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Background: Effective screening and prevention strategies for bladder cancer require accurate risk stratification models. We developed models to predict the risk of bladder cancer based on clinical and sociodemographic data on participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial. Methods: Baseline clinical and sociodemographic data were obtained from 149,542 PLCO participants, ages 55 to 74 years, without a prior history of bladder cancer. Cox proportional hazards models were used to predict the risk of all bladder cancers (ABC) and of high-grade bladder cancers (HGBC) from baseline information. We used the HGBC risk model to design a hypothetical bladder cancer mortality prevention trial. Results: Over a median follow-up of 12 years, 1,124 men and 259 women developed bladder cancer (including 392 and 72 with HGBC, respectively). The incidence in men and in women was 133.6 and 29.6 cases per 100,000 person-years, respectively. Nomograms constructed for predicting the risk of ABC and HGBC had c-indices of 0.746 and 0.759, respectively. Age, race, education, smoking (intensity and duration), comorbidity, prostatitis, syphilis, and hormone replacement therapy use were statistically significant predictors in the models. We show that our risk model can be used to design a bladder cancer mortality prevention trial half the size of a trial designed without risk stratification. Conclusion: Models to predict the risk of ABC and HGBC have been developed and validated. Impact: Using the upper 40th percentile from the HGBC model, a suitable cohort for a screening or chemoprevention trial could be identified, although the size and follow-up of such a trial would be costly. Cancer Epidemiol Biomarkers Prev; 22(12); 2241–9. ©2013 AACR.

Purpose: Despite more than 70,000 new cases of bladder cancer in the United States annually, patients with advanced disease have a poor prognosis due to limited treatment modalities. We evaluated Aurora kinase A, identified as an upregulated candidate molecule in bladder cancer, as a potential therapeutic target. Experimental Design: Gene expression in human bladder cancer samples was evaluated using RNA microarray and quantitative reverse transcriptase PCR. Effects of the Aurora kinase A inhibitor MLN8237 (Millennium) on cell dynamics in malignant T24 and UM-UC-3 and papilloma-derived RT4 bladder cells were evaluated in vitro and in vivo in a mouse xenograft model. Results: A set of 13 genes involved in the mitotic spindle checkpoint, including Aurora kinases A and B, were upregulated in human urothelial carcinoma compared with normal urothelium. The Aurora kinase A inhibitor MLN8237 induced cell-cycle arrest, aneuploidy, mitotic spindle failure, and apoptosis in the human bladder cancer cell lines T24 and UM-UC-3. MLN8237 also arrested tumor growth when administered orally over 4 weeks in a mouse bladder cancer xenograft model. Finally, in vitro sequential administration of MLN8237 with either paclitaxel or gemcitabine resulted in synergistic cytotoxic effects in T24 cells. Conclusions: Mitotic spindle checkpoint dysfunction is a common characteristic of human urothelial carcinoma and can be exploited with pharmacologic Aurora A inhibition. Given our demonstration of the ability of the Aurora A inhibitor MLN8237 to inhibit growth of bladder cancer in vitro and in vivo, we conclude that Aurora kinase inhibitors warrant further therapeutic investigation in bladder cancer. Clin Cancer Res; 19(7); 1717–28. ©2013 AACR.

BACKGROUND Several studies have demonstrated the usefulness of monitoring an RNA transcript, such as PCA3, in post-prostate massage (PM) urine for increasing the specificity of prostate-specific antigen (PSA) in the detection of prostate cancer (PCa). However, a single marker may not necessarily reflect the multifactorial nature of PCa. METHODS We analyzed post-PM urine samples from 154 consecutive patients, who presented for prostate biopsies because of elevated serum PSA (>4 ng/ml) and/or abnormal digital rectal exam. We tested whether the putative PCa biomarkers PSMA, PSGR, and PCA3 could be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings to test if a combination of these biomarkers could improve the specificity of actual diagnosis. Afterwards, we specifically tested our model for clinical usefulness in the PSA diagnostic “gray zone” (4–10 ng/ml) on a target subset of 82 men with no prior biopsy. RESULTS By univariate analysis, we found that the PSMA, PSGR, and PCA3 scores were significant predictors of PCa. Using a multiplex model, the area under the multi receiver-operating characteristic curve was 0.74 versus 0.82 in the diagnostic “gray zone.” Fixing the sensitivity at 96%, we obtained a specificity of 34% and 50% in the gray zone. CONCLUSIONS Taken together, these results provide a strategy for the development of a more accurate model for PCa diagnosis. In the future, a multiplexed, urine-based diagnostic test for PCa with a higher specificity, but the same sensitivity as the serum-PSA test, could be used to determine better which patients should undergo biopsy. Prostate 71:1736–1745, 2011. © 2011 Wiley Periodicals, Inc.

What’s known on the subject? and What does the study add? This is a short series of unclassified RCC with positivity for TFE3 staining an association with poor outcome on those patients’ follow-up. The paper supports the idea of TFE3 positivity as a marker for poor outcome in RCC patients. It has already been stated in some manuscripts; however, not in this number of patients. OBJECTIVES • To evaluate the clinical and pathologic features and the prognostic relevance of unclassified RCC with – TFE3 over-expression in our adult series. • Recent studies suggest that renal cell carcinomas (RCCs) associated with the newly recognized Xp11.2 translocation (transcription factor E3 [TFE3] gene fusions) can be found among adults with RCC showing a very aggressive disease-course. MATERIAL AND METHODS • We evaluated tumour specimens from 25 patients with unclassified RCC morphology out of 298 RCCs in the last 12 years in a tertiary academic centre. • Immunohistochemistry was performed using monoclonal antibody for TFE3 C-terminal section, taking nuclear label into consideration. RT-PCR technique was performed for ASPL-TFE3 gene fusion on two tumours with available frozen tissue. RESULTS • Of the 25 cases analyzed, 8 (32%) showed positivity for TFE3 and 17 were negative for TFE3 staining. Two tumors with ASPL-TFE3 gene fusion also showed TFE3 over-expression. • Fifty percent of the positive patients had lymph node metastatic disease, whereas only one TFE3-negative patient (5.8%) showed evidence of lymph node spread and cava thrombus at diagnosis. Of the TFE3-positive patients, three had a vena cava thrombus (37.5%). Seven of the eight positive cases (87.5%) were diagnosed with a high Fuhrman grade (III/IV). In comparison, five of 17 (29.4%) TFE3-negative patients had a high Fuhrman grade. Five of eight TFE3-positive patients relapsed rapidly at 3 month follow-up; conversely none of the negative cases relapsed. At 36-month mean follow-up, 5-year cancer-specific survival was 15.6% for TFE3-positive patients and 87.5% for TFE3-negative patients (P

