Trimethoprim-Sulfamethoxazole is a common antibiotic used to treat urinary tract infections, as well as a prophylactic agent in HIV patients with low CD4 counts. Exceedingly rare are stones consisting purely of its metabolite, N4-acetyl-sulfamethoxazole, and management strategies are not well documented in the literature. We present a case of a patient with HIV who was found to have obstructing ureteral calculi composed of 100% N4-acetyl-sulfamethoxazole. Our report contributes a unique case of a Bactrim-induced stone in an immunocompromised patient. Similar patients can be prophylactically treated with diuresis and urinary alkalinization, as well as consideration for alternative medication use.

Medical expulsive therapy (MET) for ureteral stones involves the administration of pharmaceutical agents to facilitate passage of stones by ideally increasing the rate of passage and reducing time for expulsion. Several medications have been studied for this use. The most commonly studied off-label medications include α1-antagonists and calcium channel blockers. This article reviews the data available for the use of MET and controversies in the use of medications to aid stone passage based on more recent randomized controlled trials and meta-analyses. Based on the latest guidelines, α-blockers have been the most studied medication type and may have some benefit in the passage of distal ureteral stones greater than 4 mm in size. This review contains 2 figures and 34 references. Keywords: α1-antagonists, α-blockers, calcium channel blockers, medical expulsion therapy, phosphodiesterase inhibitors, ureteral stones

Background: Bilateral ureteroceles in adult males are a rare occurrence, made even more so with simultaneous presence of bladder calculi. Management strategies for such patients are not well documented in the literature. We present a rare case of bilateral open ureteroceles with large concomitant bladder calculi to contribute to the paucity of literature on management of such patients. Case Presentation: We present the case of a 35-year-old man whose gross hematuria work-up demonstrated right-sided hydroureteronephrosis in the setting of bilateral ureteroceles and multiple large bladder calculi up to 3.8 cm. Conclusion: Bilateral orthotopic single-system ureteroceles in an adult male are a rare finding especially when intraoperatively found to be open secondary to traumatic effects of large calculi. Ultrasonic and pneumatic lithotripsy is a safe, appropriate, and effective option for bilateral ureteroceles contributing to a large bladder stone burden. Our report contributes to the growing body of literature on orthotopic bilateral single-system ureteroceles in the adult population with concomitant significant stone burden.

Therapeutic living donor nephrectomy is defined as a nephrectomy that is performed as therapy for an underlying medical condition. The patient directly benefits from having their kidney removed, but the kidney is deemed transplantable. The kidney is subsequently used as an allograft for an individual with advanced renal disease. Therapeutic donor nephrectomy can be successfully utilized for a heterogenous cohort of disease processes as both treatment for the donor and to increase the number of suitable organs available for transplantation. We describe four cases of therapeutic donor nephrectomy that were performed at our institution. Of the four cases, two patients elected to undergo therapeutic donor nephrectomy as treatment for loin pain hematuria syndrome; one after blunt abdominal trauma that resulted in complete proximal ureteral avulsion; and the fourth after being diagnosed with a small renal mass. Based on our data presented to the United Network for Organ Sharing Board of Directors (UNOS) in December 2015, living donor evaluation has been made simpler for patients electing to undergo therapeutic donor nephrectomy. UNOS eliminated the requirement for a psychosocial evaluation for these patients. As the organ shortage continues to limit transplantation, therapeutic donor nephrectomy should be considered when appropriate.

