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OBJECTIVES To compare the outcomes of laparoendoscopic single-site (LESS) surgery with conventional laparoscopic pyeloplasty (CLP) before LESS can be widely accepted. LESS surgery is a novel technique for performing laparoscopic pyeloplasty through a single incision. METHODS Fourteen patients undergoing less pyeloplasty were matched 2:1 with regard to age and side of surgery to a previous cohort of 28 patients who underwent CLP. All patients underwent surgery for symptomatic ureteropelvic junction obstruction and/or delayed urinary excretion based on functional imaging. Intracorporeal suturing was aided through a 5-mm instrument placed in the eventual drain site. RESULTS No difference was observed between the LESS and CLP cohorts in regard to preoperative characteristics. Postoperatively, no difference was noted between LESS and CLP cases in regard to length of stay (77 vs 74 hours; P = .69), morphine equivalents required (34 vs 38; P = .93), minor postoperative complications (14.3% vs 14.3%; P = 1.0), or major postoperative complications (21.4% vs 10%; P = .18). Median operative times (207 vs 237.5 minutes; P

OBJECTIVE To evaluate the effect of body mass index (BMI, kg/m2) on the cost and clinical variables after radical cystectomy (RC), as studies show that obesity might adversely affect the outcomes after RC. PATIENTS AND METHODS The charts of patients who had RC from January 2004 to March 2007 were reviewed retrospectively. Complete cost and clinical information was available for 99 patients; the patient and tumour characteristics and peri-operative outcomes were recorded. Detailed cost information (room and board, laboratory, pharmacy, radiology, operating room, surgical supply, anaesthesia, and recovery room) was obtained from hospital billing. Patients were stratified and compared in three groups of BMI, i.e. normal weight (

There is a paucity of information on the association of preoperative parameters with surgical outcomes and cost. We identified preoperative predictors of direct cost and examined the association of these factors with the perioperative outcomes of percutaneous nephrostolithotomy.We reviewed the records of 200 consecutive patients who underwent percutaneous nephrostolithotomy at our hospital from September 2005 to May 2007. Complete cost and clinical information were available on 179 patients (89.5%). Patient and stone characteristics, and perioperative outcomes were recorded. Direct and component costs, including room and board, laboratory, pharmacy, radiology, operating room, surgical supplies, anesthesia and recovery room, were obtained from our hospital billing department. Univariate and multivariate linear regression analyses were performed to identify preoperative predictors of cost. We evaluated the association of independent predictors of cost with perioperative outcomes.On univariate analysis stone size category, preoperative urinary tract infection and allopurinol were associated with direct cost. On multivariate analysis only stone burden was an independent predictor of nephrostolithotomy cost. Large stone burden was associated with an increased need for multiple access (p = 0.0003), longer operative time (p0.0001), longer hospitalization duration (p0.0001), a lower stone-free rate (p = 0.038) and the need for second look flexible nephroscopy (p = 0.0005). Large stone burden was not associated with a greater transfusion requirement (p = 0.25) or an increased complication rate (p = 0.46).A large stone burden independently predicts higher costs in patients who undergo percutaneous nephrostolithotomy despite no associated increase in the complication or transfusion rate. Other patient characteristics, including age, body mass index and comorbidity status, do not increase cost.

We report a case of metastatic collecting duct carcinoma (CDC) incidentally found on computer assisted tomography in an 18-year-old male who presented status post a motor vehicle crash (MVC). The patient underwent total nephrectomy/renal vein thrombectomy with retroperitoneal lymph node dissection, followed by multimodal therapy, with gemcitabine and platinum salt therapy, effecting a short lived complete response, followed by single agent paclitaxel chemotherapy effecting a similarly short lived partial response. We conclude that cytoreductive nephrectomy and lymphadenectomy combined with chemotherapy may be useful for extending and increasing the quality of life of selected patients with CDC.

We evaluated whether screening high risk asymptomatic individuals with a bladder tumor marker can lead to earlier detection and resultant down staging of bladder cancer.Subjects at high risk for bladder cancer based on age and smoking or occupational status were solicited from 2 well patient clinics from March 2006 to November 2007. NMP22 BladderChek testing was performed on voided urine samples. Those with positive test results underwent office cystoscopy and cytology testing. Participants were contacted for followup at 12 months after study enrollment to evaluate for unrecognized bladder cancer.A total of 1,175 men and 327 women underwent BladderChek testing. Mean participant age was 62.5 years (range 46 to 92). Based on 10-year or greater smoking history 1,298 participants were enrolled while 513 were enrolled based on a greater than 15-year high risk occupation for bladder cancer. Positive BladderChek testing was observed in 85 (5.7%) participants and 69 agreed to undergo cystoscopy. Three types of lesions were diagnosed including multifocal, high grade Ta (1); Ta, low grade tumor (1) and marked atypia (1). Followup was available in 1,309 subjects. Mean followup was 12 months (range 0.9 to 25.5) and 2 of 1,309 participants had low grade noninvasive bladder cancer. Evaluation of patient records revealed that 73.4% of participants had urinalysis within 3 years before screening.NMP22 BladderChek for screening an asymptomatic, high risk population can detect noninvasive cancers but the low prevalence of bladder cancer in this population did not permit assessment of intervention efficacy. Frequent use of urinalyses in high risk persons may attenuate future efforts to study the effects of bladder cancer screening tests.