BACKGROUND Several studies have demonstrated the usefulness of monitoring an RNA transcript in urine, such as PCA3, for prostate cancer (PCa) diagnosis. PCa screening would benefit from additional biomarkers of higher specificity and could be used in conjunction with prostate-specific antigen (PSA) testing, in order to better determine biopsy candidates. METHODS We used urine sediments after prostate massage (PM) from 215 consecutive patients, who presented for prostate biopsy. We tested whether prostate-specific G-protein coupled receptor (PSGR), a biomarker previously described to be over-expressed in PCa tissue, could also be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings with prostate cancer gene 3 (PCA3), the current gold standard for PCa diagnosis in urine, to test if a combination of both biomarkers could improve the sensitivity of PCA3 alone. RESULTS By univariate analysis we found that PSGR and PCA3 were significant predictors of PCa. Receiver operator characteristic curve analysis and its multivariate extension, multivariate ROC (MultiROC), were used to assess the outcome predictive values of the individual and the paired biomarkers. We obtained the following area under the curve values: PSA (0.602), PSGR (0.681), PCA3 (0.656), and PSGRvPCA3 (0.729). Then, we tested whether a combination of PSGR and PCA3 could improve specificity by fixing the sensitivity at 95%. We obtained specificities of 15% (PSGR), 17% (PCA3), and 34% (PSGRvPCA3). CONCLUSIONS A multiplexed model including PSGR and PCA3 improves the specificity for the detection of PCa, especially in the area of high sensitivity. This could be clinically useful for determining which patients should undergo biopsy. Prostate 70: 1760–1767, 2010. © 2010 Wiley-Liss, Inc.

Partial nephrectomy is the reference standard for the management of small renal tumors and is commonly used for localized kidney cancer. A primary goal of partial nephrectomy is to preserve as much renal function as possible. New baseline glomerular filtration rate after partial nephrectomy can have prognostic significance with respect to long-term outcomes. Recent studies provide an increased understanding of the factors that determine functional outcomes after partial nephrectomy as well as preventive measures to minimize functional decline. We review these advances, highlight ongoing controversies and stimulate further research.A comprehensive literature review consistent with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria was performed from January 2006 to April 2014 using PubMed®, Cochrane and Ovid Medline. Key words included partial nephrectomy, renal function, warm ischemia, hypothermia, nephron mass, parenchymal volume, surgical approaches to partial nephrectomy, preoperative and intraoperative imaging, enucleation, hemostatic agents and energy based resection. Relevant reviews were also examined as well as their cited references. An additional Google Scholar search was conducted to broaden the scope of the review. Only English language articles were included in the analysis. The primary outcomes of interest were the new baseline level of function after early postoperative recovery, percent decline in function, potential etiologies and preventive measures.Decline in function after partial nephrectomy averages approximately 20% in the operated kidney, and can be due to incomplete recovery from the ischemic insult or loss of nephron mass related to parenchymal excision or collateral damage during reconstruction. Compensatory hypertrophy in the contralateral kidney after partial nephrectomy in adults is marginal and decline in global renal function for patients with 2 kidneys averages about 10%, although there is some variance based on tumor size and location. Irreversible ischemic injury can be minimized by pharmacological intervention or surgical approaches such as hypothermia, limited warm ischemia, or zero or segmental ischemia. Excessive loss of nephron mass can be minimized by improved preoperative or intraoperative imaging, use of a bloodless field, enucleation and vascular microdissection. Hemostatic agents or energy based resection that minimizes the need for parenchymal and capsular suturing can also optimize preservation of the vascularized nephron mass.Our understanding of the decline in renal function after partial nephrectomy has advanced considerably, including better appreciation of its magnitude and impact in various settings, possible etiologies and potential preventive measures. Many controversies persist and this remains an important area of investigation.

Each subtype of renal cell carcinoma (RCC) has distinct clinical, pathologic, and imaging features that can strongly impact presentation, diagnosis, management, and prognosis, although considerable overlap exists. In general, clear cell tumors tend to be more aggressive than papillary or chromophobe tumors, while collecting duct and medullary cell RCC are even more ominous. Metastasis is most common with clear cell RCC, yet this tumor type is also the most likely to respond to high-dose interleukin 2 (IL-2) or targeted treatments. Each subtype of RCC has a familial counterpart, and the implications of sporadic versus familial etiology should be recognized because they can greatly impact clinical management. The treatment paradigms for localized RCC, locally advanced RCC, and metastatic RCC must be tailored to histologic subtype to optimize patient outcomes.

We endeavored to summarize the most relevant data in regards of oncologic patient outcome prediction in the transitional cell carcinoma (TCC) topic. Nomograms have been used to standardize this outcome and more accurately predict future events. Bladder cancer still remains a very poor field compared to other areas such as prostate or kidney cancer. In order to facilitate understanding, we organized the chapter by tumor depth of invasion meaning, noninvasive versus invasive bladder cancer. We included a short paragraph about upper tract TCC nomograms. None of the presented nomograms is currently used on a daily basis for patient clinical care due to the lack of external validity in most environments.

