The role of prostate-specific antigen and multiparametric magnetic resonance imaging in the diagnosis of granulomatous prostatitis induced by intravesical Bacillus Calmette-Guérin vaccine therapy in patients with nonmuscle invasive bladder cancer.

AIMS: This study aimed to evaluate the role of serum prostate-specific antigen (PSA) levels and multiparametric magnetic resonance imaging (mpMRI) in the diagnosis of granulomatous prostatitis (GP) induced by intravesical Bacillus Calmette-Guérin vaccine (BCG) therapy in patients with nonmuscle invasive bladder cancer (NMIBC). SUBJECTS AND METHODS: We retrospectively analyzed eight patients with bladder cancer who underwent intravesical BCG therapy after transurethral resection of bladder tumor (TURBt) cancer. All these eight patients received 12-core transrectal ultrasound-guided prostate systemic biopsies. Clinical data on PSA with T1-weighted imaging (T1WI), T2WI, diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) on mpMRI were enrolled in the study. H and E and acid-fast staining was performed to pathologically prove GP. RESULTS: Four of all eight cases were above 4 ng/ml total PSA (tPSA) levels and four cases were within normal ranges, while free PSA/tPSA levels decreased to lower than 16% in all patients. Every patient had hard prostatic nodules through digital rectal examination (DRE). All characters of prostate mpMRI did not show signal intensity (SI) of prostate cancer before BCG therapy but showed abnormal signals after BCG therapy. All nodular lesions showed equal SI on T1WI, lower SI on T2WI, higher SI on DWI, and lower SI on ADC after BCG therapy. Pathologic results were GP and acid-fast staining outcomes were positive in all biopsies. CONCLUSIONS: Perioperative serum PSA levels, prostate magnetic resonance imaging, and DRE may help in the diagnosis of GP induced by intravesical BCG therapy. In general, male patients with middle- and high-risk NMIBC are recommended to undertake DRE, PSA, and prostate mpMRI, if possible, before and after TURBt."

T2 Peptide Represents a Major Autoantigen Epitope in Experimental Autoimmune Prostatitis.

Chronic prostatitis/chronic pelvic pain syndromes (CP/CPPS) is a clinical tricky problem due to its enigmatic etiology, low cure rate, and high recurrence rate. The research on its pathogenesis has never stopped. In this experimental autoimmune prostatitis (EAP) model, male C57BL/6 mice were subcutaneously immunized with prostate extracts in an adequate adjuvant. For mice in the antibody intervention group, anti-T2 polyclonal antibodies were intraperitoneally injected during the induction of EAP. Animals were periodically monitored for pelvic pain. Hematoxylin and eosin staining was used to assess prostate inflammation. Tumor necrosis factor-α (TNF-α) levels in serum were measured by ELISA kits. The immunized animals developed prostatitis as a consequence of the immune response against prostate antigens. Pelvic pain thresholds were gradually decreased and TNF-α expression significantly increased. T2 plays an important role in the disease since polyclonal antibodies to T2 greatly ameliorated symptoms in animals induced for EAP. T2 peptide may represent the major autoantigen epitope in EAP, which could serve for a better understanding of the etiology of CP/CPPS.

Serum Levels of miR-223-3p and miR-223-5p in Prostate Diseases.

