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Background With the Afro-Caribbean population increasing in the United States, their complication profiles following open (ORP) and robot-assisted laparoscopic (RALP) radical prostatectomy warrants investigation. The purpose of this pilot study was to evaluate differences in long-term complications between ORP and RALP in Afro-Caribbeans. Methods A retrospective review of patients undergoing ORP or RALP between April 2010 and August 2019 at an academic medical center and county hospital was conducted. Patients who identified as Afro-Caribbean with complete data were analyzed. Complications were classified using the Clavien-Dindo system. Age, transrectal ultrasound prostate volume, preoperative prostate-specific antigen, Gleason scores, and long-term complications (persisting to at least 18 months postoperatively) were compared between procedures using the Mann-Whitney U test or Fisher's exact test for statistical significance. Multivariable logistic regression was used to assess the odds of complications. Results This study included 53 Afro-Caribbean patients (mean age±SD; 65.9±6.8 years, 30 ORP, and 23 RALP). Patients treated by RALP were younger and had lower Gleason scores. Patients who were treated by RALP had a lower association to having ≥1 complications compared to those treated by ORP (OR=0.28, 95%CI 0.09-0.89, p=0.024). In addition,60% of complications had a Clavien-Dindo grade≤II for both procedures. RALP resulted in fewer grade II complications compared to ORP (OR=0.25, 95%CI 0.08-0.81, p=0.046). Conclusions Treatment of Afro-Caribbeans with RALP allows for fewer complications, especially Clavien-Dindo Grade II complications. While previous investigations show that Black populations experience more complications when treated with ORP or RALP compared to other groups, their complication profile is likely not homogenous when considering their sub-ethnic background and must be investigated to understand optimal interventions for prostate cancer.

Background and Objectives: The National Cancer Database (NCDB) captures nearly 70% of all new cancer diagnoses in the United States, but there exists significant variation in this capture rate based on primary tumor location and other patient demographic factors. Prostate cancer has the lowest coverage rate of all major cancers, and other genitourinary malignancies likewise fall below the average NCDB case coverage rate. We aimed to explore NCDB coverage rates for patients with genitourinary cancers as a function of race. Materials and Methods: We compared the incidence of cancer cases in the NCDB with contemporary United States Cancer Statistics data. Results: Across all malignancies, American Indian/Alaskan Natives subjects demonstrated the lowest capture rates, and Asian/Pacific Islander subjects exhibited the second-lowest capture rates. Between White and Black subjects, capture rates were significantly higher for White subjects overall and for prostate cancer and kidney cancer in White males, but significantly higher for bladder cancer in Black versus White females. No significant differences were observed in coverage rates for kidney cancer in females, bladder cancer in males, penile cancer, or testicular cancer in White versus Black patients. Conclusions: Differential access to Commission on Cancer-accredited treatment facilities for racial minorities with genitourinary cancer constitutes a unique avenue for health equity research.

Introduction Bladder cancer care has been increasingly concentrated in high-volume metropolitan medical centers (i.e., "regionalization" of care). We aimed to assess the potential role of geographic factors, including facility region and distance to treatment center, as determinants of neoadjuvant chemotherapy (NAC) delivery in patients with non-metastatic urothelial muscle-invasive bladder cancer (MIBC) using nationally-representative data from the United States. Methods We queried the National Cancer Database to identify patients with cT2-cT4a, N0, M0 urothelial MIBC who underwent radical cystectomy from 2006-2015. Patients who received radiation therapy, single-agent chemotherapy, adjuvant chemotherapy, or systemic therapies other than multiagent chemotherapy were excluded. Multivariate logistic regression analysis was performed to identify independent predictors of receiving NAC. Results A total of 5,986 patients met the criteria for inclusion, of whom 1,788 (29.9%) received NAC and 4,108 received RC alone. Younger age, increased Charlson-Deyo score, increased cT stage, increased annual income, increased distance from cancer treatment center, treatment at an Academic Research Program or Integrated Network Cancer Program, and a later year of diagnosis were independently predictive of NAC receipt. Older age, Medicare insurance, and treatment in the East South Central or West South Central regions were independently associated with decreased odds for NAC receipt. Conclusions Distance to treatment center and United States geographic region were found to affect the likelihood of NAC receipt independently of other established predictors of success in this quality-of-care metric. Access to transportation and related resources merits consideration as additional pertinent social determinants of health in bladder cancer care.

