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Background and Objective: Symptomatic benefit and urodynamic obstruction relief represent relevant outcomes of therapies for lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). We summarized evidence from studies concurrently assessing variations in terms of symptoms severity and invasive urodynamic measures of obstruction following medical and surgical therapies for LUTS/BPH., Methods: We performed a systematic review of PubMed, Scopus, and Web of Science in June 2023., Key Findings and Limitations: We identified 29 publications: 14 (872 patients) and 15 (851 patients) studies addressing medical and surgical therapies, respectively. The mean percentage total International Prostate Symptom Score (IPSS) improvements ranged from -2.5% to 56.3% and from 35.1% to 82.1% following medical and surgical therapies, respectively. The corresponding mean percentage Bladder Outlet Obstruction Index (BOOI) improvements ranged from 7.8% to 53.5% and from 22.4% to 138.6%, respectively. Holmium laser enucleation of the prostate (HoLEP) provided IPSS improvements in the higher range and the greatest BOOI reduction., Conclusions and Clinical Implications: Globally, based on available evidence, more pronounced symptomatic benefits are observed following treatments providing greater deobstructive effect. In detail, patients undergoing surgery exhibit greater IPSS and BOOI improvements than those receiving medical therapy., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: Lower urinary tract symptoms (LUTS) are common, often bothersome, and have multifactorial aetiology., Objective: To present a summary of the 2023 version of the European Association of Urology guidelines on the management of male LUTS., Evidence Acquisition: A structured literature search from 1966 to 2021 selected the articles with the highest certainty evidence. The Delphi technique consensus approach was used to develop the recommendations., Evidence Synthesis: The assessment of men with LUTS should be practical. A careful medical history and physical examination are essential. Validated symptom scores, urine test, uroflowmetry, and postvoid urine residual, as well as frequency-volume charts for patients with nocturia or predominately storage symptoms should be used. Prostate-specific antigen should be ordered if a diagnosis of prostate cancer changes the treatment plan. Urodynamics should be performed for selected patients. Men with mild symptoms are candidates for watchful waiting. Behavioural modification should be offered to men with LUTS prior to, or concurrent with, treatment. The choice of medical treatment depends on the assessment findings, predominant type of symptoms, ability of the treatment to change the findings, and the expectations to be met in terms of the speed of onset, efficacy, side effects, and disease progression. Surgery is reserved for men with absolute indications, and for patients who fail or prefer not to receive medical therapy. Surgical management has been divided into five sections: resection, enucleation, vaporisation, and alternative ablative and nonablative techniques. The choice of surgical technique depends on patient's characteristics, expectations, and preferences; surgeon's expertise; and availability of modalities., Conclusions: The guidelines provide an evidence-based approach for the management of male LUTS., Patient Summary: A clinical assessment should identify the cause(s) of symptoms and define the clinical profile and patient's expectations. The treatment should aim to ameliorate symptoms and reduce the risk of complications., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: Urinary incontinence (UI) is a common condition in elderly men causing a severe worsening of quality of life, and a significant cost for both patients and health systems., Objective: To report a practical, evidence-based, guideline on definitions, pathophysiology, diagnostic workup, and treatment options for men with different forms of UI., Evidence Acquisition: A comprehensive literature search, limited to studies representing high levels of evidence and published in the English language, was performed. Databases searched included Medline, EMBASE, and the Cochrane Libraries. A level of evidence and a grade of recommendation were assigned., Evidence Synthesis: UI can be classified into stress urinary incontinence (SUI), urge urinary incontinence (UUI), and mixed urinary incontinence. A detailed description of the pathophysiology and diagnostic workup has been reported. Simple clinical interventions, behavioural and physical modifications, and pharmacological treatments comprise the initial management for all kinds of UI. Surgery for SUI includes bulking agents, male sling, and compression devices. Surgery for UUI includes bladder wall injection of botulinum toxin A, sacral nerve stimulation, and cystoplasty/urinary diversion., Conclusions: This 2022 European Association of Urology guideline summary provides updated information on definition, pathophysiology, diagnosis, and treatment of male UI., Patient Summary: Male urinary incontinence comprises a broad subject area, much of which has been covered for the first time in the literature in a single manuscript. The European Association of Urology Non-neurogenic Male Lower Urinary Tract Symptoms Guideline Panel has released this new guidance, with the aim to provide updated information for urologists to be able to follow diagnostic and therapeutic indications for optimising patient care., (Copyright © 2022. Published by Elsevier B.V.)

Context: Understanding men's values and preferences in the context of personal, physical, emotional, relational, and social factors is important in optimising patient counselling, facilitating treatment decision-making, and improving guideline recommendations., Objective: To systematically review the available evidence regarding the values, preferences, and expectations of men towards the investigation and treatment (conservative, pharmacological, and surgical) of male lower urinary tract symptoms (LUTS)., Evidence Acquisition: We searched electronic databases until August 31, 2020 for quantitative and qualitative studies that reported values and preferences regarding the investigation and treatment of LUTS in men. We assessed the quality of evidence and risk of bias using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) and GRADE Confidence in the Evidence from Reviews of Qualitative Research (CERQual) approaches., Evidence Synthesis: We included 25 quantitative studies, three qualitative studies, and one mixed-methods study recruiting 9235 patients. Most men reported urodynamic testing to be acceptable, despite discomfort or embarrassment, as it significantly informs treatment decisions (low certainty evidence). Men preferred conservative and less risky treatment options, but the preference varied depending on baseline symptom severity and the risk/benefit characteristics of the treatment (moderate certainty). Men preferred pharmacological treatments with a low risk of erectile dysfunction and those especially improving urgency incontinence (moderate certainty). Other important preference considerations included reducing the risk of acute urinary retention or surgery (moderate certainty)., Conclusions: Men prefer lower-risk management options that have fewer sexual side effects and are primarily effective at improving urgency incontinence and nocturia. Overall, the evidence was rated to be of low to moderate certainty. This review can facilitate the treatment decision-making process and improve the trustworthiness of guideline recommendations., Patient Summary: We thoroughly reviewed the evidence addressing men's values and preferences regarding the management of urinary symptoms and found that minimising adverse effects is particularly important. Further research to understand other factors that matter to men is required., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the preclinical and clinical performance of the pivoting lens rigid Endocameleon (ECAM) endoscope in white light cystoscopy (WLC)., Materials and Methods: Preclinical evaluation was performed ex vivo in CT-based, anatomically accurate and validated bladder phantoms. Six defined tasks with objective endpoints were compared between ECAM-WLC and rigid WLC (30° view angle, rWLC) in 30 interventions. Subsequently, the comparison was transferred to in vivo n = 21 interventions. A validated usability score (System Usability Scale, SUS) as well as physician and patient-related outcomes were assessed using Likert-scale-based questionnaires. Intra- and postinterventional complications were recorded according to the Clavien-Dindo classification., Results: The ex vivo evaluation showed a significant superiority of ECAM-WLC in 4 of 6 endoscopic tasks. Noteworthy is the lower pressure on the bladder neck due to the endoscopesalteration of the endoscope (4/60 vs 17/60, P <.0001) and a more precise imaging of all bladder regions (22/30 vs 30/30, P = .046), including the anterior wall (0/30 vs 28/30, P <.0001). In vivo, surgeons rated the ECAM-WLC with an "excellent" SUS