The incidence of erosion of inflatable penile prosthesis (IPP) components into adjacent organs is low (<0.1 %). During a transurethral resection of the prostate (TURP) in a patient with prior IPP placement, we encountered IPP tubing that had eroded into the prostate. The pump and cylinders were later explanted through a penoscrotal approach, with the reservoir drained and retained with plan for follow up cystoscopy in 4-6 weeks. Cystoscopy 1 month later demonstrated reservoir erosion into the bladder lumen. An open cystotomy was performed to retrieve the reservoir. This is the first reported case of IPP tubing eroding into the prostate.

The NCCN Guidelines for Survivorship include recommendations for screening, evaluation, and treatment of psychosocial and physical problems resulting from adult-onset cancer and its treatment. They also include recommendations to promote healthy behaviors and im-munizations in survivors and provide a framework for care coordination. These NCCN Guidelines Insights summarize the panel's current recommendations regarding sexual health and fertility.

The NCCN Guidelines for Survivorship include recommendations for screening, evaluation, and treatment of psychosocial and physical problems resulting from adult-onset cancer and its treatment. They also include recommendations to promote healthy behaviors and immunizations in survivors and provide a framework for care coordination. These NCCN Guidelines Insights summarize the panel’s current recommendations regarding sexual health and fertility.

OBJECTIVE:To introduce the Penile Trauma Score (PTS), a new statistically driven classification system aimed at enhancing the management of penile trauma by providing clinically relevant treatment protocols. METHODS:A retrospective review was conducted of 34 men with penetrating penile injuries at the Elvis Presley Level 1 Trauma Center, Memphis, from January 2014 to December 2016. Variables assessed included injury mechanism, location, depth, and follow-up outcomes related to voiding and erectile function. Odds ratios were calculated using superficial penile injury as the control group. RESULTS:Based on physical examination findings and odds ratios calculated, the PTS was developed. Results indicated that higher PTS scores necessitated surgical intervention, while lower scores could be managed nonoperatively. Follow-up showed no missed injuries or reported dysfunctions, validating the PTS's effectiveness. CONCLUSION:The PTS represents an important modification in the classification and management of penile trauma. By integrating practical, easily identifiable injury characteristics, the PTS facilitates more streamlined surgical decision-making and potentially reduces unnecessary diagnostic procedures. However, further prospective studies with larger sample sizes and longer follow-up are needed to fully validate the PTS's clinical utility.

The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.