Background: Primary small cell carcinoma of the kidney (PSCCK) is exceedingly rare and data on disease characteristics and outcomes are sparse. This study examines a nationally-representative cancer registry to better characterize PSCCK. Methods: We queried the National Cancer Database to identify patients with histology-confirmed PSCCK from 2004 to 2015. Adjusted Cox proportional hazards regression and Kaplan&ndash, Meier analyses were employed to assess predictors of mortality and estimate median survival time, respectively. Results: A total of 110 patients were included (47:53% female:male, 77% &ge, 60 years of age, 86% Caucasian). Significant predictors of mortality included female sex, age 60&ndash, 69 years, treatment at an Integrated Network Cancer Program, stage cM1, and lack of surgical and chemoradiotherapy treatment. Independent protective factors were high socioeconomic status and treatment at an Academic Research Program. The estimated median overall survival time was 9.31 (95% CI 7.28&ndash, 10.98) months for all patients. No differences in estimated survival time were observed across individual treatment modalities among those patients who underwent treatment (p = 0.214). Conclusions: PSCCK is an aggressive malignancy with a median survival time of less than one year. Future studies that correlate clinical tumor staging with specific treatment modalities are needed to optimize and individualize management.

Purpose Pathologic upstaging in renal cell carcinoma (RCC) is common and confers a significant risk of poor surgical and survival outcomes. Preoperative predictors of upstaging are of great clinical relevance but empirical evidence specific to racial minorities remains scarce. Methods National Cancer Database (NCDB) analysis of T3a-specific upstaging among White, African-American, Hispanic and Asian Pacific Islander (API) patients with AJCC cT1N0M0 RCC who underwent partial or radical nephrectomy between 2010 and 2015. Independent preoperative predictors of tumour upstaging were identified using multivariate logistic regression analyses. Results A total of 81 002 patients met the criteria for inclusion (5.6% T3a-specific upstaging). Increased age, increased Charlson-Deyo comorbidity index, clinical stages cT1b and unspecified cT1, and increased Fuhrman nuclear grade were identified as independent risk factors for upstaging. Independent protective factors for upstaging were younger age, female sex, African-American race and papillary, chromophobe, and unspecified RCC histologic subtypes. Significant risk factors and protective factors within individual racial subgroups were highly consistent with those observed in the overall study sample. All independent factors identified on race-specific subgroup analyses were significant in the same direction relative to the overall study sample. Variables found to be non-significant in the overall study sample remained non-significant across all racial subgroup analyses. Conclusion The present study of nationally representative data found no clinically significant differences in upstaging risk across individual racial subgroups relative to the overall study sample. Preoperative factors that can be used to predict pT3a-specific tumour upstaging in CT1N0M0 RCC likely persist across different racial groups.

Introduction and objective The lethal necrotizing fasciitis, Fournier's Gangrene, is initially managed with resuscitation, broad-spectrum antibiotics, and aggressive surgical debridement. While the initial management steps are widely described, the subsequent management of skin loss is sparse. Our objective was to focus on the reconstruction of the penile shaft skin loss after wide surgical debridement. Methods A single case was documented from presentation, to treatment, and to recovery. The primary focus was the reconstruction of the penile shaft skin. The combined planning and efforts of genitourinary and plastic surgery were used to reconstruct the penile shaft skin using a split thickness skin graft. Results The penis was tunneled into a viable skin flap of the suprapubic fat pad in response to the wide surgical debridement from the treatment of Fournier's Gangrene. The penis maintained its anatomic function during the healing process. A 12/1000-in. split thickness skin graft from the lateral thigh was chosen to replace the skin deficient. 13 months later, we were able to excise around the preputial collar, un-tunnel the penis and place the skin graft around the penile shaft. A vacuum dressing and foley catheter remained in place for 7 days during an uneventful post-operative course. Ultimately, we found split thickness skin graft successful in this penile reconstruction after Fournier's Gangrene. Conclusion Complete penile shaft skin loss can be managed acutely with tunneling in the suprapubic fat pad, and can be reconstructed with a split thickness skin graft from the lateral thigh.

Background The purpose of the study was to identify patient and disease characteristics that have an adverse effect on renal function after partial nephrectomy. Patients and Methods We conducted a retrospective review of 387 patients who underwent partial nephrectomy for renal tumors between 2006 and 2014. A line plot with a locally weighted scatterplot smoothing was generated to visually assess renal function over time. Univariable and multivariable longitudinal regression analyses incorporated a random intercept and slope to evaluate the association between patient and disease characteristics with renal function after surgery. Results Median age was 60 years and most patients were male (255 patients [65.9%]) and white (343 patients [88.6%]). In univariable analysis, advanced age at surgery, larger tumor size, male sex, longer ischemia time, history of smoking, and hypertension were significantly associated with lower preoperative estimated glomerular filtration rate (eGFR). In multivariable analysis, independent predictors of reduced renal function after surgery included advanced age, lower preoperative eGFR, and longer ischemia time. Length of time from surgery was strongly associated with improvement in renal function among all patients. Conclusion Independent predictors of postoperative decline in renal function include advanced age, lower preoperative eGFR, and longer ischemia time. A substantial number of subjects had recovery in renal function over time after surgery, which continued past the 12-month mark. These findings suggest that patients who undergo partial nephrectomy can experience long-term improvement in renal function. This improvement is most pronounced among younger patients with higher preoperative eGFR.

