[Pathology and Pathophysiology of BPH and Relevant Incidental Findings in TUR-P]. / Pathologie und Pathophysiologie der BPH und relevante Zufallsbefunde in der TUR-P.

Pathology and Pathophysiology of BPH and Relevant Incidental Findings in TUR-P Abstract: Benign prostatic hyperplasia (BPH) is defined as nodular prostate enlargement due to cellular proliferation of prostate glands and stroma. Beside adenocarcinoma, BPH is one of the most common diseases in the prostate. Transurethral resection of the prostate (TURP) is surgical treatment of choice for BPH. Resected tissue fragments are examined in the pathology and belong to the most commonly submitted urologic specimens. Up to date, pathophysiology of BPH is not yet completely understood. Different hormones such as androgens, dihydrotestosterone, estrogens as well as growth factors, inflammation, and environmental influences are important in the process. The diagnosis of BPH is usually straightforward. In this context, it is important to mention incidental findings, which may come along as "bad surprises" while examining TURP tissue fragments. Prostatic intraepithelial neoplasia (PIN) or incidental acinar adenocarcinoma of the prostate as well as the potential preneoplastic atypical adenomatoid hyperplasia (AAH) represent a few examples. According to literature, the histologic examination of TURP tissue reveals a high-grade PIN in up to 5%. Incidental adenocarcinoma is encountered in 5-13%. These frequencies justify a relatively laborious examination of the entire or majority resected TURP tissue.

Grape Powder Supplementation Attenuates Prostate Neoplasia Associated with Pten Haploinsufficiency in Mice Fed High-Fat Diet.

SCOPE: Previous studies have identified potent anticancer activities of polyphenols in preventing prostate cancer. The aim of the current study is to evaluate the chemopreventive potential of grape powder (GP) supplemented diets in genetically predisposed and obesity-provoked prostate cancer. METHODS AND RESULTS: Prostate-specific Pten heterozygous (Pten+/f ) transgenic mice are fed low- and high-fat diet (LFD and HFD, respectively) supplemented with 10% GP for 33 weeks, ad libitum. Prostate tissues are characterized using immunohistochemistry and western blots, and sera are analyzed by ELISA and qRT-PCR. Pten+/f mice fed LFD and HFD supplemented with 10% GP show favorable histopathology, significant reduction of the proliferative rate of prostate epithelial cells (Ki67), and rescue of PTEN expression. The most potent protective effect of GP supplementation is detected against HFD-induced increase in inflammation (IL-1ß; TGF-ß1), activation of cell survival pathways (Akt, AR), and angiogenesis (CD31) in Pten+/f mice. Moreover, GP supplementation reduces circulating levels of oncogenic microRNAs (miR-34a; miR-22) in Pten+/f mice. There are no significant changes in body weight and food intake in GP supplemented diet groups. CONCLUSIONS: GP diet supplementation can be a beneficial chemopreventive strategy for obesity-related inflammation and prostate cancer progression. Monitoring serum miRNAs can facilitate the non-invasive evaluation of chemoprevention efficacy.

Green tea catechins for chemoprevention of prostate cancer in patients with histologically-proven HG-PIN or ASAP. Concise review and meta-analysis.

A focused, single outcome meta-analysis on the protective role of extracts of green tea catechins against prostate cancer. Randomized, placebo-controlled studies enrolling patients with a histologically confirmed diagnosis of high-grade Prostate Intraepithelial Neoplasia or Atypical Small Acinar proliferation but no prostate cancer were included. Meta-analysis for binary data was performed using Mantel-Haenszel statistics, using a random-effects model. Heterogeneity was investigated by calculating the I2. Four studies matched the inclusion criteria for the review. The pooled population was 223 patients; 114 and 109 patients were randomized to catechin and placebo groups, respectively. Nine cases of prstate cancer occurred in the catechin arm (7.9%), and 24 cases were reported in the placebo arm (22%). Pooled analysis resulted in a significant reduction of cancer risk in favor of the catechin arm (risk-ratio = 0.41; 95% CI: 0.19- 0.86; I2 = 0). In conclusion, our data suggest that the intake of concentrated green tea catechin preparations may confer a significant protective effect to carriers of early neoplastic lesions in the prostate. The quality of the evidence is moderate, and additional, largescale studies are warranted to substantiate these preliminary findings.

