Geographic variation of mutagenic exposures in kidney cancer genomes.

International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden1. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence2. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics.

The effects of a low carbohydrate diet on erectile function and serum testosterone levels in hypogonadal men with metabolic syndrome: a randomized clinical trial.

PURPOSE: Metabolic syndrome is a risk factor for several diseases. The relationship between metabolic syndrome and hypogonadism is well known. Our objetive is to assess whether a low carbohydrate diet can increase total serum testosterone and improve erectile function in hypogonadal men with metabolic syndrome. METHODS: An open label randomized clinical trial was conducted comparing a low carbohydrate diet and controls, during three months, in hypogonadal men with metabolic syndrome. Anthropometric measurements were evaluated as well as total serum testosterone levels, and symptoms of hypogonadism, using the ADAM and AMS scores, and sexual function using IIEF-5 score. RESULTS: Eighteen men were evaluated. Anthropometric measures were improved only in low carbohydrate diet group. The intervention group also had a statistically increase in IIEF-5 score and a significant reduction in AMS and ADAM scores (p < 0.001). The increase in serum total testosterone levels was statistically significant in the low carbohydrate group compared to the control group as well as calculated free testosterone (p < 0.001). CONCLUSIONS: Low carbohydrate diet may increase serum levels of testosterone and improve erectile function in hypogonadal men with metabolic syndrome. However, larger studies are necessary to strongly prove the effectiveness of low carbohydrate diet in treating male hypogonadism.

Association of nerve-sparing grading in robotic radical prostatectomy and trifecta outcome.

PURPOSE: To evaluate the neurovascular bundle preservation grades during robotic-assisted radical prostatectomy and compared to the trifecta combined outcome (oncologic control, continence, and sexual function) twelve months after the surgery. METHODS: Cohort of patients who underwent nerve-sparing robotic-assisted radical prostatectomy had the neurovascular bundle preservation retrospectively graded from 0 to 8 according to the Hopkins subjective visual classification. Patients then were divided into two groups, according to the median of nerve-sparing grading: those with score six or high and those with score less than six. Main outcome was the trifecta combined outcome and secondary outcomes was the individual trifecta criteria (prospective analysis). A secondary analysis with groups divided according to pre-operatory SHIM score was made. RESULTS: One hundred robotic-assisted nerve-sparing radical prostatectomy were performed, of which 83 were included. There were 53 patients with grading greater than or equal to six (group 1) and 30 patients less than six (group 2). 66.6% patients (35/53) in group 1 had a trifecta combined outcome of compared to 33.3% (10/30) in group 2 (p = 0.017). Individually, the erectile function was higher in group 1 (73.6%) compared to group 2 (46.7%) (p = 0.014). Both the results of the combined endpoint trifecta and erection were also maintained in the group with preoperative SHIM ≥ 17. CONCLUSIONS: The grading of preservation of the neurovascular bundle in radical prostatectomy is related to a better combined trifecta outcome one year after surgery.

Laparoscopic resection of large oncocytoma with metaplastic ossification: Case report and video.

Renal oncocytoma (RO) represents about 7% of kidney tumors. They usually behave in a benign fashion, with a slow-growth rate. Patients are often asymptomatic and the tumour is found incidentally on imaging. Due to its wide variation of presentations and multiple radiological findings it is difficult to differentiate RO from renal-cell carcinomas. Interpretation of the images in the appropriate clinical context is crucial and supports the surgeon to avoid aggressive surgical procedures in favor of a nephron-sparing approach, whenever possible. We report a case of a 71-year-old female patient with a large calcified RO which was resected laparoscopically.

Smoking Is Associated With Basal Cell Hyperplasia on Prostate Biopsy Specimens.

OBJECTIVES: To the best of our knowledge, no study has analyzed the association between cigarette smoking and prostate basal cell proliferation. Therefore, we sought to evaluate whether smoking status is associated with the presence of basal cell hyperplasia (BCH). METHODS: We performed a retrospective analysis of 8,196 men aged 50 to 75 years with prostate-specific antigen values between 2.5 µg/mL and 10 µg/mL and prior negative biopsy who were enrolled in the (REDUCE) trial. Cigarette smoking status was divided into current, former, or never categories at enrollment. The association between smoking and baseline BCH was evaluated, with logistic regression in univariable and multivariable analysis. RESULTS: A total of 1,233 (15.1%) men were current smokers, 3,206 (39.1%) were former smokers, and 3,575 (45.8%) were never smokers. In univariable analysis, current smoking was associated with higher baseline BCH occurrence compared with never (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.14-3.10) and former smokers (OR, 1.77; 95% CI, 1.06-2.95). Similar results were found after adjusting for patient characteristics (current vs never smokers: OR, 1.92; 95% CI, 1.14-3.26; current vs former smokers: OR, 1.71; 95% CI, 1.01-2.91). CONCLUSIONS: Among men undergoing prostate biopsy, all of whom had a negative biopsy result, current smoking at enrollment was independently associated with BCH in standard peripheral zone prostate biopsies.

