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Introduction This study aimed to evaluate if race impacted outcomes or risk of disease progression in men on active surveillance (AS) for prostate cancer. We present the results from our majority African-American cohort of men in an equal access setting over a 5-year follow-up period. Patients and Methods All patients who elected AS for prostate cancer at the Southeast Louisiana Veterans Health Care System are entered into a prospectively managed observational database. Patients were divided into groups based on self-reported race. Grade group progression was defined as pathologic upgrading above International Society of Urological Pathology Grade Group 1 disease on subsequent biopsies following diagnostic biopsy. All tests were 2 sided using a significance of .05. Results A total of 228 men met inclusion criteria in the study, including 154 non-Hispanic African American and 74 non-Hispanic Caucasian American men, with a median follow-up of 5 years from the initiation of AS. Race was not predictive of Gleason grade progression, AS discontinuation, or biochemical recurrence on Cox multivariate analysis (HR = 1.01, 0.94, 0.85, P = .96, .79, .81, respectively). On Kaplan-Meier analysis at 5 years, African-American progression-free, AS discontinuation free, and overall survival probability was comparable to their Caucasian American counterparts (P > .05 for all). Conclusions Active surveillance is a safe treatment option for low and very low risk prostate cancer, regardless of race. African-American and Caucasian-American men did not have any significant difference in Gleason grade group progression in our cohort with 5-year follow-up.

Cytotoxic dose of NIR for individual cell lines

Supplemental Figure 1: Expression of EGFR in cell lines; Supplemental Figure 2: In vitro analysis of pan IR700; Supplemental Figure 4: Pan IR700 based PIT induces cell death in 5637 cells; Supplemental Figure 5: Panitumumab or IR700 alone have no effects on bladder cancer cell lines; Supplemental Figure 7: Staurosporine induces early apoptosis in UMUC-5 cells; Supplemental Figure 8: Forward scatter and side scatter plots for PIT treated UMUC-5 cells 60 minutes post-NIR; Supplemental Figure 9: DCFDA assay to detect the generation of ROS in the presence and absence of pan IR700 PIT; Supplemental Figure 10: Tumor measurements of individual control and experimental mice; Supplemental Figure 11: Effect of pan IR700 based PIT on UMUC-3 xenograft

Pan IR700 mediated PIT has no effect on normal urothelial cell line, UPS54.

Figure legends for all supplemental files

Objective To evaluate the risk upgrading of active surveillance (AS), we reviewed the outcomes of African American men (AA) after electing AS. AS is the standard of care for men with low-grade prostate cancer (PCa). AA are known to have more advanced PCa features and are more likely to die from PCa, thus subsequent disease progression for AA on AS is unclear. Methods A prospectively maintained AS database from the Southeast Louisiana Veterans Administration Medical Center, New Orleans, Lousiana was queried. We identified men with low- and very low-risk PCa (Gleason 3 + 3, PSA Results From a total of 274 men on AS (70% AA), 158 men met inclusion criteria (104 AA [66%]). All patients underwent at least 2 biopsies, and 29% underwent 3 or more biopsies. The median follow-up was 2.7 years. At 3 years on AS protocol, 57% AA and 61% Caucasians demonstrated no evidence of upgrading or treatment. No significant difference was observed between upgrading or progression to treatment when comparing racial groups. Seven (4%) patients in this cohort died from non PCa-specific causes, but no patients demonstrated metastasis or death from PCa over the course of study. Conclusion AA men with low-risk PCa can be safely followed with the same AS protocol as non-AA men. Further analysis with longer follow up is ongoing.

Introduction: Neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios (PLR) are useful clinical biomarkers for prognosis in several malignancies. Their predictive value has been less clearly demonstrated with prostate cancer (PCa), particularly, their utility within active surveillance (AS) protocols. We aim to evaluate NLR and PLR in AS patients.Methods: We identified 98 patients who met inclusion criteria in our cohort of 274 men diagnosed with PCa on AS. Patients were then categorized into high and low NLR and PLR groups.Results: The 2.5 and 5-year Gleason upgrading free probability for our high NLR cohort was 73.9%(CI 56.3% to 97.0%) and 46.2%(CI 22.4% to 95.1%) compared to 76.3%(CI 65.7% to 88.7%) and 61.7%(CI 47.7% to 80.0%) in the low NLR cohort(p = .73). The 2.5 and 5-year Gleason upgrading free probability for our High PLR cohort was 73.5%(CI 57.3% to 94.2%) and 60.1(CI 41.4% to 87.4%) compared to 76.8%(CI 65.8% to 89.65) and 58.1%(CI 42.2% to 80.1%) in our low PLR group(p = .41). A multivariant analysis demonstrated these groups were not significant predictors of upgrading or treatment.Conclusion: Despite their usefulness in many types of malignancy, NLR and PLR were not predictors of upgrading or treatment in men on AS for localized PCa in our cohort.

Accurate detection and diagnosis of prostate cancer remains challenging even with MRI fusion ultrasound biopsy procedures. These challenges contribute to diagnostic errors that can lead to repeat procedures. This study explores the application of ex vivo structured illumination microscopy (SIM) to generate pathology images of fresh biopsies to inform diagnostic decisions. Samples from the lesion of interest and a benign area of each patient were obtained, stained with fluorescent H&E analog dyes, imaged on a custom SIM system and diagnosed by a pathologist. This procedure could be extrapolated to a “see-and-treat” paradigm for localized prostate cancer ablation in the future.

