Giovanni La Croce

The fatty acid amide hydrolase inhibitor oleoyl ethyl amide counteracts bladder overactivity in female rats

To study micturition and bladder overactivity in female rats after chronic treatment with the fatty acid amide hydrolase (FAAH) inhibitor oleoyl ethyl amide (OEtA).

Preoperative Favorable Characteristics in Bladder Cancer Patients Cannot Substitute the Necessity of Extended Lymphadenectomy During Radical Cystectomy: A Sensitivity Curve Analysis

OBJECTIVE To investigate the staging of lymphadenectomy during radical cystectomy (RC) due to bladder cancer. No data exist about the possibility to limit the extension of pelvic lymph node dissection (PLND) on the basis of preoperative or intraoperative parameters without losing accuracy in the staging procedure. MATERIALS AND METHODS Between 1995 and 2012, 1016 RC due to bladder cancer were performed at a single tertiary care institution. The relationship between the number of nodes removed and the probability to find node metastases at final pathology examination was assessed using receiver operating characteristic analyses. RESULTS Among the patients who underwent RC plus PLND, the lymph node metastases prevalence was 35.7% (363 of 1016). Receiver operating characteristic curve analyses were used to explore graphically the relationship between the numbers of removed and examined nodes and the probability of finding one or more metastatic nodes in the overall population. The curve indicated that 25, 35, and 45 nodes need to be removed to achieve 75%, 90%, and 95% probability, respectively, of detecting one or more lymph node metastases. When the analyses were stratified according to preoperative characteristics, only slight differences were recorded among the sensitivity analyses stratified for pathological stage, primary or progressive status, or radiological N status. CONCLUSION Our results show that it is necessary to extend PLND to improve the ability to stage node metastases accurately. Preoperative parameters can minimally change this indication and an extended PLND should be always performed.

Follow-up After Treatment for Renal Cell Carcinoma: The Evidence Beyond the Guidelines

CONTEXT Postoperative follow-up is considered the standard of care for nonmetastatic renal cell carcinoma (RCC). However, level 1 evidence regarding a proper follow-up protocol for RCC is still lacking, making clinical practice extremely heterogeneous. OBJECTIVE To evaluate systematically and summarise the evidence supporting the current clinical guidelines on follow-up after RCC treatment. EVIDENCE ACQUISITION A search of Medline, PubMed and Scopus was performed to identify articles published in the last 5 yr addressing the role of follow-up in the RCC setting. Relevant studies were then screened, and the data were extracted, analysed, and summarised. The Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria were applied. EVIDENCE SYNTHESIS Although several series regarding oncologic outcomes and protocols of surveillance after nephrectomy for localised RCC have been published in the literature, the individual preferences of the treating urologist make the daily clinical scenario extremely heterogeneous regarding follow-up indications and modality. Clinical guidelines support a stage-specific stratification of patient prognosis based on pathologic staging or prognostic models. In the context of a prospectively durable follow-up protocol exposing patients to several imaging tests, concerns about radiation exposure must be taken into account. A better understanding of tumour biology, which would lead to a correct individualisation of patient prognosis through the use of validated prognostic tools, would allow for a more tailored follow-up treatment. CONCLUSIONS A consensus regarding the pattern and modalities of surveillance after treatment for RCC is still lacking. A standardised evidence-based surveillance protocol that would allow for the early detection of recurrences and limit unnecessary radiation exposure and unwarranted costs is mandatory. PATIENT SUMMARY A surveillance protocol after treatment for a renal tumour is essential for the early detection and treatment of eventual metastases. A general consensus regarding timing and modalities for follow-up protocol still does not exist, but published evidence commonly sustains some general principles.

Latest pharmacotherapy options for benign prostatic hyperplasia

Introduction: Benign prostatic hyperplasia (BPH) is a very common condition in men over 50 years, often resulting in lower urinary tract symptoms (LUTS). Medical therapy aims at improving quality of life and preventing complications. The range of drugs available to treat LUTS is rapidly expanding. Areas covered: Silodosin is a relatively new α1-adrenoreceptor antagonist that is selective for α1A-adrenergic receptor. While causing smooth muscle relaxation in the lower urinary tract, it minimizes blood pressure-related adverse effects. Tadalafil, a PDEs type 5 inhibitor, is a drug recently approved for the treatment of BPH/LUTS that challenges the standard therapy with α1-blockers, especially in men with concomitant erectile dysfunction (ED). Mirabegron is the first β3-adrenoceptor agonist approved for the treatment of symptoms of overactive bladder. BPH-related detrusor overactivity (DO) may be successfully targeted by mirabegron. Gonadotropin-releasing hormone antagonists, intraprostatic injections with NX-1207 and vitamin D3 receptor analogues exerted beneficial effects on LUTS but need further evaluation in clinical studies. Expert opinion: Choosing the right treatment should be guided by patients’ symptoms, comorbidities and potential side effects of available drugs. Silodosin is a valid option for elderly and for people taking antihypertensive drugs. BPH patients affected by ED can target both conditions with continuous tadalafil therapy. The encouraging data on mirabegron use in BPH-DO have to be further assessed in larger prospective randomized clinical trials.

