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To describe our technique for robot-assisted radical nephrectomy (RARN) with inferior vena cava (IVC) tumor thrombectomy and to present initial results for our first two patients.Two patients with renal masses with infrahepatic IVC extension underwent RARN with IVC tumor thrombectomy using a four-arm configuration. Both cases were right-sided tumors. Vascular control was obtained with complete cross-clamping of the vena cava with robotic bulldog clamps. Intraoperative ultrasound was used to delineate extent of tumor extension. Specimens were removed en-bloc, and the IVC was closed with 2-layers of 4-0 Prolene. The specimen is extracted through a lower midline incision.Two robotic IVC thrombectomies were successfully completed. There were no conversions, intraoperative or postoperative complications. Median operative time was 243 minutes with a median estimated blood loss of 150 mL. Both patients were able to ambulate independently free of intravenous opioids on postoperate day 1. Median length of stay was 4.5 (range 3-6) days. Final pathology revealed clear cell RCC in both cases with negative surgical margins.Robotic technology may facilitate RN and IVC thrombectomy in the well selected patient and appears to be a safe and feasible approach.

Objective To investigate the rate of premature instrument exchange during robot-assisted laparoscopic radical prostatectomy (RALRP) and robot-assisted partial nephrectomy (RAPN). The majority of robotic instruments have a predetermined lifespan of 10 uses; however, it is unknown if instruments are routinely exchanged before 10 uses in clinical practice. Methods We retrospectively reviewed instrument use in consecutive RALRP and RAPN cases performed by high-volume robotic surgeons at 1 tertiary care center between January 2011 and October 2014. The number of instruments used per case was evaluated and instances of additional instrument utilization were noted. Exchange number was compared between the first and second half of cases performed. Operative times were compared between cases with and without exchange. Student's t-test and Pearson's χ2-test were used to determine statistical significance. Results Three surgeons performed 1579 RALRP procedures and 2 surgeons performed 313 RAPN procedures. During RALRP, monopolar curved scissors required exchange in 12.4% cases. Other instruments were exchanged in less than 2% of cases. Exchange rates were similar to those for RAPN. Only exchange of Prograsp forceps decreased with increasing surgeon experience (P = .02) and instrument exchange did not lengthen operative times (P >.05 for all instruments). Conclusion During RALRP and RAPN, monopolar curved scissors required exchange in approximately 10% of cases whereas other instruments were rarely exchanged. Robotic instrument lifetime may not uniformly be 10 uses. The preset lifetime of robotic instruments and/or pricing should be reevaluated.

INTRODUCTION: Treatment options for small renal masses include partial nephrectomy (PN), ablation and active surveillance. We sought to compare patients who met the criteria for percutaneous ablation but underwent robotic PN to the rest of our robotic PN cohort. This was done in order to detect any safety concerns and to define any risk factors that might contraindicate the use of robotic PN, an oncologically superior procedure, in patients who qualify for ablation. MATERIAL AND METHODS: Our departmental renal mass registry was queried for patients who underwent robotic PN but also met criteria for percutaneous ablation. These were compared to the rest of the robotic PN cohort. Demographics, perioperative characteristics and recurrence data were compared. RESULTS: Overall, 321 robotic PNs were identified. Of these, 26 (8.1%) met ablation criteria. Among patient characteristics, age and BMI were similar in both groups. Among operative characteristics, estimated blood loss (EBL) and operative time were similar. Warm ischemia time was significantly less for patients who met ablation criteria (14 vs. 17 minutes, p = 0.002). Mean tumor size was smaller for patients who met ablation criteria (2.3 vs. 2.7 cm, p = 0.012). Among postoperative characteristics, complications were similar overall and when present, stratified by Clavien grade. CONCLUSIONS: Robotic PN is a safe, effective treatment option for small renal masses, even in patients who meet ablation criteria. There were no recurrences in our cohort and the majority of complications were Clavien grade 1.

Approximately 50% of penile squamous cell carcinomas (SCC) are associated with high-risk human papillomavirus (HR-HPV) infection. We evaluated the correlation of p16(INK4a) expression and HR-HPV with clinicopathological features and outcome in a cohort of patients with penile SCC. Two tissue microarrays were constructed from 53 invasive penile SCC at our hospital. p16(INK4a) expression was assessed by immunohistochemistry (CINtec Kit). High-risk human papillomavirus status was assessed by in situ hybridization (INFORM HPV III family 16 probe B cocktail). High-risk human papillomavirus was detected in 8 cases (15%), and p16(INK4a) overexpression was found in 23 cases (44%). Both markers showed a significant association with histologic subtype (P = .017 and P = .01, respectively) and lymphovascular invasion (P = .015 and P = .015, respectively). Regarding outcome analyses, neither HPV infection nor p16(INK4a) overexpression significantly predicted overall survival or cancer-specific survival using Cox proportional hazards regression model. High-risk human papillomavirus positivity and p16(INK4a) overexpression were significantly associated with histologic subtype and presence of lymphovascular invasion. Human papillomavirus status was not predictive of outcome in our cohort.