The aim of our report was to describe the feasibility of robotic retroperitoneal lymph node dissection in the contemporary era. We suggest the linear port location and 90° robotic docking as the main key to minimizing instrument clashing and improving the range of surgical accessibility.

e557 Background: Despite being widely used in many countries to assess health-related quality of life for patients undergoing treatment for localized prostate cancer(PC), seldom research has been done to investigate the five domain scores generated by 26 question short form of the Expanded Prostate Cancer Index Composite Short (EPIC-26). We conducted exploratory and confirmatory factor analyses searching for evidence of five unique domains of dysfunction in men being treated for PC in the US and Spain.Methods: Using two-year post treatment information, data from 400 men who were part of the original EPIC (OE) validation cohort [T1 or T2, 87% Radical Prostatectomy (RP), 10% External Beam Radiation (EBR), 3% Brachytherapy (BR)] and 450 men who were treated for prostate cancer at Institut Hospital del Mar d'Investigacions Mèdiques in Spain [33% RP, 33% EBR, 33% BR], were subjected to exploratory (EFA) and confirmatory factor analysis (CFA).Results: EFA analyses on both the OE and Spanish cohorts provides support for three, four or five factor models (accounting for approximately 83, 91 or 97% of variance in either cohort) to describe the EPIC-26 variables and weak evidence for the hormonal domain. There is evidence of separate urinary, sexual and bowel factors, but limited evidence of a separate hormonal domain. With the exception of the questions which could be described as assessing depression (lack of energy and depression and in some models weight gain), items within the hormonal domain frequently failed to consistently load onto a single factor (orthogonal communalities ranging from .22 to .27 in the OE cohort and .10 to .21 in the Spanish for hot flashes, breast tenderness and weight gain). CFA looking for the published five domain solution in the Spanish data provides mediocre support for a five factor solution (Standardized RMR = .0624, RMSEA Estimate = .07, Bentler Comparative Fit Index = .91). Conclusions: While all questions asked on the EPIC-26 are of clinical value, there is limited evidence to continue to treat the hormonal domain as a single entity. Urologists should consider looking at the questions linked to depression separately from the other hormonal questions

We assessed compensatory hypertrophy in the contralateral kidney after partial and radical nephrectomy in adults. We also examined predictive factors to facilitate more accurate estimation of global renal function after surgery.We analyzed the records of 172 patients who underwent partial or radical nephrectomy with appropriate studies to determine function and parenchymal mass specifically in the operated and contralateral kidneys. All patients required renal scans to provide split renal function preoperatively and postoperatively. Parenchymal volume was measured by computerized tomography. All studies were done less than 2 months preoperatively and 4 to 12 months postoperatively.A total of 113 and 59 patients underwent partial and radical nephrectomy, and median tumor size was 3.5 and 7.0 cm, respectively (p0.0001). Of patients treated with partial nephrectomy 19% had high complexity tumor compared to 80% of those treated with radical nephrectomy (p0.0001). Median ipsilateral parenchymal volume was reduced 18% after partial nephrectomy and the median glomerular filtration rate in this kidney decreased 24.4%. The median contralateral kidney function increase after partial nephrectomy was 2.3% vs 21.1% after radical nephrectomy (p0.0001). Median global function decreased 9.6% after partial nephrectomy vs 32.2% after radical nephrectomy (p 0.0001). A larger percent parenchymal volume loss (p = 0.0001) and fewer comorbidities (p = 0.0072) significantly correlated with greater compensatory hypertrophy in the contralateral kidney on multivariable analysis.Compensatory hypertrophy in adults was limited after partial nephrectomy and it correlated significantly with the amount of parenchymal volume excised. Healthier patients also appeared to respond better. These results may allow for more accurate estimation of global renal function after partial and radical nephrectomy.

Background: There is equipoise regarding the optimal management of clinical stage (CS) I testicular seminoma. Surveillance protocols have increasingly been embraced given the low relapse rate reported (15-20%) at 5 years. We analyzed the relapse rate of CS I seminoma patients under surveillance in a contemporary series. Patients and methods: Between 2005-2012, 48 of 74 (65%) consecutive patients diagnosed with CS I seminoma at our institution were managed by surveillance. Clinical information and follow-up data was obtained through retrospective chart review. The decision to be treated or observed was largely physician-dependent and was not based on the presence/absence of specific risk factors. Results: Among 48 patients on surveillance, 18 (37%) had tumor size ≥ 4 cm, 16 (33%) had rete testes invasion, and 4 (8%) had lymphovascular invasion. Over a median follow-up of 39 months (IQR, 18-61), 2 patients relapsed and the 3-year relapse-free survival (RFS) was 94% (95% CI: 86-100). Both relapsed in the retroperitoneum at 10 and 29 months, and are disease-free following first-line chemotherapy. Retrospectively, the patient with late relapse had a 1.8 x 1.3 mm retrocaval mass retrospectively identified on the non-contrast CT at diagnosis and at 4 months on observation which may have represented metastatic disease that was missed. This patient did not undergo further transaxial surveillance imaging and relapsed with a large retroperitoneal mass at this location. Excluding this patient, the 3-year RFS was 98% (95% CI: 93-100). Conclusions: Contemporary CS I seminoma patients appropriately staged and observed at our institution had a very low-risk of relapse. This evidence further supports surveillance as the preferred standard option for these patients.

