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(1) Background: To identify a particular setting of biopsy-naïve patients in which it would be reasonable to offer only cognitive targeted prostate biopsy (PBx) with a transrectal approach. (2) Methods: We designed an observational retrospective pilot study. Patients with a prostatic specific antigen (PSA) level > 10 ng/mL, either a normal or suspicious digital rectal examination (DRE), and a lesion with a PI-RADS score ≥ 4 in the postero-medial or postero-lateral peripheral zone were included. All patients underwent a transrectal PBx, including both systematic and targeted samples. The detection rate of clinically significant prostate cancer (csPCa) (Gleason Score ≥ 7) was chosen as the primary outcome. We described the detection rate of csPCa in systematic PBx, targeted PBx, and overall PBx. (3) A total of 92 patients were included. Prostate cancer was detected in 84 patients (91.30%) with combined biopsies. A csPCa was diagnosed in all positive cases (100%) with combined biopsies. Systematic PBxs were positive in 80 patients (86.96%), while targeted PBxs were positive in 84 men (91.30%). Targeted PBx alone would have allowed the diagnosis of csPCa in all positive cases; systematic PBx alone would have missed the diagnosis of 8/84 (9.52%) csPCa cases (4 negative patients and 4 not csPCa) (p = 0.011). (4) Conclusions: Cognitive targeted PBx with a transrectal approach could be offered alone to diagnose csPCa in biopsy-naïve patients with PSA ≥ 10 ng/mL, either normal or suspicious DRE, and a lesion with PI-RADS score ≥ 4 in the postero-medial or postero-lateral peripheral zone.

Bladder cancer ranks as the 10th most prevalent cancer globally with an increasing incidence. Radical cystectomy combined with urinary diversion represents the standard treatment for muscle-invasive bladder cancer, offering a range of techniques tailored to patient factors. Overall, urinary diversions are divided into non-continent and continent. Among the first category, cutaneous ureterostomy and ileal conduit represent the most common procedures while in the second category, it could be possible to describe another subclassification which includes ureterosigmoidostomy, continent diversions requiring catheterization and orthotopic voiding pouches and neobladders. In this comprehensive review, urinary diversions are described in their technical aspects, providing a summary of almost all alternatives to urinary diversion post-radical cystectomy.

To the Editor, Although postoperative pain associated with robot-assisted radical prostatectomy (RARP) is less than pain following the open technique, it remains a fundamental issue as it can be a significant source of discomfort for the patient and lengthen recovery times after surgery. The optimal management of pain after RARP is far from being fully elucidated and many factors have to be evaluated to choose the best analgesic approach. [...]

Objectives: To assess YouTube™ videos’ quality on prostate checks, especially on the digital rectal exam (DRE), and to investigate if they can inform patients correctly and eradicate their beliefs and myths. Methods: A search using as keywords “digital rectal exam for prostate cancer” was performed on the YouTubeTM platform. We selected the first 100 videos. To assess video quality content, Patient Education Materials Assessment Tool for audio-visual content (PEMAT A/V) and Misinformation tool were used. Results: Seventy-three videos were suitable for the analyses. The median PEMAT A/V Understandability score and PEMAT A/V Actionability score were 46.2% (interquartile range [IQR]: 30.8-76.9) and 50.0% (IQR: 25.0-75.0), respectively. The medi-an PEMAT A/V Understandability and Actionability scores were 69.2% (IQR: 46.2-88.5) vs 46.2% (IQR: 30.8-61.5) (p = 0.01) and 100.0% (IQR: 87.5-100.0) vs 25.0% (IQR: 25.0-68.8) (p < 0.001), for healthcare workers vs patients, respectively. According to the Misinformation tool, the median misinforma-tion score of the overall videos was 2.2 (IQR:1.7-2.8). According to the target audience, the misinformation score was 2.8 (IQR: 2.4-3.5) vs 2.0 (IQR: 1.5-2.8) (p = 0.02), for healthcare workers vs patients, respectively. Conclusions: Currently, based on our analyses, YouTubeTM videos’ quality on DRE resulted unsatisfactory according to the PEMAT A/V score and the Misinformation tool. Videos targeted to healthcare workers got higher quality scores if compared to videos targeted to patients. Therefore, YouTubeTM videos’ may not be considered a reliable source of information on DRE for patients.

Bladder cancer (BC) is common worldwide, and has aggressive features and high rates of relapse despite treatments. Approximately 30% of patients present with muscle invasive disease, and therefore, high risk of metastasis. This review provides an overview of the state of the art for the ‘Vesical Imaging Reporting and Data System’ (VI-RADS). This scoring system presents a tool for the local staging of BC and has been validated across several institutions. We discuss the current application and the potential future clinical implications of VI-RADS in BC diagnosis, management and follow-up.

Objective: The Internet is an important and easily accessible source of information. The aim of the current study was to investigate the quality of YouTube videos on cystoscopy and to establish if they can be used as a reliable information tool for internet users. Materials and methods: The search term “cystoscopy” was used on YouTube platform and the first 120 YouTube videos were analyzed. To assess the video quality Patient Education Materials Assessment Tool (PEMAT) for Audiovisual (A/V) Materials (Understandability and Actionability sections), Misinformation score and Global Quality Score (GQS) were used. Results: Of all 120 videos, 72 were included in the analyses. Of all videos, 59.7% (n = 43), and 40.3% (n = 29) were targeted to General Public and Healthcare Workers. Moreover, “technical aspects” was the main topic addressed (n = 29, 40.3%). The median PEMAT A/V Understandability and Actionability scores were 50.0% (IQR: 39.1-70.0) and 66.7% (IQR: 33.3- 100.0), respectively. The median Misinformation score ranged from 1.0 to 3.0. According to GQS, 22 (30.6%), 26 (36.1%), 16 (22.2%), 8 (11.1%) videos were poor, generally poor, moderate, and good, respectively. No video was evaluated as excellent. Conclusions: Today, YouTube videos on cystoscopy are more frequently uploaded by healthcare workers, who share information about specific aspects of this procedure. However, the quality of YouTube contents on cystoscopy is still poor. Therefore, currently users interested in cystoscopy cannot rely on YouTube to get good informative material on this topic. In consequence, future authors should focus on improving the quality of video contents on cystoscopy

The purpose of this mini review is to provide data about pre-clinical and clinical evidence exploring the impact of circadian desynchrony on spermatogenesis. Several lines of evidence exist demonstrating that disruption of circadian rhythms may interfere with male fertility. Experimental knock-out or knock-down of clock genes, physiologically involved in the regulation of circadian rhythms, are associated with impairments of fertility pathways in both animal and human models. Moreover, disruption of circadian rhythms, due to reduction of sleep duration and/or alteration of its architecture can negatively interfere in humans with circulating levels of male sexual hormones as well as with semen parameters. Unfortunately, current evidence remains low due to study heterogeneity.