To determine preoperative predictors associated with renal cell carcinoma (RCC) and unfavorable pathology in small renal masses treated with partial nephrectomy (PN).PN records from 5 centers were retrospectively queried for patients with a clinically localized single tumor4 cm on imaging (clinical T1a). Between 2007 and 2013, 1,009 patients met the inclusion criteria. Unfavorable pathology was defined as any grade III or IV RCC or tumors upstaged to pathologic T3a disease. Logistic regression models were used to determine preoperative characteristics associated with RCC and with unfavorable pathology.A total of 771 (76.4%) patients were found to have RCC and 198 (19.6%) had unfavorable pathology. On multivariate, bootstrap-adjusted logistic regression analysis, factors associated with the presence of malignancy were imaging tumor size ≥ 3 cm (odds ratio [OR] = 1.46; P = 0.040), male sex (OR = 1.88; P0.0001), and nephrometry score ≥ 8 (OR = 1.64; P = 0.005). These same factors were independently associated with risk of unfavorable pathology: size ≥ 3 cm (OR = 1.46; P = 0.021), male sex (OR = 2.35; P0.0001), and nephrometry score ≥ 8 (OR = 1.49; P = 0.015). The c statistic was 0.62 for the predicting malignancy and 0.63 for unfavorable pathology.In this multi-institutional cohort, male sex, imaging tumor size ≥ 3 cm, and nephrometry score ≥ 8 were predictors of RCC and adverse pathology following PN. These factors may assist in risk stratification and selective renal mass biopsy before decision making. Further studies are necessary to validate these findings.

Robotic-assisted adrenalectomy is an increasingly used intervention for patients with a variety of surgical adrenal lesions, including adenomas, aldosteronomas, pheochromocytomas, and metastases to the adrenal gland. Compared with traditional laparoscopy, robotic adrenalectomy has comparable perioperative outcomes and is associated with improved hospital length of stay and blood loss, though it does come at a cost premium. Emerging literature also supports a role for robotics in partial adrenalectomy and metastasectomy. Ultimately, well-conducted prospective trials are needed to fully define the role of robotics in the surgical management of adrenal disease.

We sought to evaluate the financial impact of robotic technology for partial nephrectomy (PN) and radical nephrectomy (RN) in the state of Maryland.The Maryland Health Services Cost Review Commission (HSCRC) documents all acute care hospital charges data. This database was queried for patients who underwent laparoscopic or robot-assisted RN and PN from 2008 to 2012. Total hospital charge, subcharge, and length of stay (LOS) were analyzed separately for RN and PN.Overall, 2834 patients were identified. Of those, 282 were laparoscopic PN (LPN), 1078 robot-assisted PN (RPN), 1098 laparoscopic RN (LRN), and 376 robot-assisted RN (RRN). For PN, the total hospital charge was $19,062 for LPN and $18,255 for RPN (P=0.138), with a charge savings of $807 per case in favor of robotics. For RN, the total hospital charge was $23,391 for RRN and $18,280 for LRN (P=0.004), with a charge premium of $5111 for robotic cases. LOS was shorter for RPN compared with LPN (2.51 vs 2.99 days, P0.0001) and for RRN compared with LRN (3.52 vs 3.98, P=0.0498).RPN is associated with lower hospital charges than LPN, while RRN is associated with higher hospital charges than LRN. Savings for RPN are driven by decreased room and board charge, while the premium for RRN is driven by higher operating room and supply charges. Because RRN use is increasing, the financial implications of RRN use for routine cases warrants further study.

Despite the widespread use of minimally invasive radical prostatectomy (MIRP), there remain concerns regarding its safety in patients with a history of prior abdominopelvic or inguinal surgery.A prospective database of 1165 MIRP procedures performed by a single surgeon at a high-volume tertiary care center from 2001 to 2013 was analyzed. After an initial period of transperitoneal MIRP (TP), an extraperitoneal (EP) approach was used preferentially beginning in 2005 (for both laparoscopic and robotic cases), and robotics were used preferentially beginning in 2010. Overall perioperative complications, major complications (Clavien-Dindo III or IV), and abdominal complications (e.g., ileus, bowel/organ injury, or vascular injury) were compared for patients with and without a prior surgical history. Uni- and multivariate logistic regression were used to control the impact of robotics, approach, operative time, estimated blood loss, case number, prostate weight, and primary Gleason on complications.Three hundred patients undergoing MIRP had prior abdominopelvic or inguinal surgery (25.8%). Of these, 102 (34%) underwent TP and 198 (66%) EP MIRP. Robotics was used in 286 cases (24.6%) and pure laparoscopy in 879 (75.4%). Complications occurred in 111 patients (9.5%) from the total cohort, with major complications in 32 (2.75%) and abdominal complications in 19 (1.63%). Prior surgery was not associated with overall, major, or abdominal complications. Of the controlling factors, only increasing operative time was associated with postoperative abdominal complications (most of which were ileus) on multivariate analysis.In this large single-surgeon series where both EP and TP approaches to MIRP are utilized, prior abdominopelvic or inguinal surgery was not associated with an increased risk of perioperative complications.

