Bladder cancer exosomes contain EDIL-3/Del1 and facilitate cancer progression.

PURPOSE: High grade bladder cancer is an extremely aggressive malignancy associated with high rates of morbidity and mortality. Understanding how exosomes may affect bladder cancer progression could reveal novel therapeutic targets. MATERIALS AND METHODS: Exosomes derived from human bladder cancer cell lines and the urine of patients with high grade bladder cancer were assessed for the ability to promote cancer progression in standard assays. Exosomes purified from the high grade bladder cancer cell line TCC-SUP and the nonmalignant urothelial cell line SV-HUC were submitted for mass spectrometry analysis. EDIL-3 was identified and selected for further analysis. Western blot was done to determine EDIL-3 levels in urinary exosomes from patients with high grade bladder cancer. shRNA gene knockdown and recombinant EDIL-3 were applied to study EDIL-3 function. RESULTS: Exosomes isolated from high grade bladder cancer cells and the urine of patients with high grade bladder cancer promoted angiogenesis and migration of bladder cancer cells and endothelial cells. We silenced EDIL-3 expression and found that shEDIL-3 exosomes did not facilitate angiogenesis, and urothelial and endothelial cell migration. Moreover, exosomes purified from the urine of patients with high grade bladder cancer contained significantly higher EDIL-3 levels than exosomes from the urine of healthy controls. EDIL-3 activated epidermal growth factor receptor signaling while blockade of epidermal growth factor receptor signaling abrogated this EDIL-3 induced bladder cell migration. CONCLUSIONS: Exosomes derived from the urine of patients with bladder cancer contains bioactive molecules such as EDIL-3. Identifying these components and their associated oncogenic pathways could lead to novel therapeutic targets and treatment strategies.

Analysis of a large single-center experience with robot-assisted pyeloplasty.

OBJECTIVES: To report a single-center experience with robot-assisted pyeloplasty. METHODS: Medical records of 100 consecutive robot-assisted pyeloplasty cases carried out between May 2004 and August 2010 were retrospectively reviewed, and major perioperative parameters were recorded. Patients underwent functional (renal scan) and/or anatomical (ultrasound or computerized tomoghraphy) imaging at 6 months. RESULTS: The mean patient age was 39.8 years. A total of 12 patients underwent prior attempts at repair. Ureteral stents were placed in all patients except one, and closed-suction drains were placed in 59 patients. There were two intraoperative complications and two postoperative complications requiring surgical intervention. One patient with a complex prior surgical history developed a urine leak that was managed with prolonged drainage. A total of 42 patients were discharged on postoperative day 1, and 44 were discharged on postoperative day 2. Mean length of follow up was 22.8 months. The operative success rate was 96%. CONCLUSIONS: The majority of patients undergoing robot-assisted pyeloplasty can expect a short hospitalization with minimal morbidity. The operative success rate is high, even in patients with prior attempts at repair. Complication rates including urine leaks are quite low, and routine placement of a closed-suction drain is likely to be unnecessary.

Identifying additional lymph nodes in radical cystectomy lymphadenectomy specimens.

Lymph node count has prognostic implications in bladder cancer patients who are treated with radical cystectomy. Lymph nodes that are too small to identify grossly can easily be missed, potentially leading to missed nodal metastases and inaccurate nodal counts, resulting in inaccurate prognoses. We investigated whether there is a benefit to submitting the entire lymph node packet for histological examination to identify additional lymph nodes. We prospectively assessed 61 pelvic lymphadenectomy specimens in 14 consecutive patients undergoing radical cystectomy. The specimens were placed in Carnoy's solution overnight, then analyzed for lymph nodes. The residual tissue was entirely submitted to assess for additional lymph nodes. In 61 specimens, we identified 391 lymph nodes, ranging from 4-44 nodes per patient. We identified 238 (61%) lymph nodes with standard techniques and 153 (39%) lymph nodes in submitted residual tissue. The number of additional lymph nodes found in the residual tissue ranged from 0 to 26 (0-75%) per patient. These lymph nodes ranged in size from 0.05 to 1 cm. All additional lymph nodes were negative for metastatic disease. Submitting the entire specimen for histological examination allowed for identification of more lymph nodes in radical cystectomy pelvic lymphadenectomy specimens. However, as none of the additional lymph nodes contained metastatic disease, it is unclear if there is a clinical benefit in evaluating lymph nodes that are neither visible nor palpable in lymphadenectomy specimens.

