Tadalafil once daily and extracorporeal shock wave therapy in the management of patients with Peyronie's disease and erectile dysfunction: results from a prospective randomized trial.

Extracorporeal shock wave therapy improves erectile function in patients with Peyronie's disease. However, erectile dysfunction still persists in many cases. We aimed to investigate the effects of extracorporeal shock wave therapy plus tadalafil 5 mg once daily in the management of patients with Peyronie's disease and erectile dysfunction not previously treated. One hundred patients were enrolled in a prospective, randomized, controlled study. Patients were randomly allocated to receive either extracorporeal shock wave therapy alone for 4 weeks (n = 50) or extracorporeal shock wave therapy plus tadalafil 5 mg once daily for 4 weeks (n = 50). Main outcome measures were: erectile function (evaluated through the shortened version of the International Index of Erectile Function), pain during erection (evaluated through a Visual Analog Scale), plaque size, penile curvature and quality of life (evaluated through an internal questionnaire). Follow-up evaluations were performed after 12 and 24 weeks. In both groups, at 12 weeks follow-up, mean Visual Analog Scale score, mean International Index of Erectile Function score and mean quality of life score ameliorated significantly while mean plaque size and mean curvature degree were unchanged. Intergroup analysis revealed a significantly higher mean International Index of Erectile Function score and quality of life score in patients receiving the combination. After 24 weeks, intergroup analysis revealed a significantly higher mean International Index of Erectile Function score and mean quality of life score in patients that received extracorporeal shock wave therapy plus tadalafil. In conclusion extracorporeal shock wave therapy plus tadalafil 5 mg once daily may represent a valid conservative strategy for the management of patients with Peyronie's disease and erectile dysfunction.

Are insulin resistance and non-alcoholic fatty liver disease associated with Peyronie's disease? A pilot study.

Risk factors for Peyronie's disease (PD) are serum lipid abnormalities, hypertension and type 2 diabetes mellitus (T2DM). Oxidative stress and inflammation are key-players in the pathogenesis of arterial diseases, leading to insulin resistance (IR), which is a major determinant of non-alcoholic fatty liver disease (NAFLD). We studied the potential relationship between PD, IR, and NAFLD. Forty-nine male patients were enrolled, fulfilling the well-accepted diagnostic criteria of stable PD. Fifty male individuals without PD, well-matched for age and BMI, were selected as the control group. Comorbidities (T2DM and hypertension), as well as the lipid profile and the glucometabolic asset, were evaluated. The triglycerides/HDL ratio (TG/HDL-C ratio) with a cut-off of ≥3 and the triglycerides-glucose index (TyG) with an optimal cut-point of 8.5 were used for diagnosis of IR and NAFLD, respectively. NAFLD diagnosis was confirmed by the presence of bright liver at ultrasonography. Hypertension was found more frequently in PD patients than in no-PD subjects (P=0.017), independently of age (P=0.99). Both IR and NAFLD were significantly associated with the presence of PD in our population of men (P=0.043 and 0.0001, respectively), no matter how old (P=0.11 and 0.74, respectively). At logistic regression, NAFLD was the only predictor of the PD presence (p=0.021). The AUROC of TyG to predict PD was 0.7437 (sensitivity 67.35% and specificity 80%) with a percentage of correctly classified patients of 73.74%. Oxidative stress markers were significantly associated with NAFLD. Testosterone level was significantly low in the subjects with NAFLD in cross-sectional analyses. Both factors, i.e., oxidative stress and hypogonadism, are central to PD pathogenesis. In conclusion, NAFLD and IR are strongly associated with PD. The pathogenic link between these conditions and the underlying mechanisms are only hypothetical and thoroughly summarized in the discussion.

The role of multiparametric resonance and biopsy in prostate cancer detection: comparison with definitive histological report after laparoscopic/robotic radical prostatectomy.