Papillary renal cell carcinomas (PRCC) are a histologically and genetically heterogeneous group of tumors that represent 15-20% of all kidney neoplasms and may require diverse therapeutic approaches. Alteration of the NF2 tumor suppressor gene, encoding a key regulator of the Hippo signaling pathway, is observed in 22.5% of PRCC. The Hippo signaling pathway controls cell proliferation by regulating the transcriptional activity of Yes-Associated Protein, YAP1. Loss of NF2 results in aberrant YAP1 activation. The Src family kinase member Yes also regulates YAP1 transcriptional activity. This study investigated the importance of YAP and Yes activity in three NF2-deficient PRCC cell lines. NF2-deficency correlated with increased expression of YAP1 transcriptional targets and siRNA-based knockdown of YAP1 and Yes1 downregulated this pathway and dramatically reduced cell viability. Dasatinib and saracatinib have potent inhibitory effects on Yes and treatment with either resulted in downregulation of YAP1 transcription targets, reduced cell viability, and G0-G1 cell cycle arrest. Xenograft models for NF2-deficient PRCC also demonstrated reduced tumor growth in response to dasatinib. Thus, inhibiting Yes and the subsequent transcriptional activity of YAP1 had a substantial anti-tumor cell effect both in vitro and in vivo and may provide a viable therapeutic approach for patients with NF2-deficient PRCC.

Development of ureteroanastamotic strictures (UAS) after urinary diversion is not uncommon, but is challenging to treat. Poor outcomes are likely with endoscopic and radiologic management, and definitive surgical treatment can cause significant morbidity. The comparative advantages of an operative approach have not yet been fully described in the literature. We retrospectively reviewed the prospectively maintained Tulane University Department of Urology quality assurance database of 12 patients who underwent operative UAS repair between 2012 and 2018. Data were reviewed for operative approach, demographics, baseline disease characteristics, operative variables, and perioperative and pathological outcomes. Of the 12 patients analyzed, 5 underwent open repair (OR) (2 bilateral, 2 right, 1 left) and 7 underwent robotic repair (RR) (3 right, 4 left). One robotic case required conversion to open due to significant intestinal and peri-ureteral adhesions. The median ages were 59 years in OR and 60 years in RR. Two patients in each group had failed previous endoscopic repair. Median time from cystectomy to treatment of enteroanastamotic stricture was 13 months for OR and 10 months for RR (p = 0.25). Median estimated blood loss was 80 mL in both OR and RR (p = 1.0), median operative time was 260 min in OR and 255 min in RR (p = 0.13), and median hospital stay was 8 and 4 days, respectively (p = 0.06). There were two intra-operative and one post-operative complication in the OR group, one of whom required further surgical intervention, and no complications in the robotic cohort. A minimally invasive, robotic approach offers a non-inferior alternative to OR with similar outcomes for appropriately selected patients with UAS. High success rates combined with minimal morbidity may provide definitive therapy at an earlier stage of the stricture state.

The objective of this study was to characterize the demographic, prognostic, and treatment factors for patients with primary adenocarcinoma of the bladder by analyzing the impact of histologic subtype in a large sample size and interpreting newly released Surveillance, Epidemiology, and End Results (SEER) chemotherapy data.The SEER 18 Registry was utilized to identify cases of primary adenocarcinoma diagnosed from 1973 to 2015. Demographic data, tumor and disease characteristics, treatment information, and survival outcome data were collected. Overall survival and disease-specific survival were determined using Kaplan-Meier curve analysis. Univariate and multivariate Cox regression analysis were then completed using SAS JMP.A total of 2305 cases of primary adenocarcinoma of the bladder were identified. Overall survival at 2-, 5- and 10-year intervals was 54.8%, 36.1%, and 25.4%, respectively. Disease-specific survival at 2-, 5- and 10-year intervals was 62.0%, 47.1%, and 40.1%, respectively. Patients were treated with surgery (86.4%), chemotherapy (21.9%), and radiation (15.0%) (P .0001). Multivariate Cox regression analysis showed independent prognostic value for gender, stage, grade, primary tumor location, and histologic subtype. The urachus/dome location conferred survival advantage over non-urachal locations on univariable and multivariable Cox regression analysis. The papillary adenocarcinoma subtype conferred the best survival outcome, whereas signet cell carcinoma (hazard ratio, 2.069; P .0001) and unclassified adenocarcinoma (not otherwise specified) (hazard ratio, 1.524; P .0001) conferred the worst prognoses.This study utilized a population-based analysis to showcase the utility of various prognostic features in primary bladder adenocarcinoma cases. In characterizing treatments, we find the prevailing treatment remains surgical intervention, whereas a sizable minority receives chemotherapy and/or radiation, often in combination with surgery.

We present a urologic case report associated with retinoblastoma (RB1) mutation. A 65-year-old man, who has a history of bilateral retinoblastoma treated with primary radiation therapy at approximately 1 year of age. He presented with a 3-month history of gross hematuria and, on initial workup, was found to have synchronous renal and urothelial malignancies. The patient underwent complete transurethral resection of high grade Ta urothelial cancer and robotic-assisted partial nephrectomy for a pT3a leiomyosarcoma. He remains responsive to Bacillus Calmette-Guerin, and shows no recurrence of his renal malignancy. Through targeted sequencing, Rb mutations can predispose patients to several urologic malignancies.

INTRODUCTION AND OBJECTIVES:Renal Cell Carcinoma is newly diagnosed in 58,000 individuals in the United States annually. Papillary Renal Cell Carcinoma (pRCC) is the second most common variant of r...

INTRODUCTION AND OBJECTIVES:Active surveillance (AS) is becoming the de facto standard of care for men with low risk prostate cancer. Due to various risk factors, certain groups of men are deemed t...

INTRODUCTION AND OBJECTIVES:Micro RNAs (miRNA) are short non-coding RNA which are associated with post-transcriptional regulation of gene expression. As clear cell renal cell carcinoma (ccRCC) rema...