You have accessJournal of UrologyStone Disease: Surgical Therapy II (MP17)1 Apr 2019MP17-15 AMBULATORY PERCUTANEOUS NEPHROLITHOTOMY PERFORMED IN A FREE-STANDING SURGERY CENTER: OUTCOMES OF THE FIRST 420 CASES Mark V. Silva, MD Meagan M. Dunne, MD* Joel E. Abbott, andDO Julio G. DavalosMD Mark V. SilvaMark V. Silva More articles by this author , Meagan M. DunneMeagan M. Dunne More articles by this author , Joel E. AbbottJoel E. Abbott More articles by this author , and Julio G. DavalosJulio G. Davalos More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000555440.22544.ecAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: Percutaneous Nephrolithotomy (PNL) is a procedure that has traditionally been performed in an inpatient setting with at least an overnight stay. Many surgical procedures have evolved over time from an inpatient setting to an ambulatory surgery center (ASC) setting. Feasibility of Ambulatory PNL (aPNL) was shown in our initial pilot series of 25 cases [1]. This 420 case series is reviewed to further evaluate outcomes with a more robust data set. METHODS: We present our initial series of 420 patients who underwent PNL in an ASC from April 2015 to October 2018. Each aPNL was performed by one of two surgeons with the same operative team. All procedures were performed with the operative surgeon obtaining renal access and all procedures were performed tubeless (ureteral stent without a nephrostomy tube). All patients also had hemostatic plugs placed into the access tract with a local intercostal block performed to aid with pain control.[2] All cases were reviewed and demographic data and case details were analyzed. RESULTS: Our initial 420 consecutive aPNL cases were reviewed, identifying 192 men and 228 women, 202 right side and 218 left, one bilateral, mean age 57.2 years (16-86), mean BMI 30.6 (16-49), mean ASA of 2.3 (range 1-4) and mean stone burden 30.4 mm (5-140mm), mean fluoroscopy time 86 sec (0-299). Mean OR time was 105 min (range 32-305 min). Mean PACU time was 98 min (range 37-240 min). A mini-PCNL procedure was conducted in 80 (23%) patients. Stone free rate was 83%. Twenty patients had complications ranging from Clavien I-IVa, of which 12 were hospital transfers. CONCLUSIONS: This consecutive 420 case series further demonstrates the safety of aPNL. While twenty patients experienced complications, the site of service did not lead to an alteration in the outcomes of the adverse events. Each complication that occurred was managed in an appropriate fashion without notable treatment delay. Our complication rate in the ASC is lower than reported in large cohort studies and lower than our hospital based patient population, however recognizing these patients are preselected. With an experienced surgeon, well trained operative team and with modifications to the procedure focusing on post-operative pain control, PNL can be safely and effectively performed in an ASC. 1. Davalos JG, Abbott JE. Ambulatory PCNL: Initial Case Series. J Urology. April 2016. Vol. 195 (4), Supplement 1: MP51-20, e688-e689. 2 2. Abbott JE, Cicic, A, Jump III RW, Davalos JG. Hemostatic Plug: Novel Technique for Closure of Percutaneous Nephrostomy Tract. J Endourol. March 2015, 29(3): 263-269. Source of Funding: None Baltimore, MD© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e261-e261 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mark V. Silva More articles by this author Meagan M. Dunne More articles by this author Joel E. Abbott More articles by this author Julio G. Davalos More articles by this author Expand All Advertisement PDF downloadLoading ...

OBJECTIVE To determine stone clearance rates using endoscopic combined intrarenal surgery (ECIRS) and assess the accuracy of intraoperative prediction of stone-free (SF) status compared to postoperative CT scan. METHODS A single institution, prospectively maintained database of ECIRS was queried for procedures performed 8/2017 to 1/2018. Retrograde access was performed using a ureteral sheath and flexible ureteroscope. Percutaneous nephrolithotomy was performed through a 30fr or 18fr sheath in prone position. Residual stone status was estimated at the end of each procedure and was verified with postoperative CT scan. SF was defined as no single stone >2mm(3) on CT. RESULTS One hundred and ten procedures were reviewed. Average age was 58.9 +/- 12.6 years (range 26-87) and 69 (63%) were male. The mean stone size was 33.3 +/- 23.5 mm (range 4-140 mm). Ninty-three patients (84.5%) were endoscopically estimated to be SF, of which 84 (90% of predicted SF cohort, 76% of total cohort) were confirmed SF via CT scan. The sensitivity for estimating SF status with ECIRS was 65.4% (95%CI 44.3%-82.8%), specificity was 100% (95%CI 95.7%-100.0%) and accuracy was 91.8% (95%CI 85.0%-96.2%). SF patients had significantly smaller stones than those with residual fragments (28.5 +/- 2.1 vs 48.4 +/- 5.7mm, P <.0001). On logistic regression, the factors associated with residual stones were preoperative stone burden (OR 1.03 per mm, 95%CI 1.01-1.05, P = .0004) and fluoroscopy time (OR 1.01 per minute, 95%CI 1.0-1.02, P = .0081). CONCLUSION ECIRS accurately predicts clinical SF status and may obviate the need for additional CT scans. Consistent with prior studies, the primary determinant of residual stone after percutaneous nephrolithotomy is initial stone size. (C) 2019 Elsevier Inc.

Retrograde flexible ureteroscopy is a widely utilized technique for evaluation and treatment of both benign and malignant upper urinary tract pathology. In this chapter, we review the preoperative evaluation of these patients, the equipment and techniques for standard and difficult ureteral access, and the role and technique for ureteral access sheath placement.