PURPOSE: Magnetic Resonance Imaging (MRI) targeted biopsy increases overall detection rates and decreases the risk of clinically insignificant PCa detection. The aim of this retrospective study is to compare concordance rates regarding side of lesion and Gleason Score at fusion targeted/systematic biopsy and MRI with the definitive histologic report of prostatectomy specimen. METHODS: 115 patients underwent multiparametric (mp) MRI and successively fusion targeted/systematic biopsy. 107 patients, with a positive biopsy for PCa, further underwent laparoscopic/robotic radical prostatectomy. We compared surgical histologic report with biopsy histologic report for side of lesion and Gleason Score. We further compared PIRADS score at mpMRI with Gleason Score of both histologic reports. RESULTS: Concordance rate for mpMRI lesion side was 74% compared to biopsy and 52.3% compared to surgical histologic report (p < 0.0001). Fusion targeted/systematic biopsy reported a concordance rate with surgical histologic report of 67.3% for side of the lesion, while Gleason Score was concordant for 73.6% for clinically significant cancer (Gleason Score ≥ 7) (p < 0.0001). PIRADS score ≥ 3 was further associated with clinically significant cancer at surgical histologic report in 92.4% of cases (p = 0.359). CONCLUSION: Multiparametric MRI of the prostate reaches a good and improvable accuracy in the detection of suspicious PCa before biopsy. A combined approach of fusion targeted and systematic biopsy could further increase the overall accuracy in PCa diagnosis, especially in biopsy-naïve patients, reaching concordance rates with definitive histologic report up to 52.3% and 85.5%.

Advanced/metastatic bladder cancer: current status and future directions.

In 2015 bladder cancer was the fourth most frequent malignancy and the eighth cause of death for cancer. At diagnosis, about 30% of bladder cancer (BC) patients present a muscle-invasive bladder cancer (MIBC) and 5% a metastatic bladder carcinoma (MBC). For fit MBC patients, combination chemotherapy (CC) is the standard of care for first-line treatment. CC includes both the treatment with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) either the classical or the dose-dense MVAC regimen, and the doublet therapy with cisplatin and gemcitabine (CG). Median progression free survival (PFS) was 7 months and median overall survival (OS) was 15 months. The present review provides an update on the management of MBC, with focus on target therapies, immune checkpoint inhibition, looking for prognostic and predictive factors.

Prognostic and predictive factors in testicular cancer.

OBJECTIVE: Testicular cancer is a relatively rare neoplasia, with an incidence of about 1,5% among male malignancies, usually in the third and fourth decade of life. Although several histological variants are known, with some histotypes affecting older patients (e.g., spermatocytic seminoma), there is a clear predominance (90-95%) of germ cell tumors among young adults patients1. Testicular Germ Cell Tumor (TGCT), undoubtedly the seminoma histological variant more than non-seminoma one, is definitely a highly curable disease, with a distinctive sensitivity to cisplatin-based therapy (and for seminomas to radiotherapy) and an outstanding cure rate of nearly 80% even for patients with advanced disease. So far, clinical and pathohistological features supported our efforts to choose the best treatment option for patients suffering from this malignancy, but we don't clearly enough know molecular and pathological features underlying different clinical behaviors, mostly in early-stage disease: by improving this knowledge, we should better "shape" therapeutic or surveillance programs for each patient, also in order to avoid unnecessary, if not harmful, treatments.

General and sex profile of women with partner affected by premature ejaculation: results of a large observational, non-interventional, cross-sectional, epidemiological study (IPER-F).

BACKGROUND: Couple distress is a crucial point in premature ejaculation (PE). PE has been associated with significant bother, interpersonal problems, and dissatisfaction with sexual intercourse for both men and their partners. OBJECTIVES: The primary objective of this study was to assess the effect of PE on female sexuality in female partners of men affected from PE. Secondary objectives were to assess the impact of PE on female sexual quality of life, to assess the presence of sexual problems of the male partner, and to evaluate the prevalence and characteristics of comorbidities. MATERIALS AND METHODS: Adult women aged 18 to 80 years old, sexually active, were randomly sampled from the patient lists of General Practitioners in Italy and were included in this observational, non-interventional, cross-sectional epidemiological study. Subjects were asked to fill: a general questionnaire regarding anthropometric data, lifestyle, marital status, education, occupation, economic conditions, general health status, comorbidities, and sexual habits; the Sexual Quality of Life Questionnaire-Female (SQoL-F); the Female Sexual Distress Scale (FSDS-R-PE); the Self-rating Depression Scale (SDS); and Self-rating Anxiety Scale (SAS). In addition, females reported about their partner's ejaculation time and the presence of sexual dysfunctions. RESULTS: A total of 3,104 women were included. Mean age was 45.1 years. Woman with PE partners presented a higher percentage of sexual dysfunction and reported more anxiety compared with female partners of men not affected from PE (42.69% vs. 20.56% and 30.95% vs. 15,34%, respectively). In addition, they referred more sexual dysfunction in their partners. Hypertension, hypercholesterolemia, arthritis, heart diseases, thyroid disease, a history of menopause, or hysterectomy resulted in significantly more prevalence in women with PE partners. DISCUSSION AND CONCLUSIONS: Female partners of PE patients present an increased prevalence of sexual distress, a reduced quality of sexual life, and an increased anxiety score when compared to women whose partners are not affected from PE.