INTRODUCTION AND OBJECTIVES:In the formation of cancer, DNA alterations known as “driver mutations” promote carcinogenesis, giving cells an invasive and malignant phenotype. One of the most common ...

340 Background: Over the last decade, medical treatment for metastatic renal cell carcinoma has made significant advances through the development of tyrosine kinase inhibitors (TKI) like sunitinib. However, of patients initiated on TKI therapy, 70% respond well while 30% are believed to be primarily resistant to treatment. Additionally, 30% of patients who initially respond to treatment gain secondary drug resistance and present with increased tumor burden. In this study, we seek to develop a combination therapy of Tipifarnib + Sunitinib to target exosome conferred drug resistance. Methods: 786-O, 786-0 Sunitinib Resistant (SR), and 293-T cells were cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum, 2mM L-glutamine, and 1% penicillin/streptomycin (P/S). Exosomes were collected from conditioned media treated with Tipifarnib and isolated using differential ultracentrifugation. Exosomes were analyzed using the qNano IZON system. Colony forming units assay and Immunoblot analysis were used to further characterize or samples. Results: Exosomes collected from 786-O, 786-0 SR, and 293-T cells treated with 0.5 uM of Tipifarnib were compared using our qNANO IZON system. Exosome concentrations of all cell lines showed a decrease after Tipifarnib treatment. However, our 293-T cells showed a 16% decrease in exosome concentration while our 786-O and 786-0 SR lines displayed a 66% and 75% decrease respectively. To assess the pathway Tipifarnib used to decrease exosome concentrations, immunoblot assay was used after treating cells with 0, 0.1, 0.25, 0.5, 1 uM of tipifarnib. 293-T cells showed a dose dependent increase in ESCRT-dependent marker Alix and no change in either ESCRT-independent marker nSMase or trafficking marker Rab27a. Conversely, our 786-O and 786-0 SR cell lines showed a decrease in all 3 markers: Alix, nSMase, and Rab27a. Furthermore, a colony forming units assay was used to assess the drug combination of tipifarnib + sunitinib ability to alter cell growth. After 48hr, 293-T cell showed no decrease in colony forming units when compared to DMSO control. Our drug combination showed a synergistic ability to decrease colony forming units in the RCC 786-O cell line. 786-O SR cells were resistant to sunitinib treatment, showing comparable CFUs to DMSO control. When treated with the combination of sunitinib and tipifarnib, CTUs of 786-0 SR cells dropped significantly when compared to unaccompanied sunitinib and tipifarnib treatments. Conclusions: Tipifarnib has the ability to attenuate both the exosome ESCRT–dependent and –independent pathways. Our study also showed that when used injunction with sunitinib, tipifarnib is effective at decreasing cell proliferation. This drug combination is also pre-clinically useful in sunitinib resistance cancer cells. We believe this drug combination to be efficacious at decreasing tumor burden through blocking exosome biogenesis and secretion.

210 Background: The UroNav fusion biopsy system allows for the real time visualization of the prostate using multi-parametric MRI (mpMRI) data. This technology has become a valuable instrument for staging prostate cancer at the time of PSA elevation. However, data is still yet emerging over the use of this tool for patients currently being followed on an active surveillance (AS) protocol. In this study we sought to evaluate the efficacy of the UroNav system in patients on AS. Methods: Patients were enrolled into our prospective study, at a single center institution, approved by the Southeast Louisiana Veterans Health Care System (SLVHCS) IRB. Inclusion criteria for this study was men previously enrolled in an active surveillance protocol with a life expectancy ≥10 years. Statical analysis was performed using R 4.0.2 (Ann Arbor, MI). Results: A total of 103 patients were entered into this study for analysis. These patients had a median age of 67.1(62.8 - 70.8) and BMI of 28.6(25.5 - 32.3). The clinical profiles of these patients were median PSA of 6.36(4.65 - 8.89) with a velocity slope of (0.065 (-0.14 - 0.27), TRUS volume of 39.5(32.2 - 56.8), PSAD of 0.15(0.09 - 0.23), and a PI-RAD score of 4(3 – 5). A logistic regression was performed using upgrading on UroNav or Template bx as the outcome. Patients with an increased PSA were more likely to upgrade of Bx (OR = 1.2 (1.05 - 1.39)). Additionally, patients with decreasing MRI volumes were also more likely to upgrade on Bx (OR = 0.97 (0.94 - 0.98)). A total of 42 (40%) patients upgraded on either MRI or Template bx from their initial AS workup. MRI found 13 (12.6%) patients with an upgraded GG that displayed consistent or benign disease on template. Conversely, template also found 13 (12.6%) unique patients who upgraded but were found to have constant or benign disease on mpMRI. Conclusions: mpMRI guided biopsy is a useful tool that can further assist physicians in characterizing prostate cancer in patients being concurrently followed on an active surveillance protocol. MRI is able to find clinically significant cancer that would have otherwise been missed on traditional template biopsies. [Table: see text]

Papillary renal cell carcinomas (PRCC) are a histologically and genetically heterogeneous group of tumors that represent 15–20% of all kidney neoplasms and may require diverse therapeutic approaches. Alteration of the NF2 tumor suppressor gene, encoding a key regulator of the Hippo signaling pathway, is observed in 22.5% of PRCC. The Hippo signaling pathway controls cell proliferation by regulating the transcriptional activity of Yes-Associated Protein, YAP1. Loss of NF2 results in aberrant YAP1 activation. The Src family kinase member Yes also regulates YAP1 transcriptional activity. This study investigated the importance of YAP and Yes activity in three NF2-deficient PRCC cell lines. NF2-deficency correlated with increased expression of YAP1 transcriptional targets and siRNA-based knockdown of YAP1 and Yes1 downregulated this pathway and dramatically reduced cell viability. Dasatinib and saracatinib have potent inhibitory effects on Yes and treatment with either resulted in downregulation of YAP1 transcription targets, reduced cell viability, and G0-G1 cell cycle arrest. Xenograft models for NF2-deficient PRCC also demonstrated reduced tumor growth in response to dasatinib. Thus, inhibiting Yes and the subsequent transcriptional activity of YAP1 had a substantial anti-tumor cell effect both in vitro and in vivo and may provide a viable therapeutic approach for patients with NF2-deficient PRCC.

