Effect of ejaculatory abstinence period on fertilization and clinical outcomes in ICSI cycles: a retrospective analysis.

RESEARCH QUESTION: Does ejaculatory abstinence impact fertilization outcomes in intracytoplasmic sperm injection (ICSI) cycles in infertile couples? DESIGN: This single-centre retrospective observational study included 6919 ICSI cycles from 2013 to 2022. The primary outcome was the assessment of oocyte fertilization, measured in terms of the rate of formation of two-pronuclear (2PN), 3PN and 1PN zygotes. Secondary outcomes were blastulation, cumulative positive ß-human chorionic gonadotrophin test and clinical pregnancy rates. Relationships between ejaculatory abstinence and fertilization outcomes, and ejaculatory abstinence and clinical outcomes were evaluated with multivariable analysis, including possible confounders. RESULTS: A positive association was observed between ejaculatory abstinence and semen sample volume (P < 0.001), sperm concentration (P < 0.001) and total motile sperm count (P < 0.001). No association was found between the 1PN zygote rate and ejaculatory abstinence (P = 0.97). Conversely, for each additional day of ejaculatory abstinence, the likelihood of obtaining 2PN zygotes from all inseminated oocytes decreased by 3% [adjusted odds ratio (aOR) 0.97, 95% CI 0.94-0.99], whilst the likelihood of obtaining 3PN zygotes from all inseminated oocytes increased significantly by 14% (aOR 1.14, 95% CI 1.07-1.22). No significant associations were found between ejaculatory abstinence and blastulation, cumulative pregnancy or miscarriage rates. CONCLUSIONS: A longer ejaculatory abstinence period significantly decreases the rate of 2PN zygotes, and increases the rate of 3PN zygotes without directly affect blastulation and pregnancy rates.

Micro-mechanical fingerprints of the rat bladder change in actinic cystitis and tumor presence.

Tissue mechanics determines tissue homeostasis, disease development and progression. Bladder strongly relies on its mechanical properties to perform its physiological function, but these are poorly unveiled under normal and pathological conditions. Here we characterize the mechanical fingerprints at the micro-scale level of the three tissue layers which compose the healthy bladder wall, and identify modifications associated with the onset and progression of pathological conditions (i.e., actinic cystitis and bladder cancer). We use two indentation-based instruments (an Atomic Force Microscope and a nanoindenter) and compare the micromechanical maps with a comprehensive histological analysis. We find that the healthy bladder wall is a mechanically inhomogeneous tissue, with a gradient of increasing stiffness from the urothelium to the lamina propria, which gradually decreases when reaching the muscle outer layer. Stiffening in fibrotic tissues correlate with increased deposition of dense extracellular matrix in the lamina propria. An increase in tissue compliance is observed before the onset and invasion of the tumor. By providing high resolution micromechanical investigation of each tissue layer of the bladder, we depict the intrinsic mechanical heterogeneity of the layers of a healthy bladder as compared with the mechanical properties alterations associated with either actinic cystitis or bladder tumor.

Surgical and minimally invasive treatment of ischaemic and non-ischaemic priapism: a systematic review by the EAU Sexual and Reproductive Health Guidelines panel.

Surgical treatments for ischemic priapism (IP) include shunts or penile implants. Non-ischemic priapism (NIP) is usually the result of penile/perineal trauma causing an arterial fistula and embolisation may be required. We conducted a systematic review on behalf of the EAU Sexual and Reproductive health Guidelines panel to analyse the available evidence on efficacy and safety of surgical modalities for IP and NIP. Outcomes were priapism resolution, sexual function and adverse events following surgery. Overall, 63 studies (n = 923) met inclusion criteria up to September 2021. For IP (n = 702), surgery comprised distal (n = 274), proximal shunts (n = 209) and penile prostheses (n = 194). Resolution occurred in 18.7-100% for distal, 5.7-100% for proximal shunts and 100% for penile prostheses. Potency rate was 20-100% for distal, 11.1-77.2% for proximal shunts, and 26.3-100% for penile prostheses, respectively. Patient satisfaction was 60-100% following penile prostheses implantation. Complications were 0-42.5% for shunts and 0-13.6% for IPP. For NIP (n = 221), embolisation success was 85.7-100% and potency 80-100%. The majority of studies were retrospective cohort studies. Risk of bias was high. Overall, surgical shunts have acceptable success rates in IP. Proximal/venous shunts should be abandoned due to morbidity/ED rates. In IP > 48 h, best outcomes are seen with penile prostheses implantation. Embolisation is the mainstay technique for NIP with high resolution rates and adequate erectile function.

