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Objective: To test the prevalence and predictors of major acute cardiovascular events (MACE) after transurethral prostate surgery (TPS)., Material and Methods: The American College of Surgeons National Surgical Quality Improvement Program database (2011-2016) was queried for patients who underwent transurethral resection of the prostate, photoselective vaporization, or laser enucleation. MACE included: cerebrovascular events, cardiac arrest, myocardial infarction, deep venous thrombosis requiring therapy, and pulmonary embolism episodes occurred up to 30 days after discharge. Univariable and multivariable logistic regression models tested MACE predictors and effect of MACE on perioperative mortality. Within covariates significant at univariable analyses a stepwise selection, based on Akaike Information Criterion values, was performed to fit the most appropriate multivariable model., Results: Overall 44,939 patients were included in our analyses. Of these 365 (0.8%) had MACE within 30 days after surgery. The strongest MACE predictors were recent congestive heart failure (odds ratio [OR]: 2.1, 95% confidence interval [CI]: 1.2-3.7, P = .007), transfusions (OR: 2.5, 95% CI: 1.5-4.1, P <.001) and preoperative Systemic Inflammatory Response Syndrome or sepsis (OR: 2.6, 95% CI: 1.6-4.2, P <.001). Similarly, inpatient (OR: 2.0, 95% CI: 1.6-2.5, P <.001) and nonelective (OR: 1.5, 95% CI: 1.1-2.1, P = .012) patients experienced higher MACE rates. Perioperative mortality rates were statistical significantly higher in MACE patients (OR: 13.1, 95% CI: 8.2-21.0, P <.001)., Conclusion: Up to 1% of patients undergoing transurethral prostate surgery experience MACE. MACE are burdened by high mortality rates (up to 14% in MACE patients). Proper patient selection and postoperative monitoring are necessary to reduce MACE incidence and mortality rates., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Context: The optimal ischemia technique at partial nephrectomy (PN) for renal masses is yet to be determined., Objective: To summarize and analyze the current evidence about surgical, oncological, and functional outcomes after different ischemia techniques (cold, warm, and zero ischemia) at PN., Evidence Acquisition: A computerized systematic literature search was performed by using PubMed (MEDLINE) and Science Direct. Identification and selection of the studies were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria. Outcomes of interest were estimated blood loss (EBL), overall complications, positive surgical margins, local tumor recurrence, and renal function preservation. Meta-analysis and forest-plot diagrams were performed. Overall pooled estimates, together with 95% confidence intervals (CIs), of the incidence of all parameters were obtained using a random effect model (RE-Model) on the log transformed means (MLN), proportion, or standardized mean change, as deemed appropriate., Evidence Synthesis: One hundred and fifty-six studies were included. No clinically meaningful differences were found in terms of EBL after cold (mean: 215.5; 95% CI: 154.2-276.8m), warm (mean: 201.8; 95% CI: 175.0-228.7ml), or zero (mean: 261.2; 95% CI: 171.0-351.3ml) ischemia technique. Overall, postoperative complications were recorded in 14.1% (95% CI: 6.7-27.4), 11.1% (95% CI: 10.0-12.3), and 9.7% (95% CI: 7.7-12.2) of patients after cold, warm, and zero ischemia (p<0.01), respectively. Positive surgical margins were recorded in 4.8% (95% CI: 1.9-10.9), 4.0% (95% CI: 3.4-4.8), and 5.6% (95% CI: 3.1-9.8) of patients after cold, warm, and zero ischemia (p<0.01), respectively. Local recurrence was recorded in 3.2% (95% CI: 1.9-5.2) and 3.1% (95% CI: 0.7-11.5) of patients after warm and zero ischemia (p<0.01), respectively. The log 2 of estimated glomerular filtration ratio mean changes were-1.37 (95% CI:-3.42 to 0.68),-1.00 (-2.04 to 0.03), and-0.71 (-1.15 to-0.27) ml/min after cold, warm, and zero ischemia, respectively. Low level of evidence, retrospective nature of most of included studies, a high risk of selection bias, and heterogeneity within included studies limited the overall quality of the analysis., Conclusions: The effect of ischemia technique at PN is still debatable and subject to confounding by several factors, namely, patients' selection criteria, surgical technique used, and percentage of functional parenchyma spared during surgery. These confounders bias available evidence and were addressed by only a small part of available studies. Unfortunately, the overall quality of literature evidences and the high risk of selection bias limit the possibility of any causal interpretation about the relationship between the ischemia technique used and surgical, oncological, or functional outcomes. Thus, none of the available ischemia technique could be recommended over the other., Patient Summary: The present analysis shows that none of the available ischemia techniques, namely, cold, warm, or zero ischemia, is universally superior to the others, and other factors play a role in the surgical outcome., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate a new hybrid technique, which we defined as mini-laparoendoscopic single-site partial nephrectomy (MILESS-PN), for renal masses presenting an intermediate PADUA score., Materials and Methods: Forty consecutive cases of MILESS-PN performed between April 2013 and November 2015 were included in this study. Mini-laparoendoscopic single-site surgery consisted of the simultaneous use of two 3-mm pararectal trocars and an umbilical SILS trocar; the sequence of steps of MILESS-PN was comparable with standard laparoscopic partial nephrectomy. Demographic data and the main perioperative and oncological outcome parameters were gathered and analyzed., Results: The median operative time was 134.6 (interquartile range [IQR] 110-180) minutes with a median warm ischemia time of 12.1 (IQR 9.5-15.5) minutes. Postoperatively, 4 early complications were recorded and the median hospital stay was 4.2 (IQR 3.5-6.0) days. The median renal tumor size was 3.6 (IQR 2.4-5.3) cm with a median PADUA score of 8.3 (IQR 8-9). The definitive pathologic results revealed a renal cell carcinoma in 32 cases (80%), an angiomyolipoma in 3 cases (7.5%), and an oncocytoma in 5 cases (12.5%). All tumors were removed with negative surgical margins, and at the median follow-up of 34.5 (IQR 24-48) months, all patients were alive without evidence of tumor recurrence or port-site metastasis. A statistically significant decrease in the estimated glomerular filtration rate (eGFR) was observed postoperatively (postoperative vs preoperative median eGFR: 87.6 [IQR 70.4-101.8] and 104.7 [IQR 82.7-123.3], P <.0001) and at 6 months (6 months vs preoperative eGFR 93.6 [IQR 79.1-110.2] and 104.7 [IQR 82.7-123.3], P <.0001)., Conclusion: MILESS-PN for renal tumors with an intermediate PADUA score in well-selected patients is not associated with increased risks for the patients, presenting excellent oncological and functional results at the midterm follow-up. Mini-laparoendoscopic single-site surgery could represent a valid alternative to laparoendoscopic single-site surgery or minilaparoscopy because of its higher surgical reproducibility., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To evaluate whether it is always necessary to test for the presence of asymptomatic bacteriuria (AB) in patients undergoing urologic surgical procedures, and if present, whether to treat AB with antimicrobial prophylaxis., Materials and Methods: All patients who underwent urologic surgical procedures from December 2008 to October 2013 in a tertiary referral urologic center were considered for this study. All patients received antimicrobial prophylaxis in line with European Association of Urology guidelines on urologic infections. AB was diagnosed if ≥10 5 colony-forming units/mL were cultured. The population was subdivided into 2 groups: group A, patients with preoperative AB, and group B, patients without AB. Data on postoperative symptomatic urinary tract infections (UTIs) were compared for the 2 groups., Results: A total of 2201 patients were considered eligible for this study and were analyzed; 668 (30.4%) patients were found to harbor AB (group A), and 1533 (69.6%) patients did not have AB (group B). Microbiologically verified symptomatic postoperative UTIs occurred in 198 patients (8.9%). No difference in terms of overall rate of postoperative symptomatic UTI was found between the 2 groups (group A: 70 [10.4%] and group B: 128 [8.3%]; OR: 1.28 95%CI 0.94-1.74; P = .12), as well as in terms of urosepsis (group A: 2 [0.30%] and group B: 4 [0.26%]; P = 1.0)., Conclusion: In patients undergoing urologic surgical procedures who are receiving antimicrobial prophylaxis in accordance with European Association of Urology guidelines, the preoperative presence of AB in this study was not associated with a higher incidence of postoperative symptomatic UTI., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Urinary tract infections (UTIs) are common in women and many patients with recurrent UTIs do not eradicate the condition albeit being treated with multiple courses of antibiotics. The use of nutritional supplements might reduce the risk of recurrent UTIs. However, the role of supplements taken as single agents appears to be limited. We hypothesized that a combination of cranberries, Lactobacillus rhamnosus, and vitamin C might produce a clinical benefit due to their additive or synergistic effects. We prospectively enrolled 42 consecutive women with recurrent UTIs treated with 120mg cranberries (minimum proanthocyanidin content: 32mg), 1 billion heat-killed L. rhamnosus SGL06, and 750mg vitamin C thrice daily for 20 consecutive d. Patients were advised to stop taking these supplements for 10 d and then to repeat the whole cycle three times. Patients were contacted three mo and six mo following the end of the administration of these supplements and evaluated with a semistructured interview and urinalysis. Responders were defined as the absence of symptoms and negative urinalysis or urine culture. Follow-up data were available for 36 patients. Overall, 26 (72.2%) and 22 patients (61.1%) were responders at the 3-mo and 6-month follow-up. No major side effects were recorded. The administration of cranberries, L. rhamnosus, and vitamin C might represent a safe and effective option in women with recurrent UTIs., Patient Summary: We evaluated the effectiveness of cranberries, Lactobacillus rhamnosus, and vitamin C thrice daily for 20 consecutive d monthly for 3 mo for the management of recurrent urinary tract infections in women. Our results show that this approach might represent a safe and effective option., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To analyze the prevalence of cardiovascular disease (CVD) and osteoporosis in patients treated with androgen deprivation therapy (ADT) for prostate cancer (PCa) but not adherent to European Association of Urology (EAU) guidelines., Materials and Methods: The CHOosIng Treatment for Prostate CanCEr (CHOICE) study was an Italian multicenter, cross-sectional study conducted from December 2010 to January 2012. A total of 1386 patients treated with ADT for PCa (first prescription or renewal of ADT) were selected. According to EAU guidelines, the cohort was categorized in discordant ADT (Group A) and concordant ADT (Group B). The prevalence of CVD and osteoporosis after ADT was recorded., Results: The final cohort included 1075 patients. According to EAU guidelines adherence, 285 (26.51%) and 790 (73.49%) were considered discordant and concordant, respectively. The proportion of men with Charlson Comorbidity Index  > 2 at baseline was statistically similar in Group A (81.8%) compared to Group B (80.8%) (P = .96). The number of complications reported at enrollment was as follows: cardiovascular in 351 (32.7%), endocrine in 166 (15.4%), sexual in 498 (46.3%), osteoporosis in 181 (16.8%), and gynecomastia in 274 (25.5%) subjects. At the multivariate logistic regression analysis adjusted for confounding factors, discordant ADT was associated with greater risk of cardiovascular complications (odds ratio: 2.07; P < .01) and osteoporosis (odds ratio: 1.75; P = .04)., Conclusion: About one-third of patients with PCa received inappropriate ADT and showed a greater risk of CVD and osteoporosis. These results could be useful for setting better policy strategies to limit the inappropriateness of ADT prescription., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Context: Several preclinical reports, randomized controlled trials, systematic reviews, and posthoc analyses corroborate the role of phosphodiesterase type 5 inhibitors (PDE5-Is) in the treatment of men with lower urinary tract symptoms (LUTS) associated with benign prostatic enlargement (BPE)., Objective: Update of the latest evidence on the mechanisms of action, evaluate the current meta-analyses, and emphasize the results of pooled data analyses of PDE5-Is in LUTS/BPE., Evidence Acquisition: Literature analysis of basic researches on PDE5-Is, systematic literature search in PubMed and Scopus until May 2015 on reviews of trials on PDE5-Is, and collection of pooled data available on tadalafil 5mg., Evidence Synthesis: Latest evidences on the pathophysiology of LUTS/BPE has provided the rationale for use of PDE5-Is: (1) improvement of LUT oxygenation, (2) smooth muscle relaxation, (3) negative regulation of proliferation and transdifferentiation of LUT stroma, (4) reduction of bladder afferent nerve activity, and (5) down-regulation of prostate inflammation are the proven mechanisms of action of PDE5-Is. Data from eight systematic reviews demonstrated that PDE5-Is allow to improve LUTS (International Prostate Symptom Score mean difference vs placebo: 2.35-4.21) and erectile function (International Index of Erectile Function mean difference vs placebo: 2.25-5.66), with negligible change in flow rate (Qmax mean difference vs placebo: 0.01-1.43). Pooled data analyses revealed that tadalafil 5mg once daily allows the clinically-meaningful improvement of LUTS and nocturnal voiding frequency independent of both erectile dysfunction severity and improvement., Conclusions: PDE5-Is are safe and effective in improving both LUTS and erectile function in appropriately selected men with LUTS/BPE. Data on the reduction of disease progression, long-term outcomes, and cost-effectiveness analyses are still lacking., Patient Summary: We reviewed recent literature on phosphodiesterase type 5 inhibitors in men with lower urinary tract symptoms associated with prostatic enlargement. We found evidence to confirm that phosphodiesterase type 5 inhibitors are a valid treatment option for men affected by bothersome urinary symptoms with or without erectile dysfunction., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: The urodynamic outcomes for α1-blockers (ABs) treatment in patients with lower urinary tract symptoms related to benign prostatic enlargement (LUTS/BPE) is a matter of debate., Objective: To perform a systematic review and meta-analysis of studies evaluating the ABs urodynamic outcomes in patients with LUTS/BPE. The primary endpoint was variation in bladder outlet obstruction index (BOOI). Secondary endpoints were the maximum urinary flow rate (Qmax) and detrusor pressure at Qmax (PdetQmax). A meta-analysis of placebo-controlled randomized clinical trials (RCTs) was performed to compare ABs with placebo., Evidence Acquisition: A systematic review of PubMed/Medline, ISI Web of Knowledge, and Scopus databases was performed in May 2015. Seventeen studies were selected for inclusion., Evidence Synthesis: The overall pooled data showed a mean BOOI change of -14.19 (p<0.0001), a mean PdetQmax change of -11. 39cm H2O (p<0.0001), and a mean Qmax improvement of 2.27ml/s (p<0.0001). Subgroup analysis showed a mean BOOI change of -14.88 (p=0.01) for alfuzosin, -19.41 (p=0.01) for doxazosin, -16.47 (p<0.0001) for naftopidil, -30.45 (p<0.0001) for silodosin, -14.27 (p=0.002) for tamsulosin, and -6.69 (p=0.005) for terazosin. Subanalysis of RCTs containing a placebo arm showed a significant improvement in BOOI in patients undergoing ABs treatment. Meta-regression revealed a significant positive association between the percentage of patients with obstruction at baseline and the improvement in BOOI after treatment with ABs., Conclusion: ABs improve BOOI in patients with LUTS/BPE mainly by reducing PdetQmax, and this effect is higher in patients presenting with urodynamic obstruction at baseline. The free Qmax variation underestimates the real effect of ABs on benign prostatic obstruction., Patient Summary: Results of this meta-analysis suggest that α1-blockers objectively improve urinary voiding function in patients with benign prostatic obstruction., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The evolution of resistant pathogens is a worldwide health crisis and adherence to European Association of Urology (EAU) guidelines on antibiotic prophylaxis may be an important way to improve antibiotic stewardship and reduce patient harm and costs., Objective: To evaluate the prevalence of antibiotic-resistant bacterial strains and health care costs during a period of adherence to EAU guidelines in a tertiary referral urologic institution., Design, Setting, and Participants: A protocol for adherence to EAU guidelines for antibiotic prophylaxis for all urologic procedures was introduced in January 2011. Data for 3529 urologic procedures performed between January 2011 and December 2013 after protocol introduction were compared with data for 2619 procedures performed between January 2008 and December 2010 before protocol implementation. The prevalence of bacterial resistance and health care costs were compared between the two periods., Outcome Measurements and Statistical Analysis: The outcome measures were the proportion of resistant uropathogens and costs related to antibiotic consumption and symptomatic postoperative infection. We used χ2 and Fisher's exact tests to test the significance of differences., Results and Limitations: The proportion of patients with symptomatic postoperative infection did not differ (180/3529 [5.1%] vs. 117/2619 [4.5%]; p=0.27). A total of 342 isolates from all patients with symptomatic postoperative infections were analysed. The rate of resistance of Escherichia coli to piperacillin/tazobactam (9.1% vs. 5.4%; p=0.03), gentamicin (18.3% vs. 11.2%; p=0.02), and ciprofloxacin (32.3% vs. 19.1%; p=0.03) decreased significantly after protocol introduction. The defined daily dose (DDD) use of ciprofloxacin fell from 4.2 to 0.2 DDD per 100 patient-days after implementation (p<0.001). Antibiotic drug costs (€76,980 vs. €36,700) and costs related to postoperative infections (€45,870 vs. €29,560) decreased following introduction of the protocol (p<0.001)., Conclusions: Adherence to EAU guidelines on antibiotic prophylaxis reduced antibiotic usage without increasing post-operative infection rate and lowered the prevalence of resistant uropathogens., Patient Summary: We analysed the impact of adherence to European Association of Urology guidelines on antibiotic prophylaxis for all surgical urologic procedures on the prevalence of infections and resistant bacterial strains and on costs. We found that adherence to the guidelines reduced the rate of bacterial resistance, in particular against piperacillin/tazobactam, gentamicin, and ciprofloxacin, and reduced costs without increasing the risk of postoperative infection after urologic procedures. We recommend adherence to the guidelines as an important part of antibiotic stewardship programmes., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To assess health-related quality of life (HRQoL) parameters in patients who received radical cystectomy (RC) with ileal orthotopic neobladder (IONB) reconstruction and to identify clinic-pathologic predictors of HRQoL., Patients and Methods: From January 2010 to December 2013, a multicenter, retrospective on 174 RC-IONB patients was carried out. All patients completed the following questionnaires: the European Organization for Research and Treatment of Cancer (EORTC) generic (QLQ-C30) and bladder cancer-specific instruments (QLQ-BLM30) and the IONB-Patient Reported Outcome (IONB-PRO). Univariate and multivariate analyses were computed to identify clinic-pathologic predictors of HRQoL., Results: Median age was 66 years (range, 31-83), and 91.4% of patients were men. Median follow-up period was 37 months (range, 3-247). The EORTC QLQ-C30 revealed that age >65 years, absence of urinary incontinence, and absence of peripheral vascular disease were independent predictors of deteriorated body image. A follow-up > 36 months and the presence of urinary incontinence were independent predictors of worsened urinary symptoms, whereas the absence of urinary incontinence was an independent predictor of a worsened body image according to EORTC QLQ-BLM30 results. A follow-up >36 months and the absence of urinary incontinence were independent predictors of better functioning in terms of relational life, emotional life, and fatigue as revealed by the IONB-PRO., Conclusion: Age, presence of urinary incontinence, length of follow-up, and comorbidity status may influence postoperative HRQoL and should all be taken into account when counseling RC-IONB patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To evaluate the concordance and prognostic role of histologic variants of bladder urothelial carcinoma in transurethral resection of bladder tumor (TURBT) and radical cystectomy (RC) specimens., Methods: Clinicopathologic information available at the time of RC and follow-up data from 4110 RC specimens, collected between January 2000 and December 2009 at 17 tertiary referral centers were retrospectively analyzed and evaluated for the presence or absence of uncommon variants of bladder urothelial carcinoma. The presence or absence of uncommon variants of bladder urothelial carcinoma was evaluated on previous TURBT specimens of patients undergoing RC. Cox regression was used to assess the impact of these parameters on cancer-specific survival, and the Kaplan-Meier test for disease-free survival was plotted for survival estimate., Results: Of 4110 patients, 579 were found to have uncommon variants of bladder urothelial carcinoma at RC (14.1%), whereas 266 (6.4%) at TURBT. A lack of agreement about uncommon variants was observed between TURBT and RC specimens in the entire population (P <.001). The presence of uncommon variants at TURBT was associated with an increased risk of pathologic upstage (hazard ratio, 3.24; confidence interval, 1.19-6.37; P <.003) and significant decrease in cancer-specific survival and recurrence-free survival (P <.001)., Conclusion: Although the concordance of presence of uncommon histologic variants of urothelial bladder carcinoma between TURBT and RC is low, the presence of uncommon histologic variants of urothelial bladder carcinoma at TURBT is associated with a less favorable clinical outcome., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Dapoxetine hydrochloride is a selective serotonin reuptake inhibitor and the first drug approved for the on-demand treatment of premature ejaculation (PE). Its safety was established in a thorough clinical development program., Objective: To characterize the safety profile of dapoxetine in PE treatment and to report the incidence, severity, and type of adverse events., Design, Setting, and Participants: We conducted a 12-wk, open-label, observational study with a 4-wk, postobservational contact. A total of 10,028 patients were enrolled, with 6712 patients (67.6%) treated with dapoxetine 30-60 mg (group A) and 3316 (32.4%) treated with alternative care/nondapoxetine (group B)., Interventions: Treatment with dapoxetine or alternative care/nondapoxetine., Outcome Measurements and Statistical Analysis: Treatment-emergent adverse events (TEAEs) and concomitant therapy use during the 12-wk observational and the postobservational period were reported., Results and Limitations: The mean age for all patients was 40.5 yr. In group A, 93.0% of the patients were initially prescribed dapoxetine 30 mg. Treatment options for group B patients included clomipramine, paroxetine, fluoxetine, sertraline, topical drugs, condoms, and behavioral counseling. Both treatment regimens were well tolerated. TEAEs were reported by 12.0% and 8.9% of group A and group B, respectively, with the highest incidence observed in patients aged >65 yr for group A (21.4%) and 30-39 yr (9.8%) for group B. The most commonly reported TEAEs were nausea, headache, and vertigo, with a higher incidence in group A (3.1%, 2.6%, and 1.0%, respectively) than in group B (oral drugs: 2.3%, 1.3%, and 0.9%, respectively). There were no cases of syncope in group A and one case in group B. A major limitation is that this was a nonrandomized, open-label, short-term study lacking efficacy data., Conclusions: The results of this postmarketing observational study demonstrated that dapoxetine for treatment of PE has a good safety profile and low prevalence of TEAEs. Syncope and major cardiovascular adverse events were not reported. The high level of adherence by healthcare providers to the contraindications, special warnings, and precautions for dapoxetine minimizes the risk for its use in routine clinical practice. The current risk minimization measures for its identified and potential risks are effective., (Copyright © 2013. Published by Elsevier B.V.)