Introduction: We compared characteristics of patients undergoing prostate biopsy in a high-risk inner city population before and after the 2012 USPSTF recommendation against PSA based prostate cancer screening to determine its effect on prostate biopsy practices. Materials and Methods: This was a retrospective study including patients who received biopsies after an abnormal PSA measurement from October 2008-December 2015. Patients with previously diagnosed prostate cancer were excluded. Chi-square tests of independence, two sample t-tests, Mann-Whitney U tests, and Fisher's exact tests were performed. Results: There were 202 and 208 patients in the pre-USPSTF and post-USPSTF recommendation cohorts, respectively. The post-USPSTF cohort had higher median PSA (7.8 versus 7.1ng/mL, p=0.05), greater proportion of patients who were black (96.6% versus 90.5%, p=0.01), and greater percentage of biopsy cores positive for disease (58% versus 29.5%, p

PURPOSE: Patients undergoing endoscopic management for upper tract urothelial carcinoma often progress to definitive therapy with radical nephroureterectomy. This study examined the rate of progression as well as risk factors for transitions in treatment over time. METHODS: Retrospective review at 2 institutions identified patients undergoing endoscopic management for upper tract urothelial carcinoma. Patients were assessed for progression to radical nephroureterectomy. Baseline characteristics were compared using Chi-Square analysis. Kaplan Meier method analyzed the probability of patients not progressing to radical nephroureterectomy. Cox proportional hazards identified factors associated with progression to radical nephroureterectomy. RESULTS: Eighty-one patients had endoscopic management alone, and 89 progressed to radical nephroureterectomy. The two groups had similar age, histories of bladder cancer, and Charlson Comorbidity Index. Positive urinary cytology, ureteroscopic visualization, and biopsy grade were higher in those progressing to RNU (p

INTRODUCTION AND OBJECTIVES:Primary small cell carcinoma (PSCC) of the kidney represents a rare disease entity. There is little data about the characteristics, optimal therapies, and survival assoc...

INTRODUCTION AND OBJECTIVES:Recent data suggests clear cell renal cell carcinoma (ccRCC) evolutionary subtypes, defined by specific driver mutations and mutation clonality, correlate with clinical ...

INTRODUCTION AND OBJECTIVES:Neoadjuvant chemotherapy (NAC) combined with radical cystectomy (RC) and urinary diversion is the standard of care in the treatment of urothelial muscle invasive bladder...

Improved understanding of renal carcinoma disease biology has led to the discovery and approval of five novel therapies targeting specific molecules in the vascular endothelial growth factor (VEGF) biochemical pathway. Biomarker studies attempting to predict response to VEGF-targeted therapies have largely focused on circulating proteins, tissue-based molecules, and germline polymorphisms. Thus far studies have yielded conflicting results that require prospective validation; therefore no definitive biomarker has yet been integrated into the clinician's armamentarium. However, early analyses featuring genomic biomarkers have generated promising findings. This article provides an overview of available biomarkers evaluated with respect to VEGF-targeted therapies in patients with advanced renal cell carcinoma.

Objective To assess the impact on recovery of bowel function using an 80 mm versus 60 mm gastrointestinal anastomosis (GIA) stapler following radical cystectomy and urinary diversion (RC/UD) for bladder cancer. Methods We identified 696 patients using a prospectively maintained RC/UD database from January 2006 to November 2010. Two nonrandomized consecutive cohorts were compared. Patients between January 2006- and December 2007 (n = 180) were treated using a 60 mm GIA stapler, and 331 patients between January 2008 and December 2010 were subject to an 80 mm GIA stapler. All patients were treated on the same standardized postoperative recovery pathway. After accounting for baseline patient and perioperative characteristics, using a multivariable logistic regression model, we directly compared rates of postoperative ileus using a standardized definition. Results Of 511 evaluable patients, ileus was observed in 32% (57/180) for 60 mm GIA versus 33% (110/331) for the 80 mm GIA. Preoperative renal function, age, gender, body mass index, and type of diversion were comparable between cohorts. On multivariate analysis, stapler size was not significantly associated with the development of ileus (GIA-60 vs GIA-80: OR 1.11; 95% CI 0.75, 1.66; P = .6). Positive fluid balance was associated with an increased risk ( P = .019) and female sex a decreased risk ( P = .008) of developing ileus compared to patients with negative fluid balance. Conclusion The size of the intestinal bowel anastomosis (GIA 80 mm vs 60 mm) does not independently impact the time to bowel recovery following RC/UD.

