Tommaso Castelli

Polyphenols: Key Issues Involved in Chemoprevention of Prostate Cancer

Prostate cancer is is the most common solid neoplasm and it is now recognized as one of the most important medical problems facing the male population. Due to its long latency and its identifiable preneoplastic lesions, prostate cancer is an ideal target tumor for chemoprevention. Different compounds are available and certainly polyphenols represent those with efficacy against prostate cancer. This review take a look at activity and properties of major polyphenolic substances, such as epigallocatechin-3-gallate, curcumin, resveratrol and the flavonoids quercetin and genistein. Although the current studies are limited, mechanisms of action of polyphenols added with the lack of side effects show a a start for future strategies in prostate chemoprevention.

Relationship between lower urinary tract symptoms and serum levels of sex hormones in men with symptomatic benign prostatic hyperplasia

Study Type – Aetiology (case series)
Level of Evidence 4

Effects of Serenoa Repens, Selenium and Lycopene (Profluss®) on chronic inflammation associated with Benign Prostatic Hyperplasia: results of “FLOG” (Flogosis and Profluss in Prostatic and Genital Disease), a multicentre Italian study

OBJECTIVE To evaluate the efficacy of Profluss® on prostatic chronic inflammation (PCI). MATERIALS AND METHODS We prospectively enrolled 168 subjects affected by LUTS due to bladder outlet obstruction submitted to 12 cores prostatic biopsy for suspected prostate cancer + 2 cores collected for PCI valuation. First group consisted of 108 subjects, with histological diagnosis of PCI associated with BPH and high grade PIN and/or ASAP, randomly assigned to 1:1 ratio to daily Profluss® (group I) for 6 months or to control group (group Ic). Second group consisted of 60 subjects, with histological diagnosis of BPH, randomly assigned to 1:1 ratio to daily Profluss® + a-blockers treatment (group II) for 3 months or to control group (group IIc). After 6 months first group underwent 24 cores prostatic re-biopsy + 2 cores for PCI while after 3 months second group underwent two-cores prostatic for PCI. Specimens were evaluated for changes in inflammation parameters and for density of T-cells (CD3, CD8), B-cells (CD20) and macrophages (CD68). RESULTS At follow-up there were statistical significant reductions of extension and grading of flogosis, mean values of CD20, CD3, CD68 and mean PSA value in group I compared to Ic, while extension and grading of flogosis in group II were inferior to IIc but not statistical significant. A statistically significant reduction in the density of CD20, CD3, CD68, CD8 was demonstrated in group II in respect to control IIc. CONCLUSIONS Serenoa repens+Selenium+Lycopene may have an anti-inflammatory activity that could be of interest in the treatment of PCI in BPH and/or PIN/ASAP patients.

Insulin Resistance Is an Independent Predictor of Severe Lower Urinary Tract Symptoms and of Erectile Dysfunction: Results from a Cross-Sectional Study

INTRODUCTION Several studies have linked the association between lower urinary tract symptoms (LUTS), erectile dysfunction (ED), and the presence of insulin resistance (IR) due to an underlined metabolic syndrome (MetS). AIM This study aims to determine the relationship between IR, sexual function, and LUTS and to demonstrate the ability of IR in predicting ED and severe LUTS. METHODS Between January 2008 to January 2013, 544 consecutive patients with benign prostatic hyperplasia-related LUTS were enrolled. LUTS and sexual function of the patients were evaluated by the International Index of Erectile Function (IIEF) and the International Prostate Symptom Score (IPSS). MetS was defined by the International Diabetes Federation. IR was defined as a homeostasis model assessment (HOMA) index of 3 or greater. MAIN OUTCOME MEASURES Uni- and multivariate logistic regression analysis was performed to assess significant predictors of severe LUTS (IPSS ≥ 20) and ED (IIEF-Erectile Function [IIEF-EF] <26), including MetS component, prostate volume, prostate-specific antigen, total testosterone, and HOMA index. RESULTS IR patients resulted in higher values of IPSS (19.0 vs. 15.0; P<0.01), IPSS-storage (6.0 vs. 5.0; P<0.01), IPSS-voiding (12.0 vs. 9.0; P<0.01), total prostate volume (54.8 vs. 36.5; P<0.01), and lower values of IIEF-EF (17.0 vs. 20.0; P<0.01), IIEF-Intercourse Satisfaction (3.0 vs. 10.0; P<0.01), IIEF-Orgasmic Function (8.0 vs. 9.0; P<0.01), IIEF-Overall Satisfaction (6.0 vs. 8.0; P<0.01), and total testosterone (3.83 vs. 4.44; P<0.01). IR was demonstrated to be a strong predictor of ED (IIEF-EF <26) (odds ratio [OR] =6.20, P<0.01) after adjusting for confounding factors. Finally, IR was also an independent predictor of severe LUTS (IPSS ≥ 20) (OR=2.0, P<0.01) after adjusting for confounding factors. CONCLUSIONS IR patients are at high risk of having severe LUTS and contemporary sexual dysfunctions. We strongly suggest to prevent LUTS and ED by reducing insulin resistance.