Objective: To compare the last generation of 3-dimensional imaging (3D) vs standard 2-dimensional imaging (2D) laparoscopy., Materials and Methods: A prospective observational study was conducted during the 4th Minimally Invasive Urological Surgical Week Course held in Braga (Portugal) in April 2013. The course participants and faculty were asked to perform standardized tasks in the dry laboratory setting and randomly assigned into 2 study groups; one starting with 3D, the other with 2D laparoscopy. The 5 tasks of the European Training in Basic Laparoscopic Urological Skills were performed. Time to complete each task and errors made were recorded and analyzed. An end-of-study questionnaire was filled by the participants., Results: Ten laparoscopic experts and 23 laparoscopy-naïve residents were included. Overall, a significantly better performance was obtained using 3D in terms of time (1115 seconds, interquartile range [IQR] 596-1469 vs 1299 seconds, IQR 620-1723; P = .027) and number of errors (2, IQR 1-3 vs 3, IQR 2-5.5; P = .001). However, the experts were faster only in the "peg transfer" task when using the 3D, whereas naïves improved their performance in 3 of the 5 tasks. A linear correlation between level of experience and performance was found. Three-dimensional imaging was perceived as "easier" by a third of the laparoscopy-naïve participants (P = .027)., Conclusion: Three-dimensional imaging seems to facilitate surgical performance of urologic surgeons without laparoscopic background in the dry laboratory setting. The advantage provided by 3D for those with previous laparoscopic experience remains to be demonstrated. Further studies are needed to determine the actual advantage of 3D over standard 2D laparoscopy in the clinical setting., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To assess both the acceptance and the discontinuation rates from dapoxetine, the first oral pharmacological agent indicated for the treatment of premature ejaculation (PE)., Methods: One hundred twenty consecutive potent patients (mean age 40.3 years; range 18-63 years) seeking medical treatment for lifelong PE were enrolled in a prospective phase II study. Moreover, they were assessed regarding detailed medical and sexual history, intravaginal ejaculatory latency time (IELT), International Index of Erectile Function (IIEF), and complete physical examination. The patients received a dapoxetine prescription (30 mg on demand) and unresponded cases received increased dose (60 mg after 3 months). The patients were evaluated at 1, 3, 6, and 12 months, and requested to complete a multiple-choice global assessment questionnaire regarding specific reasons for eventual therapy discontinuation., Results: Twenty-four of the patients (20%) decided not to start dapoxetine. Fear of using a "drug" was the most frequently reported reason for treatment nonacceptance (50%) and the cost of treatment was the reason for 25% of the patients. Ninety-six patients (80%) started the therapy. Twenty-six percent dropped out after 1 month, 42.7% dropped out after 3 months, 18.7% dropped out at 6 months, 2% dropped out at 12 months, and 10.4% are continuing the therapy after 1 year. The main reasons were effect below expectations 24.4%, costs 22.1%, side effects 19.8%, loss of interest in sex 19.8%, and no efficacy 13.9%., Conclusion: Twenty percent of lifelong PE patients seeking medical treatment for early ejaculation freely decided not to start treatment with dapoxetine, and roughly 90% of the patients who started therapy discontinued after 1 year., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Approximately 10-20% of recurrences in patients treated with nephrectomy for renal cell carcinoma (RCC) develop beyond 5 yr after surgery (late recurrence)., Objective: To determine features associated with late recurrence., Design, Setting, and Participants: A total of 5009 patients from a multicenter database comprising 13 107 RCC patients treated surgically had a minimum recurrence-free survival of 60 mo (median follow-up [FU]: 105 mo [range: 78-135]); at last FU, 4699 were disease free (median FU: 103 mo [range: 78-134]), and 310 patients (6.2%) experienced disease recurrence (median FU: 120 mo [range: 93-149])., Interventions: Patients underwent radical nephrectomy or nephron-sparing surgery., Outcome Measurements and Statistical Analysis: Multivariable regression analyses identified features associated with late recurrence. Cox regression analyses evaluated the association of features with cancer-specific mortality (CSM)., Results and Limitations: Lymphovascular invasion (LVI) (odds ratio [OR]: 3.07; p<0.001), Fuhrman grade 3-4 (OR: 1.60; p=0.001), and pT stage >pT1 (OR: 2.28; p<0.001) were significantly associated with late recurrence. Based on accordant regression coefficients, these parameters were weighted with point values (LVI: 2 points; Fuhrman grade 3-4: 1 point, pT stage >1: 2 points), and a risk score was developed for the prediction of late recurrences. The calculated values (0 points: late recurrence risk 3.1%; 1-3 points: 8.4%; 4-5 points: 22.1%) resulted in a good-, intermediate- and poor-prognosis group (area under the curve value for the model: 70%; 95% confidence interval, 67-73). Multivariable Cox regression analysis showed LVI (HR: 2.75; p<0.001), pT stage (HR: 1.24; p<0.001), Fuhrman grade (HR: 2.40; p<0.001), age (HR: 1.01; p<0.001), and gender (HR: 0.71; p=0.027) to influence CSM significantly. Limitations are based on the multicenter and retrospective study design., Conclusions: LVI, Fuhrman grade 3/4, and a tumor stage >pT1 are independent predictors of late recurrence after at least 5 yr from surgery in patients with RCC. We developed a risk score that allows for prognostic stratification and individualized aftercare of patients with regard to counseling, follow-up scheduling, and clinical trial design., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Phosphodiesterase type 5 inhibitors (PDE5-Is) are effective in the treatment of lower urinary tract symptom (LUTS), although their mechanism of action is still unclear. PDE5-Is cause bladder detrusor relaxation, and this effect is partially independent of nitric oxide. Hydrogen sulfide (H(2)S) is a newly discovered transmitter with myorelaxant properties. It is predominantly formed from L-cysteine by cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE)., Objective: To evaluate whether the L-cysteine/H(2)S pathway contributes to the relaxing effect of sildenafil on the human detrusor dome., Design, Setting, and Participants: Samples of bladders obtained from men undergoing open prostatectomy for benign prostatic hyperplasia (BPH) were used. The presence of CBS and CSE enzymes was assessed by western blot. H(2)S production was measured by a colorimetric assay in basal and stimulated conditions with L-cysteine and in response to sildenafil (1, 3, 10, and 30 μM), 8-bromo-cyclic guanosine monophosphate (8-bromo-cGMP; 100 μM) or dibutyryl-cyclic adenosine monophosphate (dibutyryl-cAMP; 100 μM). A curve concentration effect of sodium hydrosulfide (NaHS), H(2)S donor (0.1 μM to 10mM), L-cysteine (0.1 μM to 10mM), and sildenafil (0.1-10 μM) was performed on precontracted detrusor dome strips. To investigate H(2)S signaling in a sildenafil effect, CBS and CSE inhibitors were used., Outcome Measurements and Statistical Analysis: Analysis of variance was used, followed by the Bonferroni post hoc test., Results and Limitations: CBS and CSE are present in the human bladder dome and efficiently convert L-cysteine into H(2)S. Both NaHS and L-cysteine relaxed human strips. Sildenafil caused (1) a relaxation of bladder dome strips and (2) a concentration-dependent increase in H(2)S production. Both effects were significantly reduced by CBS and CSE inhibitors. Similar to sildenafil, both 8-bromo-cGMP and dibutyryl-cAMP caused an increase in H(2)S production., Conclusions: The sildenafil relaxant effect on the human bladder involves the H(2)S signaling pathway. This effect may account in part for the efficacy of PDE5-Is in LUTS. A better definition of the pathophysiologic role of the H(2)S pathway in the human bladder may open new therapeutic approaches., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Tadalafil improved lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH; LUTS/BPH) in clinical studies but has not been evaluated together with an active control in an international clinical study., Objective: Assess tadalafil or tamsulosin versus placebo for LUTS/BPH., Design, Setting, and Participants: A randomised, double-blind, international, placebo-controlled, parallel-group study assessed men ≥45 yr of age with LUTS/BPH, International Prostate Symptom Score (IPSS) ≥13, and maximum urinary flow rate (Q(max)) ≥4 to ≤15ml/s. Following screening and washout, if needed, subjects completed a 4-wk placebo run-in before randomisation to placebo (n=172), tadalafil 5mg (n=171), or tamsulosin 0.4mg (n=168) once daily for 12 wk., Measurements: Outcomes were assessed using analysis of covariance (ANCOVA) or ranked analysis of variance (ANOVA) (continuous variables) and Cochran-Mantel-Haenszel test or Fisher exact test (categorical variables)., Results and Limitations: IPSS significantly improved versus placebo through 12 wk with tadalafil (-2.1; p=0.001; primary efficacy outcome) and tamsulosin (-1.5; p=0.023) and as early as 1 wk (tadalafil and tamsulosin both -1.5; p<0.01). BPH Impact Index significantly improved versus placebo at first assessment (week 4) with tadalafil (-0.8; p<0.001) and tamsulosin (-0.9; p<0.001) and through 12 wk (tadalafil -0.8, p=0.003; tamsulosin -0.6, p=0.026). The IPSS Quality-of-Life Index and the Treatment Satisfaction Scale-BPH improved significantly versus placebo with tadalafil (both p<0.05) but not with tamsulosin (both p>0.1). The International Index of Erectile Function-Erectile Function domain improved versus placebo with tadalafil (4.0; p<0.001) but not tamsulosin (-0.4; p=0.699). Q(max) increased significantly versus placebo with both tadalafil (2.4ml/s; p=0.009) and tamsulosin (2.2ml/s; p=0.014). Adverse event profiles were consistent with previous reports. This study was limited in not being powered to directly compare tadalafil versus tamsulosin., Conclusions: Monotherapy with tadalafil or tamsulosin resulted in significant and numerically similar improvements versus placebo in LUTS/BPH and Q(max). However, only tadalafil improved erectile dysfunction., Trial Registration: Clinicaltrials.gov ID NCT00970632., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: Several randomized controlled trials (RCTs) on phosphodiesterase type 5 inhibitors (PDE5-Is) have showed significant improvements in both lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) in men affected by one or both conditions, without a significant increase in adverse events. However, the results are inconsistent., Objective: Perform a systematic review and meta-analysis of available prospective and cross-sectional studies on the use of PDE5-Is alone or in combination with α1-adrenergic blockers in patients with LUTS/benign prostatic hyperplasia (BPH)., Evidence Acquisition: A systematic search was performed using the Medline, Embase, and Cochrane Library databases through September 2011 including the combination of the following terms: LUTS, BPH, PDE5-Is, sildenafil, tadalafil, vardenafil, udenafil, α-blockers, and α1-adrenergic blocker. The meta-analysis was conducted according to the guidelines for observational studies in epidemiology., Evidence Synthesis: Of 107 retrieved articles, 12 were included in the present meta-analysis: 7 on PDE5-Is versus placebo, with 3214 men, and 5 on the combination of PDE5-Is with α1-adrenergic blockers versus α1-adrenergic blockers alone, with 216 men. Median follow-up of all RCTs was 12 wk. Combining the results of those trials, the use of PDE5-Is alone was associated with a significant improvement of the International Index of Erectile Function (IIEF) score (+5.5; p<0.0001) and International Prostate Symptom Score (IPSS) (-2.8; p<0.0001) but not the maximum flow rate (Q(max)) (-0.00; p=not significant) at the end of the study as compared with placebo. The association of PDE5-Is and α1-adrenergic blockers improved the IIEF score (+3.6; p<0.0001), IPSS score (-1.8; p = 0.05), and Q(max) (+1.5; p<0.0001) at the end of the study as compared with α-blockers alone., Conclusions: The meta-analysis of the available cross-sectional data suggests that PDE5-Is can significantly improve LUTS and erectile function in men with BPH. PDE5-Is seem to be a promising treatment option for patients with LUTS secondary to BPH with or without ED., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Previously published preliminary findings showed promising activity of paclitaxel in chemotherapy-pretreated metastatic penile cancer., Objective: To evaluate the activity and safety of paclitaxel in pretreated metastatic penile cancer., Design, Setting, and Participants: Twenty-five patients were enrolled in a single-arm phase 2 multicentre study and treated with 175 mg/m² paclitaxel at 3-wk intervals until disease progression or irreversible toxicity., Measurements: The objective response rate was the primary end point. Safety, progression-free survival (PFS), and overall survival (OS) were secondary end points., Results and Limitations: Partial responses were observed in 20% (5 of 25 patients). Grade 1-2 neutropenia, nausea, and oral mucositis were the most common side effects, noted in 13, 9, and 8 patients, respectively. Grade 3-4 neutropenia was reported in seven patients (28%). Median PFS was 11 wk (95% confidence interval [CI], 7-30); median OS was 23 wk (95% CI, 13-48). Median survival in responders was 32 wk (95% CI, 20-48). One limitation of our study was the limited accrual, which did not reach the target of 27 patients, due to the typical slow enrolment of a rare disease., Conclusions: Final results of this study demonstrate that paclitaxel is moderately active and well tolerated. Further trials, which may also explore the combination of paclitaxel with other agents, are required to confirm our findings., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Tadalafil is being investigated for the treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH-LUTS)., Objective: To assess efficacy, including onset, and safety of tadalafil on BPH-LUTS and the subject's and clinician's perception of changes in urinary symptoms., Design, Setting, and Participants: This randomized, double-blind, placebo-controlled, 12-week trial enrolled men ≥45 yr of age with BPH-LUTS for >6 mo, International Prostate Symptom Score (IPSS) ≥13, and maximum urine flow rate (Q(max)) ≥4 to ≤15 ml/s., Intervention: Tadalafil 5mg (n=161) or placebo (n=164), once daily., Measurements: Analysis of covariance (ANCOVA) modeling evaluated change from baseline in continuous efficacy variables. Categoric efficacy variables were analyzed with the Cochran-Mantel-Haenszel test, and between-group differences in treatment-emergent adverse events (TEAEs) were assessed using the Fisher exact test. RESULTS AND LIMITATION: Tadalafil significantly improved IPSS results, from baseline to endpoint, compared to placebo (-5.6 vs -3.6; p=0.004). Reduction in IPSS results was apparent after 1 wk and significant after 4 wk (tadalafil -5.3 vs placebo -3.5; p=0.003). The BPH Impact Index (BII) was not assessed at week 1; however, BII improvement was apparent at 4 wk (tadalafil -1.8 vs placebo -1.2; p=0.029) and continued at 12 wk (tadalafil -1.8 vs placebo -1.3; p=0.057). Tadalafil significantly improved the International Index of Erectile Function-Erectile Function score in sexually active men with erectile dysfunction (ED; 6.7 vs 2.0; p<0.001) at 12 wk (not assessed at week 1). Few subjects reported one TEAE or more (p=0.44). For tadalafil, the most common TEAEs were headache (3.7%) and back pain (3.1%). Tadalafil did not significantly improve Q(max) or reduce postvoid residual volume., Conclusions: Tadalafil 5mg once daily for 12 wk resulted in a clinically meaningful reduction in total IPSS results as early as 1 wk and achieved statistical significance at 4 wk in men with BPH-LUTS. The adverse event profile was consistent with that previously reported in men with ED., Trial Registration: This clinical trial is registered on the clinicaltrials.gov website (http://www.clinicaltrials.gov). The registration number is NCT00827242., (Copyright © 2011. Published by Elsevier B.V.)

