Peri-operative outcomes following radical prostatectomy in the setting of advanced prostate cancer.

OBJECTIVE: To compare the peri-operative outcomes of radical prostatectomy (RP) for locally advanced, node-positive, and metastatic prostate cancer (PCa), as determined through pathological staging, using the American College of Surgeons National Surgical Quality Improvement Project. METHODS: We identified RP procedures performed between 2019 and 2021. Patients were stratified by pathological staging to compare the effect of locally advanced disease (T3-4), node positivity (N+) and metastasis (M+) vs localised PCa (T1-2 N0 M0). Baseline demographics and 30-day outcomes, including operating time, length of hospital stay (LOS), 30-day mortality, readmissions, reoperations, major complications, minor complications and surgery-specific complications, were compared between groups. RESULTS: Pathological staging data were available for 9276 RPs. Baseline demographics were comparable. There was a slightly higher rate of minor complications in the locally advanced cohort, but no significant difference in major complications, 30-day mortality, readmissions, or rectal injuries. Node positivity was associated with longer operating time, LOS, and some slightly increased rates of 30-day complications. RP in patients with metastatic disease appeared to be similarly safe to RP in patients with M0 disease, although it was associated with a longer LOS and slightly increased rates of certain complications. CONCLUSIONS: For patients with pathologically determined locally advanced, node-positive, and metastatic PCa, RP appears to be safe, and is not associated with significantly higher rates of 30-day mortality or major complications compared to RP for localised PCa. This study adds to the growing body of literature investigating the role of RP for advanced PCa; further studies are needed to better characterise the risks and benefits of surgery in such patients.

Percutaneous Microwave Ablation versus Cryoablation for Small Renal Masses (≤4 cm): 12-Year Experience at a Single Center.

PURPOSE: To determine whether microwave ablation (MWA) has equivalent outcomes to those of cryoablation (CA) in terms of technical success, adverse events, local tumor recurrence, and survival in adult patients with solid enhancing renal masses ≤4 cm. MATERIALS AND METHODS: A retrospective review was performed of 279 small renal masses (≤4 cm) in 257 patients (median age, 71 years; range, 40-92 years) treated with either CA (n = 191) or MWA (n = 88) between January 2008 and December 2020 at a single high-volume institution. Evaluations of adverse events, treatment effectiveness, and therapeutic outcomes were conducted for both MWA and CA. Disease-free, metastatic-free, and cancer-specific survival rates were tabulated. The estimated glomerular filtration rate was employed to examine treatment-related alterations in renal function. RESULTS: No difference in patient age (P = .99) or sex (P = .06) was observed between the MWA and CA groups. Cryoablated lesions were larger (P < .01) and of greater complexity (P = .03). The technical success rate for MWA was 100%, whereas 1 of 191 cryoablated lesions required retreatment for residual tumor. There was no impact on renal function after CA (P = .76) or MWA (P = .49). Secondary analysis using propensity score matching demonstrated no significant differences in local recurrence rates (P = .39), adverse event rates (P = .20), cancer-free survival (P = .76), or overall survival (P = .19) when comparing matched cohorts of patients who underwent MWA and CA. CONCLUSIONS: High technical success and local disease control were achieved for both MWA and CA. Cancer-specific survival was equivalent. Higher adverse event rates after CA may reflect the tendency to treat larger, more complex lesions with CA.

Artificial intelligence improves urologic oncology patient education and counseling.