Survival of patients undergoing cytoreductive surgery for metastatic renal cell carcinoma in the targeted-therapy era.

BACKGROUND/AIM: In the cytokine era, cytoreductive nephrectomy (CN) improves survival for patients with metastatic renal cell carcinoma (mRCC). We analyzed the effect of CN on the survival of patients diagnosed with mRCC in the era of tyrosine kinase inhibitors (2005-present). PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify adult patients diagnosed with mRCC between 2005 and 2009. The primary outcome was overall survival, analyzed with multivariable Cox models. RESULTS: Out of 7,143 incident mRCC cases reported to SEER between 2005-2009, 2,629 (37%) underwent CN. Patients undergoing CN were younger, and more likely to be white, male, and married. Patients with stage T3 tumors were most likely to undergo CN (64%). Patients that underwent CN had improved one-year survival (61% vs. 22%). On multivariable analysis, CN was associated with improved overall survival(hazard ratio[HR]=0.40 95% confidence interval [CI]=0.37-0.43). CONCLUSION: In the targeted-therapy era, patients with mRCC undergoing CN have improved survival after adjusting for tumor stage and demographic characteristics.

Complications associated with extraperitoneal robot-assisted radical prostatectomy using the standardized Martin classification.

OBJECTIVE: To report and identify the predictors of early and long-term complications in a large series of extraperitoneal robot-assisted radical prostatectomy using the standardized Martin criteria. MATERIALS AND METHODS: A total of 1503 patients underwent extraperitoneal robot-assisted radical prostatectomy for the treatment of clinically localized prostate cancer from July 2003 to August 2010 at a tertiary referral center. The median follow-up was 28.9 months. Fisher's exact test was used to examine the association of multiple variables in a bivariate analysis with the incidence and types of complications. Independent predictors were also examined in a multivariate analysis using logistic regression models. RESULTS: A total of 151 complications were recorded in 127 of 1503 patients (8.45%). Approximately one third (30.5%) were classified as major complications requiring intervention (Clavien grade III and IV). The most commonly encountered complications were lymphocele (1.46%), bladder neck contracture (1.33%), and anastomotic leak (1.20%). The operative time was a significant predictor of all complications and of major complications on multivariate analysis. Surgeon experience was also predictive of complications on multivariate analysis. CONCLUSION: Extraperitoneal robot-assisted radical prostatectomy remains an underused alternative approach for the treatment of localized prostate cancer. Its safety profile is equivalent to that of other approaches in experienced hands.

Robot-assisted partial nephrectomy: analysis of the first 100 cases from a single institution.

Robot-assisted partial nephrectomy (RAPN) is an alternative to open and laparoscopic partial nephrectomy for small renal tumors. Our objectives were to report our experience and short-term outcomes from the first 100 cases of robot-assisted partial nephrectomy (RAPN) performed at a single institution, as well as to evaluate the effect of the learning curve and identify any factors associated with adverse perioperative outcomes. Patient records of the first 100 RAPN cases performed by three surgeons between October 2007 and March 2010 were retrospectively reviewed. The cases were divided into two groups to analyze a possible learning curve effect. Group 1 consisted of the first half (chronologically) of the cases performed by each surgeon, and Group 2 consisted of the second half. For the entire series, the median warm ischemia time was 24 min (range 11-49), mean length of follow-up was 13.4 months, and the median postoperative change in glomerular filtration rate (GFR) was -6.6 mL/min/1.73 m(2). Three patients had microscopically positive margins on final pathology, three intraoperative complications occurred, and 13 postoperative complications were recorded (10 Clavien grade IIIa or less). Median operative time was significantly longer in Group 1 (193 min) than in Group 2 (165 min, P = 0.003). Multivariate analysis identified male gender and cases done in Group 1 to be associated with increased operative time, while male gender and higher nephrometry scores were associated with increased blood loss. Tumor characteristics associated with greater reductions in GFR included higher nephrometry scores, endophytic tumors, and hilar tumors. In conclusion, RAPN appears to be safe and the major effect of the learning curve appears to be on operative time. Warm ischemia times are sufficiently low to prevent significant renal impairment, while male gender and higher nephrometry scores may be predictors of longer operative times and more intraoperative blood loss. Overall operative time decreased with increasing case volume, although this was not uniform among the three surgeons in the study. Further longitudinal study is necessary to establish oncologic outcomes.