Health-related quality of life and psychosocial implications in testicular cancer survivors. A literature review.

OBJECTIVE: In this review, we focused our attention on Quality of Life (QoL) of testicular cancer survivors (TCSs), in general and in the most relevant areas. Several key findings have been highlighted in our review. MATERIALS AND METHODS: PubMed, MEDLINE and PsycINFO databases were consulted to find published studies, from 1980 to May 2017, that met our inclusion criteria. RESULTS: The majority of studies investigated older adult TCSs, while few studies on adolescent and young adult patients were available. Many studies indicate that health-related QoL (HRQoL) is similar among the TCSs and the general population. Even if QoL deteriorates so clear at the time of diagnosis and throughout treatment, afterward returns to normal levels, as defined by the matched controls. However, there are numerous chronic conditions consequent to diagnosis and treatment of testicular cancer that plague survivors and affect QoL, like Raynaud-like phenomena, peripheral neuropathy, fatigue, anxiety, sexual, fertility and body image problems. Even if these problems can have no effects on the measures of global QoL, they have an impact on the quality of life. Differences between TCSs with and without a partner bring to different outcomes in the adjustments to cancer. CONCLUSIONS: It is necessary to identify TCSs with higher risks of poorer QoL outcomes, to focus interventions on the areas with the greatest impairments. Further researches should consider the effects of testicular cancer on the impaired areas, collecting more data to better identify survivor's needs and consequent interventions, with a special focus on adolescent and young adult TCSs. Other works are requested on therapies, preventive and ameliorative, to reduce chronic side effects of testicular cancer treatment.

Systematic review and meta-analysis of non RCT's on health related quality of life after radical cystectomy using validated questionnaires: Better results with orthotopic neobladder versus ileal conduit.

PURPOSE: The current literature on the impact of different urinary diversions on patients' health related quality of life (HR-QoL) showed a marginally better quality of life scores of orthotopic neobladder (ONB) compared to ileal conduit (IC). The aim of this study was to update the review of all relevant published studies on the comparison between ONB and IC. MATERIALS AND METHODS: Studies were identified by searching multiple literature databases, including MEDLINE, CINAHL, the Cochrane Library, PubMed Data were synthesized using meta-analytic methods conformed to the PRISMA statement. RESULTS: The current meta-analysis was based on 18 papers that reported a HR-QoL comparison between IC and ONB using at least a validate questionnaire. Pooled effect sizes of combined QoL outcomes for IC versus ONB showed a slight, but not significant, better QoL in patients with ONB (Hedges' g = 0.150; p = 0.066). Patients with ileal ONB showed a significant better QoL than those with IC (Hedges' g = 0.278; p = 0.000); in case series with more than 65% males, ONB group showed a slight significant better QoL than IC (Hedges' g = 0.190; p = 0.024). Pooled effects sizes of all EORTC-QLQ-C30 aspects showed a significant better QoL in patients with ONB (Hedges' g = 0.400; p = 0.0000). CONCLUSIONS: This meta-analysis of not-randomized comparative studies on the impact of different types of urinary diversions on HR-QoL showed demonstrated a significant advantage of ileal ONB compared to IC in terms of HR-QoL.

Peripheral relaxant activity of apomorphine and of a D1 selective receptor agonist on human corpus cavernosum strips.