INTRODUCTION: Patients seek support from online resources when facing a troubling urologic cancer diagnosis. Physician-written resources exceed the recommended 6-8th grade reading level, creating confusion and driving patients towards unregulated online materials like AI chatbots. We aim to compare the readability and quality of patient education on ChatGPT against Epic and Urology Care Foundation (UCF). MATERIALS AND METHODS: We analyzed prostate, bladder, and kidney cancer content from ChatGPT, Epic, and UCF. We further studied readability-adjusted responses using specific AI prompting (ChatGPT-a) and Epic material designated as Easy to Read. Blinded reviewers completed descriptive textual analysis, readability analysis via six validated formulas, and quality analysis via DISCERN, PEMAT, and Likert tools. RESULTS: Epic met the recommended grade level, while UCF and ChatGPT exceeded it (5.81 vs. 8.44 vs. 12.16, p < 0.001). ChatGPT text was longer with more complex wording (p < 0.001). Quality was fair for Epic, good for UCF, and excellent for ChatGPT (49.5 vs. 61.67 vs. 64.33). Actionability was overall poor but particularly lowest (37%) for Epic. On qualitative analysis, Epic lagged on all quality measures. When adjusted for user education level (ChatGPT-a and Epic Easy to Read), readability improved (7.50 and 3.53), but only ChatGPT-a retained high quality. CONCLUSIONS: Online urologic oncology patient materials largely exceed the average American's literacy level and often lack real-world utility for patients. Our ChatGPT-a model indicates that AI technology can improve accessibility and usefulness. With development, a healthcare-specific AI program may help providers create content that is accessible and personalized to improve shared decision-making for urology patients.

Sarcomatoid renal cell tumor harboring a novel BYSL::TFEB fusion with concurrent TFEB amplification.

Transcription factor EB (TFEB)-rearranged renal cell carcinoma (RCC) exhibits diverse gene fusion patterns and heterogeneous clinicopathologic features. Rare TFEB-amplified RCCs have been described recently and are associated with a more aggressive clinical course. Herein, we report a case of an 86-year-old man with a solid 9.2-cm kidney tumor that showed a diffuse high-grade sarcomatoid morphology. The tumor demonstrated a novel BYSL::TFEB fusion containing exons 1-2 of the BYSL gene fused to exons 3-10 of TFEB via next-generation sequencing by using NextSeq sequencer. Fluorescence in situ hybridization (FISH) studies displayed concurrent high-copy number TFEB amplification in two distinct patterns, a balanced increase of 5' and 3' copies, and solely increased 5' copies, and mouse double minute 2 (MDM2) gene amplification by using TFEB (6p21.1) dual-color break-apart probe and MDM2 FISH probe. Notably, the tumor showed a distinctive immunoprofile with overexpressions of TFEB, epithelial membrane antigen, Cathepsin K, and PDL-1 (SP263). FISH test for transcription factor binding to IGHM enhancer 3 (TFE3) was negative for rearrangement and corresponding immunonegativity of TFE3. These findings not only expand the repertoire of known TFEB fusion partners implicated in tumorigenesis, but also may provide novel information for target therapy.

Enhancing bladder cancer care through the multidisciplinary clinic approach.

INTRODUCTION: To report the impact of our 25-year multidisciplinary care delivery model experience on patients with muscle invasive bladder cancer treated at our National Cancer Institute (NCI)-designated Sidney Kimmel Cancer Center at Jefferson University. To our knowledge, our multidisciplinary genitourinary cancer clinic (MDC) is the longest continuously operating center of its kind at an NCI Cancer Center in the United States. MATERIALS AND METHODS: We selected a recent group of patients with cT2-4 N0-1 M0 bladder cancer seen in the Sidney Kimmel Cancer Center Genitourinary Oncology MDC from January 2016 to September 2019. These patients were identified retrospectively. SEER-18 (Surveillance, Epidemiology, and End Results) database, November 2019 submission was queried to obtain patients with similarly staged disease diagnosed between 2015 and 2017. Completion rates of radical cystectomy, use of neoadjuvant therapies, and survival outcomes were compared between the two cohorts. RESULTS: Ninety-one patients from the MDC form this time period were identified; 65.9% underwent radical cystectomy and 71.8% received neoadjuvant therapy in the form of chemotherapy, immune checkpoint inhibition or a combination of the two - higher than reported national trends for neoadjuvant therapies. Progression of disease was seen in 24.2% of patients. A total of 8675 patients met inclusion criteria in the SEER database. Rates of radical cystectomy were significantly higher in MCD patients when compared to SEER derived data (65.9% vs. 37.7%, p =< 0.001). MCD patients had significantly better cancer-specific survival (mean 20.4 vs. 18.3 months p = 0.028, median survival not reached). CONCLUSION: Our long term experience caring for patients with genitourinary malignancies such as bladder cancer in a uniform multidisciplinary team results in a high utilization of neoadjuvant therapies. When compared to a contemporary SEER-derived cohort, multidisciplinary patients were more likely to undergo radical cystectomy and had longer cancer-specific survival.