The use of light as a means of therapy for bladder cancer has a long history but has been hampered by a lack of tumor specificity and therefore, damage to the normal bladder mucosa. Here, we describe a targeted form of phototherapy called photoimmunotherapy (PIT), which targets EGFR-expressing bladder cancer. Anti-EGFR antibody panitumumab was labeled with the photoabsorber (PA), IRDye 700Dx (IR700), to create a panitumumab-IR700 antibody–PA conjugate that is activated by near-infrared radiation (NIR). Bladder cancer tissue microarray (TMA) and bladder cancer cell lines were analyzed for expression of EGFR. Mechanism of PIT-induced cell death was studied using proliferation assays, transmission electron microscopy (TEM), and production of reactive oxygen species. Finally, the in vivo effect was studied in xenografts. EGFR staining of TMAs showed that while most bladder cancers have expression of EGFR to a varying degree, squamous cell carcinomas (SCC) have the highest expression of EGFR. Panitumumab-IR700 activated by NIR light rapidly killed UMUC-5 cells, a bladder SCC line. Panitumumab alone, panitumumab-IR700 without NIR, or NIR alone had no effect on cells. TEM demonstrated that cell death is due to necrosis. Singlet oxygen species contributed toward cell death. NIR-PIT with panitumumab-IR700 reduced growth compared with only panitumumab-IR700–treated UMUC-5 xenograft tumors. PIT is a new targeted treatment for bladder cancer. Panitumumab-IR700–induced PIT selectively kills EGFR-expressing bladder cancer cells in vitro and in vivo and therefore warrants further therapeutic studies in orthotopic xenografts of bladder cancer and ultimately in patients. Mol Cancer Ther; 16(10); 2201–14. ©2017 AACR.

Heat shock protein 90 (HSP90) inhibition is an attractive strategy for cancer treatment. Several HSP90 inhibitors have shown promising effects in clinical oncology trials. However, little is known about HSP90 inhibition-mediated bladder cancer therapy. Here, we report a quantitative proteomic study that evaluates alterations in protein expression and histone post-translational modifications (PTMs) in bladder carcinoma in response to HSP90 inhibition. We show that 5 HSP90 inhibitors (AUY922, ganetespib, SNX2112, AT13387, and CUDC305) potently inhibited the proliferation of bladder cancer 5637 cells in a dose- and time-dependent manner. Our proteomic study quantified 518 twofold up-regulated and 811 twofold down-regulated proteins common to both AUY922 and ganetespib treatment. Bioinformatic analyses revealed that those differentially expressed proteins were involved in multiple cellular processes and enzyme-regulated signaling pathways, including chromatin modifications and cell death-associated pathways. Furthermore, quantitative proteome studies identified 14 types of PTMs with 93 marks on the core histones, including 34 novel histone marks of butyrylation, citrullination, 2-hydroxyisobutyrylation, methylation, O-GlcNAcylation, propionylation, and succinylation in AUY922- and ganetespib-treated 5637 cells. Together, this study outlines the association between proteomic changes and histone PTMs in response to HSP90 inhibitor treatment in bladder carcinoma cells, and thus intensifies the understanding of HSP90 inhibition-mediated bladder cancer therapeutics.

To evaluate if statin medications (3-hydroxyl-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitors) improve either oncologic or renal functional outcomes for patients undergoing robot-assisted partial nephrectomy (RPN).Patients undergoing RPN between March 2008 and October 2013 were evaluated from a prospectively maintained database for statin usage. The rate of perioperative acute kidney injury (AKI), as defined according to the RIFLE criteria, and the progression of chronic kidney disease (CKD) were compared between users and nonusers. Oncologic outcomes and rate of progression were compared between users and nonusers.One hundred four (31%) of 339 patients were on statin therapy preoperatively and continued this medication peri- and postoperatively. Statin patients were older and had higher rates of comorbidities, including coronary artery disease, diabetes, and hypertension (p0.0001 for all).The rate of AKI in the statin (16%) and nonstatin patients (14%) (p=0.60) and CKD progression based on Kaplan-Meier estimates (p=0.57) were similar between both the groups. Subgroup analysis of the 271 (80%) patients with hilar clamping also had similar rates of AKI, in statin users 10% vs 12% in nonusers (p=0.50). Multivariate analysis of factors affecting CKD progression confirmed these findings. Oncologic progression was not affected by statin therapy (p=0.90).Statin medications do not appear to influence perioperative renal function following RPN, in either clamped or unclamped procedures. Continuation of these medications may be continued perioperatively, but any effect on renal functional or oncologic outcomes was not elucidated in this study.

The technique of robotic partial nephrectomy continues to evolve, but the goals remain the same. Achievement of pentafecta outcomes is difficult to obtain; however, surgeons should continue to strive for this standard of excellence. The future continues to be bright for patients and surgeons alike in continuing to perform robot-assisted partial nephrectomy.

