disease or low-grade Ta will receive a maintenance course of therapy (3 weekly instillations of BCG plus ALT-803). Patients with residual CIS and/or high-grade Ta will receive a re-induction course of therapy. Presence of Ta will require a TURBT. Patients with greater than or equal to T1 disease or new CIS will be deemed treatment failures. Patients with a Complete Response (CR) or low-risk disease at Months 6, 9 and 12 are eligible for continued BCG plus ALT-803 maintenance. Patients will be followed for recurrence, progression, and survival. The primary endpoint is to assess complete response (CR; absence of lesions on cystoscopy or negative, for cause, biopsies along with negative urine cytology) of CIS at six months. Enrollment is underway. Clinical trial information: NCT03022825.

Cytoreductive radical nephrectomy (cRN) improves survival in select patients with metastatic renal cell carcinoma (mRCC). It is unclear, however, whether cytoreductive partial nephrectomy (cPN) compromises oncologic efficacy. We evaluated trends in utilization of cPN and compared overall survival (OS) in patients who underwent cRN or cPN for mRCC.We queried the National Cancer Database from 2006 to 2013 and identified patients who underwent cPN and cRN for mRCC. We analyzed rates of cPN over time. Logistic regression identified predictors of cPN. We matched patients based on propensity score for treatment. We used matched Kaplan-Meier survival analyses to compare OS, stratified by tumor size. We used multivariable Cox proportional hazards models to determine the effect of cPN and cRN on OS.A total of 10,144 patients met inclusion criteria, with 9,764 (96.2%) undergoing cRN and 381 (3.8%) undergoing cPN. Rates of cPN increased over time from 1.8% to 4.3% over the study period. Treatment at an academic/research facility, papillary and chromophobe histology, and more recent year of treatment were associated with increased odds of cPN. In a matched survival analysis, cPN was associated with improved OS compared with cRN (log rank, P = 0.001). This effect was limited to primary tumors4cm. In a propensity-score adjusted multivariable Cox model, cPN was associated with improved OS (hazard ratio = 0.81; 95% CI: 0.71-0.93; P = 0.002).The use of cPN in patients with mRCC is increasing. cPN is associated with improved OS in patients with mRCC, although this effect is limited to patients with primary tumors4cm.

Patients with metastatic renal cell carcinoma (mRCC) have limited treatment options. Cytoreductive nephrectomy (CN) in select patients has been associated with improved survival. We aim to assess the survival in patients with mRCC and cN1 disease who underwent CN with and without lymph node dissection (LND).Data were abstracted from the National Cancer Database for patients diagnosed with mRCC and cN1 from 2003 to 2014. Using propensity matching, we compared overall survival (OS) in patients who underwent a LND. Kaplan-Meier survival analysis and multivariable Cox proportional hazards modeling were used. We performed a logistic regression to assess predictors of LND.We identified 1,780 patients in the matched cohort, of which 71% underwent a LND. Patients undergoing LND were younger (P = 0.01) and had similar size tumors (5cm; P = 0.31). Increased LN yield was associated with LND at an academic center (odds ratio = 1.91; 95% CI: 1.51-2.42; P0.01). LND was associated with worse OS on KM analysis (log rank; P = 0.01). However, on multivariable analysis, we found no significant difference in OS (hazard ratio = 1.10; 95% CI: 0.94-1.29; P = 0.22). However, when adjusting for number of positive LN removed, an increase in LN yield was associated with improved OS (hazard ratio = 0.97; 95% CI: 0.95-0.99; P = 0.01).We demonstrate that patients with mRCC and cN1 disease undergoing LND did not have a survival benefit when compared with patients undergoing CN. However, lymph node yield showed an increase in survival when adjusting for the number of positive lymph nodes. Further research and validation of the ideal number of LN removed that may benefit patients is warranted.