INTRODUCTION: Prostate Cancer (PCa) is the second most common cancer in males and the fifth in cancer-associated mortality. Although the Prostate-Specific Antigen (PSA) test is widely used in PCa screenings, it has significant limitations in the differential diagnosis of PCa. Therefore, studies on developing new biomarkers for PCa diagnosis are ongoing. MiRNAs are good candidate biomarkers for the diagnosis of cancers, including prostate cancer, as they can be easily detected from circulation. OBJECTIVE: In this study, it is aimed to determine the diagnostic value of serum levels of miR-223-3p and -223-5p in Benign Prostate Hyperplasia (BPH), Chronic Prostatitis (CP) and Prostate Cancer (PCa). METHODS: Serum samples were collected from 68 patients in total (25 BPH, 10 CP, 33 PCa). MiR-223- 3p and -223-5p levels were measured in serum with qRT-PCR. The Ct values of miRNAs were normalized according to the Ct value of ce-miR-39 and calculated -ΔCt values were used for statistical analyses. RESULTS: The serum levels of miR-223-3p and -223-5p were downregulated in the PCa and CP groups, compared to the BPH group. There was no statistically significant difference between PCa and CP groups. The sensitivity and specificity of miR-223-3p, -223-5p and their combination were calculated as 88% and 88%; 86% and 79%; 93% and 92% in discriminating BPH and PCa groups, respectively. CONCLUSION: In this study, it was shown that miR-223-3p and -223-5p were both detectable in circulation. miR-223-3p, -223-5p, and their combination may be good candidate biomarkers for prostate cancer diagnosis. Also, observation of similar serum levels of miR-223-3p and -223-5p between CP and PCa groups suggests that miR-223 may play a role in prostate cancer development originated from chronic inflammation.

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.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Patients with chronic prostatitis/chronic pelvic pain syndrome show T helper type 1 (Th1) and Th17 self-reactive immune responses specific to prostate and seminal antigens and diminished semen quality.

OBJECTIVES: To assess the presence of self-reactive immune responses to seminal and prostate antigens (PAg), biomarkers of inflammation of the male genital tract, and semen quality parameters in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). PATIENTS, SUBJECTS AND METHODS: Peripheral blood and semen samples were collected from patients with CP/CPPS and age-matched healthy control volunteers. We analysed the lymphoproliferative responses of peripheral blood mononuclear cells (PBMC) to different seminal plasma (SP)-derived and purified PAg, serum autoantibodies specific to PAg, leucocyte subpopulations, and inflammatory cytokines in semen, sperm apoptosis/necrosis, and semen quality parameters. RESULTS: Significantly greater PBMC proliferative responses specific to PAg, with elevated secretion of interferon (IFN)γ and interleukin (IL)-17, were detected in the patients with CP/CPPS vs the controls. Moreover, the patients with CP/CPPS had significantly greater serum immunoglobulin G immune reactivity to SP proteins, such as prostate-specific antigen and prostatic acid phosphatase, than the controls. Inflammation of the male genital tract was exemplified by high levels of IFNγ, IL-17, IL-1ß and IL-8, as well as higher counts of leukocytes, mainly CD4 T lymphocytes and macrophages, in the semen. In addition, this local inflammation was associated with an overall diminished semen quality, i.e., reduced sperm concentration, motility and viability; and higher levels of sperm apoptosis/necrosis in patients with CP/CPPS vs controls. CONCLUSION: Patients with CP/CPPS show T helper type 1 (Th1) and Th17 immune responses specific to PAg associated with chronic inflammation of the male genital tract and reduced semen quality. These immune responses may underlie the induction and development of chronic pelvic pain and inflammation of the male genital tract, which in turn could alter normal prostate functioning and impair semen quality.

Free prostate-specific antigen outperforms total prostate-specific antigen as a predictor of prostate volume in patients without prostate cancer.

OBJECTIVE: In the management of benign prostatic hyperplasia (BPH), urology guide- lines recommend medical or surgical treatments according to different prostate volumes (PV). The aim of this study was to analyze the relationships between PV and age, total and free prostate specific antigen (tPSA, fPSA) and fPSA/tPSA ratio in patients without histologically proven prostate cancer. MATERIALS AND METHODS: A retrospective analysis was made of the data of 1334 patients who underwent transrectal ultra- sound (TRUS)-guided prostate biopsy between January 2016 and October 2018. A total of 438 patients with available data for age, tPSA and fPSA levels and PV calculated by TRUS were enrolled in the study. Patients with chronic prostatitis pathology in addition to BPH were also noted and evaluated as a separate group. RESULTS: There were significant correlations between PV and age, tPSA, fPSA, fPSA/tPSA ratio (r = 0.210, r = 0.338, r = 0.548, r = 0.363 respectively). In multivariate linear regression analysis, fPSA was found to be the only predictor for PV (p < 0.001) when compared to age (p = 0.097), tPSA (p = 0.979) and fPSA/tPSA ratio (p = 0.425). In patients with chronic prostatitis pathology there were significant correla- tions between PV and age, tPSA, fPSA, fPSA/tPSA ratio (r = 0.279, r = 0.379, r = 0.592, r = 0.359, respectively). The multivariate linear regression analysis showed a signifi- cant correlation only between PV and tPSA and fPSA/tPSA ratio but not with fPSA and age (p = 0.008, p = 0.015, p = 0.430, p = 0.484, respectively). In men with only BPH pathology there were significant correlations between PV and age, tPSA, fPSA, fPSA/tPSA ratio (r = 0.223, r = 0.385, r = 0.520, r = 0.287, respectively) In multivariate linear regression model the significant correlation was shown only between PV and fPSA (p < 0.001). CONCLUSIONS: Although tPSA was significantly correlated with PV in patients without prostate cancer, the correlation between fPSA and PV was much stronger. However, it should be kept in mind that the efficacy of fPSA may be limited in patients with clinically unknown prostatic inflammation.

