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Cystinuria is an autosomal recessive disorder of dibasic amino acid transport in the kidney that leads to an abundance of cystine in the urine. This molecule is poorly soluble in urine and it is prone to crystallization and stone formation at concentrations above 300 mg./l. Medical treatment in these patients has incorporated increasing urine volumes, alkalinization and thiol medications that decrease the availability of free cystine in urine. Despite a reasonable prognosis for reduced stone formation we and others have noted difficulties in patients complying with medical management recommendations. Therefore, we evaluated the durability of treatment success in our patients with cystinuria.A retrospective chart review was performed in all patients with cystinuria referred to the comprehensive kidney stone center at our institution for an 8-year period. Medical therapy, stone recurrence rates, compliance with medications and scheduled followup, and the results of metabolic evaluations via 24-hour urine collections were reviewed. The average concentrations of urinary cystine in initial and followup 24-hour samples were compared in patients compliant and noncompliant with medical treatment. In addition, each patient was mailed a 1-page questionnaire to assess the self-perception of medical compliance.We identified 26 patients with a mean age of 32 years at referral (range 13 to 67) who were followed an average of 38.2 months (range 6 to 83). Females represented 58% of those with cystinuria. Overall compliance with medical recommendations was poor with a short duration of success. Of the 26 patients followed at our stone center only 4 (15%) achieved and maintained therapeutic success, as defined by urine cystine less than 300 mg./l. An additional 11 patients (42%) achieved therapeutic success but subsequently had failure at an average of 16 months (range 6 to 27). Of these patients 7 (64%) regained therapeutic success at an average of 9.4 months (range 4 to 20). Five patients (19%) never achieved therapeutic success, while an additional 6 (23%) failed to present to followup appointments or provide subsequent 24-hour urine studies despite referral to a tertiary care center. Patient self-assessment of medical compliance was uniformly high regardless of physician perceptions or treatment results. CONCLUSIONS The durability of medically treating patients with cystinuria is limited with only a small percent able to achieve and maintain the goal of decreasing cystine below the saturation concentration. Greater physician vigilance in these complicated stone formers is required to achieve successful prophylactic management. Furthermore, these patients require better insight into the own disease to improve compliance.

Dendritic cells (DCs) transfected with mRNA encoding human telomerase reverse transcriptase (hTERT) have been shown to represent potent inducers of CTLs and antitumor immunity. However, it has become widely accepted that not only CTLs but also CD4(+) T helper cells are critical to the generation, as well as to the maintenance, of potent antitumor responses in vivo. In this study, we sought to determine whether human DCs transfected with mRNA encoding a chimeric hTERT/lysosome-associated membrane protein (LAMP-1) protein, carrying the endosomal/lysosomal sorting signal of the LAMP-1, are capable of stimulating concomitant hTERT-specific CD8(+) and CD4(+) T-cell responses in vitro. We show that processing of hTERT/LAMP-1 transcripts leads to enhanced stimulation of hTERT-specific CD4(+) T cells and does not negatively affect intracellular generation and subsequent presentation of MHC class I epitopes, hence, generating a CTL response. These findings provide a preclinical rationale of using DCs transfected with the chimeric hTERT/LAMP-1 RNA in vaccine trials to facilitate generation of antigen-specific CD4(+) T-cell responses that may be required to stimulate and maintain an optimal CD8(+) CTL response in vivo.

