Intraprostatic Inflammation Research Articles

Influence of microbiome in intraprostatic inflammation and prostate cancer.

Chronic infection and inflammation have been linked to the development of prostate cancer. Dysbiosis of the oral and gut microbiomes and subsequent microbial translocation can lead to pathogenic prostate infections. Microbial-produced metabolites have also been associated with signaling pathways that promote prostate cancer development. A comprehensive discussion on the mechanisms of microbiome infection and the prostate microenvironment is essential to understand prostate carcinogenesis. Published studies were used from the National Center for Biotechnology Information (NCBI) database to conduct a narrative review. No restrictions were applied in the selection of articles. Microbiome-derived short-chain fatty acids (SCFAs) have been found to upregulate multiple signaling pathways, including MAPK and PI3K, through IGF-1 signaling and M2 macrophage polarization. SCFAs can also upregulate Toll-like receptors, leading to chronic inflammation and the creation of a pro-prostate cancer environment. Dysbiosis of oral microbiota has been correlated with prostate infection and inflammation. Additionally, pathogenic microbiomes associated with urinary tract infections have shown a link to prostate cancer, with vesicoureteral reflux potentially contributing to prostate infection. This review offers a comprehensive understanding of the impact of microbial infections linked to intraprostatic inflammation as a causative factor for prostate cancer. Further studies involving the manipulation of the microbiome and its produced metabolites may provide a more complete understanding of the microenvironmental mechanisms that promote prostate carcinogenesis.

Association between prostatic 18F-FDG uptake and lower urinary tract symptoms assessed by International Prostate Symptom Score.

PURPOSE Inflammation is known to induce prostatic growth and lower urinary tract symptoms (LUTS) progression in patients with benign prostatic hyperplasia (BPH), but clinical indicators for intraprostatic inflammation other than biopsy have not yet been established. While 2-deoxy- 2-[18F]fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) is a useful tool for investigating inflammatory conditions, prostatic FDG uptake in patients with BPH has not been elucidated. Therefore, we evaluated the association between prostatic FDG uptake and LUTS. METHODS A total of 391 men in their 50s who underwent FDG PET/CT during health examinations were included. Mean and maximal prostatic standard uptake values (SUVs) on FDG PET/CT were measured. Prostatic volume, focal FDG uptake, and calcification were also evaluated. The International Prostate Symptom Score (IPSS) for LUTS was collected at baseline and follow- ups. The correlation between IPSS and other variables was analyzed. RESULTS The mean age of the study participants was 51.7 years, and the mean follow-up interval was 39.7 months. The average of the mean and maximal SUV for prostatic FDG uptake was 1.8 and 2.6, respectively. The prostate volume was 18.5 cm3. The mean IPSS was 4.82 at baseline and 5.46 at follow-ups. Neither the mean SUV nor the maximal SUV of prostatic FDG uptake was correlated with IPSS at baseline or follow-ups. Conversely, prostate volume was associated with baseline IPSS and follow-up IPSS. CONCLUSION Prostatic FDG uptake did not show a significant association with IPSS on FDG PET/CT as well as at follow-ups. FDG uptake may not reflect prostatic growth in nonmalignant cases.

Presence of Specific Periodontal Pathogens in Prostate Gland Diagnosed With Chronic Inflammation and Adenocarcinoma.