Analysis of Prostate-Specific Antigen-Related Indexes, Neutrophil-to-Lymphocyte Ratio in Patients with Concurrent Benign Prostatic Hyperplasia and Histologic Prostatitis.

BACKGROUND: This study was performed to explore the total prostate-specific antigen (tPSA) concentration, free PSA (fPSA) concentration, free-to-total PSA ratio (% fPSA), tPSA density (tPSAD), and neutrophil-to-lymphocyte ratio (NLR) in blood in patients with concurrent benign prostatic hyperplasia (BPH) and histologic prostatitis, and to provide new ideas for the diagnosis of prostatitis. METHODS: Patients who underwent transurethral bipolar plasmakinetic prostatectomy from June 2017 to June 2018 were retrospectively divided into two groups according to the degree of pathological inflammation of the resected prostate tissue: group A (BPH with histologic acute and chronic inflammation), group B (BPH with histologic chronic inflammation). The preoperative PSA-related indexes and NLR in blood were respectively compared between two groups. RESULTS: Groups A and B comprised 59 and 41 cases, respectively. The values of tPSA, tPSAD, and NLR were all significantly higher in group A than B, and the value of % fPSA was significantly lower in group A than B (p < 0.05). There was no significant difference for the value of fPSA between the two groups (p > 0.05). CONCLUSIONS: Histologic acute prostatitis can cause changes of PSA-related indexes and NLR in blood, which has important clinical significance in diagnosis of prostatitis.

Clinical pharmacokinetics of flomoxef in prostate tissue and dosing considerations for prostatitis based on site-specific pharmacodynamic target attainment.

Flomoxef is used to treat bacterial prostatitis; however, its prostatic pharmacokinetics have not been fully clarified. Flomoxef (500 or 1000 mg) was administered to patients with benign prostatic hypertrophy (n = 54). After a 0.5-h infusion, venous blood samples were drawn at time points of 0.5-5 h, and prostate tissue samples were collected at time points of 0.5-1.5 h during transurethral resection of the prostate. The drug concentrations in plasma and prostate tissue were analyzed pharmacokinetically and used for a stochastic simulation to predict the probability of attaining pharmacodynamic target in prostate tissue. Showing dose linearity in the prostatic pharmacokinetics, flomoxef rapidly penetrated into prostate tissue, with a prostate/plasma ratio of 0.48-0.50 (maximum drug concentration) and 0.42-0.55 (area under the drug concentration-time curve). Against the tested populations of Escherichia coli, Klebsiella and Proteus species isolates, 0.5-h infusion of 1000 mg three times daily achieved a ≥90% expected probability of attaining the bactericidal target (70% of the time above the minimum inhibitory concentration [MIC]) in prostate tissue. The site-specific pharmacodynamic-based breakpoint (the highest MIC at which the target-attainment probability in prostate tissue was >90%) values were 0.25 mg/L (MIC for 90th percentile of E. coli and Klebsiella species) for 500 mg four times daily and 0.5 mg/L (MIC90 of Proteus species) for 1000 mg four times daily. These results help to fully characterize the prostatic pharmacokinetics of flomoxef, while also helping to rationalize and optimize the dosing regimens for prostatitis based on site-specific pharmacodynamic target attainment.