Level-1 evidence supports the use of neoadjuvant chemotherapy (NAC) in the management of muscle-invasive bladder cancer.1,2 In recent years, these findings have resulted in the increased use of NAC before radical cystectomy (RC) in the United States.3 The enrollment criteria for the 2 largest randomized trials of NAC in bladder cancer2,4 required a clinical diagnosis of muscle-invasive disease (clinical stage T2-T4). After the completion of NAC, patients proceeded directly to cystectomy without a repeat staging examination. Based on these study protocols, this management strategy has become the standard of care for muscle-invasive bladder cancer. At our institution, we routinely perform a restaging evaluation after the completion of NAC but before proceeding to RC. This evaluation involves a chest radiography or chest computed tomography scan (CT), cross-sectional imaging of the abdomen and pelvis (either CT or magnetic resonance imaging), endoscopic examination of the bladder under anesthesia, and a bimanual examination. This extensive restaging evaluation, including endoscopic and bimanual examination, is not routinely performed by all urologists, and its clinical utility is unclear. Furthermore, in patients managed with RC alone, there are often discrepancies between the clinical stage assigned at the time of diagnosis and the pathologic stage determined by analysis of the RC specimen.5–7 The lack of correlation between clinical and pathologic stage compromises accurate assessment of patient prognosis at the time of diagnosis.8 In patients receiving NAC, there is likely to be an even greater discrepancy between clinical and pathologic stage, as NAC leads to pathologic downstaging in a significant percentage of patients.2 It is unknown whether a restaging evaluation performed after the completion of NAC allows for the more accurate prediction of pathologic stage after RC. The purpose of the present study was thus 2-fold. First, we aimed to assess the clinical utility of an extensive restaging evaluation after NAC and determine how often the results of this restaging evaluation change patient management. Second, we investigated the correlation between clinical stage on postchemotherapy restaging evaluation and pathologic stage after RC, to determine whether restaging improves the assessment of patient prognosis.

To compare the perioperative outcomes of robot-assisted partial nephrectomy (RAPN) with open partial nephrectomy (OPN) in solitary kidneys.Records of 1542 consecutive RAPN performed in five high-volume centers (2007-2013) were reviewed for patients with solitary kidneys. RESULTS were compared with solitary OPN cases performed during the same period. Cases were divided into simple (R.E.N.A.L. nephrometry score 4-8) and complex (R.E.N.A.L. 9-12) groups. Demographics, surgical, pathologic, and follow-up data were compared between OPN and RAPN in each group.40 RAPN and 85 OPN cases were identified. For both tumor complexity groups, patients in each treatment modality were comparable. There were higher proportions of OPN cases in the complex group (61.2% vs 25%; P=0.001). For both complexity tumor groups, there was no statistical difference between the treatment modalities in overall intraoperative/postoperative complications, transfusion rate, and positive surgical margin (PSM) rates. Patients in the RAPN group had a shorter length of hospital stay. For the entire cohort, there was no difference in estimated glomerular filtration rate preservation beyond 1 month (OPN 80.51%, RAPN 81.29%). Limitations include retrospective, nonrandomized nature of the series and small number of cases in the RAPN groups.In the solitary kidney, RAPN offers comparable perioperative and short-term functional outcomes for localized tumors with low R.E.N.A.L. score. For more complex tumors, our early experience suggests comparability, but these results were obtained in selected cases and future studies will need to validate these results.

Understanding the degree of phenotypic heterogeneity in a small renal mass may have implications for interpreting renal mass biopsy data. In this study we quantify nuclear grade heterogeneity in small renal masses.Our institutional renal mass database was queried for patients with T1a (less than 4 cm) renal masses stratified by the criteria of imaging diameter less than 2 cm or 2 cm or greater, clear cell or papillary histology, low grade (Fuhrman 1-2) or high grade (Fuhrman 3-4) with tissue available for review. Four consecutive specimens were chosen from each of the 8 strata for a total of 32. All specimens were reanalyzed and the highest Fuhrman grade present in each 10× powered field was recorded. A case was classified as heterogeneous if multiple grades were present and as discordant if the highest Fuhrman grade was present in less than 50% of the specimen.A median of 5 slides (IQR 3.5-7.5) and 59, 10× powered fields (IQR 34-109) were examined per patient. Overall 26 samples (81.3%) were heterogeneous, including 15 of 16 (93.8%) high grade specimens. Among all cases 10 (31.3%) were discordant and of high grade specimens 4 (25%) were discordant. Median fraction of low grade tissue in high grade specimens was 38.9% (IQR 12.2-57.2).The majority of small renal masses demonstrated considerable nuclear grade heterogeneity. The greatest degree of heterogeneity and discordance was observed in high grade tumors. One should consider these findings when interpreting renal mass biopsy data as the risk of under sampling high grade tumors may not be insignificant.