Could pollen extract in association with vitamins be favorable in the reduction of chronic prostatic inflammation? A case-series analysis.

The aim of the present case-series analysis was to assess the safety and efficacy of pollen extract in association with vitamins in order to reduce the chronic prostatic inflammation in patients with class IV chronic prostatitis (CP). Nineteen non-consecutive patients performed a prostate biopsy for a suspect of prostate cancer. The biopsy histopathological examination showed a class IV CP, in presence of mild/moderate/high degree of inflammation, in association with an extensive (multiple biopsy sites, i.e., ≥ 3) high-grade prostatic intraepithelial neoplasia PIN (HGPIN) and/or atypical small acinar proliferation (ASAP). According to EAU Prostate Cancer Guidelines prostate biopsy was repeated after 6 months, because of the presence of extensive HGPIN or ASAP. Oral administration of pollen extract in association with vitamins (two capsules every 24 h) was prescribed until the repeat biopsy. Repeat biopsy histopathological examination showed, in 13 patients (68.4%), a lower degree of inflammation (absent/mild/moderate).

"Finding the needle in a haystack": oncologic evaluation of patients treated for LUTS with holmium laser enucleation of the prostate (HoLEP) versus transurethral resection of the prostate (TURP).

PURPOSE: To evaluate oncologic parameters of men with bothersome LUTS undergoing surgical treatment with HoLEP or TURP. METHODS: Five hundred and eighteen patients undergoing HoLEP (n = 289) or TURP (n = 229) were retrospectively analyzed for total PSA, prostate volume, PSA density, history of prostate biopsy, resected prostate weight, and histopathological features. Univariate and multivariate logistic regression models were used to identify independent predictors of incidental PCa (iPCa). RESULTS: Men undergoing HoLEP had a significantly higher total PSA (median 5.5 vs. 2.3 ng/mL) and prostate volume (median 80 vs. 41 cc), and displayed a greater reduction of prostate volume after surgery compared to TURP patients (median 71 vs. 50%; all p < 0.001). With a prevalence of incidental PCa (iPCa) of 15 and 17% for HoLEP and TURP, respectively, the choice of procedure had no influence on the detection of iPCa (p = 0.593). However, a higher rate of false-negative preoperative prostate biopsies was noted among iPCa patients in the HoLEP arm (40 vs. 8%, p = 0.007). In multivariate logistic regression, we identified patient age (OR 1.04; 95% CI 1.01-1.07, p = 0.013) and PSA density (OR 2.13; 95% CI 1.09-4.18, p = 0.028) as independent predictors for the detection of iPCa. CONCLUSIONS: Despite differences in oncologic parameters, the choice of technique had no influence on the detection of iPCa. Increased patient age and higher PSA density were associated with iPCa. A higher rate of false-negative preoperative prostate biopsies was noted in HoLEP patients. Therefore, diagnostic assessment of LUTS patients requires a more adapted approach to exclude malignancy, especially in those with larger prostates.

Chemoprevention of prostate cancer in men with high-grade prostatic intraepithelial neoplasia (HGPIN): a systematic review and adjusted indirect treatment comparison.

BACKGROUND: High-grade prostatic intraepithelial neoplasia (HGPIN) is the precursor or premalignant form of prostate cancer. At least 30% patients with a confirmed HGPIN will develop prostate cancer within 1 year after repeated biopsy. HGPIN patients are the appropriate at-risk population for chemoprevention strategies investigation against prostate cancer. However the commonly used chemoprevention agents that targeted on hormonal imbalance or lifestyle-related factors showed varied results in HGPIN patients. METHODS: Literature searches were conducted in PubMed, EMBASE and Cochrane library according to Cochrane guidelines before January 31st, 2017. Direct meta-analysis were performed to summarize the efficacy of candidate chemopreventative agents Dutasteride, Flutamide, Toremifene, Selenium, Green tea components, Lycopene and natural food products combination. Adjusted indirect meta-analyses were employed to compare the relative efficacy of these candidate chemoprevention agents head-to-head. RESULTS: The overall incidence of prostate cancer in HGPIN was slightly decreased by chemoprevention agents (25.7% vs 31.5%, RR = 0.92, 95% CI: 0.83-1.03, P = 0.183), with minor heterogeneity (I2 = 22.3%, 𝟀2 = 15.08, P = 0.237), but without statistical significance. Subgroup analysis showed that green tea catechins significantly decreased prostate cancer in HGPIN patients (7.60% vs 23.1%, RR = 0.39, 95% CI: 0.16-10.97, P P = 0.044), with moderate heterogeneity (I2 = 47.9%, 𝟀2 = 1.92, P = 0.166). The adjusted indirect meta-analysis favored green tea catechins over other chemoprevention agents, and significantly when compared to natural food products combination (RR = 0.355, 95% CI: 0.134-0.934). CONCLUSION: The overall efficacy of chemoprevention agents in HGPIN patients is limited. But Green tea catechins showed the superiority to decrease prostate cancer in HGPIN patients.

