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663 Background: Intratumoral heterogeneity (ITH) relates to aggressiveness in clear cell renal cell carcinoma (ccRCC), the most common and aggressive subtype of kidney cancer. Percutaneous biopsies have high diagnostic accuracy. However, ITH lowers their reliability in larger, heterogeneous tumors. Haralick texture features extracted from a gray level co-occurrence matrix (GLCM) is a robust method to assess intrinsic tumor imaging characteristics. Some of these features, including entropy as a measure of ITH, have recently been used in differentiating malignant from benign tumors in various organs. We aim to understand how tumor entropy extracted from magnetic resonance (MR) imaging correlate with tumor grade (aggressiveness) and gene expression heterogeneity in ccRCC. Methods: This IRB-approved, prospective study included T2-weighted (T2W) and arterial spin labeled (ASL) MR images of 62 patients with ccRCC. The GLCM was constructed for regions-of interest (ROI) within the tumor and 13 Haralick texture features were estimated. Correlations between texture features and tumor grade were evaluated by logistic regression and quantified by the area under the receiving operating characteristic (ROC) curve (AUC). RNA sequencing of 182 tumor samples in 49 resected tumors was performed. Entropy was correlated with standard deviation (SD) of normalized gene expression levels in multiple samples from the same tumor. Spearman correlation (rho) was computed for each gene. False discovery rate q values < 0.05 were considered statistically significant. Results: Entropy was higher in high-grade than low-grade tumors (11.28 ± 0.52 vs. 10.95 ± 0.65) on T2W (q = 0.028) and ASL (10.45 ± 1.15 vs. 9.65 ± 1.29) (q = 0.013). Entropy had an AUC of 0.70 (T2) for high-grade prediction and was weakly correlated with tumor size (R2 = 0.2). Higher T2 and ASL entropy correlated with higher SD of gene expression. Gene ontology analysis of top correlated genes revealed strong enrichment of genes in metabolic processes. Conclusions: Higher MRI entropy predicts high tumor grade and correlates with increased heterogeneity in gene expression of metabolic processes.

Objectives To prospectively test whether a panel of biomarkers could identify patients with organ-confined disease likely to be upstaged at radical cystectomy (RC), as retrospective studies have found that cell-cycle- and proliferation-related biomarkers can help improve prognostic accuracy after RC. Patients and Methods We prospectively performed p53, p21, p27, Ki67, and cyclin E1 immunohistochemical staining on transurethral resection of the bladder (TURB) specimens from 87 patients treated with RC for organ-confined urothelial carcinoma of the bladder (UCB). The number of altered biomarkers was categorised as ‘favourable’ (≤2 altered markers) or ‘unfavourable’ (>2). Results Expression of p53, p21, p27, cyclin E1, and Ki67 were altered in 61 (70%), 19 (22%), 26 (30%), four (5%), and 70 (80%) patients, respectively. The median number of positive markers was two. In all, 47 (54%) patients were upstaged when T-stage was considered alone and 49 (56%) when T- and/or N-stage were considered both as upstaging. In multivariable analyses that adjusted for the effects of age, clinical stage, concomitant carcinoma in situ, and time from TURB to RC, an ‘unfavourable’ biomarker score was independently associated with T-stage upstaging (hazard ratio [HR] 3.3, P = 0.024) but not T- and/or N-stage upstaging (HR 2.76, P = 0.06). Addition of p27, number of positive markers, and biomarker score each increased the discrimination of a base model for prediction of T-stage upstaging (5%, 6%, and 5%, respectively) and T- and/or N-stage upstaging (4%, 6%, and 3%, respectively). Conclusions Cell-cycle- and proliferation-related markers in the TURB specimen improve the prediction of upstaging at RC. Such a marker panel may help identify patients with non-muscle-invasive UCB who are clinically under-staged needing RC and patients with muscle-invasive UCB who are likely to be non-organ-confined thereby potentially benefiting from neoadjuvant chemotherapy.

Objective To evaluate our 5-year experience with deep lateral transurethral incisions of bladder neck contracture (TUIBNC), identify risk factors associated with failure of procedure, and assess outcomes of men subsequently treated for concomitant or de novo stress urinary incontinence (SUI). Materials and Methods We reviewed 50 consecutive patients who underwent TUIBNC between June 2007 and January 2012. TUIBNC was standardized to include initial dilation followed by deep transurethral incisions. All patients were evaluated cystoscopically after a 2-month interval; those with recurrent bladder neck contracture (RBNC) underwent a second TUIBNC. For patients with concomitant SUI, we assessed the timing between TUIBNC and subsequent artificial urinary sphincter (AUS) placement and its outcome. Perioperative characteristics were reviewed to identify factors associated with failure. Results Of the 50 patients analyzed, most were refractory, 78% having failed previous TUIBNC. After TUIBNC, 72% required no further surgery for obstruction at a mean follow-up of 12.9 months. Of the 14 who failed initial TUIBNC, 7 underwent repeat TUIBNC with success, representing an overall success rate of 86% after 2 procedures. Significant factors associated with treatment failure were >10 pack/year smoking history (P = .039) and ≥2 previous endoscopic BNC procedures (P = .03). Of 39 men (78%) with concomitant SUI, two-thirds underwent AUS placement after an average of 2.9 months after TUIBNC. Only 2 of 26 (8%) patients required repeat transurethral procedures after AUS placement for RBNC. Conclusion Deep lateral TUIBNC alone is a highly effective treatment modality for RBNC. Smokers and those having 2 or more previous transurethral procedures appear to have greater risk for failure. Subsequent AUS placement can be safely performed with >90% long-term urethral patency.

PURPOSE OF REVIEW To give insight into the current literature on feasibility, safety and outcome of presurgical targeted molecular therapies (TMTs) before nephron-sparing surgery (NSS) in patients with renal cell carcinoma. RECENT FINDINGS Presurgical TMTs have been proven to be effective and well tolerated for patients with previously unresectable primary tumors and known metastatic disease. Current evidence suggests that this also is true for patients with bulky tumors not amenable to NSS, but with imperative indications for NSS like solitary kidney, bilateral tumors, pre-existing chronic kidney disease, or tumor predisposing syndromes. TMT is generally well tolerated in this regimen and complication rates around surgery are low when TMT is withheld around the half-life time of the agent used. SUMMARY In selected cases, TMT before NSS is well tolerated, effective and feasible. Still, this topic is considered experimental because it has not been thoroughly studied to fully assess the indications, the timing of therapy, and its effect on outcomes. Further evidence is needed to draw definitive conclusions.