To investigate the post-prostatectomy and long-term outcomes of men presenting with an elevated pretreatment prostate-specific antigen (PSA) level (10 ng/mL), but otherwise low-risk features (biopsy Gleason score ≤6 and clinical stage ≤T2a).PSA-incongruent intermediate-risk (PII) cases were defined as those patients with preoperative PSA10 and ≤20 ng/mL but otherwise low-risk features, and PSA-incongruent high-risk (PIH) cases were defined as men with PSA20 ng/mL but otherwise low-risk features. Our institutional radical prostatectomy database (1992-2012) was queried and the results were stratified into D'Amico low-, intermediate- and high risk, PSA-incongruent intermediate-risk and PSA-incongruent high-risk cases. Prostate cancer (PCa) features and outcomes were evaluated using appropriate comparative tests. Multivariable analyses were adjusted for age, race and year of surgery.Of the total cohort of 17 608 men, 1132 (6.4%) had PII-risk disease and 183 (1.0%) had PIH-risk disease. Compared with the low-risk group, the odds of upgrading at radical prostatectomy (RP) were 2.20 (95% CI 1.93-2.52; P0.001) for the PII group and 3.58 (95% CI 2.64-4.85; P0.001) for the PIH group, the odds of extraprostatic disease at RP were 2.35 (95% CI 2.05-2.68; P0.001) for the PII group and 6.68 (95% CI 4.89-9.15; P0.001) for the PIH group, and the odds of positive surgical margins were 1.97 (95% CI 1.67-2.33; P0.001) for the PII group and 3.54 (95% CI 2.50-4.95, P0.001) for the PIH group. Compared with low-risk disease, PII-risk disease was associated with a 2.85-, 2.99- and 3.32-fold greater risk of biochemical recurrence (BCR), metastasis and PCa-specific mortality, respectively, and PIH-risk disease was associated with a 5.32-, 6.14- and 7.07-fold greater risk of BCR, metastasis and PCa-specific mortality, respectively (P ≤ 0.001 for all comparisons). For the PII group, the higher risks of positive surgical margins, upgrading, upstaging and BCR were dependent on PSA density (PSAD): men in the PII group who had a PSAD0.15 ng/mL/g were not at higher risk compared with those in the low-risk group. Men in the PII group with a PSAD ≥0.15 ng/mL/g and men in the PIH group were more likely to have an anterior component of the dominant tumour (59 and 64%, respectively) compared with those in the low- (35%) and intermediate-risk group (39%) and those in the PII-risk group with PSAD0.15 ng/mL/g (29%).Men with PSA20 ng/mL or men with PSA10 and ≤20 ng/mL with a PSAD ≥0.15 ng/mL/g, but otherwise low-risk PCa, are at greater risk of adverse pathological and oncological outcomes and may be inappropriate candidates for active surveillance. These men are at greater risk of having anterior tumours that are undersampled at biopsy, so if treatment is deferred, ancillary testing such as anterior zone sampling or magnetic resonance imaging should be strongly encouraged. Men with elevated PSA levels10 and ≤20 ng/mL but low PSAD have outcomes similar to those in the low-risk group, and consideration of surveillance is appropriate in these cases.

INTRODUCTION AND OBJECTIVES: A growing body of retrospective literature has emerged regarding active surveillance (AS) for select patients with small renal masses (SRM). The prospective, multi-institutional DISSRM Registry was opened January 1, 2009, enrolling patients with SRM 4.0 cm who chose intervention or AS. METHODS: Patients were enrolled following consultation and choice of AS or intervention. Those electing AS followed an imaging protocol every 4-6 months for 2 years, then every 6-12 months for 3 years. The Registry was designed and powered as a non-inferiority study, able to distinguish a maximally clinically-significant unimportant difference in disease-specific survival (DSS) of 5% at 5 years. Survival analyses were performed using the KaplanMeier method and Cox proportional hazards regression. Recurrence was defined as progression of a previously insignificant synchronous lesion, metachronous tumor, persistence of enhancement following ablation, local or distant metastatic recurrence in the intervention cohort. Progression was defined by growth rate >0.5cm/ year, greatest tumor diameter >4.0cm, metastatic progression or elective crossover to intervention in the AS cohort. Analyses were performed in an intention to treat manner crossover patients were considered AS. RESULTS: At 57 months, among 4 institutions, 438 patients are enrolled: 177 elected AS, 261 primary intervention and 21 patients have crossed over from AS to intervention. AS patients were on average older, with higher ECOG scores, more comorbidities and had smaller, more complex tumors. In the AS and intervention cohort, overall survival was 96.0% and 98.1% at 2, and 93.2% and 87.8% at 4 years respectively (log-rank, p1⁄40.65). DSS was 100% and 99% at 4 years respectively (p1⁄40.73); only 1 patient undergoing intervention died of renal cell cancer. 4-year recurrence-free survival in the intervention cohort was 95.4%. Progression-free survival was 57.5% at 2 and 53.0% at 4-years in the AS cohort. 39 patients in AS experienced a progression: 24 with growth rate 0.5cm/year, 2 with tumor >4.0cm of which 8 elected crossover, the remaining 13 crossovers were elective. No patient undergoing AS progressed to metastatic disease. CONCLUSIONS: In a well-selected cohort with 5-years of prospective data, overall and DSS are not significantly different among patients with a SRM undergoing intervention and AS. Therefore, AS is a safe and efficacious management strategy for patients with SRM.

