patients with primary metastatic renal cell carcinoma (mRCC) have been offered cytoreductive nephrectomy (CN) followed by targeted therapy, but the optimal sequence of surgery and systemic therapy is unknown. OBJECTIVE To examine whether a period of sunitinib therapy before CN improves outcome compared with immediate CN followed by sunitinib. DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial began as a phase 3 trial on July 14, 2010, and continued until March 24, 2016, with a median follow-up of 3.3 years and a clinical cutoff date for this report of May 5, 2017. Patients with mRCC of clear cell subtype, resectable primary tumor, and 3 or fewer surgical risk factors were studied. INTERVENTIONS Immediate CN followed by sunitinib therapy vs treatment with 3 cycles of sunitinib followed by CN in the absence of progression followed by sunitinib therapy. MAIN OUTCOMES AND MEASURES Progression-free survival was the primary end point, which needed a sample size of 458 patients. Because of poor accrual, the independent data monitoring committee endorsed reporting the intention-to-treat 28-week progression-free rate (PFR) instead. Overall survival (OS), adverse events, and postoperative progression were secondary end points. RESULTS The study closed after 5.7 years with 99 patients (80 men and 19 women; mean [SD] age, 60 [8.5] years). The 28-week PFR was 42% in the immediate CN arm (n = 50) and 43% in the deferred CN arm (n = 49) (P = .61). The intention-to-treat OS hazard ratio of deferred vs immediate CN was 0.57 (95% CI, 0.34-0.95; P = .03), with a median OS of 32.4 months (95% CI, 14.5-65.3 months) in the deferred CN arm and 15.0 months (95% CI, 9.3-29.5 months) in the immediate CN arm. In the deferred CN arm, 48 of 49 patients (98%; 95% CI, 89%-100%) received sunitinib vs 40 of 50 (80%; 95% CI, 67%-89%) in the immediate arm. Systemic progression before planned CN in the deferred CN arm resulted in a per-protocol recommendation against nephrectomy in 14 patients (29%; 95% CI, 18%-43%). CONCLUSIONS AND RELEVANCE Deferred CN did not improve the 28-week PFR. With the deferred approach, more patients received sunitinib and OS results were higher. Pretreatment with sunitinib may identify patients with inherent resistance to systemic therapy before planned CN. This evidence complements recent data from randomized clinical trials to inform treatment decisions in patients with primary clear cell mRCC requiring sunitinib.

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In patients with ureteral transitional cell carcinoma segmental ureterectomy does not undermine cancer control outcomes relative to nephroureterectomy (with or without bladder cuff removal). Therefore, segmental ureterectomy may be offered to virtually all patients with ureteral transitional cell carcinoma when it is technically feasible, which also includes carefully selected patients with T3 or even T4 lesions.

What ' s known on the subject? and What does the study add?In a previous randomized controlled trial, barbed polyglyconate suture for vesicourethral anastomosis was associated with more frequent cystogram leaks, longer mean catheterization times and greater suture costs per case.In the current randomized controlled trial, we show that barbed polyglyconate suture is associated with decreased anastomosis time, decreased need to readjust suture tension, cost reduction, and equal continence and early/late urinary complication rates. OBJECTIVE• To examine the effectiveness of barbed polyglyconate suture (V-Loc 180; Covidien, Mansfi eld, MA, USA) compared with standard monofi lament for posterior reconstruction (PR) and vesico-urethral anastomosis (VUA) during robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS• A prospective randomized controlled trial was conducted in 70 consecutive RARP cases by a single surgeon (K.C.Z.).• Standard VUA was performed using three 4-0 poliglecaprone 25 (Monocryl; Ethicon Endosurgery, Cincinnati, OH, USA) sutures secured with absorbable suture clips (LapraTy, Ethicon; one single 6-inch [ 15.2 cm ] for PR and two attached 6-inch [ 15.2 cm ] for VUA).• Barbed suture VUA was performed using two 3-0 6-inch (15.2 cm) barbed polyglyconate sutures.• Time to complete the suture set-up by the nursing team, anastomosis time and need to adjust suture tension were recorded. Suture-related complications, validated-questionnaire continence and cost were also examined. RESULTS• Compared with a conventional reconstruction technique, there was a signifi cant reduction in mean nurse set-up time (31 vs. 294 s; P < 0.01) and reconstruction time (13.1 vs. 20.8 min; P < 0.01) for the barbed suture technique.• Need to readjust suture tension or to place additional suture clips for watertight closure was greater in the standard monofi lament group than in the barbed suture group (6% vs. 24%; P = 0.03).• A cost reduction was recorded at our institution (48.05 vs. 70.25 $CAN) with the barbed suture technique.• With a mean follow-up of 6.2 months, no delayed anastomotic leak or bladder neck contracture was observed in either group.• Pad-free continence outcomes for the monofi lament suture vs the barbed suture groups at 1 (64 vs. 69%, P = 0.6), 3 (76 vs. 81%, P = 0.5) and 6 months (88 vs. 92%, P = 0.7) were similar. CONCLUSIONS• Compared with standard monofi lament suture, the unidirectional barbed polyglyconate suture appears to provide safe, effi cient and cost-effective PR and VUA during RARP.• Use of the interlocked barbed polyglyconate suture technique prevents slippage, precluding the need for assistance, knot-tying and constant reassessment of anastomosis integrity.

