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IDH2 R172 mutations occur in sinonasal undifferentiated carcinoma (SNUC), large-cell neuroendocrine carcinoma (LCNEC), sinonasal adenocarcinomas, and olfactory neuroblastoma (ONB). We performed a clinical, pathologic, and genetic/epigenetic analysis of a large IDH2-mutated sinonasal tumor cohort to explore their distinct features. A total 165 sinonasal/skull base tumors included 40 IDH2 mutants studied by light microscopy, immunohistochemistry, and genome-wide DNA methylation, and 125 IDH2 wild-type tumors used for comparison. Methylation profiles were analyzed by unsupervised hierarchical clustering, t-distributed stochastic neighbor embedding dimensionality reduction and assessed for copy number alterations (CNA). Thirty-nine histologically assessable cases included 25 (64.1%) SNUC, 8 (20.5%) LCNEC, 2 (5.1%) poorly differentiated adenocarcinomas, 1 (2.7%) ONB, and 3 (7.7%) IDH2-mutated tumors with ONB features. All cases were high-grade showing necrosis (82.4%), prominent nucleoli (88.9%), and median 21 mitoses/10 HPFs. AE1/AE3 and/or CAM 5.2 were positive in all and insulinoma-associated protein 1 (INSM1) in 80% cases. All IDH2 mutants formed one distinct group by t-distributed stochastic neighbor embedding dimensionality reduction separating from all IDH2 wild-type tumors. There was no correlation between methylation clusters and histopathologic diagnoses. Recurrent CNA included 1q gain (79.3%), 17p loss (75.9%), and 17q gain (58.6%). No CNA differences were observed between SNUC and LCNEC. IDH2 mutants showed better disease-specific survival than SMARCB1-deficient (P=0.027) and IDH2 wild-type carcinomas overall (P=0.042). IDH2-mutated sinonasal tumors are remarkably homogeneous at the molecular level and distinct from IDH2 wild-type sinonasal malignancies. Biology of IDH2-mutated sinonasal tumors might be primarily defined by their unique molecular fingerprint rather than by their respective histopathologic diagnoses.

Background Decision-making for pulse generator implantation for sacral nerve stimulation in the management of fecal incontinence is based on the results of a test phase. Its duration is still a matter of debate. Objective The purpose of this study was to determine whether an early positive response during the test phase could predict implantation of a permanent sacral nerve pulse generator. Design This was a short-term observational cohort study. A positive response was defined as a >50% decrease of fecal leaks compared with baseline. A multivariate logistic regression was computed to predict pulse generator implantation after the first week of the test phase. Settings The study was conducted in 3 national referral centers. Patients From January 2006 to December 2012, 144 patients with fecal incontinence enrolled in a prospectively maintained database completed a 2- to 3-week bowel diary, at baseline and during test phase. Main outcome measures The primary outcome was the clinical decision to implant a pulse generator. The primary predictor was a calculated score including the number of leak episodes, bowel movements, and urgencies and the time to defer defecation expressed in minutes during the first screening test week. Results After the first, second and third week of the test phase, 81 (56%) of 144, 96 (67%) of 144, and 93 (70%) of 131 patients had a positive test. A permanent pulse generator was implanted in 114. Time to defer defecation increased during the 3 weeks of screening. Urgencies were unchanged. The computed score was predictive of a permanent pulse generator implantation (Se = 72.6% (95% CI, 59.8-83.1); Sp = 100% (95% CI, 78.2-100); c-index = 0.86 (95% CI, 0.78-0.94)). Limitations No cost analysis or projection based on our proposal to reduce the test phase has been made. Conclusions Permanent pulse generator implantation can be safely proposed early (1-week screening) to fast responders. Nonetheless, permanent implantation may be decided as well in patients exhibiting a delayed response. Whether a rapid response to sacral nerve stimulation could be predictive of a long-term response remains to be determined. See Video Abstract at http://links.lww.com/DCR/A452.