highest volume hospitals there was a lower likelihood of IPOMC administration (OR 0.6, p1⁄40.04). Patient gender, race, insurance status, hospital location, size and teaching affiliation did not affect IPOMC administration. CONCLUSIONS: Despite the abundance of data supporting the use of intravesical MMC within 24 hours after endoscopic management of bladder tumors, adoption of this practice in the United States is severely limited. Our findings are particularly concerning as young patients who would most likely benefit from IPOMC are the ones least likely to receive the therapy. Barriers to more widespread use may include surgeon experience and biases and institutional restrictions.

INTRODUCTION AND OBJECTIVES: Time to recovery of continence after robotic-assisted radical prostatectomy (RARP) remains the most bothersome complaint by patients. Many techniques have been described to shorten recovery to continence, none have thus far been validated. We propose a technique that creates a “hammock” around the urethra at the time of vesico-urethral anastomosis. We believe that this may lead to very early (

INTRODUCTION AND OBJECTIVES: Active surveillance (AS) is a management option for patients with small renal masses (SRM). Retrospective data indicates that patient and tumor characteristics may influence the likelihood of benign, indolent and malignant pathology. We hypothesize that tumor kinetics and growth rate (GR) may also be mitigated by patient comorbidities or initial tumor characteristics. We therefore examined the prospective, multi-institutional Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) Registry, opened January 1, 2009, enrolling patients with SRM 4.0 cm undergoing AS. METHODS: Patients were enrolled following consultation and choice of AS or intervention. Those electing AS followed an imaging protocol every 4-6 months for 2 years, then every 6-12 months for 3 years. The last GR was calculated for each patient as the linear change in greatest tumor diameter over time since initial imaging. Univariable linear regression modeling was used to determine patient and tumor characteristics predictive of GR at last follow-up. RESULTS: Of 177 patients initially undergoing AS, 95 had their most recent follow-up imaging at a median of 643 days (range 64-1647). Median growth rate was 0.156 cm/year (range -1.81-2.5). Obesity was the only patient characteristic predictive of GR (Coefficient -0.355, p1⁄40.02); neither age, sex, ECOG, Charlson Comorbidity Index nor any individual comorbidity predicted GR. Tumor size at initial imaging did not predict GR; however, enhancement in the nephrogenic (venous) phase of CT scan (Coef. 0.017, p1⁄40.024) and hilar tumors (Coef. 0.293, p1⁄40.035) predicted GR; nearness to the collecting system (p1⁄40.057) and tumors crossing polar lines (p1⁄40.08) by RENAL Nephrometry were suggestive of GR. CONCLUSIONS: Patient and tumor characteristics may have implications for tumor growth kinetics in patients undergoing AS for SRM. Consideration of these factors may be important in the choice of AS and may influence the timing of intervention in order to preserve an opportunity for nephron-sparing surgery.

The objectives of the present study were analyze specific comorbidities associated with survival and actual causes of death for patients with small renal masses, and to suggest a simplified measure associated with decreased overall survival specific to this population.The Surveillance, Epidemiology and End Results-Medicare database (1995-2007) was queried to identify patients with localized T1a kidney cancer undergoing partial nephrectomy, radical nephrectomy or deferring therapy. We explored independent associations of specific comorbidities with causes of death, and developed a simplified cardiovascular index. Cox proportional hazards, and Fine and Gray competing risks regression were used.Of 7177 Medicare beneficiaries in the study population, 754 (10.5%) deferred therapy, 1849 (25.8%) underwent partial nephrectomy and 4574 (63.7%) underwent radical nephrectomy with none of the selected comorbidities identified in 3682 (51.3%) patients. Congestive heart failure, chronic kidney disease, peripheral vascular disease, chronic obstructive pulmonary disease, diabetes and cerebrovascular disease were associated with decreased overall survival. The cardiovascular index provided good survival risk stratification, and reclassified 1427 (41%) patients with a score ≥1 on the Charlson Comorbidity Index to a 0 on the cardiovascular index with minimal concession of 5-year survival.Congestive heart failure, chronic kidney disease, peripheral vascular disease, chronic obstructive pulmonary disease, diabetes and cerebrovascular disease were associated with decreased overall survival among Medicare beneficiaries with small renal masses. The cardiovascular index could serve as a clinically useful prognostic aid when advising older patients that are borderline candidates for surgery or active surveillance.