What is the effectiveness of surgical and non-surgical therapies in the treatment of ischemic priapism in patients with sickle cell disease? A systematic review by the EAU Sexual and Reproductive Health Guidelines Panel.

Sickle cell disease (SCD) is an inherited hemoglobin disorder characterized by the occlusion of small blood vessels by sickle-shaped red blood cells. SCD is associated with a number of complications, including ischemic priapism. While SCD accounts for at least one-third of all priapism cases, no definitive treatment strategy has been established to specifically treat patients with SC priapism. The aim of this systematic review was to assess the efficacy and safety of contemporary treatment modalities for acute and stuttering ischemic priapism associated with SCD. The primary outcome measures were defined as resolution of acute priapism (detumescence) and complete response of stuttering priapism, while the primary harm outcome was as sexual dysfunction. The protocol for the review has been registered (PROSPERO Nr: CRD42020182001), and a systematic search of Medline, Embase, and Cochrane controlled trials databases was performed. Three trials with 41 observational studies met the criteria for inclusion in this review. None of the trials assessed detumescence, as a primary outcome. All of the trials reported a complete response of stuttering priapism; however, the certainty of the evidence was low. It is clear that assessing the effectiveness of specific interventions for priapism in SCD, well-designed, adequately-powered, multicenter trials are strongly required.

Andrological effects of SARS-Cov-2 infection: a systematic review and meta-analysis.

PURPOSE: The short- and long-term andrological effects of coronavirus disease 2019 (COVID-19) have not been clarified. Our aim is to evaluate the available evidence regarding possible andrological consequences of COVID-19 either on seminal or hormonal parameters. The safety of the COVID-19 vaccines in terms of sperm quality was also investigated. METHODS: All prospective and retrospective observational studies reporting information on severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) mRNA semen and male genitalia tract detection (n = 19), as well as those reporting data on semen analysis (n = 5) and hormonal parameters (n = 11) in infected/recovered patients without any arbitrary restriction were included. RESULTS: Out of 204 retrieved articles, 35 were considered, including 2092 patients and 1138 controls with a mean age of 44.1 ± 12.6 years, and mean follow-up 24.3 ± 18.9 days. SARS-CoV-2 mRNA can be localized in male genitalia tracts during the acute phase of the disease. COVID-19 can result in short-term impaired sperm and T production. Available data cannot clarify long-term andrological effects. Low T observed in the acute phase of the disease is associated with an increased risk of being admitted to the Intensive Care Unit or death. The two available studies showed that the use of mRNA COVID-19 vaccines does not affect sperm quality. CONCLUSIONS: The results of our analysis clearly suggest that each patient recovering from COVID-19 should be monitored to rule out sperm and T abnormalities. The specific contribution of reduced T levels during the acute phase of the infection needs to be better clarified.

Does the administration of preoperative pembrolizumab lead to sustained remission post-cystectomy? First survival outcomes from the PURE-01 study☆.

