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Purpose: IFN-α is a pleiotropic cytokine possessing immunomodulatory properties that may improve the efficacy of therapeutic cancer vaccines. The aim of this study was to evaluate the effectiveness and compatibility of combining recombinant IFN-α with poxvirus vaccines targeting the human carcinoembryonic antigen (CEA) in murine models of colorectal and pancreatic adenocarcinomas, where CEA is a self-antigen.Experimental Design: The phenotypic and functional effects of IFN-α were evaluated in the draining inguinal lymph nodes of tumor-free mice. We studied the effect of the site of IFN-α administration (local versus distal) on antigen-specific immune responses to poxvirus vaccination. Mechanistic studies were conducted to assess the efficacy of IFN-α and CEA-directed poxvirus vaccines in tumor-bearing CEA transgenic mice.Results: We identified a dose and schedule of IFN-α that induced a locoregional expansion of the draining inguinal lymph nodes and improved cellular cytotoxicity (natural killer and CD8+) and antigen presentation. Suppression of the vaccinia virus was avoided by administering IFN-α distal to the site of vaccination. The combination of IFN-α and vaccine inhibited tumor growth, improved survival, and elicited CEA-specific CTL responses in mice with CEA+ adenocarcinomas. In mice with pancreatic tumors, IFN-α slowed tumor growth, induced CTL activity, and increased CD8+ tumor-infiltrating lymphocytes.Conclusions: These data suggest that IFN-α can be used as a biological response modifier with antigen-directed poxvirus vaccines to yield significant therapeutic antitumor immune responses. This study provides the rationale and mechanistic insights to support a clinical trial of this immunotherapeutic strategy in patients with CEA-expressing carcinomas.

Supplementary Figures S1-S7 from The Antitumor and Immunoadjuvant Effects of IFN-α in Combination with Recombinant Poxvirus Vaccines

A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders). While baseline titers did not predict treatment response, 3-mo titer800 was associated with a higher likelihood of durable response (p = 0.026). Peak post-treatment titers800 were noted in 42 (89%) responders versus 26 (59%) nonresponders (p = 0.001; assay sensitivity, 89%; negative predictive value, 78%). Moreover, 22 (47%) responders compared with eight (18%) nonresponders had a combination of peak post-treatment titers800 and peak antibody fold change8 (p = 0.004; assay specificity, 82%; positive predictive value, 73%). A majority of responders continued to have post-treatment antibody titers800 after the first 6 mo of therapy. In conclusion, serum antiadenovirus antibody quantification may serve as a novel predictive marker for nadofaragene firadenovec response durability. Future studies will focus on large-scale validation and clinical utility of the assay. PATIENT SUMMARY: This study reports on a planned secondary analysis of a phase 3 multicenter clinical trial that established the benefit of nadofaragene firadenovec, a novel intravesical gene therapeutic, for the treatment of patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer. Prospective assessment of serum anti-human adenovirus type-5 antibody levels of patients in this trial indicated that a combination of post-treatment titers and fold change from baseline can predict treatment efficacy. While this merits additional validation, our findings suggest that serum antiadenovirus antibody levels can serve as an important predictive marker for the durability of therapeutic response to nadofaragene firadenovec.

INTRODUCTION AND OBJECTIVE:Nadofaragene firadenovec is a recombinant adenoviral vector-based intravesical therapeutic that delivers a copy of human IFNα2b gene to urothelial cells. A recent phase 3...

Better prostate cancer risk stratification is necessary to inform medical management, especially for African American (AA) men, for whom outcomes are particularly uncertain.To evaluate the utility of both a cell cycle progression (CCP) score and a clinical cell-cycle risk (CCR) score to predict clinical outcomes in a large cohort of men with prostate cancer highly enriched in an AA patient population.Patients were diagnosed with clinically localized adenocarcinoma of the prostate and treated at The Ochsner Clinic (New Orleans, LA, USA) from January 2006 to December 2011. CCP scores were derived from archival formalin-fixed, paraffin-embedded biopsy tissue. CCR scores were calculated as the combination of molecular (CCP score) and clinical (Cancer of the Prostate Risk Assessment [CAPRA] score) components.Active treatment (radical prostatectomy, radiation therapy alone, or radiation and hormone therapy) or watchful waiting.The primary outcome was progression to metastatic disease. Association with outcomes was evaluated via Cox proportional hazards survival analysis and likelihood ratio tests.The final cohort included 767 men, of whom 281 (36.6%) were AA. After accounting for ancestry, treatment, and CAPRA in multivariable analysis, the CCP score remained a significant predictor of metastatic disease (hazard ratio [HR] 2.04; p0.001), and there was no interaction with ancestry (p=0.20) or treatment (p=0.09). The CCR score was highly prognostic (HR 3.86; p0.001), and as with the CCP score, there was no interaction with ancestry (p=0.24) or treatment (p=0.32). Limitations include the retrospective study design and the use of self-reported ancestry information.A CCR score provided significant prognostic information regardless of ancestry. The findings demonstrate that AA men in this study cohort appear to have similar prostate cancer outcomes to non-AA patients after accounting for all available molecular and clinicopathologic variables.In this study we evaluated the ability of a combined molecular and clinical score to predict the progression of localized prostate cancer. We found that the combined molecular and clinical score predicted progression to metastasis regardless of patient ancestry or treatment. This suggests that the combined molecular and clinical score may be a valuable tool for determining the risk of metastasis in men with newly diagnosed prostate cancer in order to make appropriate treatment decisions.