INTRODUCTION AND OBJECTIVES: To quantify the effect of dutasteride (D) vs. placebo (P) on reducing the for-cause re-biopsy rate (FCRBR) among men with a prior negative prostate biopsy randomized in the REDUCE trial and to quantify the harms of reducing FCRBR by missing high-grade cancers. METHODS: Patient data from 6608 patients randomized in the REDUCE trial were obtained to determine FCRBR using 8 frequently utilized criteria for the prior negative biopsy population (any rise in PSA from nadir, PSA rise from baseline > 0.2, PSA rise from baseline or 1⁄4 0.35, PSA rise from baseline > or 1⁄4 0.75, abnormal digital rectal examination [DRE], absolute PSA > or 1⁄4 2.5, absolute PSA > or 1⁄4 4) and the rate of cancer detection (including Gleason 2-6, 7, and 8-10 cancers) based on the results of the biopsies performed in years 1-2. A “missed” cancer was defined as that detected on protocol-mandated biopsy in patients who did not fulfill for-cause biopsy criteria. All dutasteride post-baseline PSA values were multiplied by 2.3. RESULTS: Compared to P, Dwas associated with a significantly decreased FCRBR for 2 of 8 criteria; for the 2 criteria based on an absolute PSA, there was no relative reduction in the rate of FCRBR. In the post-baseline PSA criteria the relative reduction was 56-77% for 2 criteria that showed statistical significance (Any PSA rise from nadir, PSA change 0-0.35 ng/mL) (P < 0.001). D did not significantly affect FCRBR based on DRE compared to P (P 1⁄4 0.7). Biopsy Gleason 8-10 cancers were missed using FCRBR criteria in the P arm in 3 of 8 criteria whereas Gleason8-10 cancersweremissed in theDarm for 6 of 8 criteria. The rate of missed Gleason 8-10 cancers was 0-0.5% and 0-0.6% in the P and D arms, respectively. In the 8 re-biopsy criteria, there was no significant difference in the rate of missed biopsy Gleason 8-10 cancers (p1⁄40.06) CONCLUSIONS: D was associated with a relative reduction in FCRBR by up to 77% compared to P and did not increase the likelihood of missing a Gleason 8-10 cancer in the 8 criteria evaluated.

several years (Hexvix) and has recently been approved in the US (Cysview) and is being used by select centers. In the video we demonstrate use of Cysview for detection of NMIBC. METHODS: From August 2012 to August 2013, 96 patients scheduled for TURBT at our institution have undergone instillation of Cysview and cystoscopy under blue light. Several cases are highlighted in the video demonstrating cystosocpic view under normal and blue light with pathology results. RESULTS: Use of Cysview to detect NIMBC is demonstrated in 2 select cases as seen in figure 1. The top images are under normal cystoscopy and the bottom images demonstrate the same view under blue light cystoscopy following administration of Cysview. The fluorescent areas were biopsied and revealed high-grade pT1 in the patient on the left and high grade pT1 and CIS in the patient on the right. CONCLUSIONS: Use of Cysview can help with the detection of NMIBC as well as CIS in patients undergoing TURBT for bladder cancer.

Poorly functioning kidneys may not recover from ischemia as well as strongly functioning kidneys. This could impact surgical approaches to partial nephrectomy.We analyzed the records of 155 consecutive patients treated with partial nephrectomy who underwent appropriate studies to facilitate analysis of function and parenchymal mass in the operated kidney, including computerized tomography and glomerular filtration rate measurement within 2 months preoperatively and 4 to 12 months postoperatively. Patients with a contralateral kidney also underwent renal scan in the same time frame to provide split renal function. Computerized tomography was done to measure functional parenchymal volume before and after partial nephrectomy. Recovery from ischemia, defined as percent glomerular filtration rate saved/percent volume saved, was considered 100% if all nephrons recovered from the ischemic insult.The median R.E.N.A.L. nephrotomy score was 8. Cold ischemia was used in 64 patients and limited warm ischemia was used in 91 (median 27 and 20 minutes, respectively). The median percent glomerular filtration rate saved in the operated kidney was 80% and the median parenchymal volume saved was 83%. The overall median rate of recovery from ischemia was 95%, including 100% for cold ischemia and 92% for limited warm ischemia. Recovery from ischemia was approximately 100% and was similar for all strata of preoperative estimated glomerular filtration rates in the operated kidney (p = 0.24), even in the warm ischemia subgroup.Our results suggest that the quantity of parenchyma preserved is the main determinant of the postoperative glomerular filtration rate after partial nephrectomy as long as limited warm ischemia or hypothermia is used. Even poorly functioning kidneys recover well from the ischemic insult proportionate to the amount of parenchyma preserved.

Maria C Mir,1 Binoy Joseph,1 Rona Zhao,1 Damien M Bolton,1 Dennis Gyomber,1 Nathan Lawrentschuk1,21University of Melbourne, Department of Surgery, Austin Hospital, Melbourne, VIC, Australia; 2Ludwig Institute for Cancer Research, Austin Hospital, Melbourne, VIC, AustraliaObjectives: Our objectives were to analyze the effectiveness of epidural anesthesia in patients who underwent open retropubic radical prostatectomy (RRP) at our institution over the past decade, and to examine subsequent oncologic outcomes, comparing those receiving with those not receiving epidural anesthesia.Methods: A comprehensive database of all patients undergoing RRP from November 1996 to December 2006 was analyzed; 354 patients underwent RRP at our institution and were divided into those receiving or not receiving an epidural. An independent pain management team scoring technical success found epidural technique to be consistent. Oncological outcome was an endpoint of our study, comparing both analysis groups. We classed prostate-specific antigen (PSA) recurrence after RRP as a serum PSA ≥ 0.2 ng/mL at any stage of postoperative follow-up. Complications were recorded to 30 days using the modified Clavien system, and full statistical analyses were undertaken.Results: Records were available for 239 men; we observed a decreased trend in the use of epidural for pain management, along with a decrease in average hospital stay and an overall epidural success rate of 64%. When dividing data into RRP with and without epidural, we found a median hospital stay of 7 days for patients receiving an epidural compared with 6 days for those not receiving an epidural. The differences were statistically significant (P < 0.048) and remained so after adjusting for complications (P < 0.0001). Regarding oncological outcome, PSA recurrence was further analyzed in this cohort. Percentage of recurrence was higher (14.8%) for patients receiving an epidural than for the non-epidural group (4.8%). The differences were statistically significant (P = 0.012).Conclusion: Epidural analgesia increased length of hospital stay and technical problems related to the epidural. Furthermore, men receiving an epidural showed an increased recurrence of PSA. In light of our findings, epidurals are probably not indicated for men undergoing RRP. However, as minimally invasive techniques are becoming more widespread, and epidural analgesia is being used less frequently, large randomized controlled trials to definitively support our hypotheses are unlikely to be undertaken.Keywords: prostate neoplasm, surgery, prostatectomy, analgesia, epidural