Prostate Volume Index Is Able to Differentiate between Prostatic Chronic Inflammation and Prostate Cancer in Patients with Normal Digital Rectal Examination and Prostate-Specific Antigen Values <10 ng/mL: Results of 564 Biopsy Naïve Cases.

INTRODUCTION: To assess the association of prostate volume index (PVI), defined as the ratio of the central transition zone volume to the peripheral zone volume, and prostatic chronic inflammation (PCI) as predictors of prostate cancer (PCA) risk in patients presenting with normal digital rectal exam and prostate-specific antigen (PSA) ≤10 ng/mL at baseline random biopsies. METHODS: We evaluated patients with a negative digital rectal examination (DRE) and a PSA ≤10 ng/mL who underwent initial baseline prostate biopsy from 2010 to 2017. Parameters evaluated included age, PSA, total prostate volume (TPV), PSA density (PSAD), PVI and PCI. All patients underwent 14 core trans-perineal standard biopsies. The association of factors with the risk of PCA was evaluated by logistic regression analysis, utilizing 2 multivariate models: model I included age, TPV, PVI and PCI; model II included age, PSAD, PVI and PC. RESULTS: Overall, 564 Caucasian patients were included. PCA and PCI were detected in 242 (42.9%) and 129 (22.9%) cases respectively. In patients with PCA, the median PVI was 0.83 (interquartile range [IQR] 0.62-1.04). In patients with PCI, the median PVI was 1.12 (IQR 0.81-1.47). In model I, age (OR 1.080) TPV (OR 0.961), PVI (OR 0.517) and PCI (OR 0.249) were associated with PCA risk. In model II, the age (OR 1.074), PSAD (OR 3.080), PVI (OR 0.361) and PCI (OR 0.221) were associated with PCA risk. CONCLUSIONS: Higher PVI and PCI predicted decreased PCA risk in patients presenting with normal DRE, and a PSA ≤10ng/mL at baseline random biopsy. In this subset of patients, PVI is able to differentiate patients with PCI or PCA.

A Systematic Review and Meta-analysis of Associations between Clinical Prostatitis and Prostate Cancer: New Estimates Accounting for Detection Bias.

BACKGROUND: Previous meta-analyses have estimated summary positive associations between clinical prostatitis and prostate cancer. However, none have accounted for detection bias, the possibility for increased prostate cancer screening and detection in men with clinical prostatitis, in their pooled estimates. METHODS: We searched for studies that investigated the relation between clinical prostatitis and prostate cancer through November 2018. Random effects meta-analysis was used to calculate summary odds ratios (OR) among all studies and in strata defined by methods used to reduce detection bias.Results: Although an increased odds of prostate cancer was seen among men with a history of clinical prostatitis in all 38 eligible studies combined [OR, 2.05; 95% confidence interval (CI), 1.64-2.57], this estimate attenuated to null among studies that performed the most rigorous analyses to limit detection bias (OR, 1.16; 95% CI, 0.77-1.74). CONCLUSIONS: Our findings indicate that previously reported positive associations between clinical prostatitis and prostate cancer are likely due to detection bias. IMPACT: Studies using rigorous detection bias methods are warranted to replicate these findings, as well as to examine the possible relation between prostate inflammation and prostate cancer directly, rather than indirectly through the diagnosis of "prostatitis," which includes a large proportion of men without evidence of prostate inflammation.

Serum C-reactive protein level is not associated with prostatic inflammation but with overactive detrusor in patients with benign prostatic hyperplasia.