African Americans (AA) have higher incidence and mortality rates for several cancer types in comparison to their European American (EA) counterparts. Increasing participation in clinical research and patient registries, related to precision cancer medicine, will significantly improve cancer health equity. Many AA cancer patients are treated in community oncology clinics. Unfortunately, these health systems have limited access to Clinical Laboratory Improvement Amendments (CLIA) next generation sequence (NGS) germline and somatic DNA and RNA testing that are used to inform oncologists on the best treatment and/or clinical trial options for cancer patients. Indeed, AA CLIA NGS sample sets are poorly represented, which could presumably result in incomplete knowledge of genomic variants that could affect their treatment and overall outcomes. Hence, it is crucial to implement CLIA NGS efforts for all cancer patients. To address these disparities, Morehouse School of Medicine has formed the Comprehensive Approach to Reimagine health Equity Solutions (CARhES) consortium with Tuskegee University that has engaged community oncology practices in Alabama and Georgia - two of five Black Belt states. The CARhES consortium aims to implement precision cancer medicine to underserved and underrepresented communities that will improve the standard of cancer care by providing access to CLIA NGS testing, clinical trials, and personalized cancer care. Here we describe the first proof of concept of this approach with community oncology partners, i.e., Grady Health System, Wellstar Health System, Georgia Urology, Midtown Urology, and Maui Memorial Medical Center. At the time of consent, saliva, buccal, and tumor samples were collected from participants. Germline and somatic CLIA NGS was performed, and medical reports were returned to practitioners within 14 days. Prior to the COVID pandemic, the study enrolled over 880 patients with a 88% consent rate (n = 1000) in the first 11months of the program. At the start of the COVID pandemic, recruitment efforts were suspended for four months with a slow restart by June 2020. A decrease in the number of staff, office visits (67% reduction), and increase in COVID cases significantly limited recruitment efforts. During this slowdown, we established and improved eConsenting capabilities, which exist today. Community anxiety, due to the pandemic and SARS-CoV-19 vaccine efforts, resulted in a significant reduction in consent rates (88% to 60%). Nevertheless, this study began in April of 2019 and consented 1,750 participants in less than 2 years. Taken together, our study shows that a community-focused precision medicine approach requires meeting people where they are and providing them with access and understanding the benefit of clinical trial participation. The approximate 2,000 clinically annotated genomic AA datasets will greatly contribute to our understanding of cancer health disparities and among the first steps to democratize precision medicine. This study was funded by the American Association for Cancer Research, The Pelotonia Foundation, the M2Gen Foundation, and the National Cancer Institute (U54CA118638). Citation Format: Latrisha L. Horne, Gabriella M. Oprea-Ilies, Eddie R. Stanley, Carla M. Holloway, Margaret P. Hooker, Amina Isom, Derrick J. Beech, Ana Gaonkar, Shavette Harden, Jeffrey F. Hines, LaTonya Randolph, James K. Bennett, Daniel Canter, Darrell J. Carmen, Pooja Mishra, Giuseppe Del Priore, Roland Matthews, Brian M. Rivers, James W. Lillard. AACR President's initiative - 2020 by 2020: Democratizing precision cancer medicine and advancing health equity in the black belt [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB173.

// Jessie Gills 1, * , Ravan Moret 2, * , Xin Zhang 2 , John Nelson 1 , Grace Maresh 2 , Linh Hellmers 2 , Daniel Canter 1 , M’Liss Hudson 1, 6 , Shams Halat 3 , Marc Matrana 4 , Michael P. Marino 5 , Jakob Reiser 5 , Maureen Shuh 2 , Eric Laborde 1 , Maria Latsis 1 , Sunil Talwar 1 , Stephen Bardot 1 and Li Li 2 1 Department of Urology, Ochsner Clinic Foundation, New Orleans, LA, USA 2 Institution of Translational Research, Ochsner Clinic Foundation, New Orleans, LA, USA 3 Department of Pathology, Ochsner Clinic Foundation, New Orleans, LA, USA 4 Department of Hematology and Oncology, Ochsner Clinic Foundation, New Orleans, LA, USA 5 Division of Cellular and Gene Therapies, The Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA 6 Current address: Memorial Urology Associates, Houston, TX, USA * These authors contributed equally to this work Correspondence to: Stephen Bardot, email: sbardot@ochsner.org Li Li, email: lli@ochsner.org Keywords: patient-derived orthotopic xenograft; high-grade/muscle invasive urothelial cell carcinoma; lymph node stromal cells Received: June 26, 2018 Accepted: August 10, 2018 Published: August 24, 2018 ABSTRACT High-grade urothelial cell carcinoma of the bladder has a poor prognosis when lymph nodes are involved. Despite curative therapy for clinically-localized disease, over half of the muscle-invasive urothelial cell carcinoma patients will develop metastases and die within 5 years. There are currently no described xenograft models that consistently mimic urothelial cell carcinoma metastasis. To develop a patient-derived orthotopic xenograft model to mimic clinical urothelial cell carcinoma progression to metastatic disease, the urothelial cell carcinoma cell line UM-UC-3 and two urothelial cell carcinoma patient specimens were doubly tagged with Luciferase/RFP and were intra-vesically (IB) instilled into NOD/SCID mice with or without lymph node stromal cells (HK cells). Mice were monitored weekly with bioluminescence imaging to assess tumor growth and metastasis. Primary tumors and organs were harvested for bioluminescence imaging, weight, and formalin-fixed for hematoxylin and eosin and immunohistochemistry staining. In this patient-derived orthotopic xenograft model, xenograft tumors showed better implantation rates than currently reported using other models. Xenograft tumors histologically resembled pre-implanted primary specimens from patients, presenting muscle-invasive growth patterns. In the presence of HK cells, tumor formation, tumor angiogenesis, and distant organ metastasis were significantly enhanced in both UM-UC-3 cells and patient-derived specimens. Thus, we established a unique, reproducible patient-derived orthotopic xenograft model using human high-grade urothelial cell carcinoma cells and lymph node stromal cells. It allows for investigating the mechanism involved in tumor formation and metastasis, and therefore it is useful for future testing the optimal sequence of conventional drugs or the efficacy of novel therapeutic drugs.

Introduction: Neutrophil/lymphocyte ratio (NLR) is an indicator of systemic inflammation and has been proven to be associated with an increased risk of extravesical disease, decreased cancer specific survival and overall survival in bladder cancer patients. A large proportion of healthy African Americans have a WBC count that is persistently lower than the normal range defined for individuals of European ancestry, this condition has been called “benign ethnic neutropenia”. The purpose of our study was to determine if NLR was different in patients of African ancestry (AA) vs European ancestry (EA) across different tumor grades and stages at the time of transurethral resection of bladder tumor(s) (TURBT). Materials and Methods: The records of consecutive patients who underwent TURBT were reviewed from the University of Wisconsin and the Atlanta Veterans’ Administration Medical Center (2000–2012). NLR was compared across tumor stage, tumor grade and ethnicity. Results: 297 consecutive patients met study criteria. 89% and 86%, were males and of European ancestry (EA) respectively. NLRs were different across T-stages (Ta-2.5, T1-3.9, T2-3.8; p = 0.001). but not across tumor grades in Ta (LG-2.5 vs HG-3.9, p = 0.57). EA had higher NLRs than AA (3.4 vs 1.9; p

INTRODUCTION AND OBJECTIVES:Renal cell carcinoma (RCC) incidence is increasing, and metastatic disease effects up to 25% of RCC patients. Additionally, RCC has varying prognoses and therapy respons...