Objective To validate the impact of Ki67 expression on oncological outcomes of patients treated for clinically localized clear-cell renal cell carcinoma (ccRCC). Patients and Methods Immunohistochemistry for Ki67 was performed on tissue microarray constructs of patients treated with radical or partial nephrectomy for clinically localized (M0) ccRCC and Ki67 expression >10% was considered abnormal. Clinical and pathological data elements were entered into an institutional review board-approved database. The Kaplan–Meier method and Cox regression models were used to analyse disease-free survival (DFS) and cancer-specific survival (CSS) probabilities. Results Of 401 patients, 59.6% were males. The median (range) age was 58 (17–85) years, follow-up was 22 (0–150) months and time to death was 27 (0–150) months. A total of 20.2% of patients had advanced stage (pT3–T4) and 31% had advanced grade (3–4) disease. Abnormal expression of Ki67 was seen in 6.5% of our cohort and was associated with adverse pathological features (P < 0.05). Patients with high expression of Ki67 were found to have 5-year DFS and CSS rates of 67 and 84%, respectively, vs 87 and 95%, respectively, in those with normal expression (P < 0.001 and P < 0.05, respectively). In multivariable analyses, adjusting for stage and grade, abnormal Ki67 expression was an independent predictor of DFS (hazard ratio [HR] 3.77, P = 0.011, 95% confidence interval [CI] 1.35–10.52), but not of CSS (HR 3.51 P = 0.137, 95% CI 0.671–18.35). Conclusions Our findings support the role of Ki67 as a powerful independent predictor of inferior oncological outcomes in patients with ccRCC. Further prospective studies are needed to determine the clinical applicability of these findings.

Objective To report an international, multi-institutional series of laparoendoscopic single-site pyeloplasty (LESS-P) with analysis of functional outcomes. Materials and Methods LESS-P cases performed between October 2007 and June 2012 at 7 institutions worldwide per individual institutional protocols, entry criteria, and techniques were included. Patient characteristics, operative indications, perioperative outcomes, and postoperative follow-up were retrospectively collected and analyzed. Results The study included 140 adult patients (age 39.9 ± 15.7 years; body mass index 24.8 ± 4.2 kg/m 2 ; 15% with previous abdominal surgery) who underwent unilateral LESS-P, most of whom (94.3%) had dismembered reconstructions. Mean operative time was 202.1 ± 47 minutes with an estimated blood loss of 61.2 ± 44.6 mL. Robotic laparoendoscopic single-site surgery was applied in 31 patients (22.1%). A single 2-3 mm accessory port was used in 44 patients (31.4%) and a single 5-12 mm accessory port was added in 9 patients (6.4%), whereas 10 patients (7.1%) were converted to conventional multiport laparoscopy. No patients required conversion to open surgery, nor were any intraoperative complications reported. Length of hospitalization was 2.4 ± 1.6 days. The overall 90-day postoperative complication rate was 18.6%, mostly low-grade complications (Clavien I-II). With a mean follow-up of 14.0 ± 10.8 months, 93.4% had resolution of symptoms and 94.4% had radiographic evidence demonstrating resolution of ureteropelvic junction obstruction. Assessment of drainage with diuretic nuclear renal scan provided evidence of improvement in 86.5% of patients on their first postoperative renal scan. Conclusion This study highlights the most comprehensive experience with LESS-P reported to date. Outcome measures parallel those of large published series of conventional laparoscopic pyeloplasty. Despite these encouraging findings, longer follow-up is needed to determine the efficacy and durability of this approach for the treatment of ureteropelvic junction obstruction.

Patients with renal cell carcinoma who present with pulmonary embolism and venous thrombus may not be offered surgery because of presumed poor postoperative outcomes. In this multicenter study we evaluated perioperative mortality, recurrence and cancer specific survival in patients with renal cell carcinoma and venous thrombus diagnosed with preoperative pulmonary embolism.We reviewed consecutive patient records from our 3 tertiary hospitals to identify patients with renal cell carcinoma and venous thrombus treated with surgery from 2000 to 2011. Univariate and multivariate Cox proportional hazards analysis was used to evaluate whether preoperative pulmonary embolism or other clinical variables were associated with postoperative disease recurrence or cancer specific survival.Pulmonary embolism was identified preoperatively in 35 of 782 patients (4.4%) with renal cell carcinoma. Those with pulmonary embolism preoperatively were more likely to have higher level thrombus and higher T stage (p0.01). No differences were found in other clinical or pathological features between the groups. There was no difference in 90-day mortality in patients diagnosed with pulmonary embolism preoperatively. Of 395 patients without metastasis preoperatively 147 (37.2%) showed metastatic renal cell carcinoma at a median followup of 22 months. There was no difference in the recurrence rate of renal cell carcinoma in patients with pulmonary embolism (p = 0.36). Recurrence in the lung was not more common in patients with vs without pulmonary embolism preoperatively (p = 0.71). Also, preoperative pulmonary embolism was not predictive of worse cancer specific survival (p = 0.58).Preoperative pulmonary embolism is not associated with worse early mortality, recurrence or cancer specific survival in patients with renal cell carcinoma and tumor thrombus.

Objective To compare oncologic outcomes in an international cohort of patients who underwent either partial ureterectomy (PU) or radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Methods A subgroup of patients from the UTUC Collaboration with operation classified as PU or RNU was used (n = 835). Clinicopathologic outcomes were evaluated. Survival was assessed using the Kaplan-Meier method. Cox regression addressed recurrence-free survival (RFS) and cancer-specific survival (CSS). Results Median age and follow-up were 69 years (range 32-97 years) and 34 months (range 1-246 months), respectively. Relapse occurred in 28.5% of patients (19.6% local, 8.9% systemic). At analysis, 180 patients (21.6%) died of UTUC. Eighty-one patients (9.7%) underwent PU and 754 (90.3%) underwent RNU. High tumor grade (77.3% vs 55.6%, P T1, 41.7% vs 30.9%, P

We present patient reported outcomes from our 5-year experience using penile plication to correct a wide variety of Peyronie disease malformations.We reviewed the records of all men who underwent penile plication for Peyronie disease, as performed by one of us (AFM). All patients were treated with tunical plication without penile degloving via a 2 cm longitudinal penile incision regardless of curvature severity or erectile function. A concomitant inflatable penile prosthesis was placed in men with refractory erectile dysfunction. A questionnaire was administered to assess the patient perception of postoperative penile curvature, length, rigidity and adequacy for intercourse.Of 154 treated patients 78 (51%) and 65 (42%) had simple (less than 60 degrees) and complex (biplanar curvature, or curvature 60 degrees or greater) malformation, respectively, while 11 (7%) underwent plication plus inflatable penile prosthesis placement. A total of 132 patients responded to the questionnaire a mean 14 months after surgery. Overall, 96% of patients reported curvature improvement after penile plication, 93% reported erection adequate for sexual intercourse and 95% considered that the overall condition improved after surgery. Despite a significant difference in the number of plication sutures (mean 10 vs 7) and curvature angle correction (mean 57 vs 30 degrees, each p0.005), self-reported outcomes of complex cases were equivalent to those of simple cases. While 84% of patients had no measureable decrease in stretched penile length, 103 of 154 (78%) reported a perceived penile length reduction after surgery.Penile plication without degloving is effective for correcting a wide variety of Peyronie disease malformations. It can be safely combined with inflatable penile prosthesis placement.