BACKGROUND: Initial studies of preoperative checkpoint inhibition before radical cystectomy (RC) have shown promising pathologic complete responses. We aimed to analyze the survival outcomes of patients enrolled in the PURE-01 study (NCT02736266). PATIENTS AND METHODS: We report the results of the secondary end points of PURE-01 in the final population of 143 patients. In particular, we report the event-free survival (EFS) outcomes, defined as the time from the first cycle of pembrolizumab to radiographic disease progression precluding RC, initiation of neoadjuvant chemotherapy (NAC), recurrence after RC, or death from any cause. Other end points were recurrence-free survival (RFS) and overall survival (OS). Subgroup analyses were carried out, including pathological response category, clinical complete responses (CR) assessed via multiparametric magnetic resonance imaging (mpMRI), and molecular subtyping. Cox regression analyses for EFS were also carried out. RESULTS: After a median [interquartile range (IQR)] follow-up of 23 (15-29) months, 12- and 24-month EFS were 84.5% [95% confidence interval (CI): 78.5-90.9] and 71.7% (62.7-82). The prognosis was favorable across all the different pathological response subgroups, with the exception of ypN+ (N = 21), showing a 24-month RFS (95% CI) of 39.3% (19.2% to 80.5%). A statistically significant EFS benefit was observed in patients with a clinical CR (P = 0.002). Programmed cell-death-ligand-1 combined positive score was significantly associated with longer EFS in multivariable analyses. Four patients refused RC after clinical evidence of CR, and none of them have recurred after a median follow-up of 10 months (IQR: 11-15). The claudin-low subtype displayed a numerically longer EFS after pembrolizumab and RC compared with the other subtypes. CONCLUSIONS: The EFS results from PURE-01 revealed that the immunotherapy effect was maintained post-RC in most patients. Pembrolizumab compared favorably with neoadjuvant chemotherapy, irrespective of the biomarker status. Molecular subtyping may be a useful tool to select the patients who are predicted to benefit the most from neoadjuvant pembrolizumab.

The anti-tumoral potential of the saporin-based uPAR-targeting chimera ATF-SAP.

The development of personalized therapies represents an urgent need owing to the high rate of cancer recurrence and systemic toxicity of conventional drugs. So far, targeted toxins have shown promising results as potential therapeutic compounds. Specifically, toxins conjugated to antibodies or fused to growth factors/enzymes have been largely demonstrated to selectively address and kill cancer cells. We investigated the anti-tumor potential of a chimeric recombinant fusion protein formed by the Ribosome Inactivating Protein saporin (SAP) and the amino-terminal fragment (ATF) of the urokinase-type plasminogen activator (uPA), whose receptor has been shown to be over-expressed on the surface of aggressive tumors. ATF-SAP was recombinantly produced by the P. pastoris yeast and its activity was assessed on a panel of bladder and breast cancer cell lines. ATF-SAP resulted to be highly active in vitro, as nano-molar concentrations were sufficient to impair viability on tumor cell lines. In contrast to untargeted toxins, the chimeric fusion protein displayed a significantly improved toxic effect in uPAR-expressing cells, demonstrating that the selective activity was due to the presence of the targeting moiety. Fibroblasts were not sensitive to ATF-SAP despite uPAR expression, indicating that cell-specific receptor-mediated internalization pathway(s) might be considered. The in vivo anti-tumor effect of the chimera was shown in a bladder cancer xenograft model. Current findings indicate ATF-SAP as a suitable anti-tumoral therapeutic option to cope with cancer aggressiveness, as a single treatment or in combination with traditional therapeutic approaches, to appropriately address the intra- and inter- tumor heterogeneity.

Impact of time from diagnosis to treatment on erectile function outcomes after radical prostatectomy.

BACKGROUND: Concerns exist about the effect of delaying treatment for prostate cancer (PCa) regarding both oncological and functional outcomes after radical prostatectomy (RP). OBJECTIVE: To assess the impact of time from diagnosis to RP on post-operative erectile function (EF) outcomes. MATERIALS AND METHODS: We analyzed data for 827 patients treated with RP at a single center from 2002 to 2017. The International Index of Erectile Function-EF (IIEF-EF) was compiled by every patient (EF recovery equal to IIEF-EF ≥ 22). Time from diagnosis to treatment was defined as the interval between biopsy and RP. Cox regression analysis was used to test the impact of time to surgery on the probability of EF recovery. Kaplan-Meier analysis compared the cumulative incidence of EF recovery according to time from diagnosis to surgery. The impact of time to RP on EF was tested also in a sub-cohort of patients eligible for active surveillance (AS). RESULTS: Overall, low-, intermediate-, and high-risk PCa was found in 306 (37%), 422 (51%), and 99 (12%) patients. Of them, 148 (17.9%) would have been eligible for AS. A total of 152 (18%) and 22 (2.7%) patients were treated after 6 and 12 months from diagnosis. The overall probability of EF recovery was 32% (95% CI: 29-36) at 24 months. Cox regression analysis showed that time from biopsy to surgery was not associated with a different chance of EF recovery (HR: 1.01; 95% CI: 0.97-1.05; p = 0.7). At Kaplan-Meier analysis, the cumulative incidence of EF recovery did not differ between patients treated within 6 months, from 6 to 12 months and after 12 months from diagnosis. Similar findings were obtained for patients eligible for AS. DISCUSSION: Patients may be reassured regarding their chance of post-operative EF recovery in the case of a delayed surgical treatment. CONCLUSIONS: Delaying surgery after PCa diagnosis does not affect post-operative EF recovery outcomes regardless of oncological risk.

