The use of laser as a therapeutic modality as compared to TURP for the small prostate ≤40 mL: a collaborative review.

INTRODUCTION: In the last decade therapeutic options for patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic enlargement (BPE) have constantly increased. Although transurethral resection of the prostate (TURP) is still considered the surgical gold standard, different lasers and advanced techniques have been introduced as alternatives to TURP. EVIDENCE ACQUISITION: A non-systematic Medline/Pubmed literature search was performed with different combination of terms including: "BPH," "M-TURP," "B-TURP" "bladder outlet obstruction," "YAG laser," "Diode laser," "Potassium titanyl phosphate," "KTP," "bladder outlet obstruction" (BOO), "BOO in small prostate". Only studies reporting prostate volume ≤40 cc were considered for this review. EVIDENCE SYNTESIS: Current evidence on the use of laser as a therapeutic modality as compared to TURP reported similar functional results of bipolar-TURP, Thulium laser and Greenlight. For prostate gland ≤40 cc, HoLEP can be technically more difficult while Holmium-TUIP seems to be a valid option but with a higher rate of retrograde ejaculation which is considerably higher than the rate in electrocautery series. The diode laser showed excellent intra-operatively haemostasis with clear endoscopic vision and durable improvements in functional results, but may produce greater passive thermal energy conduction that can cause scrotal edema and anal pain. However, conclusions need to be drawn after median to long term evaluation of patients and consideration of the economic implications, coupled with the potential for reducing morbidity. CONCLUSIONS: Evidence acquisition from the literature showed that mini-invasive surgeries, including Greenlight laser and Holmium laser incision represent valid alternatives to TURP in prostate ≤40 g. We reported effective results of laser therapy as therapeutic modalities as compared to TURP for the small prostate ≤40 mL, both for enucleation and excision or cauterization, however cost effective of laser in the current literature are still scarce and it should be implemented.

Multidisciplinary approach to prostatitis.