AIM: Chronic prostatic inflammation is a critical factor that exacerbates lower urinary tract symptoms (LUTS). The serum C-reactive protein (CRP) level is one of the most common markers with which to assess the degree of inflammation, and it has been reported to be related to the severity of LUTS. However, it is not clear whether the CRP level is linked to the magnitude of prostatic inflammation. We evaluated the relationship between the serum CRP level and the magnitude of prostatic inflammation and assessed the influence of CRP on the severity of LUTS. METHODS: We evaluated the tissue specimens of 121 benign prostatic hyperplasia (BPH) patients who underwent surgery for BPH and preoperative measurement of the serum CRP level. We quantified the magnitude of prostatic inflammation histologically by determining the number of high endothelial venule (HEV)-like vessels and assessed the relationship between the serum CRP level and the HEV-like vessels. We divided the patients into two groups based on the median serum CRP level and compared the clinical parameters of the two groups. RESULTS: The serum CRP level was correlated with the overactive bladder symptom score, whereas it was not correlated with the number of HEV-like vessels. In filling cystometry and pressure-flow study, the proportion of patients with detrusor overactivity in the higher-CRP group was higher than that in the lower-CRP group. CONCLUSIONS: Our present study showed that the serum CRP level was significantly associated with storage dysfunction; in contrast, it was not a surrogate marker of prostatic inflammation.

Role of native thiol, total thiol and dynamic Disulphide in diagnosis of patient with prostate cancer and prostatitis

ABSTRACT Background: Our study investigates whether Native Thiol, Total Thiol and disulphide levels measured in serum of patients with prostate cancer and prostatitis and of healthy subjects, have any role in differential diagnosis. Materials and Methods: Patients followed up for histopathologically verified diagnosis of prostate cancer and prostatitis in 2016-2017 at the Medicalpark Gaziantep Hospital Urology Clinic were included in the study. Native Thiol (NT), Total Thiol (TT), Dynamic Disulphide (DD) levels in serum were measured by a novel automated method. Results: NT, TT, DD, NT / TT ratios, DD / TT ratio and DD / NT ratio were measured as 118.4 ± 36.8μmoL / L, 150.3 ± 45.3μmoL / L, 15.9 ± 7μmoL / L, 78.8 ± 7μmoL / L, 10.5 ± 3.5μmoL / L, 13.8 ± 5.8μmoL / L respectively in patients with prostate cancer; as 116.4 ± 40.5μmoL / L, 147.5 ± 50.1μmoL / L, 15.5 ± 8.7μmoL / L, 79.7 ± 9μmoL / L, 10.1 ± 4.5μmoL / L, 13.5 ± 7.2μmoL / L in patients with prostatitis and as 144.1 ± 21.2μmoL / L, 191 ± 32.3μmoL / L, 23.4 ± 10.1μmoL / L, 76.1 ± 98.3μmoL / L, 11.9 ± 4.1μmoL / L, 16.4 ± 6.9μmoL / L in healthy subjects. Significant difference was detected between groups of NT, TT and DD levels (p = 0.008, p = 0.001, p = 0.002). No significant difference was detected in terms of the NT / TT, DD / TT and DD / NT rates (p = 0.222, p = 0.222, p = 0.222). Conclusions: Serum NT, TT, DD levels in patients with prostatitis and prostate cancer were found significantly lower compared to the control group. This indicates that just as inflammation, prostate cancer also increases oxidative stress on tissues.

Role of native Thiol, total Thiol and dynamic Disulphide in diagnosis of patient with prostate cancer and prostatitis.

BACKGROUND: Our study investigates whether Native Thiol, Total Thiol and disulphide levels measured in serum of patients with prostate cancer and prostatitis and of healthy subjects, have any role in differential diagnosis. MATERIALS AND METHODS: Patients followed up for histopathologically verified diagnosis of prostate cancer and prostatitis in 2016-2017 at the Medicalpark Gaziantep Hospital Urology Clinic were included in the study. Native Thiol (NT), Total Thiol (TT), Dynamic Disulphide (DD) levels in serum were measured by a novel automated method. RESULTS: NT, TT, DD, NT / TT ratios, DD / TT ratio and DD / NT ratio were measured as 118.4 ± 36.8µmoL / L, 150.3 ± 45.3µmoL / L, 15.9 ± 7µmoL / L, 78.8 ± 7µmoL / L, 10.5 ± 3.5µmoL / L, 13.8 ± 5.8µmoL / L respectively in patients with prostate cancer; as 116.4 ± 40.5µmoL / L, 147.5 ± 50.1µmoL / L, 15.5 ± 8.7µmoL / L, 79.7 ± 9µmoL / L, 10.1 ± 4.5µmoL / L, 13.5 ± 7.2µmoL / L in patients with prostatitis and as 144.1 ± 21.2µmoL / L, 191 ± 32.3µmoL / L, 23.4 ± 10.1µmoL / L, 76.1 ± 98.3µmoL / L, 11.9 ± 4.1µmoL / L, 16.4 ± 6.9µmoL / L in healthy subjects. Significant difference was detected between groups of NT, TT and DD levels (p = 0.008, p = 0.001, p = 0.002). No significant difference was detected in terms of the NT / TT, DD / TT and DD / NT rates (p = 0.222, p = 0.222, p = 0.222). CONCLUSIONS: Serum NT, TT, DD levels in patients with prostatitis and prostate cancer were found significantly lower compared to the control group. This indicates that just as inflammation, prostate cancer also increases oxidative stress on tissues.