The role of neutrophil-to-lymphocyte ratio in men with erectile dysfunction-preliminary findings of a real-life cross-sectional study.

The aim of this study was to investigate the role of systemic inflammation by means of the neutrophil-to-lymphocyte ratio (NLR) in men with erectile dysfunction (ED). Complete demographic, clinical, and laboratory data from 279 consecutive men with newly diagnosed ED were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). A complete blood count was requested for every man, and the NLR was calculated for every individual. Patients were invited to complete the IIEF questionnaire. Logistic regression models tested the odds (OR, 95% CI) of severe ED (defined as IIEF-EF <11, according to Cappelleri's criteria) after adjusting for age, BMI, comorbidities (CCI >0), metabolic syndrome, NLR, cigarette smoking, and color duplex Doppler ultrasound parameters. Likewise, LNR values were also dichotomized according to the most informative cutoff predicting severe ED using the minimum p value approach. Median [IQR] age of included men was 51 [40-64] years. Of all, 87 (31%) men had severe ED. Men with severe ED were older (median [IQR] age: 61 [47-67] vs. 49 [39-58] years) and had a higher rate of CCI>0 [46/87 (53%) vs. 44/192 (23%) patients]. Thereof, NLR was dichotomized according to the most informative cutoff (NLR>3); patients with severe ED more frequently had NLR>3 as compared to all other ED patients [namely, 18/87 (21%) vs. 13/192 (7%)]. At multivariable logistic regression analysis, NLR>3.0 emerged as an independent predictor (OR [CI] 2.43 [1.06; 5.63]) of severe ED, after accounting for other clinical variables. A NLR>3 increased the risk of having severe ED in our cohort, boosting the already existing evidence linking systemic inflammation to ED. Moreover, this easily obtainable index can be clinically useful in better risk-stratifying patients with ED.

Long-term penile morphometric alterations in patients treated with robot-assisted versus open radical prostatectomy.

Neglected side effects after radical prostatectomy have been previously reported. In this context, the prevalence of penile morphometric alterations has never been assessed in robot-assisted radical prostatectomy series. We aimed to assess prevalence of and predictors of penile morphometric alterations (i.e. penile shortening or penile morphometric deformation) at long-term follow-up in patients submitted to either robot-assisted (robot-assisted radical prostatectomy) or open radical prostatectomy. Sexually active patients after either robot-assisted radical prostatectomy or open radical prostatectomy prospectively completed a 28-item questionnaire, with sensitive issues regarding sexual function, namely orgasmic functioning, climacturia and changes in morphometric characteristics of the penis. Only patients with a post-operative follow-up ≥ 24 months were included. Patients submitted to either adjuvant or salvage therapies or those who refused to comprehensively complete the questionnaire were excluded from the analyses. A propensity-score matching analysis was implemented to control for baseline differences between groups. Logistic regression models tested potential predictors of penile morphometric alterations at long-term post-operative follow-up. Overall, 67 (50%) and 67 (50%) patients were included after open radical prostatectomy or robot-assisted radical prostatectomy, respectively. Self-rated post-operative penile shortening and penile morphometric deformation were reported by 75 (56%) and 29 (22.8%) patients, respectively. Rates of penile shortening and penile morphometric deformation were not different after open radical prostatectomy and robot-assisted radical prostatectomy [all p > 0.5]. At univariable analysis, self-reported penile morphometric alterations (either penile shortening or penile morphometric deformation) were significantly associated with baseline international index of erectile function-erectile function scores, body mass index, post-operative erectile function recovery, year of surgery and type of surgery (all p < 0.05). At multivariable analysis, robot-assisted radical prostatectomy was independently associated with a lower risk of post-operative penile morphometric alterations (OR: 0.38; 95% CI: 0.16-0.93). Self-perceived penile morphometric alterations were reported in one of two patients after radical prostatectomy at long-term follow-up, with open surgery associated with a potential higher risk of this self-perception.

