Impact of facility type and volume on survival in patients with metastatic renal cell carcinoma.

INTRODUCTION: To investigate the impact of facility type and volume on survival in patients with metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS: We investigated the National Cancer Database for patients with mRCC. Patients were stratified according to treatment facility type (academic vs. non-academic) and facility volume (high, intermediate, and low). Kaplan-Meier survival estimates and Cox proportional hazard models were fitted to evaluate overall survival (OS) as a function of facility type, volume, and different treatment modalities. RESULTS: A total of 27,598 patients were identified, of which 10,938 (40%) were treated at academic centers (AC) and 16,131 (60%) at non-academic centers (non-AC). Overall, 19,904 patients (72%) were treated in high-volume hospitals (HVH). Among patients treated at AC, 94% were treated at HVHs. Patients treated at AC were more likely to receive immunotherapy, undergo cytoreductive nephrectomy (CN) and metastasectomy. The 2 and 5 year OS rates for patients treated in AC were 29.7% (CI 28.8%-30.6%) and 13% (CI 12%-14%) vs. 21.7% (CI 21%-22.4%) and 8.4% (CI %7.91-%8.99) in the Non-AC, respectively (p < 0.001). Multivariate Cox regression analysis identified treatment at AC as an independent predictor of survival (HR 0.85, 95% CI 0.81-0.91, p < 0.001). Undergoing CN and receipt of immunotherapy was also associated with a survival benefit (HR 0.41, CI 0.40-0.43 and HR 0.63, CI 0.59-0.68 respectively, p < 0.001). CONCLUSIONS: Treatment at ACs and HVHs was associated with a survival benefit in patients with mRCC. Patients treated at AC were more likely to receive immunotherapy, undergo CN and metastasectomy.

The NLRP3 Inflammasome Mediates Inflammation Produced by Bladder Outlet Obstruction.

PURPOSE: While bladder outlet obstruction is well established to elicit an inflammatory reaction in the bladder that leads to overactive bladder and fibrosis, little is known about the mechanism by which this is initiated. NLRs (NOD-like receptors) and the structures that they form (inflammasomes) have been identified as sensors of cellular damage, including pressure induced damage, and triggers of inflammation. Recently we identified these structures in the urothelium. In this study we assessed the role of the NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome in bladder dysfunction resulting from bladder outlet obstruction. MATERIALS AND METHODS: Bladder outlet obstruction was created in female rats by inserting a 1 mm outer diameter transurethral catheter, tying a silk ligature around the urethra and removing the catheter. Untreated and sham operated rats served as controls. Rats with bladder outlet obstruction were given vehicle (10% ethanol) or 10 mg/kg glyburide (a NLRP3 inhibitor) orally daily for 12 days. Inflammasome activity, bladder hypertrophy, inflammation and bladder function (urodynamics) were assessed. RESULTS: Bladder outlet obstruction increased urothelial inflammasome activity, bladder hypertrophy and inflammation, and decreased voided volume. Glyburide blocked inflammasome activation, reduced hypertrophy and prevented inflammation. The decrease in voided volume was also attenuated by glyburide mechanistically as an increase in detrusor contraction duration and voiding period. CONCLUSION: Results suggest the importance of the NLRP3 inflammasome in the induction of inflammation and bladder dysfunction secondary to bladder outlet obstruction. Arresting these processes with NLRP3 inhibitors may prove useful to treat the symptoms that they produce.