Objective To assess the correlation of the Gleason score on biopsy and the final pathology after radical prostatectomy (RP) for prostate adenocarcinoma. Patients and methods In a retrospective analysis within a tertiary-care centre, the charts of 537 patients who had undergone radical prostatectomy from April 1989 to November 2000 were reviewed. The RPs were undertaken in one institution; 167 biopsies were taken and interpreted in the referring centres, and 355 were taken and interpreted in the authors' institution by up to 15 pathologists. All the final pathology specimens were interpreted by the same group of pathologists. The main outcome measures were: the pathological report of the biopsy including the primary and secondary Gleason grade; the final pathological grade (primary and secondary); the margin status; and the identification of the pathologist for the biopsy and final pathology. Results In all, 390 patients had inclusion criteria (the Gleason grade before and after RP) available. For the individual scores 38.2% of tumours were undergraded, 32.6% overgraded and only 29.2% had identical grading in preoperative biopsies and final specimens. When grouped into more meaningful categories (Gleason 2-4, 5-6, 7 and 8-10) the correlation improved, with 48.5% of patients remaining in the same group after RP. For 39 patients the same pathologist assessed the biopsy and final specimen; in these cases individual scores were identical in 49% and group scores were identical in 64%. Conclusion Gleason grading of the prostate biopsy remains a poor predictor of pathological outcome. Assessment by the same pathologist reduces the discrepancy but over half the patients are under-or overgraded on final pathology. Clinicians should be aware of these limitations when using the biopsy Gleason grade in decision making.

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This study investigated the mechanisms underlying tubular apoptosis in diabetes by identifying proapoptotic genes that are differentially upregulated by reactive oxygen species in renal proximal tubular cells (RPTCs) in models of diabetes. Total RNAs isolated from renal proximal tubules (RPTs) of 20-week-old heterozygous db/m+, db/db, and db/db catalase (CAT)-transgenic (Tg) mice were used for DNA chip microarray analysis. Real-time quantitative PCR assays, immunohistochemistry, and mice rendered diabetic with streptozotocin were used to validate the proapoptotic gene expression in RPTs. Cultured rat RPTCs were used to confirm the apoptotic activity and regulation of proapoptotic gene expression. Additionally, studies in kidney tissues from patients with and without diabetes were used to confirm enhanced proapoptotic gene expression in RPTs. Bcl-2–modifying factor (Bmf) was differentially upregulated (P < 0.01) in RPTs of db/db mice compared with db/m+ and db/db CAT-Tg mice and in RPTs of streptozotocin-induced diabetic mice in which insulin reversed this finding. In vitro, Bmf cDNA overexpression in rat RPTCs coimmunoprecipated with Bcl-2, enhanced caspase-3 activity, and promoted apoptosis. High glucose (25 mmol/L) induced Bmf mRNA expression in RPTCs, whereas rotenone, catalase, diphenylene iodinium, and apocynin decreased it. Knockdown of Bmf with small interfering RNA reduced high glucose–induced apoptosis in RPTCs. More important, enhanced Bmf expression was detected in RPTs of kidneys from patients with diabetes. These data demonstrate differential upregulation of Bmf in diabetic RPTs and suggest a potential role for Bmf in regulating RPTC apoptosis and tubular atrophy in diabetes.