Purpose Owing to its exquisite chemotherapy sensitivity, most patients with metastatic germ cell tumors (GCTs) are cured with cisplatin-based chemotherapy. However, up to 30% of patients with advanced GCT exhibit cisplatin resistance, which requires intensive salvage treatment, and have a 50% risk of cancer-related death. To identify a genetic basis for cisplatin resistance, we performed whole-exome and targeted sequencing of cisplatin-sensitive and cisplatin-resistant GCTs. Methods Men with GCT who received a cisplatin-containing chemotherapy regimen and had available tumor tissue were eligible to participate in this study. Whole-exome sequencing or targeted exon-capture–based sequencing was performed on 180 tumors. Patients were categorized as cisplatin sensitive or cisplatin resistant by using a combination of postchemotherapy parameters, including serum tumor marker levels, radiology, and pathology at surgical resection of residual disease. Results TP53 alterations were present exclusively in cisplatin-resistant tumors and were particularly prevalent among primary mediastinal nonseminomas (72%). TP53 pathway alterations including MDM2 amplifications were more common among patients with adverse clinical features, categorized as poor risk according to the International Germ Cell Cancer Collaborative Group (IGCCCG) model. Despite this association, TP53 and MDM2 alterations predicted adverse prognosis independent of the IGCCCG model. Actionable alterations, including novel RAC1 mutations, were detected in 55% of cisplatin-resistant GCTs. Conclusion In GCT, TP53 and MDM2 alterations were associated with cisplatin resistance and inferior outcomes, independent of the IGCCCG model. The finding of frequent TP53 alterations among mediastinal primary nonseminomas may explain the more frequent chemoresistance observed with this tumor subtype. A substantial portion of cisplatin-resistant GCTs harbor actionable alterations, which might respond to targeted therapies. Genomic profiling of patients with advanced GCT could improve current risk stratification and identify novel therapeutic approaches for patients with cisplatin-resistant disease.

(5.4% of all TC cases). In terms of ART 225 men (8.5%) with TC were prescribed testosterone. The OR of receiving a prescription was 4.5 95% CI [4.2,5.5] times higher than in men without TC and disproportionately high in younger men, with an 8.1 fold increase in the third decade of life. CONCLUSIONS: Men with a diagnosis of TC are four times more likely to have a serum testosterone checked, be diagnosed with hypogonadism, and receive ART. Serum testosterone is measured and more frequently found to be low in elderly patients with a history of TC compared to age-matched controls. Additionally, hypogonadism often predates the diagnosis of testis cancer. Finally, despite higher detection in elderly patients, ART is prescribed more often to young men with TC.

Urothelial carcinoma is a highly heterogeneous disease that can arise throughout the entire urothelial lining from the renal pelvis to the proximal urethra. Upper tract urothelial carcinoma (UTUC) is rare, and while it shares many similarities with urothelial carcinoma of bladder (UCB), there are also significant differences between UTUC and UCB regarding clinical management and outcomes. No major advances have been made recently in the development of new systemic therapies for urothelial carcinoma, partly due to the lack of understanding of underlying molecular pathogenetic mechanisms. In the past decade, the emergence of next-generation sequencing has greatly enabled genomic characterization of tumor samples. Researchers are currently exploring a personalized approach to augment traditional clinical decision-making based on genetic alterations. In the present review, we summarize current genomic advances in UTUC and discuss the potential implications of these developments for developing prognostic and predictive biomarkers.

Within the last decade, the adaptation of robotic urologic surgery has had a profound impact on surgical practice, with robotic upper tract reconstruction for ureteropelvic junction obstruction gaining rapid acceptance. Recent advances in robotic reconstruction demonstrate efficacious outcomes of robotic pyeloplasty, as compared with conventional laparoscopic pyeloplasty, even in the case of secondary surgery. Furthermore, efforts to continue to reduce the morbidity of laparoscopic surgery have led to the development and implementation of laparoendoscopic single-site (LESS) surgery. The recent applications of the da Vinci robotic surgical platform to LESS pyeloplasty (R-LESS) has demonstrated the potential to further decrease morbidity, improve surgeon ergonomics, and improve cosmesis.

We tested the hypothesis that surgeon fatigue results in worse outcomes for laparoscopic and robot-assisted laparoscopic prostatectomy, and percutaneous nephrolithotomy by comparing outcomes of sequentially scheduled procedures.We identified days when 2 procedures of the same type were performed by the same surgeon, including 72 laparoscopic and 340 robot-assisted laparoscopic prostatectomies, and 110 percutaneous nephrolithotomies. Clinical data and outcomes were compared.For percutaneous nephrolithotomy multiple access (16% vs 9%, p = 0.2), transfusion (3.6% vs 5.4%, p = 0.5), complication (20% vs 18%, p = 0.5), residual fragment (53% vs 45%, p = 0.3), second look (38% vs 35% p = 0.4) and stone-free (86% vs 89% p = 0.3) rates did not differ for the first and second procedures. For laparoscopic prostatectomy nerve sparing (100% vs 97.1%, p = 0.5), operative complications (0% vs 0%, p = 0.7), drain requirement (36% vs 42%, p = 0.6) and lymphadenectomy (13.5% vs 25.7%, p = 0.16) rates were comparable. Positive margins (19.4% vs 36.1% p = 0.08), continence (66.7% vs 66.7%, p = 0.9), potency (58.3% vs 52.8%, p = 0.76) and prostate specific antigen recurrence (10.8% vs 20%, p = 0.45) did not significantly differ for the first and second procedures. For robot-assisted laparoscopic prostatectomy operative complications (3% vs 3.5%, p = 0.8), drain requirement (7.7% vs 9.8%, p = 0.5), positive margins (41.7% vs 39.3%, p = 0.37), continence (78.6% vs 84.4%, p = 0.12), potency (51% vs 50%, p = 0.15) and prostate specific antigen recurrence (9.5% vs 11.6%, p = 0.2) did not significantly differ. Nerve sparing was more common in the second case cohort (86.9% vs 75.7%, p = 0.03).Despite concern that surgeon fatigue may impact outcomes, our data suggests that performing several complex urological procedures consecutively is not associated with worse outcomes.

Purpose of review Small renal masses (SRMs) are frequently encountered due to the ubiquitous use of abdominal cross-sectional imaging. Enhanced risk prediction in the management of SRMs would allow for a more informed decision of which, if any, patients would benefit from the available intervention modalities. Recent findings Data suggest that a substantial proportion of SRMs are benign and that a significant proportion demonstrate indolent clinical behavior, leading to increased implementation of active surveillance strategies. Extirpative treatment of SRMs may be associated with worse outcomes, particularly in the elderly and infirm. Patient characteristics, including advanced age and comorbidity, and tumor anatomy are being increasingly recognized as having significant prognostic importance in terms of which type of treatment to offer. Further, a recent renewed interest in renal mass biopsy for risk stratification in SRMs has occurred as tumor size, radiographic characteristics, and growth kinetics are limited in their predictive capacity. Summary Within the last decade, the reference standard treatment of SRMs evolved from radical nephrectomy to nephron-sparing approaches. This evolution continues, as we learn more about the complex interplay between patient and tumor characteristics and, as outcomes data mature, to ablative therapies and active surveillance.