Bladder cancer is the fifth most prevalent cancer in the U.S., yet is understudied, and few laboratory models exist that reflect the biology of the human disease. Here, we describe a biobank of patient-derived organoid lines that recapitulates the histopathological and molecular diversity of human bladder cancer. Organoid lines can be established efficiently from patient biopsies acquired before and after disease recurrence and are interconvertible with orthotopic xenografts. Notably, organoid lines often retain parental tumor heterogeneity and exhibit a spectrum of genomic changes that are consistent with tumor evolution in culture. Analyses of drug response using bladder tumor organoids show partial correlations with mutational profiles, as well as changes associated with treatment resistance, and specific responses can be validated using xenografts in vivo. Our studies indicate that patient-derived bladder tumor organoids represent a faithful model system for studying tumor evolution and treatment response in the context of precision cancer medicine.

You have accessJournal of UrologyStone Disease: Surgical Therapy VI1 Apr 2018MP89-02 AMBULATORY PERCUTANEOUS NEPHROLITHOTOMY PERFORMED IN A FREE-STANDING SURGERY CENTER: OUTCOMES OF THE FIRST 219 CASES Joel E. Abbott, Mark V. Silva, and Julio G. Davalos Joel E. AbbottJoel E. Abbott More articles by this author , Mark V. SilvaMark V. Silva More articles by this author , and Julio G. DavalosJulio G. Davalos More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2942AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Percutaneous Nephrolithotomy (PNL) is a procedure that has traditionally been performed in an inpatient setting with at least an overnight stay. Many surgical procedures have evolved over time from an inpatient setting to an ambulatory surgery center (ASC) setting. Feasibility of Ambulatory PNL (aPNL) was shown in our initial pilot series of 25 cases [1]. This 219 case series is reviewed to further evaluate outcomes with a more robust data set. METHODS We present our initial series of 219 patients who underwent PNL in an ASC from April 2015 to November 2017. Each aPNL was performed by one of two surgeons with the same operative team. The surgeon and operative team have extensive experience with PNL performed in a hospital setting. All procedures were performed with the operative surgeon obtaining renal access and all procedures were performed tubeless (ureteral stent without a nephrostomy tube). All patients also had hemostatic plugs placed into the access tract with a local intercostal block performed to aid with pain control.2 All cases were reviewed and demographic data and case details were analyzed. RESULTS Our initial 219 consecutive aPNL cases were reviewed, identifying 121 women, 114 left side, one bilateral, mean age 55 (21-86), mean BMI 31 (17-49), and mean stone burden 29 mm (8-110), mean fluoroscopy time 83 sec (27-299). Stone free rate was 94%. 12 patients had complications ranging Clavien I-IIIb, of which two were hospital transfers. CONCLUSIONS This consecutive 219 case series further demonstrates the safety of aPNL. While twelve patients experienced complications, the site of service did not lead to an alteration in the outcomes of the adverse events. Each complication that occurred was managed in an appropriate fashion without notable treatment delay. Our complication rate in the ASC is lower than reported in large cohort studies and lower than our hospital based patient population, however recognizing these patients are preselected. With an experienced surgeon, well trained operative team and with modifications to the procedure focusing on post-operative pain control, PNL can be safely and effectively performed in an ASC. 1. Davalos JG, Abbott JE. Ambulatory PCNL: Initial Case Series. J Urology. April 2016. Vol. 195 (4), Supplement 1: MP51-20, e688-e689. 2. Abbott JE, Cicic, A, Jump III RW, Davalos JG. Hemostatic Plug: Novel Technique for Closure of Percutaneous Nephrostomy Tract. J Endourol. March 2015, 29(3): 263-269. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1206 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Joel E. Abbott More articles by this author Mark V. Silva More articles by this author Julio G. Davalos More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I1 Apr 2018MP54-13 BLUE LIGHT IN COMBINATION WITH HEAMINOLEVULINATE (CYSVIEW®) LEADS TO BLADDER CANCER CELL DEATH IN AN IN VITRO MODEL Justin T. Matulay, Alanna B. Williams, Mark V. Silva, James M. McKiernan, and Michael M. Shen Justin T. MatulayJustin T. Matulay More articles by this author , Alanna B. WilliamsAlanna B. Williams More articles by this author , Mark V. SilvaMark V. Silva More articles by this author , James M. McKiernanJames M. McKiernan More articles by this author , and Michael M. ShenMichael M. Shen More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1704AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Blue