Objectives Hydronephrosis at the time of diagnosis of bladder cancer is associated with advanced disease and is a predictor of poorer outcomes. There is, however, limited information addressing whether a similar relationship exists for upper-tract urothelial carcinoma (UTUC). We investigate the prognostic impact of hydronephrosis on preoperative axial imaging on clinical outcomes after radical nephroureterectomy. Materials and Methods The records for 106 patients with UTUC who underwent radical nephroureterectomy at 2 medical centers were reviewed. Preoperative computed tomography (CT) images were evaluated for ipsilateral hydronephrosis by radiologists blinded to clinical outcomes. Association of hydronephrosis with pathologic features and oncologic outcomes after surgery was assessed. Results Sixty-seven men and 39 women with a median age of 69 years (range, 36 to 90) were evaluated. One-third of these patients had muscle invasive disease or greater (≥T2), 44% had high grade tumors, and 3% had lymph node (LN) metastases. At a median follow-up of 47 months (range, 1 to 164), 43% of patients experienced disease recurrence, 18% developed metastasis, and 12% died of their cancer. Thirty-nine patients (37%) had hydronephrosis on preoperative axial imaging; 35% of these patients had ureteral tumors, and 27% had multifocal disease. The presence of hydronephrosis was associated with advanced pathologic stage ( P = 0.03) and disease in the ureter (vs. renal pelvis) ( P = 0.007). Hydronephrosis was a predictor of non-organ confined disease on final pathology (hazard ratio [HR] 3.7, P = 0.01). On preoperative multivariable analysis controlling for age, gender, tumor location, ureteroscopic biopsy grade, and urinary cytology, hydronephrosis was independently associated with cancer metastasis (HR 8.2, P = 0.02) and cancer-specific death (HR 12.1, P = 0.03). Conclusions Preoperative hydronephrosis on axial imaging is associated with features of aggressive disease and predicts advanced pathologic stage for UTUC. Hydronephrosis can be a valuable prognostic tool for preoperative planning and counseling regarding disease outcomes.

We reviewed the natural history of residual fragments after percutaneous nephrostolithotomy.From April 1999 to January 2007 a total of 728 patients underwent percutaneous nephrostolithotomy at our medical center including 527 with a minimum documented radiographic followup of 6 months. Of these patients 42 (8%) with residual fragments on postoperative computerized tomography were observed rather than subjected to second look flexible nephroscopy. Computerized tomography was reviewed to define location, size and number of residual fragments. The primary study end point was a stone related event defined as growth of a residual fragment, or need for emergency room visit, hospitalization or additional intervention attributable to the residual fragment. Univariate and multivariate analyses were performed to determine predictors of a stone related event.The median residual fragment size was 2 mm (range, 1 to 12). There were 18 patients (43%) who experienced a stone related event at a median of 32 months after percutaneous nephrostolithotomy (range 4 to 95). On univariate analysis residual fragment location in the renal pelvis or ureter (p = 0.02), maximum residual fragment size larger than 2 mm (p = 0.03) and cumulative residual fragment size (p = 0.03) predicted a stone related event. On multivariate analysis only maximum residual fragment size larger than 2 mm (HR 3.9, p = 0.01) and location in the renal pelvis or ureter (HR 4.4, p = 0.01) independently predicted a stone event.The size and location of post-percutaneous nephrostolithotomy residual fragments correlate with stone related events. Larger fragments are more likely to require secondary surgical intervention. Second look flexible nephroscopy may be of benefit in patients with residual fragments larger than 2 mm or in those with fragments located in the renal pelvis or ureter.