Both acute and chronic inflammation are associated with less perineural invasion in men with prostate cancer on repeat biopsy.

OBJECTIVES: To evaluate the association between acute and chronic inflammation with the presence of perineural invasion (PNI) in prostate biopsies positive for prostate cancer (PCa). MATERIAL AND METHODS: We conducted a retrospective analysis of 1 399 prostate biopsies positive for PCa in the Reduction by Dutasteride of PCa Events (REDUCE) study. PCa, acute and chronic prostate inflammation and PNI were assessed by central pathology review. The association between acute and chronic inflammation with PNI was evaluated using chi-squared and Kruskal-Wallis tests, and logistic regression adjusting for clinicopathological and biochemical variables. RESULTS: The presence of PNI was identified in 133 biopsies (9.5%). In all, 267 biopsies (19.1%) had acute inflammation, 1 038 (74.2%) had chronic inflammation, and 255 (18.2%) had both. The presence of both acute and chronic inflammation had a mutual association (P < 0.001). Chronic inflammation was associated with a lower Gleason score (P = 0.009) and lower tumour volume (P < 0.001), while acute inflammation was associated with lower Gleason score (P = 0.04), lower tumour volume (P = 0.004) and higher prostate-specific antigen levels (P = 0.05). In both univariable and multivariable analyses, chronic prostate inflammation was significantly associated with less PNI (univariable odds ratio [OR] 0.54, 95% confidence interval [CI] 0.37-0.79, P = 0.001; multivariable OR 0.65, 95% CI 0.43-0.99, P = 0.045). Acute prostate inflammation was associated with less PNI only in univariable analysis (univariable OR 0.51, 95% CI 0.29-0.89, P = 0.018; multivariable OR 0.63, 95% CI 0.35-1.13, P = 0.12). CONCLUSION: Acute and chronic prostate inflammation were both associated with a lower prevalence of PNI in prostate biopsies positive for PCa. If confirmed, this suggests that inflammation and immunomodulation can serve as areas of potential therapeutic design to mitigate PNI in patients with PCa.

Early diagnostic role of PSA combined miR-155 detection in prostate cancer.

OBJECTIVE: As a kind of malignant tumor in the male genitourinary system, prostate cancer exhibits significantly increased occurrence. Prostate-specific antigen (PSA) expression can be seen in the prostate cancer, prostatitis, and other diseases, therefore, lack of diagnostic specificity. The miR-155 expression is abnormally increased in the tumors. Therefore, this study aims to explore the clinical significance of PSA combined miR-155 detection in the early diagnosis of prostate cancer. PATIENTS AND METHODS: A total of 86 patients diagnosed with prostate cancer were enrolled in this study. PSA and miR-155 gene expression in tumor tissue were detected by using Real-time PCR. The serum levels of PSA were measured by using enzyme-linked immunosorbent assay (ELISA). The correlation of PSA and miR-155 expression with age, body mass index (BMI), tumor volume, tumor-node-metastasis (TNM) stage, lymph node metastasis (LNM), and other clinicopathological features were analyzed, respectively. RESULTS: Serum PSA expression and PSA gene in tumor tissue were significantly higher compared to that in adjacent tissues (p<0.05). PSA gene and protein increased significantly with the clinical stage of TNM and decreased following the increase of grade (p<0.05). The miR-155 level was significantly elevated in the tumor tissue compared with para-carcinoma tissue (p<0.05). PSA and miR-155 expressions were positively correlated with TNM stage, tumor volume, and LNM, and negatively correlated with grade (p<0.05). CONCLUSIONS: PSA and miR-155 were closely related to the clinicopathological features of prostate cancer. Combined detection is helpful for the early diagnosis of prostate cancer.