Purpose: Neoadjuvant chemotherapy and pelvic surgery are significant risk factors for thromboembolic events. Our study objectives were to investigate the timing, incidence and characteristics of thromboembolic events during and after neoadjuvant chemotherapy and subsequent radical cystectomy in patients with muscle invasive bladder cancer. Materials and Methods: We performed a multi-institutional retrospective analysis of 761 patients who underwent neoadjuvant chemotherapy and radical cystectomy for muscle invasive bladder cancer from 2002 to 2014. Median followup from diagnosis was 21.4 months (range 3 to 272). Patient characteristics included the Khorana score, and the incidence and timing of thromboembolic events (before vs after radical cystectomy). Survival was calculated using the Kaplan-Meier method. The log rank test and multivariable Cox proportional hazards regression were used to compare survival between patients with vs without thromboembolic events. Results: The Khorana score indicated an intermediate thromboembolic event risk in 88% of patients. The overall incidence of thromboembolic events in patients undergoing neoadjuvant chemotherapy was 14% with a wide variation of 5% to 32% among institutions. Patients with thromboembolic events were older (67.6 vs 64.6 years, p = 0.02) and received a longer neoadjuvant chemotherapy course (10.9 vs 9.7 weeks, p = 0.01) compared to patients without a thromboembolic event. Of the thromboembolic events 58% developed preoperatively and 72% were symptomatic. On multivariable regression analysis the development of a thromboembolic event was not significantly associated with decreased overall survival. However, pathological stage and a high Khorana score were adverse risk factors for overall survival. Conclusions: Thromboembolic events are common in patients with muscle invasive bladder cancer who undergo neoadjuvant chemotherapy before and after radical cystectomy. Our results suggest that a prospective trial of thromboembolic event prophylaxis during neoadjuvant chemotherapy is warranted.

Tailoring perioperative management to minimize the postoperative complication rates depends on reliable prognostication of patients most at risk. The Surgical Apgar Score is an objective measure of the operative course validated to predict major complications and death after general/vascular surgery. We assessed the ability of the Surgical Apgar Score to identify patients most at risk for postoperative morbidity and mortality after renal mass excision.Data for 886 patients undergoing renal mass excision via radical or partial nephrectomy from 2010 to 2013 were extracted from a prospectively collected database. The Surgical Apgar Score was calculated using electronic anesthesia records. Major postoperative complications, readmission and reoperation within 30 days of surgery as well as 90-day mortality were examined.Overall 13.2% of patients experienced major postoperative complications at 30 days. Clavien grade I, II, III, IV and V complications were experienced by 1.7%, 2.9%, 5.8%, 1.9% and 0.9%, respectively. The 90-day all cause mortality rate was 1.4%. The Surgical Apgar Score was significantly lower in patients experiencing major complications (mean 7.3 vs 7.8, p=0.004) and death (6.3 vs 7.7, p=0.03). Patients with a Surgical Apgar Score of 4 or less were 3.7 times more likely to experience a major complication (p=0.01) and 24 times more likely to die within 90 days of surgery (p=0.0007) compared to patients with a Surgical Apgar Score greater than 8.The Surgical Apgar Score is an easily collected metric that can identify patients at higher risk for major complications and death after renal mass excision. A prospective trial to help further delineate the optimal use of this tool in an adjusted perioperative management approach with patients undergoing renal mass excision is warranted.

Background and Objectives Among patients with disseminated malignancy (DMa), bowel obstruction is common with high operative morbidity. Since preoperative risk stratification is critical, we sought to compare three standard risk indices, the American Society of Anesthesiology (ASA) classification, Charlson comorbidity index (CCI), and modified frailty index (mFI). Methods We identified 1928 DMa patients with bowel obstruction who underwent an abdominal operation from 2007 to 2012 American College of Surgeons National Surgical Quality Improvement Program. Multivariate analyses assessed predictors of prolonged length of stay (LOS), 30-day serious morbidity and mortality. Receiver operating characteristics’ areas under the curves (AUCs) for risk indices scores and 30-day mortality were assessed. Results Serious morbidity and mortality rates were 20.4% and 14.8%. ASA and CCI did not predict serious morbidity or prolonged LOS, but were predictors of mortality. The mFI did not predict prolonged LOS, but did predict serious morbidity and mortality. Subgroup analyses showed similar results. There were no significant differences between ASA, CCI, and mFI AUCs for mortality. Conclusions ASA, CCI, and mFI are limited in their ability to predict postoperative adverse events among DMa patients undergoing surgery for bowel obstruction. These data suggest that a more tailored preoperative risk stratification tool would improve treatment planning.

Objectives To incorporate C-reactive protein into nomograms estimating survival in patients with renal cell carcinoma. Methods Patients undergoing surgery for renal cell carcinoma from 2005–2012 were studied retrospectively. Multivariable Cox proportional hazards regression and competing risks regression models including stage, grade, C-reactive protein levels and presence of metastatic disease were constructed. Outcomes analyzed include overall mortality overall mortality and renal cell carcinoma-specific mortality. Results The cohort included 516 patients with a mean follow up of 1.7 years (SD 1.4 years). One- and 3-year renal cell carcinoma-specific mortality was 8.8% and 13.5%, respectively. Four nomograms were generated using overall mortality and renal cell carcinoma-specific mortality as end-points, two each for pre- and postoperative counseling. The factor with the largest effect on all nomograms was preoperative C-reactive protein. Based on the internal validation with bootstrapping, the concordance indices for renal cell carcinoma-specific mortality in the preoperative nomogram, postoperative nomogram, and the Mayo Clinic stage, size, grade and necrosis score were 0.889, 0.893, and 0.832, respectively (P = 0.005 and 0.002 comparing with stage, size, grade and necrosis scores for preoperative or postoperative nomograms). For overall mortality, the preoperative nomogram, postoperative nomogram, and stage, size, grade and necrosis score showed concordance indices of 0.866, 0.897, and 0.828, respectively (P = 0.123 and 0.008 compared with stage, size, grade and necrosis score for preoperative or postoperative nomograms). Conclusions We have generated nomograms incorporating serum C-reactive protein levels that effectively predict overall mortality and renal cell carcinoma specific mortality. Our findings warrant external validation.