You have accessJournal of UrologyCME1 May 2022PD60-07 OBJECTIVE RISK SCORE RELIABLY PREDICTS MAJOR MORBIDITY AND MORTALITY AFTER RADICAL PROSTATECTOMY Kristen Maatman, Christopher Ledbetter, A. Lynn Patterson, and Robert Wake Kristen MaatmanKristen Maatman More articles by this author , Christopher LedbetterChristopher Ledbetter More articles by this author , A. Lynn PattersonA. Lynn Patterson More articles by this author , and Robert WakeRobert Wake More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002645.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radical prostatectomy (RP) is the gold-standard treatment for localized prostate cancer. We have previously developed and validated a 30-day mortality risk score after radical cystectomy and radical nephrectomy and hypothesized that this risk score could be applied to patients undergoing RP for prostate cancer. METHODS: The National Surgical Quality Improvement Program (NSQIP) identified 48,285 patients that underwent RP for malignancy from 2014-2018. Only patients with complete data for risk score calculation were included in this analysis. Risk factors for 30-day mortality were identified on multivariable analysis using backward stepwise binary logistic regression. A previously developed and validated mortality risk score (Figure 1A) was calculated for each patient undergoing RP. A receiver operating characteristic (ROC) curve was created to quantify the discriminatory ability of the risk calculator. P values <0.05 were accepted as statistically significant. The primary aim of this study was to stratify the risk of 30-day mortality after RP; secondary aims included risk stratification of major morbidity and all-cause morbidity. RESULTS: 17,699 RP patients were included. Most underwent robotic assisted laparoscopic prostatectomy (89%, n=15,695). Mean age was 62±7 years. Rates of 30-day major morbidity and all-cause morbidity were 6.0% and 10.6%, respectively. Postoperative 30-day mortality was 0.19% (n=34). Multivariable analysis associated chronic obstructive pulmonary disorder, lower albumin and hematocrit, and elevated alkaline phosphatase with 30-day mortality (p <0.05). After RP 30-day mortality increased exponentially with escalating risk category (Figure 1B). The area under the ROC curve for the mortality risk score in patients that underwent RP was 0.702 (95% CI, 0.609-0.796; p <0.0001). The risk score additionally stratified the risk of 30-day major morbidity (AUC, 0.867; 95% CI, 0.788-0.947; p <0.0001) and all-cause morbidity (AUC, 0.860; 95% CI, 0.785-0.934; p <0.0001) after RP (Figure 1C). CONCLUSIONS: A previously established mortality risk score can be employed in patients undergoing RP for prostate cancer to stratify 30-day mortality risk as well as risk of major morbidity. This risk score is reliable, accurate, and applicable to both minimally invasive and open RP. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1027 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kristen Maatman More articles by this author Christopher Ledbetter More articles by this author A. Lynn Patterson More articles by this author Robert Wake More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyKidney Cancer: Localized: Surgical Therapy II (PD16)1 Sep 2021PD16-01 OBJECTIVE RISK SCORE RELIABLY PREDICTS MORTALITY AFTER RADICAL NEPHRECTOMY Kristen Marley, Bradley Houston, Christopher Ledbetter, Robert Wake, A. Lynn Patterson, and Maurizio Buscarini Kristen MarleyKristen Marley More articles by this author , Bradley HoustonBradley Houston More articles by this author , Christopher LedbetterChristopher Ledbetter More articles by this author , Robert WakeRobert Wake More articles by this author , A. Lynn PattersonA. Lynn Patterson More articles by this author , and Maurizio BuscariniMaurizio Buscarini More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001998.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Radical nephrectomy (RN), with or without resection of the ureter, is the treatment of choice for patients with advanced malignancy of the kidney and/or upper urinary tract. We have previously developed and validated a mortality risk score to stratify postoperative outcomes in patients undergoing radical cystectomy. We hypothesized that this 30-day mortality risk score could be applied to patients undergoing RN for malignancy. METHODS: The National Surgical Quality Improvement Program (NSQIP) identified 16,617 patients that underwent RN for upper urinary tract or renal malignancy from 2013-2017. Patients with complete data were included in the analysis. Risk factors for 30-day mortality were identified on multivariable analysis using backward stepwise binary logistic regression. A previously developed and validated mortality risk score (Figure 1A) was calculated for each RN patient. A receiver operating characteristic (ROC) curve quantified the discriminatory ability of the risk calculator. Statistical significance was defined as p values <0.05. RESULTS: Of 9,345 patients included, laparoscopic/robotic technique was applied in 6,112 (65%) patients. The mean age was 64±12 years and most patients were male (n=5950, 64%). Postoperative 30-day mortality was 1.2% (n=116). Older age, elevated creatinine, lower albumin and hematocrit, congestive heart failure, exertional dyspnea, >10% weight loss, disseminated cancer, and open surgery as mortality risk factors. After RN, 30-day mortality increased nearly exponentially with escalating risk category (Figure 1B), p<0.00001. The ROC curve for the risk score is shown in Figure 1C; the area under the curve (AUC) was 0.794 (95% CI, 0.755-0.832; p<0.00001). Relative risk of 30-day mortality increased with escalating risk category: moderate risk=4.8 (2.5-9.1, p<0.00001), high risk=16.8 (9.0-31.5, p<0.00001), and extremely high risk=36.8 (13.4-101.2, p<0.00001). The risk score applied to minimally invasive (AUC, 0.785; 95% CI, 0.722-0.849; p<0.00001) and open RN (0.781; 0.730-0.832; p<0.00001). CONCLUSIONS: A previously established mortality risk score can be employed preoperatively in patients undergoing RN for malignancy to stratify 30-day mortality risk. This 30-day mortality risk score is reliable, accurate, and applicable to both minimally invasive and open RN. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e278-e278 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kristen Marley More articles by this author Bradley Houston More articles by this author Christopher Ledbetter More articles by this author Robert Wake More articles by this author A. Lynn Patterson More articles by this author Maurizio Buscarini More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyHealth Services Research: Practice Patterns, Quality of Life and Shared Decision Making III (MP23)1 Sep 2021MP23-17 SOCIOECONOMIC FACTORS PREDICT DELAY IN PROSTATE CANCER TREATMENT DECISION AND INITIATION Patrick Probst, Hunter Kraus, Will Fry, Aditya Sathe, Jackson Eber, Jay Fowke, Patricia Goedecke, Maurizio Buscarini, Christopher Ledbetter, Anthony Patterson, and Robert Wake Patrick ProbstPatrick Probst More articles by this author , Hunter KrausHunter Kraus More articles by this author , Will FryWill Fry More articles by this author , Aditya SatheAditya Sathe More articles by this author , Jackson EberJackson Eber More articles by this author , Jay FowkeJay Fowke More articles by this author , Patricia GoedeckePatricia Goedecke More articles by this author , Maurizio BuscariniMaurizio Buscarini More articles by this author , Christopher LedbetterChristopher Ledbetter More articles by this author , Anthony PattersonAnthony Patterson More articles by this author , and Robert WakeRobert Wake More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002014.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Although prostate cancer is typically a slow-growing malignancy, pathology and risk stratification can progress in as quick as 3 months. Socioeconomic status (SES) and health disparities have been identified as predictors of worse oncologic and survival outcomes in men with prostate cancer. We sought to identify specific SES characteristics that contribute to delayed treatment decision (TD) and initiation (TI) in a majority black patient population. METHODS: After receiving IRB approval, men with a positive prostate biopsy between Jan. 2013 and Dec. 2019 at the Memphis VA Medical Center were retrospectively reviewed. Those with a known prostate cancer diagnosis or metastatic disease were excluded. Demographic data was compiled using census information corresponding to patient zip codes at time of biopsy. Time from biopsy to TD and time from TD to TI, were recorded (Table 1a.) Univariate chi-square analyses were performed to determine predictors of treatment selection while multivariable logistic regression analysis determined predictors of delayed TD and delayed TI. Delayed TD was defined as >100 days while delayed TI was defined as >150 days. RESULTS: 630 men with mean age of 63.3 years (41-79) and predominantly black (71.9%) met inclusion criteria. Race, age group and cancer risk stratification were strongly associated with type of therapy selected (p <0.0006). When controlling for age and risk, no demographic or socioeconomic factors were significantly associated with delayed TD. However, race and income approached statistical significance. Non-white men were 39% more likely to have a delayed time to decision (p=0.0633). Patients with average income <$40,000 were 78% more likely to have delayed TD (p=0.0769). Men <60 years old were 38% less likely to have delayed TI (p=0.0418). Those with low risk disease and poverty level >30% were 7.4x (p <0.0001) and 2x (p=0.0132) more likely to have delayed TI, respectively. Finally, white men were 67% more likely to have a delay in treatment initiation (p=0.0411). CONCLUSIONS: Individualized patient-specific education and adequate time to consider all therapies should be given to men with newly diagnosed prostate cancer. However, particular attention to those with lower SES is needed to avoid delays in therapy decision and ultimately treatment initiation. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e408-e409 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Patrick Probst More articles by this author Hunter Kraus More articles by this author Will Fry More articles by this author Aditya Sathe More articles by this author Jackson Eber More articles by this author Jay Fowke More articles by this author Patricia Goedecke More articles by this author Maurizio Buscarini More articles by this author Christopher Ledbetter More articles by this author Anthony Patterson More articles by this author Robert Wake More articles by this author Expand All Advertisement Loading ...