Diagnostic imaging has a central role in the evaluation and management of urolithiasis. A variety of modalities are available, each with benefits and limitations. Without careful consideration of imaging modalities in quantity and type patients may receive excessive doses of radiation during initial diagnostic and followup evaluations. Therefore, we determined the effective radiation dose associated with an acute stone episode and short-term followup.A multicenter retrospective study of all patients who presented with an acute stone episode was performed. The analysis included all imaging studies related to stone disease performed within 1 year of the acute event. Using accepted effective radiation dose standards for each of these examinations, the total radiation dose administered was calculated and compared by patient characteristics including stone location, stone number and intervention strategy. The primary outcome assessed was a total radiation dose greater than 50 mSv, the recommended yearly dose limit for occupational exposure by the International Commission on Radiological Protection.We identified 108 patients who presented to our respective institutions with a primary acute stone episode between 2000 and 2006. The mean age in our cohort was 48.6 years and 50% of the patients were men. Patients underwent an average of 4 radiographic examinations during the 1-year period. Studies performed included a mean of 1.2 plain abdominal films of the kidneys, ureters and bladder (range 0 to 7), 1.7 abdominopelvic computerized tomograms (range 0 to 6) and 1 excretory urogram (range 0 to 3) during the first year of followup. The median total effective radiation dose per patient was 29.7 mSv (IQR 24.2, 45.1). There were 22 (20%) patients who received greater than 50 mSv. Analysis of stone location, number of stones, stone composition, patient age, sex and surgical intervention indicated no statistically significant difference in the probability of receiving a total radiation dose greater than 50 mSv.A fifth of patients receive potentially significant radiation doses in the short-term followup of an acute stone event. Radiographic imaging remains an integral part of the diagnosis and management of symptomatic urolithiasis. While debate exists regarding the threshold level for radiation induced fatal malignancies, urologists must be cognizant of the radiation exposure to patients, and seek alternative imaging strategies to minimize radiation dose during acute and long-term stone management.

Objectives The 22 modifier was designed to provide surgeons with additional reimbursement for performing complex procedures. We evaluated whether urologists at a tertiary referral center are reimbursed when using the 22 modifier. Methods We evaluated the charts and billing data of all adult urology noncharity cases using the 22 modifier from January 2006 and September 2007. Results The 22 modifier was used in 317 of 7494 (4.2%) unique procedures performed. Of these 317 procedures, 99 (31%) were reimbursed at a greater rate than the contract level, with a mean increase greater than the contract of $388 (median $260, range $62-$3524), for a mean of 28% greater than the contract. Of the 317 cases, 114 were within $50 of the contract level and 104 were reimbursed at less than the contract level. Additionally, 56 cases were paid at the initial request and ≤4 appeals were sent in 228 cases, with a successful result in 57 (25%). When analyzed by payor (n = 289), private insurance paid 81 of 187 (43.3%), Medicare paid 23 of 95 (24.2%), and Medicaid paid 1 of 7 (14.3%). Most payments took >2 months to be paid. The reasons for using the 22 modifier code included extensive surgery, previous surgery, staghorn calculus, extended lymphadenectomy for bladder cancer, adhesions, difficult anatomy, complex dissection, morbid obesity, previous chemotherapy, scarring, previous radiotherapy, difficult debulking, and pregnancy. Of the 317 cases, >121 had several confounding factors. Conclusions The 22 modifier does not provide consistent reimbursement for urologists performing complex procedures. The long-term implications of financial disincentives to performing difficult surgeries need to be further evaluated.

OBJECTIVE To describe our initial experience with single keyhole nephrectomy in a porcine model and in human subjects. METHODS Eight nonsurvival laparoscopic nephrectomies were performed in 4 female farm pigs. In 3 renal units, the laparoscopic nephrectomy was performed via a novel single 25-mm trocar, while the remaining 5 nephrectomies were performed using one 10-mm and two 5-mm adjacent trocars. Articulating laparoscopic graspers, conventional endoshears, clips, and a stapler were used for dissection. Three human subjects underwent a single keyhole umbilical laparoscopic nephrectomy with similar instrumentation. Indications for nephrectomy included chronic infection in a nonfunctioning kidney in 2 patients, and a 4.5-cm enhancing renal mass in the other patient. RESULTS Single keyhole nephrectomy was successfully completed in all 8 porcine renal units and in all 3 human subjects. The mean operative time for the porcine nephrectomies was 49 minutes (range, 20 to 85), with a mean blood loss of 20 mL (range, 5 to 100). Incision size ranged from 3 to 5 cm. The mean operative time for the human nephrectomy cases was 133 minutes (range, 90 to 160). Estimated blood loss was 30 mL, and the kidneys were extracted through a solitary 2 to 4.5 cm periumbilical incision. There were no perioperative complications, and all 3 patients were discharged on hospital day 2. CONCLUSIONS Keyhole umbilical nephrectomy utilizing articulating laparoscopic instrumentation to facilitate triangulation is feasible. We demonstrate safe and successful completion both in a porcine model and in the 3 human patients. Future studies will need to assess the benefits of single-access surgery in comparison to conventional laparoscopy.