The modern clinical research on prostatitis started with the work of Stamey and coworkers who developed the basic principles we are still using. They established the segmented culture technique for localizing the infections in the males to the urethra, the bladder, or the prostate and to differentiate the main categories of prostatitis. Such categories with slight modifications are still used according to the NIH classification: acute bacterial prostatitis, chronic bacterial prostatitis, Chronic Pelvic Pain Syndrome (CPPS) and asymptomatic prostatitis. Prostatic inflammation is considered an important factor in influencing both prostatic growth and progression of symptoms of benign prostatic hyperplasia and prostatitis. Chronic inflammation/neuroinflammation is a result of a deregulated acute phase response of the innate immune system affecting surrounding neural tissue at molecular, structural and functional levels. Clinical observations suggest that chronic inflammation correlates with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH) and an history of clinical chronic prostatitis significantly increases the odds for prostate cancer. The NIHNIDDK classification based on the use of the microbiological 4- glasses localization test or simplified 2-glasses test, is currently accepted worldwide. The UPOINT system identifies groups of clinicians with homogeneous clinical presentation and is used to recognize phenotypes to be submitted to specific treatments. The UPOINTS algorithm implemented the original UPOINT adding to the urinary domains (U), psycho-social (P), organspecific (O), infection (I), neurological (N), muscle tension and tenderness (T) a further domain related to sexuality (S). In fact sexual dysfunction (erectile, ejaculatory, libido loss) has been described in 46-92% of cases with a high impact on the quality of life of patients with CP/CPPS. Prostatic ultrasound represents the most popular imaging test in the work-up of either acute and chronic prostatitis although no specific hypo-hyperechoic pattern has been clearly associated with chronic bacterial prostatitis and CPPS. Use of a digital-processing software to calculate the extension of prostatic calcification area at ultrasound demonstrated a higher percentage of prostatic calcification in patients with chronic bacterial prostatitis. Multiparametric Magnetic Resonance Imaging (mpMRI) is the current state-of-the art imaging modality in the assessment of patients with prostate cancer although a variety of benign conditions, including inflammation, may mimic prostate cancer and act as confounding factors in the discrimination between neoplastic and non-neoplastic lesions. Bacteria can infect prostate gland by: ascending the urethra, reflux of urine into the prostatic ducts, direct inoculation of bacteria through inserted biopsy needles or hematogenous seeding. Enterobacteriaceae are the predominant pathogens in acute and chronic bacterial prostatitis, but an increasing role of Enterococci has been reported. Many strains of these uropathogens exhibit the ability to form biofilm and multidrug- resistance. Sexually Transmitted Infections (STI) agents, in particular Chlamydia trachomatis and Mycoplasma genitalium, have been also considered as causative pathogens of chronic bacterial prostatitis. On the contrary the effective role in genital diseases of other "genital mycoplasmas" is still a much debated issue. Sexually Transmitted Infections agents should be investigated by molecular methods in both patient and sexual partner. "Next generation" investigations, such as cytokine analysis, cytological typing of immune cells could help stratifying the immune response. Epigenetic dysregulation of inflammatory factors should be investigated according to systemic and compartment-specific signals. The search for biomarkers should also include evaluation of hormonal pathways, as measurement of estrogen levels in semen. Antimicrobials are the first line agents for the treatment of bacterial prostatitis. The success of antimicrobial treatment depends on the antibacterial activity and the pharmacokinetic characteristics of the drug which must reach high concentrations in prostate secretion and prostate tissue. Acute bacterial prostatitis can be a serious infection with a potential risk for urosepsis For iInitial treatment of severely ill patients, intravenous administration of high doses of bactericidal antimicrobials, such as broad-spectrum penicillins, third-generation cephalosporins or fluoroquinolones, is recommended in combination with an aminoglycoside. Use of piperacillin-tazobactam and meropenem is justified in presence of multiresistant gramnegative pathogens. The antibiotic treatment of chronic prostatitis is currently based on the use of fluoroquinolones that, given for 2 to 4 weeks, cured about 70% of men with chronic bacterial prostatitis. For the treatment of Chlamydial prostatitis macrolides were shown to be more effective than fluoroquinolones, whereas no differences were observed in microbiological and clinical efficacy between macrolides and tetracyclines for the treatment of infections caused by intracellular pathogens. Aminoglycosides and fosfomycin could be considered as a therapeutic alternative for the treatment of quinolone resistant prostatitis. Use of alpha-blockers in CP/CPPS patients with urinary symptoms and analgesics +/- non steroidal anti-inflammatory drugs (NSAID), in presence of pain demonstrated a reduction of symptoms reduction and an improvement of quality of life, although long term use of NSAID is limited by side effect profile. However, the multimodal therapeutic regimen by contemporary use of alphablockers, antibiotics and anti-inflammatory showed a better control of prostatitis symptoms than single drug treatment. Novel therapeutic substances for the treatment of pain, such as the cannabinoid anandamide would be highly interesting to test. An alternative for the treatment of chronic prostatitis/chronic pelvic pain syndrome is phytotherapy, as primary therapy or in association with other drugs. Quercetin, pollen extract, extract of Serenoa repens and other mixtures of herbal extracts showed a positive effect on symptoms and quality of life without side effects. The association of CP/CPPS with alterations of intestinal function has been described. Diet has its effects on inflammation by regulation of the composition of intestinal flora and direct action on the intestinal cells (sterile inflammation). Intestinal bacteria (microbiota) interacts with food influencing the metabolic, immune and inflammatory response of the organism. The intestinal microbiota has protective function against pathogenic bacteria, metabolic function by synthesis of vitamins, decomposition of bile acids and production of trophic factors (butyrate), and modulation of the intestinal immune system. The alteration of the microbiota is called "dysbiosis" causing invasive intestinal diseases pathologies (leaky gut syndrome and food intolerances, irritable bowel syndrome or chronic inflammatory bowel diseases) and correlating with numerous systemic diseases including acute and chronic prostatitis. Administration of live probiotics bacteria can be used to regulate the balance if intestinal flora. Sessions of hydrocolontherapy can represent an integration to this therapeutic approach. Finally, microbiological examination of sexual partners can offer supplementary information for treatment.