Introduction: Telemedicine has been adopted successfully in various urological scenarios. The aim of the present study was to explore attitudes and perceptions by urology residents toward the use of telementoring in the context of residents-faculty physicians communication for patient-related care. Methods: An online survey consisting of 19 multiple choice questions was designed including three sections: respondents’ demographics, attitudes and perceptions towards the use of telementoring. Invitations to participate in this anonymous survey were e-mailed to urology residents at University of Naples Federico II. Results: In total 60 responses were received (participation rate 86%). The frequency of telementoring use was described as occasional, frequent, very frequent, and rare by 51,3%, 41.0%, 5,1%, and 2,6% of respondents, respectively. WhatsApp messenger was used by 89.5% of respondents and photos were the most common type of media content shared (73.7%). Most of respondents declared a moderate and a strong agreement with respect to the utility of telementoring in improving the communication in relation to the interpretation of clinical, radiological, endoscopic, and functional findings. Overall, 78% of participants individuated risks of information flow distortions and misinterpretations as the major limit of telementoring. Conclusions: The use of telementoring is widespread and perceived as useful by urology residents in the context of residentsfaculty physicians communication in multiple settings of patientrelated care.

It is now well established that the urothelium does not act as a passive barrier but contributes to bladder homeostasis by releasing several signaling molecules in response to physiological and chemical stimuli. Here, we investigated the potential contribution of the hydrogen sulfide (H2S) pathway in regulating human urothelium function in β3 adrenoceptor-mediated relaxation. The relaxant effect of BRL 37344 (0.1–300 µM), a selective β3 adrenoceptor agonist, was evaluated in isolated human bladder strips in the presence or absence of the urothelium. The relaxant effect of BRL 37344 was significantly reduced by urothelium removal. The inhibition of cystathionine-γ-lyase (CSE), but not cystathionine-β-synthase (CBS), significantly reduced the BRL 37344 relaxing effect to the same extent as that given by urothelium removal, suggesting a role for CSE-derived H2S. β3 adrenoceptor stimulation in the human urothelium or in T24 urothelial cells markedly increased H2S and cAMP levels that were reverted by a blockade of CSE and β3 adrenoceptor antagonism. These findings demonstrate a key role for urothelium CSE-derived H2S in the β3 effect on the human bladder through the modulation of cAMP levels. Therefore, the study establishes the relevance of urothelial β3 adrenoceptors in the regulation of bladder tone, supporting the use of β3 agonists in patients affected by an overactive bladder.

Background: Lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) are a bothersome frequent symptom in adult males. This systematic review analyzed the available evidence on the pharmacokinetic and pharmacodynamic features of alfuzosin, and its clinical efficacy both as monotherapy and in combination with other drugs for the treatment of male LUTS/BPH. Methods: A systematic review of the last 10 years was performed using the MEDLINE, EMBASE and Cochrane libraries in March 2020. The protocol for this systematic review was registered on PROSPERO (Central Registration Depository: CRD42020136120) and is available in full on the University of York website. Results: Alfuzosin is a quinazoline derivative and, although a nonspecific α1-blocker, exhibits a selective concentration in the prostate compared with plasma in patients with BPH. Three registration trials assessed the safety and efficacy of alfuzosin. The 10 mg daily formulation has a three-layered matrix containing the active substance between two inactive coats allowing a drug release over 20 h. Alfuzosin showed high tolerability, few vasodilatory effects and a low rate of ejaculation disorders over older alpha-blocking compounds thanks to the high uroselectivity of alfuzosin and its preferential concentration at urinary level. Six randomized clinical trials (RCTs) assessed efficacy and safety of alfuzosin versus other alpha-blockers ± placebo: three studies comparing with tamsulosin, one with doxazosin, and two with silodosin or tamsulosin. One RCT investigated the clinical outcomes of alfuzosin with finasteride, two with propiverine and two with phosphodiesterase-5 inhibitors. Conclusions: Alfuzosin is an effective drug for the treatment of LUTS/BPH, with a lower rate of sexual disorders compared with other alpha-blockers. Alfuzosin is also safe with low adverse events in case of concomitant antihypertensive therapy and in patients with cardiovascular morbidity. Safety and efficacy of alfuzosin has been reported also in case of combination therapy with antimuscarinic agents and PDE5i.

The management of patients with prostate cancer (PCa) and previous or synchronous colorectal cancer (CRC) represents a challenging issue. A systematic review was performed in May 2022 to summarize available evidence about the diagnosis, management, and outcomes of these patients. Twenty-seven studies involving 252 patients were identified. Overall, 163 (64.7%) and 89 (35.3%) patients had synchronous and metachronous PCa and CRC, respectively. In patients with synchronous diseases, PCa treatment involved active surveillance in 1 patient, radical prostatectomy (RP) in 36 patients, radiotherapy (RT) in 60 patients, RP plus RT in 1 patient, proton beam therapy in 1 patient, and cryoablation in 1 patient. In patients with previous CRC treatment, prostate biopsy was mostly performed by transrectal approach (n = 24). The trans-perineal and suprapubic approaches were adopted in 12 and 6 cases, respectively. Surgical PCa treatment in these cases involved endoscopic extraperitoneal RP, robot-assisted RP, and not otherwise specified RP in 30, 15, and 2 cases, respectively. Biochemical recurrence rates ranged from 20% to 28%. Non-surgical PCa treatment options included brachytherapy, RT plus androgen deprivation therapy, and RT alone in 23, 2 and 4 patients, respectively. PCa specific survival was reported by one study and was 100%.