Dietary tocopherols inhibit PhIP-induced prostate carcinogenesis in CYP1A-humanized mice.

Tocopherols, the major forms of vitamin E, exist as alpha-tocopherol (α-T), ß-T, γ-T and δ-T. The cancer preventive activity of vitamin E is suggested by epidemiological studies, but recent large-scale cancer prevention trials with high dose of α-T yielded disappointing results. Our hypothesis that other forms of tocopherols have higher cancer preventive activities than α-T was tested, herein, in a novel prostate carcinogenesis model induced by 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), a dietary carcinogen, in the CYP1A-humanized (hCYP1A) mice. Treatment of hCYP1A mice with PhIP (200 mg/kg b.w., i.g.) induced high percentages of mouse prostatic intraepithelial neoplasia (mPIN), mainly in the dorsolateral glands. Supplementation with a γ-T-rich mixture of tocopherols (γ-TmT, 0.3% in diet) significantly inhibited the development of mPIN lesions and reduced PhIP-induced elevation of 8-oxo-deoxyguanosine, COX-2, nitrotyrosine, Ki-67 and p-AKT, and the loss of PTEN and Nrf2. Further studies with purified δ-T, γ-T or α-T (0.2% in diet) showed that δ-T was more effective than γ-T or α-T in preventing mPIN formations and p-AKT elevation. These results indicate that γ-TmT and δ-T could be effective preventive agents of prostate cancer.

A Phase II Randomized Trial of Lycopene-Rich Tomato Extract Among Men with High-Grade Prostatic Intraepithelial Neoplasia.

A diverse body of evidence suggests that lycopene might inhibit prostate cancer development. We conducted a 6-mo repeat biopsy randomized trial among men with high-grade prostatic intraepithelial neoplasia (HGPIN). Here we report results for serum lycopene, prostate specific antigen (PSA) and insulin-like growth factor (IGF) proteins, histopathological review, and tissue markers for proliferation [minichromosome maintenance protein 2 (MCM-2)] and cell cycle inhibition (p27). Participants consumed placebo or tomato extract capsules containing 30 mg/day lycopene. Pre- and posttreatment biopsies were immunostained and digitally scored. Serum lycopene was determined by LC-MS-MS. In secondary analyses, pathologists blindly reviewed each biopsy to score histological features. Fifty-eight men completed the trial. Serum lycopene increased 0.55 µmol/L with treatment and declined 0.29 µmol/L with placebo. We observed no meaningful differences in PSA, IGF-1, or IGF binding protein 3 concentrations between groups, nor any differences in expression of MCM-2 or p27 in epithelial nuclei. Prevalences of cancer, HGPIN, atrophy, or inflammation posttreatment were similar; however, more extensive atrophy and less extensive HGPIN was more common in the lycopene group. Despite large differences in serum lycopene following intervention, no treatment effects were apparent on either the serum or benign tissue endpoints. Larger studies are warranted to determine whether changes observed in extent of HGPIN and focal atrophy can be replicated.

A randomized double-blind placebo controlled phase I-II study on clinical and molecular effects of dietary supplements in men with precancerous prostatic lesions. Chemoprevention or "chemopromotion"?