Study Type – Therapy (prospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Erectile dysfunction (ED) is a form of endothelial dysfunction that is prevalent in patients with chronic kidney disease (CKD). We hypothesized that partial nephrectomy (PN) would limit development of ED compared with radical nephrectomy (RN), primarily due to renal function preservation, and found that patients undergoing RN had significantly higher de novo ED compared with a contemporary, well-matched cohort undergoing PN; in addition to RN, hypertension, CKD and diabetes mellitus were associated with developing ED. To our knowledge, this is the first study demonstrating an increased risk of ED after RN compared with PN. OBJECTIVES • To evaluate prevalence and risk factors for development of erectile dysfunction (ED) in patients who underwent radical nephrectomy (RN) and partial nephrectomy (PN). • ED is a form of endothelial dysfunction that is prevalent in patients with chronic kidney disease (CKD). PN confers superior renal functional preservation compared with RN; however, the impact on ED is unclear. METHODS • This was a retrospective study of 432 patients (264 RN/168 PN, mean age 58 years, mean follow-up 5.8 years) who underwent surgery for renal tumours between January 1998 and December 2007. • The primary outcome was rate of de novo ED postoperatively. Secondary outcomes included development of CKD (estimated GFR < 60 mL/min/1.73 m2) and response to phosphodiesterase-5 inhibitors. • Multivariate analysis was performed to determine risk factors for de novo ED postoperatively. RESULTS • RN and PN groups had similar demographics and comorbidities. • Tumour size (cm) was larger for RN (RN 7.0 vs PN 3.7, P < 0.001) and more preoperative ED existed in PN vs RN (P= 0.042). No differences were observed for preoperative CKD, hyperlipidaemia and diabetes mellitus. • Postoperatively, higher rates of de novo ED (29.5% vs 9.5%, P < 0.001) and CKD (33.0% vs 9.8%, P < 0.001) developed in RN vs PN cohorts, respectively. • Of men with ED, 63% responded to phosphodiesterase inhibitors, without significant difference between the two groups (P= 0.896). • Multivariate analysis demonstrated de novo ED to be associated with RN (odds ratio [OR] 3.56, P < 0.001), hypertension (OR 2.32, P= 0.014), preoperative (OR 8.77, P < 0.001) and postoperative (OR 2.64, P= 0.001) CKD, and postoperative diabetes mellitus (OR 2.93, P < 0.001). CONCLUSIONS • Patients undergoing RN had significantly higher de novo ED compared with a contemporary, well-matched cohort undergoing PN. In addition to RN, hypertension, CKD and diabetes mellitus were associated with developing ED. • Further investigation on effects of surgically induced nephron loss on ED is requisite.

OBJECTIVE To examine the incidence of and risk factors for the development of anaemia and erythropoiesis-stimulation agent (ESA) treatment in patients undergoing radical nephrectomy (RN) and partial nephrectomy (PN) because anaemia is a significant cause of morbidity in chronic kidney disease. PATIENTS AND METHODS The study comprised a retrospective review of 905 patients (610 RN/295 PN; mean age, 57.5 years; mean follow-up, 6.4 years) who underwent surgery for renal tumours at two institutions from July 1987 to June 2007. Demographics, disease characteristics and pre- and postoperative (i.e. renal function, metabolic parameters, anaemia and ESA treatment) were recorded. Data were analyzed within subgroups based on treatment (RN vs PN). Multivariate analysis was conducted to determine the risk factors for developing anaemia after surgery. RESULTS Tumour size (cm) was significantly larger for RN (RN 7.0 vs PN 3.7; P < 0.001). No significant differences were noted with respect to demographics and preoperative anaemia (RN 16.4% vs PN 18.6%; P = 0.454) and ESA-treatment (RN 0.7% vs PN 1.4%; P = 0.499). After surgery, significantly less de novo anaemia (PN 4.1% vs RN 17.5%; P < 0.001) and ESA utilization (PN 2.7% vs RN 13.4%; P < 0.001) occurred in the PN cohort. Multivariate analysis showed that age ≥60 years (odds ratio, OR, 1.62; P = 0.008), African American ethnicity (OR, 2.30; P < 0.001), smoking (OR, 1.60; P = 0.013), glomerular filtration rate (GFR)

To examine incidence of and risk factors for development of osteoporosis and fractures in patients who underwent radical nephrectomy (RN) and partial nephrectomy (NSS), as osteoporosis is an important cause of morbidity in chronic kidney disease.This was a retrospective review of 905 patients (mean age 57.5 years, mean follow-up 6.4 years) who underwent RN or NSS for renal tumors at 2 institutions from July 1987 to June 2007. Demographics, renal function, metabolic parameters, and history of preoperative and postoperative osteoporosis and fractures were recorded. Data were analyzed within subgroups based on treatment (RN vs NSS). Multivariate analysis was conducted to elucidate risk factors for developing osteoporosis following surgery.A total of 610 patients underwent RN and 295 underwent NSS. Tumor size (cm) was significantly larger for RN (RN 7.0 vs NSS 3.7, P.0001). No significant differences were noted with respect to demographic factors and preoperative osteoporosis (RN 8.7% vs NSS 9.5%, P=.785) and fractures (RN 1.7% vs NSS 0.7%, P=.382). Postoperatively, significantly less osteoporosis (NSS 12.5% vs RN 22.6%, P.001) and fewer fractures (NSS 4.4% vs RN 9.8%, P=.007) developed in the NSS cohort. MVA demonstrated female (OR 1.85, P=.001), Caucasian (OR 2.33, P.0001), preoperative eGFR60 mL/min/1.73 m2, (OR=3.02, P.0001), preoperative metabolic acidosis (OR=4.22, P=.0006), and RN (OR 2.59, P.0001) were risk factors for developing osteoporosis.Patients undergoing RN had a significantly higher incidence of osteoporosis and fractures compared with a well-matched cohort of patients who underwent NSS. In addition to RN, female gender, Caucasian background, preoperative eGFR60, and preoperative metabolic acidosis were associated with developing osteoporosis.

Purpose To describe robot-assisted complex reconstruction of the lower urinary tract in children with neurogenic bladder and sphincteric incompetence. Patients and methods Four sequential patients with spinal dysraphism, neurogenic bladder, and sphincteric incompetence based on urodynamic parameters had persistent urinary incontinence on maximal anticholinergic therapy and clean intermittent catheterization (CIC). They underwent robot-assisted Mitrofanoff appendicovesicostomy along with Leadbetter/Mitchell bladder neck reconstruction and bladder neck sling. All patients received cystography 3 weeks postoperatively. Patient demographics, medical history, perioperative parameters, and urinary continence status were collected prospectively. Results Mean predicted bladder capacity was 353 mL (range 210-450 mL) while actual preoperative bladder capacity was 216 mL(range 180-275 mL). Preoperatively, one-patient demonstrated uninhibited bladder contractions; none had trabeculated bladders. Mean detrusor leak point pressure was 29 cm H(2)0. Three of four (75%) cases were completed robotically; one necessitated conversion to open and Monti channel creation because of a marginal appendix. Mean operative time (hours:minutes) was 7:45 (range 5:56-12:18). Mean length of stay and blood loss were 85.7 hours and 117.8 mL, respectively. Postoperatively, all patients were completely dry on CIC and anticholinergics. None of the bladders demonstrated trabeculation on follow-up cystography. Unilateral de novo grade II vesicoureteral reflux developed in two patients, and anticholinergics were dose escalated. Conclusion Our initial series of robot-assisted appendicovesicostomy with bladder neck reconstruction and sling placement expands the scope of complex robotic reconstruction in children. The preliminary data demonstrate the procedure to be feasible and safe. Comparison with traditional "open" series of the same procedure is necessary.