The management of patients with oligometastatic urothelial carcinoma (UC) represents an evolving field in uro-oncology, and the role of metastasis-directed therapies, including metastasectomy and metastasis-directed radiation therapy (MDRT), is gaining increasing attention. Herein, we summarize available evidence about the role of MDRT with consolidative intent in oligometastatic UC patients. A systematic review was performed in December 2021. Six studies involving 158 patients were identified. Most patients (n = 120, 90.2%) had a history of bladder cancer and the most frequent sites of metastases were lymph nodes (n = 61, 52.1%) followed by the lungs (n = 34, 29%). Overall, 144 metastases were treated with MDRT. Median follow-up ranged from 17.2 to 25 months. Local control rates ranged from 57% to 100%. Median Overall Survival (OS) ranged from 14.9 to 51.0 months and median progression-free survival ranged from 2.9 to 10.1 months. Rates of OS at one and two years ranged from 78.9% to 96% and from 26% to 63%, respectively. Treatment-related toxicity was recorded in few patients and in most cases a low-grade toxicity was evident. MDRT with consolidative intent represents a potential treatment option for selected patients with oligometastatic UC.

We performed a monocentric longitudinal study on sexually active male patients, from May 2021 to October 2021, with SARS-CoV-2 infection confirmed with a nasopharyngeal reverse transcriptase polymerase chain reaction (RT-PCR). The questionnaires were delivered by email. The study period was divided into the periods before getting tested (T1), during quarantine (T2), 1 month after a negative test (T3), and 3 months after a negative test (T4). All participants were invited to complete these questionnaires: 10- and 6-item questionnaires, a sexual distress schedule (SDS), and the international index of erectile function questionnaire of 15 items (IIEF-15). The primary endpoint was to evaluate the impact of quarantine on male sexual function (SF) during and after the SARS-CoV-2 infection. A total of 22 male patients met the inclusion criteria. The differences for both SDS and IIEF-15 scores, between T1–T2 (27 (IQR 24.0–32.2) vs. 37.5 (IQR 34.2–45.5), 45 (IQR 38.0–50.2) vs. 28.5 (IQR 19.5–38.0)), T2–T3 (37.5 (IQR 34.2–45.5) vs. 28 (IQR 24.0–31.0), and 28.5 (IQR 19.5–38.0) vs. 39.5 (IQR 35.5–44.2)) were statistically significant (p < 0.001), respectively. Moreover, between T1–T4, no statistically significant difference (p > 0.05) was recorded in both SDS (27 (IQR 24.0–32.2) vs. 26.5 (IQR 24–30.2)) and IIEF-15 (45 (IQR 38.0–50.2) vs. 28.5 (IQR 19.5–38.0)). In 20 patients (90.9%), SARS-CoV-2 had a huge impact on relationship and sexual life, but no patient attended a clinic for sexual difficulties. In conclusion quarantine has negatively influenced SF in infected patients; however, 3 months after the rRT-PCR negative test, a promising return to the preinfection SF values is observed.

Spinal cord injury (SCI) is a relevant medical and social problem. According to the World Health Organization, the commonly estimated worldwide annual incidence of SCI is 40 to 80 cases per million population. After the SCI experience, most men present with sexual dysfunction (erectile dysfunction (ED) and ejaculatory dysfunction), fertility problems (such as impaired spermatogenesis, abnormalities in sperm viability, motility, and morphology), and systemic disorders such as genitourinary infection and endocrine imbalances. The best options available for managing the ejaculatory disorders in patients suffering from SCI are penile vibratory stimulation (PVS) and electroejaculation (EEJ). Furthermore, the treatment of ED in SCI patients consists of medical therapies including phosphodiesterase 5 inhibitors (PDE5i), intracavernosal injections (ICI), vacuum erection devices (VEDs), and surgical as penile prosthesis (PP). This review provides a snapshot of the current evidence for the mechanisms of sexual dysfunction and infertility in SCI patients, discusses the best management strategies for these conditions, and offers our perspective on the direction of future research.

Objective: We aimed to assess the attitudes and perceptions towards multiparametric magnetic resonance imaging (mpMRI) of the prostate among Italian urologists. Material and Methods: A national, web-based survey was performed. A questionnaire composed of 18 multiple choice questions was e-mailed to 941 currently active urologists, members of the Italian Society of Urology. Preserving anonymity, respondents’ demographics were collected (e.g. geographic region, type of workplace, prostate procedures performed) as well as data concerning their attitudes and perceptions towards mpMRI (e.g. indications deemed appropriate, degree of confidence in mpMRI results). Data were expressed as raw numbers and percentages of survey answers. Results: In total, 98 responses were received (participation rate = 10.4%). Respondents mostly worked in urban areas (96%) and primarily in hospital settings (89%), while 48% of them worked in southern Italy. 97% of respondents considered mpMRI useful to detect Prostate Cancer (PCa) in patients with prior negative biopsy, 64% in biopsy-naïve patients and 60% for PCa pre-operatory staging. About half (42%) of the participants declared that mpMRI results frequently lead them to change PCa management strategy. Standardization of mpMRI acquisition and reporting was partially unsatisfactory. Reported waiting time for mpMRI scans was longer than 4 weeks for 51% of respondents. The major limitation of this survey includes the small number of participants. Conclusions: Prostate mpMRI is used by Italian urologists mainly for detection and for pre-operative staging of PCa. Further improvements in terms of mpMRI availability and report standardization are required.