light cystoscopy with hexaminolavulinate (HAL, Cysview®) improves detection of bladder cancer over white light cystoscopy alone, and has been FDA-approved for this purpose. Photodynamic therapy (PDT) is used as a treatment for various malignancies, but aside from some small phase I trials, has not been utilized in treatment of bladder cancer. The purpose of this study was to measure the cell death effect of HAL/Blue light on patient-derived bladder cancer organoids. METHODS Fresh bladder cancer specimens were collected as part of an IRB approved protocol (AAAN8850) and grown as 3D bladder cancer organoids per lab protocol. Organoids were treated with saline 100uM, HAL 10uM, HAL 100uM, camptothecin 10uM, or camptothecin 100uM, then incubated for 4 hours. One group of HAL treated organoids at each drug concentration was exposed to blue light while the groups remained in the incubator. The blue light source was calibrated to deliver a peak wavelength of 410nm at an energy of 1J/cm2. Cell viability was assessed using the Promega CellTiter-Glo® luminescent cell viability assay at 18 hours and caspase-3 activity was assessed on histologic specimens at 6, 12, and 18 hours. RESULTS Bladder cancer organoid cell viability was significantly reduced by 95% and 97% for HAL+Blue Light treated organoids at drug concentrations of 10uM and 100uM, respectively. HAL treatment alone reduced cell viability by 19% and 21% for concentrations of 10uM and 100uM, respectively. P-value < 0.0001 for all comparison groups (figure). Histologic staining for caspase-3 was sparse and did not show significant difference between saline controls, HAL alone, or HAL+Blue Light treated organoids but was increased in the camptothecin treated group. CONCLUSIONS The combination of HAL and Blue Light drastically reduces cell survival in patient-derived bladder cancer organoids. These results suggest that beyond the diagnostic utility of Blue Light Cystoscopy with HAL there is a potential for therapeutic benefit. Further investigation into the apoptotic pathway is warranted based on IHC staining results. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e716-e717 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Justin T. Matulay More articles by this author Alanna B. Williams More articles by this author Mark V. Silva More articles by this author James M. McKiernan More articles by this author Michael M. Shen More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

You have accessJournal of UrologyStone Disease: Surgical Therapy IV1 Apr 2018MP68-14 ARE TWO VIEWS BETTER THAN ONE? MULTI-SCOPE PERCUTANEOUS NEPHROLITHOTOMY HAS HIGH STONE CLEARANCE RATES ON POSTOPERATIVE CT Mark V. Silva, Alexander C. Small, Joel E. Abbott, and Julio G. Davalos Mark V. SilvaMark V. Silva More articles by this author , Alexander C. SmallAlexander C. Small More articles by this author , Joel E. AbbottJoel E. Abbott More articles by this author , and Julio G. DavalosJulio G. Davalos More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2218AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Percutaneous nephrolithotomy (PCNL) is often the preferred treatment modality for non-lower pole stones >20mm and for lower pole stones >10mm due to high stone clearance rates. Recently, simultaneous ureteroscopy (URS) has been used to facilitate percutaneous renal access and intraoperative manipulation of stones. This technique of ″multi-scope PCNL″ has grown in popularity and may improve stone free outcomes. This study aimed to determine the stone clearance rates of multi-scope PCNL and assess the accuracy of intraoperative stone-free prediction as compared to postoperative CT scan. METHODS A prospectively maintained database of multi-scope PCNL was queried for procedures performed 8/2017 to 11/2017. Retrograde access was performed using a 11/13fr 36cm sheath and flexible URS. Percutaneous access was guided by endoscopy and fluoroscopy and performed through a 30fr (standard) or 18fr (minimally invasive PCNL, or MIP) sheath. At the end of each procedure, patients′ residual stone (RS) status was estimated. To verify or refute this estimation, a CT scan was performed on the first post-operative or prior to stent removal. Stone-free (SF) was defined as no single stone >2mm on CT. Characteristics of SF patients and accurately-estimated patients were analyzed using t-tests, logistic regression and linear regression with p<0.05. RESULTS A total of 53 procedures were reviewed. Average age was 56 years (range 26-86) and 36 (68%) were female. The mean stone size was 29 ± 16 mm (range 7-93). PCNL access was standard in 46 (87%). Twenty three (43%) were done at the ambulatory surgery center while 30 (57%) were done at the hospital. Forty five patients (84%) were endoscopically estimated to be SF, of which 42 (79%) were confirmed SF via CT scan. Patients with RS had significantly larger preoperative stone burdens