of 86.79%, also expressing that ECAM-WLC would enhance bladder surface visualization (4.52/5.0 ± 0.51), with a preferred use for ECAM-WLC during their next cystoscopy (4.62 ± 0.50). Patients reported ECAM-WLC to be less painful (4.5/5.0 ± 0.84) compared to rWLC. No intervention-related complications were observed., Conclusion: ECAM-WLC is a safe and accessible procedure that could improve conventional diagnostic WLC by combination of the advantages of fWLC and rWLC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Context: Oral pharmacotherapy consisting of antimuscarinics, β3-adrenoreceptor agonists, or combinations of these agents forms the mainstay of overactive bladder (OAB) management., Objective: To evaluate the efficacy and safety of combination therapy in patients with OAB., Evidence Acquisition: A literature search was conducted in June 2018 using Embase, MEDLINE, and Cochrane databases via Ovid and relevant congress abstracts. Studies reporting the efficacy/safety of two antimuscarinics or a β3-adrenoreceptor agonist plus an antimuscarinic were included., Evidence Synthesis: Publications reported on clinical efficacy, safety, and health-related quality of life (HRQoL) for mirabegron (M) plus solifenacin (S) from three 12-wk randomised controlled trials (RCTs)-SYMPHONY, SYNERGY, and BESIDE-and a 12-mo RCT, SYNERGY II. SYMPHONY reported statistically significant improvements in clinical symptoms and HRQoL with combination therapy versus solifenacin 5 mg (S5) and placebo. In SYNERGY, there were consistent improvements in urinary incontinence (UI) episodes/24 h and micturitions/24 h (coprimary endpoints), and in secondary efficacy parameters with mirabegron 25 mg (M25) + S5 and mirabegron 50 mg (M50) + S5 versus respective monotherapies. In patients with an inadequate response to S5 monotherapy (BESIDE), greater improvements in UI (primary endpoint) were noted for M50 + S5 versus S5 (p = 0.001). Combination therapy was noninferior to solifenacin 10 mg (S10) for reduction in UI and superior to S10 for improvement in micturition frequency (p < 0.001), and resulted in greater improvements from baseline in OAB-5 Dimension scores versus S5 and S10 (p < 0.01). In SYNERGY II, clinically meaningful and sustained improvements in clinical outcomes were observed for M50 + S5 versus M50 or S5. Combination therapy was well tolerated in all four trials. The incidence of adverse events (AEs) was similar across groups, and there were no notable differences in the incidence of specific AEs. Positive efficacy outcomes were observed in five studies of dual antimuscarinic therapy (trospium + solifenacin)., Conclusions: Mirabegron plus solifenacin provides effective, well-tolerated treatment for patients with OAB. Limited data for dual antimuscarinic therapy suggest a benefit in patients with moderate-to-severe symptoms., Patient Summary: Overactive bladder (OAB) is treated with medicines called antimuscarinics, such as solifenacin, propiverine, or trospium, or another β-adrenoreceptor agonist medicine called mirabegron, which works in a different way. We looked at published scientific studies of patients with OAB treated with mirabegron plus solifenacin together, or with two antimuscarinics. We found that mirabegron plus solifenacin can help reduce symptoms and improve quality of life. Patients tolerate this treatment well, with few patients experiencing side effects., (Copyright © 2019. Published by Elsevier B.V.)

Context: Practice patterns for the management of urinary retention (UR) secondary to benign prostatic obstruction (BPO; UR/BPO) vary widely and remain unstandardized., Objective: To review the evidence for managing patients with UR/BPO with pharmacological and nonpharmacological treatments included in the European Association of Urology guidelines on non-neurogenic male lower urinary tract symptoms., Evidence Acquisition: Search was conducted up to April 22, 2018, using CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform. This systematic review included randomized controlled trials (RCTs) and prospective comparative studies. Methods as detailed in the Cochrane handbook were followed. Certainty of evidence (CoE) was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach., Evidence Synthesis: Literature search identified 2074 citations. Twenty-one studies were included (qualitative synthesis). The evidence for managing patients with UR/BPO with pharmacological or nonpharmacological treatments is limited. CoE for most outcomes was low/very low. Only α1-blockers (alfuzosin and tamsulosin) have been evaluated in more than one RCT. Pooled results indicated that α1-blockers provided significantly higher rates of successful trial without catheter compared with placebo [alfuzosin: 322/540 (60%) vs 156/400 (39%) (odds ratio {OR} 2.28, 95% confidence interval {CI} 1.55 to 3.36; participants=940; studies=7; I 2 =41%; low CoE); tamsulosin: 75/158 (47%) vs 40/139 (29%) (OR 2.40, 95% CI 1.29 to 4.45; participants=297; studies=3; I 2 =30%; low CoE)] with rare adverse events. Similar rates were achieved with tamsulosin or alfuzosin [51/87 (59%) vs 45/84 (54%) (OR 1.28, 95% CI 0.68 to 2.41; participants=171; studies=2; I 2 =0%; very low CoE)]. Nonpharmacological treatments have been evaluated in RCTs/prospective comparative studies only sporadically., Conclusions: There is some evidence that usage of α1-blockers (alfuzosin and tamsulosin) may improve resolution of UR/BPO. As most nonpharmacological treatments have not been evaluated in patients with UR/BPO, the evidence is inconclusive about their benefits and harms., Patient Summary: There is some evidence that alfuzosin and tamsulosin may increase the rates of successful trial without catheter, but little or no evidence on various nonpharmacological treatment options for managing patients with urinary retention secondary to benign prostatic obstruction., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Salvage lymph node dissection (SLND) represents a possible treatment option for prostate cancer patients affected by nodal recurrence after local treatment. However, SLND may be associated with intra- and postoperative complications, and the oncological benefit may be limited to specific groups of patients., Objective: To identify the optimal candidates for SLND based on preoperative characteristics., Design, Setting, and Participants: The study included 654 patients who experienced prostate-specific antigen (PSA) rise and nodal recurrence after radical prostatectomy (RP) and underwent SLND at nine tertiary referral centers. Lymph node recurrence was documented by positron emission tomography/computed tomography (PET/CT) scan using either 11 C-choline or 68 Ga-labeled prostate-specific membrane antigen ligand., Intervention: SLND., Outcome Measurements and Statistical Analysis: The study outcome was early clinical recurrence (eCR) developed within 1 yr after SLND. Multivariable Cox regression analysis was used to develop a predictive model. Multivariable-derived coefficients were used to develop a novel risk calculator. Decision-curve analysis was used to evaluate the net benefit of the predictive model., Results and Limitations: Median follow-up was 30 (interquartile range, 16-50) mo among patients without clinical recurrence (CR), and 334 patients developed CR after SLND. In particular, eCR at 1 yr after SLND was observed in 150 patients, with a Kaplan-Meier probability of eCR equal to 25%. The development of eCR was significantly associated with an increased risk of cancer-specific mortality at 3 yr, being 20% versus 1.4% in patients with and without eCR, respectively (p<0.0001). At multivariable analysis, Gleason grade group 5 (hazard ratio [HR]: 2.04; p<0.0001), time from RP to PSA rising (HR: 0.99; p=0.025), hormonal therapy administration at PSA rising after RP (HR: 1.47; p=0.0005), retroperitoneal uptake at PET/CT scan (HR: 1.24; p=0.038), three or more positive spots at PET/CT scan (HR: 1.26; p=0.019), and PSA level at SLND (HR: 1.05; p<0.0001) were significant predictors of CR after SLND. The coefficients of the predictive model were used to develop a risk calculator for eCR at 1 yr after SLND. The discrimination of the model (Harrel'sC index) was 0.75. At decision-curve analysis, the net benefit of the model was higher than the "treat-all" option at all the threshold probabilities., Conclusions: We reported the largest available series of patients treated with SLND. Roughly 25% of men developed eCR after surgery. We developed the first risk stratification tool to identify the optimal candidate to SLND based on routinely available preoperative characteristics. This tool can be useful to avoid use of SLND in men more likely to progress despite any imaging-guided approach., Patient Summary: The risk of early recurrence after salvage lymph node dissection (SLND) was approximately 25%. In this study, we developed a novel tool to predict the risk of early failure after SLND. This tool will be useful to identify patients who would benefit the most from SLND from other patients who should be spared from surgery., (Copyright © 2018 European Association of Urology. All rights reserved.)