Utilizing a recently identified Sox10 distal enhancer directing Cre expression, we report S4F:Cre, a transgenic mouse line capable of inducing recombination in oligodendroglia and all examined neural crest derived tissues. Assayed using R26R:LacZ reporter mice expression was detected in neural crest derived tissues including the forming facial skeleton, dorsal root ganglia, sympathetic ganglia, enteric nervous system, aortae, and melanoblasts, consistent with Sox10 expression. LacZ reporter expression was also detected in non-neural crest derived tissues including the oligodendrocytes and the ventral neural tube. This line provides appreciable differences in Cre expression pattern from other transgenic mouse lines that mark neural crest populations, including additional populations defined by the expression of other SoxE proteins. The S4F:Cre transgenic line will thus serve as a powerful tool for lineage tracing, gene function characterization, and genome manipulation in these populations.

Androgen receptor (AR)–mediated oncogenic pathways have not been fully elucidated. In this study, we used high-throughput microarray analysis on two AR-positive prostate cancer (CaP) cell lines to identify 16 AR-responsive microRNAs (miRNA). We focused on miR-21 because of its previously reported oncogenic activity in other cancers. We show androgen-induced AR binding to the defined miR-21 promoter, miPPR-21, suggesting direct transcriptional regulation. Inhibition of miR-21 diminished androgen-induced CaP cell proliferation, providing new evidence that miRNAs can contribute to androgen-driven cell growth. Elevated expression of miR-21 enhanced CaP tumor growth in vivo and, surprisingly, was sufficient for androgen-dependent tumors to overcome castration-mediated growth arrest. Thus, elevated miR-21 expression alone is sufficient to impart castration resistance. Moreover, quantitative reverse transcription-PCR analysis revealed elevated miR-21 expression in CaP when compared with adjacent normal tissue. These results suggest that miR-21 may contribute to CaP pathogenesis. [Cancer Res 2009;69(18):7165–9]

The complications of lower urinary tract reconstruction have been well documented in children with neurogenic bladders. While most series include small numbers of nonneurogenic diagnoses, this group is typically underrepresented. Despite a number of fundamental anatomical and functional differences, a direct comparison of surgical complications of lower urinary tract reconstruction in patients with neurogenic vs nonneurogenic bladders has not been performed.We identified patients undergoing lower urinary tract reconstruction incorporating enterocystoplasty from 1996 to 2006. We performed a retrospective review of operative notes and medical records of patients who met inclusion criteria. Patients were divided into a neurogenic group and a nonneurogenic group based on the underlying diagnosis. The 2 groups were compared with respect to demographics, historical data, operative techniques, perioperative morbidity, long-term complications and need for surgical revision.Of the 127 patients who met inclusion criteria 72 were assigned to the nonneurogenic group and 55 to the neurogenic group. Overall the rates of significant perioperative morbidity (39%), long-term complications (54%) and need for surgical revision (39%) were substantial. The rates of catheter related complications, rehospitalization for dehydration and spontaneous bladder rupture were higher in the neurogenic group (p0.05).Reconstruction of the lower urinary tract in children is associated with a considerable rate of complications and need for surgical revision regardless of whether the bladder is neurogenic or nonneurogenic. Children with neurogenic bladders are more prone to spontaneous rupture, catheter mishaps and early rehospitalization for dehydration.

Objectives: The role of endogenous cannabinoids in ischemia/reperfusion induced germ cell apoptosis in rats was investigated. Methods: Baseline group was for basal normal values. The Sham operated group served as a control group. The torsion/detorsion (T/D) group underwent torsion (1 h) and detorsion; AN1, AN2, and AN3 groups received anandamide (10 mg/kg) 30 min before torsion, 30 min after torsion, and just after detorsion, respectively. In the AM251 group, AM251 (0.5 mg/kg) was injected 45 min before torsion and in the AN/AM group, AM251 and anandamide were injected 45 and 30 min before torsion, respectively. Lipid peroxidation, antioxidant enzymes, and germ cell apoptosis was determined. Results: Malondialdehyde (MDA) levels in the T/D group were significantly higher than the control group. Moreover, MDA values in the AN1, AN2, and AN3 groups were significantly lower than T/D. There were significant decreases in catalase and superoxide dismutase activities in the T/D group versus the control group. These values in the AN1, AN2, and AN3 groups were significantly higher than T/D. It was also shown that MDA levels in the AN/AM group were significantly higher than the AN1 group. In the AN/AM group, catalase and superoxide dismutase activities were significantly lower versus the AN1 group. The mean germ cell apoptosis scores in all animals with testicular T/D were significantly higher than the control group. There was no difference between the apoptotic indices in the AN1, AN2, AN3, and T/D groups. Apoptosis scores in AM251 and AN/AM were significantly higher compared with the T/D and AN1 groups. Conclusions: Although anandamide increased antioxidant markers, it failed to reduce germ cell apoptosis. AM251 worsened the antioxidant defense system, which is reflected as higher germ cell apoptosis.