Introduction We investigated the incidence, clinical course and risk factors for symptomatic lymphoceles after radical retropubic prostatectomy with pelvic lymph node dissection. Moreover, we explored parameters for the failure of percutaneous lymphocele drainage. Methods The incidence of symptomatic lymphoceles in patients with prostate cancer who underwent radical retropubic prostatectomy with pelvic lymph node dissection in our department between 2008 and 2013 was investigated retrospectively. The occurrence of lymphoceles was correlated with several clinical and histopathological parameters. In addition, logistic regression analysis was performed to assess the value of independent variables with regard to the development of symptomatic lymphoceles and failure of percutaneous drainage. Results A total of 599 consecutive patients treated with radical retropubic prostatectomy with pelvic lymph node dissection were included in the study, of whom symptomatic lymphocele had developed in 5%. Median time to diagnosis of symptomatic lymphocele was 22.5 days. Median time of percutaneous drainage was 16 days. Overall 43% of patients required surgical unroofing. On multivariate analysis age greater than 67 years (OR 3.27, p=0.005) and removal of more than 10 lymph nodes (OR 2.57, p=0.018) were independent predictors for the development of symptomatic lymphoceles. A significantly increased risk of percutaneous drainage failure was observed in patients who had a body mass index greater than 27 kg/m2 (OR 7.0, p=0.03), followed by a trend for those with a drainage volume of more than 375 ml 24 hours after puncture (OR 3.89, p=0.12). Conclusions Symptomatic lymphocele will develop in 1 of 20 patients after radical retropubic prostatectomy with pelvic lymph node dissection. The number of lymph nodes removed constitutes an independent risk factor. Percutaneous drainage failure is associated with high body mass index and high drainage volume within the first 24 hours after puncture.

We evaluated the outcome in female patients with classic bladder exstrophy and continent urinary diversion for sexual function and fertility.We reviewed the medical records of female exstrophy patients who underwent continent urinary diversion in our department between 1969 and 2014. Patients were invited for followup examination and asked to complete questionnaires relating to sexual function, social integration and maternity.Of 38 eligible patients 29 (response rate 76%) with a followup of 22.3 years were included in study. Primary continent urinary diversion was done in 62% of patients and 38% underwent secondary continent urinary diversion after failed reconstruction of the exstrophic bladder. Sexual function as measured by the Female Sexual Function Index was only little affected in all domains except desire. Mean total Female Sexual Function Index score was 28.4 of a possible 36. Of the women 31% were classified as at risk for sexual dysfunction, 72% had a stable relationship, 41% were married and 31% had completed higher education. The incidence of pelvic organ prolapse requiring surgical repair was 38%. A total of 16 healthy children were conceived by 12 patients. The pregnancy rate after primary continent urinary diversion was higher than after secondary diversion.The sexuality and fertility of female patients with exstrophy after continent urinary diversion appears to be comparable with those in previously reported series of patients in whom the bladder was preserved. Management of sexual function, gynecologic pathologies and fertility should be an active part of long-term followup.

Introduction Open simple prostatectomy is a well-established and effective operation for prostate volumes greater than 80 gm but also associated with bleeding and urinary incontinence. To benefit from the advances of laparoscopy, robot-assisted simple prostatectomy was established. We determined the learning curve of this minimally invasive surgery by evaluating the first procedures by an experienced robotic surgeon. Methods Patients presenting for surgical therapy with prostate volumes greater than 80 gm were considered for the study. Evaluation included validated questionnaires preoperatively, and at 6 and 12 weeks postoperatively. Blood loss, transfusions, operation time and pad use after catheter removal were documented. The experience based on the results from 18 cases treated with robot-assisted simple prostatectomy by one of us (JWT) is presented. Results Mean age of the 18 patients was 71.2 years, mean enucleated prostate volume was 91 gm and mean preoperative flow was 9.0 ml/second. I-PSS and QoL values improved significantly from 25 to 6.1 (p Conclusions Robot-assisted simple prostatectomy is a safe and effective operation for benign prostatic hyperplasia, which can be learned with good results in a rather short time.

BACKGROUND: Anal incontinence is most often linked with sphincter rupture and/or stretching the pudendal nerves. OBJECTIVE: The aim of our study was to investigate the involvement of the puborectal part of the levator ani muscle in anal incontinence. PATIENTS AND MAIN OUTCOME MEASURES: Seventy-eight female patients were studied by anorectal manometry, 3-dimensional ultrasound examination, and concentric needle electromyography of the external anal sphincter, puborectal muscle, and bulbocavernous muscles, completing with the evaluation of the pudendal nerve terminal motor latencies. Damage to the puborectal muscle was defined by an abnormal ultrasound and/or abnormal electromyography. RESULTS: Rupture of the anal sphincter apparatus and puborectal muscle was found in 23% and 3.8%. The EMG showed damage to the puborectal part in 39 cases: this was isolated in 4 cases and combined with external anal sphincter damage in 35 patients. Unilateral or bilateral increase in the terminal motor latencies of the pudendal nerves was found in 36% (28/78) of the patients. The frequency of peripheral neurogenic lesions varied from 36% to 90% according to the electromyographic tests used. There was no correlation between puborectal part damage and resting pressure, perception threshold, and maximum tolerable rectal volume. The mean Wexner index score was not increased by the existence of a defect involving the puborectal part found by echography or by damage to the puborectal part shown by the EMG. Investigating puborectal muscle lesions reduced the percentage of idiopathic anal incontinence to 2.5%. CONCLUSION: Our study confirms the feasibility and usefulness of combined electromyography and 3-dimensional ultrasound examination of the puborectal muscle in anal incontinence.