You have accessJournal of UrologyStone Disease: Surgical Therapy II (MP18)1 Sep 2021MP18-15 INCREASED STONE BURDEN, ANATOMY COMPLEXITY, CYSTINE STONE COMPOSITION AND IR ACCESS PREDICT LOWER STONE FREE RATES Patrick Probst, Hunter Kraus, Jackson Eber, Maurizio Buscarini, Christopher Ledbetter, Anthony Patterson, and Robert Wake Patrick ProbstPatrick Probst More articles by this author , Hunter KrausHunter Kraus More articles by this author , Jackson EberJackson Eber More articles by this author , Maurizio BuscariniMaurizio Buscarini More articles by this author , Christopher LedbetterChristopher Ledbetter More articles by this author , Anthony PattersonAnthony Patterson More articles by this author , and Robert WakeRobert Wake More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002003.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL) are mainstay therapies for nephroureterolithiasis. Our aim was to determine predictors of stone-free rate (SFR) following URS and PCNL in a large series of patients. METHODS: Retrospective review identified 3051 patients undergoing 5586 PCNLs or URSs for nephroureterolithiasis from 2008-2018. Stone size, durility and composition, number and type of operations, SFR, infundibular stenosis, specialty performing access, and complications were noted. Durility was stratified by Hounsfield Units on CT – <60, 60-100 and >100. One endourologist performed all procedures utilizing consistent techniques. All patients underwent CT stone protocol 1 week post-operatively to determine SFR. RESULTS: 3051 patients with a mean stone burden (SB) of 1.18cm underwent 5586 procedures (Table 1a and 1b). The mean number of procedures per patient was 1.8. Patients undergoing >1 procedure were more likely to have larger SB (p <0.001). Patients were 33% more likely to require another procedure with each centimeter increase in SB (p <0.001). Cystine stones were 105x more likely to require more than 1 surgery (p <0.001). Although infundibular stenosis was associated with lower SFR (p=0.021) stone durility was not associated with need for more than one procedure (p=0.791). However increased stone durility was 3.3x as likely to have PCNL (p <0.001). PCNL was 2.4x more likely to require a second procedure than URS (p <0.001). However, stones treated with PCNL were significantly bigger than stones treated with URS (p <0.001). Flexible nephroscopy before concluding PCNL was associated with a higher SFR than just PCNL alone (p <0.001). SFR was significantly better if PCNL access was achieved by urology and not interventional radiology (p=0.001). Complications were more common in those that were not stone free (p=0.003). CONCLUSIONS: Increased SB, complex anatomy and cystine composition predicted lower SFR while stone durility was not associated with SFR. PCNL had lower SFR than URS but was used on larger and harder stones. SFR improved with concurrent flexible nephroscopy during PCNL and if percutaneous access was done by the urologist. This information can be used to guide surgical planning especially since complications appear more common in those with lower SFR. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e324-e324 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Patrick Probst More articles by this author Hunter Kraus More articles by this author Jackson Eber More articles by this author Maurizio Buscarini More articles by this author Christopher Ledbetter More articles by this author Anthony Patterson More articles by this author Robert Wake More articles by this author Expand All Advertisement Loading ...