The Correlation of Prostate Volume and Prostate-specific Antigen Levels With Positive Bacterial Prostate Tissue Cultures.

OBJECTIVE: To compare prostate volume and prostate-specific antigen (PSA) levels with bacterial growth in prostate tissue cultures. MATERIALS AND METHODS: Fifty male patients who underwent transurethral prostate resection were investigated prospectively. Resection chips from the prostate gland were added to brain-heart infusion medium and incubated. PSA levels were determined preoperatively at our urology ward. The prostate gland volume was estimated by transabdominal ultrasound examination preoperatively. RESULTS: Persons with positive bacterial prostate tissue cultures have a greater prostate volume. This is significant in patients with and without histopathologic signs of prostatitis. Persons with positive bacterial prostate tissue cultures have higher PSA values. This is significant in patients without histopathologic signs of prostatitis. CONCLUSION: People with positive bacterial prostatic tissue culture have a higher prostate volume in comparison with patients with negative culture findings and show a tendency toward increased PSA levels as well.

Diagnostic and prognostic value of serum miR-15a and miR-16-1 expression among egyptian patients with prostate cancer.

Prostate cancer (PCa) is considered the most common malignancy in men. The aim of this study is to assess the role of serum miR-15a and miR-16-1 expression in PCa development, diagnosis and prognosis aiming to find a specific noninvasive biomarker. This study comprised 70 patients with PCa, 70 patients complaining of benign prostatic hyperplasia (BPH), 30 patients with chronic prostatitis and 70 controls. Circulating miR-15a and miR-16-1 expression was detected by real-time polymerase chain reaction. Prostate specific antigen levels were measured by enzyme-linked immunosorbent assay. The expression levels of serum miR-15a were decreased in PCa patients compared with controls, chronic prostatitis and BPH patients (0.43 ± 0.12, 1.7 ± 0.76, 1.56 ± 0.34 and 1.53 ± 0.65, respectively). The expression levels of serum miR-16-1 were decreased in PCa patients compared with controls, chronic prostatitis and BPH patients (0.55 ± 0.23, 2.15 ± 0.87, 2.08 ± 0.54 and 1.96 ±0.61, respectively). Downregulation of miR-15a and miR-16-1 correlated with higher Gleason score (P = 0.002 and P = 0.006, respectively), higher tumor stage (P = 0.001 and P = 0.01, respectively), PCa metastasis (P = 0.002 and P = 0.025, respectively) and lymph node involvement (P = 0.02 and P = 0.007, respectively). Moreover, Receiver operating characteristic curve analysis revealed that combined miR-15a/miR-16-1 and PSA increased the sensitivity and specificity for the diagnosis of PCa (97.1% and 94.3%, respectively) more than prostate specific antigen alone (82.9% sensitivity and 75.7% specificity). Combined serum miR-15a/miR-16-1 expression and PSA level can be used as promising specific noninvasive biomarkers in the diagnosis and prognosis of PCa better than prostate specific antigen alone. © 2018 IUBMB Life, 70(5):437-444, 2018.

Establishment of experimental autoimmune prostatitis model by T2 peptide in aluminium hydroxide adjuvant.