BACKGROUND The exonic single-nucleotide variant rs11762213 located in the MET oncogene has recently been identified as a prognostic marker in clear cell renal cell carcinoma (ccRCC). This finding was validated with The Cancer Genome Atlas (TCGA) cohort, and the biologic implications were explored. METHODS The genotype status for rs11762213 was available for 272 patients. Paired tumor-normal data, genomic data, and clinical information were acquired from ccRCC TCGA data sets. Cancer-specific survival (CSS) was analyzed with the competing risk method, and Cox proportional hazards regression was used for the analysis of the time to recurrence (TTR). Multivariate competing risk models were fitted to adjust for the validated Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score. RESULTS The variant allele of rs11762213 was detected in 10.3% of the cohort. After adjustments for the SSIGN score, the risk allele remained a significant predictor for adverse CSS (hazard ratio [HR], 3.88; 95% confidence interval [CI], 1.99-7.56; P

PURPOSE: To evaluate the impact of timing of blood transfusion in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). METHODS: Outcomes of consecutive patients with UTUC treated with RNU were analyzed. Clinicopathologic factors were compared using Fisher’s exact test or the Wilcoxon rank-sum test between patients that received any transfusion and no transfusion, and between patients receiving intraoperative transfusion only and patients receiving no transfusion. Cancer-specific and overall survival were estimated and multivariable analyses were performed to assess the impact of timing of transfusion on clinical outcomes. RESULTS: Among 402 patients included in this study, 71 (17.6%) patients received a transfusion at any point and 27 (6.7%) patients received an intraoperative blood transfusion. Transfusion at any time, patient comorbidity, high grade, advanced stage, positive surgical margins, low preoperative hemoglobin, longer operative duration, and increased blood loss were significantly associated with cancer-specific survival (DSS) on univariable analysis (HR 1.85, 95% CI 1.20–2.85, p

The utility of cancer cell lines is affected by the similarity to endogenous tumour cells. Here we compare genomic data from 65 kidney-derived cell lines from the Cancer Cell Line Encyclopedia and the COSMIC Cell Lines Project to three renal cancer subtypes from The Cancer Genome Atlas: clear cell renal cell carcinoma (ccRCC, also known as kidney renal clear cell carcinoma), papillary (pRCC, also known as kidney papillary) and chromophobe (chRCC, also known as kidney chromophobe) renal cell carcinoma. Clustering copy number alterations shows that most cell lines resemble ccRCC, a few (including some often used as models of ccRCC) resemble pRCC, and none resemble chRCC. Human ccRCC tumours clustering with cell lines display clinical and genomic features of more aggressive disease, suggesting that cell lines best represent aggressive tumours. We stratify mutations and copy number alterations for important kidney cancer genes by the consistency between databases, and classify cell lines into established gene expression-based indolent and aggressive subtypes. Our results could aid investigators in analysing appropriate renal cancer cell lines., Cell lines are central to cancer research, but knowing which cell lines are the best representative of actual tumours is a major challenge. Here the authors provide a resource assessment of 65 renal cell lines to assist researchers in selecting suitable lines for studying specific renal carcinoma subtypes.

Background We evaluated the incidence and effect of thromboembolic events (TEEs) in patients with muscle-invasive bladder cancer treated with preoperative chemotherapy (POC) and radical cystectomy (RC) with pelvic lymph node dissection (PLND). Patients and Methods We performed a retrospective review of all patients who had undergone POC followed by RC plus PLND for muscle-invasive bladder cancer from June 2000 to January 2013 (n = 357). The chemotherapy type (neoadjuvant vs. induction), incidence and timing of TEE diagnosis (preoperatively vs. ≤ 90 days postoperatively), and effect of TEEs on clinical outcomes were recorded. Results Overall, 79 patients (22%; 95% confidence interval [CI], 18%-27%) experienced a TEE: 57 (16%) occurred during POC and 22 (6.2%) were diagnosed postoperatively. Forty patients (11%; 95% CI, 8.1%-15%) required an inferior vena cava filter. We found no significant differences in neoadjuvant versus induction chemotherapy and the risk of TEEs (difference, 3.3%; 95% CI, −5% to 12%; P = .5). No significant difference were found in the rates of POC completion according to the presence of a TEE (difference, 1.0%; 95% CI, −11% to 13%; P = .9). The occurrence of TEE did not significantly affect other perioperative outcomes. The risk of recurrence and overall survival were not associated with TEE on multivariable analysis. Conclusion We found a high incidence of TEEs (22%) in patients undergoing POC before RC plus PLND, with a 16% incidence in the preoperative period. TEEs in the POC setting leads to invasive procedures; however, we did not find a significant effect on POC completion or postoperative complication risk. Further research is required to determine whether preventative TEE measures during POC can improve clinical outcomes.