Association between dietary flavonoids intake and prostate cancer risk: A case-control study in Sicily.

OBJECTIVES: The aim of this study is to test the association between dietary flavonoids intake and prostate cancer (PCa) in a sample of southern Italian individuals. DESIGN: A population-based case-control study on the association between PCa and dietary factors was conducted from January 2015 to December 2016, in a single institution. SETTING: Patients with elevated PSA (Prostate Specific Antigen) and/or suspicion of PCa underwent transperineal prostate biopsy (≥12 cores). A total of 118 histopathological-verified PCa cases were collected and matched with controls, which were selected from a sample of 2044 individuals randomly recruited among the same reference population. Finally, a total of 222 controls were selected. MAIN OUTCOME MEASURES: Prevalence of PCa. RESULTS: Consumption of certain groups of flavonoids significantly differed between controls and cases, in particular: flavonols (63.36 vs 37.14 mg/d, P < 0.001), flavanols (107.61 vs. 74.24 mg/d, P = .016), flavanones (40.92 vs. 81.32 mg/d, P < 0.001), catechins (63.36 vs. 36.18 mg/d, P = .006). In the multivariate model, flavanols and flavones were associated with reduced risk of PCa, despite not in the highest quartile of intake. Higher flavonol and catechin intake was consistently associated with reduced risk of PCa (Odds Ratio (OR) = 0.19, 95% CI: 0.06-0.56 and OR = 0.12, 95% CI: 0.04-0.36). In contrast, the highest intake of flavanones was positively associated with PCa. CONCLUSION: Flavonols and catechins have proved to be the most promising molecules for a potential protective role against PCa. Nevertheless, further research on flavanones is needed to better establish whether they are associated with PCa.

Serenoa repens + selenium + lycopene vs tadalafil 5 mg for the treatment of lower urinary tract symptoms secondary to benign prostatic obstruction: a Phase IV, non-inferiority, open-label, clinical study (SPRITE study).

OBJECTIVE: To compare in a randomised, open-label, non-inferiority clinical study, the efficacy and tolerability of Serenoa repens (SeR) + selenium (Se) + lycopene (Ly) (SeR-Se-Ly) therapy vs tadalafil 5 mg in men with lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: From May 2015 to January 2017, 427 patients were enrolled in 21 different centres (International Standard Randomised Controlled Trial Number Register [ISRCTN] 73316039). Inclusion criteria included: age between 50 and 80 years, International Prostate Symptom Score (IPSS) ≥12, maximum urinary flow rate (Qmax ) ≤ 15 mL/s, and post-void residual (PVR) <100 mL. Patients were randomised into two groups in a 2:1 ratio: Group A (SeR-Se-Ly, 1 tablet daily for 6 months) and Group B (tadalafil 5 mg, 1 tablet daily for 6 months). The primary endpoint of the study was the non-inferior variation in the IPSS and Qmax in Group A vs Group B after 6 months of treatment. RESULTS: In all, 404 patients completed the full protocol. When comparing both therapies, Group A was statistically not inferior to Group B considering the median change in IPSS (-3.0 vs -3.0; P < 0.01), IPSS quality of life (-2.0 vs -2.0; P < 0.05), and Qmax (2.0 vs 2.0 mL/s; P < 0.01). We found statistically significant differences in the increase of at least 3 points in Qmax (38.2% vs 28.1%; P = 0.04) and of at least 30% of Qmax (39.2% vs 27.3%; P < 0.01) in Group A compared to Group B. The percentage of patients with an increase of at least 3 points in the IPSS and a decrease of at least 25% of the IPSS was not statistically different between the two groups. For adverse events, four patients in Group A (1.44%) and 10 in Group B (7.81%) (P < 0.05) reported side-effects. CONCLUSION: We have shown that treatment with SeR-Se-Ly was not inferior to tadalafil 5 mg for improving IPSS and Qmax in men with LUTS.

Association between dietary phytoestrogens intakes and prostate cancer risk in Sicily.