BackgroundIntraprostatic inflammation is frequently observed in the prostate and linked to prostatic diseases, including prostatitis, benign prostatic hyperplasia (BPH), and cancer. The etiology of prostate diseases is unclear. Periodontal diseases are associated with an increased risk of prostate diseases. In men, chronic prostatitis and moderate/severe periodontitis have significantly elevated serum prostate-specific antigen (PSA) levels. Treatment of periodontal disease reduced PSA levels in men. The presence of periodontal pathogens deoxyribonucleic acid (DNA) was identified in the prostate fluid of prostatitis patients. These pathogenic bacteria might have the potential to trigger prostatitis progressing to prostatic adenocarcinoma. The mechanism(s) explaining the etiology of association between periodontal disease and prostate cancer remains unclear. However, the presence of periodontal pathogens has not been analyzed in the prostate gland.ObjectiveTo identify and compare the presence of specific periodontal pathogens in the areas of BPH, inflammation, and cancer of the prostate glands diagnosed with malignancy.Materials and methodsWhole-mount radical prostatectomy sections from men (n=30) were identified for BPH, inflammation, and cancer areas and marked for tissue procurement. The tissues were subjected to DNA isolation and analysis of microbial DNA and total bacterial load for the following pathogens, including Porphyromonas gingivalis strain ATCC 33277, Prevotella intermedia strain B422, Treponema denticola strain 35405, Fusobacterium nucleatum subsp. fusiform strain, Tannerella forsythia strain ATCC 43037, and Campylobacter​​​​​​​ rectus strain ATCC 33238performed real-time PCR. The universal bacterial primer pairs were used to detect genomic DNA (gDNA) from the total bacteria present in the samples. All species-specific primers were designed to target the variable regions of the 16S ribosomal RNA (rRNA). Data were analyzed using the 2-ΔΔCT method, statistically validated using unpaired t-test and ANOVA test.ResultsA total of 90 samples of prostate tissue specimens were analyzed for periodontal pathogens; only one pathogen (F. nucleatum subsp. fusiform strain ATCC 51190) showed a significant difference compared to the expression of S. epidermidis (internal control). In particular, F. nucleatum expression was 9, 11.9, and 10.3-fold higher in BPH, inflammation, and cancer, respectively, at p-value <0.05. Moreover, the bacterial load abundance/expression was almost similar in BPH (46.8-fold), inflammation (40.9 fold), and cancer (41.5 fold) higher. There was no significant difference in bacterial load (folder change) among the three areas of BPH, inflammation, and cancer (p-valve>0.05). Similarly, there was no significant difference between F. nucleatum (folder change) among the three areas (p-valve>0.05).Conclusion Fusobacterium nucleatum is identified in the prostates that harbor cancer, chronic inflammation, and BPH.

PSA Density Help to Identify Patients With Elevated PSA Due to Prostate Cancer Rather Than Intraprostatic Inflammation: A Prospective Single Center Study.

The association between PSA density, prostate cancer (PCa) and BPH is well established. The aim of the present study was to establish whether PSA density can be used as a reliable parameter to predict csPCa and to determine its optimal cutoff to exclude increased PSA levels due to intraprostatic inflammation. This is a large prospective single-center, observational study evaluating the role of PSA density in the discrimination between intraprostatic inflammation and clinically significant PCa (csPCa). Patients with PSA ≥ 4 ng/ml and/or positive digito-rectal examination (DRE) and scheduled for prostate biopsy were enrolled. Prostatic inflammation (PI) was assessed and graded using the Irani Scores. Multivariable binary logistic regression analysis was used to assess if PSA density was associated with clinically significant PCa (csPCa) rather than prostatic inflammation. A total of 1988 patients met the inclusion criteria. Any PCa and csPCa rates were 47% and 24% respectively. In the group without csPCa, patients with prostatic inflammation had a higher PSA (6.0 vs 5.0 ng/ml; p=0.0003), higher prostate volume (58 vs 52 cc; p<0.0001), were more likely to have a previous negative biopsy (29% vs 21%; p=0.0005) and a negative DRE (70% vs 65%; p=0.023) but no difference in PSA density (0.1 vs 0.11; p=0.2). Conversely in the group with csPCa, patients with prostatic inflammation had a higher prostate volume (43 vs 40 cc; p=0.007) but no difference in the other clinical parameters. At multivariable analysis adjusting for age, biopsy history, DRE and prostate volume, PSA density emerged as a strong predictor of csPCA but was not associated with prostatic inflammation. The optimal cutoffs of PSA density to diagnose csPCa and rule out the presence of prostatic inflammation in patients with an elevated PSA (>4 ng/ml) were 0.10 ng/ml2 in biopsy naïve patients and 0.15 ng/ml2 in patients with a previous negative biopsy. PSA density rather than PSA, should be used to evaluate patients at risk of prostate cancer who may need additional testing or prostate biopsy. This readily available parameter can potentially identify men who do not have PCa but have an elevated PSA secondary to benign conditions.

