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Bladder cancer (BCa) represents the second most common malignancy of the genitourinary tract. The major risk factors include age, gender, smoking attitude, and occupational exposure, while the exact etiopathogenesis is still uncertain. Patients diagnosed with a BCa showing invasion of the muscle layer below the submucosa must undergo radical cystectomy (RC) with urinary diversion (UD). Many different surgical approaches to UD have been developed. Packaging an orthotopic neobladder (ON) with a bowel tract represents the gold standard when certain patient selection criteria are satisfied. Using PRISMA guidelines, we performed a systematic review assessing early (within 90 days) and late (beyond 90 days) post-procedural complications of different ON surgical approaches. A comprehensive systematic search was conducted in PubMed, Scopus, and Google Scholar databases to identify papers starting from 2012 using dedicated keywords ("neobladder", "orthotopic neobladder", "complications'' and "outcomes"). A total of 27 articles were found to satisfy the inclusion criteria and selected. Although the ON is a safe procedure that guarantees the patient the best quality of life (QoL), it is not free from risks. Many complications could occur during and after the surgical time which imposes the necessity of strict follow-up and careful checks over time, which should be properly discussed with patients before., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To examine the different and health-related quality of life (HR-QoL) outcomes between ileal conduit (IC) and ileal orthotopic neobladder (IONB) in patients who underwent radical cystectomy (RC), by using validated self-reported cancer-specific instruments., Patients and Methods: This retrospective, cross-sectional, multicenter cohort study included 148 and 171 patients with either IC or IONB. HR-QoL was evaluated with Quality of Life Core Questionnaire and bladder module (BLM)-30 European Organisation for Research and Treatment of Cancer questionnaires. Baseline HR-QoL scores were dichotomized at the median to give "good" or "poor" score profiles. A matched-pair analysis compared HR-QoL aspects between 79 IC patients and 79 IONB patients., Results: At univariate analysis IONB resulted favorable for physical functioning, emotional functioning, cognitive functioning (CF), fatigue, dyspnea, appetite loss, constipation (CO), and abdominal bloating flatulence (AB). At multivariate analyses, IONB showed better scores for emotional functioning (85 vs 79, P = .023), CF (93 vs 85, P <.001), CO (16 vs 31, P <.001), and AB (12 vs 25, P <.001). A significant worsening of sexual and urinary function was observed for IONB patients in the long-term. At matched-pair analysis, global health status was similar (65 vs 62, P = .385). Significantly better scores were observed in the IONB group for the following items: CF (P = .007), fatigue (P = .003), pain (P = .019), dyspnea (P = .016), CO (P = .001), and AB (P = .00)., Conclusion: IONB and IC after RC were similar in terms of global health status. IONB provides better results in some aspects of HR-QoL related to bowel function, but a worsening of urinary and sexual functions. Further randomized controlled trials are needed to confirm these data., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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

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

We describe a 69-year-old man who came to our observation with a history of persistent left flank abdominal pain, fever for several weeks, and a previous history of passing renal stones. Radiological examinations with computed tomography and magnetic resonance imaging revealed a solid mass within the left side of a horseshoe kidney, with associated large renal stones. The patient subsequently underwent partial left nephrectomy. The final diagnosis was consistent with squamous cell carcinoma arising in a horseshoe kidney, with associated renal stones., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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

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

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

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

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

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

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

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

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

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

Objectives: We analysed the role of smoking on the risk of erectile dysfunction (ED) using data from a cross-sectional study on prevalence and risk factors for ED in the general population in Italy., Methods: A total of 2010 men aged more than 18 years were randomly identified and interviewed by 143 general practitioners among their registered patients. Patients were asked "about their ability to achieve and maintain an erection sufficient for satisfactory sexual performance." If they were dissatisfied, they were defined as having ED., Results: In comparison with never smokers, current smokers had an odds ratio (OR) of ED of 1.7 (95% confidence interval (CI), 1.2-2.4) and ex-smokers of 1.6 (95% CI, 1.1-2.3). The association between smoking and ED risk was present in subjects without a history of any cardiovascular disease, cardiopathy, hypertension, diabetes and neuropathy, but not in those with a history of these conditions. For example, the ORs of ED in smokers, in comparison with never smokers, were respectively 2.4, 2.0 and 1.7 in men with no history of any cardiovascular disease, diabetes and neuropathy, but respectively 1.0, 1.0 and 1.2 in those with a history of the conditions., Conclusions: This study shows that the risk of ED is influenced by smoking and that the duration of the habit increases the risk. Further, it highlights the potential interaction of smoking with medical history on ED risk.