Background: We aimed to compare the efficacy of tamsulosin 0.4 mg once a day alone and the combination therapy involving tamsulosin 0.4 mg once a day plus the complementary and alternative medicine consisting of vitamins (C and D), herbal products (Cucurbita maxima, Capsicum annum, Polygonum capsicatum) and amino acid L-Glutamine bid in patients with lower urinary tract symptoms related to benign prostatic hyperplasia (LUTS/BPH). Methods: We performed a retrospective matched paired comparison. The clinical records of LUTS/BPH patients who underwent medical therapy with tamsulosin 0.4 mg/day plus the complementary and alternative medicine consisting of vitamins (C and D), herbal products (Cucurbita maxima, Capsicum annum, Polygonum capsicatum) and amino acid L-Glutamine bid between January 2019 to September 2019 were reviewed (Group 1). These patients were compared in a 1:1 fashion with LUTS/BPH patients who underwent therapy with tamsulosin 0.4 mg/day alone (Group 2). Total, storage, voiding and Quality of Life (QoL) international prostate symptom (IPSS) score, as well as overactive bladder (OAB)-v8 score and treatment- related adverse events recorded at 40 days follow-up in both groups were compared. Results: At 40 days follow-up mean total, storage, voiding and QoL IPSS sub-scores as well as OAB-v8 score significantly improved in both groups. Intergroup comparison showed statistically significant lower mean total IPSS score (11.6 vs 12.4, p = 0.04) mean storage IPSS sub-score (6.5 vs 7.5, p = 0.01), and mean OAB v8 score (16.7 vs 18.8, p = 0.03) in patients in the Group 1. Conclusions: The combination of tamsulosin 0.4 mg/die plus the complementary and alternative medicine consisting of vitamins (C and D), herbal products (Cucurbita maxima, Capsicum annum, Polygonum capsicatum) and amino acid LGlutamine bid provides statistically significant advantages in terms of storage LUTS improvements in patients with LUTS/BPH compared to tamsulosin 0.4 mg/day alone. These findings are preliminary and further prospective studies on a greater number of patients are needed to confirm it.

Background: Bladder cancer is the eleventh most commonly diagnosed cancer worldwide. The recurrence rate of this cancer can be very high, up to 45%. Photodynamic diagnosis (PDD) is more sensitive than standard procedures for the detection of malignant tumours. The aim of the study was to evaluate oncological outcomes in white light TURB (WL-TURB) and hexaminolevuninate blue light TURB (Hal-TURB). Patients and methods: This was a retrospective longitudinal single-center study. In the period between January 2016 and October 2016 WL-TURB was the only therapeutic option available. From November 2016 until April 2017 all TURBs were fluorescence-guided (Hal-TURB). Kaplan-Meier curves have been used to estimate recurrence free survival rates. Results: One hundred and eleven patients underwent Hal- TURB and 137 underwent WL-TURB. Recurrence rate after 12 months was 19.8% (22 out of 111 patients) and 37.2% (51 out of 137 patients) in HAL-group and WL-group respectively (p < 0.01). The recurrence-free period was longer in HAL-group rather than WL-group (8.9 months vs 7.3 months, p < 0.05). Moreover, the recurrence rate during the first 6 months was 3.7% in patients who underwent HAL-TURB and 16% in those who received WL-TURB (p < 0.01). Conclusion: The results of the study show that recurrence-free survival was longer in patients undergoing HAL-TURB compared to the patients who received standard WL-TURB.

Abstract Background To preliminary investigate the effects of silodosin 8 mg once daily on obstruction urodynamic parameters and subjective symptoms in Caucasian patients with lower urinary tract symptoms suggestive of benign prostatic enlargement. Methods We performed a single-center, open-label, single-arm, post-marketing interventional clinical trial. Inclusion criteria were: Caucasian subjects aged ≥50 years waiting to undergo surgery for lower urinary tract symptoms suggestive of benign prostatic enlargement, international prostate symptom total score ≥ 13, international prostate symptom-quality of life score ≥ 3, prostate volume ≥ 30 ml, maximum urine flow rate ≤ 15 mL/s, bladder outlet obstruction index > 40. Eligible subjects received one capsule of silodosin 8 mg once daily for 8 weeks. Invasive urodynamic evaluations were performed at baseline and at 8-weeks follow-up. International prostate symptom questionnaire was administered at baseline, after 4-weeks and 8-weeks of treatment. Results Overall, 34 subjects were included. Mean bladder outlet obstruction index significantly decreased from 70.6 to 39.2 and bladder outlet obstruction index class improved in 16 patients (53.3%). Statistically significant improvements of mean total international prostate symptom score, mean storage sub-score, mean voiding sub-score and mean quality of life sub-score were evident after 4-weeks of treatment with further improvements after 8-weeks. At the end of the treatment, all patients declared that their condition improved enough to spare or delay surgery. Conclusions Silodosin 8 mg once daily significantly improves benign prostatic obstruction in Caucasian patients with lower urinary tract symptoms suggestive of benign prostatic enlargement waiting for surgery. Trial registration EudraCT n. 2015-002277-38 Date of registration: 15th December 2017.

Objective: We investigated the efficacy of intravesical instillations of combined hyaluronic acid (HA) and chondroitin sulphate (CS) in patients with bacillus Calmette-Guérin (BCG)-induced chemical cystitis unresponsive to first-line therapies. Patients and methods: We retrospectively reviewed the clinical records of patients with grade 2 BCG-induced chemical cystitis unresponsive to first line therapeutic options performed according to the International Bladder Cancer Group guidelines who underwent intravesical instillations of HA/CS. Bladder pain, urinary urgency, voiding volume and number of voids/24 hours recorded prior to treatment, at the end of the treatment, at six months and at one-year follow-up were recorded and analyzed. Results: The records of 20 patients were identified. All patients underwent eight weekly instillations of HA/CS. Mean baseline visual analogue scale (VAS) scores ± Standard Deviation (SD) for urinary urgency and bladder pain were 7.8 ± 0.5 and 7.2 ± 1.0, respectively. Mean number of voids/24 hours ± SD was 15.4 ± 2.3 and mean urine volume per void ± SD was 85.8 ± 21.0 mL. At the end of the treatment, mean VAS scores ± SD for urgency and pain significantly decreased to 4.7 ± 1.1 and 4.2 ± 0.9, respectively (p < 0.05 in both cases). Mean number of voids/24 hours ± SD decreased to 9.6 ± 1.4 (p < 0.05) and mean urine volume per void ± SD significantly increased to 194.1 ± 59.5 mL (p < 0.05). At six months and one-year followup, all outcome measures remained stable. Conclusions: Bladder instillations of HA/CS provide significant and durable improvement of bladder pain, urinary urgency, urinary volume per void and urinary frequency in patients with refractory BCG-induced chemical cystitis.