Background: The long-term potential of solifenacin and mirabegron combination treatment for patients with overactive bladder (OAB) has not been previously assessed., Objectives: To evaluate the safety and efficacy of solifenacin succinate 5mg plus mirabegron 50mg tablets (combination treatment) versus solifenacin or mirabegron monotherapy in patients with OAB over 12 mo., Design, Setting, and Participants: Randomised, double-blind, multicentre, phase 3 trial (SYNERGY II) of patients with "wet" OAB symptoms (urinary frequency and urgency with incontinence) for ≥3 mo. The study was conducted from March 2014 to September 2016; with 1829 patients randomised. The full analysis set was comprised of 1794 patients., Outcome Measurements and Statistical Analysis: The primary objective was safety, measured as treatment-emergent adverse events (TEAEs). Efficacy was measured as the change from baseline to the end of treatment in the mean number of incontinence episodes/24h and micturitions/24h., Results and Limitations: The median age was 60 yr (range 19-86 yr) and 1434 patients (80%) were female. Overall, 856 patients (47%) experienced ≥1 TEAE. TEAE frequency was slightly higher in the combination group (596 patients, 49%; mirabegron 126 patients, 41%; solifenacin 134 patients, 44%). Serious TEAEs were reported by 67 patients (3.7%); one was considered possibly treatment-related (mirabegron group, atrial fibrillation). Dry mouth was the most common TEAE (combination 74 patients, 6.1%; solifenacin 18 patients, 5.9%; mirabegron 12 patients, 3.9%). Combination therapy was statistically superior to mirabegron and solifenacin for the number of incontinence episodes (vs mirabegron: adjusted mean difference [AMD] -0.5, 95% confidence interval [CI] -0.7 to -0.2, p<0.001; vs solifenacin: AMD -0.1, 95% CI -0.4 to 0.1, p=0.002) and micturitions (vs mirabegron: AMD -0.5, 95% CI -0.8 to -0.2, p<0.001; vs solifenacin: AMD -0.4, 95% CI -0.7 to -0.1, p=0.004)., Conclusions: Mirabegron and solifenacin combination treatment for OAB symptoms was well tolerated over 12 mo and led to efficacy improvements over each monotherapy. This innovative combination is a treatment option that could become widely used in the clinic., Patient Summary: This study looked at the safety and efficacy of a combination of solifenacin succinate 5mg plus mirabegron 50mg tablets over 12 mo in patients with the overactive bladder (OAB) symptoms of increased urination frequency, heightened urgency to urinate, and unintentional passing of urine. We compared this treatment with solifenacin succinate 5mg or mirabegron 50mg alone, and found that the combination treatment was well tolerated by patients and led to greater improvements in symptoms. This novel combination could be an improved treatment option in the clinical setting for patients with OAB. This study is registered at ClinicalTrials.gov as NCT02045862., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Alpha1-adrenoceptors induce prostate smooth muscle contraction, and hold a prominent role for pathophysiology and therapy of lower urinary tract symptoms in benign prostatic hyperplasia. G protein-coupled receptors are regulated by posttranslational regulation, including phosphorylation by G protein-coupled receptor kinases 2 and 3 (GRK2/3). Although posttranslational adrenoceptor regulation has been recently suggested to occur in the prostate, this is still marginally understood. With the newly developed CMPD101, a small molecule inhibitor with assumed specificity for GRK2/3 is now available. Here, we studied effects of CMPD101 on smooth muscle contraction of human prostate tissue. Electric field stimulation caused frequency-dependent contractions, which were inhibited concentration-dependently by CMPD101 (5 µM, 50 µM). 50 µM of CMPD101 did not affect myosin light chain (MCL) phosphorylation or Rho kinase activity, and did not alter contractions induced by highmolar KCl. Noradrenaline, the α 1 -adrenoceptor agonist phenylephrine, endothelin-1, and the thromboxane A 2 analogue U46619 induced concentration-dependent contractions, which were inhibited by CMPD101 (50 µM). CMPD101 (50 µM) did not change phosphorylation of β 2 -adrenoceptors or β 2 -adrenergic relaxation of prostate strips. Molecular detection by Western blot and peroxidase staining suggested expression of GRK2 and GRK3 in human prostates. Double labeling in fluorescence staining confirmed that immunoreactivity for GRK2 and GRK3 was located to smooth muscle cells in the prostate stroma. In conclusion, CMPD101 inhibits adrenergic, neurogenic, and non-adrenergic smooth muscle contractions in the human prostate. Underlying mechanisms may be independent from GRK inhibition, and from inhibition of MLC kinase and Rho kinase. This may point to unknown properties of CMPD101., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Context: Lower urinary tract symptoms (LUTS) are one of the most common and troublesome nonmalignant conditions affecting quality of life in aging men. A spectrum of established medical and surgical options is available to provide relief of bothersome LUTS. Both the adverse events of medication and the morbidity with surgical treatment modalities have to be counterbalanced against efficacy. Novel minimally invasive treatment options aim to be effective, ideally to be performed in an ambulatory setting under local anaesthesia and to offer a more favourable safety profile than existing reference techniques., Objective: A comprehensive, narrative review of novel minimally invasive treatment modalities for the management of male LUTS due to benign prostatic enlargement is presented., Evidence Acquisition: Medline, PubMed, Cochrane database, and Embase were screened for randomised controlled trials (RCTs), clinical trials, and reviews on novel minimally invasive treatment options for male LUTS due to benign prostatic enlargement., Evidence Synthesis: With regard to newly devised intraprostatic injectables (botulinum neurotoxin A, NX1207, PRX302), PRX302 is currently the only substance that was superior to placebo in a phase 3 RCT providing proof of efficacy and safety. The prostatic urethral lift technique has been evaluated in several phase 3 trials showing rapid and durable relief of LUTS without compromising sexual function in carefully selected patients without a prominent median lobe. The first clinical experience of the temporary implantable nitinol device demonstrated that implantation of this novel device is a safe procedure, easy, and fast to perform. Further studies are required to evaluate efficacy, durability, and to define appropriate patient selection. New ablative approaches like the image guided robotic waterjet ablation (AquaBeam) or procedures based on convective water vapour energy (Rezūm) are in the early stages of development. Prostatic artery embolization performed by interventional radiologists at specialised centres shows a high technical success rate in the treatment of bothersome LUTS. However, a substantial clinical failure rate and a particular spectrum of complications not commonly seen after urologic interventions do occur and need to be critically evaluated., Conclusions: Initial promising clinical results on novel minimally invasive treatment options indicate efficacy comparable to standard techniques, often associated with a more favourable safety profile, in particular with preservation of sexual function. Many of these techniques are in their infancy and based on experience of new developments in the past. Further RCTs are required to evaluate efficacy, safety, and durability of novel techniques with long-term follow-up and careful evaluation of the selection criteria, which have been applied in clinical trials. The prostatic urethral lift is the only procedure with Level 1 evidence data and that can therefore be recommended for treatment of male LUTS in clinical practice for selected patients., Patient Summary: Minimally invasive treatment options have been developed to provide relief of lower urinary tract symptoms comparable to standard surgical techniques with a more favourable safety profile. However, long-term clinical evaluation is still needed for most of these innovations before they can be recommended to be an effective replacement for standard surgical treatment., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: The treatment of nocturia is a key challenge due to the multi-factorial pathophysiology of the symptom and the disparate outcome measures used in research., Objective: To assess and compare available therapy options for nocturia, in terms of symptom severity and quality of life., Evidence Acquisition: Medical databases (Embase, Medline, Cochrane Systematic Reviews, Cochrane Central) were searched with no date restriction. Comparative studies were included which studied adult men with nocturia as the primary presentation and lower urinary tract symptoms including nocturia or nocturnal polyuria. Outcomes were symptom severity, quality of life, and harms., Evidence Synthesis: We identified 44 articles. Antidiuretic therapy using dose titration was more effective than placebo in relation to nocturnal voiding