Purpose To compare renal function outcomes in patients undergoing radical nephroureterectomy (RNU) or partial (distal) ureterectomy (PU) for upper tract urothelial carcinoma (UTUC). Methods Clinicopathologic data of patients undergoing RNU or PU for UTUC from 1998 to 2012 were compiled. Glomerular filtration rate was calculated preoperatively and postoperatively using the Modification of Diet in Renal Disease equation. We defined “event” as new-onset stage III chronic kidney disease (CKD) or worsening of CKD stage with preexisting CKD. Event-free survival was assessed with Kaplan-Meier methods. Cox regression analyses were performed to identify predictors of events. Results In total, 193 patients underwent RNU ( n = 143) or PU ( n = 50) over a median follow-up of 25.9 months. Overall, 15% of patients died of UTUC. High tumor grade (85.9% vs. 66.0%, P = 0.003) and locally advanced stage (>pT2, 37.8% vs. 18.0%, P = 0.014) were significantly more frequent in the RNU cohort. Stage III or higher CKD was present in 61% of RNU patients vs. 48% of PU patients ( P = 0.135) at baseline. Although total event rate was higher in the PU cohort (66% vs. 43.4%, P = 0.008), event rates within the first 3 months of surgery were similar between the groups ( P = 0.572). Adjuvant chemotherapy was the only predictor of events on Cox regression. Conclusions Rates of new-onset CKD or worsening of CKD stage were similar in patients treated with RNU and PU. Adjuvant chemotherapy may have a more significant effect on renal outcomes than surgical approach, warranting further investigation. Consideration should be given to preoperative chemotherapy, as adjuvant chemotherapy is limited by decreased renal function following surgery.

4510 Background: 20% of patients (pts) with aGCT progress after initial chemotherapy (chemo), displaying at least partial cisR. We sought to characterize the genetic alterations in aGCT and identif...

301 Background: Urothelial carcinoma is characterized by multifocal and metachronous tumors. To explain this phenomenon, two hypotheses have been proposed: the ‘field defect’ hypothesis - urothelial cells are primed to undergo transformation by exposure to carcinogens, and the clonal, or ‘single progenitor cell,’ hypothesis - tumors arise from intraluminal seeding of transformed cells. Methods: To examine their clonal relationships, we compared the genomic profiles of primary upper tract urothelial carcinoma (UTUC) tumors and metachronous bladder tumors (intravesical recurrences) in patients treated with radical nephroureterectomy (RNU) and subsequent transurethral resection. Specimens were analyzed using a next-generation, targeted sequencing assay designed to identify point mutations, indels, and copy number alterations in 341 cancer-associated genes. Results: We analyzed 16 primary UTUC tumors and 41 intravesical recurrences in patients treated with RNU. The median number of intravesical recurrences per patient was 2 (range 1-7) and the interval from RNU to intravesical recurrence ranged from 3.5 months to 129 months. With an average sequencing coverage of 516x, we found strong evidence delineating the clonal relationship between primary UTUC tumors and subsequent bladder tumors. The majority of somatic mutations present in the primary UTUC tumors (median=7, range 4-39) were detected in all subsequent bladder tumors (128/146, 88%). In an illustrative case, one patient followed with periodic cystoscopy/cytology who had been NED for 5.5 years then developed 7 bladder tumors over the next 44 months, each with the identical mutation profile (8 mutations) as the primary tumor. Conclusions: We demonstrate that bladder tumors following RNU represent true intravesical recurrences, with almost all tumors sharing the same somatic mutation profile as the primary UTUC tumor. This has important implications for surgical techniques to minimize the risk of intraluminal seeding, the delivery of intravesical therapy following RNU, and the development of strategies employing systemic chemotherapy or targeted agents.

371 Background: To validate the independent predictive value of Ki-67 in patients with high-grade upper tract urothelial carcinoma (UTUC). Methods: 475 patients from the international UTUC collaboration who underwent extirpative surgery for high-grade UTUC were included in this study. Immunohistochemical staining for Ki-67 was performed on tissue microarray (TMA) formed from this patient cohort. Ki-67 expression was assessed in a semi-quantitative fashion and considered overexpressed at a cut-off of 20%. Multivariate analyses (MVA) were performed to assess independent predictors of oncological outcomes and Harrell’s C indices (HCI) were calculated for predictive models. Results: Median age of the cohort was 69.7 years and 55.2% of patients were male. Ki-67 was overexpressed in 25.9% of patients. Ki-67 overexpression was significantly associated with ureteral tumor location, higher pT-stage, lymphovascular invasion, sessile tumor architecture, tumor necrosis, concomitant carcinoma in situ (CIS), and regional lymph node metastases. In Kaplan-Meier analyses, overexpressed Ki-67 was associated with worse recurrence-free (RFS) (HR 12.6, p