Immunological alterations in patients with chronic prostatitis/chronic pelvic pain syndrome and experimental autoimmune prostatitis model: A systematic review and meta-analysis

BackgroundAs one of the most common conditions in urological outpatients, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) puzzles many individuals because of its unclear etiology and lack of effective treatment. Recently, immunological alterations underpinning CP/CPPS have been extensively investigated. MethodsThe PubMed, Web of Science, Cochrane library, and EMBASE databases were used to search original articles on immune mediators in patients with CP/CPPS and in experimental autoimmune prostatitis (EAP) models through April 10, 2020. Standardized mean differences (SMD) were calculated to summarize the differences in immune mediator levels between groups. Funnel plot, Begg’s funnel plot, Egger’s regression test, and the sensitivity analysis were applied to determine and visualize the stability of our findings. ResultsA total of 34 original studies were included in the meta-analysis, including 24 studies on patients with CP/CPPS and 10 studies on EAP models. We found that TNF-α, IL-1β, IL-6, and IL-8 were the four immune mediators that elevated in most of the samples derived from patients with CP/CPPS and the EAP models. The adjusted publication bias analysis indicated that publication bias was not existed, and the sensitivity analyses showed that the results were stable. ConclusionsImmune responses play significant roles during the pathogenesis of CP/CPPS by promoting intraprostatic inflammation. Our findings provide potential diagnostic and therapeutic targets for CP/CPPS patients.

Why Do Epidemiologic Studies Find an Inverse Association Between Intraprostatic Inflammation and Prostate Cancer: A Possible Role for Colliding Bias?

Inflammation is an emerging risk factor for prostate cancer based largely on evidence from animal models and histopathologic observations. However, findings from patho-epidemiologic studies of intraprostatic inflammation and prostate cancer have been less supportive, with inverse associations observed in many studies of intraprostatic inflammation and prostate cancer diagnosis. Here, we propose collider stratification bias as a potential methodologic explanation for these inverse findings and provide strategies for conducting future etiologic studies of intraprostatic inflammation and prostate cancer.

Association of Serum Carotenoids and Retinoids with Intraprostatic Inflammation in Men without Prostate Cancer or Clinical Indication for Biopsy in the Placebo Arm of the Prostate Cancer Prevention Trial

Non-supplemental carotenoids and retinol may potentiate antioxidant and anti-inflammatory mechanisms. Chronic intraprostatic inflammation is linked to prostate carcinogenesis. We investigated the association of circulating carotenoids and retinol with intraprostatic inflammation in benign tissue. We included 235 men from the Prostate Cancer Prevention Trial placebo arm who had a negative end-of-study biopsy, most (92.8%) done without clinical indication. α-carotene, β-carotene, β-cryptoxanthin, lycopene, and retinol were assessed by high-performance liquid chromatography using pooled year 1 and 4 serum. Presence and extent of intraprostatic inflammation in benign tissue was assessed in 3 (of 6–10) biopsy cores. Logistic (any core with inflammation vs none) and polytomous logistic (some or all cores with inflammation vs none) regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of intraprostatic inflammation by concentration tertile adjusting for age, race, prostate cancer family history, and serum cholesterol. None of the carotenoids or retinol was associated with intraprostatic inflammation, except β-cryptoxanthin, which appeared to be positively associated with any core with inflammation [vs none, T2: OR (95% CI) = 2.67 (1.19, 5.99); T3: 1.80 (0.84, 3.82), P-trend = 0.12]. These findings suggest that common circulating carotenoids and retinol are not useful dietary intervention targets for preventing prostate cancer via modulating intraprostatic inflammation.

SC114 - PSA density help to identify patients with elevated PSA due to prostate cancer rather than intraprostatic inflammation: a prospective single-center study

SC114 - PSA density help to identify patients with elevated PSA due to prostate cancer rather than intraprostatic inflammation: a prospective single-center study

Prostate carcinogenesis: inflammatory storms.

Prostate cancer is a major cause of cancer morbidity and mortality. Intra-prostatic inflammation is a risk factor for prostate carcinogenesis, with diet, chemical injury and an altered microbiome being causally implicated. Intra-prostatic inflammatory cell recruitment and expansion can ultimately promote DNA double-strand breaks and androgen receptor activation in prostate epithelial cells. The activation of the senescence-associated secretory phenotype fuels further 'inflammatory storms', with free radicals leading to further DNA damage. This drives the overexpression of DNA repair and tumour suppressor genes, rendering these genes susceptible to mutagenic insults, with carcinogenesis accelerated by germline DNA repair gene defects. We provide updates on recent advances in elucidating prostate carcinogenesis and explore novel therapeutic and prevention strategies harnessing these discoveries.

The association between serum sex steroid hormone concentrations and intraprostatic inflammation in men without prostate cancer and irrespective of clinical indication for biopsy in the placebo arm of the Prostate Cancer Prevention Trial.