frequency and duration of undisturbed sleep; baseline serum sodium is a key selection criterion. Screening for hyponatremia (< 130 mmol/l) must be undertaken at baseline, after initiation or dose titration, and during treatment. Medications to treat lower urinary tract dysfunction (α-1 adrenergic antagonists, 5-α reductase inhibitors, phosphodiesterase type 5inhibitor, antimuscarinics, beta-3 agonist, and phytotherapy) were generally not significantly better than placebo in short-term use. Benefits with combination therapies were not consistently observed. Other medications (diuretics, agents to promote sleep, nonsteroidal anti-inflammatories) were sometimes associated with response or quality of life improvement. The recommendations of the Guideline Panel are presented., Conclusions: Issues of trial design make therapy of nocturia a challenging topic. The range of contributory factors relevant in nocturia makes it desirable to identify predictors of response to guide therapy. Consistent responses were reported for titrated antidiuretic therapy. For other therapies, responses were less certain, and potentially of limited clinical benefit., Patient Summary: This review provides an overview of the current drug treatments of nocturia, which is the need to wake at night to pass urine. The symptom can be caused by several different medical conditions, and measuring its severity and impact varies in separate research studies. No single treatment deals with the symptom in all contexts, and careful assessment is essential to make suitable treatment selection., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Male lower urinary tract symptoms (LUTS) due to bladder outlet obstruction are characterized by abnormal smooth muscle contractions in the lower urinary tract. Alpha 1 -adrenoceptor antagonists may induce smooth muscle relaxation in the outflow region and represent the current gold standard of medical treatment. However, results may be unsatisfactory or inadequate. Apart from α 1 -adrenoceptor agonists, smooth muscle contraction in the outflow region may be induced by thromboxane A 2 (TXA 2 ), endothelins, or muscarinic receptor agonists. Here, we studied effects of the thromboxane A 2 receptor (TP receptor) antagonist picotamide on contraction in the human male bladder trigone and prostate. Carbachol, the α 1 -adrenoceptor agonist phenylephrine, the thromboxane A 2 analog U46619, and electric field stimulation (EFS) induced concentration- or frequency-dependent contractions of trigone tissues in an organ bath. Picotamide (300µM) inhibited carbachol-, phenylephrine-, U46619-, and EFS-induced contractions. Endothelins 1-3 induced concentration-dependent contractions of prostate tissues, which were inhibited by picotamide. Analyses using real time polymerase chain reaction and antibodies suggested expression of thromboxane A 2 receptors and synthase in trigone smooth muscle cells. Thromboxane B 2 (the stable metabolite of thromboxane A 2 ) was detectable by enzyme immune assay in trigone samples, with most values ranging between 50 and 150pg/mg trigone protein. Picotamide inhibits contractions induced by different stimuli in the human lower urinary tract, including cholinergic, adrenergic, thromboxane A 2 - and endothelin-induced, and neurogenic contractions in different locations of the outflow region. This distinguishes picotamide from current medical treatments for LUTS, and suggests that picotamide may induce urodynamic effects in vivo., (Copyright © 2017. Published by Elsevier B.V.)

Context: Several noninvasive tests have been developed for diagnosing bladder outlet obstruction (BOO) in men to avoid the burden and morbidity associated with invasive urodynamics. The diagnostic accuracy of these tests, however, remains uncertain., Objective: To systematically review available evidence regarding the diagnostic accuracy of noninvasive tests in diagnosing BOO in men with lower urinary tract symptoms (LUTS) using a pressure-flow study as the reference standard., Evidence Acquisition: The EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central, Google Scholar, and WHO International Clinical Trials Registry Platform Search Portal databases were searched up to May 18, 2016. All studies reporting diagnostic accuracy for noninvasive tests for BOO or detrusor underactivity in men with LUTS compared to pressure-flow studies were included. Two reviewers independently screened all articles, searched the reference lists of retrieved articles, and performed the data extraction. The quality of evidence and risk of bias were assessed using the QUADAS-2 tool., Evidence Synthesis: The search yielded 2774 potentially relevant reports. After screening titles and abstracts, 53 reports were retrieved for full-text screening, of which 42 (recruiting a total of 4444 patients) were eligible. Overall, the results were predominantly based on findings from nonrandomised experimental studies and, within the limits of such study designs, the quality of evidence was typically moderate across the literature. Differences in noninvasive test threshold values and variations in the urodynamic definition of BOO between studies limited the comparability of the data. Detrusor wall thickness (median sensitivity 82%, specificity 92%), near-infrared spectroscopy (median sensitivity 85%, specificity 87%), and the penile cuff test (median sensitivity 88%, specificity 75%) were all found to have high sensitivity and specificity in diagnosing BOO. Uroflowmetry with a maximum flow rate of <10ml/s was reported to have lower median sensitivity and specificity of 68% and 70%, respectively. Intravesical prostatic protrusion of >10mm was reported to have similar diagnostic accuracy, with median sensitivity of 68% and specificity of 75%., Conclusions: According to the literature, a number of noninvasive tests have high sensitivity and specificity in diagnosing BOO in men. However, although the majority of studies have a low overall risk of bias, the available evidence is limited by heterogeneity. While several tests have shown promising results regarding noninvasive assessment of BOO, invasive urodynamics remain the gold standard., Patient Summary: Urodynamics is an accurate but potentially uncomfortable test for patients in diagnosing bladder problems such as obstruction. We performed a thorough and comprehensive review of the literature to determine if there were less uncomfortable but equally effective alternatives to urodynamics for diagnosing bladder problems. We found that some simple tests appear to be promising, although they are not as accurate. Further research is needed before these tests are routinely used in place of urodynamics., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

We evaluated the accuracy of 68 Ga-prostate-specific membrane antigen-HBED-CC ( 68 Ga-PSMA) positron emission tomography/computed tomography (PET/CT) for nodal staging prior to lymph node dissection (LND) in patients with prostate cancer (PCa). Thirty-four patients with histologically proven PCa underwent 68 Ga-PSMA-HBED-CC PET/CT prior to radical prostatectomy with primary LND (pLND; n=20) and PET/CT prior to secondary LND (sLND; n=14). Accuracy of PET and CT were analysed separately for staging of the following 71 lymph node (LN) regions: pelvic left (n=30), pelvic right (n=31), presacral (n=3), and para-aortic (n=7). Postoperative histopathology was taken as a reference standard. Thirty-seven of 71 (52%) regions showed LN metastases on histopathology. Sensitivity, specificity, positive predictive value, and negative predictive value for detection of LN metastases were 84%, 82%, 84%, and 82% for PET criteria and 65%, 76%, 75%, and 67% for CT criteria. PET was more accurate for nodal staging compared with CT both at pLND (88% vs 75%) and sLND (77% vs 65%). Overall, 68 Ga-PSMA PET/CT provides accurate nodal staging prior to pLND and sLND for PCa. PATIENT SUMMARY: 68 Ga-PSMA positron emission tomography/computed tomography is accurate in detecting tumour spread to lymph nodes before patients undergo surgery for prostate cancer., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: Premature ejaculation (PE) is the most prevalent male sexual dysfunction. In the last few years, several pharmacologic approaches for oral or topical treatment of PE have been studied., Objective: To systematically review the literature on the outcome of pharmacologic interventions for PE on intravaginal ejaculation latency time (IELT) in comparison to placebo., Evidence Acquisition: A systematic literature search of PubMed and Scopus using the term "premature ejaculation" was performed on 10 April 2015. Full-text articles on prospective randomized controlled trials (RCTs) investigating pharmacotherapy were included. The main outcome measure was IELT., Evidence Synthesis: Out of 266 unique records, a total of 22 were reviewed. The majority of RCTs were of unclear methodological quality because of limited reporting of methods. Pooled evidence suggests that selective serotonin reuptake inhibitors (SSRIs), topical anesthetic creams (TAs), tramadol, and phosphodiesterase type 5 inhibitors (PDE5is) are more effective than placebo