OBJECTIVE: In this study we aimed to investigate the association between dietary phytoestrogen consumption and prostate cancer in a sample of southern Italian individuals. METHODS: A population-based case-control study on the association between prostate cancer and dietary factors was conducted from January 2015 to December 2016 in a single institution of the municipality of Catania, southern Italy (Registration number: 41/2015). A total of 118 histopathological-verified prostate cancer (PCa) cases and a total of 222 controls were collected. Dietary data was collected by using two food frequency questionnaires. RESULTS: Patients with PCa consumed significantly higher levels of phytoestrogens. Multivariate logistic regression showed that lignans (Q[quartile]4 vs. Q1, OR [odds ratio] = 4.72; p < .05) and specifically, lariciresinol (Q4 vs. Q1, OR = 4.60; p < .05), pinoresinol (Q4 vs. Q1, OR = 5.62; p < .05), matairesinol (Q4 vs. Q1, OR = 3.63; p < .05), secoisolariciresinol (Q4 vs. Q1, OR = 4.10; p < .05) were associated with increased risk of PCa. Furthermore, we found that isoflavones (Q3 vs. Q1, OR = 0.28; p < .05) and specifically, genistein (Q4 vs. Q1, OR = 0.40; p < .05) were associated with reduced risk of PCa. CONCLUSION: We found of an inverse association between dietary isoflavone intake and PCa, while a positive association was found with lignans intake.

Association between selenium and lycopene supplementation and incidence of prostate cancer: Results from the post-hoc analysis of the procomb trial.

BACKGROUND: Many potential chemopreventive agents have been used in PCa prevention, including selenium (Se) and lycopene (Ly). However, their role has been matter of debate over the years, due to potential of promotion of PCa. PURPOSE: In this study we aimed at evaluating the incidence risk of prostate cancer (PCa) in a cohort of patients treated with Se and Ly. METHODS: The Procomb trial design has been previously published (ISRCTN78639965). From April 2012 to April 2014 209 patients were followed and underwent prostate biopsy when PSA ≥4 ng/ml and/or suspicion of PCa. The all cohort was composed by patients treated with Se and Ly (Group A = 134 patients) and control (Group B = 75 patients). RESULTS: During the follow-up time of 2 years, a total of 24 patients (11.5%) underwent prostate biopsy, of which 9 (4.3%) where diagnosed with PCa and 15 (7.2%) where diagnosed with benign prostatic hyperplasia. We did not observe statistical differences in terms of mean changes of PSA between the two groups (p-value for trend = 0.33). The relative risk (RR) for PCa was 1.07 and 0.89 in group A and B, respectively (p = 0.95). At the multivariate Cox regression analysis supplementation with Se and Ly was not associated with greater risk of PCa (hazard ratio: 1.38; p = 0.67). CONCLUSION: In this analysis we did not show evidences supporting a detrimental role of Selenium and Lycopene supplementation in increasing PCa after 2 years of therapy, nor supporting a protective role.

A phase II, randomized, single-blinded, placebo-controlled clinical trial on the efficacy of Curcumina and Calendula suppositories for the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome type III.