To evaluate if hematologic parameters and inflammatory markers could predict extravesical tumor and overall survival after radical cystectomy for patients with recurrent high grade T1 or muscle-invasive bladder cancer.A total of 68 consecutive cases of radical cystectomy performed with curative intent at our institution between April 2005 and October 2011 with preoperative hematologic parameters are included in this analysis. We evaluated preoperative characteristics with univariable and multivariate Cox proportional hazard ratios to assist in risk stratification for overall survival. Relative risk (RR) ratios and 95% confidence intervals (CI) were created. We also identified factors associated with extravesical tumor extension with logistic regression analysis.Median overall survival in the total cohort was 25 months (95% CI 13-61). In multivariate analysis, neutrophil/lymphocyte ratio2.5 (RR 2.49; 95% CI 1.14-6.09), hypoalbuminemia (RR 4.96; 95% CI 2.18-11.67), pT3/4 (RR 7.97, 95% CI 3.16-24.83), and lymph node positive disease (RR 2.62, 95% CI 1.26-5.46) predicted overall survival. These were statistically significant for cancer-specific survival as well. Both elevated neutrophil/lymphocyte ratio (RR 3.18, 95% CI 1.09-9.79) and hypoalbuminemia (RR 3.72, 95% CI 1.12-15.00) were associated with risk for extravesical disease.Serum neutrophil/lymphocyte ratio and hypoalbuminemia predict overall and cancer-specific survival in patients undergoing radical cystectomy for muscle-invasive bladder cancer. These parameters also predict risk for extravesical disease. These could be combined with other established preoperative parameters to improve risk stratification and preoperative counseling.

Objective To compare perioperative morbidity and oncological outcomes of robot-assisted laparoscopic radical cystectomy (RARC) to open RC (ORC) at a single institution. Patients and Methods A retrospective analysis was performed on a consecutive series of patients undergoing RC (100 RARC and 100 ORC) at Wake Forest University with curative intent from 2006 until 2010. Complication data using the Clavien system were collected for 90 days postoperatively. Complications and other perioperative outcomes were compared between patient groups. Results Patients in both groups had comparable preoperative characteristics. The overall and major complication (Clavien ≥3) rates were lower for RARC patients at 35 vs 57% (P = 0.001) and 10 vs 22% (P = 0.019), respectively. There were no significant differences between groups for pathological outcomes, including stage, number of nodes harvested or positive margin rates. Conclusion Our data suggest that patients undergoing RARC have perioperative oncological outcomes comparable with ORC, with fewer overall or major complications. Definitive claims about comparative outcomes with RARC require results from larger, randomised controlled trials.

Objective To evaluate the impact of increased experience in robot-assisted partial nephrectomy (RAPN) on perioperative and oncological outcomes To detail the complications encountered in establishing a RAPN programme at a tertiary referral centre and the factors associated with these complications Patients and Methods The initial consecutive 233 patients undergoing RAPN between March 2008 and May 2012 at our institution were identified. Patients were divided into quartiles to evaluate outcomes, and uni- and multivariate predictors of complications were calculated Results In progressive quartiles, patients tended to have more complex renal tumours as evaluated by R.E.N.A.L. nephrometry (P

An integral component of many urologic reconstructive surgical procedures is the positioning of a Double-J stent to span the anastomosis. Some surgeons prefer to place a retrograde stent during cystoscopy, either during or after the reconstruction. In this communication, we describe our straightforward and effective approach of performing this critical step intracorporeally using robotic assistance in a variety of upper tract urologic reconstructive procedures.We examined our Institutional Review Board-approved database of robotic surgeries to identify reconstructive operations that included the intracorporeal placement of a Double-J stent since 2008. Our step-by-step method for stent placement during various robotic urologic reconstructions is detailed, including procedures involving the proximal, mid, and distal ureter. With the aid of a bedside assistant-surgeon, we delineate how the console surgeon is able to perform this step of the procedure completely intracorporeally, without the need for repositioning or cystoscopy.Since the inception of our robotic surgical program in 2008, we have used these robotic stent placement techniques in 150 patients. The average time of robotic intracorporeal stent placement across the anastomosis was 3.5 minutes. Three patients did experience proximal stent migration, as documented on postoperative radiographs, but all were treated with conservative measures, because their anastomosis was not affected and severe symptoms did not develop. No patient needed stent replacement, and each stent was subsequently removed ureteroscopically without sequelae.Our robotic intracorporeal Double-J stent placement approach is simple and effective, avoids the need for cystoscopy and fluoroscopy, and can be used in any type of upper urinary tract urologic reconstruction.

Pathologic upgrading to Gleason 7 or higher on radical prostatectomy (RP) specimens occurs in many patients with Gleason 6 prostate cancer on preoperative biopsy. We evaluated whether biopsy characteristics and preoperative factors, including preoperative PSA velocity (PSAV), are predictive of pathologic upgrading.We identified 235 consecutive Gleason 6 prostate cancer patients who underwent biopsies at our institution, had multiple pre-biopsy PSA values, and eventually underwent RP. Preoperative biopsy, clinical characteristics, and PSAV were analyzed to determine the risk of pathologic upgrading or extracapsular extension. These clinical factors were evaluated for association with biochemical recurrence following RP.Overall, 48% of patients were upgraded to Gleason grade 7 or higher following RP. Median PSAV was 0.61 ng/mL/y, and PSAV was similar between upgraded and non-upgraded patients (1.01 vs. 0.78, P = 0.1). PSA velocity level was not associated with extracapsular disease (P = 0.4). PSA velocity1 was associated with biochemical recurrence (HR 3.23, P = 0.01) but this was not statistically significant in a multivariable model. Increasing PSA density (HR 2.18, P0.001), bilateral cores positive (HR 1.89, P0.05), and any biopsy core involvement50% (HR 2.52, P0.05) were most associated with pathologic upgrading. On multivariate analysis, only bilateral cancer detection at biopsy (HR 1.90, P0.05) significantly predicted upgrading.PSAV has a limited role in predicting Gleason 6 upgrading. Patients with bilateral cancer detected on transrectal biopsy should be encouraged to have radical local therapy due to high risk of harboring more aggressive disease.