at increasing IELT (all p<0.05). However, interpretation of the current meta-analyses may be impaired as a result of frequent heterogeneity in the pooled analyses (all I(2) > 70%). Only pooled analyses for dapoxetine 30mg and 60mg were characterized by homogeneous data (both I(2)<30%) while showing a modest but statistically significant improvement in IELT compared with placebo (mean difference 1.39min, 95% confidence interval 1.23-1.54min; p<0.00001)., Conclusions: Meta-analysis revealed that treatment with dapoxetine significantly improves IELT in patients with PE but with modest efficacy. The efficacy of SSRIs, TAs, tramadol, and PDE5is remains unclear owing to high heterogeneity of the available RCT data. There is a persisting need for drug research and development in the field., Patient Summary: Premature ejaculation is a condition for which the cause is not well understood. Several types of treatment with medium to low efficacy are available. More research is necessary to identify the ideal treatment., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Current trials are investigating radical intervention in men with metastatic prostate cancer. However, there is a lack of safety data for radical prostatectomy as therapy in this setting., Objective: To examine perioperative outcomes and short-term complications after radical prostatectomy for locally resectable, distant metastatic prostate cancer., Design, Setting, and Participants: A retrospective case series from 2007 to 2014 comprising 106 patients with newly diagnosed metastatic (M1) prostate cancer from the USA, Germany, Italy, and Sweden., Intervention: Radical prostatectomy and extended pelvic lymphadenectomy., Outcome Measurements and Statistical Analysis: Descriptive statistics were used to present margin status, continence, and readmission, reoperation, and overall complication rates at 90 d, as well as for 21 specific complications. Kaplan-Meier plots were used to estimate survival function. Intercenter variability and M1a/ M1b subgroups were examined., Results and Limitations: Some 79.2% of patients did not suffer any complications; positive-margin (53.8%), lymphocele (8.5%), and wound infection (4.7%) rates were higher in our cohort than in a meta-analysis of open radical prostatectomy performed for standard indications. At a median follow-up of 22.8 mo, 94/106 (88.7%) men were still alive. The study is limited by its retrospective design, differing selection criteria, and short follow-up., Conclusions: Radical prostatectomy for men with locally resectable, distant metastatic prostate cancer appears safe in expert hands for meticulously selected patients. Overall and specific complication rates related to the surgical extirpation are not more frequent than when radical prostatectomy is performed for standard indications, and the use of extended pelvic lymphadenectomy in all of this cohort compared to its selective use in localized/locally advanced prostate cancer accounts for any extra morbidity., Patient Summary: Men presenting with advanced prostate cancer that has spread beyond the prostate are increasingly being considered for treatments directed at the prostate itself. On the basis of results for our international series of 106 men, surgery appears reasonably safe in this setting for certain patients., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Robot-assisted radical prostatectomy (RARP) is a widespread option for the treatment of patients with clinically localised prostate cancer. Modifications in the surgical technique may help to further improve functional outcomes., Objective: To assess the outcome of early catheter removal 48h after surgery, as opposed to standard catheter removal 6 d after surgery following RARP, using a newly developed surgical technique for posterior reconstruction and anastomosis (Aalst technique)., Design, Setting, and Participants: Patients scheduled for RARP were prospectively scheduled for early catheter removal at postoperative d 2 (group A, n=37) and standard catheter removal at postoperative d 6 (group B, n=37)., Surgical Procedure: RARP was performed using the Da Vinci Si system. The Aalst technique for the urethro-vesical anastomosis including posterior reconstruction was used as previously described., Outcome Measurements and Statistical Analysis: The primary endpoint was spontaneous voiding after catheter removal. Secondary endpoints were rate of anastomotic urinary leakage after catheter removal, presence and severity of urethral, perineal, and abdominal pain, as well as patient's bother after catheter removal using visual analogue scale (VAS) scores. Rate and severity of urinary incontinence after catheter removal were assessed using the International Consultation on Incontinence Questionnaire-Male Lower Urinary Tract Symptoms Module (ICIQ-MLUTS) questionnaire., Results and Limitations: There was no significant difference between the groups with regard to baseline and perioperative parameters, as well as pathological features; however, significantly more patients underwent bilateral nerve-sparing procedures in group A (34 vs 23, p=0.008). After catheter removal, patients in both groups showed spontaneous voiding, whereas only 11% and 8% of the patients in group A and group B experienced urinary retention after catheter removal (p=0.7). Patients in group B had significantly higher maximum flow rates, but lower voided volumes after catheter removal in comparison with patients in group A (21ml/s vs 10ml/s, p≤0.001 and 170ml vs 200ml, p≤0.001, respectively). ICIQ-MLUTS questionnaire and VAS scores showed no significant differences between the groups at any time point., Conclusions: The Aalst technique allows the removal of catheters 2 d after RARP and results in spontaneous voiding. Early removal showed no increased rate of urinary leakage, no negative impact on short-term continence and on perineal, urethral or penile pain, and no increase in urinary retention rates. Future studies have to confirm these results with longer follow-up including detailed parameters on return to daily activity., Patient Summary: We provide evidence that it is possible to remove the bladder catheter as early as 2 d after robot-assisted radical prostatectomy without any negative effects on voiding and pain parameters. Thus, leaving the hospital early without a catheter in place could represent a significant and relevant benefit for the patient., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: A detailed understanding of renal surgical anatomy is necessary to optimize preoperative planning and operative technique and provide a basis for improved outcomes., Objective: To evaluate the literature regarding pertinent surgical anatomy of the kidney and related structures, nephrometry scoring systems, and current surgical strategies for partial nephrectomy (PN)., Evidence Acquisition: A literature review was conducted., Evidence Synthesis: Surgical renal anatomy fundamentally impacts PN surgery. The renal artery divides into anterior and posterior divisions, from which approximately five segmental terminal arteries originate. The renal veins are not terminal. Variations in the vascular and lymphatic channels are common; thus, concurrent lymphadenectomy is not routinely indicated during PN for cT1 renal masses in the setting of clinically negative lymph nodes. Renal-protocol contrast-enhanced computed tomography or magnetic resonance imaging is used for standard imaging. Anatomy-based nephrometry scoring systems allow standardized academic reporting of tumor characteristics and predict PN outcomes (complications, remnant function, possibly histology). Anatomy-based novel surgical approaches may reduce ischemic time during PN; these include early unclamping, segmental clamping, tumor-specific clamping (zero ischemia), and unclamped PN. Cancer cure after PN relies on complete resection, which can be achieved by thin margins. Post-PN renal function is impacted by kidney quality, remnant quantity, and ischemia type and duration., Conclusions: Surgical renal anatomy underpins imaging, nephrometry scoring systems, and vascular control techniques that reduce global renal ischemia and may impact post-PN function. A contemporary ideal PN excises the tumor with a thin negative margin, delicately secures the tumor bed to maximize vascularized remnant parenchyma, and minimizes global ischemia to the renal remnant with minimal complications., Patient Summary: In this report we review renal surgical anatomy. Renal mass imaging allows detailed delineation of the anatomy and vasculature and permits nephrometry scoring, and thus precise, patient-specific surgical planning. Novel off-clamp techniques have been developed that may lead to improved outcomes., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Transurethral resection of the prostate (TURP) is considered the gold standard for male lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). However, TURP may lead to sexual dysfunction and incontinence, and has a long recovery period. Prostatic urethral lift (PUL) is a treatment option that may overcome these limitations., Objective: To compare PUL to