Abstract Background Bladder outlet obstruction is a common urological condition. We aimed to summarize available evidences about bladder outlet obstruction-induced molecular and morphological alterations occurring in human bladder. Methods We performed a literature search up to December 2017 including clinical and preclinical basic research studies on humans. The following search terms were combined: angiogenesis, apoptosis, bladder outlet obstruction, collagen, electron microscopy, extracellular matrix, fibrosis, hypoxia, histology, inflammation, innervation, ischemia, pressure, proliferation, remodeling, suburothelium, smooth muscle cells, stretch, urothelium. Results We identified 36 relevant studies. A three-stages model of bladder wall remodeling can be hypothesized involving an initial hypertrophy phase, a subsequent compensation phase and a later decompensation. Histological and molecular alterations occur in the following compartments: urothelium, suburothelium, detrusor smooth muscle cells, detrusor extracellular matrix, nerves. Cyclic stretch, increased hydrostatic and cyclic hydrodynamic pressure and hypoxia are stimuli capable of modulating multiple signaling pathways involved in this remodeling process. Conclusions Bladder outlet obstruction leads to progressive bladder tissue remodeling in humans. Multiple signaling pathways are involved.

Treating oxidative stress through antioxidant therapy has been considered an appealing strategy in the management of male infertility. However, evidence regarding the toxicity of antioxidant therapy is controversial. We summarized the available clinical evidence on the toxicity associated with the use of antioxidants in infertile males. A systematic review was performed in March 2021. We included randomized controlled trials evaluating the incidence of adverse events in male patients with infertility receiving antioxidant therapy. Thirteen studies involving 1999 male patients were identified. Antioxidant supplementation in patients with male factor infertility was associated with a statistically significantly increased risk of nausea (Odds Ratio: 2.16, 95% Confidence Interval: 1.05–4.43, p = 0.036), headache (Odds Ratio: 3.05, 95% Confidence Interval: 1.59– 5.85 p = 0.001), and dyspepsia (Odds Ratio: 4.12, 95% Confidence Interval: 1.43–11.85, p = 0.009) compared to a placebo. Treatment discontinuation due to adverse events was not significantly higher in patients taking antioxidants compared to a placebo (Odds Ratio: 2.29, 95% Confidence Interval: 0.76–6.88, p = 0.139). When antioxidant supplementation is considered, a more accurate risk/benefit analysis is warranted.

Prostate and bladder cancer represent the two most frequently diagnosed genito-urinary malignancies. Diet has been implicated in both prostate and bladder cancer. Given their prolonged latency and high prevalence rates, both prostate and bladder cancer represent attractive candidates for dietary preventive measures, including the use of nutritional supplements. Flavonols, a class of flavonoids, are commonly found in fruit and vegetables and are known for their protective effect against diabetes and cardiovascular diseases. Furthermore, a higher dietary intake of flavonols was associated with a lower risk of both bladder and prostate cancer in epidemiological studies. In this systematic review, we gathered all available evidence supporting the anti-cancer potential of selected flavonols (kaempferol, fisetin and myricetin) against bladder and prostate cancer. A total of 21, 15 and 7 pre-clinical articles on bladder or prostate cancer reporting on kaempferol, fisetin and myricetin, respectively, were found, while more limited evidence was available from animal models and epidemiological studies or clinical trials. In conclusion, the available evidence supports the potential use of these flavonols in prostate and bladder cancer, with a low expected toxicity, thus providing the rationale for clinical trials that explore dosing, settings for clinical use as well as their use in combination with other pharmacological and non-pharmacological interventions.

Widespread use of PSA as the standard tool for prostate cancer (PCa) diagnosis led to a high rate of overdiagnosis and overtreatment. In this study, we evaluated the performance of the prostate health index (PHI) and multiparametric magnetic resonance imaging (mpMRI) for the prediction of positive biopsy and of high-grade PCa at radical prostatectomy (RP). To this end, we prospectively enrolled 196 biopsy-naïve patients who underwent mpMRI. A subgroup of 116 subjects with biopsy-proven PCa underwent surgery. We found that PHI significantly outperformed both PI-RADS score (difference in AUC: 0.14; p < 0.001) and PHI density (difference in AUC: 0.08; p = 0.002) in the ability to predict positive biopsy with a cut-off value of 42.7 as the best threshold. Conversely, comparing the performance in the identification of clinically significant prostate cancer (csPCa) at RP, we found that PHI ≥ 61.68 and PI-RADS score ≥ 4 were able to identify csPCa (Gleason score ≥ 7 (3 + 4)) both alone and added to a base model including age, PSA, fPSA-to-tPSA ratio and prostate volume. In conclusion, PHI had a better ability than PI-RADS score to predict positive biopsy, whereas it had a comparable performance in the identification of pathological csPCa.