BACKGROUND: Antioxidants effectiveness in prostate cancer (PCa) chemoprevention has been severely questioned, especially after the recent results of the Selenium and Vitamin E Cancer Prevention Trial. We present the results of a double-blind randomized controlled trial (dbRCT) on the pharmacokinetic, clinical, and molecular activity of dietary supplements containing lycopene, selenium, and green tea catechins (GTCs) in men with multifocal high grade prostatic intraepithelial neoplasia (mHGPIN) and/or atypical small acinar proliferation (ASAP). METHODS: From 2009 to 2014, we conducted a dbRCT including 60 patients with primary mHGPIN and/or ASAP receiving daily lycopene 35 mg, selenium 55 µg, and GTCs 600 mg, or placebo for 6 months. Pharmacokinetic analysis were performed with UV-Visible spectrophotometric assay under standard (SC) and accelerated (AC) conditions. Upon plasma lycopene concentrations falling within the expected range (1.2-90 mcg/l) and no side-effects of grade >1, study proceeded to phase II (n = 50). After unblinding of results, eight men (4 per arm, 2 without and 2 with PCa, respectively) were randomly selected and totRNA extracted from "non-pathological" tissues. MicroRNA profiling was performed with the Agilent platform. Raw data processing used R-statistical language and linear models for microarray analysis. RESULTS: Samples were stable except for lycopene, showing significant degradation (SC = 56%, AC = 59%) and consequently stabilized under vacuum in a dark packaging. Mean plasmatic lycopene concentration was 1,45 ± 0,4 µM. At 6 months, 53 men underwent re-biopsy and 13 (24.5%) were diagnosed with PCa (supplementation n = 10, placebo n = 3 [P = 0.053]). At a mean 37 months follow-up, 3 additional PCa were found in the placebo group. No significant variations in PSA, IPSS, and PR25 questionnaires were observed. Stronger modulation of miRNAs was present on re-biopsy in the supplementation group compared to the placebo, including: (i) overexpression of miRNAs present in PCa versus non-cancer tissue; (ii) underexpression of miRNAs suppressing PCa proliferation; (iii) detection of 35 miRNAs in PCa patients versus disease-free men, including androgen-regulated miR-125b-5p and PTEN-targeting miR-92a-3p (both upregulated). CONCLUSION: Administration of high doses of lycopene, GTCs, and selenium in men harboring HGPIN and/or ASAP was associated with a higher incidence of PCa at re-biopsy and expression of microRNAs implicated in PCa progression at molecular analysis. The use of these supplements should be avoided.

Randomized, Placebo-Controlled Trial of Green Tea Catechins for Prostate Cancer Prevention.

Preclinical, epidemiologic, and prior clinical trial data suggest that green tea catechins (GTC) may reduce prostate cancer risk. We conducted a placebo-controlled, randomized clinical trial of Polyphenon E (PolyE), a proprietary mixture of GTCs, containing 400 mg (-)-epigallocatechin-3-gallate (EGCG) per day, in 97 men with high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar proliferation (ASAP). The primary study endpoint was a comparison of the cumulative one-year prostate cancer rates on the two study arms. No differences in the number of prostate cancer cases were observed: 5 of 49 (PolyE) versus 9 of 48 (placebo), P = 0.25. A secondary endpoint comparing the cumulative rate of prostate cancer plus ASAP among men with HGPIN without ASAP at baseline, revealed a decrease in this composite endpoint: 3 of 26 (PolyE) versus 10 of 25 (placebo), P < 0.024. This finding was driven by a decrease in ASAP diagnoses on the Poly E (0/26) compared with the placebo arm (5/25). A decrease in serum prostate-specific antigen (PSA) was observed on the PolyE arm [-0.87 ng/mL; 95% confidence intervals (CI), -1.66 to -0.09]. Adverse events related to the study agent did not significantly differ between the two study groups. Daily intake of a standardized, decaffeinated catechin mixture containing 400 mg EGCG per day for 1 year accumulated in plasma and was well tolerated but did not reduce the likelihood of prostate cancer in men with baseline HGPIN or ASAP.

Plumbagin Inhibits Prostate Carcinogenesis in Intact and Castrated PTEN Knockout Mice via Targeting PKCε, Stat3, and Epithelial-to-Mesenchymal Transition Markers.