358 Background: Patients treated for urothelial carcinoma of the urinary bladder treated with radical cystectomy and pelvic lymph node dissection have worse clinical outcomes if they receive perioperative blood transfusion. We evaluated the impact of perioperative blood transfusion on oncologic outcomes in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Methods: We conducted a single-center, retrospective review of 405 patients treated with RNU for UTUC. Clinicopathologic characteristics were recorded. Hospital charts were reviewed to determine if patients received perioperative blood transfusion. Characteristics were compared between groups based on transfusion status using Chi-square analyses. Survival was assessed using the Kaplan-Meier method. Cox regression analysis addressed cancer-specific mortality (CSM). Results: Median age was 71.4 years (IQR 63.7-76.5) and the majority of patients were male (64%). Median follow up was 43.4 months (IQR 16.7-86.6). CSM occurred in 26.2% of patients. Perioperative transfusion was associated with higher rates of invasive T stage (>/=T2), (62% vs. 47%, p=0.019) and lymph node positive disease (23% vs. 10.3%, p=0.029). Three year disease-specific survival (DSS) was 80% for the entire cohort. DSS was significantly shorter (p=0.003) for patients receiving transfusion (66.3%, 95% CI 53.7%-76.3%) than those who did not (83.3%, 95% CI 78.3%-87.3%). Transfusion was an independent predictor of CSM on multivariable analysis including gender, grade, invasive T stage, nodal status, and transfusion (Table 1). Conclusions: Perioperative blood transfusion may be associated with adverse pathologic and oncologic outcomes in patients undergoing RNU for UTUC. [Table: see text]

298 Background: The type and frequency of recurrent, targetable alterations in muscle-invasive, treatment-naïve urothelial cancer (UC) have been well-catalogued through the bladder TCGA. We sought to validate these findings within a prospective cohort of patients (pts) with progressive UC treated at our institution. This cohort typifies the UC patient population managed by medical oncologists. Methods: Pts with a diagnosis of UC were enrolled onto an IRB-approved protocol between 1/14/14 and 7/29/14, which allowed for sequencing of all exons in 341 oncogenes and tumor suppressor genes using an exon capture next generation sequencing assay (NGS) platform (MSK-IMPACT) in a CLIA lab from tumor and matched germline DNA. Somatic point mutations, truncations, copy number alterations, and insertions/deletions were detected. Results: 49 UC pts were sequenced, 5 (10%) having upper tract disease. 33 (67%) tumors were pure UC histology with the remainder containing divergent differentiation. 17 samples (24%) were metastatic in origin, and 40 samples were analyzed from pts who had received prior chemotherapy. The most common alteration identified was point mutations within the TERT promoter (71%), a region not sequenced by TCGA. Additional alteration frequencies were similar between both sets. FGFR3 mutations overlapped with both PIK3CA and TSC1 alterations and co-alterations were observed between FGFR3 and CDKN2A as well as PIK3CA and CCND1. Conclusions: TERT promoter mutations were found at high frequency in the MSK-IMPACT tumor cohort. The frequency and type of alterations identified in the bladder TCGA are similar to the MSK-IMPACT cohort, suggesting that TCGA data can be used to guide clinical trials in the metastatic, pre-treated population. Overlap of alterations within and across core signaling pathways underscores the need for functional validation of alterations and for rational combinations of targeted therapies to effectively treat advanced UC. [Table: see text]

Objective To prospectively evaluate the feasibility of obtaining a reliable histochemical assessment of cell cycle biomarkers from endoscopic biopsy specimens of patients with upper tract urothelial cancer. Methods Overall, 17 patients were identified who had an available biopsy as well as those who underwent subsequent radical nephroureterectomy (RNU) or segmental ureterectomy (SU) for clinically localized high-grade upper tract urothelial cancer of the renal pelvis or ureter. Of those 17 patients, 15 (88%) had sufficient tissue to undergo immunohistochemical staining. Biopsies were obtained using various endoscopic techniques. Tumor characteristics were recorded and prospectively evaluated for immunohistochemical expression of 5 biomarkers: p21, p27, p53, cyclin E, and Ki67/pRb. Unfavorable prognostic score (PS) was defined as>2 altered markers. Results The median age of the patients was 68 years (range: 53–82 y) with 87% being males. Of the 15 specimens, 9 (60%) tumors were organ confined (T≤2 and N0), and all were high grade. Of the 15 patients, 4 (27%), 7 (46.6%), 3 (20%), and 1 (6.7%) individuals had 1, 2, 3, and 5 markers altered on biopsy marker profiling, respectively, with Ki67 being the most frequent alteration (13/15; 87.7%). An overall concordance rate of 60% (9/15) was seen between biopsy and RNU/SU PS. Those patients with favorable biopsy biomarker PS were less likely to display adverse pathological features, with organ-confined disease in 7/11 (63.6%) patients and 9/11 (81.8%) being free of carcinoma in situ in the final specimen. Additionally, 10/11 (91%) had no evidence of necrosis and 7/11 (64%) had no evidence of lymphovascular invasion on final pathologic evaluation. Conclusions Preliminary results suggest that obtaining interpretable biomarker profile of ureteroscopic biopsy specimens is feasible. Tumor heterogeneity and limited biopsy material may account for the discordance between biopsy and RNU/SU specimens. Meaningful biopsy biomarker profiling could serve as a powerful tool for individualizing treatment regimens and augmenting current predictive variables. Further studies are needed to evaluate clinical applicability.