Detrusor smooth muscle (DSM) cells present within the urinary bladder wall ultimately facilitate urine storage and voiding. Preparation of the viable, fresh, and isolated DSM cells presents an important technical challenge whose achievement provides optimal cells for subsequent functional and molecular studies. The method developed and elaborated herein, successfully used by our group for over a decade, describes dissection of human urinary bladder specimens obtained from open bladder surgeries followed by an enzymatic two-step treatment of DSM pieces and mechanical trituration to obtain freshly isolated DSM cells. The initial step involves dissection to separate the DSM layer (also known as muscularis propria) from mucosa (urothelium, lamina propria, and muscularis mucosa) and the adjacent connective, vascular, and adipose tissues present. The DSM is then cut into pieces (2-3 mm x 4-6 mm) in nominal Ca2+-containing dissection/digestion solution (DS). DSM pieces are next transferred to and sequentially treated separately with DS containing papain and collagenase at ~37 °C for 30-45 min per step. Following washes with DS containing enzyme-free bovine serum and trituration with a fire-polished pipette, the pieces release single DSM cells. Freshly isolated DSM cells are ideally suited for patch-clamp electrophysiological and pharmacological characterizations of ion channels. Specifically, we show that the TRPM4 channel blocker 9-phenanthrol reduces voltage-step evoked cation currents recorded with the amphotericin-B perforated patch-clamp approach. DSM cells can also be studied by other techniques such as single cell RT-PCR, microarray analysis, immunocytochemistry, in situ proximity ligation assay, and Ca2+ imaging. The main advantage of utilizing single DSM cells is that the observations made relate directly to single cell characteristics revealed. Studies of freshly isolated human DSM cells have provided important insights characterizing the properties of various ion channels including cation-permeable in the urinary bladder and will continue as a gold standard in elucidating DSM cellular properties and regulatory mechanisms.

Novel technologies facilitate breakthroughs in scientific discovery with concomitant advances in therapy. In the case of nanotechnology, a major focus has been on optimizing its use for targeted drug delivery, imaging, diagnosis, or a combination of therapeutics and diagnosis (“theranosis”). However, the application of nanotechnology in the research and treatment of benign urological pathologies remains underexplored. At our institution (“Einstein”), the research laboratory of Dr. Joel Friedman has developed a nanoparticledelivery system (the “Einstein” nanoparticle). We and others have applied this system to multiple research fields, including benign urology, as documented by >20 publications, several extramurally funded research projects, and licensing to a commercial entity. This nanoparticle-delivery system has intrinsic potential for modulation of its physicochemical properties, allowing use in a vast array of basic research and clinical conditions. However, the availability of these nanoparticle-delivery systems to the general urologic research community is currently limited by the absence of specific resource allocations for design and synthesis. This proposal addresses these limitations by establishing a P20 Resource Development Center with two primary goals: 1) to educate and promote the use of nanotechnology within the urologic basic and clinical research community, and 2) to create a resource development (research project) component in which the “Einstein” nanoparticle will be available for collaborative projects focused on benign urologic diseases. The proposed Resource Center will design and synthesize nanoparticles tailored to each research project until commercial entities assume this role. The Center will be highly synergistic, with investigators learning how nanotechnology can be applied to their specific field of research. Investigators will have access to resources and training, so they can apply the “Einstein” nanotechnology in their project. Investigators will require design and synthesis of novel nanoparticle formulations tailored to their specific research projects. This process would therefore lead to the development and expansion of novel nanoparticle formulations for a variety of benign urologic conditions. We anticipate that commercial entities will be positioned to synthesize nanoparticles within 2-4 years, eventually replacing the need for this P20 Resource Center. CAIRIBU P20 Exploratory Centers for Interdisciplinary Research in Benign Urology Duke University, Department of Mechanical Engineering and Materials Science 2019-2021; PI, Pei Zhong, PhD DUKE UNIVERSITY P20 EXPLORATORY CENTER FOR INTERDISCIPLINARY RESEARCH IN BENIGN UROLOGY Laser lithotripsy (LL) is the treatment of choice for urinary stone disease (USD), which is the second most costly urologic condition in the US with a healthcare cost over $2 billion annually. LL is typically performed using Holmium (Ho):YAG laser operating at wavelength () of 2.1 m with a pulse repetition frequency (F) < 10 Hz. In recent years, new Ho:YAG lasers and technologies, such as the Lumenis H120 with MOSES techno logy, have enabled LL at high power (120 W)/high frequency (80 Hz), while offering new treatment modes, such as dusting, popcorning and pop-dusting. In 2020, Olympus launched the Soltive SuperPulsed Thulium Fiber Laser (TFL), operating at  = 1.94 m with F > 200 Hz, further expanding the armaments for USD management. Despite the rapid technology advances and growing clinical enthusiasm about the new lasers, the fundamental knowledge of LL has not changed commensurately in the past two decades. The Duke University P20 Exploratory Center for Interdisciplinary Research in Benign Urology has created a comprehensive program to investigate the mechanism of stone damage in LL through a combination of experimentation and numerical modeling. This is an important endeavor because better understanding of the mechanism of stone destruction is the first step in developing improved and even less invasive surgical technologies for managing patients with USD. Most importantly, we have discovered that cavitation, i.e., the formation of an elongated vapor bubble at the laser fiber tip, plays a significant and, in some cases, even dominant role in stone damage. This finding is in distinct contradiction to the prevailing theory that stone damage in LL is predominantly produced by photothermal ablation. This paradigm-changing observation opens up opportunities to improve LL treatment strategy and patient outcome based on optimization of bubble dynamics, instead of maximizing laser energy delivery to the stone. The overarching goal of our P20 program is to promote multidisciplinary collaborations from basic to translational and clinical research applied to improve the efficiency and safety of LL treatment for USD. CAIRIBU P20 Exploratory Centers for Interdisciplinary Research in Benign Urology University of Tennessee Health Science Center 2019-2021 PI, Georgi Petkov, PhD NOVEL APPROACH IN UROLOGICAL RESEARCH REVEALS DIFFERENTIAL ION CHANNEL SUBCELLULAR LOCALIZATION IN HUMAN URINARY BLADDER SMOOTH MUSCLE M. Dennis Leo1, John Malysz1, Eric S. Rovner1,2, Robert Wake1,3, Wenkuan Xin1, Georgi V. Petkov1,3,4 1Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN; 2Department of Urology, Medical University of South Carolina, Charleston, SC; 3Department of Urology; and 4Department of Pharmacology, College of Medicine, University of Tennessee Health Science Center INTRODUCTION AND BACKGROUND: Contraction and relaxation of detrusor smooth muscle (DSM) control micturition. DSM cell excitability and contractility depend on synchronized activity of multiple ion channel types. Our group, in collaboration with urologists, has the unique advantage to study the expression, function, and regulation of human DSM ion channels. Here, we have focused on two key DSM channel families: the TRPM (activation causes membrane depolarization and contraction) and voltage-gated Kv7 (activation causes hyperpolarization and relaxation). To exert their regulatory role, these channels would be expected to be localized to the DSM plasma membrane but so far investigations confirming this are lacking. To test this hypothesis, we selected the three most important family member representatives, the TRPM4, Kv7.4 and Kv7.5 channels in order to investigate their cellular localization. METHODS: We have employed a novel technique called ‘surface biotinylation’ in conjunction with immunocytochemistry to examine the overall plasma membrane versus intracellular localization of these three ion channels. Human DSM tissue strips were incubated with non-cell permeable biotin tagged reagents that specifically bind to cysteine and lysine protein residues. Biotinylated surface proteins were then separated using avidin beads, eluted and Western blotting performed to determine the overall surface (plasma membrane) to intracellular localization of these channel proteins. Immuocytochemistry analyses for Kv7.4 and Kv7.5 channels were also performed on freshly isolated human DSM cells. RESULTS: Surface biotinylation revealed that >85% of total TRPM4 protein was localized to the surface of human DSM cells, with only ~15% appearing in the intracellular fraction. Similarly, >82% of total KV7.4 and ~66% of total Kv7.5 proteins were also localized on the surface of DSM cells. Interestingly, the Kv7.5 distribution surface/intracellular (~66%/34%) ratio was the lowest among the three channels studied. Immunocytochemistry data analyses revealed that Kv7.4 channels were predominantly surface localized while Kv7.5 displayed a uniform distribution. CONCLUSION: By employing surface biotinylation, a novel approach in urological research, along with immunocytochemistry, we revealed differential expression of ion channel subunits in human DSM. These exciting new data offer vital clues to the relative importance of the TRPM4 and Kv7 channels in regulating human bladder function. FUNDING: NIH R01 HL-149662 to M. Dennis Leo, NIH P20 DK-123971, NIH R01 DK-106964, and Van Vleet Endowment to Georgi V. Petkov. (See the 2 posters from this P20 Center for more details about this Center’s research) CAIRIBU P20 Exploratory Centers for Interdisciplinary Research in Benign Urology Vanderbilt University Medical Center 2019-2021 PI, Maria Hadjifrangiskou, PhD THE VANDERBILT UROLOGIC INFECTION REPOSITORY, A RESOURCE FOR PERSONALIZED CLINICAL DISCOVERY SUMMARY. In personalized medicine, the care of each patient is guided by his/her unique clinical circumstances. At its foundation, however, this paradigm holds a concurrent need for personalized science, in which technologies are developed and hypothesis explored in light of individual diversity. Critically, this diversity also includes unique microbial populations, which can augment the onset, progression, and treatment of disease. Within the field of benign urology, one of the most common pathologies—urinary tract infections (UTIs)—is also one of the most heterogenous, as the risk factors, symptomatology, and outcomes can vary significantly from patient to patient. Not surprisingly, the complexity of UTIs extends beyond the host, with tremendous genotypic and phenotypic diversity among the species/strains of microbes that e licit these infections. To better align the management of UTIs with the goals of precision care, our understanding of pathophysiology must become more nuanced, as we network in tandem the inherent diversity of host and microbe. To these ends, we propose a resource that provides an interconnected picture of both components, the Vanderbilt Urologic Infection Repository (VUIR). With our institution's unique foundation in medical informatics, we will create a searchable database of clinical parameters from bacteriuric patients (many thousands of cases annually), together with microbiologic data on the organisms.