Compared to T1a lesions the natural history of untreated renal masses larger than 4 cm is poorly understood. We assessed the growth kinetics and outcomes of cT1b/T2 cortical renal tumors managed by an initial period of active surveillance. We compared these cases to those treated with definitive delayed intervention.We reviewed our institutional, prospectively maintained renal tumor database to identify enhancing solid and cystic masses managed expectantly. Included in analysis were clinically localized tumors greater than 4.0 cm (T1b or greater) that were radiographically followed for more than 6 months. Tumor size at presentation, annual linear tumor growth rate, Charlson comorbidity index, followup and clinical outcomes were compared in patients who remained on active surveillance and those who underwent delayed surgical intervention.We identified 72 tumors 4 cm or greater in diameter in a total of 68 patients. Active surveillance was the only treatment in 45 patients (66%) while 23 (34%) progressed to intervention. Median tumor size at presentation was 4.9 cm and the mean linear growth rate was 0.44 cm per year. Of the masses 14.7% demonstrated no growth with time. Comparing patients treated exclusively with active surveillance and those who progressed to definitive intervention revealed no difference in median tumor size at presentation (4.9 vs 4.6 cm, p = 0.79) or the median Charlson comorbidity index (3 vs 2, p = 0.6) but significant differences were seen in median age at presentation (77 vs 60 years, p = 0.0002) and the mean linear growth rate (0.37 vs 0.73 cm per year, p = 0.02). After adjustment younger patients (OR 0.91, 95% CI 0.86-0.97) and tumors with a faster linear growth rate (OR 9.1, 95% CI 1.7-47.8) were more likely to be treated with delayed surgical intervention. At a mean ± SD 38.9 ± 24.0 months of followup (median 32, range 6 to 105) 9 patients (13%) had died of another cause and none had progressed to metastatic disease.Localized cT1b or larger renal masses show growth rates comparable to those of small tumors managed expectantly with a low rate of progression to metastatic disease at short-term followup. An initial period of active surveillance to determine tumor growth kinetics is a reasonable option in select patients with significant competing risks and limited life expectancy.

Objective To test the association between hospital type and performance of candidate quality measures for treatment of muscle-invasive bladder cancer (MIBC) using a large national tumour registry. Proposed quality measures include receipt of neoadjuvant chemotherapy, timely treatment, adequate lymph node dissection, and continent urinary diversion. Patients and Methods Using the National Cancer Database, patients with stage ≥II urothelial carcinoma treated with radical cystectomy (RC) from 2003 to 2010 were identified. Hospitals were grouped by type and annual RC volume: community, comprehensive low volume (CLV), comprehensive high volume (CHV), academic low volume (ALV), and academic high volume (AHV) groups. Logistic regression models were used to test the association between hospital group and performance of quality measures, adjusting for year, demographic, and clinical/pathological characteristics; generalised estimating equations were fitted to the models to adjust for clustering at the hospital level. Results In all, 23 279 patients underwent RC at community (12.4%), comprehensive (CLV 38%, CHV 5%), and academic (ALV 17%, AHV 28%) hospitals. While only 0.8% (175) of patients met all four quality criteria, 61% of patients treated at AHV hospitals met two or more quality metric indicators compared with ALV (45%), CHV (44%), CLV (38%), and community (37%) hospitals (P < 0.001). After adjustment, patients were more likely to receive two or more quality measures when treated at AHV (odds ratio [OR] 2.4, confidence interval [CI] 2.0–2.9), ALV (OR 1.3, CI 1.1–1.6), and CHV (OR 1.3, CI 1.03–1.7) hospitals compared with community hospitals. Conclusions Patients undergoing RC at AHV hospitals were more likely to meet quality criteria. However, performance remains low across hospital types, highlighting the opportunity to improve quality of care for MIBC.

Objective To compare overall and cancer-specific outcomes between patients with upper tract urothelial carcinoma (UTUC) managed with either radical nephroureterectomy (RNU) or nephron-sparing measures (NSM) using a large population-based dataset. Patients and Methods Using Surveillance, Epidemiology, and End Results (SEER) data, patients diagnosed with low- or moderate-grade, localised non-invasive UTUC were stratified into two groups: those treated with RNU or NSM (observation, endoscopic ablation, or segmental ureterectomy). Cancer-specific mortality (CSM) and other-cause mortality (OCM) rates were determined using cumulative incidence estimators. Adjusting for clinical and pathological characteristics, the associations between surgical type, all-cause mortality and CSM were tested using Cox regressions and Fine and Gray regressions, respectively. Results Of 1227 patients [mean (sd) age 70.2 (11.00) years, 63.2% male] meeting inclusion criteria, 907 (73.9%) and 320 (26.1%) patients underwent RNU and NSM for low- or moderate-grade, low-stage UTUC from 1992 to 2008. Patients undergoing NSM were older (mean age 71.6 vs 69.7 years, P < 0.01) with a greater proportion of well-differentiated tumours (26.3% vs 18.0%, P = 0.001). While there were differences in OCM between the groups (P < 0.01), CSM trends were equivalent. After adjustment, RNU treatment was associated with improved non-cancer cause survival [hazard ratio (HR) 0.78, confidence interval [CI] 0.64–0.94) while no association with CSM was demonstrable (HR 0.89, CI 0.63–1.26). Conclusions Patients with low- or moderate-grade, low-stage UTUC managed through NSM are older and are more likely to die of other causes, but they have similar CSM rates to those patients managed with RNU. These data may be useful when counselling patients with UTUC with significant competing comorbidities.

PurposeThe incidence of lower urinary tract symptoms (LUTS) as the sole presenting symptom for bladder cancer has traditionally been reported to be low. The objective of this study was to evaluate the prevalence and clinical characteristics of newly diagnosed bladder cancer patients who presented with LUTS in the absence of gross or microscopic hematuria.Materials and MethodsWe queried our database of bladder cancer patients at the Atlanta Veteran’s Affairs Medical Center (AVAMC) to identify patients who presented solely with LUTS and were subsequently diagnosed with bladder cancer. Demographic, clinical, and pathologic variables were examined.Results4.1% (14/340) of bladder cancer patients in our series presented solely with LUTS. Mean age and Charlson Co-morbidity Index of these patients was 66.4 years (range = 52-83) and 3 (range = 0-7), respectively. Of the 14 patients in our cohort presenting with LUTS, 9 (64.3%), 4 (28.6%), and 1 (7.1%) patients presented with clinical stage Ta, carcinoma in Situ (CIS), and T2 disease. At a median follow-up of 3.79 years, recurrence occurred in 7 (50.0%) patients with progression occurring in 1 (7.1%) patient. 11 (78.6%) patients were alive and currently disease free, and 3 (21.4%) patients had died, with only one (7.1%) death attributable to bladder cancer.ConclusionsOur database shows a 4.1% incidence of LUTS as the sole presenting symptom in patients with newly diagnosed bladder cancer. This study suggests that urologists should have a low threshold for evaluating patients with unexplained LUTS for underlying bladder cancer.