than those who were SF (42 ± 6 vs 25 ± 2 mm, p<0.001). The mean RS size was 2 ± 5 mm. Overall, the sensitivity for estimating SF status with multi-scope PCNL was 100% (95%CI 63-100) with specificity 93% (95CI 81-98%). Logistic regression revealed that preoperative stone burden was the only factor associated with RS on postoperative CT (OR 1.07, 95%CI 1.01-1.13, p = 0.00013) or inaccurate estimation of SF status (OR 1.08, 95%CI 1.00-1.18, p = 0.0021). Preoperative and RS burdens were linearly correlated (coeff 1.5, R2 0.180, p=0.002). CONCLUSIONS Multi-scope PCNL can accurately predict clinical stone free status and may obviate the need for additional CT scans and reduce ionizing radiation exposure to patients. Consistent with prior studies, the primary determinant of residual stone after PCNL is initial stone size. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e922 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Mark V. Silva More articles by this author Alexander C. Small More articles by this author Joel E. Abbott More articles by this author Julio G. Davalos More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Objectives: To determine if greater lymph node yield (LNY) during radical prostatectomy is associated with improved biochemical recurrence for men with prostate cancer and isolated seminal vesicle invasion (SVI). Previous studies have shown that total number of lymph nodes removed at RP results in improved survival, regardless of node positivity, but this has not been examined in men with isolated SVI. Methods: The IRB-approved Columbia University Urologic Oncology Database was reviewed to identify patients who underwent RP from 1990-2011 and had prostate cancer with isolated SVI (i.e. pT3bN0Mx). BCR was defined as two postoperative PSA values >0.2 ng/mL. Cox proportional hazards model was used to determine if LNY (continuous) was predictive of BCR, when controlling for clinical and pathologic features. Results: We identified 155 patients with isolated SVI. At a mean follow-up of 48 months, 96 patients (62.5%) experienced BCR. Estimated 5-year freedom from BCR rate was 45%. Mean number of LNs removed was 8.9 (1-35). Using the Cox proportional Hazards model, continuous LNY was not significantly associated with risk of BCR (p=0.25), while PSA (HR 2.3, p=0.01), pathologic Gleason score (p=0.023), and bladder neck invasion (p=0.04) were significant. Conclusion: Seminal vesicle invasion after radical prostatectomy is associated with a high risk of BCR, even in the absence of positive surgical margins or lymphatic involvement. Our study demonstrates that the lymph node yield at the time of prostatectomy does not affect the risk of BCR in men with node-negative SVI. Further studies are warranted to evaluate cancer-specific and overall survival.

INTRODUCTION:Robotic technology has been increasingly utilized for complicated reconstructive surgeries in pediatric urology, such as ureteroureterostomy (UU). The literature is limited regarding the performance of minimally invasive UU in children, and the existing published series utilize indwelling ureteral stents. We sought to report on our pediatric experience with robot-assisted laparoscopic (RAL)-UU using a temporary ureteral catheter in duplex systems with ureteral ectopia.METHODS:A retrospective chart review was performed of all pediatric patients who underwent RAL-UU at a single institution over a 2-year period. An externalized ureteral catheter was kept overnight and removed with the indwelling catheter on postoperative day 1. Intraoperative as well as postoperative complications, length of stay (LOS), and analgesia were recorded. Follow-up renal ultrasound (US) and evaluation for symptom resolution were completed 3 months postoperatively.RESULTS:Twelve patients (four male, eight female) underwent RAL-UU at a mean age of 19.4 months (range 9-48 months) during the study period. The majority of patients (83.3%) presented with hydronephrosis, and all were found to have duplicated systems with ureteral ectopia. No child had ipsilateral vesicoureteral reflux. Two children had bilateral duplicated systems, one of which required bilateral surgery. Median operative time was 138 minutes (IQR 119-180 minutes), and mean estimated blood loss was 1.5 mL. There were no intraoperative complications, and no case required open conversion. Median hospital LOS was 31 hours (IQR 30-39 hours). Median follow-up time was 11 months (range 3-22 months). One patient developed a postoperative febrile upper respiratory infection. All patients had improved hydroureteronephrosis on US at 3 months postoperatively. One patient with preoperative urinary incontinence was dry postoperatively. Therefore, the overall success rate was 100%.CONCLUSION:Our institutional results demonstrate that RAL-UU utilizing a temporary ureteral catheter is a safe and effective technique for managing duplicated, ectopic ureters in children and infants.