Ion channels of the urinary bladder smooth muscle (UBSM) determine cellular excitability and contractility and, hence, regulate the two main functions of the organ, urine storage and voiding. Preparation of the viable, fresh, and single UBSM cells presents an important technical challenge for subsequent biophysical and electrophysiological studies. Here, we describe a method for successfully obtaining freshly-isolated human single UBSM cells from patient-donors undergoing open bladder surgeries and its application for the recording of voltage-step-induced cation currents. The initial step in the method involves dissection to separate the UBSM layer (also known as detrusor smooth muscle and muscularis propria) from mucosa (urothelium, lamina propria, and muscularis mucosa). The UBSM is then cut into small pieces in Ca2+-free (nominal) dissection/digestion solution (DS). UBSM pieces are next transferred to and sequentially treated separately with DS containing papain and collagenase at ∼37 °C for 30-45 min per step. Following washes with enzyme-free DS and trituration with a fire-polished pipette, the pieces release single UBSM cells. Freshly-isolated UBSM cells are ideally suited for patch-clamp electrophysiological and pharmacological characterizations. Specifically, single UBSM cells contract in response to the muscarinic agonist carbachol (3 μM). In amphotericin-B perforated patch-clamp recordings, the TRPM4 channel blocker 9-phenanthrol concentration-dependently reduces voltage-step-induced cation currents. UBSM cells can also be studied by other techniques such as: single cell RT-PCR, microarray analysis, immunocytochemistry, in situ proximity ligation assay, and Ca2+ imaging. Studies on freshly-isolated human UBSM cells have provided important insights characterizing the properties of various ion channels including cation-permeable channels in the urinary bladder and will continue as a gold standard in elucidating UBSM cellular properties and regulatory mechanisms. Funding: NIH R01DK106964 grant to Georgi V. Petkov.