OBJECTIVE: The management of chronic prostatitis/ chronic pelvic pain syndrome type III (CP/CPPS) has been always considered complex due to several biopsychological factors underling the disease. In this clinical study, we aimed to evaluate the efficacy of the treatment with Curcumin and Calendula extract in patients with CP/CPPS III. MATERIAL AND METHODS: From June 2015 to January 2016 we enrolled 60 consecutive patients affected by CP/CPPS III in our institution. Patients between 20 and 50 year of age with symptoms of pelvic pain for 3 months or more before study, a total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score ≥ 15 point and diagnosed with NIH category III. Patients were then allocated to receive placebo (Group A) or treatment (Group B). Treatment consisted of rectal suppositories of Curcumin extract 350 mg (95%) and Calendula extract 80 mg (1 suppository/die for 1 month). Patients of Group B received 1 suppository/die for 1 month of placebo. The primary endpoint of the study was the reduction of NIH-CPSI. The secondary outcomes were the change of peak flow, IIEF-5, VAS score and of premature ejaculation diagnostic tool (PEDT). RESULTS: A total of 48 patients concluded the study protocol. The median age of the all cohort was 32.0 years, the median NIH-CPSI was 20.5, the median IIEF-5 was 18.5, the median PEDT was 11.0, the median VAS score was 7.5 and the median peak flow was 14.0. After 3 months of therapy in group A we observed a significant improvement of NIH-CPSI (-5.5; p < 0.01), IIEF-5 (+ 3.5; p < 0.01), PEDT (-6.5; p < 0.01), peak flow (+2.8; p < 0.01) and VAS (-6.5; p < 0.01) with significant differences over placebo group (all p-value significant). CONCLUSIONS: In this phase II clinical trial we showed the clinical efficacy of the treatment with Curcumin and Calendula in patients with CP/CPPS III. The benefits of this treatment could be related to the reduction of inflammatory cytokines and of inflammatory cells. These results should be confirmed in further studies with greater sample size.

Survivin and NAIP in Human Benign Prostatic Hyperplasia: Protective Role of the Association of Serenoa repens, Lycopene and Selenium from the Randomized Clinical Study.

Benign prostatic hyperplasia (BPH) treatment includes the apoptosis machinery modulation through the direct inhibition of caspase cascade. We previously demonstrated that Serenoa repens (Ser) with lycopene (Ly) and selenium (Se) reawakened apoptosis by reducing survivin and neuronal apoptosis inhibitory protein (NAIP) levels in rats. The aim of this study was to evaluate the effectiveness of Ser-Se-Ly association on survivin and NAIP expression in BPH patients. Ninety patients with lower urinary tract symptoms (LUTS) due to clinical BPH were included in this randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive placebo (Group BPH + placebo, n = 45) or Ser-Se-Ly association (Group BPH + Ser-Se-Ly; n = 45) for 3 months. At time 0, all patients underwent prostatic biopsies. After 3 months of treatment, they underwent prostatic re-biopsy and specimens were collected for molecular, morphological, and immunohistochemical analysis. After 3 months, survivin and NAIP were significantly decreased, while caspase-3 was significantly increased in BPH patients treated with Ser-Se-Ly when compared with the other group. In BPH patients treated with Ser-Se-Ly for 3 months, the glandular epithelium was formed by a single layer of cuboidal cells. PSA showed high immunoexpression in all BPH patients and a focal positivity in Ser-Se-Ly treated patients after 3 months. Evident prostate specific membrane antigen (PSMA) immunoexpression was shown in all BPH patients, while no positivity was present after Ser-Se-Ly administration. Ser-Se-Ly proved to be effective in promoting apoptosis in BPH patients.

Alga Ecklonia bicyclis, Tribulus terrestris, and glucosamine oligosaccharide improve erectile function, sexual quality of life, and ejaculation function in patients with moderate mild-moderate erectile dysfunction: a prospective, randomized, placebo-controlled, single-blinded study.

We aimed to evaluate the efficacy of oral therapy with alga Ecklonia bicyclis, Tribulus terrestris, and glucosamine oligosaccharide (Tradamix TX1000) in patients with erectile dysfunction (ED) at 3 months of follow-up. From January 2013 to September 2013, 177 patients diagnosed with mild-moderate ED (IIEF-EF < 26) were enrolled in this multicenter, single-blinded, placebo-controlled study and randomized in Group A (Tradamix, n = 87) and Group B (placebo, n = 90). Penile color Doppler ultrasound measures, IIEF-15 questionnaire, male sexual health questionnaire-ejaculation disorder (MSHQ-EjD), and sexual quality of life (SQoL-M) were collected. We observed significant changes of the IIEF-15 in Group A (mean difference: 11.54; P < 0.05) at 3 months versus Group B (P < 0.05). PSV (P < 0.05), IIEF-intercourse satisfaction (P < 0.05), IIEF-orgasmic function (mean P < 0.05), IIEF-sexual desire (P < 0.05), IIEF-overall satisfaction (P < 0.05), MSHQ-EjD (mean difference: 1.21; P < 0.05), and SQoL-M (mean difference: 10.2; P < 0.05) were significantly changed in Group A versus baseline and Group B. Patients with moderate arterial dysfunction showed significant increase of PSV (P < 0.05), IIEF-EF (P < 0.05), MSHQ-EjD (P < 0.05), and SQoL-M (P < 0.05) in Group A. Therapy with Tradamix improves erectile and ejaculation function and sexual quality of life in patients with mild-moderate ED and in particular for those with moderate arterial dysfunction.