Context: This review focuses on the relationship among sexual dysfunction (SD), lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), and related therapies., Objective: We reviewed the current literature to provide an overview of current data regarding epidemiology and pathophysiology of SD and LUTS. Moreover, we analysed the impact of currently available therapies of LUTS/BPH on both erectile dysfunction (ED) and ejaculatory dysfunction and the effect of phosphodiesterase type 5 inhibitors (PDE5-Is) in patients with ED and LUTS., Evidence Acquisition: We conducted a Medline search to identify original articles, reviews, editorials, and international scientific congress abstracts by combining the following terms: benign prostatic hyperplasia, lower urinary tract symptoms, sexual dysfunction, erectile dysfunction, and ejaculatory dysfunction., Evidence Synthesis: We conducted a comprehensive analysis of more relevant general population-based and BPH/LUTS or SD clinic-based trials and evaluated the common pathophysiologic mechanisms related to both conditions. In a further step, the overall impact of current BPH/LUTS therapies on sexual life, including phytotherapies, novel drugs, and surgical procedures, was scrutinized. Finally, the usefulness of PDE5-Is in LUTS/BPH was critically analysed, including preclinical and clinical research data as well as possible mechanisms of action that may contribute to the efficacy of PDE5-Is with LUTS/BPH., Conclusions: Community-based and clinical data demonstrate a strong and consistent association between LUTS and ED, suggesting that elderly men with LUTS should be evaluated for SD and vice versa. Pathophysiologic hypotheses regarding common basics of LUTS and SD as discussed in the literature are (1) alteration of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway, (2) enhancement of RhoA-Rho-kinase (ROCK) contractile signalling, (3) autonomic adrenergic hyperactivity, and (4) pelvic atherosclerosis. The most important sexual adverse effects of medical therapies are ejaculation disorders after the use of some α-blockers and sexual desire impairment, ED, and ejaculatory disorders after the use of α-reductase inhibitors. Minimally invasive, conventional, and innovative surgical treatments for BPH may induce both retrograde ejaculation and ED. PDE5-Is have demonstrated significant improvements in both LUTS and ED in men with BPH; combination therapy with PDE5-Is and α1-adrenergic blockers seems superior to PDE5-I monotherapy., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Sunitinib and everolimus have been approved for first- and second-line treatment, respectively, in metastatic renal cell carcinoma (mRCC). The role of sorafenib, which is approved for second-line treatment after cytokines failure, is presently to be defined., Objective: To determine whether third-line sorafenib after sequential use of sunitinib and mammalian target of rapamycin inhibitors (everolimus or temsirolimus) is feasible and effective., Design, Setting, and Participants: One hundred fifty medical records of patients with mRCC treated with first-line sunitinib between January 2006 and January 2010 were reviewed at four participating centers. Data regarding patients treated with the sequence sunitinib-everolimus or temsirolimus-sorafenib were extracted. Central analysis of radiographic images was performed using RECIST criteria to determine progression-free survival (PFS) and overall response rate (oRR) to sorafenib treatment., Measurements: PFS and oRR to sorafenib were the primary end points. Secondary outcomes were safety and overall survival (OS)., Results and Limitations: Thirty-four patients were eligible for the study. A median PFS of 4 mo (range: 3-6 mo) and a median OS of 7 mo since sorafenib treatment (range: 6-10 mo) were reported. Of the patients, 23.5% showed response to sorafenib, with an overall disease control rate (complete responses plus partial responses plus stable disease) of 44%. Selection bias, data incompleteness, and absence of study design are inevitable limitations of the study, although central review can strengthen the quality of presented data., Conclusions: Third-line sorafenib appears to be active and well tolerated in mRCC after first-line sunitinib and second-line everolimus or temsirolimus, with no patients interrupting sorafenib because of toxicity or lack of compliance. Prospective, placebo-controlled trials are completely lacking and are required in this setting., (Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: A new edition of the TNM was recently released that includes modifications for the staging system of kidney cancers. Specifically, T2 cancers were subclassified into T2a and T2b (< or =10 cm vs >10 cm), tumors with renal vein involvement or perinephric fat involvement were classified as T3a cancers, and those with adrenal involvement were classified as T4 cancers., Objective: Our aim was to validate the recently released edition of the TNM staging system for primary tumor classification in kidney cancer., Design, Setting, and Participants: Our multicenter retrospective study consisted of 5339 patients treated in 16 academic Italian centers., Intervention: Patients underwent either radical or partial nephrectomy., Measurements: Univariable and multivariable Cox regression models addressed cancer-specific survival (CSS) after surgery., Results and Limitations: In the study, 1897 patients (35.5%) were classified as pT1a, 1453 (27%) as pT1b, 437 (8%) as pT2a, 153 (3%) as pT2b, 1059 (20%) as pT3a, 117 (2%) as pT3b, 26 (0.5%) as pT3c, and 197 (4%) as pT4. At a median follow-up of 42 mo, 786 (15%) had died of disease. In univariable analysis, patients with pT2b and pT3a tumors had similar CSS, as did patients with pT3c and pT4 tumors. Moreover, both pT3a and pT3b stages included patients with heterogeneous outcomes. In multivariable analysis, the novel classification of the primary tumor was a powerful independent predictor of CSS (p for trend <0.0001). However, the substratification of pT1 tumors did not retain an independent predictive role. The major limitations of the study are retrospective design, lack of central pathologic review, and the small number of patients included in some substages., Conclusions: The recently released seventh edition of the primary tumor staging system for kidney tumors is a powerful predictor of CSS. However, some of the substages identified by the classification have overlapping prognoses, and other substages include patients with heterogeneous outcomes. The few modifications included in this edition may have not resolved the most critical issues in the previous version., (Copyright 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Phosphodiesterase 5 inhibitors (PDE5-Is) are a mainstay in the therapy of erectile dysfunction (ED). The primary end point of clinical efficacy, both in clinical studies and normal practice, is represented by the International Index of Erectile Function (IIEF)., Objective: To evaluate if platelet cyclic guanosine monophosphate (cGMP) could represent a valuable marker for PDE5-I activity in ED., Design, Setting, and Participants: The study enrolled 46 patients with psychogenic, organic, and mixed ED (20-71 yr of age; IIEF score<26). Patients were randomized to 6 wk of vardenafil, 5 mg/d at bedtime, or placebo., Intervention: All patients donated two blood samples, one before starting the protocol and the second after 6 wk of treatment., Measurements: Platelet cGMP was measured in both placebo and vardenafil groups. All the patients completed the IIEF-Erectile Function (EF) domain and the sexual encounter profile (SEP) and underwent visual sexual stimulation (VSS) coupled with Rigiscan. All the measurements were performed prior to starting the protocol and after the 6 wk of treatment., Results and Limitations: Platelet cGMP production was significantly (p<0.05) elevated in patients taking 5mg vardenafil versus placebo. Vardenafil was not superior to placebo in improving IIEF-EF and SEP scores. Conversely, VSS-Rigiscan revealed a significant amelioration (p<0.028) in the vardenafil group versus placebo. The changes in platelet cGMP level correlated well with VSS-Rigiscan (p=0.0037) but not with IIEF-EF and SEP., Conclusions: Platelet cGMP could represent a relatively simple, reliable, and objective biomarker of PDE5-I activity in ED clinical studies. Larger clinical studies are needed to further validate the use, utility, and limits of this assay.