608 Background: To investigate the association of serum uric acid (SUA) levels along with statin use in Renal Cell Carcinoma (RCC), as statins may be associated with improved outcomes in RCC and SUA elevation is associated with increased risk of chronic kidney disease (CKD). Methods: Retrospective study of patients undergoing surgery for RCC with preoperative and postoperative SUA levels between 8/2005-8/2014. Increased SUA was defined as > 7mg/dL for males and > 5.7 mg/dL for females. Analysis was carried out between patients with increased postoperative SUA vs. patients with decreased/stable postoperative SUA. Kaplan-Meier analysis (KMA) calculated overall survival (OS). Multivariable analysis (MVA) was performed to identify factors associated with increased SUA levels and all-cause mortality. Results: 905 patients were analyzed. Decreased/stable SUA levels were noted in 675(74.6%) and increased SUA levels were noted in 230(25.4%). A higher proportion of patients with decreased/stable SUA levels took statins (27.9% vs 18.3%, p = 0.004). Increased SUA had significantly greater de novo CKD (38.7% vs. 18.4%, p < 0.001) and proteinuria (30.9% vs. 20.7%, p = 0.002). KMA demonstrated improved 5-year OS for patients with decreased/stable SUA compared to increased SUA for stage I, (93% vs. 60%), stage II (87% vs. 50%), and stage III (88% vs. 62%) RCC (all p < 0.001). MVA revealed that increasing BMI (OR 1.05, p = 0.009), statin use (OR 0.11, p < 0.001), dyslipidemia (OR 2.66, p = 0.004), stage III/IV cancer (OR 1.89, p = 0.015 and OR = 10.78, p < 0.001), and postoperative de novo CKD stage 3 (OR 5.95, p < 0.001) were predictors for increased postoperative SUA levels. MVA revealed increasing BMI (OR 1.09, p = 0.002), increasing SUA (OR = 4.70, p < 0.001), stage IV RCC (OR = 7.7, p < 0.001, and de novo CKD stage 3 (OR 7.07, p < 0.001) to be independent risk factors for worsened all-cause mortality. Conclusions: Increasing SUA post operatively was associated with worsened outcomes in RCC patients. Decreased SUA levels were associated with statin intake and lower stage disease as well as lack of progression to CKD and anemia. Further investigation is requisite.

Glomus tumors are typically benign lesions that most often arise in the extremities. They are derived from the glomus body which is physiologically involved in thermoregulation. Usually these tumors are found in the subungual area of the fingers and toes; they are rarely found of the genitalia. In this study, we report the third known case of a glomus tumor of the scrotal skin. Our patient was a 53-year-old man of Middle Eastern descent who was diagnosed with a glomus tumor after a scrotal lesion was removed in our office under local anesthesia. Histopathological evaluation revealed a well circumscribed, 1 cm nodule that stained positive for alpha smooth muscle myosin and vimentin, and negative for S-100 and CD-34. Treatment of glomus tumors is primarily surgical and diagnosis is made on final pathology; low recurrence rates have been reported.

Aim and Background: To investigate the association of serum uric acid (SUA) levels along with statin use in Renal Cell Carcinoma (RCC), as statins may be associated with improved outcomes in RCC and SUA elevation is associated with increased risk of chronic kidney disease (CKD). Methods: Retrospective study of patients undergoing surgery for RCC with preoperative/postoperative SUA levels between 8/2005-8/2018. Analysis was carried out between patients with increased postoperative SUA vs. patients with decreased/stable postoperative SUA. Kaplan-Meier analysis (KMA) calculated overall survival (OS) and recurrence free survival (RFS). Multivariable analysis (MVA) was performed to identify factors associated with increased SUA levels and all-cause mortality. The prognostic significance of variables for OS and RFS was analyzed by cox regression analysis. Results: Decreased/stable SUA levels were noted in 675 (74.6%) and increased SUA levels were noted in 230 (25.4%). A higher proportion of patients with decreased/stable SUA levels took statins (27.9% vs. 18.3%, p = 0.0039). KMA demonstrated improved 5- and 10-year OS (89% vs. 47% and 65% vs. 9%, p < 0.001) and RFS (94% vs. 45% and 93% vs. 34%, p < 0.001), favoring patients with decreased/stable SUA levels. MVA revealed that statin use (Odds ratio (OR) 0.106, p < 0.001), dyslipidemia (OR 2.661, p = 0.004), stage III and IV disease compared to stage I (OR 1.887, p = 0.015 and 10.779, p < 0.001, respectively), and postoperative de novo CKD stage III (OR 5.952, p < 0.001) were predictors for increased postoperative SUA levels. MVA for all-cause mortality showed that increasing BMI (OR 1.085, p = 0.002), increasing ASA score (OR 1.578, p = 0.014), increased SUA levels (OR 4.698, p < 0.001), stage IV disease compared to stage I (OR 7.702, p < 0.001), radical nephrectomy (RN) compared to partial nephrectomy (PN) (OR 1.620, p = 0.019), and de novo CKD stage III (OR 7.068, p < 0.001) were significant factors. Cox proportional hazard analysis for OS revealed that increasing age (HR 1.017, p = 0.004), increasing BMI (Hazard Ratio (HR) 1.099, p < 0.001), increasing SUA (HR 4.708, p < 0.001), stage III and IV compared to stage I (HR 1.537, p = 0.013 and 3.299, p < 0.001), RN vs. PN (HR 1.497, p = 0.029), and de novo CKD stage III (HR 1.684, p < 0.001) were significant factors. Cox proportional hazard analysis for RFS demonstrated that increasing ASA score (HR 1.239, p < 0.001, increasing SUA (HR 9.782, p < 0.001), and stage II, III, and IV disease compared to stage I (HR 2.497, p < 0.001 and 3.195, p < 0.001 and 6.911, p < 0.001) were significant factors. Conclusions: Increasing SUA was associated with poorer outcomes. Decreased SUA levels were associated with statin intake and lower stage disease as well as lack of progression to CKD and anemia. Further investigation is requisite.