Does antithrombotic use enable earlier diagnosis of bladder cancer? A brief institutional assessment.

INTRODUCTION: Wallis et al (JAMA 2017) demonstrated use of antithrombotic medications (ATMs) is associated with increased prevalence of hematuria-related complications and subsequent bladder cancer diagnosis within 6 months. Stage of diagnosis was lacking in this highly publicized study. This study examined the association of ATM use on bladder cancer stage at the time of diagnosis. MATERIALS AND METHODS: We completed a retrospective chart review of patients with a bladder cancer diagnosis at our institution. Patient demographics and bladder cancer work up information were assessed. Patients were stratified based on use of ATMs at time diagnosis. Descriptive statistics were completed to identify association between ATM use and stage of bladder cancer diagnosis, as stratified by non-muscle invasive bladder cancer (NMIBC) versus muscle invasive bladder cancer (MIBC). RESULTS: A total of 1052 patient charts were reviewed. Eight hundred and forty-four were included and 208 excluded due to unavailability of diagnosis history. At diagnosis, 357 (42.3%) patients were taking ATMs. Patients on ATMs presented with NMIBC at similar rates as patients not taking ATMs (81.2% vs. 77.8%, p = 0.23). Subgroup analysis by ATM class similarly demonstrated no statistically significant differences in staging. CONCLUSION: While Wallis et al established that patients on blood thinners who present with hematuria are more likely to be diagnosed with genitourinary pathology, this factor does not appear to enable an earlier diagnosis of bladder cancer. Future study may assess hematuria at presentation (gross, microscopic), type of blood thinners, and low versus high risk NMIBC presentation.

How I Do It: Cost-effective 3D printed models for renal masses.

3D printing has been growing in many surgical fields including Urology. The primary use has been to print kidneys with tumors to better understand anatomy and to assist with surgical planning and education. Previous studies that utilized 3D printing of kidneys for partial nephrectomies have been limited by the cost and complexity of model creation, rendering them highly impractical to be used on a routine basis. Using a simpler and more cost-effective design and materials allow the 3D kidney models to be used in a wider range and number of patients. We describe our streamlined process to create 3D kidney models costing $30 on average and we believe this process can be repeated by others.

Effects of Contrast-Enhanced Ultrasound of Indeterminate Renal Masses on Patient Clinical Management: Retrospective Analysis From 2 Institutions.

OBJECTIVES: To investigate the long-term impact of contrast-enhanced ultrasound (CEUS) on the treatment of patients with indeterminate renal masses. METHODS: In this retrospective study, consecutive charts of all patients receiving renal CEUS at 1 of 2 academic medical centers between January 1, 2014, and December 31, 2018, were reviewed. Patients were included in the study if they had documented chronic renal disease (estimated glomerular filtration rate < 60 mL/min/1.73 m2 ) or prior nephrectomy and received CEUS for a previously untreated renal mass. RESULTS: A total of 215 lesions in 157 patients were used for analysis. Contrast-enhanced ultrasound provided a final treatment recommendation in 71.6% of lesions (154 of 215). Of these 154 lesions, 7.8% (12 of 154) were lost to follow-up despite CEUS suggesting malignancy; 15.6% (24 of 154) went directly for surgical intervention, with malignancy confirmed by pathologic results in 87.5% (21 of 24) of these cases; and the remaining 76.6% (118 of 154) were deemed benign and required no additional follow-up. Of the 118 lesions diagnosed by CEUS as benign and requiring no follow-up, none showed evidence of later renal cell carcinoma development and, only 5.1% (6 of 118) of the total population was referred for further cross-sectional imaging of the mass in question. In 28.4% of all lesions (61 of 215), CEUS resulted in a recommendation for surveillance imaging at a 6- to 12-month interval, and less than 10% (6 of 61) of these underwent additional cross-sectional imaging within the recommended 6 months after CEUS. CONCLUSIONS: These findings highlight the impact of CEUS on clinical treatment of indeterminate renal masses, including reducing the use of the potentially nephrotoxic contrast agents and providing a direct pathway to transplant.