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology III1 Apr 2016PD38-07 GENETIC MUTATIONS IN PATIENT-DERIVED BLADDER TUMOR ORGANOIDS MIMIC PARENTAL TUMOR SAMPLES Justin T. Matulay, Lamont J. Barlow, Mark V. Silva, Chee Wai Chua, Mitchell C. Benson, James M. McKiernan, Hikmat A. Al-Ahmadie, David B. Solit, and Michael M. Shen Justin T. MatulayJustin T. Matulay , Lamont J. BarlowLamont J. Barlow , Mark V. SilvaMark V. Silva , Chee Wai ChuaChee Wai Chua , Mitchell C. BensonMitchell C. Benson , James M. McKiernanJames M. McKiernan , Hikmat A. Al-AhmadieHikmat A. Al-Ahmadie , David B. SolitDavid B. Solit , and Michael M. ShenMichael M. Shen View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1487AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Three-dimensional cell culture from patient-derived tissue samples has been described for several cancers. The resulting organoids allow for the study of tumor phenotypes and treatment response in a model that more closely resembles parental tissue than traditional cell culture. Here we describe our success in establishing urothelial cancer organoids from patient derived bladder tumors. METHODS Using an Institutional Review Board-approved tissue acquisition protocol, informed consent was obtained prior to specimen acquisition. Specimens were collected during routine cystoscopy and enzymatically digested into single cells and cell clusters before plating in organoid-promoting embedded cell culture conditions (Figure 1). Organoids were then serially passaged and subjected to freezing and thawing cycles. DNA from parental tumor samples and organoids was sequenced using the MSK-IMPACT(TM) targeted exome sequencing panel to identify mutations. RESULTS Organoid and tumor samples from 4 lines have been analyzed using MSK-IMPACT(TM). Numerous genes known to be mutated in bladder cancer from the TCGA project were identified in our samples, including FGFR3, TP53, ARID1A, KDM6A, CDKN1A, and TSC1. Organoids exhibited mutations that were highly concordant with parental tumor samples (Table 1). Of the 4 organoid lines that have been sequenced, 3 (1-3) have been successfully thawed and passaged further. An additional 5 candidate cell lines are undergoing serial passaging and DNA sequencing (Table 2). CONCLUSIONS We have demonstrated our ability to grow bladder cancer organoids in three-dimensional cell culture from patient derived tumor samples. When compared to parental tumors, organoid lines contain similar mutations and may provide a platform for personalized drug-response assays. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e926 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Justin T. Matulay More articles by this author Lamont J. Barlow More articles by this author Mark V. Silva More articles by this author Chee Wai Chua More articles by this author Mitchell C. Benson More articles by this author James M. McKiernan More articles by this author Hikmat A. Al-Ahmadie More articles by this author David B. Solit More articles by this author Michael M. Shen More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History III1 Apr 2015MP14-03 SIMPLIFIED FRAILTY INDEX PREDICTS ADVERSE SURGICAL OUTCOMES AND INCREASED LENGTH OF STAY IN RADICAL PROSTATECTOMY PATIENTS: AN ANALYSIS OF THE ACS-NSQIP DATABASE Danny Lascano, Jamie S. Pak, Alexander C. Small, Mark V. Silva, James M. McKiernan, G. Joel DeCastro, Sven Wenske, and Mitchell C. Benson Danny LascanoDanny Lascano More articles by this author , Jamie S. PakJamie S. Pak More articles by this author , Alexander C. SmallAlexander C. Small More articles by this author , Mark V. SilvaMark V. Silva More articles by this author , James M. McKiernanJames M. McKiernan More articles by this author , G. Joel DeCastroG. Joel DeCastro More articles by this author , Sven WenskeSven Wenske More articles by this author , and Mitchell C. BensonMitchell C. Benson More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.865AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Frailty is usually assessed in a non-standardized manner with descriptions of patients such as appearing “older than stated age”. Currently, no suitable measure exists to qualify this parameter, despite its potentially large impact on surgical outcomes. Therefore, a modified frailty index (FI) was applied to the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) data to evaluate whether it predicts adverse post-surgical outcomes. METHODS The ACS-NSQIP Participant Utilization File was queried for the years 2005–2012 for inpatient radical prostatectomy (RP) patients (n=16848). Employing the Canadian Study of Health and Aging frailty index, 11 variables were matched to NSQIP to create a modified frailty index (FI) using including diabetes mellitus, functional status, CHF, MI, prior cardiac surgery, hypertension, peripheral vascular disease, impaired sensorium, and TIA or CVA with neurological sequela. Four variables specific to cancer were also including: chemotherapy or radiation, weight loss, renal failure, and metastasis. Outcomes assessed included 30-day mortality, surgical site infection (SSI), MI, DVT/PE, Clavien IV complications, length of stay (LOS), and combined adverse events. Chi-square analysis was used for comparing categorical variables, Kruskal-Wallis for non-parametric continuous variables, and logistic regression for comparing different clinical tests. RESULTS Increasing FI was significantly associated with Clavien IV complications, number of SSI and all combined adverse events (p<0.05 for all). A Kruskal-Wallis H test demonstrated a statistically significant difference in LOS between those with different FI (χ2 = 88.02, p<0.01) with a mean rank of 3, 4, 6, 5, 2 and 1 day(s) for FI of 1, 2, 3, 4, 5 and 6 respectively. Multivariate analysis indicated that FI was significantly correlated with Clavien IV complications (OR 1.368, p< 0.01), MI (OR 2.745, p < 0.01), and adverse events including SSI, UTIs and DVT/PE (OR 1.371, p <0.01). CONCLUSIONS Using a large national database, a modified frailty index was shown to significantly correlate with 30-day morbidity and length of stay after RP but not with mortality. This simple tool may be useful for both risk assessment and surgical planning, especially in elderly patients with multiple comorbidities. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e151-e152 Peer Review Report Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Danny Lascano More articles by this author Jamie S. Pak More articles by this author Alexander C. Small More articles by this author Mark V. Silva More articles by this author James M. McKiernan More articles by this author G. Joel DeCastro More articles by this author Sven Wenske More articles by this author Mitchell C. Benson More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Objective: To retrospectively validate and compare a modified frailty index predicting adverse outcomes and other risk stratification tools among patients undergoing urologic oncological surgeries.Materials and Methods: The American College of Surgeons National Surgical Quality Improvement Program was queried from 2005 to 2013 to identify patients undergoing cystectomy, prostatectomy, nephrectomy, and nephroureterectomy. Using the Canadian Study of Health and Aging Frailty Index, 11 variables were matched to the database; 4 were also added because of their relevance in oncology patients. The incidence of mortality, Clavien-Dindo IV complications, and adverse events were assessed with patients grouped according to their modified frailty index score.Results: We identified 41,681 patients who were undergoing surgery for presumed urologic malignancy. Patients with a high frailty index score of >0.20 had a 3.70 odds of a Clavien-Dindo IV event (CI: 2.865-4.788, P < 0.0005) and a 5.95 odds of 30-day mortality (CI: 3.72-9.51, P < 0.0005) in comparison with nonfrail patients after adjusting for race, sex, age, smoking history, and procedure. Using C-statistics to compare the sensitivity and specificity of the predictive ability of different models per risk stratification tool and the Akaike information criteria to assess for the fit of the models with the data, the modified frailty index was comparable or superior to the Charlson comorbidity index but inferior to the American Society of Anesthesiologists Risk Class in predicting 30-day mortality or Clavien-Dindo IV events. When the modified frailty index was augmented with the American Society of Anesthesiologists Risk Class, the new index was superior in all aspects in comparison to other risk stratification tools.Conclusion: Existing risk stratification tools may be improved by incorporating variables in our 15-point modified frailty index as well as other factors such as walking speed, exhaustion, and sarcopenia to fully assess frailty. This is relevant in diseases such as kidney and prostate cancer, where surveillance and other nonsurgical interventions exist as alternatives to a potentially complicated surgery. In these scenarios, our modified frailty index augmented by the American Society of Anesthesiologists Risk Class may help inform which patients have increased surgical complications that may outweigh the benefit of surgery although this index needs prospective validation. (C) 2015 Elsevier Inc. All rights reserved.

You have accessJournal of UrologyUrinary Diversion: Bladder Reconstruction, Augmentation, Substitution, Diversion I1 Apr 2015PD9-10 TIMING OF URETERAL STENT REMOVAL AND POSTOPERATIVE COMPLICATIONS FOLLOWING RADICAL CYSTECTOMY WITH URINARY DIVERSION Justin Matulay, Christopher Sayegh, Julia Finkelstein, Mark Silva, and G. Joel DeCastro Justin MatulayJustin Matulay More articles by this author , Christopher SayeghChristopher Sayegh More articles by this author , Julia FinkelsteinJulia Finkelstein More articles by this author , Mark SilvaMark Silva More articles by this author , and G. Joel DeCastroG. Joel DeCastro More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.937AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Ureteral stent placement following radical cystectomy with urinary diversion is a commonplace practice. Stenting has been shown to reduce the rate of certain surgical complications such as anastomotic stricture and urinary leak. However, there is concern that ureteral stents may increase the rate of infection. To our knowledge, there is no published data on the optimal timing for stent removal postoperatively. Therefore, we sought to evaluate if there was any association between the length of time that ureteral stents remained in place and related postoperative complications. METHODS We retrospectively analyzed data on 58 patients from our prospectively maintained cohort of radical cystectomy patients. We noted the day of each stent removal and all complications that occurred during the hospitalization as well as after discharge. A telephone questionnaire was conducted at 1 month and 3 months post-operatively. We defined stent-related complications as pelvic collection, anastamotic leak, stricture, and UTI/pyelonephritis and infectious complications as sepsis and UTI/pyelonephritis. RESULTS Baseline characteristics for the 58 patients are presented in Table 1. With a median follow-up of 3 months, there were 21 stent-related