You have accessJournal of UrologyLate-Breaking S&T Poster1 Apr 2016LB-S&T-06 NOVEL DUAL-BINDING SELECTIVE DEGRADERS OF FULL LENGTH AND SPLICE VARIANT ANDROGEN RECEPTORS FOR THE TREATMENT OF CASTRATION-RESISTANT PROSTATE CANCER Suriyan Ponnusamy, Christopher Coss, Dong-Jin Hwang, Iain McEwan, Carolyn Watt, Thirumagal Thiyagarajan, Christopher Ledbetter, Anthony Patterson, Brandy Grimes, Robert Wake, Lee Schwartzberg, James Dalton, Duane Miller, and Ramesh Narayanan Suriyan PonnusamySuriyan Ponnusamy More articles by this author , Christopher CossChristopher Coss More articles by this author , Dong-Jin HwangDong-Jin Hwang More articles by this author , Iain McEwanIain McEwan More articles by this author , Carolyn WattCarolyn Watt More articles by this author , Thirumagal ThiyagarajanThirumagal Thiyagarajan More articles by this author , Christopher LedbetterChristopher Ledbetter More articles by this author , Anthony PattersonAnthony Patterson More articles by this author , Brandy GrimesBrandy Grimes More articles by this author , Robert WakeRobert Wake More articles by this author , Lee SchwartzbergLee Schwartzberg More articles by this author , James DaltonJames Dalton More articles by this author , Duane MillerDuane Miller More articles by this author , and Ramesh NarayananRamesh Narayanan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.03.087AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The clinical success of new androgen receptor (AR)-targeted therapies in patients with castration-resistant prostate cancer (CRPC) emphasizes the continued importance of the AR signaling axis in the disease. Despite the use of this new generation of therapies, some men with CRPC do not respond and resistance to these therapies typically develops for those that do. Mechanisms attributed to the emergence of this non-responsive CRPC include the expression of ligand binding domain (LBD)-null constitutively active splice variants of the AR (AR-SV), hyperactive AR, and others. These AR-SV expressing CRPCs require alternate approaches to inhibit both the full length and AR-SVs. The objective of this work is to develop selective androgen receptor degraders (SARDs) that degrade all forms of the AR and provide advanced treatment options to men with CRPC. METHODS AR ligand binding, transactivation, fluorescence polarization, and Western blot assays were performed to screen novel SARDs. Prostate cancer cell line gene expression, proliferation, cell line and patient-derived xenografts (PDX) were performed to evaluate the efficacy of SARDs. Molecular mechanistic studies were performed to understand the mechanism of action. RESULTS A novel series of highly potent SARDs with unique pharmacology have been discovered. These compounds selectively bind to the LBD, inhibit, and degrade the AR at nanomolar concentrations. The SARDs degrade AR-V7 and other variants that lack the LBD and inhibit the proliferation of AR- and AR-SV- dependent PCa cells with potencies better than that of comparators. SARDs robustly inhibit the growth of the LNCaP androgen-dependent prostate cancer (PCa) xenograft, the 22RV1 CRPC xenograft, and AR- and AR-SV- positive CRPC patient-derived xenografts (PDX). 22RV1 and PDX Pr-3001 are dependent on AR-SV expression and the observed inhibition of growth is indicative of the SARDs′ ability to inhibit the AR-SV activity in vivo. Quenching of the steady-state fluorescence spectrum supports an interaction between the SARDs and the AR activation function domain (AF-1), making these molecules first-in-class dual-interacting AR antagonists and degraders. Ongoing studies are revealing the mechanism of action for these SARDs. CONCLUSIONS Novel highly potent SARDs that interact with both the AF-1 and LBD of the AR were discovered and characterized as a potential next-generation treatment option for CRPC. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e337-e338 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Suriyan Ponnusamy More articles by this author Christopher Coss More articles by this author Dong-Jin Hwang More articles by this author Iain McEwan More articles by this author Carolyn Watt More articles by this author Thirumagal Thiyagarajan More articles by this author Christopher Ledbetter More articles by this author Anthony Patterson More articles by this author Brandy Grimes More articles by this author Robert Wake More articles by this author Lee Schwartzberg More articles by this author James Dalton More articles by this author Duane Miller More articles by this author Ramesh Narayanan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