BACKGROUND Prior studies examining the value of lymph node (LN) dissection (LND) in patients with urothelial carcinoma of the upper urinary tract (UTUC) have produced conflicting results. The objective of the current study was to assess the relationship between LN yield and survival among patients undergoing radical nephroureterectomy (RNU). METHODS The National Cancer Data Base was used to identify patients with non-metastatic UTUC who were treated with RNU between 2004 and 2012. The association between LN yield and overall survival (OS) was assessed using Cox proportional hazards regression, with adjustment for patient, tumor, and facility characteristics. RESULTS Of the 14,472 patients, 2926 (20%) underwent LND. The median yield was 2 LNs (interquartile range 1-6 LNs). Among the entire cohort and the LN-negative (pN0) subgroup, a higher LN yield was associated with lower all-cause mortality (multivariable hazard ratio [HR] 0.94 per 5 LNs removed, 95% confidence interval [95% CI] 0.89-1.00 [P = .034] for the entire cohort and HR 0.86, 95% CI 0.79-0.94 [P = .001] for the pN0 subgroup). Among patients with positive LNs (pN+), there was no association noted between LN yield and OS; however, positive and negative LN counts were found to be independent predictors of OS (HR 1.27 per 5 positive LNs, 95% CI 1.16-1.39 [P

Infiltrating T cells in the tumor microenvironment have crucial roles in the competing processes of pro-tumor and anti-tumor immune response. However, the infiltration level of distinct T cell subsets and the signals that draw them into a tumor, such as the expression of antigen presenting machinery (APM) genes, remain poorly characterized across human cancers. Here, we define a novel mRNA-based T cell infiltration score (TIS) and profile infiltration levels in 19 tumor types. We find that clear cell renal cell carcinoma (ccRCC) is the highest for TIS and among the highest for the correlation between TIS and APM expression, despite a modest mutation burden. This finding is contrary to the expectation that immune infiltration and mutation burden are linked. To further characterize the immune infiltration in ccRCC, we use RNA-seq data to computationally infer the infiltration levels of 24 immune cell types in a discovery cohort of 415 ccRCC patients and validate our findings in an independent cohort of 101 ccRCC patients. We find three clusters of tumors that are primarily separated by levels of T cell infiltration and APM gene expression. In ccRCC, the levels of Th17 cells and the ratio of CD8+ T/Treg levels are associated with improved survival whereas the levels of Th2 cells and Tregs are associated with negative clinical outcome. Our analysis illustrates the utility of computational immune cell decomposition for solid tumors, and the potential of this method to guide clinical decision-making.

The exonic single-nucleotide variant rs11762213 located in the MET oncogene has recently been identified as a prognostic marker in clear cell renal cell carcinoma (ccRCC). This finding was validated with The Cancer Genome Atlas (TCGA) cohort, and the biologic implications were explored.The genotype status for rs11762213 was available for 272 patients. Paired tumor-normal data, genomic data, and clinical information were acquired from ccRCC TCGA data sets. Cancer-specific survival (CSS) was analyzed with the competing risk method, and Cox proportional hazards regression was used for the analysis of the time to recurrence (TTR). Multivariate competing risk models were fitted to adjust for the validated Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score.The variant allele of rs11762213 was detected in 10.3% of the cohort. After adjustments for the SSIGN score, the risk allele remained a significant predictor for adverse CSS (hazard ratio [HR], 3.88; 95% confidence interval [CI], 1.99-7.56; P.0001) and for TTR (OR, 2.97; 95% CI, 1.43-6.2; P = .003). The mapping of rs11762213 to regulatory regions within the genome suggested that it might affect a DNA enhancer region. RNA and protein sequencing data for MET did not reveal differences in steady-state expression with stratification by risk allele.The exonic MET variant rs11762213 is an independent predictor of adverse CSS and TTR in ccRCC and should be integrated into clinical practice for prognostic stratification. Genomic analysis suggests that the single-nucleotide polymorphism may affect an enhancer region located in the coding region of MET. Further biological mechanistic interrogation is currently underway.

INTRODUCTION AND OBJECTIVES: Aside from a biopsy, little information exists to guide a clinician when evaluating a patient with a solid renal mass. An elevated neutrophil-lymphocyte ratio (NLR) has been associated with adverse outcomes in clear cell renal cell carcinoma (ccRCC). However, its ability to distinguish aggressive RCC from benign, or indolent, renal tumors remains unknown. Therefore, we evaluate the association of NLR with pathologic outcomes at nephrectomy, including the ability to distinguish benign and malignant renal lesions. METHODS: From 1995-2008, 2402 patients underwent nephrectomy for localized renal masses. Of these, 2039 had an NLR collected 90 days prior to nephrectomy. Comparisons of NLR by tumor size, histologic subtype and nuclear grade were evaluated. RESULTS: Overall, benign renal masses had a significantly lower NLR than malignant renal tumors (median 2.92 vs. 3.12; p 1⁄40.037) with the greatest difference noted among renal lesions > 7 cm (median 2.79 vs 3.87; p 4 but 7 cm 1⁄4 3.09 and > 7 cm 1⁄4 3.95) and nuclear grade (G1 1⁄4 2.68, G2 1⁄4 2.87, G3 1⁄4 3.48 and G4 1⁄4 5.18) was associated with greater NLR (both p < 0.001). Finally, after stratifying ccRCC by tumor size, there was a continual increase in NLR with greater nuclear grade. CONCLUSIONS: An elevated NLR is associated with an increased risk of RCC at the time of nephrectomy as well as higher grade tumors and more aggressive histologic subtypes. Therefore, NLR appears to be a preoperative marker of aggressive RCC and may be useful in predicting malignancy and guiding management among patients with suspicious renal lesions.