Intraprostatic inflammation is an emerging prostate cancer risk factor. Estrogens are pro-inflammatory while androgens are anti-inflammatory. Thus, we investigated whether serum sex steroid hormone concentrations are associated with intraprostatic inflammation to inform mechanistic links among hormones, inflammation, and prostate cancer. We conducted a cross-sectional study among 247 men in the placebo arm of the Prostate Cancer Prevention Trial who had a negative end-of-study biopsy, most (92.7%) performed without clinical indication per trial protocol. Serum estradiol, estrone, and testosterone were previously measured by immunoassay in pooled baseline and Year 3 serum. Free estradiol and free testosterone were calculated. Inflammation was visually assessed (median of three prostate biopsy cores per man). Polytomous or logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of some or all cores inflamed (both vs none) or any core inflamed (vs none) by hormone tertile, adjusting for age, race, and family history. We evaluated effect modification by waist circumference and body mass index (BMI). In all, 51.4% had some and 26.3% had all cores inflamed. Free (P-trend = .11) but not total estradiol was suggestively inversely associated with all cores inflamed. In men with waist circumference greater than or equal to 102 cm (P-trend = .021) and BMI ≥ 27.09 kg/m2 (P-trend = .0037) free estradiol was inversely associated with any core inflamed. Estrone was inversely associated with all cores inflamed (T3: OR = 0.36, 95% CI 0.14-0.95, P-trend = .036). Total (T3: OR = 1.91, 95% CI 0.91-4.02, P-trend = .11) and free (T3: OR = 2.19, 95% CI 1.01-4.74, P-trend = .05) testosterone were positively associated with any core inflamed, especially free testosterone in men with waist circumference less than 102 cm (T3: OR = 3.51, 95% CI 1.03-12.11, P-trend = .05). In this first study in men without prostate cancer and irrespective of clinical indication for biopsy, contrary to the hypothesis, circulating estrogens appeared to be inversely associated, especially in heavy men, whereas androgens appeared to be positively associated with intraprostatic inflammation.

A Prospective Study of Intraprostatic Inflammation, Focal Atrophy, and Progression to Lethal Prostate Cancer.

Inflammation and focal atrophy are common features adjacent to prostate tumors. Limited evidence exists on whether these features have prognostic significance. In the Health Professionals Follow-Up Study and Physicians' Health Study, we studied 1,035 men diagnosed with prostate cancer. A genitourinary pathologist centrally reviewed tumor and normal areas of hematoxylin and eosin slides from prostate cancer specimens for the presence of acute and chronic inflammation, and four subtypes of focal atrophy. Cox proportional hazards models adjusted for potential confounders were used to estimate HRs and 95% confidence intervals (CI) for the association of these features with lethal prostate cancer, defined as development of metastatic disease or death during follow-up. During a median of 12 years of follow-up, 153 men developed lethal prostate cancer. A total of 84% of men had histologic evidence of chronic inflammation and 30% had acute inflammation. Both chronic and acute inflammation were inversely associated with lethal prostate cancer in age- and lifestyle-adjusted models. Chronic inflammation remained inversely associated with lethal prostate cancer after additionally adjusting for prognostic clinical features (HR = 0.45; 95% CI, 0.30-0.69 for mild and HR = 0.51; 95% CI, 0.33-0.80 for moderate to severe). None of the atrophic lesions were associated with lethal prostate cancer. Our data suggest that the presence of inflammation, particularly chronic inflammation, in prostate cancer tissue is associated with better prognosis among patients with prostate cancer. This is the largest prospective cohort study to examine the association between inflammation, focal atrophy, and lethal prostate cancer.

Is there a correlation between the aggressiveness of chronic asymptomatic prostatitis National Institutes of Health category IV and the Gleason score in patients with prostate cancer?