The precision of excision and reconstruction to optimize vascularized parenchymal preservation is a major determinant of renal function after partial nephrectomy. We assessed partial nephrectomy surgical precision using volumetric computerized tomography and analyzed predictive factors.We analyzed the records of 122 patients treated with partial nephrectomy in whom detailed analysis of the precision of excision and reconstruction specific to the operated kidney could be performed. We used volumetric computerized tomography to measure functional parenchymal volume before and after partial nephrectomy in the operated kidney. The glomerular filtration rate in the operated kidney was determined by the MDRD2 (Modification of Diet in Renal Disease 2) equation along with renal scan in patients with a contralateral kidney. Surgical precision was defined as actual postoperative parenchymal volume/predicted postoperative parenchymal volume, presuming loss of a 5 mm rim of normal parenchyma related to excision and reconstruction.Median patient age was 61 years and 64 patients (52%) underwent an open procedure. Cold ischemia was used in 50 patients (median 26 minutes) and limited warm ischemia (median 20 minutes) was used in 72. The R.E.N.A.L. (radius, exophytic/endophytic, nearness of tumor to collecting system or sinus, anterior/posterior and location relative to polar line) nephrometry score indicated low, intermediate and high complexity in 43 (35%), 55 (45%) and 24 patients (20%), respectively. A total of 45 patients (37%) with a solitary kidney were included in analysis. The median precision of excision and reconstruction was 93%. The median preserved glomerular filtration rate was 80% in the operated kidney. A solitary kidney was the only significant predictor of excision and reconstruction precision on univariable and multivariable analysis.A solitary kidney significantly impacted partial nephrectomy surgical precision. This was likely related to the recognized need to preserve as much renal parenchyma as possible to optimize renal function in the absence of a contralateral kidney.

Background: Macroautophagy is a catabolic process that can mediate cell death or survival. Apo2 ligand (Apo2L)/ tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) treatment (TR) is known to induce autophagy. Here we investigated whether SQSTM1/p62 (p62) overexpression, as a marker of autophagic flux, was related to aggressiveness of human prostate cancer (PCa) and whether autophagy regulated the treatment response in sensitive but not resistant PCa cell lines. Methods: Immunostaining and immunoblotting analyses of the autophagic markers p62 [in PCa tissue microarrays (TMAs) and PCa cell lines] and LC3 (in PCa cell lines), transmission electron microscopy, and GFP-mCherry-LC3 were used to study autophagy induction and flux. The effect of autophagy inhibition using pharmacologic (3-methyladenine and chloroquine) and genetic [(short hairpin (sh)-mediated knock-down of ATG7 and LAMP2) and small interfering (si) RNA-mediated BECN1 knock-down] approaches on TR-induced cell death was assessed by clonogenic survival, sub-G1 DNA content, and annexinV/PI staining by flow cytometry. Caspase-8 activation was determined by immunoblotting. Results: We found that increased cytoplasmic expression of p62 was associated with high-grade PCa, indicating that autophagy signaling might be important for survival in high-grade tumors. TR-resistant cells exhibited high autophagic flux, with more efficient clearance of p62-aggregates in four TR-resistant PCa cell lines: C4-2, LNCaP, DU145, and CWRv22.1. In contrast, autophagic flux was low in TR-sensitive PC3 cells, leading to accumulation of p62-aggregates. Pharmacologic (chloroquine or 3-methyladenine) and genetic (shATG7 or shLAMP2) inhibition of autophagy led to cell death in TR-resistant C4-2 cells. shATG7-expressing PC3 cells, were less sensitive to TR-induced cell death whereas those shLAMP2-expressing were as sensitive as shControl-expressing PC3 cells. Inhibition of autophagic flux using chloroquine prevented clearance of p62 aggregates, leading to caspase-8 activation and cell death in C4-2 cells. In PC3 cells, inhibition of autophagy induction prevented p62 accumulation and hence caspase-8 activation. Conclusions: We show that p62 overexpression correlates with advanced stage human PCa. Pharmacologic and genetic inhibition of autophagy in PCa cell lines indicate that autophagic flux can determine the cellular response to TR by regulating caspase-8 activation. Thus, combining various autophagic inhibitors may have a differential impact on TR-induced cell death.

Objectifs Certains auteurs ont suggere que les reins pathologiques ont une plus mauvaise recuperation fonctionnelle apres la chirurgie renale. L’objective de cette etude etait de comparer la recuperation fonctionnelle des patients avec ou sans insuffisance renale apres l’ischemie liee a une nephrectomie partielle (NP) pour cancer. Methodes Cent-cinquante-cinq patients qui ont eu une NP avec une evaluation volumetrique renale sur la TDM pre ( Resultats L’âge median (IQR) etaient de 62 (55–70). Le score RENAL median (IQR) etait de 8 (6–9). Sur l’ensemble, 59 (38 %) patients avaient un rein unique. L’ischemie froide (duree mediane : 27 min ; IQR 23-34) et chaude (duree mediane : 20 ; IQR : 14–27) a ete respectivement utilisee dans 64 (41 %) et 91 (59 %) des cas. La recuperation mediane (IQR) de la fonction renale globale etait de 95 % (87–106). Il n’y avait aucune correlation entre le DFG preoperatoire et la capacite de recuperation de la fonction des nephrons preserves que ce soit en ischemie froide en ischemie chaude en stratifiant les resultats sur le DFG preoperatoire ( Tableau 1 ). Conclusion Dans la limite d’une duree d’ischemie raisonnable, la capacite de recuperation du traumatisme chirurgical de la NP n’est pas correlee a l’etat preoperatoire des nephrons. Cette etude conforte l’idee que le volume nephronique preserve est le facteur le plus determinant de la fonction renale apres NP.

prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95. J Clin Oncol 2009;27:2924–30. [10] Goenka A, Magsanoc JM, Pei X, et al. Long-term outcomes after high-dose postprostatectomy salvage radiation treatment. Int J Radiat Oncol Biol Phys 2012;84:112–8. [11] Van der Kwast TH, Bolla M, Van Poppel H, et al. Identification of patients with prostate cancer who benefit from immediate postoperative radiotherapy: EORTC 22911. J Clin Oncol 2007;25:4178–86. [12] Ploussard G, Staerman F, Pierrevelcin J, et al. Predictive factors of oncologic outcomes in patients who do not achieve undetectable prostate specific antigen after radical prostatectomy. J Urol 2013; 190:1750–6.