Faculty Development: How Do We Encourage Faculty to Become Better Teachers and Mentors?

PURPOSE OF REVIEW: A healthy mentor relationship is a mutually beneficial experience and a necessary part of the natural progression of a career in academic medicine. We sought to explore the advantages of and challenges to becoming a mentor in current academic urology. RECENT FINDINGS: Mentorship can promote self-confidence in the ability to choose a career, drive academic productivity, and even inspire a career in academic medicine. It is necessary to help promote advancement in diverse socioeconomic groups within medical trainees. Strong mentors can serve as role models to the next generation of doctors. However, the ability to be an effective mentor is being challenged in today's world of academic medicine. By staying current with the issues surrounding mentorship, an individual can be fulfilled and successful in training and guiding doctors into the new era of medicine.

Simple frameshifts in minimally invasive surgery postoperative pain management significantly reduce opiate prescriptions.

INTRODUCTION: To evaluate the impact of an 'opt-in' non-narcotic postoperative pain regimen on narcotic utilization and patient-reported pain scores. MATERIALS AND METHODS: A prospective, non-blinded pre- and post-interventional trial was conducted, including a lead-in period for baseline evaluation. The intervention group received a new pain protocol prioritizing non-narcotic medications, an 'opt-in' requirement for opiates, and standardized patient education. Study outcomes included opiate prescription and utilization (measured in Morphine Equivalent Doses) and reported pain scores on postoperative day (POD) 1, discharge and follow up. RESULTS: At discharge, 70% fewer patients were prescribed any opioids (ARR: -0.7; p < 0.001); the amount prescribed was reduced by 95% (pre-intervention 69.3 mg versus post-intervention 3.5 mg, p < 0.001). Mean opioids used following discharge decreased by 76% (14.7 mg versus 3.5 mg, p = 0.011). In a subgroup analysis of robotic prostatectomies, there was a 95% reduction in mean opioids prescribed at discharge (64.6 mg versus 3.2 mg, p < 0.001) and 82% reduction in utilization over entire postoperative course (87.6 mg versus 15.7 mg, p = 0.001). There was no significant difference in pain scores between intervention groups at POD 1, discharge and follow up for patients (entire cohort and post-prostatectomy). CONCLUSION: A standardized pain protocol with 'opt-in' requirements for opiate prescription, emphasis on non-narcotic medications, and patient education, resulted in significant reductions in opioid use. Simple frameshifts in pain management can yield significant gains in the opioid epidemic.

Hospital-specific antibiograms and antibiotic prophylaxis for prostate biopsies: a reexamination of AUA recommendations.

INTRODUCTION: To assess whether standard American Urological Association (AUA) and other recommendations for prostate biopsy prophylaxis provide sufficient coverage of common urinary organisms responsible for post biopsy infections by comparing local antibiograms in Philadelphia-area hospitals. MATERIALS AND METHODS: De-identified culture results derived from antibiograms were collected from six academic and community hospitals in the Philadelphia region. Analysis specifically focused on four major bacterial causes of urinary tract infection following prostate biopsy (Escherichia coli (E. coli), Klebsiella pneumoniae, Proteus mirabilis and Enterococcus faecalis) along with commonly recommended antibiotics including fluoroquinolones (FQ's), trimethoprim/sulfamethoxazole, ceftriaxone, and gentamicin. RESULTS: Bacterial sensitivities to each antibiotic across institutions showed variation in E.coli sensitivities to FQs (p < 0.001), trimethoprim/sulfamethoxazole (p < 0.001), ceftriaxone (p < 0.001) and gentamicin (p < 0.001). Klebsiella pneumoniae and Proteus mirabilis exhibited similar variations. Sensitivity comparisons for Enterococcus faecalis was unable to be performed due to absent or incomplete data across institutions. CONCLUSION: Institutional antibiograms vary within our regional hospitals. Standardized recommendations for commonly used antibiotic prophylaxis such as fluoroquinolones may be inadequate for peri-procedural prostate biopsy prophylaxis based on local resistance patterns. Valuable information about the potential effectiveness of antibiotic prophylaxis for prostate biopsies can be found in local institutional antibiograms, and should be consulted when considering antibiotic prophylaxis for prostate biopsy procedures.