Background: Effects of renal transplantation (RT) on erectile dysfunction (ED) is a controversial issue., Objective: To verify the efficacy of RT in restoring erectile function (EF) in hemodialysed patients., Design, Setting, and Participants: We conducted a prospective, interventional, nonrandomised study from September 2001 to September 2005 on 78 hemodialysed male patients undergoing RT. EF was evaluated during the baseline visit and 1 yr after RT, using the International Index of Erectile Function (IIEF) questionnaire. A subanalysis was performed by splitting the total cohort into two age groups: <45 yr and ≥45 yr., Intervention: RT was performed., Measurements: EF was evaluated using the IIEF scoring system., Results and Limitations: Before RT, 68 patients with a mean total IIEF score of 42.46 complained about ED. One year after RT, 71 patients reported ED, and the mean total IIEF score had decreased to 39.97. The mean pre-RT IIEF EF domain score was 18.48, and it decreased to 17.55 after RT. Patients aged≥45 yr reported no significant variations in any IIEF domain, while patients aged<45 yr reported a significant decrease in mean total IIEF score due to variations in domain scores for erectile function, sexual desire, and overall satisfaction. In the younger age group, we found significant differences between baseline and post-RT IIEF scores in dyslipidaemic patients and in those patients using immunosuppressive (methylprednisolone and cyclosporin) or antihypertensive (ACE-inhibitors, β-blockers, and Ca-antagonists) drugs. The main limitations were the absence of any aetiological characterisation of ED and the small number of patients., Conclusions: After RT, EF worsens in patients<45 yr but is not modified in patients≥45 yr.