Silodosin and tadalafil have synergistic inhibitory effects on nerve-mediated contractions of human and rat isolated prostates.

Lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) are associated with erectile dysfunction. Alpha-1-adrenoceptor antagonists are effective drugs for treating symptomatic BPH. Clinical data show improvements in LUTS by phosphodiesterase 5 inhibitors. This study aimed to evaluate effects of silodosin, a highly selective α1A-adrenoceptor antagonist, alone or in combination with the phosphodiesterase 5 inhibitor tadalafil on contractions of isolated human and rat prostates. In organbath studies, effects of increasing concentrations of silodosin (1 nM-1 µM) and tadalafil (100 nM-100 µM) on contractions by electrical field stimulation or phenylephrine of human and rat prostate strip preparations were investigated. The combination silodosin and tadalafil reduced electrically-induced contractions of human prostate preparations better than single drugs alone. At any frequencies (1-32 Hz), inhibitory effects of combined therapy (P-values vs single drug) in human tissue were 26-42% (1 nM silodosin+100 nM tadalafil; P<0.05), 40-58% (10 nM silodosin+1 µM tadalafil; P<0.001-0.05), 56-67% (100 nM silodosin+10 µM tadalafil; P<0.01-0.05), and 33-55% (1 µM silodosin+100 µM tadalafil P<0.01-0.05). Similar findings were obtained in rat prostate preparations. In human and rat prostate tissue, the drug combination exerted similar inhibitory effect on phenylephrine contractions as silodosin alone. Silodosin plus tadalafil had greater potency than each drug alone to inhibit prostate contractions to electrical field stimulation but not to phenylephrine. This study supports the clinical application of a combination of an α1A-adrenoceptor antagonist and a phosphodiesterase 5 inhibitor for symptomatic BPH and suggests that the drug combination requires endogenous nerve-activity for optimal effect.

Peyronie's Disease and Autoimmunity—A Real-Life Clinical Study and Comprehensive Review

INTRODUCTION Although heavily investigated over the last decades, Peyronies disease (PD) pathogenesis remains unclear. AIM We sought to investigate the association between PD and autoimmune diseases (ADs) in men seeking medical help for sexual dysfunction in the real-life setting. METHODS Complete sociodemographic and clinical data from a homogenous cohort of 1,140 consecutive Caucasian-European men were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index and ADs were stratified according to International Classification of Diseases, Ninth Revision classification. MAIN OUTCOME MEASURES Descriptive statistics and multivariate logistic regression models tested the association between ADs and PD. RESULTS PD was diagnosed in 148 (13%) of the 1,140 men; of PD patients, 14 (9.5%) had a comorbid AD; conversely, the rate of ADs in non-PD patients was significantly lower (χ(2) = 24.7; P < 0.01). Both patient age and AD comorbidity achieved multivariable independent predictor status for PD (odds ratio [OR]: 1.05; P < 0.01 and OR: 4.90; P < 0.01, respectively). CONCLUSIONS Our observational findings showed that ADs are highly comorbid with PD in a large cohort of same-race individuals seeking medical help for sexual dysfunction in the real-life setting.

Serenoa repens, selenium and lycopene to manage lower urinary tract symptoms suggestive for benign prostatic hyperplasia

ABSTRACT Introduction: Benign prostatic hyperplasia (BPH) is a disease affecting most of the elderly male. α1-blockers and 5-alpha reductase inhibitors are currently used to target lower urinary tract symptoms (LUTS). Moreover phytotherapeutic agents, including Serenoa Repens (SeR), have shown to have a role in ameliorating BPH/LUTS alone or in combination of other elements like Selenium (Se) and Lycopene (Ly). Areas covered: A literature review was performed using data from articles assessing the role of of SeR+Se+Ly in the management of LUTS secondary to BPH. Diverging evidence on SeR’s efficacy is available. On one hand several studies have shown SeR efficacy in treating BPH/LUTS. SeR is effective in reducing prostate size, urinary frequency, dysuria, nocturia and in improving maximum urine flow-rate. On the other hand two long-term trials reported that SeR did not improve prostate size or urinary flow. SeR+Se+Ly in combination with tamsulosin is more effective than single therapies in improving IPSS and increasing maximal urinary flow-rate in patients affected by LUTS/BPH. Expert opinion: Despite great amount of preclinical and clinical studies, the use of SeR in BPH/LUTS is not sustained by clear evidence for a therapeutic efficacy but current data hint higher efficacy of of SeR+Se+Ly compared to SeR alone.