Patients suffering from hematological malignancies are at increased risk of Fournier’s gangrene (FG) due to immunosuppression caused by the disease itself or by disease-related treatments. A systematic review of PubMed, ISI Web of Knowledge, and Scopus databases was performed in June 2021. We included full papers that met the following criteria: original research, human studies, and describing clinical presentation, treatment, and outcomes of FG in patients with oncohematological diseases. We identified 35 papers published from 1983 to 2021 involving 44 patients (34 males, 8 females) aged between 4 days and 83 years. The most common malignant hematological disorders were acute myeloid leukemia (n = 21) and acute lymphocytic leukemia (n = 9). In 10 patients FG represented the first presentation of hematological malignancy. Scrotum (n= 27) and perineum (n = 11) were the sites most commonly involved. Pseudomonas aeruginosa (n = 21) and Escherichia coli (n = 6) were the most commonly isolated microorganisms. Surgery was performed in 39 patients. Vacuum-assisted closure and hyperbaric oxygen therapy were adopted in 4 and in 3 patients, respectively. Recovery was achieved in 30 patients. FG-related mortality was observed in 11 patients. FG should be carefully considered in patients with oncohematological diseases.

Bladder cancer (BCa) is an endocrine-related tumour and the activation of androgen signalling pathways may promote bladder tumorigenesis. We summarized the available preclinical and clinical evidence on the implications of the manipulation of androgen signalling pathways on the outcomes of BCa therapies. A systematic review was performed in December 2020. We included papers that met the following criteria: original preclinical and clinical research; evaluating the impact of androgen signalling modulation on the outcomes of BCa therapies. Six preclinical and eight clinical studies were identified. The preclinical evidence demonstrates that the modulation of androgen receptor-related pathways has the potential to interfere with the activity of the Bacillus Calmette Guerin, doxorubicin, cisplatin, gemcitabine, and radiotherapy. The relative risk of BCa recurrence after transurethral resection of the bladder tumour (TURBT) is significantly lower in patients undergoing therapy with 5 alpha reductase inhibitors (5-ARIs) or androgen deprivation therapy (ADT) (Relative risk: 0.50, 95% CI: 0.30–0.82; p = 0.006). Subgroup analysis in patients receiving 5-ARIs revealed a relative risk of BCa recurrence of 0.46 (95% CI: 0.22–0.95; p = 0.040). A significant negative association between the ratio of T1 BCa patients in treated/control groups and the relative risk of BCa recurrence was observed. Therapy with 5-ARIs may represent a potential strategy aimed at reducing BCa recurrence rate, mainly in patients with low stage disease. Further studies are needed to confirm these preliminary data.

A high percentage of patients with metastatic renal cell carcinoma (mRCC) require a second-line option. We aimed to summarize available evidences about the clinicopathological profile of mRCC patients who receive a second-line therapy. A systematic review was performed in August 2020. We included papers that met the following criteria: original research; English language; human studies; enrolling mRCC patients entering a second-line therapy. Twenty-nine studies enrolling 7650 patients (73.5% male, mean age: 55 to 70 years) were included. Clear cell histology was reported in 74.4% to 100% of cases. Tyrosine kinase inhibitors, immunotherapy, bevacizumab, mTOR inhibitors, and chemotherapy were adopted as first line option in 68.5%, 29.2%, 2.9%, 0.6%, and 0.2% of patients, respectively. Discontinuation of first-line therapy was due to progression and toxicity in 18.4% to 100% and in 17% to 48.8% of patients, respectively. Eastern Cooperative Oncology Group performance status score was 0 or 1 in most cases. Most prevalent prognostic categories according to the International Metastatic RCC Database Consortium and Memorial Sloan–Kettering Cancer Centre score were intermediate and good. About 77.8% of patients harboured ≥2 metastatic sites. In conclusion, patients who enter a second-line therapy are heterogeneous in terms of a clinical-pathological profile. Tailoring of second-line treatment strategies is strongly advocated.

Introduction: PDE5 inhibitors are the firstline treatment for erectile dysfunction. Although all these drugs share the same mechanism of action, each agent could have different characteristics in terms of selectivity, pharmacokinetics and tolerability profile. Materials and Methods: This manuscript illustrates a project, undertaken by the Italian Society of Urology in order to obtain a “snapshot” of the experience of Italian urologists with the use of PDE5 inhibitors in the clinical practice. This project included a survey, targeting a sample of 136 Italian urologists experienced in the treatment of ED, and the organization of a conference of experts who, based on the findings of the survey, the scientific literature and the clinical experience, would define some recommendations for the use of PDE5 inhibitors in clinical practice with a particular focus on Avanafil, the most recent drug in this class. Results: The following recommendations on the use of Avanafil were issued: 1) In patients who are candidates for the use of Avanafil, it is advisable to use the 200-mg dose from the first administration; 2) When used at the highest dose (200 mg), Avanafil shows a favourable tolerability profile with an efficacy similar to that of other agents; 3) The patient should be instructed to take Avanafil on an empty stomach, i.e., 30-45 minutes before or 2 hours after a meal; 4) The efficacy window of Avanafil is between 30 minutes and 6 hours after dosing, which qualifies this molecule as a new drug with an intermediate duration of action; 5) Avanafil at a dose of 50-100 mg/day may be a therapeutic option in chronic rehabilitation. Conclusions: Among PDE5 inhibitors, Avanafil is a new agent with an intermediate duration of action, characterized by high efficacy and good tolerability even at the highest dose (200 mg).

Deterioration of renal function has been reported after radical cystectomy (RC) with urinary diversion. We investigated renal function changes in elderly bladder cancer (BCa) patients who underwent RC with cutaneous ureterostomy (CU) urinary diversion. We performed a retrospective, observational study. BCa patients aged ≥75 with an American Society of Anesthesiologists (ASA) class greater than II were included. Glomerular filtration rate (GFR) was the main outcome measure. GFR values were recorded preoperatively, at discharge, at 6-month follow-up, and yearly up to 60 months. A total of 70 patients with a median age of 78.0 years were identified. Median preoperative GFR was 74.3 mL/min/1.73 m2 and declined significantly to 54.6 mL/min/1.73 m2 after 6 months (p < 0.001). A gradual GFR decline was observed thereafter, reaching a median value of 46.2 after 60 months. Preoperative GFR and acute kidney injury were significant predictors of fast deterioration of GFR and of 25% deterioration of GFR after 12 months. Elderly BCa patients with high comorbidity rates undergoing RC with CU should be carefully informed about the risk of GFR deterioration and the need for adequate monitoring.

