Giorgio Ivan Russo

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.

Prognostic accuracy of Prostate Health Index and urinary Prostate Cancer Antigen 3 in predicting pathologic features after radical prostatectomy.

OBJECTIVE To compare the prognostic accuracy of Prostate Health Index (PHI) and Prostate Cancer Antigen 3 in predicting pathologic features in a cohort of patients who underwent radical prostatectomy (RP) for prostate cancer (PCa). METHODS AND MATERIALS We evaluated 156 patients with biopsy-proven, clinically localized PCa who underwent RP between January 2013 and December 2013 at 2 tertiary care institutions. Blood and urinary specimens were collected before initial prostate biopsy for [-2] pro-prostate-specific antigen (PSA), its derivates, and PCA3 measurements. Univariate and multivariate logistic regression analyses were carried out to determine the variables that were potentially predictive of tumor volume > 0.5 ml, pathologic Gleason sum ≥ 7, pathologically confirmed significant PCa, extracapsular extension, and seminal vesicles invasions. RESULTS On multivariate analyses and after bootstrapping with 1,000 resampled data, the inclusion of PHI significantly increased the accuracy of a baseline multivariate model, which included patient age, total PSA, free PSA, rate of positive cores, clinical stage, prostate volume, body mass index, and biopsy Gleason score (GS), in predicting the study outcomes. Particularly, to predict tumor volume > 0.5, the addition of PHI to the baseline model significantly increased predictive accuracy by 7.9% (area under the receiver operating characteristics curve [AUC] = 89.3 vs. 97.2, P>0.05), whereas PCA3 did not lead to a significant increase. Although both PHI and PCA3 significantly improved predictive accuracy to predict extracapsular extension compared with the baseline model, achieving independent predictor status (all Ps < 0.01), only PHI led to a significant improvement in the prediction of seminal vesicles invasions (AUC = 92.2, P < 0.05 with a gain of 3.6%). In the subset of patients with GS ≤ 6, PHI significantly improved predictive accuracy by 7.6% compared with the baseline model (AUC = 89.7 vs. 97.3) to predict pathologically confirmed significant PCa and by 5.9% compared with the baseline model (AUC = 83.1 vs. 89.0) to predict pathologic GS ≥ 7. For these outcomes, PCA3 did not add incremental predictive value. CONCLUSIONS In a cohort of patients who underwent RP, PHI is significantly better than PCA3 in the ability to predict the presence of both more aggressive and extended PCa.

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.

Meta-analysis of metabolic syndrome and prostate cancer

Background:Metabolic syndrome (MetS) and prostate cancer (PCa) are highly prevalent conditions worldwide. Current evidence suggests the emerging hypothesis that MetS could play a role in the development and progression of several neoplasms. The aims of this study are to evaluate the impact of MetS and MetS factors on PCa incidence, on the risk of high-grade PCa and to analyze the role of MetS and single MetS components on the development of aggressive PCa features.Methods:A systematic literature search and analysis on PubMed, EMBASE, Cochrane and Academic One File databases until September 2015 was performed by 2 independent reviewers to evaluate the associations between MetS and PCa incidence, and between MetS and high-grade PCa incidence (bioptical Gleason Score⩾8, Prognostic Group 4–5 according to the novel prostate cancer grading system). Also the association between MetS and individual MetS components with pathological Gleason Score⩾8, extra-capsular extension, seminal vesicle invasion, positive surgical margins and biochemical recurrence (defined as two consecutive PSA values ⩾0.2 ng ml−1 after radical prostatectomy) was evaluated.Results:24 studies were selected including a total of 132 589 participants of whom 17.35% had MetS. There was a slight association between MetS and PCa incidence (odds ratio (OR)=1.17 (1.00–1.36), P=0.04) and between high-grade PCa and MetS (OR= 1.89 (1.50–2.38), P<0.0001) but the studies were statistically heterogeneous. No association was found between MetS components and PCa risk except for hypertension. MetS was significantly associated with pathologic Gleason Score⩾8 (OR= 1.77 (1.34–2.34); P<0.01), extra-capsular extension (OR=1.13 (1.09–1.18); P<0.01), seminal vesicle invasion (OR=1.09 (1.07–1.12); P<0.01), positive surgical margins (OR=1.67 (1.47–1.91); P<0.01) and biochemical recurrence (OR=1.67 (1.04–2.69); P<0.01).Conclusions:The presence of MetS is associated with worse oncologic outcomes in men with PCa, in particular with more aggressive tumor features, and biochemical recurrence.

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.

Serenoa repens, lycopene and selenium versus tamsulosin for the treatment of LUTS/BPH. An Italian multicenter double-blinded randomized study between single or combination therapy (PROCOMB trial)

Phytotherapy has been used to treat patients with lower urinary tract symptoms (LUTS). We evaluated the efficacy and tolerability of combination therapy between Serenoa Repens (SeR), Lycopene (Ly), and Selenium (Se) + tamsulosin versus single therapies.

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.

Genotyping analysis and 18FDG uptake in breast cancer patients: a preliminary research

BackgroundDiagnostic imaging plays a relevant role in the care of patients with breast cancer (BC). Positron Emission Tomography (PET) with 18F-fluoro-2-deoxy-D-glucose (FDG) has been widely proven to be a clinical tool suitable for BC detection and staging in which the glucose analog supplies metabolic information about the tumor. A limited number of studies, sometimes controversial, describe possible associations between FDG uptake and single nucleotide polymorphisms (SNPs). For this reason this field has to be explored and clarified. We investigated the association of SNPs in GLUT1, HIF-1a, EPAS1, APEX1, VEGFA and MTHFR genes with the FDG uptake in BC.MethodsIn 26 caucasian individuals with primary BC, whole-body PET-CT scans were obtained and quantitative analysis was performed by calculating the maximum Standardized Uptake Value normalized to body-weight (SUVmax) and the mean SUV normalized to body-weight corrected for partial volume effect (SUVpvc). Human Gene Mutation Database and dbSNP Short Genetic Variations database were used to analyze gene regions containing the selected SNPs. Patient genotypes were obtained using Sanger DNA sequencing analysis performed by Capillary Electrophoresis.ResultsBC patients were genotyped for the following nine SNPs: GLUT1: rs841853 and rs710218; HIF-1a: rs11549465 and rs11549467; EPAS1: rs137853037 and rs137853036; APEX1: rs1130409; VEGFA: rs3025039 and MTHFR: rs1801133. In this work correlations between the nine potentially useful polymorphisms selected and previously suggested with tracer uptake (using both SUVmax and SUVpvc) were not found.ConclusionsThe possible functional influence of specific SNPs on FDG uptake needs further studies in human cancer. In summary, this is the first pilot study, to our knowledge, which investigates the association between a large panel of SNPs and FDG uptake specifically in BC patients. This work represents a multidisciplinary and translational medicine approach to study BC where, the possible correlation between SNPs and tracer uptake, may be considered to improve personalized cancer treatment and care.

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.