Superb Microvascular Imaging Improves Detection of Vascularity in Indeterminate Renal Masses.

OBJECTIVES: Vascular assessment of indeterminate renal masses (iRMs) remains a crucial element of diagnostic imaging, as the presence of blood flow within renal lesions suggests malignancy. We compared the utility of Superb Microvascular Imaging (SMI; Canon Medical Systems, Tustin, CA), a novel Doppler technique, to standard color Doppler imaging (CDI) and power Doppler imaging (PDI) for the detection of vascularity within iRMs. METHODS: Patients undergoing contrast-enhanced ultrasound (CEUS) evaluations for iRMs first underwent a renal ultrasound examination with the following modes: CDI, PDI, color Superb Microvascular Imaging (cSMI), and monochrome Superb Microvascular Imaging (mSMI), using an Aplio i800 scanner with an i8CX1 transducer (Canon Medical Systems). After image randomization, each mode was assessed for iRM vascularity by 4 blinded readers on a diagnostic confidence scale of 1 to 5 (5 = most confident). The results were compared to CEUS as the reference standard. RESULTS: Forty-one patients with 50 lesions met inclusion criteria. Relative to the other 3 modalities, mSMI had the highest sensitivity (63.3%), whereas cSMI had the highest specificity (62.1%). Both cSMI and mSMI also had the highest diagnostic accuracy (0.678 and 0.680, respectively; both P < 0.001) compared to CDI (0.568) and PDI (0.555). Although the reader-reported confidence interval of mSMI (mean ± SD, 3.6 ± 1.1) was significantly lower than CDI (4.1 ± 1.0) and PDI (4.0 ± 1.0; P < 0.001), the confidence level of cSMI (4.1 ± 0.9) was not (P > 0.173). CONCLUSIONS: Preliminary data suggest that SMI is a potentially useful modality in detecting microvasculature in iRMs compared to standard Doppler techniques. Future studies should aim to compare the efficacy of both SMI and CEUS and to assess the ability of SMI to characterize malignancy in iRMs.

Overlapping surgeries: defining the 'critical portions' of the procedure.

INTRODUCTION: An important aspect of overlapping surgery is to determine the 'critical portion' of an operation. Currently, there are no guidelines that standardize the critical portions of common urologic procedures. We sought to determine the relationship between the critical portions of common urologic operations as defined by the primary surgeon compared to the trainee at a single academic medical center. MATERIALS AND METHODS: In an open-ended survey of the Urology Department at Thomas Jefferson University, attending surgeons and urology residents, were asked to list five of their most commonly performed surgeries and subsequently identify what they defined as the critical portion for each. Responses were examined for surgeon-trainee congruence. Response agreement was defined as identifying key words that provided reasonable evidence that the responders were referring to identical portions of the case. RESULTS: Nine residents and eight attending physicians provided 67 and 63 responses, respectively, encompassing 28 different procedures. Six procedures were chosen for further analysis based on high volume of responses. Overall, of the 67 resident-reported critical portions, 32 (47.8%) were in agreement with attending-reported critical portions. Year of training in residency was not a predictor of surgeon-trainee agreement. CONCLUSION: External pressures from the public and lawmakers alike may demand that providers be present during all 'critical portions' of a procedure. Our study shows that the understanding of critical portions of an operation is often incongruent between surgeons and trainees. Critical portions of all procedures should be established by the surgical team in order to accurately schedule overlapping surgeries.