complications in 18 (31%) patients. Median time from the date of surgery until first and second ureteral stent removal was 5.5 days and 6 days, respectively. There was no significant difference between the median day of either stent removal and stent-related postoperative complications (p=0.81 for first stent; p=0.97 for second stent). When considering infectious complications, there was also no significant difference (p=0.74 for first stent; p=0.82 for second stent). CONCLUSIONS The length of time that a ureteral stent remains in place after radical cystectomy with urinary diversion does not impact the occurrence of specific post-operative complications. Importantly, increased stent duration did not affect infectious complications. Nevertheless, given the small cohort and low rate of complications, further investigation into this topic is warranted. Demographic and Clinical Characteristics (n=58) Sex Male 47 Female 11 Race White 49 African American 6 Hispanic 2 Other 1 Diabetes Yes 13 No 45 Smoking status Never 28 Former 24 Current 6 Clinical tumor stage cis 12 A 2 1 16 2 23 3 5 4 0 Clinical node status 0 54 1+ 2 Pathologic tumor stage 0 4 cis 14 A 2 1 10 2 3 3 14 4 11 Pathologic node status 0 50 1 1 2 7 Neoadjuvant chemotherapy None 44 Gemcitabine/Cisplatin 13 Gemcitabine/Carboplatin 1 Diversion type Ileal conduit 42 Ileal neobladder 14 Indiana pouch 2 Pre-op nutritional labs Protein 7 Albumin 4.2 Robotic approach Yes 11 No 47 Operative time (mean, minutes) 457 Complication # UTI/pyelonephritis/sepsis 6 Ileus 6 Pelvic collection/abscess 10 Anastomotic leak 5 Length of stay (mean, days) 7 © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e198-e199 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Justin Matulay More articles by this author Christopher Sayegh More articles by this author Julia Finkelstein More articles by this author Mark Silva More articles by this author G. Joel DeCastro More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

You have accessJournal of UrologyPediatrics: Urinary Tract Infections/Vesicoureteral Reflux1 Apr 2015MP54-15 WHAT IS THE INCIDENCE OF DEFLUX CALCIFICATION ON ULTRASOUND? Julia B. Finkelstein, Mark V. Silva, Jennifer J. Ahn, Jason P. Van Batavia, Shumyle Alam, and Pasquale Casale Julia B. FinkelsteinJulia B. Finkelstein More articles by this author , Mark V. SilvaMark V. Silva More articles by this author , Jennifer J. AhnJennifer J. Ahn More articles by this author , Jason P. Van BataviaJason P. Van Batavia More articles by this author , Shumyle AlamShumyle Alam More articles by this author , and Pasquale CasalePasquale Casale More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2038AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Vesicoureteral reflux (VUR) affects approximately 1% of children. Traditionally, children with VUR underwent open ureteral reimplantation. This approach has largely been replaced by endoscopic treatment methods with use of injectable materials. Specifically, the endoscopic injection of dextranomer-hyaluronic acid (Deflux) has become widely used to treat VUR, with high reported success rates and minimal complications noted. However, there have been recent reports of implant calcifications misdiagnosed as urinary calculi. We sought to evaluate the incidence of calcification of this polymer in our pediatric population. METHODS With IRB approval, we retrospectively reviewed the charts of all pediatric patients who underwent endoscopic injection of deflux at our institution from January 1, 2011 to December 31, 2013. Twenty-two patients who underwent deflux injection into the bladder wall, bladder neck or urethra were excluded from the analysis. Postoperative ultrasounds were evaluated for the remaining children. If a hyperechogenic focus with shadowing was noted on ultrasound, it was recorded as a deflux calcification. RESULTS During the three-year study period, 76 children (25 boys, 51 girls) at a mean age of 9.1 years received endoscopic injection of Deflux. A second injection was performed in 4 children and 66 (82.5%) patients received bilateral injections. Overall, 142 ureters in total were injected. Mean follow-up was 18.8 months. Postoperative ultrasound was available in 87% of patients. In 8 children (10%), hyperechogenic foci were present and detected at a mean of 9.8 months postoperatively. One of these children became symptomatic, presenting 2.4 years after the procedure with flank pain. Ultrasound was suspicious for bilateral stones at the ureterovesical junctions. Subsequent non-contrast CT scan demonstrated coarse calcifications bilaterally without evidence of ureteral stones. None of the children who underwent repeated injection were noted to have a calcification on ultrasound. CONCLUSIONS In this series, the incidence of calcification of Deflux on postoperative ultrasound was 10%, with one symptomatic patient. Given the widespread use of Deflux for VUR, it is likely that an increasing number of both pediatric and adult urologists will be presented with this diagnostic dilemma. Therefore, it is important to keep this in mind when evaluating a patient with abdominal pain and a history of previous Deflux injection, thereby avoiding unwarranted intervention. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e670 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Julia B. Finkelstein More articles by this author Mark V. Silva More articles by this author Jennifer J. Ahn More articles by this author Jason P. Van Batavia More articles by this author Shumyle Alam More articles by this author Pasquale Casale More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...