TURP with regard to LUTS improvement, recovery, worsening of erectile and ejaculatory function, continence and safety (BPH6)., Design, Setting, and Participants: Prospective, randomized, controlled trial at 10 European centers involving 80 men with BPH LUTS., Intervention: PUL or TURP., Outcome Measurements and Statistical Analysis: The BPH6 responder endpoint assesses symptom relief, quality of recovery, erectile function preservation, ejaculatory function preservation, continence preservation, and safety. Noninferiority was evaluated using a one-sided lower 95% confidence limit for the difference between PUL and TURP performance., Results and Limitations: Preservation of ejaculation and quality of recovery were superior with PUL (p<0.01). Significant symptom relief was achieved in both treatment arms. The study demonstrated not only noninferiority but also superiority of PUL over TURP on the BPH6 endpoint. Study limitations were the small sample size and the inability to blind participants to enrollment arm., Conclusions: Assessment of individual BPH6 elements revealed that PUL was superior to TURP with respect to quality of recovery and preservation of ejaculatory function. PUL was superior to TURP according to the novel BPH6 responder endpoint, which needs to be validated in future studies., Patient Summary: In this study, participants who underwent prostatic urethral lift responded significantly better than those who underwent transurethral resection of the prostate as therapy for benign prostatic hyperplasia with regard to important aspects of quality of life., Trial Registration: ClinicalTrials.gov NCT01533038., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: Lower urinary tract symptoms (LUTS) represent one of the most common clinical complaints in adult men and have multifactorial aetiology., Objective: To develop European Association of Urology (EAU) guidelines on the assessment of men with non-neurogenic LUTS., Evidence Acquisition: A structured literature search on the assessment of non-neurogenic male LUTS was conducted. Articles with the highest available level of evidence were selected. The Delphi technique consensus approach was used to develop the recommendations., Evidence Synthesis: As a routine part of the initial assessment of male LUTS, a medical history must be taken, a validated symptom score questionnaire with quality-of-life question(s) should be completed, a physical examination including digital rectal examination should be performed, urinalysis must be ordered, post-void residual urine (PVR) should be measured, and uroflowmetry may be performed. Micturition frequency-volume charts or bladder diaries should be used to assess male LUTS with a prominent storage component or nocturia. Prostate-specific antigen (PSA) should be measured only if a diagnosis of prostate cancer will change the management or if PSA can assist in decision-making for patients at risk of symptom progression and complications. Renal function must be assessed if renal impairment is suspected from the history and clinical examination, if the patient has hydronephrosis, or when considering surgical treatment for male LUTS. Uroflowmetry should be performed before any treatment. Imaging of the upper urinary tract in men with LUTS should be performed in patients with large PVR, haematuria, or a history of urolithiasis. Imaging of the prostate should be performed if this assists in choosing the appropriate drug and when considering surgical treatment. Urethrocystoscopy should only be performed in men with LUTS to exclude suspected bladder or urethral pathology and/or before minimally invasive/surgical therapies if the findings may change treatment. Pressure-flow studies should be performed only in individual patients for specific indications before surgery or when evaluation of the pathophysiology underlying LUTS is warranted., Conclusions: These guidelines provide evidence-based practical guidance for assessment of non-neurogenic male LUTS. An extended version is available online (www.uroweb.org/guidelines)., Patient Summary: This article presents a short version of European Association of Urology guidelines for non-neurogenic male lower urinary tract symptoms (LUTS). The recommended tests should be able to distinguish between uncomplicated male LUTS and possible differential diagnoses and to evaluate baseline parameters for treatment. The guidelines also define the clinical profile of patients to provide the best evidence-based care. An algorithm was developed to guide physicians in using appropriate diagnostic tests., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: A number of transurethral ablative techniques based on the use of innovative medical devices have been introduced in the recent past for the surgical treatment of benign prostatic obstruction (BPO)., Objective: To conduct a systematic review of the literature and a meta-analysis of available randomized controlled trials (RCTs), and to evaluate the efficacy and safety of transurethral ablative procedures for BPO., Evidence Acquisition: A systematic literature search was performed for all RCTs comparing any transurethral surgical technique for BPO to another between 1992 and 2013. Efficacy was evaluated after a minimum follow-up of 1 yr based on International Prostate Symptom Score, maximum flow rate, and postvoid residual volume. Efficacy at midterm follow-up, prostate volume, perioperative data, and short-term and long-term complications were also assessed. Data were analyzed using RevMan software., Evidence Synthesis: A total of 69 RCTs (8517 enrolled patients) were included. No significant difference was found in terms of short-term efficacy between bipolar transurethral resection of the prostate (B-TURP) and monopolar transurethral resection of the prostate (M-TURP). However, B-TURP was associated with a lower rate of perioperative complications. Better short-term efficacy outcomes, fewer immediate complications, and a shorter hospital stay were found after holmium laser enucleation of the prostate (HoLEP) compared with M-TURP. Compared with M-TURP, GreenLight photoselective vaporization of the prostate (PVP) was associated with a shorter hospital stay and fewer complications but no different short-term efficacy outcomes., Conclusions: This meta-analysis shows that HoLEP is associated with more favorable outcomes than M-TURP in published RCTs. B-TURP and PVP have resulted in better perioperative outcomes without significant differences regarding efficacy parameters after short-term follow-up compared with M-TURP. Further studies are needed to provide long-term comparative data and head-to head comparisons of emerging techniques., Patient Summary: Bipolar transurethral resection of the prostate, photovaporization of the prostate, and holmium laser enucleation of the prostate have shown efficacy outcomes comparable with conventional techniques yet reduce the complication rate. The respective role of these new options in the surgical armamentarium needs to be refined to propose tailored surgical treatment for benign prostatic obstruction relief., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The pathophysiology of male lower urinary tract symptoms (LUTS) is highly complex and multifactorial. The shift in perception that LUTS are not sex or organ specific has not been followed by significant innovations regarding the available drug classes., Objective: To review pathophysiologic mechanisms and clinical and experimental data related to the development of new pharmacologic treatments for male LUTS., Evidence Acquisition: The PubMed database was used to identify articles describing experimental and clinical studies of pathophysiologic mechanisms contributing to male LUTS and, supported by them, new pharmacotherapies with clinical or experimental evidence in the field., Evidence Synthesis: Several pathologic processes (eg, androgen signaling, inflammation, and metabolic factors) and targets (eg, the urothelium, prostate, interstitial cells, detrusor, neurotransmitters, neuromodulators, and receptors) have been implicated in male LUTS. Some newly introduced drugs, such as phosphodiesterase type 5 inhibitors and β3-adrenergic agonists, have just started broad use in clinical practice. Drugs with potential benefit, such as vitamin D3 receptor analogs, gonadotropin-releasing hormone antagonists, cannabinoids, and drugs injected into the prostate, have been evaluated in experimental studies and have progressed to clinical trials. However, safety and efficacy data for these drugs are still scarce. Some compounds with interesting profiles have only been tested in experimental settings (eg, transient receptor potential channel blockers, Rho-kinase inhibitors, purinergic receptor blockers, and endothelin-converting enzyme inhibitors)., Conclusions: New pathophysiologic mechanisms of male LUTS are described that lead to the continuous development of new pharmacotherapies. To date, few drugs have been added to the current armamentarium, and several are in various phases of clinical or experimental investigation., (Copyright © 2013 European Association of Urology. All rights reserved.)