Context: Epidemiologic data demonstrate a protective role by normal androgen levels on cardiovascular health and erectile function. Low androgen levels are associated with erectile dysfunction and increased risk of cardiovascular diseases. Both conditions recognize as anatomic substrate a pathologic structural remodeling. Direct androgen effects on male external genitalia, vascular wall, and myocardium have been reported., Objective: To review current knowledge about androgen-dependent molecular signaling pathways and cellular events within penile and cardiovascular tissues involved in the homeostatic control of morphologic tissue properties and in the development of structural remodeling in presence of normal and low androgen levels, respectively., Evidence Acquisition: A literature search was performed in November 2008 using the commercially available Medline online engine search to retrieve studies (from 1998 to 2008) on the mechanisms mediating the role of androgens on penile and cardiovascular morphologic homeostasis and remodeling. A combination of the following medical subject headings was used: androgens, hypogonadism, vessel tissue architecture, remodeling, cardiovascular system, and penis., Evidence Synthesis: Androgens exert direct beneficial effects on both cardiovascular and penile tissues. Endothelial cells and smooth-muscle cells are the main cellular targets for direct androgen effects in both tissues and are involved in pathologic remodeling in hypogonadal models. At vascular level, androgens promote endothelial cell survival, reduce endothelial expression of proinflammatory markers, and inhibit proliferation and intimal migration of vascular smooth-muscle cells. At penile level, low androgen levels are associated with apoptosis of endothelial cells and smooth-muscle cells. Moreover, low androgen levels impair proliferation, migration, and homing of endothelial progenitor cells as well as myogenic differentiation of mesenchymal progenitor cells., Conclusions: Normal androgen levels promote vascular and penile homeostasis by direct mechanisms mainly involving endothelial cells and smooth-muscle cells. Low androgen levels are associated with impairments of such mechanisms, leading to pathologic structural remodeling.