Improved fiber optics and advanced intracorporeal lithotripsy devices have significantly decreased the incidence of complications during ureteroscopic procedures. Despite recent reports suggesting that radiographic imaging may not be necessary in all individuals after routine ureteroscopy silent obstruction may develop in some, ultimately resulting in renal damage. We determined the incidence of postoperative silent obstruction at our institution and assessed the need for routine functional radiographic studies after ureteroscopy.We retrospectively reviewed the charts of 320 patients who underwent a total of 459 ureteroscopic procedures for renal or ureteral calculi in a 3-year period. Complete followup with imaging was available for 241 patients (75%). Average patient age was 47.2 years. The variables of interest reviewed included preoperative pain, preoperative obstruction, targeted calculous site, stone-free rate, postoperative pain and postoperative obstruction. Mean followup was 5.4 months (range 2 to 43).A total of 241 patients with complete followup were identified in this analysis. Preoperative pain was present in 202 patients (84%) and 168 (70%) had preoperative obstruction. Overall targeted calculous clearance was successful in 73% of the patients and an additional 15.8% had residual fragments less than 4 mm. The renal, proximal or mid and distal ureteral stone-free rate was 32.1%, 81.9% and 90.5%, while in an additional 46.4%, 6.3% and 6.7% of cases, respectively, residual fragments were less than 4 mm. Of the 241 patients 30 (12.3%) had obstruction postoperatively due to residual stone in 25 (83.3%), stricture in 3 (10%), edema of the ureteral orifice in 1 (3.3%) and a retained encrusted stent in 1 (3.3%). Postoperatively obstruction correlated with postoperative pain in 23 of the 30 patients (76.7%). Pain was present postoperatively in 30 of the 211 patients (14%) without evidence of ureteral obstruction postoperatively. However, silent obstruction developed in 7 patients (23.3%) or 2.9% of the total cohort. All 7 patients underwent secondary ureteroscopy to alleviate obstruction. A single patient ultimately received chronic hemodialysis for renal failure, 1 was lost to followup and in 5 there was documented successful resolution of the cause of obstruction.Our analysis suggests that silent obstruction remains a potentially significant complication after stone management. Relying on postoperative pain to determine the necessity of postoperative imaging places patients at risk for progressive renal failure due to unrecognized obstruction. Therefore, we recommend that imaging of the collecting system should be performed by excretory urography, spiral computerized tomography or ultrasound within 3 months after routine ureteroscopic stone treatment to avoid the potential complications of unrecognized ureteral obstruction.

Malte Rieken*, Tina Schubert, Evanguelos Xylinas, Luis Kluth, New York, NY; Morgan Roupret, Paris, France; Quoc-Dien Trinh, Boston, MA; Richard Lee, Bashir Al Hussein Al Awamlh, New York, NY; Harun Fajkovic, Vienna, Austria; Giacomo Novara, Padua, Italy; Vitaly Margulis, Yair Lotan, Dallas, TX; Juan Martinez-Salamanca, Madrid, Spain; Kazumasa Matsumoto, Kanagawa, Japan; Christian Seitz, Vienna, Austria; Mesut Remzi, Korneuburg, Austria; Pierre Karakiewicz, Montreal, Canada; Douglas Scherr, New York, NY; Alberto Briganti, Milan, Italy; Alexander Bachmann, Basel, Switzerland; Shahrokh Shariat, Vienna, Austria

55 Background: Prostate cancer accounts for greater than 200,000 cases each year. Although cancer control is generally favorable with treatment, side effects are common. Among men treated with surgery, nerve-sparing prostatectomy is associated with lower rates of incontinence and erectile dysfunction. Seminal vesicle sparing (SVS) may further limit damage to the neurovascular tissue surrounding the prostate. Although some surgeons practice SVS, evidence supporting its use is lacking. We implemented a randomized control trial to determine if SVS is associated with better functional outcomes compared to non-SVS prostatectomy. Methods: 140 men with early-stage (T1c/T2N0M0, Gleason score = 21) were enrolled in the Seminal Vesicle Sparing Prostatectomy Trial (NCT01825642) and randomized to either SVS or non-SVS prostatectomy between 2006 and 2011. The Expanded Prostate Cancer Index Composite (EPIC) was used to assess quality of life outcomes following surgery. Results: 71 and 69 men were enrolled in the SVS and non-SVS arms, respectively. The predominant surgical approach was robotic assisted prostatectomy (>97% in both arms). Men in the SVS arm were slightly younger (56 vs 58 years, p = 0.02); however, there were no significant differences in other clinical or demographic factors. There were no cases of seminal vesicle invasion. PSA recurrence was noted in 3 patients (1 in SVS group and 2 in non-SVS group). At 12 months postoperatively, sexual (76 vs 75) and urinary incontinence (92 vs 94) scores were similar among SVS and non-SVS patients (both p > 0.2). Conclusions: Recovery of urinary and sexual function was common among men undergoing SVS or non-SVS prostatectomy. SVS did not negatively impact cancer control, but was not associated with enhanced recovery of sexual or urinary function, perhaps due to the high level of recovery of the control arm. Clinical trial information: NCT01825642. [Table: see text]