IntroductionHigh-grade T1 (HGT1) bladder cancer represents a clinical challenge in that the urologist must balance the risk of disease progression against the morbidity and potential mortality of early radical cystectomy and urinary diversion. Using two non-muscle invasive bladder cancer (NMIBC) databases, we re-examined the rate of progression of HG T1 bladder cancer in our bladder cancer populations.Materials and MethodsWe queried the NMIBC databases that have been established independently at the Atlanta Veterans Affairs Medical Center (AVAMC) and the University of Pennsylvania to identify patients initially diagnosed with HGT1 bladder cancer. Demographic, clinical, and pathologic variables were examined as well as rates of recurrence and progression.ResultsA total of 222 patients were identified; 198 (89.1%) and 199 (89.6%) of whom were male and non-African American, respectively. Mean patient age was 66.5 years. 191 (86.0%) of the patients presented with isolated HG T1 disease while 31 (14.0%) patients presented with HGT1 disease and CIS. Induction BCG was utilized in 175 (78.8%) patients. Recurrence occurred in 112 (50.5%) patients with progression occurring in only 19 (8.6%) patients. At a mean follow-up of 51 months, overall survival was 76.6%. Fifty two patients died, of whom only 13 (25%) patient deaths were bladder cancer related.ConclusionsIn our large cohort of patients, we found that the risk of progression at approximately four years was only 8.6%. While limited by its retrospective nature, this study could potentially serve as a starting point in re-examining the treatment algorithm for patients with HG T1 bladder cancer.

Patients with end-stage renal disease (ESRD) demonstrate a greater risk for renal cell carcinoma (RCC) than the general population. This study compared pathological and clinical outcomes in patients with RCC with and without ESRD. Patients with ESRD who underwent nephrectomy and were found to have RCC at our institution since 1999 were identified. The control group was composed of patients from the general population with RCC. The primary outcome was risk of cancer recurrence. The study included 338 RCC patients: 84 with ESRD and 243 without ESRD. In the ESRD group, mean tumor size was smaller, there was decreased prevalence of advanced T category (>3) , and the average Karakiewicz nomogram score was lower. ESRD was associated with decreased tumor recurrence and clear cell pathology. No patients with ESRD had metastatic disease. There was no difference in overall or cancer-specific mortality between the ESRD and control groups. Patients with ESRD who develop RCC have a better prognosis compared to RCC in patients without ESRD, which is likely secondary to favorable histopathologic phenotype as well as the likelihood of early diagnosis. Thus, the delay between nephrectomy and renal transplantation may not be necessary, especially in patients with asymptomatic, low grade tumors.

With the continuous rise in life expectancy, the geriatric population has come to account for more than a third of all inpatient surgical procedures. This number will undoubtedly continue to rise over the next two decades. The geriatric population is at an increased risk of perioperative complications, and therefore, the elderly deserve special attention in the perioperative period. Ideally, this should commence upon initial consultation. A thorough history and physical exam can help stratify the patient risk factors and identify which patients require further preoperative testing. Consultations with other providers should be obtained as needed. In the operating room and postoperatively, each patient should receive individualized care tailored according to his/her preoperative work-up. In this paper, we review the steps that should be taken to minimize the risk of perioperative complications in the elderly.

With the continued aging of the population, a rising proportion of surgical procedures will be performed in elderly patients. Current surgical decision-making tools rely on subjective judgments and were developed without special geriatric considerations. As a result, they have certain inadequacies that limit their utility in this population. Frailty, described for decades by the medical geriatric community, has just recently begun to be investigated as a surgical risk assessment tool. Identifying the frailty phenotype has been shown by multiple investigators to reliably predict which patients are at increased risk of adverse peri-operative outcomes. Perhaps, most importantly, it is a tool that can potentially discriminate among the elderly, identifying those that warrant heightened concern, "pre-habilitation", or special postoperative attention from those at no increased risk compared to the general population. Alternatively, some patients may be identified as “too frail” to undergo surgery, and alternative nonsurgical treatment options may be considered.

Objectives To assess regionalization trends and short-term clinical outcomes in patients undergoing radical cystectomy for urothelial carcinoma. Materials and methods Using 1996–2009 discharge data from New York (NY), New Jersey (NJ) and Pennsylvania (PA), all patients ≥18 years with urothelial carcinoma undergoing cystectomy were identified using ICD-9 coding. We assigned hospital volume status by quintiles based on relative proportions of cystectomies performed on a per hospital basis in 1996; very low volume hospitals: 0–2 (VLVH), low: 3–4 (LVH), moderate: 5–8 (MVH), high: 9–31 (HVH), and very high: ≥32 (VHVH). Changes in the proportion of procedures performed by volume categories were assessed over time, and patient characteristics were compared between groups. Results A total of 14,404 patients met inclusion criteria. For each year increase from 1996 to 2009, the odds of having surgery performed at a VHVH increased by 22% (odds ratio [OR] 1.22, confidence interval [CI] 1.04–1.44). Patients undergoing surgery at a VHVH were less likely to be African American (OR 0.59 [CI 0.39–0.91]), or insured through Medicaid (OR 0.65 [CI 0.50–0.84]) or Medicare (OR 0.84 [CI 0.75–0.94]). Controlling for year treated, total procedures performed, and patient characteristics, median hospital length of stay (HLOS) was shorter (median difference −0.89 days [CI −1.12 to −0.66]), and patients were significantly less likely to die during their hospital stay if treated at a VHVH compared with a VLVH (OR 0.33 [CI 0.22–0.49]). Conclusions There has been extensive regionalization of cystectomy to VHVHs in NY, NJ, and PA since 1996. Despite apparent improvements in mortality and HLOS in patients treated at higher volume centers in our sample, future investigations more rigorously adjusting for hospital structural characteristics and patient severity are necessary to confirm these findings. Disparities in access to VHVH care are still evident and must be addressed.

BackgroundThe modified frailty index (mFI) is an important method to risk-stratify surgical patients and has been validated for general surgery and selected surgical subspecialties. However, there are currently no data assessing the efficacy of the mFI to predict acute morbidity and mortality in patients undergoing surgery for retroperitoneal sarcoma.MethodsUsing the American College of Surgeons' National Surgical Quality Improvement Program from 2007 to 2012, we performed a retrospective analysis of patients with a diagnosis of primary malignant retroperitoneal neoplasm who underwent surgical resection. The mFI was calculated according to standard published methods. Univariate and multivariate statistical analyses including χ2 and logistic regression were used to identify predictors of 30-d overall morbidity, 30-d severe morbidity (Clavien III/IV), and 30-d mortality.ResultsWe identified 846 patients with the diagnosis of primary malignant retroperitoneal neoplasm who underwent surgical resection. The distribution mFI scores was 0 (48.5%) or 1 (36.3%), with only 4.5% of patients presenting with a score ≥3. Rates of 30-d overall morbidity, serious morbidity, and mortality were 22.6%, 12.9%, and 1.2%, respectively. Only selected mFI scores were associated with serious morbidity and overall morbidity on multivariate analysis (P0.05).ConclusionsOur data demonstrate that the majority of patients undergoing retroperitoneal sarcoma resections have few, if any, comorbidities. The mFI was a limited predictor of overall and serious complications and was not a significant predictor of mortality. Better discriminators of preoperative risk stratification may be needed for this patient population.