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To evaluate the oncological outcomes of patients with specimen Gleason 8 and 9 prostate cancers and to determine factors that predict biochemical recurrence-free survival (BCRFS) after robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS Of 4156 patients who underwent RARP from January 2001 to 2009, we identified 368 men with Gleason 8 or 9 tumours who met the inclusion criteria. BCR was defined as a PSA level of ≥0.2 ng/mL with a second rising value. The Kaplan–Meier method and log-rank test were used to compare BCRFS while factors that predict BCRFS were determined by Cox proportional hazards modelling. RESULTS The median age and PSA level were 62 years and 6.4 ng/mL for men with Gleason 8, and 63 years and 6.7 ng/mL for Gleason 9 cancers. The median (interquartile range, IQR) overall follow-up was 23 (10–46) months and 19 (7–37) months for Gleason 8 and 9 tumours, respectively. At 60 months the mean (se) overall BCRFS was 36 (5)% and for Gleason 8 it was 47 (6)% and for Gleason 9 it was 21 (7)% (P < 0.001). At 5 years, extraprostatic extension (pT3a) resulted in BCRFS of 52 (9)% for Gleason 8 tumours and 21 (11)% for Gleason 9 (P= 0.012). On multivariable analysis, lymph node invasion, specimen Gleason score, pathological stage and tumour volume predicted BCRFS. CONCLUSIONS Early results suggest RARP monotherapy performs comparably to RP for BCRFS in men with high-grade prostate cancer. There are significant oncological differences between Gleason 8 and 9 tumours.

Background Minimally invasive partial nephrectomy (PN) is most commonly performed for renal tumors ≤4cm in size. Robotic PN (RPN) for tumors >4cm has not been assessed. Objective To evaluate the safety and feasibility of RPN for tumors >4cm in the context of patients undergoing RPN for tumors ≤4cm. Design, setting, and participants We reviewed data for 71 consecutive patients who underwent transperitoneal RPN at a tertiary care center between August 2007 and September 2009 by a single surgeon. Patients were stratified into two groups: 15 with tumors >4cm on preoperative imaging (group 1) and 56 patients with tumors ≤4cm (group 2). Intervention All patients underwent transperitoneal RPN by a single surgeon. Measurements Preoperative, perioperative, pathologic, and functional outcomes data were analyzed and compared between groups. We used χ 2 and student t tests for categorical and continuous variables, respectively. A p value Results and limitations Mean radiographic tumor size was 5.0cm (4.1–7.9) for group 1 and 2.1cm (0.7–3.8) for group 2. No significant differences were found between groups for estimated blood loss, total operative time, hospital stay, complication rates, and change in estimated glomerular filtration rate. Patients with larger tumors had longer median warm ischemia times (25 vs 20min; p =0.011). Limitations of our study include the retrospective nature the analysis, small sample size, and single-surgeon experience. Conclusions In our initial experience, RPN for tumors >4cm is safe and feasible, showing comparable outcomes to RPN for smaller tumors, although with longer warm ischemia times. Future studies with extended follow-up are necessary to determine the viability of RPN for large tumors as an effective form of treatment.

Studies have suggested that statin (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors) medication use may decrease prostate specific antigen in healthy men. We determined the effect of preoperative statin use on total preoperative prostate specific antigen and the risk of biochemical recurrence in patients with prostate cancer presenting for radical prostatectomy.A retrospective review of 3,828 patients undergoing radical prostatectomy from January 2001 to July 2008 at our institution identified 1,031 on statin medications. We compared these 1,031 patients to the remaining 2,797 not on statins preoperatively. We evaluated differences in prostate specific antigen overall, and when patients were stratified by age specific groups, body mass index and Gleason grades on final pathology. We also investigated differences in biochemical recurrence rates.Overall median serum prostate specific antigen was lower in patients on preoperative statins (5.0 vs 5.2 ng/ml, p = 0.002). Median prostate specific antigen was lower in men on statins with Gleason grades 7 or 8/9 disease (p0.05). Using a multivariate logistic regression model statin therapy was associated with a 4.7% decrease in prostate specific antigen (p0.001). Statin therapy was not associated with an overall decreased risk of biochemical recurrence (p = 0.73) at a mean followup of 26 months.In this cohort of men presenting for radical prostatectomy serum prostate specific antigen is significantly lower in patients with prostate cancer on preoperative statins compared to those not taking these medications. Prospective studies are required to evaluate if this decrease in prostate specific antigen leads to later detection of prostate cancer or variations in oncological outcomes.

OBJECTIVES Patients requiring chronic anticoagulation therapy (CAT) with warfarin require special attention perioperatively. We retrospectively reviewed our experience of treating patients requiring CAT who underwent robotic-assisted radical prostatectomy (RARP) to evaluate the role of perioperative bridging therapy. METHODS A total of 60 patients receiving cat with warfarin who underwent rarp were identified as having been treated using 1 of 2 protocols: protocol 1, the cessation of CAT 7 days before surgery and its resumption the evening of catheter removal (postoperative day 4-21); or protocol 2, warfarin substituted with perioperative subcutaneous low-molecular-weight heparin, with oral anticoagulation restarted after catheter removal. The decision to use perioperative bridging was made in conjunction with the patient's primary care physician. The peri- and postoperative parameters and complications were compared with a matched control group of 181 contemporary patients who underwent RARP but did not require CAT. RESULTS The most common indications for CAT were atrial fibrillation (58%) and recurrent deep vein thrombosis (22%). Compared with the control cohort, the patients with CAT had an increased operative time (189 vs 170 minutes, P = .005) and hospital stay (1.4 vs 1.1 days, P = .004). The estimated blood loss (123.9 vs 146.6 mL, P = .07) and 24-hour change in hemoglobin (2.2 vs 2.3 g/dL, P = .44) were similar. When comparing the 2 protocols, a significantly greater transfusion rate (23% vs 2%, P = .042) occurred with protocol 2, but no increase was seen in the complication or readmission rate. One nonfatal thromboembolic event occurred in 1 patient treated using protocol 1. CONCLUSIONS The results of our study have shown that RARP can be performed safely in patients requiring CAT, with and without bridging therapy. Patients in protocol 2 had greater transfusion rates, but this did not translate into increased complications or readmissions.