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).

BACKGROUND: 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. METHODS: PROCOMB trial (ISRCTN78639965) was a randomized double-blinded, double-dummy multicenter study of 225 patients between 55 and 80 years old, PSA ≤ 4 ng/ml, IPSS ≥12, prostate volume ≤60 cc, Qmax ≤15 ml/sec, postvoid residual urine (PVR) <150 ml. Participants were randomized group A (SeR-Se-Ly), group B (tamsulosin 0.4 mg), group C (SeR-Se-Ly + tamsulosin 0.4 mg). The primary endpoints of the study were the reduction of IPSS, PVR, and increase of Qmax in group C versus monotherapy groups. RESULTS: The decrease for combination therapy was significantly greater versus group A (P < 0.05) and group B (P < 0.01) for IPSS and versus group A (P < 0.01) for PVR from baseline to 6 months. A greater decrease in IPSS was observed for Group C versus group A (P < 0.01) and increase in Qmax versus group B (P < 0.01), from 6 months to 12 months. At one year, the changes of IPSS and Qmax were greater for Group C versus monotherapies (each comparison <0.05). The proportions of men with a decrease of at least three points (each comparison P < 0.05) and decrease of 25% for IPSS (each comparison P < 0.01) were greater for Group C. CONCLUSION: SeR-Se-Ly + tamsulosin therapy is more effective than single therapies in improving IPSS and increasing Qmax in patients with LUTS.

Correlation between lipid profile and heme oxygenase system in patients with benign prostatic hyperplasia.

OBJECTIVE: To investigate the role of heme oxygenase (HO) system in moderate to severe benign prostatic hyperplasia and lower urinary tract symptom patients and the influence of metabolic syndrome (MetS) components on HO-1 or HO-2 prostatic levels. METHODS: One hundred thirty-two consecutive patients who underwent transurethral resection of the prostate were prospectively enrolled. MetS was defined by the International Diabetes Federation. Patients were divided in 2 groups: group A (high-density lipoprotein-cholesterol [HDL-C]≥40 mg/dL and triglycerides<150 mg/dL) and group B (HDL-C<40 mg/dL and triglycerides≥150 mg/dL). Surgical specimens were collected for HO level determination. HO-1 levels were determined by enzyme-linked immunosorbent assay and HO-1 levels by Western blotting. RESULTS: Patients with MetS showed lower levels of HO-1 (5.29 vs 6.28 ng/mL; P=.04), HO-2 (1.01 vs 1.83 ng/mL; P=.04), phosphorylated activated protein kinase (pAMPK; 0.62 vs 1.11 AUI; P<.01), and HO-activity (61.43 vs 70.22 AUI; P<.01) with respect to normal. The Pearson correlation analysis showed that HO-1, HO-2, and HO activity were negatively associated with waist circumference (P<.05), body mass index (P<.05), triglycerides (P<.05) and positively with HDL-C (P<.05). Group B showed lower levels of HO-1 (4.7 vs 6.6 ng/mL; P<.05), HO-2 (1.4 vs 0.4 ng/mL; P=.03), HO-activity (69.63 vs 58.42 AUI; P=.04), and higher International Prostate Symptoms Score (21.4 vs 25.0; P<.05) with respect to group A. The enzyme-linked immunosorbent assay showed that HO-1 and HO activity levels were significantly lower in group B compared with group A. Reduced HDL-C and elevated triglyceride levels decreased HO-1 expression in the prostate tissue. Western blot analysis of tissue samples showed significant differences in basal protein expression levels of HO-2 and pAMPK in group B compared with group A. CONCLUSION: Alteration of serum triglycerides and HDL-C significantly impairs HO-1 and HO-2 levels in benign prostatic hyperplasia patients.