Primary, secondary and compensated hypogonadism: a novel risk stratification for infertile men.

Recently, the cohort of men from the European Male Ageing Study has been stratified into different categories distinguishing primary, secondary and compensated hypogonadism. A similar classification has not yet been applied to the infertile population. We performed a cross-sectional study enrolling 786 consecutive Caucasian-European infertile men segregated into eugonadal [normal serum total testosterone (≥3.03 ng/mL) and normal luteinizing hormone (≤9.4 mU/mL)], secondary (low total testosterone, low/normal luteinizing hormone), primary (low total testosterone, elevated luteinizing hormone) and compensated hypogonadism (normal total testosterone; elevated luteinizing hormone). In this cross-sectional study, logistic regression models tested the association between semen parameters, clinical characteristics and the defined gonadal status. Eugonadism, secondary, primary and compensated hypogonadism were found in 80, 15, 2, and 3% of men respectively. Secondary hypogonadal men were at highest risk for obesity [OR (95% CI): 3.48 (1.98-6.01)]. Primary hypogonadal men were those at highest risk for azoospermia [24.54 (6.39-161.39)] and testicular volume <15 mL [12.80 (3.40-83.26)]. Compensated had a similar profile to primary hypogonadal men, while their risk of azoospermia [5.31 (2.25-13.10)] and small testicular volume [8.04 (3.17-24.66)] was lower. The risk of small testicular volume [1.52 (1.01-2.33)] and azoospermia [1.76 (1.09-2.82)] was increased, although in a milder fashion, in secondary hypogonadal men as well. Overall, primary and compensated hypogonadism depicted the worst clinical picture in terms of impaired fertility. Although not specifically designed for infertile men, European Male Ageing Study categories might serve as a clinical stratification tool even in this setting.

Sexual functioning mirrors overall men's health status, even irrespective of cardiovascular risk factors.

Erectile dysfunction has been described as a sentinel marker of co-existing and undetected cardiovascular disease. Beside cardiovascular diseases, a correlation between erectile dysfunction and other major comorbidities has been also reported. The study was aimed to analyze the association between sexual functioning and overall men's health in sexually active, Caucasian-European men with new-onset sexual dysfunction. Data from the last 881 consecutive patients seeking first medical help for sexual dysfunction were cross-sectionally analyzed. The International Classification of Diseases, 9th revision, Clinical Modification was used to classify health-significant comorbidities, which were scored with the Charlson Comorbidity Index (CCI). A modified CCI score from which all potential cardiovascular risk factors (CCI-CV) were subtracted was then calculated for every patient. Patients were requested to complete the International Index of Erectile Function (IIEF). The main outcome of the study was the association between the IIEF domain scores and CCI, which scored health-significant comorbidities even irrespective of cardiovascular risk factors (CCI-CV). The final sample included 757 patients (85.9%) (Median age: 48 years; IQ range: 37-59). Overall, erectile dysfunction was found in 540 (71.4%) patients. Of these, 164 (21.6%) had a CCI ≥ 1 and 138 (18.2%) had a CCI-CV ≥ 1, respectively. At the analysis of variance, IIEF-Erectile Function (EF) scores significantly decreased as a function of incremental CCI and CCI-CV scores (all p < 0.01). At multivariable logistic regression analysis, both IIEF-EF and IIEF-total score achieved independent predictor status for either CCI ≥ 1 or CCI-CV ≥ 1, after accounting for potential confounders (p < 0.01). We report novel findings of a significant association between erectile dysfunction severity and overall men's health, even irrespective of cardiovascular risk factors. Thereof, erectile dysfunction severity could serve as a proxy for general men's health, thus encouraging physicians to comprehensively assess patients complaining of sexual dysfunction in the real-life everyday clinical practice.