Metabolic syndrome in White-European men presenting for secondary couple's infertility: An investigation of the clinical and reproductive burden

We aimed to determine the impact of metabolic syndrome (MetS) on reproductive function in men with secondary infertility, a condition that has received relatively little attention from researchers. Complete demographic, clinical, and laboratory data from 167 consecutive secondary infertile men were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI; categorised 0 vs 1 vs 2 or higher). NCEP-ATP III criteria were used to define MetS. Semen analysis values were assessed based on the 2010 World Health Organization (WHO) reference criteria. Descriptive statistics and logistic regression models tested the association between semen parameters and clinical characteristics and MetS. MetS was found in 20 (12%) of 167 men. Patients with MetS were older (P < 0.001) and had a greater BMI (P < 0.001) compared with those without MetS. MetS patients had lower levels of total testosterone (P = 0.001), sex hormone-binding globulin, inhibin B, and anti-Mόllerian hormone (all P ≤ 0.03), and they were hypogonadal at a higher prevalence (P = 0.01) than patients without MetS. Moreover, MetS patients presented lower values of semen volume, sperm concentration, and sperm normal morphology (all P ≤ 0.03). At multivariate logistic regression analysis, no parameters predicted sperm concentration, normal sperm morphology, and total progressive motility. Our data show that almost 1 of 8 White-European men presenting for secondary couple′s infertility is diagnosed with MetS. MetS was found to be associated with a higher prevalence of hypogonadism, decreased semen volume, decreased sperm concentration, and normal morphology in a specific cohort of White-European men.

Spinal neuronal cannabinoid receptors mediate urodynamic effects of systemic fatty acid amide hydrolase (FAAH) inhibition in rats

To test if urodynamic effects from systemic Fatty Acid Amide Hydrolase (FAAH) inhibition involve sacral spinal cannabinoid type 1 (CB1) or type 2 (CB2) receptors.

The presence of carcinoma in situ at radical cystectomy increases the risk of urothelial recurrence: Implications for follow-up schemes

INTRODUCTION To evaluate the incidence of carcinoma in situ (CIS) in patients treated with radical cystectomy (RC) due to bladder cancer and to assess its effect on recurrence and survival rates. METHODS The study focused on 1,128 consecutive nonmetastatic patients with bladder cancer treated with RC at a single tertiary care referral center from 1994 to 2014. The Kaplan-Meier method was used to compare recurrence, cancer-specific mortality (CSM), and overall mortality-free rates in the overall population and in pT0-pT2 and pT3-pT4 patients after stratifying according to the presence of CIS. Multivariable (MVA) Cox regression analyses tested the effect of the presence of CIS on survival outcomes. MVA competing risk analyses were performed to assess the effect of CIS on urothelial recurrence. RESULTS The presence of CIS was reported in 277 (24.6%) patients. During a median follow-up of 6 years, 355 recurrences, 377 CSM, and 468 overall mortality were reported. At MVA Cox regression analyses, the presence of concomitant CIS was not associated with any survival effect when the overall population was considered (all P≥0.3). At MVA Cox regression analyses, there was no effect of CIS on survival outcomes in pT3-pT4 patients (all P>0.2); on the contrary, the presence of CIS was associated with worse CSM in pT0-pT2 patients only (hazard ratio [HR] = 1.82; CI: 1.01-3.29; P = 0.04). At MVA competing risk analyses predicting urothelial recurrence only, the presence of CIS was associated to an increased risk of urothelial recurrence in pT0-pT2 patients (HR = 2.99; CI: 1.05-8.53; P = 0.04), pT3-pT4 patients (HR = 10.29; CI: 1.40-75.75; P = 0.02), and in the overall population (HR = 4.47; CI: 1.81-11.07; P = 0.001). CONCLUSION An increased risk of developing urothelial recurrence only was recorded in patients diagnosed with CIS at RC. Physicians should consider this aspect ensuring a more severe follow-up schemes in patients who harbored this pathological feature.