As the population continues to age, there will be a concomitant increase in the need for surgical intervention for a variety of disease processes for this group of patients. To date, surgical decision-making is overly subjective, and preoperative risk assessment tools are imprecise, lacking an ability to fully predict an elderly patient’s physiologic reserve to withstand the intended insult of surgery. Frailty is an emerging concept that incorporates multiple functional, cognitive, and physiologic measurements to better grasp a patient’s reserve. The preoperative measurement of frailty may offer an improved risk assessment tool to predict for adverse peri-operative outcomes, especially in the elderly population.

Patients with unilateral synchronous multifocal renal masses represent a unique population with renal cell carcinoma. While pathological concordance rates have been studied for bilateral cases, limited data exist on unilateral multifocal disease. We characterized pathological concordance rates in this population and evaluated the outcomes of nephron preservation.Patients who underwent surgery from 2000 to 2012 for unilateral synchronous multifocal renal masses were identified from a prospectively maintained database. Demographic, surgical and pathological outcomes of this cohort were analyzed. Malignant concordance rates were defined as agreement of all malignant tumor types in a single renal unit. Histological concordance was defined as agreement of all resected mass histologies, eg all clear cell carcinomas. Nuclear grade was considered concordant if all tumors excised were low (Fuhrman 1 or 2, type 1) or high (Fuhrman 3 or 4, type 2) grade.Using our institutional database of 2,569 patients with renal tumors we identified 97 with unilateral synchronous multifocal renal masses. Malignant and benign concordance rates were 77.2% and 48.6%, and histological and grade concordance rates were 58.8% and 51.5%, respectively. In this cohort we identified 76 patients (76.3% male) with a median age of 62.5 years who had a total of 241 unilateral synchronous multifocal renal masses and underwent nephron sparing surgery. Median mass size was 2.0 cm (IQR 1.1-3.1), there was a median of 3 tumors per patient and median followup was 24 months (IQR 13-40). Identified renal cell carcinoma histologies included clear cell in 49.4% of cases, papillary in 33.5%, mixed in 4.5% and chromophobe in 2.8%.In what is to our knowledge the largest published report of unilateral synchronous multifocal renal masses we document low pathological concordance rates. As such, percutaneous biopsy of a single renal mass in these patients may not help inform treatment decisions. Nephron sparing surgery may be performed with acceptable oncological and functional results in patients with unilateral synchronous multifocal renal masses.

To evaluate usage of diagnostic angiography (DA) and renal angioembolization (RAE) for isolated renal injuries while assessing differences in utilization based on trauma-level designation.Isolated renal injuries from 2000 to 2013 were identified in the prospectively maintained Pennsylvania Trauma Outcome Study database and stratified by the American Association for the Surgery of Trauma kidney injury grade. Therapeutic intervention and International Classification of Diseases-9 codes identified DA and/or RAE performance, whereas renal injury was designated through Abbreviated Injury Scale codes. Univariate and multivariate models identified factors associated with utilization of DA or RAE.Of 449,422 patients entered into the Pennsylvania Trauma Outcome Study from 2000 to 2013, 1628 (0.4%) isolated kidney injuries were identified. The majority of patients (1190/1628, 73.1%) experienced low-grade (American Association for the Surgery of Trauma I-III) renal trauma. Although isolated grade IV (41/350, 11.7%) or grade V (10/88, 11.4%) renal trauma patients underwent DA or RAE at a greater rate (P .001), low-grade patients still underwent DA or RAE 4.3% (51/1190) of the time. Patients with grade I injuries were significantly more likely to undergo DA or RAE at level 1 trauma centers (odds ratio 5.4, 95% confidence interval 1.2-23.8, P = .03).Despite overwhelming evidence supporting conservative management for patients with isolated, low-grade traumatic renal injuries, contemporary utilization of DA and RAE in such patients treated at trauma centers is surprisingly high. Factors accounting for a significant increase in utilization at Level 1 trauma centers need to be further elucidated.

BACKGROUND. Androgen receptor (AR) signaling is regarded as the driving force in prostate carcinogenesis, and its modulation represents a logical target for prostate cancer (PC) prevention and treatment. Natural products are the most consistent source of small molecules for drug development. In this study, we investigate the functional impact of piperlongumine (PL), a naturally occurring alkaloid present in the Long pepper (Piper longum), on AR expression in PC cells and delineate its mechanism of action. METHODS. Expression and transcriptional activity of AR was examined by western blotting and luciferase reporter assay, respectively. CellTiter Blue assay was utilized to quantify cell proliferation. Reactive oxygen species (ROS) generation was examined by staining cells with a ROS indicator CM-H2DCFDA, followed by flow cytometry analysis. RESULTS. The results of our experiments demonstrate that PL rapidly reduces AR protein levels in PC cells via proteasome-mediated ROS-dependent mechanism. Moreover, PL effectively depletes a modified AR lacking the ligand-binding domain, shedding light on a new paradigm in the treatment approach to prostatic carcinoma that expresses mutated constitutively active AR. Importantly, PL effectively depletes AR in PC cells at low micromolar concentrations, while concurrently exerting a significant inhibitory effect on AR transcriptional activity and proliferation of PC cells. CONCLUSIONS. Our investigation demonstrates for the first time that PL induces rapid depletion of the AR in PC cells. As such, PL may afford novel opportunities for both prevention and treatment of prostatic malignancy. Prostate # 2012 Wiley Periodicals, Inc.

Objective With the increased diagnosis of low grade, low volume, potentially non-lethal disease, active surveillance (AS) has become an increasingly popular alternative for select men with low-risk prostate cancer. The absence of precise clinical staging modalities currently makes it difficult to predict which patients are most appropriate for AS. The goal of our study was to evaluate the ability of endorectal MRI (eMRI) to predict adverse pathologic features in patients who would otherwise qualify for an AS program. Materials and methods We retrospectively reviewed our institution's radical prostatectomy (RP) database from 1991 to 2007 and identified 172 patients who would have qualified for AS and underwent preoperative staging eMRI with T2-weighted (T2W) sequences. MRI findings were correlated to final pathology in order to assess the ability of staging eMRI to predict adverse pathologic features in patients suitable for AS. Results The mean age of our cohort was 59.8 ± 6.2 years. The mean PSA at the time of diagnosis was 5.2 ± 2.2 ng/ml. In 51% of patients, no discrete tumor was visualized on eMRI and in 49% of patients a discrete tumor was detected. At the time of RP, Gleason score upgrading, extracapsular extension, and a positive surgical margin occurred in 17%, 6%, and 5% of cases, respectively. Patients with documented tumor on eMRI did not have an increased incidence of adverse pathologic findings with regard to tumor volume ( P = 0.31), extra-capsular extension ( P = 0.82), Gleason upgrading ( P = 0.92), seminal vesicle invasion ( P = 0.97), or positive surgical margin rate ( P = 0.95) compared with those in whom no tumor was seen. Conclusion Discrete tumor identification on eMRI is not predictive of adverse pathologic features in patients who would otherwise qualify for AS. eMRI likely does not provide additional information when prospectively evaluating patients for AS protocols.