Apomorphine is used in the erectile dysfunction therapy and its action has been ascribed to the stimulation of central dopamine receptor. At the present stage, very little is known about the peripheral action of apomorphine on human corpus cavernosum (HCC). We have investigated the peripheral action of apomorphine and the role of dopamine receptors in HCC. We here demonstrate that both D1 and D2 receptors were expressed in the HCC, D1 receptors were two-fold more abundant than D2 and that both receptors were mainly localized on the smooth muscle cell component. Apomorphine in vitro exerted an anti-alpha1 adrenergic activity in human cavernosal strips since it prevented contraction induced by phenylephrine (PE), but not by U46619 or endothelin. Apomorphine elicited endothelium-independent and concentration-dependent relaxation of the strips contracted by PE, U46619 or endothelin. The EC50 values (microM) for apomorphine, in the presence and absence of endothelium, were 51.0+/-16 and 16.0+/-14, 120+/-19 and 150+/-18, 59.0+/-15 and 140+/-50 on PE-, U46619- or endothelin-induced contraction, respectively. Selective dopamine receptor agonist A-68930 (D1-like), but not quinpirole (D2-like), caused concentration-dependent relaxation of the cavernosal strips, which was partially prevented by endothelium removal or by treatment with an inhibitor of nitric oxide (NO) synthase. In conclusion, we show that (1) apomorphine has a peripheral relaxant direct effect as well as an antiadrenergic activity, (2) HCC possesses more D1-like (D1 and D5) than D2-like (D2, D3 and D4) receptors, (3) both D1- and D2-like receptors are mainly localized on smooth muscle cells and (4) the relaxant activity is most probably mediated by D1-like receptor partially through NO release from endothelium.

Controlled clinical studies of nimesulide in the treatment of urogenital inflammation.

Two double-blind, randomised studies were conducted to compare the efficacy and tolerability of nimesulide (200 mg/day) with those of placebo or bromeline (240 mg/day). Treatments were administered orally to patients of either sex (aged 19 to 70 years) with acute infection and inflammation of the urogenital tract, and were given concomitantly with antimicrobial therapy for approximately 9 days. In both studies, a clinically significant improvement in symptoms, leading to complete remission, was achieved in most patients treated with nimesulide. Furthermore, treatment with nimesulide resulted in a more rapid improvement in symptoms and complete remission in a greater number of patients than did treatment with bromeline. Both nimesulide and bromeline were well tolerated.

Current drug use as risk factor for erectile dysfunction: results from an Italian epidemiological study.

Several drugs have been associated with an increased risk of erectile dysfunction (ED). We analysed the role of pharmacological treatments on the risk of ED using data from a cross-sectional study on prevalence and risk factors for ED in the general population in Italy. A total of 2450 men aged more than 18 years were randomly identified by 143 general practioners (GP) among their registered patients and invited to a confidential interview by their GP. 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. Out of the 2450 men identified, 440 (18%) refused to participate. The present analysis therefore includes information on 2010 men. After adjustment for related pathologies, anxiolytics and antidepressants showed insignificantly higher odds ratio (ORs, respectively, 1.7 and 2.1); antipsychotic drug use significantly increased the risk of ED (OR 9.0, 95% confidence interval, CI 1.8-44.4). Diuretics (OR 3.1, 95% CI 1.4-6.9) and anticholinergic drugs (OR 12.8, 95% CI 2.7-60.1) were associated with ED risk. No association emerged between ED and H2 antagonists, anticholesterolemic or hypoglycemic drugs. In conclusion, after taking account of related pathologies, our results suggest that men treated with antipsychotic, diuretic and anticholinergic drugs are at greater risk of ED.

A standardized procedure for using human corpus cavernosum strips to evaluate drug activity.

The main problem of using human corpus cavernosum (HCC) tissue to perform bioassay is linked to its limited availability further complicated by the heterogeneous source of the tissues used. Here, we show that gender reassignment is a reliable source of human tissue without major ethical problems. Indeed, the entire corpus cavernosum is obtained from the surgery procedure, which allows creating a standardized procedure to prepare HCC strip. In addition, human tissue, if kept in the fridge in the condition described, does not loose its ability to contract to phenylephrine (PE; alpha agonist), angiotensin II (AG II) and KCl up to 4 days. Furthermore, once contracted with PE, HCC relaxes to acetylcholine (endothelium-dependent mechanism); sodium nitroprusside (endothelium-independent mechanism); cromakalim (CRK), a K(ATP) channel opener; or alprostadil, a synthetic PGE2 (ALPR). In conclusion, we have standardized a procedure that allows the use of HCC strips to evaluate drug activity and/or to study pathophysiological mechanisms with an intact functional human tissue up to 4 days from the surgery procedure.

Ciprofloxacin in the treatment of urinary tract infections.