Robot-assisted partial nephrectomy (RAPN) for posterior renal masses necessitates access to the posterior surface of the kidney either via a transperitoneal (TP) or retroperitoneal (RP) approach. While advocates of an RP approach claim reduced morbidity for posterior tumors, it is a less familiar approach to many urologists. In our institution, a TP approach is used for all patients undergoing RAPN. We compared demographics and perioperative outcomes of TP RAPN for posterior and anterior/lateral renal masses.Our institutional renal mass database was queried for patients with available preoperative imaging who underwent TP RAPN from 2007 to 2013. Posterior masses were accessed by opening the Gerota fascia and rotating the kidney anteromedially. Demographic and perioperative outcomes were compared for patients with posterior masses and anterior/lateral masses.Overall, 260 TP RAPN were identified. Of these, 92 were for posterior tumors and 168 were for anterior and lateral tumors. Renal-cell carcinoma (RCC) was found in 77.3% of cases. Patient demographic and tumor characteristics were similar between groups. Among operative characteristics, warm ischemia time (17 vs 16.5, min P=0.70), operative time (160 vs 159 min, P=0.82), estimated blood loss (100 vs 100 mL, P=0.44), RCC positive surgical margins (1.4% vs 1.5%), and postoperative complications (19.6% vs 16.1%, P=1.0) were similar for posterior and anterior/lateral tumors, respectively.TP RAPN is a safe, effective treatment option for patients with posterior renal masses with no additional morbidity compared with anterior/lateral renal masses. RP PN remains an alternative treatment option.

Outcomes in men with National Comprehensive Cancer Network (NCCN) high-risk prostate cancer (PCa) can vary substantially—some will have excellent cancer-specific survival, whereas others will experience early metastasis even after aggressive local treatments. Current nomograms, which yield continuous risk probabilities, do not separate high-risk PCa into distinct sub-strata. Here, we derive a binary definition of very-high-risk (VHR) localized PCa to aid in risk stratification at diagnosis and selection of therapy. We queried the Johns Hopkins radical prostatectomy database to identify 753 men with NCCN high-risk localized PCa (Gleason sum 8–10, PSA >20 ng ml−1, or clinical stage ⩾T3). Twenty-eight alternate permutations of adverse grade, stage and cancer volume were compared by their hazard ratios for metastasis and cancer-specific mortality. VHR criteria with top-ranking hazard ratios were further evaluated by multivariable analyses and inclusion of a clinically meaningful proportion of the high-risk cohort. The VHR cohort was best defined by primary pattern 5 present on biopsy, or ⩾5 cores with Gleason sum 8–10, or multiple NCCN high-risk features. These criteria encompassed 15.1% of the NCCN high-risk cohort. Compared with other high-risk men, VHR men were at significantly higher risk for metastasis (hazard ratio 2.75) and cancer-specific mortality (hazard ratio 3.44) (P

Lymphadenectomy is utilized in both pelvic and retroperitoneal oncological surgery as a means to eradicate locoregional disease, improve staging accuracy and guide adjuvant therapy. However, pelvic and retroperitoneal lymphadenectomy have the potential for morbidity including lymphatic injury, vascular injury, thromboembolic events and neurologic injury. Across the spectrum of urologic malignancies, the evidence supporting both the necessity and the extent of lymphadenectomy varies considerably. Awareness of the potential for injury and ways to avoid and manage the most common complications is necessary to decrease the morbidity associated with these procedures.

We evaluated the early oncological end point of recurrence-free survival in patients with renal cell carcinoma up-staged from cT1 to pT3a after partial nephrectomy. We also aimed to establish preoperative factors associated with pathological tumor up-staging.A prospective database of robotic partial nephrectomy cases performed at 5 academic centers was queried for patients who underwent surgery for a solitary cT1 renal mass. Patients with pT1-2 renal cell carcinoma were compared to those with pT3a tumors to determine the difference in recurrence-free survival. Preoperative factors associated with cT1 to pT3a up-staging were studied using multivariate logistic regression analysis.A total of 1,096 patients underwent robotic partial nephrectomy for a cT1 renal mass. At final pathological evaluation 855 tumors (78.0%) were found to be renal cell carcinoma, of which 41 (4.8%) were up-staged to pT3a. The 24-month recurrence-free survival estimates for pT1-2 and pT3a tumors were 99.2% and 91.8%, respectively (p=0.003). Multivariate analysis revealed that a high vs low R.E.N.A.L. (radius, exophytic/endophytic, nearness to collecting system or sinus, anterior/posterior and location relative to polar lines) nephrometry score was associated with tumor up-staging (OR 2.97, 95% CI 1.20-7.35, p=0.02). On separate multivariate analysis increasing tumor diameter (OR 1.66, 95% CI 1.32-2.08, p0.001) and hilar location (OR 2.83, 95% CI 1.43-5.61, p=0.003) were also associated with up-staging.At short-term followup patients with renal cell carcinoma up-staged from cT1 to pT3a have reasonable oncological outcomes after partial nephrectomy. Factors associated with tumor up-staging include high tumor complexity, increasing tumor diameter and hilar location. Further studies are needed to determine the comparative efficacy of partial vs radical nephrectomy for small pT3a tumors.