Urotensin-II (U-II) is a cyclic peptide that acts through a G protein-coupled receptor (urotensin-II receptor [UTR]) mainly involved in cardiovascular function in humans. The urotensinergic system is also implicated in the urogenital tract. Indeed, U-II relaxes human corpus cavernosum strips and causes an increase in intracavernous pressure (ICP) in rats. In light of this, the U-II/UTR pathway can be considered a new target for the treatment of erectile dysfunction. On this hypothesis, herein we report on two new UTR high affinity-agonists, P5U (H-Asp-c[Pen-Phe-Trp-Lys-Tyr-Cys]-Val-OH) and UPG84(H-Asp-c[Pen-Phe-DTrp-Orn-(pNH 2 ) Phe-Cys]-Val-OH). The effects of P5U and UPG84 were each compared separately with U-II by monitoring the ICP in anesthetized rats. Intracavernous injection of U-II (0.03-1 nmol), P5U (0.03-1 nmol) or UPG84 (0.03-1 nmol) caused an increase in ICP. P5U, in particular, elicited a significant increase in ICP as compared to U-II. The observed effect by using P5U at a dose of 0.1 nmol per rat was comparable to the effect elicited by U-II at a dose of 0.3 nmol. Moreover, UPG84 at the lowest dose (0.03 nmol) showed an effect similar to the highest dose of U-II (1 nmol). Furthermore, UPG84 was found to be more effective than P5U. Indeed, while the lowest dose of P5U (0.03 nmol) did not affect the ICP, UPG84, at the same dose, induced a prominent penile erection in rat. These compounds did not modify the blood pressure, which indicates a good safety profile. In conclusion, UPG84 and P5U may open new perspectives for the management of erectile dysfunction.

Objectives: To compare the efficacy and safety of tamsulosin and silodosin in the context of medical expulsive therapy (MET) of distal ureteric stones. Patients and methods: Observational data were collected retrospectively from patients who received silodosin (N = 50) or tamsulosin (N = 50) as MET from January 2012 to January 2013. Inclusion criteria were: patients aged ≥ 18 years with a single, unilateral, symptomatic, radiopaque ureteric stone of 10 mm or smaller in the largest dimension located between the lower border of the sacroiliac joint and the vesico-ureteric junction. Stone expulsion rate, stone expulsion time, number of pain episodes, need for analgesics use, incidence of side effects were compared. Results: Stone-expulsion rate in the silodosin and in the tamsulosin groups were 88% and 82%, respectively (p not significant). Mean expulsion times were 6.7 and 6.5 days in the silodosin and tamsulosin group, respectively (p not significant). Mean number of pain episodes were 1.6 and 1.7 in the silodosin and tamsulosin group, respectively (p not significant). The mean number of analgesic requirement was 0.84 and 0.9 for the silodosin and tamsulosin group, respectively (p not significant). Overall, incidence of side effects was similar in both groups. Patients taking silodosin experienced an higher incidence of retrograde ejaculation but a lower incidence of side effects related to peripheral vasodilation when compared to patients taking tamsulosin. Subgroup analysis demonstrated significantly lower mean expulsion times and pain episodes in patients with stones ≤ 5 mm in both groups. Conclusions: Tamsulosin and silodosin are equally effective as MET for distal ureteric stones sized 10 mm or smaller. MET with silodosin is associatd with a lower incidence of side effects related to peripheral vasodilation but an higher incidence of retrograde ejaculation when compared to tamsulosin.

Sexual dysfunctions have commonly been reported as the resulting side effects of many drugs. To understand the impact of a single drug, the mechanism of action of the most commonly prescribed drugs and the physiological mechanisms of sexual function have to be taken into dual consideration. Psychotropic drugs (Antidepressants, Antipsychotics and Antiepileptic) in particular result in both short and long-term effects on sexual function. Antihypertensive drugs have also produced evidence certifying their role in determining sexual dysfunction. Patients affected with sexual dysfunction are often aged and assume several drugs and, while Iatrogenic sexual dysfunction is prevalent in men, urological drugs are not the only drugs to be held accountable. Many different drugs acting on different sites and with several mechanisms of action can induce sexual dysfunction. The drug classes involved are widely diffused and frequently assumed in combination therapies.

Paragangliomas (PGL) are rare neuroendocrine tumors of the autonomic nervous system originating from paraganglia. Although PGL may arise at any site where physiologic paraganglionic tissue exists, the localization in the small pelvis is extremely rare. PGL may be hormonally active and release surplus catecholamines into the blood or inactive. The asymptomatic cases pose a diagnostic dilemma. We describe the case of an asymptomatic PGL arising in the small pelvis sidewall presenting as an incidentally discovered asymptomatic mass in a male subject.

The pelvic floor is a complex multifunctional structure that corresponds to the genito- urinary-anal area and consists of muscle and connective tissue. It supports the urinary, fecal, sexual and reproductive functions and pelvic statics. The symptoms caused by pelvic floor dysfunction often affect the quality of life of those who are afflicted, worsening significantly more aspects of daily life. In fact, in addition to providing support to the pelvic organs, the deep floor muscles support urinary continence and intestinal emptying whereas the superficial floor muscles are involved in the mechanism of erection and ejaculation. So, conditions of muscle hypotonia or hypertonicity may affect the efficiency of the pelvic floor, altering both the functionality of the deep and superficial floor muscles. In this evolution of knowledge it is possible imagine how the rehabilitation techniques of pelvic floor muscles, if altered and able to support a voiding or evacuative or sexual dysfunction, may have a role in improving the health and the quality of life.

Anaplastic seminoma (AS) is an uncommon histological variant of classical seminoma of the testis and account for 5%-15% of cases. It is poorly described in the scientific literature. We present the case of a 50-years-old homeless man presenting with fever, marked left scrotal hardness and a fungating left scrotal lesion. He underwent left orchiopexy 40 years before. A computed tomography with contrast media showed a suspect testis cancer with scrotal involvment, extensive intralesional necrosis and multiple systemic metastases. A wide excision of the left hemiscrotum including the testis was performed in order to prevent severe local and systemic infectious complications. Histological examination revealed an AS. General conditions showed a rapid deterioration and the patient died on post operative day 10.