The surgical management of patients with clinical stage T4 bladder cancer: A single institution experience.

INTRODUCTION: Patients with clinical T4 (cT4) bladder cancer (BCa) infrequently undergo radical cystectomy (RC). We investigated the reliability of preoperative clinical staging, perioperative and survival outcomes in patients treated with RC due to cT4a-b BCa disease at a single tertiary care institution. METHODS: The study relied on 917 BCa patients treated with RC and pelvic lymph node dissection (PLND) at a single institution between January 1995 and December 2012. We compared the accuracy of the clinical assessment with final pathology results. Moreover, we evaluated perioperative outcomes, complication rates and survival after surgery. RESULTS: The median follow-up was 62 months. Overall, 74 (8.1%) patients presented cT4 stage at preoperative evaluation. Conversely, a pathological T4 disease was confirmed only in 68.9% patients staged initially as cT4. No differences were recorded in complications, 30 days readmission or 30 days death rates between cT1-T3 vs. cT4a vs. cT4b (p > 0.1). At multivariable Cox regression analyses predicting cancer specific mortality, clinical T4 stage vs. clinical T1-2, clinical T3 stage vs. clinical T1-2 and age were predictors of worst survival after RC (all p < 0.04). CONCLUSIONS: We recorded poor concordance between preoperative imaging and pathology in cT4 patients. No differences in major perioperative outcomes and acceptable survival expectancies were reported in patients treated for cT4 disease.

Efficacy and safety of dapoxetine in treatment of premature ejaculation: an evidence-based review.

BACKGROUND: Premature ejaculation (PE) is a major issue in male sexual health, with a global prevalence estimated to be between 20% and 40%, making it the most common sexual dysfunction in men. PE causes distress and reduced quality of life for patients and has a negative impact on interpersonal relationships. Historically, it has been treated with cognitive therapy, behavioural methods and off-label use of selective serotonin reuptake inhibitors (SSRIs) usually used to treat depression and other psychological disorders. Dapoxetine is the only SSRI specifically designed to treat PE. MECHANISM OF ACTION: Dapoxetine hydrochloride is a potent inhibitor of serotonin reuptake transporters. Dapoxetine is suited for 'on-demand' treatment of PE because of its rapid absorption and short initial half-life. EFFICACY: Evidence from published studies showed that dapoxetine 30 mg or 60 mg taken 'on-demand' results in a significant increase in intravaginal ejaculatory latency time (IELT) when compared with placebo. Most patient-reported outcomes are clearly improved relative to placebo following dapoxetine therapy, indicating greater control over ejaculation, more satisfaction with intercourse, less ejaculation-related distress and significantly reduced interpersonal difficulties. SAFETY: The most common adverse events with dapoxetine are nausea, dizziness, somnolence, headache, diarrhoea and insomnia. Usually they do not lead to drug discontinuation. CONCLUSION: Dapoxetine is the only effective and safe available on-label oral treatment for PE, and its use can result in better quality of life for the patient and their sexual partner.

Long-term sexual outcomes after holmium laser enucleation of the prostate: which patients could benefit the most?