Objectifs Apres le traitement d’une tumeur de la voie excretrice urinaire superieure (TVES), les tumeurs de vessie (TV) sont frequentes, avec une incidence de 22 a 47 %. Plusieurs theories s’opposent pour expliquer leur origine : monoclonalite par dispersion intraluminale et implantation cellulaire ou oligoclonalite par cancerisation en plage de l’urothelium. L’objectif de cette etude etait de comparer le profil moleculaire entre TVES et TV metachrones. Methodes Nous avons sequence la tumeur et l’ADN germinal correspondant de 137 patients avec une tves traitee par nephroureterectomie en utilisant une plateforme de sequencage de nouvelle generation basee sur la capture ciblee d’un panel de 341 oncogenes. Les mutations somatiques ont ete analysees en fonction du risque de recidive vesicale. Pour un sous-groupe de 29 patients avec une TV metachrone, TVES et TV ont ete comparees chez le meme patient pour definir leur clonalite. Resultats Au total, 57 patients (42 %) ont developpe une tumeur de vessie apres nephroureterectomie, avec un delai median de 7,3 mois (IQR : 4,1–13,7). Apres ajustement pour le sexe, les antecedents de TV, la localisation, le grade et le stade tumoral, les mutations de FGFR3 (hr = 3,00 ; 95 % IC : 1,58–5,68 ; p = 0,001), KDM6A (hr = 2,27 ; 95 % IC : 1,29–4,02 ; p = 0,005) et CCND1 (hr = 3,10 ; 95 % IC : 1,17–8,21 ; p = 0,023) etaient significativement associees au risque de recidive vesicale, alors que les mutations de TP53 etaient significativement associees a une reduction du risque (hr = 0,32 ; 95 % IC : 0,13–0,80 ; p = 0,014). Chez les 29 patients presentant les 2 tumeurs de maniere metachrone, TVES et TV etaient toujours clonales ( Fig. 1 ). Conclusion Alors que TVES et TV presentent des differences significatives dans la prevalence des mutations somatiques, chez un meme patient presentant les 2 tumeurs, TVES et TV sont clonales. Cela implique une meilleure prevention du risque de dissemination intraluminale en peroperatoire, notamment pour les tumeurs presentant des facteurs de risque moleculaires.

Objectives To evaluate the usage of surgical staging of inguinal lymph nodes (SSILNs) in the United States for intermediate to high-risk, clinically localized penile squamous cell cancer (SCC), to explore patient and hospital factors associated with omission of this staging, and to evaluate the effect on survival. Patients and methods Retrospective, observational study using the National Cancer Database from 2004 to 2014 of 1,689 men diagnosed with pT1b–T3, cN0 penile SCC, who by current guidelines should receive SSILNs—either by inguinal lymph node (ILN) dissection or sentinel node biopsy. Binomial logistic regression analysis was performed to determine predictors of SSILNs. Multivariate Cox regression analysis was performed to determine the impact of SSILNs on survival in the overall and propensity-score matched patient populations. Results Only 25.3% of patients underwent SSILNs. Increasing patient age, higher comorbidity status, lower pathologic stage, Medicaid insurance, and treatment at a nonacademic facility were independent factors associated with the omission of SSILNs. Omission of SSILNs was an independent predictor of overall mortality, both in the overall patient population after multivariate adjustment, HR = 1.46 [(95% CI: 1.14–1.88), P = 0.003], and in the propensity-score matched adjusted population, HR = 1.59 [(95% CI: 1.20–2.13), P = 0.001]. Limitations include an inability to distinguish biopsy from ILN dissection and those inherent in observational study design. Conclusion Utilization of SSILN for penile SCC is low and has not changed significantly since the publication of guidelines in the United States. In particular, nonacademic institutions were less likely to adhere to recommendations for performance of SSILNs. We found the omission of SSILNs is associated with a significant increase in mortality.

502 Background: Impaired DDR is associated with response to platinum-based chemotherapy. Several genomically directed trials have been proposed using DDR alteration status for enrolment. In this study, we characterized the deleterious DDR alteration (DDRa) landscape of UCB across various clinical states. Methods: Targeted exon capture and sequencing of at least 341 cancer-associated genes was performed prospectively on 451 UCB specimens (MSK-IMPACT assay). We assessed sequencing data for deleterious alterations in 34 genes representing canonical DDR pathways. Deleterious alterations included truncating mutations, homozygous deletions, and functionally validated missense mutations. Results: Table 1. In NMIBC, deleterious DDRa were enriched in high-grade disease ([39/136, 28.7%] high grade vs. low-grade [2/28, 7.1%]; p=0.02). The frequency of deleterious DDRa in chemo-naïve MIBC was enriched relative to unmatched post-neoadjuvant chemotherapy (NAC) residual MIBC ([33/112, 29.5%] vs. [8/55, 14.5%]; p=0.01). Patients with metastatic disease had similar rates of deleterious DDRa to MIBC ([31/116, 26.7%] vs. [33/112, 29.5%]). The percentage of patients having any type of DDR alteration was similar across states. The proportion of patients with a deleterious DDRa relative to any DDRa was 41/77 (53.2%) in NMIBC, 33/65 (50.8%) in chemo-naïve MIBC, 8/27(29.6%) in post-NAC residual MIBC, and 31/68 (45.6%) in metastatic disease. Conclusions: DDRa are found across the UCB disease spectrum. ERCC2 and ATM are the most common DDRa although alterations were seen in most other DDR genes. Many alterations are of unknown significance and further characterization is needed to develop genomically directed treatment. [Table: see text]

586 Background: Targeted therapy (TT) is the first-line option for metastatic renal cell carcinoma (mRCC) however, it is not curative and associated with a high-cost and adverse events. Preliminary data suggests TT may be safely delayed in appropriately selected patient, however the utilization and impact of delayed TT has not been evaluated on larger-scale. Methods: The National Cancer Database (NCDB) was queried from 2006-2012 for patients with mRCC treated with cytoreductive nephrectomy and TT. Time to initiation of TT was defined as ‘early’ (within 2 months), ‘moderately delayed’ (2-4 months), and ‘delayed’ (4-6 months), and ‘late’ ( > 6 months) based on time from diagnosis to initiation of therapy. Multivariable logistic regression was performed to determine factors associated with delayed TT. The impact time to initiation of TT on OS was estimated by Kaplan-Meier and Cox multivariable survival analysis. Results: For2,716 patients in the analysis, the median (interquartile range [IQR]) follow-up was 18.8 (9.1-32.9) months, and 71.8% of patients had died at last follow-up. The median (IQR) time from diagnosis to initiation of TT was 2.1 (1.3-3.23) months, with the longest delay being 20.1 months. 1,255 patients (46.2%) had early TT, 1,072 patients (39.5%) had moderately delayed TT, 284 patients (10.5%) had delayed TT, and 105 patients (3.9%) had late TT. Delay in TT was not found to be a predictor of mortality in multivariable analysis; early TT (reference), moderately delayed TT (HR 0.98, p = 0.74), delayed TT (HR 0.95, p = 0.51), and late TT (HR 0.86, p = 0.20). Time from diagnosis to initiation of TT and time from initiation of TT to patient death were not correlated after control for covariates ( r= 0.04, p = 0.08). Conclusions: Delay in initiation of TT for mRCC was not an independent predictor of worse OS. Although this study is subject to limitations of observation study design and selection bias, the results are consistent with the notion that in carefully selected patients, outcomes might not be compromised with initial observation. Prospective, randomized evaluation is warranted.