Decision Support and Shared Decision Making About Active Surveillance Versus Active Treatment Among Men Diagnosed with Low-Risk Prostate Cancer: a Pilot Study.

This study aimed to explore the effects of a decision support intervention (DSI) and shared decision making (SDM) on knowledge, perceptions about treatment, and treatment choice among men diagnosed with localized low-risk prostate cancer (PCa). At a multidisciplinary clinic visit, 30 consenting men with localized low-risk PCa completed a baseline survey, had a nurse-mediated online DS session to clarify preference for active surveillance (AS) or active treatment (AT), and met with clinicians for SDM. Participants also completed a follow-up survey at 30 days. We assessed change in treatment knowledge, decisional conflict, and perceptions and identified predictors of AS. At follow-up, participants exhibited increased knowledge (p < 0.001), decreased decisional conflict (p < 0.001), and more favorable perceptions of AS (p = 0.001). Furthermore, 25 of the 30 participants (83 %) initiated AS. Increased family and clinician support predicted this choice (p < 0.001). DSI/SDM prepared patients to make an informed decision. Perceived support of the decision facilitated patient choice of AS.

Preoperative nomogram to predict the likelihood of complications after radical nephroureterectomy.

OBJECTIVES: To construct a nomogram based on preoperative variables to better predict the likelihood of complications occurring within 30 days of radical nephroureterectomy (RNU). PATIENTS AND METHODS: The charts of 731 patients undergoing RNU at eight academic medical centres between 2002 and 2014 were reviewed. Preoperative clinical, demographic and comorbidity indices were collected. Complications occurring within 30 days of surgery were graded using the modified Clavien-Dindo scale. Multivariate logistic regression determined the association between preoperative variables and post-RNU complications. A nomogram was created from the reduced multivariate model with internal validation using the bootstrapping technique with 200 repetitions. RESULTS: A total of 408 men and 323 women with a median age of 70 years and a body mass index of 27 kg/m2 were included. A total of 75% of the cohort was white, 18% had an Eastern Cooperative Oncology Group (ECOG) performance status ≥2, 20% had a Charlson comorbidity index (CCI) score >5 and 50% had baseline chronic kidney disease (CKD) ≥ stage III. Overall, 279 patients (38%) experienced a complication, including 61 events (22%) with Clavien grade ≥ III. A multivariate model identified five variables associated with complications, including patient age, race, ECOG performance status, CKD stage and CCI score. A preoperative nomogram incorporating these risk factors was constructed with an area under curve of 72.2%. CONCLUSIONS: Using standard preoperative variables from this multi-institutional RNU experience, we constructed and validated a nomogram for predicting peri-operative complications after RNU. Such information may permit more accurate risk stratification on an individual cases basis before major surgery.

Endoscopic Treatment of Upper Tract Urothelial Carcinoma.

PURPOSE OF REVIEW: This study aims to make the reader be aware of recent trends regarding the endoscopic management of upper tract urothelial carcinoma (UTUC) via review of the urologic literature over the past 5 years. Given the rare incidence of this disease, and the lack of level 1 evidence, systematic reviews and meta-analyses were also evaluated. Studies of importance are also considered and outlined in the annotated reference section. RECENT FINDINGS: The PubMed database was queried using the following medical subject headings (MeSH terms): "carcinoma, transitional cell," "ureter," "ureteral neoplasms," "kidney pelvis," "endoscopy," "laser therapy," "ureteroscopy," "urologic surgical procedures," and "ureteroscopes." MeSH terms were linked together in varying combinations and limited to human studies in English. Given the relatively rare nature of upper tract urothelial carcinoma (UTUC), level 1 evidence regarding the efficacy of endoscopic treatment does not exist, even after 30+ years of experience. Rather, the literature available mostly is in the form of single institutional retrospective series consisting of relatively small numbers of patients with short to intermediate follow-up. Only within the last 3 years have published series with larger numbers of patients and mean follow-up over 5 years been made available. Even with these more robust experiences, comparisons among series are difficult given variable treatment and follow-up approaches. Most endoscopically managed UTUC will locally recur, especially with longer follow-up. Renal preservation rate is high, however, approaching 80% with follow-up well over 3 years. Patients with high-grade disease often fare poorly regardless of treatment modality. As such, endoscopic management for high-grade urothelial carcinoma should only be used in exceptional circumstances (i.e., in those patients medically unfit for NU or those with solitary kidneys wishing to avoid the morbidity of dialysis). No level 1 evidence exists for the routine use of intraluminal adjuvant therapy for UTUC (i.e., BCG and Mitomycin C) and multiple retrospective observational series claim there is no overt benefit. The recent formation of multiple international groups with interest in UTUC may eventually lead to the production of level 1 studies regarding optimal treatment; however, uniformity in treatment approach will likely still offer challenges.