Assess rate and predictors of erectile function (EF) outcomes at long-term follow-up (FU) after holmium laser enucleation of the prostate (HoLEP). Cross-sectional analyses were performed on 135 patients with a mean FU of 12 years post HoLEP. Patients completed both a baseline and a FU International Index of Erectile Function (IIEF)-EF domain and the International Prostatic Symptoms Score (IPSS). Postoperative EF outcomes, including rate and predictors of EF improvement considering minimal clinically important differences (MCIDs) criteria, were assessed. Logistic regression models tested the association between predictors and EF. At a mean (median) FU of 152.1 (163) months, patients showed a significant decrease in the IIEF-EF score P<0.01) and significant IPSS improvement (P<0.01). Overall, 50 (37%) patients worsened by at least one IIEF-EF category. Conversel, 23 (17%) patients reported an improvement in postoperative IIEF-EF score; 75 (55.6%) and 10 (7.4%) patients maintained and eventually improved their IIEF-EF category, respectively. Patients reporting a decrease in the postoperative IIEF-EF score were significantly older (P=0.03) and showed a significantly longer mean FU (P<0.01) than those reporting postoperative improvements of IIEF-EF. Nine (6.7%) patients showed significant EF improvement according to MCIDs criteria. Both higher IPSS scores (odds ratio (OR): 1.12; P=0.02) and lower IIEF-EF (OR: 0.88; P<0.01) at baseline, emerged as independent predictors of postoperative EF improvement. HoLEP was associated with a decrease in EF and a persistent amelioration of BPH-related urinary symptoms at long-term FU. Almost one third of patients worsened by at least one IIEF-EF category. However, a clinically meaningful EF improvement was observed in roughly 7% of the individuals. Patients with more severe preoperative urinary symptoms and ED benefited more from HoLEP in terms of EF.

Metabolic syndrome in white European men presenting for primary couple's infertility: investigation of the clinical and reproductive burden.

Despite complex interactions between obesity, dyslipidemia, hyperinsulinaemia, and the reproductive axis, the impact of metabolic syndrome on human male reproductive function has not been analysed comprehensively. Complete demographic, clinical, and laboratory data from 1337 consecutive primary infertile men were analysed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (categorised 0 vs. 1 vs. 2 or higher). NCEP-ATPIII criteria were used to define metabolic syndrome. Semen analysis values were assessed based on the 2010 World Health Organisation (WHO) reference criteria. Descriptive statistics and logistic regression models tested the association between semen parameters and clinical characteristics and metabolic syndrome. Metabolic syndrome was found in 128 (9.6%) of 1337 men. Patients with metabolic syndrome were older (p < 0.001) and had a greater Charlson Comorbidity Index of 1 or higher (chi-square: 15.6; p < 0.001) compared with those without metabolic syndrome. Metabolic syndrome patients had lower levels of total testosterone (p < 0.001), sex hormone-binding globulin (p = 0.004), inhibin B (p = 0.03), and anti-Müllerian hormone (p = 0.009), and they were hypogonadal at a higher rate (chi-square: 32.0; p < 0.001) than patients without metabolic syndrome. Conversely, the two groups did not differ significantly in further hormonal levels, semen parameters, and rate of either obstructive or non-obstructive azoospermia. At multivariate logistic regression analysis, testicular volume (OR: 0.90; p = 0.002) achieved independent predictor status for WHO pathological semen concentration; conversely, age, Charlson Comorbidity Index scores, metabolic syndrome, and inhibin B values did not. No parameters predicted normal sperm morphology and total progressive motility. Metabolic syndrome accounts for roughly 9% of men presenting for primary couple's infertility. Although metabolic syndrome patients have a lower general male health status, semen analysis values seem independent of the presence of metabolic syndrome.

Patterns and prognostic significance of clinical recurrences after radical cystectomy for bladder cancer: A 20-year single center experience.

OBJECTIVE: Patients treated with radical cystectomy (RC) due to bladder cancer (BCa) face high risk of clinical recurrence. The aim of our study was to describe recurrence patterns and characteristics related to survival in patients treated with RC due to BCa. METHODS: Years 1992-2012 of a prospectively maintained institutional RC registry were queried for clinical localized urothelial BCa patients. Clinical recurrences were categorized as local, distant or secondary urothelial recurrences. Kaplan Meier analysis assessed time to cancer specific mortality (CSM). Multivariable Cox regression models were constructed to predict recurrence and CSM after recurrence. RESULTS: Data from 1110 patients with urothelial non-metastatic BCa at RC were analyzed with 7.5 years of median follow up. Overall, 324 patients experienced recurrence and 200 (61.7%) were single site recurrence. The locations were: 43 local (22 cystectomy bed and 21 pelvic lymph node dissection template), 138 distant (36 lung, 19 liver, 52 bone, 17 extra pelvic LN, 7 peritoneal, 4 brain and 3 others) and 19 secondary urothelial carcinoma (11 upper urinary tract, 8 urethra). Significant independent predictors of overall recurrence were pathological stage pT3/T4 vs. pT0-2, pathological N positive status and positive surgical margin. Median overall survival after recurrence was 18 months. At multivariate analysis, pathological T3 (Hazard ratio [HR]: 1.62), T4 (HR: 1.58), interval from RC to recurrence (HR: 0.92) and distant (HR: 2.57) recurrences were independently associated with CSM (all p < 0.05). CONCLUSIONS: Overall, one out of three patients treated with RC face recurrence during follow up. Early and distant recurrences are associated with shortest survival expectancies.