Study Type – Prevalence (retrospective cohort) Level of Evidence 2b OBJECTIVE To examine incidence of and risk factors for the development of nephrolithiasis in patients treated with radical nephrectomy (RN) or partial nephrectomy (nephron-sparing surgery, NSS). PATIENTS AND METHODS The study comprised a single-centre review of 749 patients treated with RN or NSS from August 1987 to June 2006. Demographics, medical and stone history, metabolic variables and postoperative stone events were recorded. Data were analysed within subgroups based on treatment (RN vs NSS). Multivariate analysis was used to identify risk factors for postoperative stone formation. RESULTS In all, 499 patients had RN and 250 had NSS (mean age 57.9 years; mean follow-up 6.3 years). There were no significant differences in their demographic factors, but tumours were significantly larger in RN (P < 0.001). There was no significant difference in preoperative urinary pH < 6.0 or stone history. Significantly fewer patients after NSS than RN formed calculi (NSS 1.6% vs RN 8.4%, P < 0.001), developed hypobicarbonataemia (NSS 7.2% vs RN 12.8%, P= 0.020), and a urinary pH of

Given the rarity of testicular germ cell tumors (TGCTs) and the complex aspects of management, we evaluate the effect of hospital TGCT case volume on overall survival outcomes and practice patterns.The National Cancer Database was queried for patients diagnosed with seminoma or nonseminomatous germ cell tumor (NSGCT). Hospitals were classified by case volume as high (99th percentile, ≥26.1 cases annually), high-intermediate (95-99th percentile, 14.6-26.0 cases annually), intermediate (75-95th percentile, 6.1-14.5 cases annually), low-intermediate (25-75th percentile, 1.8-6.0 cases annually), and low (25th percentile,1.8 cases annually). The median (interquartile range) number of TGCT cases per institution per year was 3.4 (1.8-6.1).A total of 33,417 patients with TGCT diagnosed from 1,239 institutions met inclusion criteria. Despite worse disease characteristics of patients treated at higher volume institutions, hospital volume was positively associated with survival outcomes in more advanced cases of TGCT. In the overall cohort, compared to the high-volume hospitals, patients treated at high-intermediate, intermediate, low-intermediate, and low volume hospitals the hazard ratio for overall mortality was 1.28, 1.45, 1.48, and 1.83, respectively (P0.05). The association between survival and hospital volume was not apparent for seminoma or stage I NSGCT. Patients treated at higher volume hospitals were more likely to undergo surveillance for stage I seminoma, primary retroperitoneal lymph node dissection (RPLND) for stage I NSGCT, and postchemotherapy RPLND for stage II/III NSGCT.Our analysis of a nationwide cancer registry demonstrated that increased hospital TGCT case volume was associated with significant differences in management strategies and improved survival outcomes, in particular for more advanced disease.

Objectives To compare oxygenation profiles and renal function outcomes between 3 methods of vascular control during porcine partial nephrectomy. Methods To create a solitary kidney model, 18 pigs were subjected to a laparoscopic nephrectomy. Following a 7-day recovery, a contralateral open partial nephrectomy was performed with vascular control by either total renal artery clamping (TRAC, n=6), partial renal artery clamping (PRAC, n=6), or selective renal parenchymal clamping (SRPC, n=6). Renal partial oxygen pressure (rPO 2 ) was monitored using a Licox probe. Serum creatinine was assessed on day 0 and postoperative days 3 and 7. Pigs were sacrificed on the seventh day and the kidney sent for pathological examination. Results Intraoperative oxygenation profiles demonstrated a lower percentage decline ( P = .01), longer interval to nadir ( P = .04), improved percentage recovery of baseline rPO 2 ( P = .04), and a shorter duration to recover baseline rPO 2 ( P = .03) in the PRAC and SRPC groups than in the TRAC. Despite not occluding the renal vasculature, the SRPC group experienced declines in rPO 2 profiles of almost 50% from baseline. Serum creatinine levels increased significantly more in the TRAC group at days 3 and 7 ( P = .04 and .01, respectively). Histological examination demonstrated patchy inflammation of parenchyma in all groups. Conclusions The rPO 2 monitoring may provide a novel means to allow real-time assessment and titration of kidney perfusion during partial nephrectomy. PRAC and SRPC demonstrate favorable renal oxygenation profiles compared with TRAC. Interestingly, SRPC kidneys experienced a significant decline in tissue oxygenation profiles. Further work is necessary to better delineate the mechanism underlying this decline.

Purpose: We compared patient and urologist perceptions regarding the medical management of stone disease.Materials and Methods: A total of 159 patients were prospectively interviewed. Patients were asked 3 questions concerning subjective tolerance of stone passage and surgical intervention weighed against the use of daily preventive medication. The same questions were sent to members of the Endourological Society.Results: Mean ± SD patient age was 51 ± 14 years. Recurrent stone formers comprised 72% of patients and 76% had undergone a prior surgical procedure while 43% were taking prophylactic medication. Overall 81% and 88% of patients responded that they would rather take medication than tolerate a single stone event at home or in the emergency room, respectively. Likewise 92% of patients stated that they would prefer daily medication compared to any surgical procedure. Among 61 urologists 26%, 38% and 18% responded that patients would likely tolerate 1, 2 or an unlimited number of stone passages at hom...