Background and Objectives The use of patient-controlled epidural analgesia after various operations has been associated with an early return of bowel function, thus decreasing patients’ length of stay (LOS). The primary aim of this study was to compare LOS after radical cystectomy between patients who received epidural analgesia versus those who received intravenous patient-controlled analgesia. Our secondary analysis included the assessment of other metrics such as total opioid requirements, pain scores, return of bowel function, and complication rates between the 2 groups. Methods We conducted a retrospective review using the electronic medical records of 308 patients who underwent radical cystectomies at Memorial Sloan Kettering between 2006 and 2011. We aimed to understand if epidural analgesia was associated with a reduced LOS compared with patient-controlled intravenous opioid analgesia. We also aimed to identify performance improvements as a function of epidural analgesia status using various metrics such as pain management, bowel function return, and complication rates. We used both univariate and multivariate analyses to identify if epidural analgesia was associated with meaningful differences in the aforementioned metrics. Results Median age at radical cystectomy, body mass index, sex, American Society of Anesthesiologists score, and T stage were similar for both groups. For our primary objective of LOS, we found no significant difference between the 2 cohorts (8 vs 7 days, P = 0.2). Analysis of our secondary outcome measures revealed that epidural analgesia use was associated with less total opioid requirement for the first 3 postoperative days (PODs) (P = 0.0001). In addition, epidural analgesia was found to be associated with improved postoperative pain scores compared with intravenous patient-controlled analgesia on PODs 1 (P = 0.0001) and 2 (P = 0.004), and there was a slight improvement on POD 3, but this was not significant (P = 0.77). In contrast, we found no difference between pain management types with regard to proportion of patients who experienced a delay in gastrointestinal recovery, fluid bolus requirements within the first 3 perioperative days, rates of infection, pulmonary complications, and grade 3 or greater complications. Conclusions We have demonstrated that, despite significant improvements in initial pain control and less opioid requirement with patient-controlled epidural analgesia, there was no association between analgesic approach and LOS, return of bowel function, or complications.

Tumor size and stage are important prognostic parameters in renal cell carcinoma. While pathological stage T1 and T2 are defined by size alone, the presence of certain intrinsic features can up stage a tumor to pathological stage T3a regardless of size. We investigate the effect of pathological tumor stage on the relationship between tumor size and risk of disease recurrence.Data were reviewed on patients who underwent nephrectomy at our institution between 2006 and 2013 to identify all those with pathological stage T1, T2 and T3a tumors. A proportional hazards Cox model was built with time to recurrence as outcome, and pathological stage and tumor size as covariates. An interaction term for stage and tumor size was included.The final cohort included 1,809 patients. On multivariable analysis, when adjusted for tumor size, patients with pT3a tumors had a greater risk of tumor recurrence compared to those with pT1/T2 tumors (HR 3.70; 95% CI 2.31, 5.92; p0.0001). The risk of disease recurrence increased more rapidly as tumor size increased only with the presence of perinephric fat invasion (p=0.006).Using the AJCC 2010 staging criteria we validated pathological stage T3a as a poor prognostic factor in renal cell carcinoma regardless of tumor size. Our results also demonstrated an increased rate of risk of recurrence with perinephric fat invasion. Given this increased risk of recurrence, even in tumors less than 4 cm, closer surveillance is warranted in such cases and the role of perinephric involvement necessitates further investigation.