Background: Testosterone (T) induces a rapid relaxation in vascular tissues of different species due to a nongenomic effect of this steroid on vessels. Different mechanisms have been proposed to explain T-induced vasodilatation but the effective mechanism(s) and the mediators involved are still a matter of debate., Objectives: We have evaluated if H(2)S pathway is involved in T vascular effects., Design and Setting: Male Wistar rats were sacrificed and thoracic aorta was rapidly dissected and cleaned from fat and connective tissue. Rings of 2-3 mm length were cut and placed in organ baths filled with oxygenated Krebs solution at 37 degrees C and mounted to isometric force transducers. H(2)S determination was performed on thoracic aortic rings incubated with T or vehicle and in presence of inhibitors. H2S concentration was calculated against a calibration curve of NaHS (3-250 microM). Results were expressed as nmoles/mg protein., Measurements: Vascular reactivity was evaluated by using isometric transducers. H(2)S determination was performed by using a cystathionine beta-synthetase (CBS) and cystathionine gamma lyase (CSE) activity assay. CSE and CBS protein levels were assessed by Western blot analysis. Statistical analysis was performed by using two-way ANOVA and unpaired Student's t-test where appropriate., Results: T significantly increased conversion of L-cysteine to H(2)S. This effect was significantly reduced by PGG and BCA, two specific inhibitors of CSE. T (10 nM-10 microM) induced a concentration-dependent vasodilatation of rat aortic rings in vitro that was significantly and concentration-dependent inhibited by PGG, BCA, and glybenclamide. Incubation of aorta with T up to 1 h did not change CBS/CSE expression, suggesting that T modulates enzymatic activity., Conclusions: Here we demonstrate that T vasodilator effect involves H(2)S, a novel gaseous mediator. T modulates H(2)S levels by increasing the enzymatic conversion of L-cysteine to H(2)S.