Fluorescence in situ hybridization (FISH) in the diagnosis of bladder and upper tract urothelial carcinoma: the largest single-institution experience to date.

INTRODUCTION: We evaluated the UroVysion (Abbott Molecular, IL, USA) fluorescence in situ hybridization (FISH) assay for the diagnosis of urothelial cancer in patients diagnosed with or suspected to have bladder, upper tract urothelial carcinoma (UTUC), and combined upper and lower tract urothelial carcinoma (BC). MATERIALS AND METHODS: A single institution retrospective analysis comparing sensitivity, specificity, positive predictive value, and negative predictive values for FISH and urinary cytology. FISH within 6 months of endoscopic evaluation were obtained from outpatient voided urine samples. Our institutional pathology department confirmed pathologic disease from specimens obtained during endoscopic evaluations for lower tract disease. For upper tract disease, disease was confirmed by retrograde ureteroscopy, biopsies of visual lesions, and site-specific upper tract cytology. RESULTS: A total of 415 patients submitted FISH specimens. Overall, FISH was more sensitive than cytology 54.9% in comparison with cytology 42.2% (p = 0.01), specificity favored cytology 92.9% compared to 73.5% with FISH (p < 0.01). For BC only patients, the same significant finding of increased sensitivity and decreased specificity was identified, but for UTUC alone and combined UTUC and BC, there was no significant difference. Cytology had improved positive predictive value (PPV) over FISH, 76.9% in comparison to 64.6% (p = 0.02). Negative predictive value (NPV) also favored cytology 74.2% versus 64.9% (p = 0.02). When analyzing individual cohorts, cytology had improved PPV for BC alone patients. UTUC showed no difference for PPV and NPV. For both UTUC and BC, NPV was slightly favored for FISH over cytology 93.2% versus 91.2% (p = 0.03). CONCLUSIONS: Voided urine FISH testing does offer a higher detection of urothelial carcinoma for BC compared to voided cytology; however, specificity was worse. FISH does not appear to improve detection of urothelial carcinoma in patients with either UTUC only or both BC and UTUC.

Prevalence and Characteristics of Patients with Suspected Inherited Renal Cell Cancer: Application of the ACMG/NSGC Genetic Referral Guidelines to Patient Cohorts.

Patients with suspected hereditary renal cell cancer (RCC) are under-referred for genetic evaluation. Characterizing the prevalence and characteristics of suspected inherited RCC is a crucial step toward advancing personalized, genetically-based cancer risk management for patients and their families. To evaluate the prevalence and characteristics of suspected inherited RCC syndromes based on consensus criteria, we performed a cross-sectional analysis of patients with a diagnosis of RCC in SEER (2001-2011, n = 105,754) and in our institutional cancer registry (2004-2013, n = 998). Consensus criteria for referral of patients with RCC for genetic evaluation from the American College of Medical Genetics and Genomics and National Society of Genetic Counselors (ACMG/NSGC) were applied to the two cohorts. The associations between meeting referral criteria with demographic characteristics were assessed with chi-square tests. Overall, 24.0 % of the SEER cohort and 33.7 % of our institutional cohort met ACMG/NSGC referral criteria for genetic counseling. While white patients more commonly met early onset clear cell RCC criteria, black patients met papillary RCC criteria at twice the rate of whites in both cohorts (p < 0.0001). As many as 1 in 5 individuals with RCC meet referral criteria for genetic evaluation based on newly emerging guidelines, with differences in pathology noted by race. Prospective genetic testing studies utilizing emerging referral guidelines should help to refine the genetic spectrum of inherited kidney cancer. This study supports efforts to increase awareness of referral of patients with RCC for genetic counseling particularly among urologic providers.