Background: Several drugs are approved for the treatment of lower urinary tract symptoms (LUTS) in men, but these are mostly used by clinicians as monotherapies. The combination of different compounds, each of which targets a different aspect of LUTS, seems appealing. However, only few clinical trials have evaluated the effects of combination therapies., Objective: This systematic review analyzes the efficacy and adverse events of combination therapies for male LUTS., Evidence Acquisition: PubMed and Cochrane databases were used to identify clinical trials and meta-analyses on male LUTS combination therapy. The search was restricted to studies of level of evidence ≥ 1b. A total of 49 papers published between January 1988 and March 2012 were identified., Evidence Synthesis: The α1-adrenoceptor antagonist (α1-blocker)/5α-reductase inhibitor (5-ARI) combination provides the most data. This combination seems to be more efficacious in terms of several outcome variables in patients whose prostate volume is between 30 ml and 40 ml when treatment is maintained for >1 yr; when given for <1 yr, α1-blockers alone are just as effective. The combination of α1-blocker/5-ARI shows a slightly increased rate of adverse events. It remains unknown whether its safety and superiority over either drug as monotherapy are sustained after >6 yr. The α1-blocker/muscarinic receptor antagonist (antimuscarinic) combination was most frequently assessed as an add-on therapy to already existing α1-blocker therapy. Inconsistent data derive from heterogeneous study populations and different study designs. Currently, the α1-blocker/antimuscarinic combination appears to be a second-line add-on for patients with insufficient symptom relief after monotherapy. The combination seems to be safe in men with postvoid residual <200 ml. However, there are no trials >4 mo concerning safety and efficacy of this combination. The α1-blocker/phosphodiesterase type 5 inhibitor combination is a new treatment option with only preliminary reports. More studies are needed before definitive conclusions can be drawn., Conclusions: An α1-blocker/5-ARI combination is beneficial for patients whose prostate volume is between 30 ml and 40 ml when medical treatment is intended for >1 yr. Based on short-term follow-up studies, add-on of antimuscarinics to α1-blockers is an option when postvoid residual is <200 ml., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Pelvic lymphoceles (LCs) following radical prostatectomy (LC-RPs) are a well-described complication. Symptomatic LC-RPs are the most frequent, nonfunctional, postradical prostatectomy complications., Objectives: Description of the clinical presentations of LC-RPs and the detailed technique of laparoscopic pelvic LC marsupialisation (LM), including perioperative results and follow-up., Design, Setting, and Participants: Data from 105 patients (age range: 57-76 yr) with symptomatic LC-RPs who underwent surgery in our institute were evaluated retrospectively. Pelvic ultrasound (US) and computed tomography scans, performed on all patients, revealed LC volumes ranging from 100 to 1200 ml. Fifty-five patients were refractory to prior percutaneous tube drainage and/or sclerotherapy. LM was performed using a three-trocar (n=60 patients) or two-trocar technique (n=45 patients)., Surgical Procedure: With the patient in Trendelenburg position, LCs were accurately identified by inspection, compressibility, and/or laparoscopic needle aspiration. A Foley catheter was inserted. Through one or two working trocars in the left lower abdomen, an adequate peritoneal window (wide ellipse) was excised. The LC cavity was inspected and septae, membranes, and haematomas were removed., Outcome Measurements and Statistical Analysis: Perioperative surgical outcomes, analgesic medication, and inflammation parameters were recorded. Follow-up and success rates were estimated with US for LC recurrence., Results and Limitations: Five pelvic LC locations could be identified: paravesical, lateral pelvic (encapsulated and uncapsulated), prevesical, and with retroperitoneal extension. These were relevant for clinical diagnosis and management options. Pelvic LCs were right-sided in 37 patients, left-sided in 15, and on both sides in 53. All LM were uneventful and operating time (mean) ranged from 15 to 265 (31.7) min, which became shorter with increasing experience. One conversion with postoperative blood transfusion was necessary. Patients were discharged between 2 and 4 (mean: 2.3) d postoperatively. Postoperative US revealed primary success in all cases. Three patients developed recurrence from 1 to 3 wk posthospitalisation; otherwise, none had treatment for LC during a mean follow-up of 20 mo. Limitations include the retrospective study design and the small number of patients., Conclusions: LC-RPs are common and can be classified into five different patterns of clinical/anatomic presentation. LM is simple, feasible, and safe as the first-line treatment for large, noninfected, symptomatic or refractory LC-RPs with fewer complications and an overall 97% success rate., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate expression and α1-adrenergic regulation of caldesmon in the human prostate. Caldesmon is an important mediator and regulator of contraction in different smooth muscle types. However, this has not been investigated in the prostate to date. The activity of caldesmon may be tightly regulated by serine-789 phosphorylation., Materials and Methods: Prostate tissue was obtained from patients undergoing radical prostatectomy. Caldesmon expression was studied by Western blot analysis and immunohistochemistry. The adrenergic regulation of caldesmon phosphorylation was investigated by Western blot analyses with a site- and phosphospecific antibody., Results: Caldesmon expression was detectable by Western blot analysis in all investigated samples of human prostates (n = 8 patients). Immunoreactivity after staining with a caldesmon antibody was strong in smooth muscle cells, but not observed in glandular or epithelial cells (n = 5 patients). In double fluorescence staining, caldesmon co-localized with α1A-adrenoceptors and α-smooth muscle actin (n = 6 patients). Stimulation of prostate tissue with noradrenaline (30 μM, n = 6 patients) or the α1-adrenergic agonist phenylephrine (10 μM, n = 6 patients) resulted in progressive phosphorylation of caldesmon at serine-789. Noradrenaline-induced caldesmon phosphorylation was 1.5 ± 0.2-fold after 5 minutes (P<.04 vs basal phosphorylation), and 1.6 ± 0.2-fold after 10 minutes (P<.04). Phenylephrine-induced caldesmon phosphorylation was 1.7 ± 0.2-fold after 10 minutes (P<.02 vs basal phosphorylation), and 2.4 ± 0.6-fold after 20 minutes (P<.05)., Conclusions: Caldesmon is an effector of α1-adrenoceptors in the human prostate. Caldesmon activation may be of importance for α1-adrenergic prostate contraction, and during therapy with α1-blockers., (Copyright © 2012. Published by Elsevier Inc.)

Background: Cannabinoid receptor (CB)-mediated functions may be involved in the regulation of bladder function, but information on endocannabinoid signals during micturition is scarce., Objective: Investigate the expression of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) in human, rat, and mouse bladders and study the effects of inhibition of FAAH during urodynamics in awake rats., Design, Setting, and Participants: Bladder tissue from humans, mice, and rats was used for measurements. Female Sprague-Dawley rats were administered the FAAH inhibitor oleoyl ethyl amide (OEtA) or vehicle intravenously (IV) or intravesically (IVES) with or without rimonabant (CB1 antagonist) or SR144528 (CB2 antagonist)., Measurements: Real-time transcriptase-polymerase chain reaction, Western blot, immunohistochemistry, and cystometry in awake rats., Results and Limitations: Messenger RNA and protein for FAAH was expressed in the mucosa of human, mouse, and rat urinary bladders. Immunoreactivities for FAAH and CB2 were codistributed in rat and human urothelium. IV OEtA (0.3mg/kg) to rats increased intercontraction intervals (ICIs), micturition volume (MV), bladder capacity (BC), and threshold pressure (TP) by 17±1%, 16±1%, 17±1%, and 19±5%, respectively (all p<0.05 vs baseline). IVES OEtA (1 and 10mg/l) in rats dose-dependently increased (p<0.05 vs baseline) ICI (19±2% and 35±5%), MV (15±3% and 32±4%), BC (16±2% and 34±4%), and TP (15±1%, 21±3%). SR144528 (IVES 5mg/l) abolished all effects of OEtA, whereas rimonabant only counteracted effects of OEtA on TP., Conclusions: Bladder mucosa of all species expressed FAAH. Rat and human urothelium coexpressed FAAH and CB2. The FAAH inhibitor OEtA altered urodynamic parameters that reflect sensory functions of micturition in rats. Suggesting a role for the endocannabinoid system in bladder mechanoafferent functions of rats, effects of IVES OEtA were abolished by an IVES CB2 antagonist and partly counteracted by an IVES CB1 antagonist., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate whether 1-adrenoceptor signaling in the human prostate involves regulation of the mitogen-activated protein kinase (MAPK) p38. Although α1-adrenoceptors are an important target for therapy of lower urinary tract symptoms in patients with prostate hyperplasia, intracellular signaling by prostate α1-adrenoceptors is not sufficiently understood., Methods: Prostate tissue was obtained from patients undergoing radical prostatectomy. The effect of phenylephrine (10 μM) on p38 activity was assessed by Western blot analysis with a phospho-specific antibody. Expression of p38 was studied by immunohistochemistry and immunofluorescence staining. The