Urology Residents Simulation Training Improves Clinical Outcomes in Laparoscopic Partial Nephrectomy.

BACKGROUND: Partial nephrectomy (PN) is the preferred modality of treatment for small renal masses. Laparoscopic partial nephrectomy (LPN) has been adopted worldwide and a fundamental role is played by surgical skills. The need for skill instruction outside the operating room is well recognized in the modern models of surgery residency training. We aim to investigate the impact of residents' laparoscopic surgical skills training on the successful implementation of LPN in a reference public teaching hospital in southern Brazil. METHODS: We accessed all patients undergoing LPN by senior's urology residents at Hospital de Clínicas de Porto Alegre. Patients were stratified in 2 periods of time named 'LPN eras' 1 and 2, to report the training impact on the outcome. LPN era 1 was from October 2012 to February 2017 and LPN era 2 from March 2017 to June 2019. All the senior residents of LPN era 2 followed a simulation training divided into 4 years with a total training time of 244 hours before performing the LPN. Residents from LPN era 1 did not have simulation training. RESULTS: 124 patients underwent LPN during the study period, 53 (42.7%) of those were performed in LPN era 1 and 71 (57.3%) in LPN era 2. Baseline characteristics of the patients in the two groups were similar. The training performed by LPN era 2 residents was able to significantly reduce estimated blood loss, ischemia time and LOS with p value respectively 0.007, 0.001 and 0.001. LPN era 2 group also reached Trifecta in 77.5% of patients, being significantly more than in the LPN era 1 (p = 0.007). CONCLUSIONS: Simulation in residents surgical training was able to improve clinical outcomes in LPN. These data reinforce the fundamental importance of adequate residents training before performing surgery on a patient.

The impact of 5-alpha-reductase inhibitors on mortality in a prostate cancer chemoprevention setting: a meta-analysis.

PURPOSE: This study aims to evaluate the impact of 5-alpha-reductase inhibitors (5ARI) for prostate cancer (PCa) primary prevention on specific and overall mortality (primary outcomes), the incidence of PCa diagnosis and disease aggressiveness (secondary outcomes). METHODS: We searched MEDLINE, EMBASE, Cochrane, ClinicalTrials and BVS through April 2018 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement to identify randomized clinical trials (RCT) and cohort studies (CS). We included articles with data on mortality or PCa incidence for men using 5ARI previously to PCa diagnosis. RESULTS: Regarding the included studies, nine had data on mortality, 16 on PCa incidence and 12 on Gleason scores (GS). We found that the use of 5ARI had no impact on overall mortality (RR 0.93 95% CI 0.78-1.11) and PCa-related mortality (RR 1.35 95% CI 0.50-3.94), nor on high-grade PCa diagnosis (RR 1.06 95% CI 0.72-1.56). We identified a relative risk reduction of 24% in moderate-grade PCa diagnosis (RR 0.76 95% CI 0.59-0.98) and low-grade PCa diagnosis (RR 0.76 95% CI 0.59-0.97) Also, a reduction of 26% in overall PCa diagnosis was observed in the RCT subgroup analysis (RR 0.74 95% CI 0.65-0.84). CONCLUSION: 5ARI significantly reduced the risk of being diagnosed with PCa, not increasing high-grade disease, overall or cancer-specific mortality. Due to the relatively short mean follow-up of most studies, the mortality analysis is limited.

Can dynamic ultrasonography replace urodynamics in the follow-up of patients with myelomeningocele? A prospective concurrent study.