Laparoendoscopic single site (LESS) surgery is increasingly performed for a multitude of urologic procedures. There has been considerable debate regarding the benefit of LESS surgery. Laboratory evaluation of acute-phase markers in patients receiving conventional laparoscopic and LESS nephrectomy provides new insight.

525 Background: There have been multiple reports implicating the role of hydronephrosis (HN) as a predictor of outcome in patients diagnosed with upper tract urothelial carcinoma (UTUC). However, this was done in mixed populations (low-/high-grade) and degree of HN (DOH) was not taken into account. We evaluated the impact of severity of hydronephrosis on systemic and bladder relapse in patients with UTUC. Methods: We retrospectively reviewed the records of 141 patients with localized UTUC that underwent extirpative surgery. Preoperative imaging was used to evaluate ipsilateral DOH. We analyzed the association between DOH (none/mild vs. moderate/severe), pathological findings and oncological outcomes in high-grade vs. low-grade patients. Bladder recurrence was assessed separately from local or systemic (L/S) recurrence. Results: High-grade UTUC was present in 80% of patients, 35% had muscle-invasive disease (≥pT2), and 29% had non-organ-confined disease. At a median follow-up of 34 months (range, 1-149), 35% of patients experienced intravesical recurrence, 20% developed L/S recurrence, and 17% died of UTUC. No difference in outcomes was seen between patients without HN and mild HN. DOH was none/mild in 55% and moderate/severe in 45% of cases. In patients with high-grade UTUC, moderate/severe HN was associated with advanced pathologic stage (p

323 Background: Alterations in the MTOR and HIF pathways may have prognostic significance in bladder carcinoma. We evaluated the predictive value of altered MTOR-pathway biomarkers in upper tract urothelial carcinoma (UTUC). Methods: Multi-institutional review of clinicopathological data on patients receiving extirpative surgery for UTUC from 1990-2008. Immunohistochemistry for phosphorylated-S6, mTOR, phosphorylated-mTOR, PI3K, p4E-BP, phosphorylated-AKT, PTEN, HIF-1a, Raptor and Cyclin D was performed on tissue microarrays from radical nephroureterectomy specimens. Predictive markers were identified by regression analyses. Significance of altered markers was assessed with Kaplan-Meier and Cox regression analysis. Results: 620 patients with a mean age of 69 years were included. 37% of patients had non-organ confined (T3/T4 and/or N+) disease. 74% of patients had high-grade disease and 22% had LVI on final pathology. Over a median follow-up of 27.3 months, 24.6% of patients recurred and 21.8% died of UTUC. On multivariable analysis, PI3K (OR 1.28, p=0.001) and Cyclin D (OR 3.45, p=0.05) were significant predictors of clinical outcomes. Cumulative marker-score was defined as low-risk (zero/one altered marker) or high-risk (Cyclin D AND PI3K altered). Patients with high-risk marker-score had a significantly higher proportion of high-grade disease (91% vs. 71%, p

493 Background: Epithelial to mesenchymal transition (EMT) is thought to play a crucial role in cancer progression and development of metastasis. Thus, we evaluated dysregulation of beta-catenin as a part of EMT and its clinical implications in patients with clear cell renal cell carcinoma (ccRCC). Methods: Immunohistochemical staining was performed for beta-catenin on tissue microarrays of patients with ccRCC. Membranous and cytoplasmatic beta-catenin expression patterns were assessed separately. Beta-catenin was considered normal if none or only one component was abnormal and was considered dysregulated if both components were abnormal. Differences in pathological characteristics between both groups were investigated. Differences in recurrence-free survival (RFS) and cancer-specific survival (CSS) were assessed with the Kaplan-Meier method. Uni- and multivariate Cox proportional hazard models were used to assess independent predictors of oncological outcomes. Results: 406 patients with a median follow-up of 58 months were included. Overall, 52 (12.8%) and 25 (6.2%) patients recurred and died of ccRCC. Beta-catenin was dysregulated in 70 (17.2%) patients. Dysregulation of beta-catenin was significantly associated with adverse pathologic features, such as higher T-stage, nodal positivity, higher grade, presence of tumor thrombus, sarcomatoid features, necrosis and LVI (all p