Interleukin (IL)–12 has antitumor effects in murine studies. To evaluate this clinically, we investigated whether high levels of circulating IL-12 in patients after allogeneic hematopoietic stem cell transplantation (HSCT) are associated with improved relapse-free survival. We prospectively studied 134 patients undergoing HSCT. Median follow-up was 1158 days (range, 70-1792 days). Plasma IL-12 levels were measured before transplantation and on days 0, +4, +7, and +14 after transplantation. The highest levels were seen on days +4 and +7 and were categorized by a cluster analysis of the logarithmically transformed IL-12 concentrations, which were then correlated with relapse-free survival. Forty-six patients had low levels of IL-12 (median, 2 pg/mL; range, 0-6.5 pg/mL), 49 patients had medium levels (median, 20.5 pg/mL; range, 7-75.5 pg/mL), and 25 patients had high levels (median, 181 pg/mL; range, 84-623 pg/mL). Patients with high IL-12 levels before transplantation had the highest increase after transplantation. With a multivariate Cox model for relapse onset, with the low IL-12 level as the reference, patients in the high–IL-12 group had an adjusted hazard ratio of 0.27 (95% confidence interval, 0.09-0.79), and medium group patients had a hazard ratio of 0.65 (95% confidence interval, 0.31-1.36). The incidences of relapse at 500 days by Kaplan-Meier analysis by IL-12 group were 23.0% (high group), 40.3% (medium group), and 48.8% (low group). There was no association between IL-12 levels and the risk of acute graft-versus-host disease (GVHD; P = .51) or chronic GVHD (P = .28). In conclusion, high IL-12 levels after HSCT are associated with improved relapse-free survival without increasing the risk for GVHD. Patients with high pretransplantation IL-12 levels have an increased likelihood of higher posttransplantation IL-12 levels, possibly because of a host-graft interaction, and this may predispose to better clinical outcomes.

Introduction Lymph node dissection (LND) performed during radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) remains controversial and difficult to evaluate. The aim of this study was to investigate whether removal of more lymph nodes during RNU is safe and improves oncologic outcomes. Methods We evaluated 422 patients who underwent RNU with concomitant LND for upper tract urothelial carcinoma between 1976 and 2015, assessing for an association between total nodes removed, recurrence-free survival, and cancer-specific survival using Cox proportional hazards models. We also investigated the relationship between nodal yield and perioperative metrics and intersurgeon variability using linear regression. Results In our cohort of 442 patients, 239 developed recurrences and 94 patients died of disease. Median follow-up among survivors was 3.7 years (interquartile range: 1.2, 7.4). The median nodal yield was 9 (interquartile range: 4, 16). Among patients with node-positive disease (pN1), we observed a significant improvement in recurrence-free survival (hazard ratio = 0.84 per 5 nodes removed, P = 0.039) and a nonsignificant improvement in cancer-specific survival with an increase in the nodal yield (hazard ratio = 0.90 per 5 nodes removed, P = 0.2). There was no evidence of an association between node yield and operative time, estimated blood loss, or 30-day complications on multivariable analysis. There was significant heterogeneity among surgeons regarding the extent of LND ( P Conclusions We found that a more extensive node dissection may improve oncologic outcomes in a subset of high-risk patients without significantly increasing operative time or serious complications. Additionally, we identified considerable intersurgeon heterogeneity regarding the extent of LND furthering the notion of surgeon variability as a nonstandardized factor.

Objective To evaluate clinicopathologic characteristics and treatment outcomes of patients undergoing partial nephrectomy (PN) or radical nephrectomy (RN) for unilateral synchronous multifocal renal tumors. Methods We retrospectively reviewed medical records for 128 patients with nonmetastatic, unilateral, synchronous, multifocal renal tumors who underwent surgical resection at our institution from 1995 to 2012. Five patients with hereditary renal cell carcinoma were excluded. Differences between patient and tumor characteristics from the 2 nephrectomy groups were evaluated. Outcomes in terms of recurrence-free survival, overall survival, and chronic kidney disease upstaging were estimated using Kaplan-Meier methods. The log-rank test was used for group comparisons. Results The study cohort included 78 PN patients (63%) and 45 RN patients (37%); 17 of 95 planned PN (18%) were converted to RN. Tumor diameter and RENAL nephrometry scores were greater in RN patients ( P P = .0002, respectively). Pathologic stage T3 was seen in 40% of RN patients and 10% of PN patients ( P = .0002). Histologic concordance was apparent in 60 of 123 patients (49%). Median follow-up for patients alive without a recurrence was 4 years. Five-year recurrence-free survival was 98% for PN and 85% for RN. Five-year overall survival was 96% for PN and 86% for RN ( P = .5). Five-year freedom from chronic kidney disease upstaging was 74% for PN and 55% for RN ( P = .11). Conclusion Partial nephrectomy for the treatment of unilateral, synchronous, multifocal, renal tumors with favorable characteristics was associated with a low recurrence rate. These findings suggest PN is an appropriate management strategy for this group of carefully selected patients.