You have accessJournal of UrologyScience & Technology Posters1 Apr 2016S&T-02 PERCENTAGE OF RENAL PARENCHYMAL PRESERVATION AND RENAL TUMOR MORPHOLOGY ARE DETERMINANTS OF RENAL FUNCTIONAL OUTCOME FOLLOWING PERCUTANEOUS CRYOABLATION Catherine Dufour, Alp Beksac, Zachary Hamilton, Unwanaobong Nseyo, Sean Berquist, Abdel-rahman Hassan, Song Wang, Jason Woo, Gerant Rivera-Sanfeliz, Michael Liss, Robert Wake, and Ithaar Derweesh Catherine DufourCatherine Dufour More articles by this author , Alp BeksacAlp Beksac More articles by this author , Zachary HamiltonZachary Hamilton More articles by this author , Unwanaobong NseyoUnwanaobong Nseyo More articles by this author , Sean BerquistSean Berquist More articles by this author , Abdel-rahman HassanAbdel-rahman Hassan More articles by this author , Song WangSong Wang More articles by this author , Jason WooJason Woo More articles by this author , Gerant Rivera-SanfelizGerant Rivera-Sanfeliz More articles by this author , Michael LissMichael Liss More articles by this author , Robert WakeRobert Wake More articles by this author , and Ithaar DerweeshIthaar Derweesh More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2831AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Percutaneous renal cryoablation (PRC) is an option for management of small renal mass (SRM). We investigated renal functional outcomes in PRC focusing on percent parenchyma spared and RENAL nephrometry score as a measure of tumor morphology. METHODS Multicenter retrospective analysis of patients who underwent PRC for SRM from 09/2005-08/2014. A cut off of 25% decrease (6 months post procedure-pre procdure) in estimated glomerular filtration rate (eGFR, MDRD) was utilized as a surrogate for significant renal functional decline. We divided the cohort into patients who had >25% and ≤25% decline in eGFR post PRC. RENAL score was assigned to all tumors. Percent parenchymal preservation (PPP) was calculated with 3-dimensional imaging. Demographic, perioperative factors, RENAL score, and PPP were analyzed between the two groups. Multivariable analysis (MVA) was performed to identify risk factors associated with renal functional decline. RESULTS 153 patients [23.5% (36 with >25% decline)/76.5% (117 with ≤25% decline); median follow up 48 months] were analyzed. More female (63.9% vs. 28.2%, p=0.0001) and diabetic (41.7% vs. 26.2%, p=0.021) patients had decrease of eGFR>25%. Median tumor size was significantly higher in the >25% eGFR decrease (2.8 vs. 2.4 cm, p=0.005) as was median RENAL score (7 vs. 5, p<0.001). Complication rates were not significantly different (p=0.079). Significantly less PPP (70% vs. 85%, p<0.0001) and higher median number of probes (3 vs. 2, p<0.001) were noted in >25% eGFR decline group. MVA demonstrated decreasing PPP (OR 1.4, p<0.0001), increasing RENAL score (OR 2.41, p=0.004) and female sex (OR 7.18, p=0.013) as independent risk factors for decrease in eGFR >25%. CONCLUSIONS Absence of global renal ischemic insult does not protect the kidney from renal functional decline and a significant proportion of patients may yet go on to suffer significant decreases in GFR. Increasing tumor complexity and decreasing percentage parenchyma spared and female sex were independently associated with significant renal functional decline. Development of predictive computer modeling to aid in optimal patient selection and procedure planning may aid in optimizing renal functional outcomes. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e308-e309 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Catherine Dufour More articles by this author Alp Beksac More articles by this author Zachary Hamilton More articles by this author Unwanaobong Nseyo More articles by this author Sean Berquist More articles by this author Abdel-rahman Hassan More articles by this author Song Wang More articles by this author Jason Woo More articles by this author Gerant Rivera-Sanfeliz More articles by this author Michael Liss More articles by this author Robert Wake More articles by this author Ithaar Derweesh More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer Early Detection provide recommendations for prostate cancer screening in healthy men who have elected to participate in an early detection program. The NCCN Guidelines focus on minimizing unnecessary procedures and limiting the detection of indolent disease. These NCCN Guidelines Insights summarize the NCCN Prostate Cancer Early Detection Panel's most significant discussions for the 2016 guideline update, which included issues surrounding screening in high-risk populations (ie, African Americans, BRCA1/2 mutation carriers), approaches to refine patient selection for initial and repeat biopsies, and approaches to improve biopsy specificity.

Prostate cancer represents a spectrum of disease that ranges from nonaggressive, slow-growing disease that may not require treatment to aggressive, fast-growing disease that does. The NCCN Guidelines for Prostate Cancer Early Detection provide a set of sequential recommendations detailing a screening and evaluation strategy for maximizing the detection of prostate cancer that is potentially curable and that, if left undetected, represents a risk to the patient. The guidelines were developed for healthy men who have elected to participate in the early detection of prostate cancer, and they focus on minimizing unnecessary procedures and limiting the detection of indolent disease.