What's known on the subject? and What does the study add? Partial nephrectomy for the pT1 renal mass has demonstrated acceptable oncological outcomes in addition to improved overall long-term survival when compared with radical nephrectomy. Previous reports for lesions ≥7 cm have shown mixed data concerning oncological outcomes and technological success. We demonstrate that partial nephrectomy for renal masses ≥7 cm has acceptable oncological, technical, and functional outcomes. As such, partial nephrectomy should be a surgical option when feasible regardless of tumour size. Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE • To present outcomes for patients with renal masses ≥7 cm in size who are treated with partial nephrectomy (PN) at our institution and to summarize the cumulative published experience. PATIENTS AND METHODS • We reviewed our prospectively maintained institutional kidney cancer database and identified patients undergoing PN for tumours >7 cm in size. • Technical, oncological and renal functional data were analyzed and compared with the existing published experience of PNs for tumours >7 cm in size. RESULTS • In total, 46 patients with 49 renal tumours >7 cm in size who underwent PN were identified. • With a median (range) follow-up of 13.1 (0.2–170.0) months, there were 16 complications, including four (8.2%) blood transfusions and six (12.2%) urinary fistulae. • The 5- and 10-year overall and renal cell carcinoma (RCC)-specific survivals were 94.5% and 70.9%. There were five (10.9%) patients who had an upward migration in their chronic kidney disease status after PN. • There were six previous series totalling 280 tumours encompassing the published experience of PN for tumours >7 cm in size. The incidence of urinary fistulae and postoperative haemorrhage, respectively, was in the range 3.3–18.8% and 0–3%. • Although oncological outcomes showed cancer-specific survival in the range 66–97.0%, series matching PN and RN in patients with T2 RCC show equivalency in RCC-specific and overall survivals. When reported, PN for tumours >7 cm in size was associated with better renal functional preservation. CONCLUSION • The findings of the present study show that PN can safely be performed in tumours ≥7 cm in size with acceptable technical, oncological and functional outcomes. Further studies are warranted.

UNLABELLED: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Penetrating trauma to the scrotum often requires operative intervention, with testicular salvage only possible when enough testicular tissue can be re-approximated in the traumatic setting. The present report represents the largest series of gunshot wound trauma to the scrotum in the literature. Further, it validates recommendations of the European Association of Urology guidelines on urological trauma that advocate operative intervention due to minimal rates of patient morbidity and the inherent limitations of scrotal ultrasonography in discerning testicular compromise. OBJECTIVE: To report our 20-year experience of gunshot wounds (GSWs) to the scrotum and outline the management of this traumatic injury. PATIENTS AND METHODS: We queried our institutional database for patients presenting with GSWs to the scrotum between 1985 and 2006. All patients underwent the standard trauma evaluation upon presentation, including physical examination of the external genitalia. Management was dictated by the presence or absence of a penetrating injury to the scrotum and associated traumatic injuries. Nonoperative and operative management of traumatic injury to the scrotum were used. Testicular salvage was performed when anatomically feasible. If testicular salvage was not feasible, an orchiectomy was performed. RESULTS: Scrotal exploration was performed in 91 (94%) patients while six (6%) patients were treated nonoperatively. Testicular injury was found in 44 (48%) patients undergoing exploration, six (7%) of whom had bilateral testicular injuries, which gave a total of 50 injured testicles. Of the injured testicles, 24 (48%) could not be salvaged and required orchiectomy, while 26 (52%) were debrided and repaired. The most common associated genitourinary (GU) injuries were to the corpora cavernosum (n= 20 [21%]) and urethra (n= 10 [10%]). Soft tissue injury of the extremities occurred in 54 patients (56%), representing the most common non-GU-associated injury. Postoperative complications occurred infrequently: one patient (1%) returned for abscess drainage and one (1%) for haematoma evacuation. CONCLUSIONS: The present report confirms that any patient with a penetrating injury to the scrotum should undergo immediate scrotal exploration. A low clinical suspicion for performing additional studies to rule out associated urethral and/or penile injury is clinically warranted. Testicular loss occurs in ≈50% of injured testicles.

Zinc accumulation is lost during prostate carcinogenesis. Recent studies reveal a strong association between prostate cancer progression and the downregulation of the zinc uptake transporters hZip1 and hZip3. The aim of this work was to assess the involvement of epigenetic processes in the disruption of zinc uptake homeostasis in prostate adenocarcinoma. In this report, we demonstrate an increase in hZip1 and hZip3 zinc transporters' expression and zinc uptake by the prostate cancer cells DU-145 and LNCaP in response to 5-aza-2'-deoxycytidine. This effect is due to demethylation of the promoter region of the activator protein (AP)-2alpha protein, which is crucial for hZip1 and hZip3 genes expression. Loss of AP-2alpha expression in DU-145 and LNCaP prostate cancer cells is due to hypermethylation of its promoter region. Similarly, we found higher AP-2alpha promoter methylation levels in clinical samples of early-stage prostate adenocarcinoma when compared with adjacent non-malignant prostate tissue. Taken together, our findings provide a better understanding of the epigenetic mechanisms that are involved in the loss of AP-2alpha protein in prostate cancer cells which lead to decreased cellular zinc uptake-a sine qua non of prostate cancer development.

We assessed whether incidental screening due to imaging performed for other purposes has resulted in earlier detection or better outcomes in patients with adrenocortical carcinoma.We used the National Cancer Database to assemble a cohort diagnosed with adrenocortical carcinoma from 1985 to 2007. Trends in the distribution of grouped tumor sizes were assessed with the Cochran-Armitage chi-square test. Relative 5-year survival rates were calculated for cases diagnosed through 2002.Median survival in the full cohort of 4,275 patients was 24 months. Localized adrenocortical carcinoma accounted for 43.9% of cases. No stage migration was noted with time. No statistical trends were noted in tumor size changes during the years in patients who underwent surgery for localized disease (p=0.32). No improvement was observed in 5-year survival during the period (p0.1).In this cohort of patients with adrenocortical carcinoma, which is to our knowledge the largest cohort reported to date, 43.9% presented with localized disease. No shift was noted toward lower stage or smaller tumor size in a 22-year period despite the advent of abdominal imaging and its resulting incidental screening of the adrenal gland. These data contrast with the well documented stage and size migration of tumors of the kidney, a neighboring retroperitoneal organ. Furthermore, no improvement in survival was noted. As such, better risk stratification of patients with adrenal incidentaloma, while improving treatment efficacy for those with proven adrenocortical carcinoma, is an essential clinical and epidemiological task.