We evaluated the correlation between the International Society of Urological Pathology (ISUP) grades and the aggressiveness grades of prostate inflammation in newly diagnosed prostate cancer patients with chronic asymptomatic prostatitis National Institiutes of Health (NIH) category IV (CAPNIHIV). The study comprised 357 consecutive patients with prostate cancer in whom a cancer diagnosis had been made via a prostate needle biopsy. Histological sections of the prostate biopsy specimens of the patients were reviewed and scored. Prostatic inflammation was scored using the aggressiveness grade of inflammation. The associations between the ISUP grades and the aggressiveness grades of inflammation were analyzed using logistic regression. The limitations of the study were its retrospective design and the limited number of cases. In 110 (31%) patients, CAPNIHIV was detected: 56 (51%) patients had a grade 0 aggressiveness score, 34 (31%) patients had a grade 1 aggressiveness score, and 20 (18%) patients had a grade 2 aggressiveness score. The patients who had prostatic inflammation had 1.65 times (95% confidence interval [CI] 1.05-2.61) greater likelihood of a high ISUP grade (grade ≥3) compared with the patients who did not have prostatic inflammation. The association between the ISUP grade and the aggressiveness grade of inflammation was more pronounced for a grade 2 aggressiveness score (n= 20; odds ratio 2.97; 95% CI 1.14-7.71). In prostate cancer patients with CAPNIHIV, there was a positive correlation between the inflammation aggressiveness grade and the ISUP grade. The aggressiveness of intraprostatic inflammation may be an important morphological factor affecting the Gleason score.

Abstract 3293: Serum and intraprostatic lipidome level shift during statin use among prostate cancer patients

Abstract Prostate cancer patients using cholesterol-lowering statins have 30 % lower risk of prostate cancer death compared to non-users. The effect is attributed to the inhibition of the mevalonate pathway which is active in prostate cancer cells. Statin intervention also causes lipidome level shift in the serum. However, it is unknown whether statin intervention also affects intraprostatic lipidome (IPL) as well. We studied the lipidome level shift among Finnish males diagnosed with prostate cancer and scheduled for radical prostatectomy in a randomized, placebo-controlled double-blind clinical trial. Total number of participants was 86 where 41 were given placebo and 45 were treated daily with 80 mg of atorvastatin (AS) for a median of 27 days preceeding the surgery. The serum lipidome (SL) level was measured before and after the intervention using mass spectrometer, whereas the IPL level was measured after the surgery. SL contains 213 lipid aggregates, while the IPL contains 4,652 single-molecule lipids. Furthermore, we investigated if the baseline lipidome level or the shift during intervention displays relationship with tumor Gleason grade, PSA level, Ki67 proliferation marker level in the tissue, and / or intraprostatic inflammation. The relationship was studied using supervised random forest classification (RFC), and linear regression (LR) adjusted for age and body mass index. RFC robustness with respect to the intrinsic randomization was measured by repeating RFC 100 times. The 4,652 IPL molecules were reduced to 101 after limiting analysis to ones demonstrating statistically significant difference between placebo and AS group. The statistically significant difference was tested with t-test and Mann-Whitney test depending on the sample distribution. The SL difference before-after intervention separates the two groups with extremely low RFC error of 8.1 – 9.3 %. This indicates that the intervention has systematically altered the SL. The RFC error for the IPL was 29 – 37.7 % and does not separate the placebo and AS group as well as in the serum. Thus, the AS effect on IPL is not as strong as in the serum, although a suggestion of differing lipid profiles by treatment arm was observed. One serum lipid, Glycoproteinacetylsmainlya1acidglycoprotein (GP), did show a clear linear relationship with the PSA level change; however, it was independent of the AS intervention. Baseline SL did not predict high-grade prostate cancer, Ki67 level, or inflammation level in general, according to RFC or LR. AS intervention displays a clear effect on SL level, but only a modest effect on the IPL. Our finding suggests the AS affects the lipids in the prostate as well. GP serum lipid aggregate shows linear relationship with the PSA level change but it is independent of AS intervention. IPL does not correlate with the tumor Gleason grade or Ki-67 proliferation activity. Citation Format: Paavo V. Raittinen, Kati Niemistö, Seppo Auriola, Pauliina Ilmonen, Teemu J. Murtola. Serum and intraprostatic lipidome level shift during statin use among prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3293.

Serum Urate, Genetic Variation, and Prostate Cancer Risk: Atherosclerosis Risk in Communities (ARIC) Study.

Evidence is mounting that intraprostatic inflammation influences prostate cancer development. Uric acid crystals depositing in the prostate could result in injury and inflammation, increasing prostate cancer risk. Included were 6,574 men ages 45-64 years who enrolled in the Atherosclerosis Risk in Communities study in 1987 to 1989. We used Cox proportional hazards regression to estimate the association of serum urate concentration alone and to improve accuracy, jointly with a genetic risk score (GRS, N = 4,983) derived from variants predictive of urate concentration, with prostate cancer (N = 813) risk. Serum urate concentration or joint categories of urate concentration and GRS were not associated with prostate cancer risk (P trend for quartiles = 0.3). Results were generally similar by race and after excluding users of medications that influence uric acid. Serum urate alone and with a urate-associated GRS were not associated with prostate cancer risk. It is unlikely that circulating urate concentration influences prostate cancer development.