Background: Extracorporeal shock wave therapy (ESWT) is a conservative therapy for patients with Peyronie's disease (PD)., Objective: To investigate the effects of ESWT in patients with PD., Design, Setting, and Participants: One hundred patients with a history of PD not >12 mo who had not had previous PD-related treatments were enrolled in a prospective, randomized, double-blind, placebo-controlled study. Patients were randomly allocated to either ESWT (n=50) or placebo (n=50). Erectile function (EF), pain during erection, plaque size, penile curvature, and quality of life (QoL) were assessed at baseline, at 12 wk, and at 24 wk follow-up., Intervention: Four weekly treatment sessions were administered. Each ESWT session consisted of 2000 focused shock waves. For the placebo group, a nonfunctioning transducer was employed., Measurements: EF was evaluated with the shortened version of the International Index of Erectile Function (IIEF-5), pain was evaluated with a visual analog scale (VAS; 0-10), plaque size was measured in cm(2), and penile curvature was measured in degrees., Results and Limitations: After 12 wk, mean VAS score, mean IIEF-5 score, and mean QoL score ameliorated significantly in patients receiving ESWT. Mean plaque size and mean curvature degree were unchanged in the ESWT group, while a slight increase was reported in the placebo group (p-value not significant vs baseline). After 24 wk, mean IIEF-5 score and mean QoL score were stable in the ESWT group, while mean VAS score was significantly lower when compared with baseline in both groups. Interestingly, after 24 wk, mean plaque size and mean curvature degree were significantly higher in the placebo group when compared with both baseline and ESWT values. The main limitations were that the QoL questionnaire was not validated, ED was not etiologically characterized, and inclusion criteria were restricted., Conclusions: In patients with PD, ESWT leads to pain resolution and ameliorates both EF and QoL.

Background: Knowledge of baseline factors that influence outcomes for men with benign prostatic hyperplasia (BPH) receiving medical therapy may help to improve outcomes and cost effectiveness., Objectives: To examine the influence of baseline parameters on changes in International Prostate Symptom Score (IPSS) and maximum urinary flow rate (Q(max)) in men with BPH receiving dutasteride, tamsulosin, or a combination of the two using 2-yr Combination of Avodart and Tamsulosin (CombAT) study data., Design, Setting, and Participants: CombAT is an ongoing, 4-yr, multicentre, randomised, double-blind study in 4844 men aged >or=50 yr with clinical diagnosis of BPH, IPSS >or=12, prostate volume >or=30 cm(3), prostate-specific antigen (PSA) 1.5-10 ng/ml, and Q(max) >5 and or=125 ml., Intervention: Daily tamsulosin 0.4 mg, dutasteride 0.5 mg, or the combination., Measurements: Post hoc analyses of mean IPSS and Q(max) changes from baseline by treatment group and by baseline prostate volume, PSA, age, body mass index (BMI), IPSS, IPSS quality of life (QoL) score, BPH Impact Index score, Q(max), and previous BPH medical therapy., Results and Limitations: Combination therapy was more effective than either monotherapy after 24 mo in improving IPSS in all baseline subgroups, with benefit onset varying by baseline prostate volume. Combination therapy was also more effective in improving Q(max) versus tamsulosin in all subgroups and versus dutasteride in 10 of 18 subgroups. At 24 mo, dutasteride monotherapy resulted in significantly greater IPSS improvements versus tamsulosin in men with lower age, worse symptoms, worse QoL, less bother, higher BMI, greater Q(max), higher prostate volume, and higher PSA at baseline. Post hoc analyses, the lack of placebo control, and the exclusion of men with unsuccessful medical BPH treatment are study limitations., Conclusions: Combination therapy with tamsulosin and dutasteride affords the greatest and the most rapid symptomatic benefit among men with higher baseline prostate volume and is effective regardless of previous BPH medical therapy. Dutasteride monotherapy is more effective than tamsulosin in men with higher baseline prostate volume or PSA and worse symptoms.

Objective: Although the taxanes represent the most active agents for the first-line treatment of metastatic hormone-refractory prostate cancer (HRPC), most patients eventually progress while receiving taxane-based treatments. No agents are approved for second-line therapy in HRPC, but common standard practice for the oncologists is to treat patients also after docetaxel failure., Methods: Twenty highly pretreated patients with HRPC received bevacizumab (10mg/kg) and docetaxel (60mg/m(2)) every 3 wk. All patients had bone metastases and eight had measurable lesions., Results: Eleven patients (55%) had major prostate-specific antigen (PSA) responses, and 3 (37.5%) had objective responses. Seven major PSA responses were recorded in the same patients who had reported a >50% PSA decrease after first-line docetaxel. However, four major PSA responses were observed in patients previously nonresponsive to docetaxel alone. The treatment was well tolerated., Conclusions: Our results show that the combination of bevacizumab and docetaxel is active and well tolerated. Continued investigation of bevacizumab with cytotoxic chemotherapy is warranted in HRPC.

Objectives: Combining antineoplastic agents is the key to improving the treatment options for men with hormone refractory prostate cancer (HRPC). The current study investigated the combination of docetaxel, vinorelbine, and zoledronic acid as a first-line treatment for HRPC., Methods: Patients were treated repeatedly with docetaxel (25 mg/mq) and vinorelbine (10 mg/mq) intravenously for three consecutive weeks followed by a 1-wk rest until disease progression or side effects. Zoledronic acid was administered every 4 wk. Changes in prostate-specific antigen (PSA) levels and objective responses were evaluated after two and three cycles, respectively. Toxicity and pain evaluation, based on pain intensity reduction and analgesic drug reduction, were assessed every cycle., Results: Forty men with HRPC (median age: 65 yr) were treated. Among 38 evaluable patients, complete and major PSA responses were observed in seven (18%) and 12 (32%), respectively; a partial objective response was observed in six of 15 (40%) patients with measurable disease. Neutropenia (25%) was the most important grade 3 haematologic toxicity observed. Only three patients (7.5%) reported grade 4 neutropenia. Nineteen patients (47.5%) achieved a reduction of pain intensity and analgesic drug use after two cycles. Median progression-free survival was 7 mo (95% CI: 2-10 mo), with a median overall survival of 17 mo (95% CI: 6-22 mo)., Conclusions: The combination of docetaxel, vinorelbine, and zoledronic acid is associated with improvement in biochemical, objective, and pain responses and is well tolerated as a first-line treatment for HRPC.

Objective: Incidence of venous thromboembolism (VTE) and need for thromboprophylaxis in urologic surgery have received little attention since only one randomised study has addressed this issue in the last 20 yr. The present prospective observational study evaluated incidence and risk factors for clinically overt VTE in a wide spectrum of consecutive patients undergoing surgery for cancer and compared findings in urologic patients with those in patients undergoing general or gynaecologic surgery., Methods: Patients having cancer surgery (general surgery, gynaecology, urology) were assessed for clinically overt VTE occurring up to 30+/-5 d after intervention or more if the hospital stay was longer. All suspected VTE events were evaluated by an external independent Adjudication Committee., Results: A total of 2373 patients, 1238 (52%) undergoing general surgery, 685 (29%) urologic, and 450 (19%) gynaecologic surgery were evaluated. In urologic patients, most procedures (61%) were endoscopic, with bladder and prostate cancer being the most frequent tumours. In-hospital thromboprophylaxis was given to 71.7% of patients, whereas 32.5% received prophylaxis after discharge. The incidence of VTE in urologic patients was lower (0.87%) than that in general surgery and gynaecologic patients (2.8% and 2.0%, respectively). VTE consisted of three cases of nonfatal and three cases of fatal pulmonary embolism (PE). In four of the six cases, VTE occurred during prophylaxis., Conclusions: VTE still represents a severe complication and remains the most common cause of death after urologic cancer surgery. Efforts should be made to optimise prophylactic measures to further reduce such risk.

Objectives: Benign prostatic hyperplasia (BPH) is considered a frequent cause of bladder outlet obstruction (BOO) and lower urinary tract symptoms (LUTS), although the physiopathologic mechanism through which BPH causes LUTS is not clear. Several morphologic and functional modifications of the bladder detrusor have been described in patients with BPH and could play a direct role in determining symptoms. The opinion is spreading that the enlarged prostates in patients with LUTS is nothing more than a mere bystander. Evidence has accumulated, however, supporting the role of BPH-related BOO as the direct cause determining bladder dysfunction and indirectly causing urinary symptoms. The present review addresses the bladder response to BOO, particularly focusing on the physiopathologic cascade that links obstructive BPH to bladder dysfunction., Methods: A literature review of peer-reviewed articles has been performed, including both in vivo and in vitro studies on human tissue and animal model experiments., Results: Epithelial and smooth muscle cells in the bladder wall are mechanosensitive, and in response to mechanical stretch stress caused by BOO, undergo modifications of gene expression and protein synthesis. This process involves several transduction mechanisms and finally alter the ultrastructure and physiology of cell membranes, cytoskeleton, contractile proteins, mitochondria, extracellular matrix, and neuronal networks., Conclusions: BOO is the initiator of a physiopathologic cascade leading to deep changing of bladder structure and function. Before being a direct cause of storing-phase urinary symptoms, the bladder is the first innocent victim of prostatic obstruction.