AIMS: To evaluate the accuracy of dynamic ultrasonography (DUS), as a feasible alternative diagnostic method to identify detrusor overactivity (DO) in patients with neurogenic bladder. METHODS: We performed concurrent analysis of 81 pairs of urodynamic study (UDS) and DUS, in 63 patients with myelomeningocele (MMC), from June 2014 to February 2017. The assessment focused on bladder behavior during the filling phase, DO evaluation, DO with leakage, compliance, and maximum cystometric capacity (MCC). RESULTS: Patient age ranged from 3 months to 34 years (median, 84 months); 47.6% were male. Overall, 9.5% of patients had chronic kidney disease, 20.6% had recurrent urinary tract infection, 19.05% had vesicoureteral reflux, and 69.8% had constipation. Anticholinergic therapy was used by 41.3% of patients. DO was observed in 45.67% of patients and DO with leakage in 42.6%. Mean bladder compliance was 10.39 mL/cmH2 O and normal MCC was 56.79%. DUS had 91.89% sensitivity in identifying DO, 88.64% specificity, 87.18% positive predictive value, 92.86% negative predictive value, and 90.12% accuracy, with a kappa coefficient of 0.8 (P < 0.001). CONCLUSION: MMC follow-up is essential because urinary parameters can change during patient growth. The standard examination is invasive and has related complications, making noninvasive evaluation a desirable alternative, like DUS. Our data suggest that DO and MCC can be evaluated using DUS in patients with MMC. UDS should be performed in patients with abnormal findings on ultrasound evaluation or those with worsening of urinary tract function.

Androgen receptor isoforms expression in benign prostatic hyperplasia and primary prostate cancer.

The role of molecular changes in the androgen receptor (AR) as AR variants (AR-Vs) is not clear in the pathophysiology of benign prostatic hyperplasia (BPH) and hormone-naïve PCa. The aim of the current work was to identify the presence of AR isoforms in benign tissue and primary PCa, and to evaluate the possible association with tumor aggressiveness and biochemical recurrence in primary PCa. The mRNA levels of full length AR (AR-FL) and AR-Vs (AR-V1, AR-V4 and AR-V7) were measured using RT-qPCR. The protein expression of AR-FL (AR-CTD and AR-NTD) and AR-V7 were evaluated by the H-Score in immunohistochemistry (IHC). All investigated mRNA targets were expressed both in BPH and PCa. AR-FL mRNA levels were similar in both groups. AR-V4 mRNA expression showed higher levels in BPH, and AR-V1 and AR-V7 mRNA expression were higher in PCa. The AR-V7 protein showed a similar H-Score in both groups, while AR-CTD and AR-NTD were higher in nuclei of epithelial cells from BPH. These results support the assumption that these constitutively active isoforms of AR are involved in the pathophysiology of primary PCa and BPH. The role of AR-Vs and their possible modulation by steroid tissue levels in distinct types of prostate tumors needs to be elucidated to help guide the best clinical management of these diseases.

Ileal Continent Reservoir: A Feasible Option for Bladder Augmentation and Urinary Diversion.

OBJECTIVE: To present the results of technique of continent urinary diversion, described by Macedo, that allows the configuration of a tunnel with a flap of the ileal tube at the same segment created for the reservoir. METHODS: From January 2006 to November 2016, 29 patients were underwent a urinary diversion by Macedo's technique. Patients' demographics, hospitalization time, surgical time, follow up, continence rate, reservoir capacity, and postoperative complications were evaluated. RESULTS: Sixty-nine percent were male and the median age was 16.9 years. The main etiology was meningomyelocele (69.1%). The mean surgical time was 4.2 hours (standard deviation [SD] 0.9 range 2.9-6.3). The median length of hospital stay was 10 days (interquartile range: 11.3 range 5-51). The mean follow up was 3.3 years (SD 2.2 range 0.3-9.8). Procedure in the bladder neck was performed in 12 patients (41.3%). A continence rate of the catheterizable conduit was 82.8%.The reservoir capacity increased from 134.4 to 364.4 ml (P <.0001). The continence rate improved significantly (20 vs 74%, P <.0001). There was no change in glomerular filtration rates in the long term (143.1 vs 147, P = .45). Morbidity rate was 58% (25 complications in 17 patients), 72% occurred within the first 60 days and 60% were classified as Clavien-Dindo I or II. CONCLUSION: Except for publications from the original author, this is the first series described. The outcomes are similar, adding important data with respect to this technique. They show that the ileal reservoir is feasible, reproducible, and with good results.

Female epispadias: Single-stage approach - A technique to achieve continence.

This video provides a case report of a 3 year old girl with epispadia and the highlights of the surgery. A cystoscopic guided bladder neck plication was performed to achieve continence. Key points include: (1) Skin incision planning; (2) Cutaneous flap liberation to create a new urethra; (3) Complete bladder neck release to allow a controlled plication; (4) Use of cystoscopy to achieve the ideal bladder neck closure; (5) Bladder neck manipulation to achieve continence.