Increase of Framingham cardiovascular disease risk score is associated with severity of lower urinary tract symptoms

To determine the relationship between lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) and 10‐year risk of cardiovascular disease (CVD) assessed by the Framingham CVD risk score in a cohort of patients without previous episodes of stroke and/or acute myocardial infarction.

Emerging links between non-neurogenic lower urinary tract symptoms secondary to benign prostatic obstruction, metabolic syndrome and its components: A systematic review.

We carried out a systematic review in order to determine the connection between lower urinary tract symptoms secondary to bladder outlet obstruction and metabolic syndrome with its components. We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, the Cochrane Database of Systematic Review and Web of Science from their inception until January 2015 to identify all eligible studies on the effect of metabolic syndrome (or component factors) on the presence or severity of lower urinary tract symptoms/bladder outlet obstruction in men. This analysis was carried out according to the STrengthening the Reporting of OBservational studies in Epidemiology guidelines. In total, 19 studies were identified as eligible for this systematic review. The quality assessment score was ≥50% in more than half of the studies (11/19). The evidence synthesis showed a positive association between metabolic syndrome, number of components and lower urinary tract symptoms/bladder outlet obstruction. In particular, the major endocrine aberrations of this connection are central obesity and hypertriglyceridemia. The links between insulin resistance and lower urinary tract symptoms/bladder outlet obstruction should be better investigated. Ethnic disparities in all examined studies showed a different impact of metabolic syndrome on lower urinary tract symptoms/bladder outlet obstruction severity and such influence still remain unclear. The relationship between metabolic syndrome and lower urinary tract symptoms/bladder outlet obstruction open the way for introducing physical activity and diet as recognized first‐line interventions for treating lower urinary tract symptoms. However, this connection should be investigated in two different ethnic cohorts (i.e. Asian vs Caucasian) in order to better understand the impact of ethnic disparities on metabolic syndrome and lower urinary tract symptoms/bladder outlet obstruction severity.

Impact of combination therapy 5-alpha reductase inhibitors (5-ARI) plus alpha-blockers (AB) on erectile dysfunction and decrease of libido in patients with LUTS/BPH: a systematic review with meta-analysis

Abstract Lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO) represent one of the most common clinical complaints in adult men. Several drugs used for LUTS/BPO may strongly affect sexual function and bother. The aim of this systematic review and meta-analysis was to evaluate the impact of combination therapy with alpha-blockers (AB), 5-alpha reductase inhibitors (5-ARI) on the risk of erectile dysfunction(ED) and libido alterations (LA) from randomized clinical trial (RCT). Based on the inclusion and exclusion criteria, five RCTs involving 6131 patients were included in the analysis. According to the analysis, the overall prevalence of ED and LA were significantly greater in the combination treatment group than in the AB group (7.93% versus 4.66%; OR 1.81; p < 0.0001 and 3.69% versus 2.36%; OR 1.58; p = 0.003, respectively). The combination therapy increased the risk of ED compared to monotherapy with 5-ARI (7.93% versus 6.47%; OR 1.25; p = 0.04) but not the risk of LA (3.51% versus 3.37; OR 1.03; p = 0.84). In our systematic meta-analysis, we demonstrated that combination therapy with ABs and 5-ARIs was associated with significantly higher risk of ED and LA compared with single monotherapy. Combination therapy showed similar risk of LA compared with 5-ARI monotherapy.