We assessed the effectiveness of sildenafil administration during ischemic period in a rat model of testicular torsion/detorsion (T/D).Sprague-Dawley rats were divided into four groups (n = 10). In those animals that underwent T/D, right testes were rotated 720 degrees for 1 h. Base line group was for basal normal values. Sham operated group was served as a control group. T/D group underwent 1 h testicular torsion. Sildenafil group received sildenafil (0.7 mg/kg) intraperitoneally 30 min after initiation of ischemic period. For measurement of lipid peroxidation and antioxidant enzyme activities, right testes of five animals in each group were excised after 4-h reperfusion. Germ cell apoptosis indices were determined 24 h following detorsion in right testes of remaining five animals in each group.Malondialdehyde (MDA) levels in T/D group were significantly higher versus control and base line groups. Moreover, testicular MDA values in sildenafil group were significantly lower than T/D. There were also significant decreases in catalase and superxide dismutase activities in T/D group compared with control and base line groups. These values were significantly higher in sildenafil group versus T/D. Germ cell apoptosis indices were significantly higher in both groups that experienced T/D in comparison to control and base line groups; however, sildenafil treatment significantly reduced the apoptosis in sildenafil group compared with T/D group.Sildenafil administration during testicular torsion decreased ischemia/reperfusion cellular damage. The results of biochemical studies suggest that, reduction of oxidative stress by sildenafil may have a major role in its cytoprotective effects.

Bladder rupture is rare during infancy and most of reported cases had urethral obstruction or neurogenic bladder. We report two cases of infantile bladder rupture during voiding cystourethrography (VCUG). This report reinforces the criteria for proper VCUG imaging procedure. Consideration of expected bladder volume for body weight, and close monitoring of bladder pressure and injection speed could prevent such complications.

To describe a new approach to the treatment of primary obstructive megaureter (POMU) using endoscopic endoureterotomy. The results obtained with this technique are reviewed with long-term follow-up.A total of 47 children (mean age 3.7 years) with 52 POMU units and a history of failed conservative management underwent endoureterotomy of obstructed juxtavesical and intramural ureter. A 3F Double-J ureteral stent was introduced up to the obstructed segment of ureter. Then a zebra catheter was inserted into the affected ureter beside the stent, followed by a neonatal-size ureteroscope. Following delineation of the length of the narrowed portion of the ureter, a guidewire with a plastic sheath replaced the zebra catheter. A longitudinal incision was made through the detrusor muscle at the 6 o'clock position, leaving the bladder adventitia untouched. The Double-J stent was left in place, while its distal tip was fixed by long nylon suture and single knot to the external genitalia to permit easy removal 1 week after the procedure.With a mean follow-up of 39 months (range 14-62 months), no leakage, ureteral-orifice obstruction, or reflux was observed. The postoperative success rate was 90% (47 of 52 ureters), defined as resolution or decrease in hydroureteronephrosis and improvement or stability of renal function determined by renal scan. In 37 ureterorenal units (71%), there was complete resolution of hydroureteronephrosis.On the basis of previous studies demonstrating the value of endoureterotomy with stenting for the treatment of benign ureteral strictures in adults, we developed a modified endoscopic approach for the treatment of POMU and applied this technique in meticulously selected cases. Our results showed that this approach is a valid option for the treatment of children with POMU.