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

Objectives To better understand the risk of short-term complications associated with perioperative intravesical mitomycin-C (MMC) therapy for patients undergoing endoscopic management of non–muscle invasive bladder cancer. Methods and Materials Using an institutional database of patients with bladder cancer, we performed a retrospective case-control study of patients receiving perioperative MMC after tumor resection (2008–2012). MMC cases were matched by clinical stage to controls receiving endoscopic resection alone. Demographic information, clinicopathologic details, and outcomes were compared between groups. Outcomes of interest included overall, genitourinary, and major complications. Chi-square tests and multivariable logistic regression were used to evaluate associations among patient characteristics, clinical factors, exposure to MMC, and outcomes of interest. Results One-hundred sixteen patients treated with MMC were matched to 116 controls. Patients receiving MMC were younger ( P = 0.04) and more likely to have invasive disease (i.e. T1 or greater) (23% vs. 15%, P = 0.02). Complications were more frequent among patients who were treated with MMC (34.5% vs. 19.8%, Odds Ratio 2.89, 95% Confidence Interval 1.43–5.81). The most common complication among MMC patients that required medical management was dysuria (17%). Major complications were more common among MMC patients (5.2% vs. 0.9%), but this difference did not reach statistical significance ( P = 0.11). Conclusions Use of MMC is associated with a greater odds of complications compared with controls. Patients should be counseled regarding both the benefits and potential risks of perioperative intravesical MMC. Continued research is required to understand the safety implications associated with the use of perioperative, intravesical MMC.

281 Background: The aim of the current study was to assess the prognostic value of extranodal extension (ENE) and other lymph node (LN) parameters in a large multicenter cohort of patients with LN metastasis (LNM) following radical nephroureterectomy (RNU). Methods: Retrospective analysis of 222 patients with LNM treated with RNU for upper tract urothelial carcinoma (UTUC) without neoadjuvant therapy. Microscopically, each LN metastasis was evaluated for presence of ENE. Results: The median number of LNs removed, number of positive LNs, and LN density were 4 (IQR: 8), 2 (IQR: 2), and 51.3% (IQR: 71.7%), respectively. Overall, 110 patients (49.5%) had ENE. Presence of ENE was associated with more advanced pT stage (p=0.026). In multivariable analyses, ENE was associated with disease recurrence (p=0.01) and cancer-specific mortality (p=0.013). LN density, when stratified by 30% cutoff, was associated with disease recurrence and cancer-specific mortality (p=0.048 and p=0.049) in univariable, but not in multivariable analyses. Addition of ENE to a multivariable model including pT stage and tumor architecture improved predictive accuracy for disease recurrence from 70.3% to 74.5% (p Conclusions: ENE is a powerful predictor of clinical outcomes in UTUC patients with LNM. While other LN parameters seem to have limited clinical value, ENE could help risk stratify UTUC patients with LNM for better counseling and clinical trial design.

267 Background: Novel prognostic factors for patients after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) have recently been described. We tested the prognostic value of pathologic characteristics and developed models to predict the individual probabilities of recurrence-free survival (RFS) and cancer-specific survival (CSS) after RNU. Methods: Our study included 2,244 patients treated with RNU without neoadjuvant or adjuvant therapy at 23 international institutions. Tumor characteristics included T classification, grade, lymph node status, lymphovascular invasion, tumor architecture, location, and concomitant CIS. The cohort was split for development (12 centers, n=1273) and external validation (11 centers, n=971). Results: At a median follow-up of 45 months, 501 patients (22.3%) experienced disease recurrence and 418 patients (18.6%) died of UTUC. On multivariable analysis, T classification (p-for-trend Conclusions: Using standard pathologic features, we developed highly accurate prognostic models for the prediction of RFS and CSS after RNU for UTUC. These models offer improvements in calibration over AJCC stage grouping and can be utilized for individualized patient counseling, follow-up scheduling, risk stratification for adjuvant therapies, and inclusion criteria for clinical trials.