Prostate cancer continues to remain the most common cancer and the second leading cause of cancer-related deaths in American males. The Pten deletions and/or mutations are frequently observed in both primary prostate cancers and metastatic prostate tissue samples. Pten deletion in prostate epithelium in mice results in prostatic intraepithelial neoplasia (PIN), followed by progression to invasive adenocarcinoma. The Pten conditional knockout mice [(Pten-loxp/loxp:PB-Cre4(+)) (Pten-KO)] provide a unique preclinical model to evaluate agents for efficacy for both the prevention and treatment of prostate cancer. We present here for the first time that dietary plumbagin, a medicinal plant-derived naphthoquinone (200 or 500 ppm) inhibits tumor development in intact as well as castrated Pten-KO mice. Plumbagin has shown no signs of toxicity at either of these doses. Plumbagin treatment resulted in a decrease expression of PKCε, AKT, Stat3, and COX2 compared with the control mice. Plumbagin treatment also inhibited the expression of vimentin and slug, the markers of epithelial-to-mesenchymal transition (EMT) in prostate tumors. In summary, the results indicate that dietary plumbagin inhibits growth of both primary and castration-resistant prostate cancer (CRPC) in Pten-KO mice, possibly via inhibition of PKCε, Stat3, AKT, and EMT markers (vimentin and slug), which are linked to the induction and progression of prostate cancer.

Death receptor 5 expression is inversely correlated with prostate cancer progression.

Prostate carcinoma (PCa) is one of the most common cancers in men. Prostate-specific antigen (PSA) has been widely used to predict the outcome of PCa and screening with PSA has resulted in a decline in mortality. However, PSA is not an optimal prognostic tool as its sensitivity may be too low to reduce morbidity and mortality. Consequently, there is a demand for additional robust biomarkers for prostate cancer. Death receptor 5 (DR5) has been implicated in the prognosis of several cancers and it has been previously shown that it is negatively regulated by Yin Yang 1 (YY1) in prostate cancer cell lines. The present study investigated the clinical significance of DR5 expression in a prostate cancer patient cohort and its correlation with YY1 expression. Immunohistochemical analysis of protein expression distribution was performed using tissue microarray constructs from 54 primary PCa and 39 prostatic intraepithelial neoplasia (PIN) specimens. DR5 expression was dramatically reduced as a function of higher tumor grade. By contrast, YY1 expression was elevated in PCa tumors as compared with that in PIN, and was increased with higher tumor grade. DR5 had an inverse correlation with YY1 expression. Bioinformatic analyses corroborated these data. The present findings suggested that DR5 and YY1 expression levels may serve as progression biomarkers for prostate cancer.

CD4 helper T cells, CD8 cytotoxic T cells, and FOXP3(+) regulatory T cells with respect to lethal prostate cancer.

Prostate cancer represents a major contributor to cancer mortality, but the majority of men with prostate cancer will die of other causes. Thus, a challenge is identifying potentially lethal disease at diagnosis. Conflicting results have been reported when investigating the relationship between infiltration of lymphocytes and survival in prostate cancer. One of the mechanisms suggested is the recruitment of regulatory T cells (T(regs)), a subpopulation of T cells that have a role in promoting tumor growth. T(regs) counteract tumor rejection through suppressive functions on the anti-immune response but their prognostic significance is still unknown. We report here the results of a conducted case-control study nested in a cohort of men treated with transurethral resection of the prostate and diagnosed incidentally with prostate cancer. Cases are men who died of prostate cancer (n=261) and controls are men who survived >10 years after their diagnosis (n=474). Infiltration of both T(helper) and T(cytotoxic) cells was frequently observed and the majority of the T(regs) were CD4(+). T(helper) or T(cytotoxic) cells were not associated with lethal prostate cancer. However, we found a nearly twofold increased risk of lethal prostate cancer when comparing the highest with the lowest quartile of CD4(+) T(regs) cells (95% confidence interval: 1.3-2.9). Our conclusion is that men with greater numbers of CD4(+) T(regs) in their prostate tumor environment have an increased risk of dying of prostate cancer. Identification of CD4(+) T(regs) in tumor tissue may predict clinically relevant disease at time of diagnosis independently of other clinical factors.

Optimizing prostate biopsy.

Prostate biopsy (PBx) techniques have changed significantly since the original Hodge's scheme. Although the use of transrectal ultrasound (TRUS) guided (PBx) is considered the gold standard for the diagnosis of prostate cancer (Pca), the strategies for initial and repeat biopsies remain controversial. Even with the widespread application of extended prostate biopsy (ePBx) protocols, the false negative rate remains substantial and early PCa detection remains limited. Optimization of the PBx procedures reduce the likelihood of facing a "repeat biopsy dilemma". The aim of this review is to provide an evidence-based update on current methods of PBx and discuss the strategies to optimise biopsy procedures.