Late onset hypogonadism is becoming a more relevant topic because of the aging population, and many older patients are questioning their physicians about treatment for symptoms of declining testosterone. Low testosterone is present in 6% to 12% of the US adult male population and has several known etiologies. The clinician needs to be able to recognize the signs and symptoms of hypogonadism and initiate an appropriate workup. Historically, assays measuring serum testosterone levels have been difficult to interpret for many reasons. This article aims to provide the physician with basic directions for interpreting testosterone test results and to create an algorithm for determining which patients are candidates for hormone replacement therapy.

Introduction: Bladder cancer (CaB) is the 4th most common cancer among men in the US. It is the most expensive malignancies to treat from diagnosis to death. No new pharmacological agents have been approved for treatment of bladder cancer since the approval of BCG in 1990. Thus, there is an urgent need for development of new treatment therapies. Quantitative high throughput screening (qHTS) of representative cancer lines with oncology drugs may identify new treatments or re-purpose already existing therapies for different disease. We utilized this technique to identify new therapies in two primary bladder lines (T24 and UMUC3) and their metastatic lines (T24T, SLT3 and FL3 of T24 and LUL-2 for UMUC3). Methods: We screened 7 bladder cancer cell lines against 1,912 oncology drugs using a 48 hour cell proliferation assay with an ATP−based readout (CellTiterGlo) to determine activity and potency of compounds in a dose response manner. One of the candidate drugs inhibitory in all cell lines tested is flavopiridol, a pan CDK inhibitor. We further characterized the mechanism of action and in vivo effects of flavopiridol using various cell based assays and mouse xenograft studies. Results: The initial screen identified 95 compounds active in 7 cell lines. The top 50 compounds were further analyzed for molecular size of >200 g/mol and TPSA Conclusions: qHTS can identify novel compounds. Flavopiridol seems to be a very effective inhibitor both in vitro and in vivo. Physical properties of Flavopiridol are most suited for intravesical use which may lead to it being an effective inhibitor of CaB in the bladder at higher doses without any/few systemic toxicities. Studies are underway to elucidate the use of flavopiridol as a single intravesical agent. Citation Format: Reema Railkar, Thomas Sanford, L. Spencer Krane, Piyush K. Agarwal. Quantitative high throughput screening as a tool to identify novel therapies in bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 110. doi:10.1158/1538-7445.AM2017-110

Background and Objectives Urachal adenocarcinoma with peritoneal dissemination is an unusual presentation of a rare disease. It is associated with patients experiencing significant pain, poor outcomes, and historical median survival times between 12 and 24 months. We describe our 18-year experience in managing these patients with cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Methods Five patients who underwent six CRS with HIPEC for disseminated urachal cancer were identified. Demographics, perioperative data, and oncologic results were reviewed. Results All patients successfully completed CRS followed by HIPEC with Mitomycin C. Three patients had prior urachal mass excision and one had previous cystoprostatectomy with ileal conduit. At time of surgery, complete resection of all visible disease was only achieved in two patients. All patients developed local or distant disease recurrence at a median of 13 months postoperatively (range 7–31). The majority of patients (3/5) underwent postoperative intravenous chemotherapy for recurrence (2) or residual disease (1). All patients died of their disease, with median survival following date of surgery of 27 months (range 21–87). Symptomatic control of peritoneal disease was achieved in 2/5 (40%) of the cases. Conclusions Urachal adenocarcinoma with peritoneal dissemination is an aggressive, rare disease, which is uniformly fatal. In our experience, CRS followed by HIPEC with Mitomycin C may increase patient survival and palliation, although further treatment improvements are clearly required. J. Surg. Oncol. 2012; 105:258–260. © 2011 Wiley Periodicals, Inc.

Background:Vulvovaginitis has a known association with urinary tract infections (UTIs) in girls. We hypothesize that vulvovaginitis is a major contributor to UTIs in prepubertal girls by increasing periurethral colonization with uropathogens.Methods:Periurethral swabs and urine specimens were obtained from a total of 101 girls (58 with vulvovaginitis and 43 without vulvovaginitis). Specimens were cultured for bacterial growth. The dominant organism in the periurethral swabs and urine cultures was recorded and antibiotic sensitivity profiles were compared.Results:Periurethral swabs from children with vulvovaginitis were associated with a statistically significant increase in uropathogenic bacteria (79% Enterococcus species or Escherichia coli) as the dominant culture compared with swabs from girls without vaginitis (18%) ( p Conclusions:Vulvovaginitis may cause UTIs by altering the perineal biome such that there is increased colonization of uropathogens.