MP06-02 SELECTIVE ESTROGEN RECEPTOR MODULATOR CAN IMPROVE BENIGN PROSTATIC HYPERPLASIA IN HIGH FAT INDUCED OBESITY RAT MODEL

INTRODUCTION AND OBJECTIVES:Central obesity is known to be involved in benign prostatic hyperplasia (BPH). Some study reports that increased fat tissue induces chronic intra-prostatic inflammation ...

Mycoplasma genitalium Infection and Chronic Inflammation in Human Prostate Cancer: Detection Using Prostatectomy and Needle Biopsy Specimens.

The evidence of association between sexually transmitted infection and prostatic inflammation in human prostate cancer (PCa) is limited. Here, we sought to examine the potential association of prostatic infection with the inflammatory environment and prostate carcinogenesis. We screened surgical and biopsy specimens from 45 patients with PCa against a panel of sexually transmitted infection-related organisms using polymerase chain reaction and examined the severity of intraprostatic inflammation by pathologic examination. Among tested organisms, the rate of Mycoplasma genitalium (Mg) infection was significantly different between the prostate cancer cohort and benign prostate hyperplasia (BPH) cohort (P = 0.03). Mg infection in the surgical specimens was associated with younger patients. The rate of extensive disease (pT2c–3b) was higher in Mg-positive patients than in Mg-negative patients (P = 0.027). No significant correlation was observed between Mg infection status and the grade of intraprostatic inflammation. The detection sensitivity of biopsy specimens was 61% for Mg and 60% for human papillomavirus (HPV)18, indicating possible clinical application of this material. A comprehensive understanding of the correlation between the urogenital microbiome and inflammation would facilitate the development of strategies for PCa prevention. Further studies are required to explore its clinical utility in recommendations of early re-biopsy, close follow-up, and treatment by antibiotics.

Atorvastatin Versus Placebo for Prostate Cancer Before Radical Prostatectomy—A Randomized, Double-blind, Placebo-controlled Clinical Trial

We tested whether intervention with atorvastatin affects the prostate beneficially compared with placebo in men with prostate cancer in a randomized clinical trial. A total of 160 statin-naïve prostate cancer patients scheduled for radical prostatectomy were randomized to use 80mg atorvastatin or placebo daily from recruitment to surgery for a median of 27 d. Blinding was maintained throughout the trial. In total, 158 men completed the follow-up, with 96% compliance. Overall, atorvastatin did not significantly lower tumor proliferation index Ki-67 or serum prostate-specific antigen (PSA) compared with placebo. In subgroup analyses, after a minimum of 28 d of atorvastatin use, Ki-67 was 14.1% lower compared with placebo (p = 0.056). Among high-grade cases (International Society of Urological Pathology Gleason grade 3 or higher), atorvastatin lowered PSA compared with placebo: median change –0.6 ng/ml; p = 0.024. Intraprostatic inflammation did not differ between the study arms (p = 0.8). Despite a negative overall result showing no effect of statins on Ki67 or PSA overall, in post hoc exploratory analyses, there appeared to be benefit after a minimum duration of 28 d. Further studies are needed to verify this. Patient summaryCholesterol-lowering atorvastatin does not lower prostate cancer proliferation rate compared with placebo overall, but exploratory analyses suggest a benefit in longer exposure.

Benign prostatic hyperplasia and intraprostatic inflammation are associated with liver inflammation: it's time for prevention.