OBJECTIVE To investigate the incidence of and risk factors for developing chronic renal insufficiency (CRI), proteinuria and metabolic acidosis (MA) in patients treated with radical nephrectomy (RN) or nephron-sparing surgery (NSS). PATIENTS AND METHODS We retrospectively reviewed 749 patients (mean age 57.7 years; mean follow-up 6.4 years) who had RN or NSS for renal tumours between July 1987 and June 2006 at our institution. The demographics and outcomes were analysed and recorded. The primary outcome variable was the development of an estimated glomerular filtration rate (eGFR) of

Background Recent reports have suggested that single-port or single-incision laparoscopic surgery (SILS) is technically feasible. Objective To present a comparison between SILS and conventional laparoscopic nephrectomy with respect to perioperative outcomes and short-term measures of convalescence. Design, setting, and participants This was a case-control study comparing 11 SILS nephrectomies (cases) and 22 conventional laparoscopic nephrectomies (controls) performed from September 2004 to April 2008. The control group was matched in a 2:1 ratio to SILS cases with respect to patient age, surgical indication, and tumor size. Intervention A single surgeon performed all SILS nephrectomy cases using three adjacent 5-mm trocars inserted through a single 2.5-cm periumbilical incision. Measurements Demographics, operative time, blood loss, perioperative complications, transfusion requirement, decrease in serum hemoglobin, analgesic requirement, length of stay, and final pathology were compared. Results and limitations Mean patient age was 53 yr for both groups, with more females in the SILS cohort (82% vs 41%). Nephrectomy was performed for benign disease in 45% of the cases. Median tumor size was 5.5cm for both groups, and all but one suspected malignancy was renal cell carcinoma on final pathology. There was no difference between SILS and conventional laparoscopy cases in median operative time (122min vs 125min, p =0.78), percent decrease from preoperative hemoglobin (14.1% vs 15.8%, p =0.52), analgesic use (8 morphine equivalents vs 15 morphine equivalents, p =0.69), length of stay (49h vs. 53h, p =0.44), or complication rate (0% for both). The SILS group did have a lower recorded median estimated blood loss (20ml vs 100ml, p =0.001). This study is retrospective and is susceptible to all limitations and biases inherent in such a design. Conclusions SILS nephrectomy is feasible with perioperative outcomes and short-term measures of convalescence comparable to conventional laparoscopic nephrectomy. Although SILS may offer a subjective cosmetic advantage, prospective comparison is needed to more clearly define its role.

Evolution of minimally invasive techniques has prompted interest in natural orifice transluminal endoscopic surgery (NOTES). Challenges for NOTES include loss of instrument rigidity, reduction in working envelopes, and collision of instrumentation. Magnetic anchoring and guidance system (MAGS) is one surgical innovation developed at our institution whereby instruments that are deployed intra-abdominally are maneuvered by the use of an external magnet. We present our initial animal experience with complete transvaginal NOTES nephrectomy using MAGS technology.Transvaginal NOTES nephrectomy was performed in two female pigs through a vaginotomy, using a 40-cm dual-lumen rigid access port inserted into the peritoneal cavity. A MAGS camera and cauterizer were deployed through the port and manipulated across the peritoneal surface by way of magnetic coupling via an external magnet. A prototype 70-cm articulating laparoscopic grasper introduced through the vaginal access port facilitated dissection after deployment of the MAGS instruments. The renal artery and vein were stapled en-bloc using an extra-long articulating endovascular stapler.NOTES nephrectomies were successfully completed in both pigs without complications using MAGS instrumentation. The MAGS camera provided a conventional umbilical perspective of the kidney; the cauterizer, transvaginal grasper, and stapler preserved triangulation while avoiding instrument collisions. Operative duration for the two cases was 155 and 125 minutes, and blood loss was minimal.NOTES nephrectomy using MAGS instrumentation is feasible. We believe this approach improves shortcomings of previously reported NOTES nephrectomies in that triangulation, instrument fidelity, and visualization are preserved while hilar ligation is performed using a conventional stapler without need for additional transabdominal trocars.

We compared clinical outcomes, cost and physician reimbursement between simultaneous bilateral percutaneous nephrostolithotomy and theoretical matched staged bilateral percutaneous nephrostolithotomy.Between September 2005 and May 2007 we performed 200 percutaneous nephrostolithotomies including 17 synchronous bilateral procedures. Complete clinical and cost information was available and recorded for 15 patients. To compare variables between comparable synchronous and staged bilateral percutaneous nephrostolithotomy 152 unilateral percutaneous nephrostolithotomies were used to obtain similar parameters that were then used to estimate the outcomes of theoretical staged bilateral percutaneous nephrostolithotomy. Operative time, hospital length of stay, cost and physician reimbursement were determined according to CPT codes for stone complexity (50080 for stones less than 2 cm, 50081 for stones 2 cm or greater) to match case complexity per renal unit.Mean patient age (+/-SD) in the synchronous bilateral percutaneous nephrostolithotomy group was 51 (+/-11) years and 25% of patients had staghorn calculi. The stone-free rate after the initial procedure was 27% (4 of 15) and second look nephroscopy was performed in 10 patients. Complications occurred in 4 patients and none required transfusion. Mean overall cost of synchronous bilateral percutaneous nephrostolithotomy was $10,129. Cumulative room time, length of stay and cost were higher in the staged than synchronous percutaneous nephrostolithotomies. Physician reimbursement was 11% to 46% less for synchronous bilateral percutaneous nephrostolithotomy.Synchronous bilateral percutaneous nephrostolithotomy benefits patients and third party payors by decreasing cumulative operating room time, length of stay and cost. However, there is a disincentive for surgeons, who are financially penalized for performing synchronous bilateral percutaneous nephrostolithotomy. Third party payors should consider revising putative reimbursement policies for synchronous bilateral percutaneous nephrostolithotomy as it is cost-effective in appropriate patients.

Prostate cancer (CaP) is the most common visceral malignancy and a leading cause of cancer death in men. Androgen deprivation therapy (ADT) is an established treatment for locally advanced and metastatic CaP, and often used as primary therapy in select patients. As ADT has continued to assume an important role in the treatment of CaP, a greater appreciation of potential adverse effects has been acknowledged in men receiving this therapy. Given that all treatments for CaP are frequently associated with some degree of morbidity and can have a negative impact on health-related quality of life (HRQOL), the potential benefits of any treatment, including ADT, must outweigh the risks, particularly in patients with asymptomatic disease. Once the choice to proceed with ADT is complete, it is imperative for the urologist to possess comprehensive knowledge of the potential adverse effects of ADT. This permits the urologist to properly monitor for, perhaps diminish, and to treat any linked morbidities. Patient complaints related to ADT such as a decrease in HRQOL, cognitive and sexual dysfunction, hot flashes, endocrine abnormalities, cardiovascular disease, and alterations in skeletal and body composition are commonly reported throughout the literature. Herein, we review the principal adverse effects linked with ADT in CaP patients and suggest various universal strategies that may diminish these potential adverse consequences associated with this therapy.

To evaluate the impact of body mass index (BMI) on clinical outcomes and costs associated with percutaneous nephrostolithotomy (PCNL).We reviewed charts of 200 consecutive patients who underwent PCNL between September 2005 and May 2007. We recorded patient and stone characteristics and perioperative outcomes. BMI was available for 150 patients (75%), who comprised our study group. We obtained direct and subcomponent costs (room and board, laboratory, pharmacy, radiology, operating room, surgical supplies, anesthesia, and recovery room). We divided patients into four BMI categories: normal weight (BMI25), overweight (25or= BMI30), obese (30or= BMI40), and morbidly obese (BMIor= 40). We compared groups with regard to baseline characteristics, intraoperative parameters, stone-free and complication rates, and hospital length of stay.Mean stone size and proportion of patients with staghorn, multiple, and bilateral calculi were similar among groups. The normal weight cohort had proportionately fewer recurrent stone formers and patients with a history of stone surgery, compared with the other groups (P = .005 and P = .03, respectively). We found no significant differences among groups with regard to stone-free and complication rates, operative time, length of stay, or need for multiple accesses. Median direct cost was marginally, but not significantly, higher in normal weight ($8124) compared with overweight ($6746), obese ($6740), and morbidly obese ($6719) patients (P = .75).Body mass index had no impact on efficacy or complication rates of PCNL. Despite greater perceived difficulty in performing these procedures in overweight and obese patients, it was not more costly.