Carcinomas of unknown primary origin (CUP) represent a diagnostic and therapeutic challenge. Squamous cell CUP located in the male pelvis are very rare. We describe a case of a locally advanced squamous cell CUP occurring in the male pelvis presenting as perineal abscess and urethral stenosis and diagnosed by means of transperineal needle biopsy.

Urothelium, the epithelial lining the inner surface of human bladder, plays a key role in bladder physiology and pathology. It responds to chemical, mechanical and thermal stimuli by releasing several factors and mediators. Recently it has been shown that hydrogen sulfide contributes to human bladder homeostasis. Hydrogen sulfide is mainly produced in human bladder by the action of cystathionine-β-synthase. Here, we demonstrate that human cystathionine-β-synthase activity is regulated in a cGMP/PKG-dependent manner through phosphorylation at serine 227. Incubation of human urothelium or T24 cell line with 8-Bromo-cyclic-guanosine monophosphate (8-Br-cGMP) but not dibutyryl-cyclic-adenosine monophosphate (d-cAMP) causes an increase in hydrogen sulfide production. This result is congruous with the finding that PKG is robustly expressed but PKA only weakly present in human urothelium as well as in T24 cells. The cGMP/PKG-dependent phosphorylation elicited by 8-Br-cGMP is selectively reverted by KT5823, a specific PKG inhibitor. Moreover, the silencing of cystathionine-β-synthase in T24 cells leads to a marked decrease in hydrogen sulfide production either in basal condition or following 8-Br-cGMP challenge. In order to identify the phosphorylation site, recombinant mutant proteins of cystathionine-β-synthase in which Ser32, Ser227 or Ser525 was mutated in Ala were generated. The Ser227Ala mutant cystathionine-β-synthase shows a notable reduction in basal biosynthesis of hydrogen sulfide becoming unresponsive to the 8-Br-cGMP challenge. A specific antibody that recognizes the phosphorylated form of cystathionine-β-synthase has been produced and validated by using T24 cells and human urothelium. In conclusion, human cystathionine-β-synthase can be phosphorylated in a PKG-dependent manner at Ser227 leading to an increased catalytic activity.

A significant percentage of patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) achieve clinically meaningful improvement when receiving placebo or tadalafil 5mg once daily. However, individual patient characteristics associated with treatment response are unknown.This integrated clinical data mining analysis was designed to identify factors associated with a clinically meaningful response to placebo or tadalafil 5mg once daily in an individual patient with LUTS-BPH. Analyses were performed on pooled data from four randomized, placebo-controlled, double-blind, clinical studies, including about 1,500 patients, from which 107 baseline characteristics were selected and 8 response criteria. The split set evaluation method (1,000 repeats) was used to estimate prediction accuracy, with the database randomly split into training and test subsets. Logistic Regression (LR), Decision Tree (DT), Support Vector Machine (SVM) and Random Forest (RF) models were then generated on the training subset and used to predict response in the test subset. Prediction models were generated for placebo and tadalafil 5mg once daily Receiver Operating Curve (ROC) analysis was used to select optimal prediction models lying on the ROC surface.International Prostate Symptom Score (IPSS) baseline group (mild/moderate vs. severe) for active treatment and placebo achieved the highest combined sensitivity and specificity of 70% and ~50% for all analyses, respectively. This was below the sensitivity and specificity threshold of 80% that would enable reliable allocation of an individual patient to either the responder or non-responder group.This extensive clinical data mining study in LUTS-BPH did not identify baseline clinical or demographic characteristics that were sufficiently predictive of an individual patient response to placebo or once daily tadalafil 5mg. However, the study reaffirms the efficacy of tadalalfil 5mg once daily in the treatment of LUTS-BPH in the majority of patients and the importance of evaluating individual patient need in selecting the most appropriate treatment.

BACKGROUND:Urotensin II (U-II) is a cyclic peptide originally isolated from the neurosecretory system of the teleost fish and subsequently found in other species, including man. U-II was identified as the natural ligand of a G-protein coupled receptor, namely UT receptor. U-II and UT receptor are expressed in a variety of peripheral organs and especially in cardiovascular tissue. Recent evidence indicates the involvement of U-II/UT pathway in penile function in human, but the molecular mechanism is still unclear. On these bases the aim of this study is to investigate the mechanism(s) of U-II-induced relaxation in human corpus cavernosum and its relationship with L-arginine/Nitric oxide (NO) pathway. METHODOLOGY/PRINCIPAL FINDINGS:Human corpus cavernosum tissue was obtained following in male-to-female transsexuals undergoing surgical procedure for sex reassignment. Quantitative RT-PCR clearly demonstrated the U-II expression in human corpus cavernosum. U-II (0.1 nM-10 µM) challenge in human corpus cavernosum induced a significant increase in NO production as revealed by fluorometric analysis. NO generation was coupled to a marked increase in the ratio eNOS phosphorilated/eNOS as determined by western blot analysis. A functional study in human corpus cavernosum strips was performed to asses eNOS involvement in U-II-induced relaxation by using a pharmacological modulation. Pre-treatment with both wortmannin or geldanamycinin (inhibitors of eNOS phosphorylation and heath shock protein 90 recruitment, respectively) significantly reduced U-II-induced relaxation (0.1 nM-10 µM) in human corpus cavernosum strips. Finally, a co-immunoprecipitation study demonstrated that UT receptor and eNOS co-immunoprecipitate following U-II challenge of human corpus cavernosum tissue. CONCLUSION/SIGNIFICANCE:U-II is endogenously synthesized and locally released in human corpus cavernosum. U-II elicited penile erection through eNOS activation. Thus, U-II/UT pathway may represent a novel therapeutical target in erectile dysfunction.