Inhibitors of apoptosis proteins in experimental benign prostatic hyperplasia: effects of serenoa repens, selenium and lycopene.

BACKGROUND: The apoptosis machinery is a promising target against benign prostatic hyperplasia (BPH). Inhibitors of apoptosis proteins (IAPs) modulate apoptosis by direct inhibition of caspases. Serenoa Repens (SeR) may be combined with other natural compounds such as Lycopene (Ly) and Selenium (Se) to maximize its therapeutic activity in BPH. We investigated the effects of SeR, Se and Ly, alone or in association, on the expression of four IAPs, cIAP-1, cIAP-2, NAIP and survivin in rats with experimental testosterone-dependent BPH. Moreover, caspase-3, interleukin-6 (IL-6) and prostate specific membrane antigen (PSMA) have been evaluated.Rats were administered, daily, with testosterone propionate (3 mg/kg/sc) or its vehicle for 14 days. Testosterone injected animals (BPH) were randomized to receive vehicle, SeR (25 mg/kg/sc), Se (3 mg/kg/sc), Ly (1 mg/kg/sc) or the SeR-Se-Ly association for 14 days. Animals were sacrificed and prostate removed for analysis. RESULTS: BPH animals treated with vehicle showed unchanged expression of cIAP-1 and cIAP-2 and increased expression of NAIP, survivin, caspase-3, IL-6 and PSMA levels when compared with sham animals. Immunofluorescence studies confirmed the enhanced expression of NAIP and survivin with a characteristic pattern of cellular localization. SeR-Se-Ly association showed the highest efficacy in reawakening apoptosis; additionally, this therapeutic cocktail significantly reduced IL-6 and PSMA levels. The administration of SeR, Se and Ly significantly blunted prostate overweight and growth; moreover, the SeR-Se-Ly association was most effective in reducing prostate enlargement and growth by 43.3% in treated animals. CONCLUSIONS: The results indicate that IAPs may represent interesting targets for drug therapy of BPH.

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.

Potential efficacy of some african plants in benign prostatic hyperplasia and prostate cancer.

Traditional medicine is very popular in Africa and it is considered as an alternative form of health care. Plants and vegetables used in folk and traditional medicine have gained wide acceptance as one of the main sources of prophylactic and chemopreventive drug discovery and this is due to the evidence of particular biological and biochemical characteristics of each plants extracts. The role of these compounds in urological field may be explained by the antiinflammatory effect through interference with prostaglandin metabolism, alteration of lipid peroxidation, direct inhibition of prostate growth and moreover through an antiandrogenic or antiestrogenic effect and a decrease of the availability of sex hormone-binding globulin. Since Benign Prostatic Hyperplasia and Prostate Cancer are two of the most diffuse diseases of aging male and considering that standard medical therapy is accompanied with different side effects, the emerging use of African plants may be justified. This review takes a look at some African plants extracts properties and their relative urological application. Different biomolecular mechanisms of action are promising, suggesting a real application in reducing prostate cells proliferation.

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® + α-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. .

An improvement in sexual function is related to better quality of life, regardless of urinary function improvement: results from the IDIProst® Gold Study.