Some evidences have supported the link between benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS) and inflammation. In this study, we aimed to evaluate the association between prostatic inflammation (PI) and non-alcoholic steatohepatitis (NASH) evaluated by a non-invasive scores in a cohort of patients affected by BPH/LUTS. Between January 2012 and January 2016, we conducted a prospective study in a single academic outpatient clinic on 132 consecutive patients who underwent surgery for lower urinary tract symptoms (LUTS) due to bladder outlet obstruction (BOO). A non-invasive non-alcoholic steatohepatitis score (NASH score) was calculated, and PI was evaluated through the Irani score. Patients with a NASH score>1.05 had an average larger prostate volume (55 vs. 45cc, p<0.05), a greater waist circumference (103 vs. 93.5cm, p<0.01), and high values of blood glucose, triglycerides, insulin, and BMI compared to patients without NASH; 36% of patients with an Irani score≥4 had NASH compared to 16.1% of patients who had a NASH score<1.05 (p<0.05). We found that non-alcoholic steatohepatitis (NASH≥1.05) was an independent risk factor for Irani score ≥4 (OR: 3.24; p<0.05) and of prostate volume ≥ 40cc (OR: 13.99; p<0.01). LUTS/BPH and NASH can be closely related, underlying common triggers of induction. In particular, inflammation seems to be associated with both conditions and with prostate gland overgrowth. Early identification of this class of patients could play a key role in preventing complications related to disease progression.

Metabolic syndrome is not associated with greater evidences of proliferative inflammatory atrophy and inflammation in patients with suspected prostate cancer

Introduction and objectivesTo evaluate the association between metabolic syndrome (MetS) and proliferative inflammatory atrophy (PIA) in patients with suspected prostate cancer (PCa). Patients and methodsFrom June 2015 to July 2016, we conducted the FIERY (Flogosis Increased Events of pRostatic biopsY) study at the Urology section, Department of Surgery of the University of Catania (Local registration number: #131/2015).A total of 205 patients with elevated prostate-specific antigen (≥ 4 ng/ml) or clinical suspicion of PCa who underwent primary transperineal prostate biopsy were included in this cross-sectional study.The assessment of PIA, HGPIN, and PCa were performed by 2 experienced pathologists and samples were investigated for the presence of an inflammatory infiltrate, according to the Irani score. Primary and secondary Gleason grade of tumor in positive biopsies were evaluated according to the 2016 ISUP Modified Gleason System. ResultsIn the entire cohort, median age was 68.0 (interquartile range: 62.0–74.5), median prostate-specific antigen was 6.5 (interquartile range: 5.51–9.57). The prevalence of MetS was 34.1%, the detection rate of PCa was 32.7%, the rate of PIA was 28.3%, the rate of HGPIN was 32.2%, whereas the rate of severe intraprostatic inflammation (Irani-score ≥4) was 28.8%.When comparing clinical and histological variables in patients without and with PIA, metabolic aberrations where not significantly different in both groups. We did not find statistical association in detection rate of PCa (29.3% vs. 34.0%; P = 0.07) and HGPIN (27.6% vs. 34.0%; P = 0.37) in patients with and without PIA, respectively. When considering metabolic aberrations, MetS was not associated with Irani-score ≥4 (28.6% vs. 28.4%; P = 0.96) and none of each component was statistically predictive of severe inflammation.At the multivariable logistic regression analysis, PIA, HGPIN, and MetS were not associated with greater risk of PCa. ConclusionIn this study, we did not show an association between MetS and PIA and PCa. Although the small sample size and the cross-sectional nature of the study, we do not suppose that MetS could be associated with greater evidence of PIA. Further studies should be conducted to evaluate the exact nature of this pathological lesion.

Associations of Transitional Zone Volume with Intraprostatic Chronic Inflammation and Prostate Cancer Risk in Patients Undergoing a First Random Biopsy Set

Objectives: To investigate associations of the transitional zone volume (TZV) with intraprostatic chronic inflammatory infiltrate (CII) and prostate cancer (PCa) risk in patients undergoing a first random biopsy set. Materials and Methods: The study included a homogenous population of 596 patients. The volume of the prostate and TZV were separately measured. Independent associations were investigated by multivariate logistic regression analysis. Results: The median TZV was 18 ml, CII was detected in 157 cases (26.3%), and PCa was present in 292 patients (49%). TZV was the only independent clinical factor associated with CII risk (OR = 1.014). After correcting for CII (OR = 0.276; p < 0.0001), independent factors associated with PCa risk included age (OR = 1.066), prostate specific antigen (OR = 1.177), TZV (OR = 0.919), and an abnormal digital rectal exam (OR = 2.024). Conclusion: In a patient population undergoing a first random prostate biopsy set because of suspected cancer, independent associations were detected among TZV, CII, and PCa. The association between TZV and CII was direct, but the relation between TZV and PCa was inverse. The measurement of the volume of the transitional zone was a useful parameter for evaluating chronic intraprostatic inflammation and PCa risk.