Connections between lower urinary tract symptoms related to benign prostatic enlargement and metabolic syndrome with its components: a systematic review and meta-analysis

Abstract A significant amount of epidemiological evidences have underlined an emerging link between metabolic syndrome (MetS) and lower urinary tract symptoms (LUTS) secondary to benign prostatic enlargement a (BPE). We aimed to assess the connections between LUTS and MetS with its components. Meta-analysis were conducted to determine the mean differences (MD) and confidence intervals of IPSS total score, IPSS-voiding, IPSS-storage and prostate volume (PV) in patients with or without MetS. Ln(odds-ratio) were calculated to estimate the risk of having moderate-to-severe LUTS (IPSS ≥ 8). Nineteen studies were identified as eligible for this systematic review, with a total of 18,476 participants, including 5554 (30.06%) with and 12 922 (69.94%) without MetS. Pooled analysis did not demonstrate significant MD of IPSS, IPSS-voiding and IPSS-storage in men with or without MetS but PV was significantly different (MD = 2.18; p = 0.03). Presence of MetS was not significantly associated with moderate-to-severe LUTS (odds ratio = 1.13; p = 0.53) and only altered serum triglycerides and diabetes were associated with this risk. The association between MetS and LUTS/BPE remain unclear and further observational studies in a population with metabolic disorders should be conducted in order to address its potential role in determining LUTS/BPE.

Percentage of cancer involvement in positive cores can predict unfavorable disease in men with low-risk prostate cancer but eligible for the prostate cancer international: active surveillance criteria

OBJECTIVES To identify predictive factors of unfavorable disease and of biochemical failure in patients treated with radical prostatectomy but eligible for active surveillance (AS) according to Prostate Cancer Research International: Active Surveillance (PRIAS) criteria. We aimed to introduce and validate the percentage of cancer involvement in positive cores (CIPC) as potential worse predictive factor. METHODS From January 2002 to December 2007, 750 consecutive subjects underwent radical prostatectomy at a single institution. We identified 147 (19.05%) patients who were eligible for AS based on PRIAS criteria: clinical stage T1c or T2 disease, prostate-specific antigen level of ≤ 10 ng/ml, Gleason score ≤ 6, prostate-specific antigen-D of<0.2 ng/ml(2), and fewer than 3 positive biopsy cores. CIPC was included in the analysis. RESULTS Of the 147 patients, 95 (66.43%) patients had favorable disease, whereas 48 (33.57%) had unfavorable disease. In multivariate logistic regression, maximum cancer length (odds ratio 12.52, P<0.01) and CIPC (odds ratio 1.70, P<0.01) represented independent predictors of unfavorable prostate cancer. The area under the receiver operating characteristics curve analysis revealed significantly higher performance after including CIPC to the PRIAS criteria (0.61 vs. 0.94, P<0.01). A cutoff of 0.4mm of CIPC was set to predict unfavorable disease with 93% specificity, 76% sensibility, and 87% accuracy based on the receiver operating characteristics curve analysis. Finally, the 3- and 5-years biochemical recurrence (BCR)-free survival were significantly lower in subjects with CIPC ≥ 0.4mm, 88.4 % and 81.0% vs. 97.8% and 95.7%, respectively (P< 0.01). CONCLUSIONS Our findings suggest that the inclusion of CIPC to the prostate biopsy features could be helpful to avoid misclassification in patients eligible for AS according to the PRIAS criteria.

Combination of intralesional verapamil and oral antioxidants for Peyronie's disease: a prospective, randomised controlled study.

The aim of this study was to evaluate the efficacy of the association of intralesional verapamil (ILV) injection with oral antioxidants compared with ILV monotherapy in patients with early onset of Peyronies disease (PD) at 12‐week follow‐up. Group A (n = 52) received ILV 10 mg weekly for 12 weeks, while group B (n = 53) received ILV 10 mg weekly for 12 weeks + antioxidants orally one tablet once a day for 3 months. The main efficacy outcomes were the change in plaque size (PS), penile curvature (PC), visual analogue score (VAS), IIEF‐15 and IIEF‐15 subdomains. Both groups showed significant improvement from baseline to week 12 relative to PS and PC, while group B also in IIEF‐15 score (mean difference: 5.51, P < 0.01) and VAS (mean difference: −2.71, P < 0.01). No significant differences were observed between both groups in PS and PC. Finally, both groups showed significant increase in orgasmic function (IIEF‐OF) and overall satisfaction (IIEF‐OS), while group B showed significant improvement also in intercourse satisfaction (IIEF‐IS). Significant differences were found relative to IIEF‐OF, IIEF‐IS, IIEF‐OS and VAS scores in the group B compared with group A. Patients affected by PD may benefit from combination treatment with ILV and oral antioxidants thanks to the improvement in IIEF‐OF, IIEF‐IS and IIEF‐OS at 12 weeks.