e540 Background: Magnetic resonance imaging (MRI)/transrectal ultrasound (TRUS) fusion-guided prostate biopsy (FBx) has rapidly proliferated in prostate cancer evaluation. FBx success may be dependent on multiple factors, including skills learned with user experience and the type of ultrasound (US) probe used. Our objective of this study was to compare the accuracy of the MRI/TRUS FBx technique utilizing an end fire versus a side fire US probe on an FBx platform. Methods: The participants of the study consisted of three different experience levels (expert ( > 1000 FBx), Urology fellows with none to minimal FBx experience, Urology residents with no FBx experience). Each participant performed three trials of the FBx with the UroNav System in separate phantom models of the prostate. Each trial involved targeting the same set of fiducials through FBx platform and then using US only; first using an end fire US probe, and then using a side fire US probe. Fusion registration error (FRE) was defined as the distance between MR target and transformed core location from the US only biopsy. Results: Six users with 3 different experience levels performed the FBx. Mean FRE with the end fire probe for the residents, fellows, expert was 7.42(±0.11), 5.10(±0.73) & 3.75(±0.75) respectively. Mean FRE with the side fire probe for the residents, fellows, expert was 6.08(±0.09), 4.76(±0.68) & 3.46(±0.08) respectively. There was no significant difference between the FRE averages for end fire vs. side fire. There was an inverse relationship of mean FRE with user experience level (corr. coefficient (r) = -0.79, p = 0.011 for end fire; r = -0.84, p = 0.004 for side-fire). Conclusions: We report the results of a pilot study comparing the efficacy of side fire and end fire US probes in MRI/TRUS FBx. Our preliminary results suggest the type of US probe used does not significantly affect FRE and FBx performance. As expected, FRE decreases with increased user experience. A larger study with more participants will be needed to compare these probes with adequately powered analysis and will dictate the practice in clinical settings as minimization of FRE will improve diagnostic accuracy of this technique in detecting clinically significant cancer.

Objective Our objective was to determine the accuracy of urethral frozen section (FS) by analyzing our clinical experience. Materials and methods A total of 298 patients undergoing radical cystectomy for bladder cancer with benign or malignant urethral FS were identified between 2000 and 2012. Urethral FS were compared with rereviewed FS to calculate the positive and negative predictive values of the FS. To assess the ability of the positive FS to be cleared with further sampling/resection, FS were then compared with the final urethral margin. The cases of positive urethral FS were then specifically analyzed to assess rates of urethral recurrence and survival. Results All negative FS were confirmed to be negative on FS rereview and on final pathology, resulting in a NPV of 100%. Urethral FS were positive in 28 (8.7%) patients, of whom 2 (7%) were negative on FS rereview, yielding a positive predictive value of 93%. Both false positives were because of contamination of detached cancer from the bladder being present in the FS. After additional sampling/resection, the final margin was negative in 13 (46%) patients. Conclusions A negative urethral FS reliably identifies individuals for whom urethrectomy is unnecessary and provides robust information for decision-making regarding the safety of orthotopic reconstruction. Nearly half of the patients with a positive FS were ultimately determined to have a negative final margin. Accordingly, we recommend that surgeons and pathologists discuss positive FS findings at the time of surgery and consider whether additional tissue should be analyzed in real time.

Understanding the development of cortical interneuron phenotypic diversity is critical because interneuron dysfunction has been implicated in several neurodevelopmental disorders. Here, tyrosine hydroxylase (TH)-immunoreactive neurons in the developing and adult rat cortex were characterized in light of findings regarding interneuron neurochemistry and development. Cortical TH-immunoreactive neurons were first observed two weeks postnatally and peaked in number three weeks after birth. At subsequent ages, the number of these cell profiles was gradually reduced, and they were seen less frequently in adults. No DNA fragmentation or active caspase 3 was observed in cortical TH cells at any age examined, eliminating cell death as an explanation for the decrease in cell number. Although cortical TH cells reportedly fail to produce subsequent catecholaminergic enzymes, we found that the majority of these cells at all ages contained phosphorylated TH, suggesting that the enzyme may be active and producing L-DOPA as an end-product. Morphological criteria and colocalization of some TH cells with glutamic acid decarboxylase suggests that these cells are interneurons. Previously, parvalbumin, somatostatin, and calretinin were demonstrated in nonoverlapping subsets of interneurons. Cortical TH neurons colocalized with calretinin but not with parvalbumin or somatostatin. These findings suggest that the transitory increase in TH cell number is not due to cell death but possibly due to alterations in the amount of detectable TH present in these cells, and that at least some cortical TH-producing interneurons belong to the calretinin-containing subset of interneurons that originate developmentally in the caudal ganglionic eminence.