Objective To evaluate the effect of distal ureter management on oncological outcomes in patients with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma. Methods and materials Retrospective review of patient records and operative reports was conducted on 122 patients who underwent RNU. Data were compared between 2 groups using substratification by distal ureter management (transvesical bladder cuff [TVBC]) vs. no TVBC). Results Mean patient age was 69.0 years and 63.1% were male. Median follow-up was 32.0 months. Most patients (n = 76, 62.3%) received a TVBC and 46 (37.7%) patients received no TVBC during RNU. There were no significant differences in clinicopathological variables between both groups except for a higher rate of lymphadenectomy during surgery in the TVBC group (38.2% vs. 15.2%). On multivariate analysis, intravesical recurrence (IVR) was not affected by distal ureter management but was affected by tumor multifocality (hazard ratio [HR] = 2.2; 95% confidence interval [CI], 1.2–4.0; P = 0.013). However, non–IVR-free survival (non–IVR FS) and cancer-specific survival (CSS) were independently influenced by T stage (HR = 4.9; 95% CI, 1.5–16.3; P = 0.010 for non–IVR FS and HR = 6.3; 95% CI, 1.7–23.1; P = 0.005 for CSS) and management of the distal ureter (HR = 3.2; 95% CI, 1.3–7.6; P = 0.010 for non–IVR FS and HR = 3.4; 95% CI, 1.3–8.8; P = 0.010 for CSS). Conclusions In our study, surgical management of the distal ureter without excision of a TVBC resulted in significantly worse non–IVR FS and CSS but had no influence on IVR. This is hypothesis generating and supports further prospective study as to standardization of BC resection during RNU.

Objectives: Hydronephrosis at the time of diagnosis of bladder cancer is associated with advanced disease and is a predictor of poorer outcomes. There is, however, limited information addressing whether a similar relationship exists for upper-tract urothelial carcinoma (UTUC). We investigate the prognostic impact of hydronephrosis on preoperative axial imaging on clinical outcomes after radical nephroureterectomy. Materials and Methods: The records for 106 patients with UTUC who underwent radical nephroureterectomy at 2 medical centers were reviewed. Preoperative computed tomography (CT) images were evaluated for ipsilateral hydronephrosis by radiologists blinded to clinical outcomes. Association of hydronephrosis with pathologic features and oncologic outcomes after surgery was assessed. Results: Sixty-seven men and 39 women with a median age of 69 years (range, 36 to 90) were evaluated. One-third of these patients had muscle invasive disease or greater (T2), 44% had high grade tumors, and 3% had lymph node (LN) metastases. At a median follow-up of 47 months (range, 1 to 164), 43% of patients experienced disease recurrence, 18% developed metastasis, and 12% died of their cancer. Thirty-nine patients (37%) had hydronephrosis on preoperative axial imaging; 35% of these patients had ureteral tumors, and 27% had multifocal disease. The presence of hydronephrosis was associated with advanced pathologic stage (P 0.03) and disease in the ureter (vs. renal pelvis) (P 0.007). Hydronephrosis was a predictor of non-organ confined disease on final pathology (hazard ratio [HR] 3.7, P 0.01). On preoperative multivariable analysis controlling for age, gender, tumor location, ureteroscopic biopsy grade, and urinary cytology, hydronephrosis was independently associated with cancer metastasis (HR 8.2, P 0.02) and cancer-specific death (HR 12.1, P 0.03). Conclusions: Preoperative hydronephrosis on axial imaging is associated with features of aggressive disease and predicts advanced pathologic stage for UTUC. Hydronephrosis can be a valuable prognostic tool for preoperative planning and counseling regarding disease outcomes. © 2011 Elsevier Inc. All rights reserved.

4581 Background: Aberrant activation of the mammalian target of rapamycin (mTOR) pathway promotes invasiveness and metastatic potential in a variety of malignancies. The aim of the present study was to evaluate the association of altered expression of mTOR pathway components with recurrence outcome in non-metastatic clear cell renal cell carcinoma (ccRCC) patients. Methods: Immunohistochemistry for phos-S6, phos-mTOR, mTOR, phos-AKT, HIF-1α, RAPTOR, PTEN, PI3K, and phos-4EBP1 was performed on tissue microarrays of patients treated for non-metastatic kidney cancer between 1997-2010. Patients were defined as having a low (5 altered biomarkers; respectively) with the actual and predicted relapse rates was assessed. Results: The study included 419 non- metastatic ccRCC patients (pT1-T2 79.5%, pT3-T4 20.5%, Fuhrman nuclear grade 1-2 in 69%, 3-4 in 31%). 219 and 200 patients had low (