Non-surgically related causes of erectile dysfunction after bilateral nerve-sparing radical prostatectomy.

BACKGROUND: Erectile dysfunction (ED) represents one of the most common long-term side effects in prostate cancer (PCa) patients treated with bilateral nerve-sparing radical prostatectomy (BNSRP). The aim of our study was to assess the influence of non-surgically related causes of ED in patients treated with BNSRP. METHODS: Overall, 716 patients treated with BNSRP were retrospectively identified. All patients had complete data on erectile function (EF) assessed by the Index of Erectile Function-EF domain (IIEF-EF) and depressive status assessed by the Center for Epidemiologic Studies-Depression (CES-D) questionnaire. EF recovery was defined as an IIEF-EF of ⩾22. Kaplan-Meier analyses assessed the impact of preoperative IIEF-EF, depression and adjuvant radiotherapy (aRT) on the time to EF recovery. Multivariable Cox regression models were used to test the impact of aRT on EF recovery after accounting for depression and baseline IIEF-EF. RESULTS: Median follow-up was 48 months. Patients with a preoperative IIEF-EF of ⩾22 had substantially higher EF recovery rates compared with those with a lower IIEF-EF (P<0.001). Patients with a CES-D of <16 had significantly higher EF recovery rates compared to those with depression (60.8 vs 49.2%; P=0.03). Patients receiving postoperative aRT had lower rates of EF compared with their counterparts left untreated after surgery (40.7 vs 59.8%; P<0.001). These results were confirmed in multivariable analyses, where preoperative IIEF-EF (P<0.001), depression (P=0.04) and aRT (P=0.03) were confirmed as significant predictors of EF recovery. CONCLUSIONS: Preoperative functional status and depression should be considered when counseling PCa patients regarding the long-term side effects of BNSRP. Moreover, the administration of aRT has a detrimental effect on the probability of recovering EF after BNSRP. This should be taken into account when balancing the potential benefits and side effects of multimodal therapies in PCa patients.

Determinants of long-term survival of patients with locally advanced prostate cancer: the role of extensive pelvic lymph node dissection.

BACKGROUND: The therapeutic effect of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) due to prostate cancer (PCa) is still under debate. We aimed at assessing the impact of more extensive PLND on cancer-specific mortality (CSM) in patients treated with surgery for locally advanced PCa. METHODS: We examined data of 1586 pT3-T4 PCa patients treated with RP and extended PLND between 1987 and 2012 at a tertiary referral care center. Univariable and multivariable Cox regression analyses tested the relationship between the number of nodes removed and CSM rate, after adjusting for potential confounders. Survival estimates were based on the multivariable models. RESULTS: The average number of nodes removed was 19 (median: 17; interquartile range: 11-23). Mean and median follow-up were 80 and 72 months, respectively. At multivariable analyses, Gleason score 8-10 (hazard ratio (HR): 2.5) and a higher number of positive nodes (HR: 1.06) were independently associated with higher CSM rate (all P<0.05). Conversely, higher number of removed LNs (HR: 0.94) and adjuvant radiotherapy (HR: 0.54) were independent predictors of lower CSM rates (all P⩽0.03). CONCLUSIONS: In pT3-T4 PCa patients, removal of a higher number of LNs during RP was associated with higher cancer-specific survival rates. This supports the role of more extensive PLNDs in this patient group. Further prospective studies are needed to validate our findings.