Penile cancer is a rare malignancy with less than 5 % being non-squamous cell carcinoma (SCC) primary malignancies. We report our 15-year experience of treating non-SCC penile cancer at a tertiary care cancer center.We identified 12 patients with non-SCC of the penis from 1996 to 2012. Demographic and clinical data were abstracted, including histological type, surgical treatment, adjuvant therapy, and clinical course.Five patients had sarcoma (three leiomyosarcoma, one spindle cell carcinoma, and one epithelioid sarcoma), four had melanoma, two had extramammary Paget's disease (EPD), and one had sebaceous carcinoma. Median follow-up was 37.5 months (mean 45.8 months). Tumor staging for melanoma was pT1aN3, pTisNx, pTxNxM1b, and pT3bN0. Patients with melanoma were treated with penile sparing surgery; two are alive without disease, one is alive with disease, and one patient with metastasis at presentation died of disease at 16.3 months. The patients with sarcoma and deep-seated or node-positive disease died of disease at a mean of 49.7 months. Two patients with EPD were treated with wide local excision of the lesions and were both pT1Nx. The remaining patient had sebaceous carcinoma treated with excisional biopsy and was free of disease at 32.0 months.Non-SCC of the penis is primarily treated surgically, with the goal of complete excision at the time of treatment. The utilization of lymphadenectomy is less clear in these malignancies, but aggressive approaches should be considered in appropriate patients. Tumor stage and nodal status are important in determining patient outcomes.

We recently found that a low number of circulating dendritic cells (DC) is predictive of increased relapse, acute GVHD, and poor survival following allogeneic SCT (Reddy V et al, Blood2004;103(11):4330–5). Interleukin-12 (IL-12) is an immunostimulatory cytokine involved in the activation of naïve T cells by DC (Rissoan et al. Science1999;283(5405):1183–6). We hypothesized that patients with high levels of circulating IL-12 in the post transplant period have improved relapse free survival. We studied 134 patients, 120 of whom were evaluable and transplanted during the period of July 1999 to April 2004. Seventy-two patients had transplants from related and 48 from unrelated donors, for predominantly high risk (88%) hematologic malignancies. Median follow up was 1158 days (range 70–1792). Blood samples were collected as baseline prior to conditioning, on day 0 prior to stem cell infusion and during the first week (day 4 and/or 7) after transplant. Plasma IL-12 levels were measured by ELISA. To determine the independent effect of post-transplant IL-12 levels and clinical outcomes, a cluster analysis was performed on the logarithmically transformed mean IL-12 concentration at days 4 and 7 post-transplant. The analysis generated a low, medium and high IL-12 group. Forty-six patients had low levels of IL-12 (median=2 pg/ml, range 0–6.5), 49 patients had medium (median=20.5 pg/ml, range 7–75.5) and 25 patients had high levels (median=181 pg/ml, range 84–623). There was a significant association between IL-12 level and onset of relapse. Using a multivariate Cox model with the low group level as reference, the high IL-12 group level had an adjusted hazard ratio (HR) of 0.27 (95% C.I. 0.09–0.79) and the medium group level a HR of 0.65 (95% C.I. 0.31–1.36). Incidence of relapse at 500 days by Kaplan-Meier analysis by IL-12 group were 23.0% (high group), 40.3% (medium group), and 48.8% (low group). Covariates in the multivariate models were gender match, disease risk, graft source, patient age, donor relation. There was a significant relationship between IL-12 levels and composite death and relapse, the high IL-12 group had a HR of 0.37 (95%C.I.=0.17–0.80) and the medium group a HR of 0.85 (95%.C.I. 0.50–1.45). There was no association between IL-12 levels and risk of AGVHD (p-value=0.51). In addition to IL-12, disease risk was a significant risk factor for the composite endpoint of relapse or death (HR=5.4, p-value=0.0052). The model generated for the outcome of relapse only did not have any additional significant risk factors. In conclusion, high post-transplant levels of IL-12 are associated with less relapse and improved relapse free survival after transplantation. This data suggests that IL-12 administration should be considered as a possible component in studies addressing treatment of relapse after transplantation. Figure Figure

Tumor-infiltrating immune cells have been linked to prognosis and response to immunotherapy; however, the levels of distinct immune cell subsets and the signals that draw them into a tumor, such as the expression of antigen presenting machinery genes, remain poorly characterized. Here, we employ a gene expression-based computational method to profile the infiltration levels of 24 immune cell populations in 19 cancer types.We compare cancer types using an immune infiltration score and a T cell infiltration score and find that clear cell renal cell carcinoma (ccRCC) is among the highest for both scores. Using immune infiltration profiles as well as transcriptomic and proteomic datasets, we characterize three groups of ccRCC tumors: T cell enriched, heterogeneously infiltrated, and non-infiltrated. We observe that the immunogenicity of ccRCC tumors cannot be explained by mutation load or neo-antigen load, but is highly correlated with MHC class I antigen presenting machinery expression (APM). We explore the prognostic value of distinct T cell subsets and show in two cohorts that Th17 cells and CD8Our analysis sheds light on the immune infiltration patterns of 19 human cancers and unravels mRNA signatures with prognostic utility and immunotherapeutic biomarker potential in ccRCC.