433 Background: Renal cell carcinoma (RCC) patients who present with pulmonary embolism (PE) and venous thrombus may not be offered surgery because of concerns with anti-coagulation and presumed poor post-surgical outcomes. The objective of this study was to evaluate post-surgical recurrence and disease specific survival (DSS) in RCC patients with venous thrombus who had PE diagnosed at initial presentation. Methods: After IRB approval, we reviewed the records from 2000-2011 at 3 tertiary hospitals (UW, UTMDACC, UTSW) for all consecutive RCC patients who had nephrectomy with thrombectomy. Clinical and pathologic predictive factors for recurrence and survival were collected for each patient. Univariate and multivariate analysis was used to evaluate whether PE at presentation was associated with RCC recurrence or DSS after nephrectomy with thrombectomy. Results: Preoperative PE was diagnosed in 35/782 (0.5%) RCC patients undergoing nephrectomy with thrombectomy with a median follow-up time of 22 months. Patients with PE at initial diagnosis were more likely to have higher level thrombus (p

404 Background: Cell cycle regulatory molecules are implicated in various stages of carcinogenesis. In this study we systematically evaluate the impact of aberrant expression of cell cycle regulators on oncological outcomes in clear cell renal carcinoma (ccRCC). Methods: After obtaining IRB approval, immunohistochemistry for Cyclin D, Cyclin E, p16, p21, p27, p53, p57, and Ki-67 was performed on tissue microarray constructs of patients treated with radical or partial nephrectomy for ccRCC between 1997-2010. Comprehensive clinical and pathologic data elements were collected. A prognostic marker score (MS) was defined as favorable if ≤4 biomarkers were altered; unfavorable if >4 biomarkers were altered. The relationship between MS and aggressive pathological features and oncological outcomes was evaluated. Results: The study included 452 patients, 277 males (61%). Median age was of 57 years (range, 17-85) and median follow up of 20 months (range, 0-150). The tumors demonstrated extrarenal extension (pT3-T4) in 120 (27%) patients and advanced grade (G 3/4) in 169 (37%). Regional nodal involvement and systemic metastases at the time of nephrectomy was present in 22 (5%) and 51(11%) patients, respectively. Unfavorable MS was found in 80 (18%) patients and was associated with distant and nodal metastasis, advanced T stage, advanced grade, tumor necrosis, sarcomatoid differentiation, lymphovascular invasion, fat invasion, adrenal involvement, and presence of venous thrombus (p < .05). A statistically significant correlation between unfavorable MS and disease recurrence (HR 6.5 and p = 0.01) and a correlation approaching significance with cancer specific mortality (HR 3.4 and p = 0.06) was demonstrated in Kaplan Meier survival analysis. In a multivariate Cox regression analysis, unfavorable MS was an independent predictor of disease recurrence (HR 2.268, CI 1.00-5.12 p = 0.049). Conclusions: The cumulative number of aberrantly expressed cell cycle biomarkers correlates with aggressive pathological features and inferior oncologic outcomes. Our findings support prospective pathway-based exploration of biomarkers to augment current clinico-pathologic predictors of oncologic outcomes in ccRCC.

multivariate analysis identified age more than 60 years, preoperative eGFR, and type of surgery as independent predictors of postoperative eGFR

multivariate analysis identified age more than 60 years, preoperative eGFR, and type of surgery as independent predictors of postoperative eGFR

Background The management of patients with renal cell carcinoma (RCC) with venous tumor thrombus (VTT) is challenging. We report our 15 year experience in the management of patients with RCC with VTT utilizing a multidisciplinary team approach, highlighting improved total and specifically Clavien III-V complication rates. Methods We reviewed the records of 146 consecutive patients who underwent radical nephrectomy with venous thrombectomy between 1998 and 2012. Data on patient history, staging, surgical techniques, morbidity, and survival were analyzed. Additionally, complication rates between two surgical eras, 1998–2006 and 2006–2012, were assessed. Results The study included 146 patients, 97 males (66 %), and a median age of 61 years (range, 24–83). Overall complications rate was 53 %, high grade complications (Clavien III -V) occurred in 10 % of patients. Most importantly, there was a lower incidence of overall and high grade complications (45 % and 8 %, respectively) in the last 6 years compared to the earlier surgeries included in the study (67 % and 13 % respectively) [p = .008 and .03, respectively). 30 day postoperative mortality was 2.7 %. 5 year overall survival (5Y- OS) and 5 year cancer specific survival (5Y- CSS) were 51 % and 40 %, respectively. Metastasis was the only independent predictor factor for CSS (HR 3.8, CI 1.9-7.6 and p