Objective To compare the outcomes of active surveillance (AS) series between African American men (AAM) and non-AAM diagnosed with low-risk prostate cancer at 3 medical centers. Methods Between 2005 and 2012, 214 men accepted AS on the basis of favorable clinical features and parameters after initial and repeat biopsy. Failure was defined as increase in Gleason score >6, total positive cores >33%, maximum cancer volume in any core >50%, or a prostate-specific antigen >10 ng/mL. Disease progression and overall AS failure were compared between the 2 groups. Results Of 214 men, 75 were excluded, leaving 67 AAM and 72 non-AAM on AS. Median age at diagnosis was 64 and 67 years for AAM and non-AAM, respectively, and median follow-up was 34 and 46 months, respectively. During this time, 44 AAM (66%) remained on AS, and 23 (34%) underwent treatment, of whom 6 (26%) were treated by patient choice and 17 (74%) because of disease progression. In the non-AAM group, 59 (82%) men remained on AS, and 13 (18%) underwent treatment, 8 (62%) were treated by patient choice and 5 (38%) because of disease progression. The 3-year freedom from overall treatment was 74% and did not differ by race (P = .06). The 3-year freedom from disease progression was 85%, where AAM were at significantly higher risk of disease progression (hazard ratio = 3.8; 95% confidence interval: 1.4-10.4; P = .01). Conclusion Our study suggests a higher disease progression rate in AAM who choose AS for low-risk prostate cancer compared with non-AAM, signifying a potential need for closer follow-up and more stringent enrollment criteria in AAM.

The aim of our report was to describe the feasibility of robotic retroperitoneal lymph node dissection in the contemporary era. We suggest the linear port location and 90° robotic docking as the main key to minimizing instrument clashing and improving the range of surgical accessibility.

INTRODUCTION AND OBJECTIVES: Ultimate decline in GFR after partial nephrectomy (PN) is influenced primarily by type and duration of ischemia and parenchymal volume preserved. The role of ischemia relative to volume preservation has been controversial. OBJECTIVES: To directly evaluate the function specifically in the operated kidney pre and post conventional PN and to assess relationships with type and duration of ischemia and percent parenchymal volume preserved. METHODS: 55 patients with localized renal tumors (2007-11) had necessary studies for analysis; there were no exclusions. This comprised 24 solitary kidneys and 31 bilateral kidneys with pre and post-operative RFS, and the analysis was exclusively focused on the operated kidney. 33 (60%) cases were open and the remainder were MIS. 24 cases (44%) utilized hypothermia and 31 were performed using limited warm ischemia. Volumetric CT scans were utilized to directly measure the volume of functional parenchyma pre (subtracting out the tumor) and post PN in the operated kidney. eGFR in the operated was determined by the MDRD2 equation, along with RFS data for patients with bilateral kidneys. Regression analysis was used to assess the relationships between ultimate GFR preserved in the operated kidney and potential predictive factors. All postoperative analyses were performed between 6-12 months. RESULTS: Median age was 61 years, median tumor size was 3.5 cm, and median RENAL score was 8. Median cold ischemia time (CIT) was 29 min (IQR 23-33) and median warm ischemia time (WIT) was 21 min (IQR 14.25-27.75). Pathology results showed pT1a in 33 (61.1%) and clear cell carcinoma in 41 (74.5%). Median preop GFR in the operated kidney was 47.2 (33.85-56) compared with 36.1 (25.0547.85) postoperatively. Median percent GFR preserved in the operated kidney was 88 (79-95.1). Median percent volume preserved was 83% (75.3-90.5). On regression analysis, percent GFR saved associated most strongly with percent parenchymal preservation (p 0.0001), but also with lower RENAL score (p 0.0174), and marginally with cold ischemia (p 0.0608). In contrast, length of ischemia did not correlate with percent GFR preserved (p 0.2487). Interestingly, function in the contralateral kidney did not change substantially ( 5% in all cases). CONCLUSIONS: Ultimate function after PN primarily correlated with parenchymal volume preservation, while ischemia played a secondary role. Thus, maximal parenchymal preservation with a precise PN should be a priority during conventional PN.

Watchful waiting (WW) is described as a decision not to actively treat a patient with prostate cancer who instead is closely followed until disease progression when treatment is initiated. This is developed in recognition of the slow growth of many tumors, competing disease entities, and a realization of the side effects of many of the treatments of prostate cancer. In advanced prostate cancer (T3-4, N0-1, M0), very few studies have focus on WW as an option, so evidence-based medicine on this topic is sparse. Nevertheless, WW is actively practiced with its main objective as a management strategy to minimize morbidity from prostate cancer and/or its active treatment. In most instances, WW in advanced prostate cancer has been utilized in elderly patients with comorbidities where the balance toward no treatment determines a better quality of life without shortening the overall survival.