Step by step male to female transsexual surgery

ABSTRACT Introduction After the diagnosis of transsexualism is confirmed therapy commences with psychotherapeutic preparation for the conversion, and after conversion, long-term patient rehabilitation is maintained for at least two years. The indication for surgery is chronic discomfort caused by discord with the patient's natural gender, intense dislike of developing secondary sex characteristics and the onset of puberty. The surgical conversion of transsexuals is the main step in the complex care of these problematic patients (1). This surgery was first described by Benjamin H, using a flap of inverted penile skin (2) and is considered the gold standard since then. Male-to-female transsexual surgical techniques are well defined and give good cosmetic and functional results. Sex reassignment surgery promotes the improvement of psychological aspects and social relationships as shown in the World Health Organization Quality of Life Assessment applied in the patients submitted to this procedure (3). Techniques include the creation of a normal appearing female introitus, a vaginoplasty allowing sexual intercourse and the capability of clitoral orgasm (4). Various methods for neovaginoplasty have been described and can be classified into five categories, i.e. pedicled intestinal transplants, penile skin grafts, penile skin flaps, non-genital skin flaps and non-genital skin grafts (5). In our Hospital, we use penile and scrotal skin flaps. Until now, 174 procedures have been performed by our team using this technique with high rates of satisfaction (3). Patients and methods We present a step-by-step male to female transsexual surgery. Conclusion Surgical gender reassignment of male transsexuals resulted in replicas of female genitalia which enabled coitus with orgasm (1). With this video we show step by step that a surgery using penile skin flaps is able to be performed with good cosmetic results.

Does Previous Laparoscopic Experience Influence Basic Robotic Surgical Skills?

OBJECTIVE: Studies addressing the effect of laparoscopic experience on robotic skills have produced conflicting results. This study aimed to compare simulated robotic surgical tasks using the virtual reality simulator dV-Trainer between laparoscopically experienced surgeons and first-year surgical residents. DESIGN: A cross-sectional study. Participants completed 4 trials of the following tasks on the dV-Trainer: Peg Board 2, Ring and Rail 1, and Suture Sponge 1. Performance was recorded using a computerized built-in scoring algorithm. Scores and metrics were compared between groups 1 and 2 and between the first and subsequent trials. SETTING: Hospital de Clínicas, Porto Alegre, Brazil, a tertiary care teaching hospital. PARTICIPANTS: Twenty laparoscopically experienced surgeons (group 1) and 20 first-year surgical residents (group 2). All participants completed the study. RESULTS: The overall scores for Peg Board 2 (738.04 ± 267.83 vs 730.39 ± 225.31; p = 0.57), Ring and Rail 1 (919.03 ± 242.69 vs 965.84 ± 222.96; p = 0.13), and Suture Sponge 1 (563.62 ± 185.50 vs 560.99 ± 152.71; p = 0.67) did not differ significantly between groups 1 and 2. Group 1 had better results for master workspace range in Peg Board 2 and Ring and Rail 1. Group 2 had higher scores for economy of motion in Peg Board 2 and Ring and Rail 1 and for excessive instrument force in Ring and Rail 1. In both groups, the overall scores in the third and fourth trials were significantly higher than those in the first trial. CONCLUSIONS: There are no significant differences in the performance of simulated robotic surgical tasks between laparoscopically experienced surgeons and laparoscopically naïve surgical residents. Some slight differences were observed in specific metrics, but these differences were not sufficient to change the final results. We may assume that laparoscopic experience should not be an essential step in the initial learning curve of robotic surgery.

Prospective evaluation of vesicourethral anastomosis outcomes in robotic radical prostatectomy during early experience in a university hospital

ABSTRACT Purpose: Robotic assisted radical prostatectomy (RARP) presents challenges for the surgeon, especially during the initial learning curve. We aimed to evaluate early and mid-term functional outcomes and complications related to vesicourethral anastomosis (VUA), in patients who underwent RARP, during the initial experience in an academic hospital. We also assessed possible predictors of postoperative incontinence and compared these results with the literature. Materials and Methods: We prospectively collected data from consecutive patients that underwent RARP. Patients with at least 6 months of follow-up were included in the analysis for the following outcomes: time to complete VUA, continence and complications related to anastomosis. Nerve-sparing status, age, BMI, EBL, pathological tumor staging, and prostate size were evaluated as possible factors predicting early and midterm continence. Results were compared with current literature. Results: Data from 60 patients was assessed. Mean time to complete VUA was 34 minutes, and console time was 247 minutes. Continence in 6 months was 90%. Incidence of urinary leakage was 3.3%, no patients developed bladder neck contracture or postoperative urinary retention. On multivariate analysis, age and pathological staging was associated to 3-month continence status. Conclusion: Our data show that, during early experience with RARP in a public university hospital, it is possible to achieve good results regarding continence and other outcomes related to VUA. We also found that age and pathological staging was associated to early continence status.