UNTIL now, ultrasound guided systematic prostate biopsy was the standard procedure for prostate cancer (PCa) detection. However, its limited ability in PCa discrimination resulting in over diagnosis of indolent tumors and under diagnosis of aggressive disease has opened the field for pre-biopsy prostate imaging. Magnetic resonance imaging (MRI) is likely the most sensitive imaging technique for the prostate. The implementation of validated scoring systems like the PI-RADS (Prostate Imaging Reporting and Data System) or the National Institutes of Health scoring system tends to improve decision making for prostate biopsy in daily clinical practice. Several recently published studies show promising sensitivity for prostate MRI to detect significant PCa compared to final pathology of prostatectomy specimens. For example, Bains et al recently reported that interobserver sensitivity and specificity of diffusion weighted MRI for the detection of significant PCa ranged from 89% to 91% and 77% to 81%, respectively. 1 In a study by Le et al the sensitivity of multiparametric MRI was 72% for the detection of high grade tumors and 80% for index lesions. 2 However, the same study clearly showed that MRI still has a limited ability to detect low risk PCa, resulting in an overall MRI sensitivity of 47% for the detection of all tumor foci in the prostatectomy specimen. Thus, from a clinical perspective a decision has to be made if the primary goal of prostate biopsy is to detect all forms of PCa or preferentially clinical significant cancers. Moreover we need a strategy to use systematic biopsies, targeted biopsies or a combination for PCa detection. In this issue of The Journal Radtke et al (page 87) contribute important information to these questions. 3 Using a well conducted prospective study design, the authors compared histopathological results of transperineal template saturation prostate biopsies vs MRI targeted biopsies with MRI/ultrasound fusion guidance in a large cohort. More Gleason score (GS) 7 or greater cancers were missed when using template saturation biopsies vs targeted biopsies (20.9% vs 12.8%), with a trend of superiority for MRI/ultrasound fusion targeted biopsies (p¼0.08). Additionally, fewer biopsy cores were needed to detect significant cancer when using targeted biopsies. Just 7.5% of all systematic cores detected GS 7 or greater cancer while 46% of targeted biopsy cores revealed GS 7 or greater disease. Thus, this study confirms the results of Pokorny et al, who showed that targeted biopsies improve the detection rate of GS 7 or greater cancer and reveal a higher proportion of positive cores compared to systematic biopsies (56.4% vs 15%). 4 Although the PI-RADS score offers valuable predictive information for the detection of clinically significant PCa, it still bears the risk of missing a certain number of these cancers. Radtke et al demonstrated that limiting biopsies to men with PI-RADS 3-5 would have missed 19.8% of all GS 7 or greater cancers. 3 Weagreethata combination ofsystematicbiopsies and targeted biopsies seems to be the safest approach for PCa detection. The combination of these techniques minimizes the risk of missing clinically significant PCa. Additionally, the detection of indolent cancers might allow MRI based active surveillance strategies as recently implemented in the PRIAS (Prostate Cancer Research International Active Surveillance) project. It is also important to note that a lethal clone might potentially also arise from a lower grade cancer focus in the primary tumor. 5 However, combination biopsy is actually not ready for daily clinical practice. Results from large prospective studies with adequate power are needed to validate the cohort studies published to date. Moreover, a standardized protocol for such a biopsy approach is needed as a variety of imaging protocols and biopsy techniques exist. An international consortium that formulated START (Standards of Reporting for MRI-targeted Biopsy Studies) of the prostate has made the first step in this direction. 6

renal biopsy (18-months, 91% vs 91% respectively, p 0.05). Although patients undergoing biopsy had larger tumors (mean 2.3 cm vs 1.8 cm, p 0.01), there was no significant difference in demographic variables, progression to intervention, or radiographic growth rate regardless of histopathology. CONCLUSIONS: Appropriately selected patients who pursue AS for a SRM rarely undergo an intervention within the first year, suggesting that AS is a viable treatment option even in patients with malignancy detected on biopsy. Further follow-up is needed to determine the long-term benefit of active surveillance in patients with small renal masses.