effect of the p38 inhibitor SB 202190 (10 μM) on phenylephrine-induced contraction was studied in myographic measurements., Results: Stimulation of human prostate tissue with phenylephrine resulted in reduced threonine180/tyrosine182 phosphorylation of p38, indicating deactivation of p38 (P = .039 after 5 minutes). Immunohistochemical staining demonstrated expression of p38 in stromal cells of human prostate tissue. Immunofluorescence staining identified these cells as smooth muscle cells, as p38 colocalized with immunoreactivity for α-smooth muscle actin. The p38 inhibitor SB 202190 was without effect on phenylephrine-induced contraction., Conclusion: Using intact human prostate tissue, we herewith describe a new signal transduction pathway of prostate α1-adrenoceptors. In addition to mediating contraction, prostate α1-adrenoceptors induce intracellular signaling, which results in deactivation of p38 MAPK. This is not involved in α1-adrenergic contraction, and points to α1-adrenoceptor functions beyond contraction., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Context: A large body of epidemiologic data suggests a causal relationship between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED). Recently reported studies on phosphodiesterase type 5 inhibitors (PDE5-Is) and LUTS have further contributed to the understanding of mechanisms involved in this relationship and of potential treatment options., Objective: A nonsystematic descriptive review was performed to summarize the literature concerning the role of PDE5-Is in men with LUTS, particularly looking at data derived from clinical trials in relation to the different PDE5-Is or their association with α-blockers., Evidence Acquisition: A comprehensive electronic search was conducted in October 2010 using the Medline database to identify all publications relating to ED and BPH and treatment with sildenafil, vardenafil, tadalafil, udenafil, UK-369003, and combination therapy with alfuzosin and tamsulosin., Evidence Synthesis: In studies in which either ED or LUTS was the entry criterion, sildenafil appears to improve both erectile function and LUTS in subjects with ED. Placebo-controlled trials of tadalafil and vardenafil showed improvement of LUTS secondary to benign prostatic hyperplasia (BPH), but none of the studies showed a significant effect on urodynamic measures. Exploratory studies with UK-369003 showed improvements in LUTS and ED. Sildenafil or tadalafil associated with alfuzosin or tamsulosin showed greater benefits for the combination therapy for both LUTS and ED. The coadministration of udenafil and an α-blocker in patients with BPH and ED also appeared to improve both LUTS and ED severity., Conclusions: Consistent evidence of improvements in LUTS has been shown with PDE5-Is, either alone or in combination with α-blockers. However, effects on urodynamics or objective measures of urinary flow are lacking. Further areas of research include investigation of mechanism of PDE5-Is, urodynamic studies, identification of new efficacy end points, head-to-head comparison with standard of care, potential benefit of add-on treatment, and long-term outcomes., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: This review focuses on the contemporary role of antimuscarinics in the management of men with symptoms of bladder outlet obstruction (BOO) and concomitant overactive bladder (OAB). Safety issues of antimuscarinics in this subpopulation of men are also reviewed., Objective: We reviewed the current literature and performed an analysis of the efficacy, suitability, and the safety of antimuscarinics in this subpopulation of men., Evidence Acquisition: We performed a systematic search of Medline/PubMed, Embase, Scopus, and the Cochrane Database of Systematic Reviews for relevant articles published between 1990 and September 2010, restricted to studies in humans published in English. In addition, published abstracts presented at the annual meetings of the European Association of Urology, the American Urological Association, and the International Continence Society in the last decade (2000-2010) were hand-searched and evaluated. Each article's title and abstract were reviewed for their appropriateness and relevance to the use of antimuscarinics in patients with BOO and concomitant OAB. Relevant articles were fully reviewed and included in the final data acquisition., Evidence Synthesis: Treatment options include combination treatment with α-blockers and antimuscarinics, sequential use of α-blockers and antimuscarinics, monotherapy with antimuscarinics, and a combination of antimuscarinics and 5α-reductase inhibitors. The sequential use of α-blockers and antimuscarinics seems to be the most appropriate approach, and the use of antimuscarinics and α-blockers appears generally to be safe and efficacious. Data are insufficient for a possible stratification of patients for a specific sequence of the drugs reviewed., Conclusions: This review infers that the existing data confirm the safety of antimuscarinics administered for the treatment of these patients. The efficacy of antimuscarinics has been proven in different trials regarding different storage symptom end points, but not all end points regarding OAB reached significance. All the reported trials are of short duration (4-12 wk) and include only men with low postvoid residual urine volumes at baseline (<200ml). Overall, the addition of an antimuscarinic to the treatment of a patient with BOO and concomitant OAB seems to offer an amelioration of the symptoms and a moderate improvement in quality of life., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: In percutaneous nephrolithotomy (PNL), the best possible way to access the collecting system is still a matter of debate. There is little possibility of correcting a suboptimal access., Objective: To describe our initial experience using a micro-optical system through a specific puncture needle to confirm the quality of the chosen access prior to dilatation of the operating tract., Design, Setting and Participants: Micro-optics of 0.9- and 0.6-mm diameter were used. The micro-optic with integrated light lead was inserted through the working sheath of the puncture needle. The modified needle had a 1.6-mm (4.85-Fr) outer diameter. The optical fiber was connected via a zoom ocular and light adapter to a standard endoscopic camera system. For sufficient intraoperative sight, an irrigation system was connected., Intervention: The optical puncture needle was used in 15 patients for renal access prior to standard PNL procedures., Measurements: The optical assessment included determination of the distortion, resolution, angle, and field of view. The irrigation flow was assessed in an ex vivo setting, with the puncture stylet or the needle shaft either empty or with a 0.018-in guidewire inserted., Results and Limitations: In all cases, visualization of the punctured kidney calyces was successful and the presence of the target calculi could be confirmed prior to guidewire placement and tract dilation. The 0.9-mm optic was found to be significantly superior in all optical parameters in contrast to the 0.6-mm optic. No significant complications were observed., Conclusions: The optical puncture needle for PNL appears to be most helpful for confirming the optimal percutaneous access to the kidney prior to dilation of the nephrostomy tract, improving the safety of the technique., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The prognosis for patients with lymph node (LN)-positive bladder cancer (BCa) is likely affected by the extent of lymphadenectomy in radical cystectomy (RC) cases. Specifically, the prognostic significance of the LN density (ratio of positive LNs to the total number removed) has been demonstrated., Objective: To evaluate the prognostic signature of lymphadenectomy variables, including the LN density, for a large, multicentre cohort of RC patients with LN-positive BCa., Design, Setting, and Participants: The clinical and histopathologic data from 477 patients with LN-positive urothelial BCa (pN1-2) were analysed. The median follow-up period for all living patients was 28 mo., Measurements: Multivariable Cox regression analysis was used to test the effect of various pelvic lymph node dissection (PLND) variables on cancer-specific survival (CSS) based on colinearity in various models., Results and Limitations: The median number of LNs removed was 12 (range: 1-66), and the median number of positive LNs was 2 (range: 1-25). Two hundred ninety (60.8%) of the patients presented with stage pN2 disease. The median and mean LN density was 17.6% and 29% (range: 2.3-100), respectively, where 268 (56.2%) and 209 (43.8%) patients exhibited am LN density of ≤20% and >20%, respectively. In separate multivariable Cox regression models adjusted for age, sex, pTN stage, grade, associated Tis, and adjuvant chemotherapy, the interval-scaled LN density (hazard ratio [HR]: 1.01; p=0.002) and the LN density, ordinal-scaled by 20% (HR: 1.65; p<0.001) exhibit independent effects on CSS. In addition, an independent contribution appears from the pT but not the pN stage. Limitations include surgeon selection bias when determining the extent of lymphadenectomy., Conclusions: Our results support the prognostic relevance of LN density in patients with LN-positive BCa, where a threshold value of 20% stratifies the population into two prognostically distinct groups. Before LN density is integrated into the clinical decision-making process, these results should be validated by prospective studies with defined LN templates and standardised histopathologic methods., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)