Testis cancer is one of the few solid organ malignancies for which reliable serum tumor markers are available to help guide disease management. Human chorionic gonadotropin, alpha fetoprotein, and lactate dehydrogenase play crucial roles in diagnosis, staging, prognosis, monitoring treatment response, and surveillance of seminomatous and nonseminomatous germ cell tumors. Herein we discuss the clinical applications of germ cell tumor markers, the limitations of these markers in the management of this disease, and additional serum molecules that have been identified with potential roles as novel germ cell tumor markers.

244 Background: Neoadjuvant cisplatin-based chemotherapy benefits patients with bladder cancer, particularly in the 30% with pathologic complete response (pCR) at cystectomy. Many patients with bladder cancer are not candidates for cisplatin. Taxane-based regimens have activity in urothelial cancer. ABI-007 is an albumin-bound paclitaxel with increased activity and decreased toxicity compared to standard paclitaxel preparations. Methods: Eligible pts have T2-4,N0,M0 or Tany,N1- 3,M0 bladder cancer with ECOG PS 0-1, and adequate marrow (granulocyte count > 1,500/mm3, platelet > 100,000/mm3, and hemoglobin > 9.0 g/dl), hepatic (transaminases < 2.5 X upper limit of normal, alkaline phosphatase < 2.5 X upper limit of normal, and bilirubin < 1.5 mg/dl) and renal function (serum creatinine < 2.0 mg/dl and/or creatinine clearance > 40 ml/min). Pts are treated with intravenous ABI-007 260 mg/m2 and carboplatin (target area under the curve=5) on day 1 with gemcitabine 800 mg/m2 on days 1 and 8, followed by radical cystectomy after three cycles of therapy. The primary study endpoint is the proportion of patients with pCR at cystectomy. Results: 27 patients have been enrolled. By clinical staging, 20 had T2 disease, 5 had T3, 2 had T4, and 2 had nodal enlargement. All are evaluable for toxicity with 22 evaluable for response (exclusions-3 for change in dose schedule, 1 each for refusal of cystectomy and withdrawal from study). 25/27 patients received all three cycles (78 total cycles) with doses reduced in 26 cycles for toxicity. All patients had transient grade 3-4 neutropenia and 17 received filgrastim, but only two had febrile neutropenia. Six pts had pCR with an additional 5 having residual carcinoma in situ (CIS) and 1 with T1 disease at cystectomy. 54% of evaluable patients had no muscle invasive disease at cystectomy. Conclusions: Neoajuvant ACG is active in bladder cancer with pCR rate nearing 30% and nearly as many patients with CIS but no residual invasive disease. Marrow toxicity is significant but manageable. [Table: see text]

5075 Background: There is relatively little literature regarding the use of adjuvant chemotherapy following radical nephroureterectomy in the management of patients with upper tract urothelial carcinoma (UTUC). Our goal was to determine the incidence of receipt of adjuvant chemotherapy in high-risk patients and the ensuing effect on overall- and cancer-specific survival. Methods: Using an international collaborative database, we identified 1390 patients who underwent nephroureterectomy for non-metastatic UTUC between the years of 1992 and 2006. Of these, 542 (39%) patients were classified as high-risk (pT3N0, pT4N0, and/or lymph node positive). These patients were separated into two groups—those who did and did not receive adjuvant chemotherapy—and were stratified by gender, age group, performance status, tumor grade and stage. Cox proportional hazard modeling and Kaplan-Meier analyses were used to determine overall- and cancer-specific survival amongst the cohorts. Results: Of the high-risk patients, 121 (22%) received adjuvant chemotherapy. Adjuvant chemotherapy was more commonly administered in the context of increased tumor grade and stage (p < 0.001). Median survival in the entire cohort was 24 months (range 0–231 months). There was no significant difference in overall- or cancer-specific survival between those who did and did not receive adjuvant chemotherapy; however age, performance status, tumor grade, and tumor stage were significant predictors of both overall and cancer-specific survival. Conclusions: Adjuvant chemotherapy is infrequently utilized in the treatment of patients with high-risk UTUC after nephroureterectomy. Despite this, it appears that adjuvant chemotherapy confers minimal impact on overall- or cancer-specific survival in this group. No significant financial relationships to disclose.