INTRODUCTION AND OBJECTIVES: Macroautophagy, also known as type II programmed cell death, is a regulated catabolic pathway to degrade cellular organelles and macromolecules. The role of autophagy in cancer is complex and may differ depending on tumor type or context. Here, we investigated the activated basal autophagy in bladder cancer cells and its roles in maintaining cancer cell growth. METHODS: Human immortalized uroepithelium (SV-Huc-1) and bladder cancer cells including RT-4 (grade I), 5637 (grade II), HT1376 and T24 (grade III) were used. We also included human prostate cancer cells (Rv1 and PC3), breast cancer cell (MCF-7) and embryonic kidney cancer cell (293T) as reference cells. The cell viability was accessed by WST-8. Autophagy was detected by the expression level of LC3-II protein. Human bladder tumor tissue array (TMA; 12 cases, paired with normal tissue) was used to detect the LC3 expression level. Detection of apoptosis level was measured by caspase 3/7 activation, caspase 3 cleavage and TUNEL assays. The ROS generation, mitochondria membrane potential in cells treated with autophagy inhibitors was assayed by staining with H2DCFCA and JC-1 dyes, respectively, and subsequently subjected to flow cytometry analysis. Disruption of lysomome membrane (LMP) by was detected by immunofluorescent of cathepsin-D in cells treated with CQ. RESULTS: We found bladder cancer cells exhibited high basal level of autophagy compared to prostate, breast or embryonic kidney cancer cells. Immunohistochemistry (IHC) detection of LC3 in human bladder TMA showed increased level of LC3 in bladder tumor tissues compared to their paired normal tissues. In the cell-based experiment, we found that autophagy inhibitors alone inhibited bladder cancer cell growth and increased apoptosis. The ROS generation and MMP disruption were not detected in cells treated with CQ or HCQ. Immunofluorescent detection of cathepsin-D in cells treated with CQ showed dispread pattern in the cytosol, suggesting the disruption of LMP in CQ-treated bladder cancer cells. CONCLUSIONS: Our results showed that human bladder cancer exhibits high basal level of autophagy. Autophagy inhibitors showed significant effects on the growth of bladder cancer cells by disruption of lysosome function and elevation of apoptotic cell death.

with the BSCC group, while the incidence of lymph node metastasis in the BSCC group was significantly higher than that in the UC group. Of the 12 EMT markers, N-cadherin expression in the UC group was significantly greater than that in the BSCC group, while the expression levels of MMP-9 and ZEB1 in the BSCC group were significantly greater than those in the UC group. Both recurrencefree and overall survivals in the BSCC group were significantly poor compared with those in the UC group. In the UC group, multivariate analyses identified pathological stage, lymph node metastasis and N-cadherin expression as independent predictors of recurrence-free survival (RFS), and age, pathological stage, lymph node metastasis and N-cadherin expression as those of overall survival (OS). In the BSCC group, pathological stage and lymph node metastasis were shown to be independently associated with RFS, while pathological stage, lymph node metastasis, MMP-9 expression and ZEB1 expression appeared to be independent predictors of OS. CONCLUSIONS: These findings suggest the important roles of EMT in the process of disease progression following radical cystectomy for both UC and BSCC; however, different molecules associated with EMT may be involved in this process between UC and BSCC.

INTRODUCTION AND OBJECTIVES: Patients with upper tract urothelial carcinoma (UTUC) may undergo endoscopic procedures for diagnostic and therapeutic intentions prior to definitive surgical management with radical nephrouretectomy (RNU). We assessed for differences in survival based on initial management strategy. METHODS: From 2004 to present, patients undergoing RNU for low grade UTUC from Memorial Sloan-Kettering Cancer Center (MSKCC) had their charts reviewed retrospectively to identify those patients who were initially managed endoscopically with ureteroscopy and tumor ablation. Those less than 66 years of age were excluded to provide an age-matched cohort for combined analysis. Data from Surveillance, Epidemiology and End Results (SEER) from this same time period was obtained and the same selection criteria was used. Survival trends were assessed with Kaplan-Meier analyses. Cox-proportional hazard models were constructed to determine the independent effect of initial management strategy on overall survival (OS) and cancer specific survival (CSS) controlling for age, race, gender, comorbidity, and data source. RESULTS: 838 patients went directly to RNU, and 167 had RNU after initial endoscopic management. We found no difference in OS between the groups (p1⁄40.632) with median follow up of 96 months. The Kaplan-Meier survival analysis for CSS comparing endoscopic management with initial RNU is shown in the figure. Conversely, CSS was significantly worse for those treated with endoscopic management first versus immediate definitive surgery (HR 1.69, 95% CI 1.07-2.69, p1⁄40.025). CONCLUSIONS: In elderly patients with low grade UTUC, there is no difference in overall survival for those that start with endoscopic management of their disease. The observed lower CSS in these patients bears further investigation of the possible contributory selection factors in this patient population.

344 Background: Historically, upper tract urothelial carcinomas (UTUC) are treated similarly to urothelial carcinoma of the bladder (UCB). However, compared to UCB, UTUC demonstrates a more aggressive clinical course which may be explained by significant differences in mutational frequencies between UTUC and UCB that were reported using a customized exon capture sequencing assay (the MSK-IMPACT assay). A major limitation in the advancement of the UTUC field is the lack of appropriate models specific to the disease. The objective of this study was to develop and evaluate preclinical models that would recapitulate treatment responses observed in patients. Methods: 35 surgical specimens from nephroureterectomy of patients with UTUC were implanted into immunocompromised NOD-SCID IL2Rg−/− (NSG) mice. The histological and the genomic characterization of patient tumors and PDXs were examined by a board certified pathologist and MSK-IMPACT assay, respectively. Cell lines were also established to assess histologic and genetic fidelity. Chemosensitivity of PDX models was assessed using a 4 week cycle of gemcitabine/cisplatin (or carboplatin) administration and analysis of tumor growth was performed using a Two-way ANOVA test. Results: 12 patient-derived xenograft (PDX) models were established with a success rate of 34% (12/35) and a 14% (3/21) success in developing cell lines. Both models were highly reflective of their original tumors in terms of histology and genomic characteristics in mutation status and copy number alterations. For a representative PDX, chemosensitivity experiments identified gemcitabine/carboplatin as a potentially effective combination, which was also used in the clinical scenario with a therapeutic response. Chemosensitivity of additional PDXs is continuing to be investigated to potentially guide post-operative decision making for treatment of the patient’s clinically. Conclusions: We developed a cohort of stable PDX models and cell lines for UTUC that maintains the genetic characteristics of the patient’s initial tumor. The continued development of these models may facilitate personalized medicine strategies in the treatment of UTUC.