586 Background: Renal cancer is associated with chronic kidney disease. Several studies have shown a 20% rate of preoperative CKD in the population undergoing partial nephrectomy. The non-neoplastic abnormalities (NNA) surrounding a tumor have been suggested as surrogates for long term renal failure. We have endeavored to describe the most relevant features within the above mentioned kidney area in patients with and without preoperative CKD. Methods: We retrospectively reviewed 201 patients who underwent nephrectomy between 2012 and 2014 with available histological assessment of NNA. Additional factors were included in the analysis such as demographic characteristics (age, sex, BMI) and comorbidities (hypertension, diabetes, Charlson comorbidity index). Pathological features were grouped as follows: glomerular (GA), interstitial (IA) or vascular abnormalities (VA). Univariate and multivariate logistic regression analyses were used to determine the associations between NNA and the presence of preoperative CKD stage III. Results: CKD stage III patients were older (68 vs. 56 years, P < .004) and presented a higher rate of DM with end-organ damage (n = 10, 13% vs N = 2 2%). Otherwise, people with and without CKD showed similar demographics. Overall, 56% of patients showed GA, 86% showed IA and 98% of patients presented with VA. In the multivariate analysis adjusted for comorbidities, the most relevant GAs were diabetic glomerulosclerosis (OR 7.32; p = 0.01), segmental sclerosis (OR 4.54; p = 0.0006) and glomerular adhesion (OR 2.80; p = 0.04). In the IA group, interstitial fibrosis (OR 7.36; p < 0.001), tubular atrophy (OR 2.75; p = 0.02) and acute interstitial inflammation (OR 12.47; p = 0.02) were significantly associated with decreased eGFR. Hyperplastic arteriolosclerosis (OR 2.30; p = 0.025) was an independent predictor of baseline eGFR < 60. Conclusions: NNA assessment from surgical specimen is feasible. Patients with baseline CKD present with several abnormalities related to inflammation and healing within the three nephron areas. The further investigation of these abnormalities might have a role in the evaluation of ultimate renal deterioration.

238 Background: Pelvic lymph node dissection (PLND) during radical prostatectomy (RP) is the most effective method for detecting lymph node metastases in patients with prostate cancer. The association between PLND during RP and morbidity, especially thromboembolic adverse events (AEs), remains unclear. We assessed the effect of PLND on 30−day postoperative AEs in patients undergoing RP using the American College of Surgeons’ National Surgical Quality Improvement Program database (NSQIP). Methods: A total of 21,895 men undergoing RP between 2006 and 2013 were classified into two groups according to surgical approach (MIS−RP vs. ORP) and whether PLND was performed. Multivariate logistic regression adjusting for approach and demographic features was performed to assess the impact of PLND for predicting two primary endpoints (overall complications and major complications defined as Clavien−Dindo ≥ 3) and for 17 types of complications. P−values were adjusted to maintain an experiment−wise p < 0.05. Results: MIS−RP and ORP was performed in 17,354 (79.3%) and 4,541 (20.7%) patients, respectively. PLND was performed in 7,579 (43.7%) and 3,597 (79.2%) patients in the MIS−RP and ORP groups, respectively. The overall postoperative complication rate was 8.7% (5.5% for MIS−RP and 21.0% for ORP). PLND was not associated with a higher risk of DVT (OR 0.99; p= 0.98) or PE (OR 1.02; p= 0.91). However, PLND was associated with a higher risk of superficial surgical site infection (OR 1.68; p = 0.013), organ space surgical site infection (OR 1.77; p = 0.02), and perioperative transfusion (OR 1.32; p = 0.002) regardless of surgical approach. PLND was not associated with overall or major AEs on multivariable analysis. ORP was associated with a significantly higher risk of overall (OR 4.64, p < 0.0001) and major (OR 1.6, p = 0.0004) AEs compared to MIS−RP. Conclusions: PLND during RP is associated with a significantly increased risk of certain types of AEs within the 30−day post−operative period. However, there appears to be no significant association between PLND and thromboembolic AEs.

Adrenocortical carcinoma (ACC) is a rare and clinically aggressive cancer. Previous studies reported increased recurrence rates associated with laparoscopic adrenalectomy (LA). We evaluated a single-center experience of LA versus open adrenalectomy (OA) for the management of ACC.Between 1993 and 2011, 44 consecutive patients with primary ACC were treated at our institution. Baseline patient characteristics and surgical and pathological outcomes were compared between OA and LA groups. Multivariable Cox proportional hazards analysis was used to estimate the association between OA versus LA with recurrence-free and overall survival.Eighteen and 26 patients underwent LA and OA, respectively. Patients who underwent OA had larger tumors and more advanced clinical stage compared with LA group. During a median follow-up of 22 months, 22 recurrences and 26 deaths were observed. The 2-year, recurrence-free and overall survivals for OA and LA were 60 vs. 39 % (P = 0.7) and 54 vs. 58 % (P = 0.6), respectively. After adjusting for clinical stage, OA was associated with lower risk of recurrence (hazard ratio (HR) 0.4; 95 % confidence interval (CI) 0.2-1.2; P = 0.099) and improved overall survival (HR 0.5; 95 % CI 0.2-1.2; P = 0.122) compared with LA, although differences were not statistically significant.A nonstatistically significant increase in recurrence and death was observed among patients undergoing LA versus OA after adjusting for clinical stage. The rarity of this disease limits the ability to assess for significant differences in a single-institution series. Patients with suspected ACC should be considered for OA.

Several studies have demonstrated the usefulness of monitoring an RNA transcript, such as PCA3, in post-prostate massage (PM) urine for increasing the specificity of prostate-specific antigen (PSA) in the detection of prostate cancer (PCa). However, a single marker may not necessarily reflect the multifactorial nature of PCa.We analyzed post-PM urine samples from 154 consecutive patients, who presented for prostate biopsies because of elevated serum PSA (4 ng/ml) and/or abnormal digital rectal exam. We tested whether the putative PCa biomarkers PSMA, PSGR, and PCA3 could be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings to test if a combination of these biomarkers could improve the specificity of actual diagnosis. Afterwards, we specifically tested our model for clinical usefulness in the PSA diagnostic "gray zone" (4-10 ng/ml) on a target subset of 82 men with no prior biopsy.By univariate analysis, we found that the PSMA, PSGR, and PCA3 scores were significant predictors of PCa. Using a multiplex model, the area under the multi receiver-operating characteristic curve was 0.74 versus 0.82 in the diagnostic "gray zone." Fixing the sensitivity at 96%, we obtained a specificity of 34% and 50% in the gray zone.Taken together, these results provide a strategy for the development of a more accurate model for PCa diagnosis. In the future, a multiplexed, urine-based diagnostic test for PCa with a higher specificity, but the same sensitivity as the serum-PSA test, could be used to determine better which patients should undergo biopsy.