OBJECTIVE: The relationship between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) has recently received increased attention. The aim of this study was to evaluate the efficacy of the Alfa-5® association of Serenoa repens, Pinus massoniana Bark Extract (PMBE) and Crocus sativus (IDIProst® Gold) in improvement of patient's quality of life, when compared with Serenoa repens alone. MATERIALS AND METHODS: All patients with clinical and instrumental diagnosis of LUTS due to Benign Prostatic Hyperplasia (BPH) and ED, attending 5 Italians Urological Institutions from May to December 2012 were enrolled in this prospective, multicentre, phase 3 study. Participants were assigned to receive oral capsules of IDIProst® Gold (one capsule q24 h) or Serenoa repens 320 mg (one capsule q24h) for 3 months. Clinical and instrumental analyses were carried out at the enrollment and at the end of therapy. IPSS, IIEF-5 and SF-36 questionnaires have been used. The main outcome measure was the improvement of quality of life at the end of the whole study period. RESULTS: 129 (mean age 45-71 ± 4.36) men were randomly allocated to IDIProst® Gold (n = 83) or Serenoa repens (n = 46). The baseline questionnaire mean scores were 17.1 ± 6.4, 14.9 ± 3.7, 96.3 ± 1.2 for IPSS, IIEF-5 and SF-36, respectively. At the follow-up examination, statistically significant differences have been reported in terms of IPSS (11.9 vs 13.8; p < 0.001), IIEF-5 and SF-36 mean scores (19.3 vs 16.1; 99.7 vs 96.3; p < 0.003; p < 0.001). Moreover, statistically significant differences were then reported between the two visits, in terms of IPSS, IIEF-5 and SF-36 scores (p < 0.003; p < 0.001; p < 0.001), only in the IDIProst® Gold group. CONCLUSIONS: In conclusions, we found that IDIProst® Gold significantly improve the quality of life of patients affected by LUTS due to BPH and ED, specifically in terms of sexual function, highlighting that a better sexual quality of life is correlated with an higher overall quality of life regardless of the urinary function.

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.

The combination of Serenoa repens, selenium and lycopene is more effective than serenoa repens alone to prevent hormone dependent prostatic growth.

PURPOSE: Serenoa repens is frequently combined with other natural compounds, such as the carotenoid lycopene and the essential trace element Se, to increase its therapeutic activity in benign prostatic hyperplasia. We noted that the lycopene-Se-Serenoa repens combination has greater, enhanced anti-inflammatory activity, which might be of particular interest for benign prostatic hyperplasia treatment. Testosterone administration in rats is a suitable tool for investigating hormone dependent benign prostatic hyperplasia. We performed a comparison experiment between Serenoa repens and the lycopene-Se-Serenoa repens combination on prostate growth induced in rats by testosterone administration. MATERIALS AND METHODS: Rats were treated daily with testosterone propionate (3 mg/kg subcutaneously) or its vehicle for 14 days. Testosterone administered animals were randomized to receive vehicle, Serenoa repens (25 mg/kg subcutaneously) or the combination of lycopene (3 mg/kg subcutaneously), Se (3 mg/kg subcutaneously) and Serenoa repens for 14 days. The rats were sacrificed and the prostate was removed for analysis. RESULTS: Lycopene-Se-Serenoa repens was more effective than Serenoa repens alone for decreasing prostate weight and hyperplasia, augmenting pro-apoptotic Bax and caspase-9, and blunting anti-apoptotic Bcl-2 mRNA. Lycopene-Se-Serenoa repens also markedly decreased epidermal growth factor and vascular endothelial growth factor expression. CONCLUSIONS: The data indicate that the lycopene-Se-Serenoa repens combination is superior to Serenoa repens alone for decreasing hormone dependent prostatic growth.

[The association of Serenoa repens, lycopene and selenium is superior to Serenoa repens alone in reducing benign prostatic hyperplasia]. / L'associazione di Serenoa repens più Licopene e Selenio è più efficace della sola Serenoa repens nel ridurre la crescita prostatica benigna.

Serenoa repens (SeR) is frequently associated with other natural compounds, such as lycopene (Ly), a carotenoid, and selenium (Se), an essential trace element, to increase its therapeutic activity in benign prostatic hyperplasia (BPH). The LY-Se-SeR association has a greater and stronger anti-inflammatory activity than SeR alone. In addition, the LY-Se-SeR combination is more effective than SeR alone in reducing prostate weight and hyperplasia, augmenting apoptosis, and reducing cell proliferation and growth factor expression. This experimental evidence suggests that Ly-Se-SeR association is superior to SeR alone in reducing benign prostate growth.