Assessment of satisfaction and Quality of Life using self - reported questionnaires after urethroplasty: a prospective analysis

ABSTRACT Objectives To assess patient satisfaction and quality of life after urethroplasty using two different self-reported outcome measures and to compare it with objective clinical data. Materials and Methods We prospectively collected data from 35 consecutive patients who underwent urethroplasty from January 2013 to September 2014. Patient demographics, International Prostate Symptom Score (IPSS), quality of life score, urethral stricture surgery patient-reported outcome measure (USS-PROM), maximum flow rate (Qmax) and post-void residual urine were collected before, two and eight months after surgery. Failure occurred when any postoperative instrumentation was performed. General estimation equation was used to compare the results and linear regression analysis to correlate both questionnaires with objective data. Results Mean age was 61 years. Urethroplasties were equally divided between anastomotic and buccal mucosa grafts and 19 patients (59.3%) had a previous urethral procedure. Overall success rate was 87.5%. IPSS improved from a mean 19 at baseline to 5.32 at 8 months (p <0.001). The mean USS-PROM score also improved from 13.21 preoperatively to 3.36 after surgery (p <0.001) and 84.3% of patients were satisfied or very satisfied with surgical results. Mean Qmax increased from 4.64mL/s to 11mL/s (p <0.001). Strong negative correlation was found respectively between flow rate and USS-PROM (r=-0.531, p <0.001) and with IPSS (r=-0.512, p <0.001). Conclusions Significant improvements in urinary symptoms and in quality of life are expected after urethroplasty and they are correlated with objective measures.

MicroRNA Expression Profile Identifies High Grade, Non-Muscle-Invasive Bladder Tumors at Elevated Risk to Progress to an Invasive Phenotype.

The objective of this study was to identify a panel of microRNAs (miRNAs) differentially expressed in high-grade non-muscle invasive (NMI; TaG3-T1G3) urothelial carcinoma that progress to muscle-invasive disease compared to those that remain non-muscle invasive, whether recurrence happens or not. Eighty-nine high-grade NMI urothelial carcinoma lesions were identified and total RNA was extracted from paraffin-embedded tissue. Patients were categorized as either having a non-muscle invasive lesion with no evidence of progression over a 3-year period or as having a similar lesion showing progression to muscle invasion over the same period. In addition, comparison of miRNA expression levels between patients with and without prior intravesical therapy was performed. Total RNA was pooled for microarray analysis in each group (non-progressors and progressors), and qRT-PCR of individual samples validated differential expression between non-progressive and progressive lesions. MiR-32-5p, -224-5p, and -412-3p were associated with cancer-specific survival. Downregulation of miR-203a-3p and miR-205-5p were significantly linked to progression in non-muscle invasive bladder tumors. These miRNAs include those implicated in epithelial mesenchymal transition, previously identified as members of a panel characterizing transition from the non-invasive to invasive phenotype in bladder tumors. Furthermore, we were able to identify specific miRNAs that are linked to postoperative outcome in patients with high grade NMI urothelial carcinoma of the bladder (UCB) that progressed to muscle-invasive (MI) disease.

Assessment of satisfaction and Quality of Life using self -reported questionnaires after urethroplasty: a prospective analysis.

OBJECTIVES: To assess patient satisfaction and quality of life after urethroplasty using two different self-reported outcome measures and to compare it with objective clinical data. MATERIALS AND METHODS: We prospectively collected data from 35 consecutive patients who underwent urethroplasty from January 2013 to September 2014. Patient demographics, International Prostate Symptom Score (IPSS), quality of life score, urethral stricture surgery patient-reported outcome measure (USS-PROM), maximum flow rate (Qmax) and post-void residual urine were collected before, two and eight months after surgery. Failure occurred when any postoperative instrumentation was performed. General estimation equation was used to compare the results and linear regression analysis to correlate both questionnaires with objective data. RESULTS: Mean age was 61 years. Urethroplasties were equally divided between anastomotic and buccal mucosa grafts and 19 patients (59.3%) had a previous urethral procedure. Overall success rate was 87.5%. IPSS improved from a mean 19 at baseline to 5.32 at 8 months (p < 0.001). The mean USS-PROM score also improved from 13.21 preoperatively to 3.36 after surgery (p< 0.001) and 84.3% of patients were satisfied or very satisfied with surgical results. Mean Qmax increased from 4.64mL/s to 11mL/s (p< 0.001). Strong negative correlation was found respectively between flow rate and USS-PROM (r=-0.531, p< 0.001) and with IPSS (r=-0.512, p < 0.001). CONCLUSIONS: Significant improvements in urinary symptoms and in quality of life are expected after urethroplasty and they are correlated with objective measures.