Jak2-Stat5a/b Signaling Induces Epithelial-to-Mesenchymal Transition and Stem-Like Cell Properties in Prostate Cancer.

Active Stat5a/b predicts early recurrence and disease-specific death in prostate cancer (PC), which both typically are caused by development of metastatic disease. Herein, we demonstrate that Stat5a/b induces epithelial-to-mesenchymal transition (EMT) of PC cells, as shown by Stat5a/b regulation of EMT marker expression (Twist1, E-cadherin, N-cadherin, vimentin, and fibronectin) in PC cell lines, xenograft tumors in vivo, and patient-derived PCs ex vivo using organ explant cultures. Jak2-Stat5a/b signaling induced functional end points of EMT as well, indicated by disruption of epithelial cell monolayers and increased migration and adhesion of PC cells to fibronectin. Knockdown of Twist1 suppressed Jak2-Stat5a/b-induced EMT properties of PC cells, which were rescued by re-introduction of Twist1, indicating that Twist1 mediates Stat5a/b-induced EMT in PC cells. While promoting EMT, Jak2-Stat5a/b signaling induced stem-like properties in PC cells, such as sphere formation and expression of cancer stem cell markers, including BMI1. Mechanistically, both Twist1 and BMI1 were critical for Stat5a/b induction of stem-like features, because genetic knockdown of Twist1 suppressed Stat5a/b-induced BMI1 expression and sphere formation in stem cell culture conditions, which were rescued by re-introduction of BMI1. By using human prolactin knock-in mice, we demonstrate that prolactin-Stat5a/b signaling promoted metastases formation of PC cells in vivo. In conclusion, our data support the concept that Jak2-Stat5a/b signaling promotes metastatic progression of PC by inducing EMT and stem cell properties in PC cells.

Risk factors for biochemical recurrence after robotic assisted radical prostatectomy: a single surgeon experience.

BACKGROUND: Radical prostatectomy is a standard surgical treatment of clinically localized prostate cancer. Margin status has been found to be an independent predictor of biochemical recurrence (BCR) after open radical prostatectomy in several large series but this is still controversy in Robotic Assisted Radical Prostatectomy (RARP) series. We therefore wanted to investigate the prognostic significance of positive surgical margin (PSM) and other pathological factors on BCR in patients treated with RARP by a single surgeon. METHODS: Prospectively collected data of 439 patients treated with RARP between October 2005 and June 2013 by a single surgeon at a single institution were analyzed. BCR was defined as follow-up PSA level > 0.2 ng/ml on two separate occasions or patients who had to undergo salvage therapy. Kaplan Meier curves and Log Rank test were used to compare the risk of BCR. Univariate and Multivariate Cox Regression analyses were performed to determine the prognostic impact of age, BMI, prostate weight, PSA prior to surgery, pathological T-stage, pathological Gleason sum, PSM and operative period. RESULTS: In this study period, 34 out of 439 had BCR, giving an overall BCR rate of 7.7% for this cohort. Overall 2- and 3-year BCR-free survival rates were 93% and 88%, respectively. Patients with a PSM had a 2-year BCR free survival of 88% compared to 94% in those with negative margins (p < .0001). On the multivariate analysis, PSM as well as pathological Gleason sum > = 8, PSA, pathological stage and operative period were significantly associated with BCR. CONCLUSIONS: In our case series of RARP performed by a single surgeon, PSM as well as pathological Gleason sum, PSA, pathological stage and early operative period for this surgeon were the independent predictors of BCR.