Objective: To analyse the relationship between smoking and erectile dysfunction (ED)., Methods: To provide further data on this issue, we analysed information gathered from men attending a free andrologic consultation in 234 Italian medical centres, in the setting of a project focused on andrologic prevention. Men were asked about "their ability to achieve and maintain an erection sufficient for satisfactory sexual performance". If they were dissatisfied, they were defined as having ED., Results: Out of 16724 subjects, ED was diagnosed in 4081 men (24.4%). After adjustment for age, marital status, education, alcohol consumption, physical activity and concomitant pathologies, in comparison with never smokers, men who currently smoked more than 10 cigarettes/day and former smokers showed significantly higher odds ratio (ORs 1.4 and 1.3, respectively) for ED. These results were confirmed performing analysis in strata of diabetes, hypertension, cardiovascular disease and hypercolesterolemia., Comments: This transversal observational study shows that the risk of ED is influenced by smoking. A dose- and duration-response effect is present; changes in smoking habits do not seem to significantly affect the risk to develop ED.

Objective: To examine the preference for 2 dosing regimens (on demand or 3 times/week) for tadalafil, a phosphodiesterase 5 inhibitor with a duration of effectiveness up to 36 hours in men with erectile dysfunction (ED)., Design and Methods: SURE is a 14 European country, multicenter, crossover, and open-label study. Men with ED (N=4262) were randomized to tadalafil 20mg treatment on demand (maximum one dose per day and before sexual activity) or 3 times/week for 5-6 weeks. After a 1-week washout period, patients were crossed over to the alternate regimen for 5-6 weeks. The patient's response to a treatment preference question (TPQ) was used to determine the preferred treatment regimen., Results: The mean age of the randomized patients was 55 years and 85.2% reported a history of ED for one year or greater. Overall, the responses of 3861 men to the TPQ assessment showed that 57.8% preferred the on-demand regimen and 42.2% preferred the 3 times/week dosing. Both regimens were efficacious and well tolerated., Conclusions: In this study, while 57.8% of men preferred the on-demand regimen of tadalafil 20mg, a substantial number (42.2%) preferred the 3 times/week treatment. The two regimens provide additional treatment options by giving men with erectile dysfunction unique flexibility in dosing with tadalafil.

Objective: We prospectively conducted a European multi-center study to assess the safety and efficacy of injecting dehydrated ethanol using a specialized injection system for the treatment of BPH., Methods: Patients with symptomatic BPH were enrolled and evaluated to undergo transurethral ethanol ablation of the prostate for their BPH condition. Procedures were performed using the ProstaJect device. Treatment dosages were based on prostate volume, prostatic urethral length and median lobe involvement. Follow-up evaluations were done at four days and one, three, six and 12 months., Results: One-hundred fifteen symptomatic patients underwent the transurethral ethanol ablation procedure and ninety-four patients have been followed and evaluated for the entire 12-month post-treatment period. The average prostate volume was 45.9 g, and average ethanol injected was 14 ml. Post-operatively, 98% of patients voided spontaneously four days following treatment. Significant reduction in reported lower urinary tract symptoms was evidenced at the one-month follow-up visit and maintained through 12 months follow-up, with International Prostate Symptom (IPSS) and Quality of Life (QoL) scores decreased by more than 50%. Peak flow rates (Q(max)) improved by 35% by the three-month evaluation and these results were sustained through to 12-months follow-up. The average prostate volume reduction was 16%. Adverse events included discomfort or irritative voiding symptoms in 26% of patients, hematuria in 16%, with retrograde ejaculation, and erectile dysfunction reported in less than 3% of patients. The majority of these events required no intervention. Two patients experienced serious adverse events (bladder necrosis) and underwent open surgery that included a urinary diversion and a ureteral implantataion. During the one year follow- up, 7% of patients required a trans-urethral resection of prostate (TURP)., Conclusions: This preliminary multi-center data, representing the largest reported cohort to date, suggests that TEAP may be considered an effective minimally invasive treatment option for lower urinary tract symptoms secondary to BPH. Analyses of safety lead to a procedure modification for needle placement more distal from the bladder neck. Objective reduction in symptoms was not correlated in prostate volume reduction suggesting a non-purely mechanical effect.

Objective: To assess determinants of ED in men who asked for a free of charge andrologic consultation during a week focused on andrologic prevention in Italy., Methods: Men were invited to attend 178 participating andrology centers for a free of charge visit for counselling about urologic or andrologic conditions. Data were recorded with a simple questionnaire used by all centers., Results: 2499 (19.9%) were diagnosed having ED. The frequency of ED increased with age, ranging from 4.6% in men under 25 years, to 37.6% in men over 74. In comparison with men with primary education the OR of ED was 0.8 (95% CI 0.7-0.9) in men with secondary education and 0.7 (95% CI 0.6-0.9) in those with university degree. After adjusting for age, the risk of ED was significantly higher in men consuming more than 3 glasses/day of alcoholic drinking (OR 1.4, 95% CI 1.1-2.0), in subjects smoking more than 10 cigarettes/day (OR 1.2, CI 95% 1.1-1.4) and in former smokers (OR 1.2, CI 95% 1.1-1.4). Men performing at least two hours per week of physical activity had a decreased risk of ED (OR 0.8, CI 95% 0.7-0.9). We found an increased risk of ED in men with diabetes (OR 1.2, 95% CI 1.1-1.4), hypertension (OR 1.3, 95% CI 1.1-1.4), cardiopathy (OR 1.5, 95% CI 1.3-1.8) and hypercholesterolemia (OR 1.4, 95% CI 1.2-1.6)., Conclusions: This study provides further data on determinants of ED risk in a large data set and underlines the relationship between ED and cardiovascular diseases.

Objectives: Pudendal nerve somatosensory evoked potentials (SEPs), the bulbocavernosus (BC) reflex, and BC perineal motor evoked potentials after transcranial magnetic cortical stimulation were performed in patients with primary premature ejaculation to investigate the somatic sensory and motor function of the genital area., Methods: Fourteen patients with primary premature ejaculation underwent psychological counseling, urologic physical examination, transrectal ultrasound examination, laboratory testing, and the Stamey test. The spinal and cortical pudendal nerve SEPs were performed by dorsal nerve stimulation at the penile shaft (DN-SEPs) in all patients and at the glans penis (GP-SEPs) in 3 of them. The BC reflex was obtained by stimulating the base of the penis., Results: The mean sensory threshold did not significantly differ between the patients and normal subjects. Cortical DN-SEPs were normal in all patients. The sensory central conduction time, calculated in 6 patients, was normal. The mean cortical DN-SEP amplitude was significantly smaller in patients than in controls. In 3 patients and in 3 controls who underwent both DN-SEP and GP-SEP testing, the glans penis sensory threshold was lower than the dorsal nerve threshold and the cortical GP-SEP latency was longer than the cortical DN-SEP latency. The BC reflex was normal in most patients. The BC motor evoked potentials were normal in all patients, but one., Conclusions: We did not confirm either a faster conduction along the pudendal sensory pathway or a greater cortical representation of the sensory stimuli from the genital area in our patients. Moreover, we did not confirm hyperexcitability of the BC reflex in them. Our results suggest that the electrophysiologic approach is probably not sufficient to clarify the causes of primary premature ejaculation. A more integrated investigation could allow better results in this field.

Objectives: Peyronie's disease is the most frequent cause of penile curvature and occurs particularly in middle-age patients. The best technique for penile biopsy, in the evaluation of albuginea and cavernous tissue, has not been delineated yet. We present a new technique of penile biopsy, useful in the study of Peyronie's plaque, fibrosis and erectile dysfunction or any other pathological condition of the penis requiring a biopsy., Methods: A treatment group (A) of 380 patients underwent Extra Shock Waves Treatment (ESWT) three times a week for 20 minutes, followed by a complete cycle of 12 injections of verapamil (10mg), every two weeks for six months. A control group (B) of 92 patients underwent verapamil injections alone. Three months after the end of the treatment, each patient underwent penile biopsy performed with Acu-Punch (Acuderm Inc.), a biopsy-punch armed with a well-sharpened rotating cylindrical blade, first used by dermatologists for cutaneous lesions., Results: A reduction of the plaque volume was found in 260/380 patients (68.4%) of group A and in 28/92 (30.4%) of group B; painful erection weaned off in 312/340 patients of group A (91.7%) and in 36/82 patients (43.9%) of group B. In all 472 patients an excellent specimen was obtained and both the tunica albuginea and the cavernous tissue were easily identified. In the 260 cases, in which the Extra Shock Waves Treatment was successful, scanning and transmission electron microscopy demonstrated a reduction in packing and clumping of the collagen fibers., Conclusions: This new technique of penile biopsy with Acu-Punch can replace surgical biopsies when a surgical operation is not indicated. Such a low-invasive technique could be performed in all cases of Peyronie's disease and allows a more extensive use of microscopic analysis in the study of Peyronie's disease.