A mouse model was developed to simulate the clinical features of chronic prostatitis/chronic pelvic pain syndrome using peptide (T2 ). Forty C57BL/6 mice were divided into four groups of 10 mice each, averagely and randomly. T2 plus aluminium hydroxide adjuvant group was given subcutaneous injection with the emulsion mixture of T2 and aluminium hydroxide adjuvant, the T2 group with T2 , the aluminium hydroxide adjuvant group with aluminium hydroxide adjuvant and the normal control group with 0.9/% NaCl solution. Haematoxylin andeosin staining was used to observe the inflammation of the prostate. Plasma levels of TNF-α and CRP were detected by ELISA kit. The expression of IL-1ßin the prostate was investigated by immunohistochemistry. The statistical differences between the groups were compared by t test. Histopathological analyses demonstrated that prostate lesions were most severe in the group immunised with T2 plus aluminium hydroxide adjuvant. Plasma levels of TNF-α and CRP were statistically elevated compared with control groups. The expression levels of IL-1ß in the prostate were more obvious than control groups. T2 in aluminium hydroxide adjuvant subcutaneous injection could successfully set up experimental autoimmune prostatitis in C57BL/6 mice. This murine model would be greatly beneficial to further comprehend the aetiology, pathogenesis and explicit treatment of CP/CPPS.

Insight into infection-mediated prostate damage: Contrasting patterns of C-reactive protein and prostate-specific antigen levels during infection.

BACKGROUND: To investigate mechanisms underlying our previous observation of a large rise in serum prostate-specific antigen, a marker of prostate pathology, during both sexually transmitted and systemic infections, we measured serum high-sensitivity C-reactive protein (hsCRP), a marker of systemic inflammation, in our previous case-control study of young, male US military members and compared our findings to those for PSA. METHODS: We measured hsCRP before and during infection for 299 chlamydia, 112 gonorrhea, and 59 non-chlamydial, non-gonococcal urethritis (NCNGU) cases; before and after infection for 55 infectious mononucleosis (IM) and 90 other systemic/non-genitourinary cases; and for 220-256 controls. RESULTS: Only gonorrhea cases were significantly more likely to have a large hsCRP rise (≥1.40 mg/L or ≥239%) during infection than controls (P < 0.01). However, gonorrhea, IM, and other systemic/non-genitourinary cases were more likely to have a rise of any magnitude up to one year post-diagnosis than controls (p = 0.038-0.077). CONCLUSIONS: These findings, which differ from those for PSA, suggest distinct mechanisms of elevation for hsCRP and PSA, and support both direct (eg, prostate infection) and indirect (eg, systemic inflammation-mediated prostate cell damage) mechanisms for PSA elevation. Future studies should explore our PSA findings further for their relevance to both prostate cancer screening and risk.

Statin Use, Serum Lipids, and Prostate Inflammation in Men with a Negative Prostate Biopsy: Results from the REDUCE Trial.

Statin use is associated with lower advanced prostate cancer risk. In addition to cholesterol lowering, statins have systemic anti-inflammatory properties. However, their effect on histologic prostate inflammation is not well understood, particularly among men at increased prostate cancer risk but with a negative prostate biopsy. We examined associations between serum lipid levels, statin use, and histologic prostate inflammation using data from 6,655 men with a negative baseline prostate biopsy in the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial. Statin use and lipid levels [total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides] were assessed at baseline. Inflammation was assessed by central review. Logistic regression was used to examine the effects of lipids and statin use on presence and extent of chronic and acute prostate inflammation [none, moderate (<20%), severe (≥20% biopsy cores)]. Chronic and acute inflammation affected 77% and 15% of men, respectively. Men with high HDL (≥60 vs. <40 mg/dL) had reduced presence of acute inflammation [OR, 0.79; 95% confidence interval (CI), 0.63-0.99] and were less likely to have severe acute inflammation (OR, 0.66; 95% CI, 0.45-0.97), but there were no other associations between lipids and inflammation. Statin users had reduced presence of chronic inflammation (OR, 0.81; 95% CI, 0.69-0.95) and were less likely to have severe chronic (OR, 0.80; 95% CI, 0.68-0.95) and severe acute inflammation (OR, 0.73; 95% CI, 0.53-1.00), relative to non-users. Given the possible role for inflammation in prostate cancer, the inverse association between statins and prostate inflammation suggests a mechanism linking statins with lower advanced prostate cancer risk. Cancer Prev Res; 10(6); 319-26. ©2017 AACR.