Indocyanine green (ICG) is emerging as a potential adjunct to robot-assisted partial nephrectomy by its ability to aid in the real-time identification of renal vasculature, renal masses, and the renal mass-parenchymal margin. The fluorescence patterns of renal masses have not been adequately described according to histology, and it remains unknown if fluorescence pattern can reliably predict histology or malignancy. We therefore describe the ICG fluorescence pattern of our first 100 robot-assisted partial nephrectomies (RAPN) and correlate with histology.We reviewed our prospective RAPN database and categorized fluorescence pattern as isofluorescent (same as surrounding parenchyma), hypofluorescent (less than surrounding parenchyma, but with uptake), or afluorescent (no visible uptake of dye). Descriptive statistics were applied.All 14 cystic lesions were afluorescent and comprised 9 malignant and 5 benign masses. Eighty-six lesions were solid, of which 3 were isofluorescent including two clear-cell and one translocation tumor. The remaining 83 solid lesions were hypofluorescent and included 65 malignant and 18 benign lesions. Clear-cell was the most common histology of which 96% were hypofluorescent and 4% isofluorescent. In determining malignant vs benign lesions, hypofluorescence had a positive predictive value of 87%, negative predictive value of 52%, sensitivity of 84%, and specificity of 57%.A three-grade classification of renal mass ICG fluorescence pattern is correlated with some histologic findings but unable to reliably predict malignant vs benign lesions.

To evaluate the impact of increased experience in robot-assisted partial nephrectomy (RAPN) on perioperative and oncological outcomes To detail the complications encountered in establishing a RAPN programme at a tertiary referral centre and the factors associated with these complications.The initial consecutive 233 patients undergoing RAPN between March 2008 and May 2012 at our institution were identified. Patients were divided into quartiles to evaluate outcomes, and uni- and multivariate predictors of complications were calculated.In progressive quartiles, patients tended to have more complex renal tumours as evaluated by R.E.N.A.L. nephrometry (P 0.01) or preoperative aspects and dimensions used for an anatomical classification (PADUA) scores (P = 0.003), and percentage endophytic (P = 0.01). Developing technique increased the patients undergoing unclamped PN (P 0.01). The mean time in the operating room (from skin incision to closure) decreased significantly from 225 to 183 min (P 0.01) and warm ischaemia time decreased from 28 to 15 min, when clamping (P 0.01). Clavien graded complication rate (P = 0.26) and positive margin rate (P = 0.32) was unchanged by quartile.We show that increasing experience allows more complex tumours to be removed with similar outcomes in patients undergoing RAPN. The complication rates and perioperative outcomes were similar in four successive quartiles of an initial experience of RAPN.

Partial nephrectomy without renal vascular occlusion has been introduced to improve outcomes in patients undergoing robotic partial nephrectomy (RPN). We prospectively evaluated unclamped RPN at our institution and compared this to other clamping techniques in a non-randomized fashion.Ninety-five consecutive patients who successfully completed RPN between June 2010 and October 2011 are included in this analysis. All RPNs were performed by a single surgeon. Clamping technique was artery and vein (AV), artery alone (AO) or unclamped (U) without hypotensive anesthesia. Clamping decision was based on surgeon preference and feasibility of minimizing ischemia. All patients had bilateral functional renal units.Eighteen (19%), 58 (61%) and 19 (20%) patients had AV, AO and U technique respectively. Preoperative characteristics including age (p = 0.43), body mass index (p = 0.40) and RENAL nephromety distribution (p = 0.10) were similar. In AV and AO, mean warm ischemia time were 19 and 17 minutes and similar between the two cohorts (p = 0.39). Mean glomerular filtration rate (GFR) and overall percentage decrease in GFR at time of at last follow up were (64, 69, 81, p = 0.12) and (6%, 6%,and 2%,p = 0.79) for AV, AO and U respectively. Median follow up for last serum creatinine was 113 days and was similar between all cohorts (p = 0.37). Complication rate (p = 0.37), positive margin rate (p = 0.84), and change in hemoglobin concentration postoperatively (p = 0.94) were similar between cohorts.Unclamped partial nephrectomy is possible in patients undergoing RPN. In this study, it does not significantly alter perioperative or postoperative renal function or change rate of complications. Minimal ischemia, irrespective of clamping technique, in patients with bilateral renal units does not appear to adversely effect intermediate term renal function in these patients.

Objective To compare a consecutive prospective cohort of patients who underwent robotic partial nephrectomy (RPN) with near infrared fluorescence (NIRF) imaging with indocyanine green dye (ICG) with a previous consecutive patient cohort. Methods A total of 47 consecutive patients with renal masses suspicious for malignancy undergoing RPN were given 5-7.5 mg of ICG before hilar clamping or tumor excision. This cohort of patients was compared with 47 immediate previous consecutive patients who had undergone RPN without NIRF real-time imaging using ICG. The intraoperative, perioperative, and postoperative parameters were collected in an institutional review board-approved prospective database. Results The preoperative demographics and tumor complexity according to the nephrometry or preoperative aspects and dimensions used for an anatomic (PADUA) scores were similar. The mean warm ischemia time was significantly decreased in the ICG group (15 vs 17 minutes, P = .01). The median hospital stay was 2 days in both groups. No significant difference was seen in the positive margin rate (ICG, 6% vs control, 8.5%; P = .69) or observed Clavien grade III-IV complications in these 2 cohorts (ICG, 4% vs control, 15%; P = .07). No adverse events were associated with ICG dye administration. Differential ICG uptake was observed with selective clamping or in patients with cystic tumors, hypofluorescent tumors with exophytic components, and angiomyelolipomas, but these benefits could not be quantified. NIRF-ICG was transiently helpful to identify the vascular anatomy and not helpful at all for endophytic tumors. Conclusion RPN using NIRF-ICG can be performed safely and effectively. A decreased warm ischemia time in the ICG cohort was observed without specific measured advantages. Differential ICG uptake by different tumors did not lead to significant differences in the positive margin rate.