Counseling patients with enhancing renal mass currently occurs in the context of significant uncertainty regarding tumor pathology.We evaluated whether radiographic features of renal masses could predict tumor pathology and developed a comprehensive nomogram to quantitate the likelihood of malignancy and high-grade pathology based on these features.We retrospectively queried Fox Chase Cancer Center's prospectively maintained database for consecutive renal masses where a Nephrometry score was available.All patients in the cohort underwent either partial or radical nephrectomy.The individual components of Nephrometry were compared with histology and grade of resected tumors. We used multiple logistic regression to develop nomograms predicting the malignancy of tumors and likelihood of high-grade disease among malignant tumors.Nephrometry score was available for 525 of 1750 renal masses. Nephrometry score correlated with both tumor grade (p0.0001) and histology (p0.0001), such that small endophytic nonhilar tumors were more likely to represent benign pathology. Conversely, large interpolar and hilar tumors more often represented high-grade cancers. The resulting nomogram from these data offers a useful tool for the preoperative prediction of tumor histology (area under the curve [AUC]: 0.76) and grade (AUC: 0.73). The model was subjected to out-of-sample cross-validation; however, lack of external validation is a limitation of the study.The current study is the first to objectify the relationship between tumor anatomy and pathology. Using the Nephrometry score, we developed a tool to quantitate the preoperative likelihood of malignant and high-grade pathology of an enhancing renal mass.

Background Docetaxel is the mainline treatment approved by the FDA for castration-resistant prostate cancer (CRPC) yet its administration only increases median survival by two to four months. Docetaxel is metabolized in the liver by hepatic CYP3A4 activity. Piperine, a major plant alkaloid/amide, has been shown to inhibit the CYP3A4 enzymatic activity in a cell-free system. Thus, we investigated whether the co-administration of piperine and docetaxel could increase docetaxel’s pharmacokinetic activity in vitro and in vivo.

The authors systematically reviewed the literature and conducted a pooled analysis of studies on small renal masses who underwent active surveillance to identify the risk progression and the characteristics associated with metastases.A search of the MEDLINE database was performed to identify all clinical series that reported the surveillance of localized renal masses. For studies that reported individual-level data, clinical and radiographic characteristics of tumors without progression were compared with the characteristics of tumors that progressed to metastases.Eighteen series (880 patients, 936 masses) met screening criteria; and, among these, 18 patients were identified who had tumors that progressed to metastasis (mean, 40.2 months). Six studies (259 patients, 284 masses) provided individual-level data for pooled analysis. At a mean (± standard deviation) follow-up of 33.5 ± 22.6 months, the mean initial greatest tumor dimension was 2.3 ± 1.3 cm, and mean linear growth rate was 0.31 ± 0.38 cm per year. Sixty-five masses (23%) exhibited zero net growth under surveillance, and none of those masses progressed to metastasis. A pooled analysis revealed increased age (age 75.1 ± 9.1 years vs 66.6 ± 12.3 years; P = .03), an initial greatest tumor dimension (4.1 ± 2.1 cm vs 2.3 ± 1.3 cm; P.0001), initial estimated tumor volume (66.3 ± 100.0 cm(3) vs 15.1 ± 60.3 cm(3) ; p = .0001), linear growth rate of (0.8 ± 0.65 cm per year vs 0.3 ± 0.4 cm per year; P = .0001), and a volumetric growth rate of 27.1 ± 24.9 cm(3) per year (vs 6.2 ± 27.5 cm(3) per year; P.0001) in the progression cohort.A substantial proportion of small renal masses remained radiographically static after an initial period of active surveillance. Progression to metastases occurred in a small percentage of patients and generally was a late event. The current results indicated that, in patients who have competing health risks, radiographic surveillance may be an acceptable initial approach, and delayed intervention may be reserved for patients who have tumors that exhibit significant linear or volumetric growth.

OBJECTIVE: • To report and review our incidence of delayed ureteric stricture (US) after complex nephron-sparing surgery (NSS). PATIENTS AND METHODS: • Using our institutional kidney cancer database, we identified 720 patients who underwent NSS from 1 January 2000 until 31 December 2010 and identified eleven (1.5%) patients with a delayed US. • Patient and tumour characteristics were reviewed. RESULTS: • Median (range) tumour size and RENAL nephrometry score was 4.1 (2-7.2) cm and 10p (4-11p), respectively. • There were eight of 10 solitary tumours (80%) located in the lower or mid-pole of the kidney. • There were eight of 11 patients with delayed US (72.7%) who experienced a postoperative urinary leak. • There were two of 11 (18.2%) patients who experienced a postoperative retroperitoneal haemorrhage, with one of these patients requiring selective embolization. • All US were in the upper third of the ureter and were diagnosed at a minimum of 10 weeks postoperatively (median 154 days, range 70-400 days). CONCLUSIONS: • US formation is an uncommon and under-reported event after complex NSS. • Risk factors appear to include tumour complexity, imperative indications, mid- or lower pole location, postoperative urinary leak and haemorrhage. • Although uncommon, postoperative US can occur after NSS for complex renal masses, necessitating patient counselling and diligent postoperative surveillance.

Objectives To evaluate the prevalence of baseline chronic kidney disease (CKD) in a large cohort of patients presenting with renal masses to a tertiary care center, omparing serum creatinine (sCr) and estimated glomerular filtration rate (eGFR). sCr inadequately reflects renal function. eGFR and chronic kidney disease CKD stage are more clinically relevant parameters to reflect the risk of morbidity and mortality in patients after nephron loss. Methods Using the prospectively maintained Fox Chase Kidney Cancer Database, we identified patients undergoing kidney surgery between January 2000 and May 2010. eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) and the CKD-Epidemiology formulas. CKD stages I-V were defined using the National Kidney Foundation definitions. Results A total of 1114 patients had adequate data available to calculate a preoperative eGFR (mL/min). Although 88% of all patients presenting for surgery at our institution had a “normal” baseline sCr (≤1.4 mg/dL), 22% of patients had CKD stage III or greater. Moreover, of the 282 patients 70 years and older, 40% (113/282) had CKD stage III. Twenty-three percent (51/220) of patients older than 70 years had CKD stage III with a seemingly normal sCr. Conclusions Many patients with a normal sCr have CKD stage III or higher, particularly patients older than 70 years old. Given the high prevalence of baseline CKD in patients with a solid renal tumor, a concerted effort must be made to preserve renal function when surgically treating solid renal masses.