Association of Pb, Cd, and Se concentrations and oxidative damage-related markers in different grades of prostate carcinoma.

Prostate cancer is known to be affected by the heavy metal levels and oxidative damage of the body, yet there are very few studies which look into the way it occurs. The aim of this study was to determine whether blood and tissue lead (Pb), cadmium (Cd), and selenium (Se) levels are associated with oxidative damage in the context of prostate cancer progression and development. Seventy-nine patients comprising 25 patients with benign prostatic hypertrophy (BPH), 23 patients with malignant prostatic carcinoma (malign Ca), 16 patients with low-grade prostatic intraepithelial neoplasia (LGPIN), and 15 patients with high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosed on the basis of their clinical profile, transrectal ultrasonography, and histopathology were included in this study. Cd and Pb levels in whole blood were found to be increased in patients with HGPIN compared with the BPH group; also, the levels of Cd in whole blood and tissue were found to be increasing in patients with malign Ca, unlike BPH patients. Moreover, the levels of malondialdehyde (MDA) in plasma and tissue were significantly increased in malign Ca, LGPIN, and HGPIN than those in BPH. However, the levels of tissue Pb were found to be decreasing in BPH, unlike the malign Ca and HGPIN patients, and the levels of tissue protein carbonyls in malign Ca were significantly lower than those in HGPIN. The levels of tissue reduced glutathione (GSH) in malign Ca were significantly lower than those in BPH. Additionally, the levels of Se in serum and tissue in LGPIN were significantly lower than those in BPH. The serum Se levels in HGPIN were also significantly lower than those in BPH and malign Ca groups. Furthermore, the concentrations of serum Se in LGPIN were significantly lower than those in malign Ca. From the Pearson correlation analysis, there were significant positive correlations between tissue Cd and MDA levels in malign Ca, LGPIN, and HGPIN and between the tissue Pb and tissue MDA and protein carbonyl levels in malign Ca. Blood Pb and tissue Pb were also significantly positively correlated with plasma MDA and protein carbonyl levels in malign Ca. In addition, blood Pb was significantly positively correlated with tissue MDA and protein carbonyl levels in malign Ca, and a significant positive correlation was also found between blood Cd and plasma protein carbonyls and tissue MDA in LGPIN. We observed that altered prooxidant-antioxidant balance and heavy metal levels may lead to an increase in oxidative damage and may consequently play an important role in prostate carcinogenesis. These findings indicate that changes in the levels of Pb, Cd, Se, MDA, protein carbonyls, and GSH in the blood and/or tissue are related to the prostatic carcinoma development and progression, although triggering one of the mentioned changes is unknown; therefore, further study is required to determine the exact steps of the process and clarify the roles of different substances in order to obtain a more detailed explanation of the phenomenon.

[Prostate biopsy: Diagnostic responsibility and recent changes]. / Biopsia prostática: responsabilidad diagnóstica y cambios recientes.

In this bibliographic review we reexamine the different features in relation to indication, performance and interpretation of prostatic biopsy (PB). The main objective is to place methodological features involving PB in the current scientific scenario, establishing the correlation between the most relevant and analyzing the historic evolution this procedure has followed, particularly over the last two decades. Prostate biopsy has evolved to be a regular element in urologists` daily practice and its learning process has been simplified to the point it can be approached with adequacy during the first years of residency in Urology. This privileged position PB enjoys in daily practice and the performance obtained from it would have not been a reality without optimization of transrectal ultrasound or local anesthesia techniques, yet reviled in some forums, the real responsible of such success. The consensus reached in the various scientific associations, the clinical guidelines of which are widely consulted worldwide, is the best to support the current state of the art, being the starting point for the addition of new improvements to PB.

Bitter melon extract impairs prostate cancer cell-cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model.

Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients. However, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment and prevention are necessary for inhibiting disease progression to a hormone refractory state. One of the approaches to control prostate cancer is prevention through diet, which inhibits one or more neoplastic events and reduces the cancer risk. For centuries, Ayurveda has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat human health related issues. In this study, we have initially used human prostate cancer cells, PC3 and LNCaP, as an in vitro model to assess the efficacy of bitter melon extract (BME) as an anticancer agent. We observed that prostate cancer cells treated with BME accumulate during the S phase of the cell cycle and modulate cyclin D1, cyclin E, and p21 expression. Treatment of prostate cancer cells with BME enhanced Bax expression and induced PARP cleavage. Oral gavage of BME, as a dietary compound, delayed the progression to high-grade prostatic intraepithelial neoplasia in TRAMP (transgenic adenocarcinoma of mouse prostate) mice (31%). Prostate tissue from BME-fed mice displayed approximately 51% reduction of proliferating cell nuclear antigen expression. Together, our results suggest for the first time that oral administration of BME inhibits prostate cancer progression in TRAMP mice by interfering cell-cycle progression and proliferation.

Phase III trial of selenium to prevent prostate cancer in men with high-grade prostatic intraepithelial neoplasia: SWOG S9917.

The threat of prostate cancer and the significant and often negative impact of its treatment underscore the importance of prevention. High-grade prostatic intraepithelial neoplasia (HGPIN) has been identified as a potential premalignant lesion marking an increased risk of prostate cancer and substantial evidence suggests that men with HGPIN are in need of prostate cancer prevention. In vitro, in vivo, epidemiologic, and clinical trial evidence that selenium supplementation protects against prostate cancer motivated the study we report here: a double-blind, randomized, placebo-controlled trial of selenium 200 (µg/d) as selenomethionine in men with HGPIN. The primary endpoint was progression of HGPIN to prostate cancer over a 3-year period. This National Cancer Institute Intergroup trial was coordinated by the Southwest Oncology Group (SWOG). Of 619 enrolled patients, 423 randomized men with HGPIN (212 selenium and 211 placebo) were eligible (by central pathology review) and included in the primary analysis. Three-year cancer rates were 36.6% (placebo) versus 35.6% (selenium; P = 0.73, adjusted). The majority of patients who developed cancer on trial (70.8%, selenium and 75.5%, placebo) had a Gleason score of 6 or less than 6; there were no differences in Gleason scores between the two arms. Subset analyses included the finding of a nonsignificantly reduced prostate cancer risk (relative risk = 0.82; 95% CI: 0.40-1.69) in selenium versus placebo patients in the lowest quartile of baseline plasma selenium level (<106 ng/mL). Overall, and in all other subsets defined by baseline blood selenium levels, selenium supplementation had no effect on prostate cancer risk. The 36% prostate cancer rate in men with HGPIN indicates the association of this lesion with an elevated prostate cancer risk. Future study in this setting should focus on selenium-deficient populations and selenium pharmacogenetics.

Prostate biopsy findings in Indian men: a hospital-based study.

AIMS: To review prostatic biopsy findings in Indian patients with elevated serum prostate-specific antigen (PSA) attending the Urology department at a tertiary care hospital. SETTINGS AND DESIGN: A retrospective study of 119 patients, who underwent TRUS-guided prostatic biopsy, was conducted. MATERIALS AND METHODS: A total of 119 patients undergoing TRUS-guided prostatic biopsy were evaluated. Age, presentation, PSA, digital rectal examination, number of cores, and final histology were analyzed. Minimum 10 cores biopsies were performed in 109/119 (92%) and 12 cores in 92/119 (77%). Patients were stratified into three groups based on their PSA: 4-10 ng/ml (group I), 10-20 ng/ml (group II), and >20 ng/ml (group III). STATISTICAL ANALYSIS: Unpaired t-test, Chi-square test, and logistic regression were calculated using an Excel (Ver 2007) and online calculators (P < 0.05 significant). RESULTS: Mean age was 67.6 years. Inflammatory pathology (30/119) was common at all PSA levels. In men with negative DRE and PSA > 10 ng/ml, inflammatory pathology was more likely (Chi 4.2798, P = 0.039). Cancer was found in 29/119 biopsies (group I 2/28, group II 3/45, and group III 24/46). Patients with PSA > 20 ng/ml were more likely to show cancer. Precursor lesions were noted in 10/119 (8.4%). On univariate analysis age, PSA, and DRE all showed significant association with histologic cancer but on multiple logistic regression analysis, only PSA (OR 1.03, P = 0.0021) and DRE (OR 8.07, P = 0.0007) were predictive of cancer. CONCLUSIONS: Cancer is less common and inflammatory lesions more common at all levels of PSA in our patients. The effect of antibiotics on PSA and biopsy in our patients needs to be explored.