Twenty patients (15 males; five females) aged 11-70 years, with urinary tract infections were treated with one 250 mg tablet of ciprofloxacin every 12 h for 5-10 days. Clinical response to this treatment was the complete disappearance of symptoms in 85% of cases and the elimination of the micro-organism responsible for infection. In only three patients, who all had urinary calculus in addition to an infection, clinical failure of the therapy occurred and the causative micro-organism persisted. Tolerance to the therapy was excellent in this study, no adverse reactions connected with the treatment being reported.

[Laparoscopic surgery in varicocele: description of the technique and preliminary data]. / Intervento di varicocele per via laparoscopica: descrizione della tecnica e dati preliminari.

UNLABELLED: The aim of this work is to remark the scientific worth of the laparoscopic approach in patients with varicocele. PATIENTS AND METHODS: From March 1993 to December of the same year 15 patients suffering from varicocele have been treated with a laparoscopic procedure. The technique is widely described in the next pages. RESULTS: Twelve patients have completed the 3 months follow-up whereas five among them have reached the 6 months control. The results are really interesting specially under a functional point of view. DISCUSSION: The noninvasive advantages provided by laparoscopy are always important, but is the worth of the results we have obtained under a functional point of view and the success in inducing pregnancy in some patients that lead us to remark the utility of this procedure comparing it, with the therapeutic proposals nowadays performed. They are: traditional surgery according to Ivanissevich or Palomo procedures percutaneous transvenous embolization under radiological guide varicocele vein ligation under local anesthesia. CONCLUSIONS: Laparoscopic varicocelectomy represents according to us and some other authors a proposal with a better response if compared to traditional surgery, specially under a functional aspect. Under a costs-benefits evaluation it may be considered more convenient than the radiological approach.

Can side-specific biopsy findings predict the side of nodal metastasis in clinically localized prostate cancer? Results from a multicenter prospective survey.

BACKGROUND: To evaluate the correlation between the side of positive biopsy (Bx) and the risk of lymph-node metastases (LNMs) on each side and to quantify the risk of contralateral LNMs in patients with unilateral positive biopsy. METHODS: We analyzed the outcomes of 1599 patients with complete data regarding the sides of positive Bx and LN (lymph-node). By dividing each prostate into two separate sides, we assessed the accuracy of the side-specific Bx details in determining the side of positive nodes; the area under the receiver-operating characteristic (ROC) (AUCs) was used. For patients with unilateral positive Bx, we assessed the risk of homolateral and contralateral LNMs according to the number of total Bx taken and the preoperative risk of LN invasion. RESULTS: Considering the 3198 prostate sides, there was a strict correlation between the side of positive Bx and the side of LNMs. The ratio of positive/total Bx was more informative than the number of positive core. The AUC for ipsilateral LNMs was significantly higher than that for contralateral LNMs (P = 0.039). In the 805 patients with unilateral positive Bx, the percentage of contralateral LNMs was >30% even considering a more meticulous biopsy scheme and increased in the patients at a higher clinical risk for LN invasion. CONCLUSION: PCa preferentially metastasizes to ipsilateral LNs but >30% of contralateral LNMs are present. A unilateral LN dissection that is limited to the tumor-bearing side of the gland should not be recommended because of the substantial risk of missing contralateral metastases.

Efficacy and safety of ciprofloxacin XR 1000 mg once daily versus ciprofloxacin 500 mg twice daily in the treatment of complicated urinary tract infections.

The aim of this trial was to compare the efficacy and safety of extended-release ciprofloxacin (CIPRO XR) versus the immediate-release formulation (CIPRO IR) in the treatment of complicated urinary tract infections (UTIs). 212 patients were randomized to CIPRO XR 1,000 mg tablet once daily or CIPROXIN IR 500 mg tablet twice daily. Treatment efficacy was evaluated by bacteriological outcome. Safety was measured by recording adverse events. The rate of bacteriological eradication was 83% in the CIPRO XR group and 75% in the CIPRO IR. the overall incidence of adverse events reported was higher in the CIPRO IR group. The authors conclude that CIPRO XR is a safe and effective treatment for complicated UTIs. Although the limited data available do not consent to support a statistically superior efficacy or safety compared to CIPRO IR, a trend in favor of CIPRO XR is clearly evident in all efficacy and safety variables. CIPRO XR is associated with reduced frequencies of drug-related adverse events compared to CIPRO IR.