Penile squamous cell carcinoma (SCC) is an uncommon condition in Western countries. Inguinal lymph nodes dissection can be curative in 20%–60% of node positive patients. However, there is a high complication rates from the dissection, thus accurate diagnosis of inguinal lymph nodes metastasis is required. Current non invasive methods to detect lymph nodes metastasis are unreliable. Dynamic Sentinel Node Biopsy (DNSB), ultrasonography (US), and fine needle aspiration (FNA) cytology were proposed to in an attempt to detect sentinel lymph node (SLN). Despite the initial high rate of false negative results, recent DSNB showed improved survival compared to wait and see policy as well as reduced mortality compared to prophylactic inguinal lymphadenectomy. In addition, the US guided FNA shown 100% of specificity in detecting clinically occult lymph nodes metastasis. We proposed an algorithm for management of lymph nodes in penile cancer and suggest that FNA with US guidance should be performed in all high risk patients and that therapeutic dissection should be performed if findings are positive.

To evaluate the clinical and pathologic features and the prognostic relevance of unclassified RCC with -TFE3 over-expression in our adult series. Recent studies suggest that renal cell carcinomas (RCCs) associated with the newly recognized Xp11.2 translocation (transcription factor E3 [TFE3] gene fusions) can be found among adults with RCC showing a very aggressive disease-course.We evaluated tumour specimens from 25 patients with unclassified RCC morphology out of 298 RCCs in the last 12 years in a tertiary academic centre. Immunohistochemistry was performed using monoclonal antibody for TFE3 C-terminal section, taking nuclear label into consideration. RT-PCR technique was performed for ASPL-TFE3 gene fusion on two tumours with available frozen tissue.Of the 25 cases analyzed, 8 (32%) showed positivity for TFE3 and 17 were negative for TFE3 staining. Two tumors with ASPL-TFE3 gene fusion also showed TFE3 over-expression. Fifty percent of the positive patients had lymph node metastatic disease, whereas only one TFE3-negative patient (5.8%) showed evidence of lymph node spread and cava thrombus at diagnosis. Of the TFE3-positive patients, three had a vena cava thrombus (37.5%). Seven of the eight positive cases (87.5%) were diagnosed with a high Fuhrman grade (III/IV). In comparison, five of 17 (29.4%) TFE3-negative patients had a high Fuhrman grade. Five of eight TFE3-positive patients relapsed rapidly at 3 month follow-up; conversely none of the negative cases relapsed. At 36-month mean follow-up, 5-year cancer-specific survival was 15.6% for TFE3-positive patients and 87.5% for TFE3-negative patients (P0.001).Patients with unclassified RCC and TFE3 positivity have a grim prognosis due to their advanced stage at presentation and aggressive biologic features compared with the TFE3-negative unclassified RCC cases.

Several studies have demonstrated the usefulness of monitoring an RNA transcript in urine, such as PCA3, for prostate cancer (PCa) diagnosis. PCa screening would benefit from additional biomarkers of higher specificity and could be used in conjunction with prostate-specific antigen (PSA) testing, in order to better determine biopsy candidates.We used urine sediments after prostate massage (PM) from 215 consecutive patients, who presented for prostate biopsy. We tested whether prostate-specific G-protein coupled receptor (PSGR), a biomarker previously described to be over-expressed in PCa tissue, could also be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings with prostate cancer gene 3 (PCA3), the current gold standard for PCa diagnosis in urine, to test if a combination of both biomarkers could improve the sensitivity of PCA3 alone.By univariate analysis we found that PSGR and PCA3 were significant predictors of PCa. Receiver operator characteristic curve analysis and its multivariate extension, multivariate ROC (MultiROC), were used to assess the outcome predictive values of the individual and the paired biomarkers. We obtained the following area under the curve values: PSA (0.602), PSGR (0.681), PCA3 (0.656), and PSGRvPCA3 (0.729). Then, we tested whether a combination of PSGR and PCA3 could improve specificity by fixing the sensitivity at 95%. We obtained specificities of 15% (PSGR), 17% (PCA3), and 34% (PSGRvPCA3).A multiplexed model including PSGR and PCA3 improves the specificity for the detection of PCa, especially in the area of high sensitivity. This could be clinically useful for determining which patients should undergo biopsy.

Dual-energy X-ray absorptiometry (DXA) is the standard method to assess bone mineral density (BMD). The International Society for Clinical Densitometry recommends the measurement of BMD at lumbar spine, total hip and femoral neck, but in certain circumstances the 33% radius may be the recommended area to measure BMD. The aim of this study has been to analyze whether 33% radius should be considered the recommended area to assess BMD in prostate cancer patients.This is a retrospective study where BMD was assessed by DXA at 33% radius, lumbar spine, total hip, and femoral neck (cDXA) in 141 prostate cancer patients. Twenty-eight patients were hormone naïve while 113 were subjected to androgen suppression (AS) during the mean period of 29 months. Osteoporosis was diagnosed when T-score was lower than -2.5 and osteopenia when it ranged between -1 and -2.5.The osteoporosis rate was 29.8% at 33% radius, 23.4% at femoral neck, 19.9% at lumbar spine, and 12.8% at total hip. The overall osteoporosis rate at cDXA was 29.1%. Osteoporosis was detected in 52.2% at 33% radius and 36.2% at cDXA. Normal BMD was found in 17.7% at 33% radius and 34.8% at cDXA. The 33% radius was the only site where a significant increase in the osteoporosis rate was detected in patients subjected to AS compared to those hormone naïve (33 and 13.8%).The 33% radius seems more sensible than the central skeleton areas to detect bone mass loss in patients with prostate cancer.

OBJECTIVES To review the relationship between the Gleason grade and prostate volume in biopsy and radical prostatectomy (RP) specimens, and thus assess the hypothesis that smaller prostates have a greater incidence of high-grade tumours. PATIENTS AND METHODS We selected 390 patients who had RP at our institution, with a prostate-specific antigen (PSA) level of