625 Background: Previous studies have correlated response to PD−1 blockade with PD−L1 over−expression, as well as cell−mediated immune transcripts). However, factors associated with long−term, durable response to nivolumab in patients with RCC have not yet been elucidated. To better understand these factors, we conducted a study to characterize the two extremes of response to therapy – exceptional responders who had durable, complete response and patients who had primary refractory disease. Methods: Patients with durable, complete response (“exceptional responders”) (n=4) and primary refractory disease (n=3) were analyzed. Immunohistochemical staining for PD−L1, CD8 and FOXP3, whole−exome sequencing and quantitative RNA expression profiling was performed and correlated with clinical outcomes. Results: Exceptional responders had trends toward greater CD8+ lymphocyte infiltrate (126.7 vs 28.8 lymphocytes/hpf), higher number of somatic mutations (67 vs 35 somatic mutations/genome), and higher number of predicted mutation associated neoantigens than primary refractory patients (44 vs 8). Expression analysis demonstrated acute phase and immune tolerance signatures in primary refractory patients, while exceptional responders had higher expression of T cell and innate immune signatures. Conclusions: Exceptional responders and primary refectory patients have distinct pathologic, genomic and RNA expression profiles. Larger studies are needed to fully elucidate the basis of response to PD−1 blockade in patients with renal cell carcinoma.

AGRO100, also known as AS1411, is an experimental anticancer drug that recently entered human clinical trials. It is a member of a novel class of antiproliferative agents known as G-rich oligonucleotides (GRO), which are non-antisense, guanosine-rich phosphodiester oligodeoxynucleotides that form stable G-quadruplex structures. The biological activity of GROs results from their binding to specific cellular proteins as aptamers. One important target protein of GROs has been previously identified as nucleolin, a multifunctional protein expressed at high levels by cancer cells. Here, we report that AGRO100 also associates with nuclear factor-κB (NF-κB) essential modulator (NEMO), which is a regulatory subunit of the inhibitor of κB (IκB) kinase (IKK) complex, and also called IKKγ. In the classic NF-κB pathway, the IKK complex is required for phosphorylation of IκBα and subsequent activation of the transcription factor NF-κB. We found that treatment of cancer cells with AGRO100 inhibits IKK activity and reduces phosphorylation of IκBα in response to tumor necrosis factor-α stimulation. Using a reporter gene assay, we showed that AGRO100 blocks both tumor necrosis factor-α-induced and constitutive NF-κB activity in human cancer cell lines derived from cervical, prostate, breast, and lung carcinomas. In addition, we showed that, in AGRO100-treated cancer cells, NEMO is coprecipitated by nucleolin, indicating that both proteins are present in the same complex. Our studies suggest that abrogation of NF-κB activity may contribute to the anticancer effects of AGRO100 and that nucleolin may play a previously unknown role in regulating the NF-κB pathway. [Mol Cancer Ther 2006;5(7):1790–9]

482 Background: Outcomes for patients with RCC are reported by pathologic stage; however, determination of therapy and patient counseling are based on clinical staging. Moreover, the development of neoadjuvant therapies that may requires knowledge of clinical stage-specific outcomes for trial design. Because of a paucity of reported outcomes, we characterized pathologic upstaging, recurrence-free survival (RFS) and cancer-specific survival (CSS) by stage at our institution. Methods: Our renal mass registry was queried for patients with localized RCC who underwent extirpative surgery with from 2003-2013 stratified by clinical stage. The proportion of cases upgraded by stage were determined. Survival outcomes were analyzed using the Kaplan-Meier method. Results: A total of 2,144 cases were captured during the study period. Median follow-up was 44.5 months. Clinical to pathologic upstaging is listed in the table. The highest degree of upstaging occured in cT2 cases, with 47% of cT2a and 48% of cT2b upstaged to ≥cT3a. RFS at 60 months for cT1a was 98.4%, cT1b 95.5%, cT2a 78.4%, cT2b 74.4%, cT3a 68.0%, cT3b 63.5%, cT3c 27.8%. CSS at 60 months for cT1a was 99.3%, cT1b 96.3%, cT2a 82.7%, cT2b 81.7%, cT3a 88.7%, cT3b 66.8%, and cT3c 76.9%. Harrell's C index for CSS was similar for both clinical (0.68) and pathologic stage (0.75). Conclusions: While the rate of upstaging increases markedly with increasing clinical stage, survival models based on clinical stage perform as well as those based on pathologic staging. The high rate of upstaging in cT2 disease supports enrollment of these patients in adjuvant clinical trials. Knowledge of these clinical stage-specific outcomes may be helpful for trial design. [Table: see text]