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Background. Prostate cancer holds one of the leading positions among malignant neoplasms in men. One of the most well-studied tumor-specific maskers is the PCA3 score in urine obtained after prostate massage. However, the study of the PCA3 score without prostate massage can significantly simplify the preanalytical phase of the study and minimize discomfort for the patient. Objective . Investigation of the diagnostic significance of PCA3, determined in urine sediment without prostate massage and its comparison with the PCA3 score after prostate massage. Materials and methods . The study included 2 groups of patients. In the first group (n = 50), the PCA3 score was assessed without prostate massage, and in the second group (n = 15) PCA3 was assessed in urine obtained before and after massage. Results. The area under the ROC-curve (AUC) for the PCA3 score without prostate massage was 0.722 (95 % confidence interval 0.579—0.865; p = 0.008). Using the ROC analysis, the threshold value, sensitivity and specificity were determined: 25, 72.41 % (95 % confidence interval 54.28— 85.30 %) and 57.14 % (95 % confidence interval 36.55—75.53 %), respectively. The PCA3 score after massage was found to be more sensitive than without prostate massage. A small volume of material, less than 20 ml, significantly affects the sensitivity of PCA3 without massage. Conclusion . PCA3 without prostate massage may serve as an option to improve the early diagnosis of prostate cancer, but its advantage over PCA3 after prostate massage has not been shown.

Levels of urinary prostatic exosomal protein (PSEP) were detected to evaluate the clinical potential of PSEP as a diagnostic marker of chronic prostatitis (CP). The level of urinary PSEP was measured in 412 cases by an enzyme-linked immunosorbent assay kit, including 202 controls and 210 CP cases. Of the CP patients, 116 cases met the definition of the USA National Institutes of Health category III (NIH-III), with 60 cases of NIH-IIIA and 56 cases of NIH-IIIB. The ages, body mass indexes (BMI), white blood cell (WBC) levels in expressed prostatic secretions (EPS), lecithin body counts in EPS, urine PSEP levels both before and after prostate massage obtained from the CP patients and NIH-CPSI scores were analyzed. In the diagnosis of CP, the PSEP contents in the urine samples before and after prostate massage manifested a sensitivity of 86.93% vs. 61.06%, and a total coincidence rate of 85.24% vs. 61.06%, respectively. The area under the ROC curve was 0.926 vs. 0.709 for the before and after massage PSEP contents, respectively. Besides, during the follow-up of patients with CP, the improvement in symptoms was not correlated with the level changes of PSEP. Measurement of PSEP levels for the clinical diagnosis of CP is objective and painless. It could be a novel, simple, and noninvasive method for the diagnosis of CP. However, differences in fluid intake may result in a concentration or dilution of urine, which would ultimately affect the judgment of PSEP results.

Metabolomics analysis of biofluids is a feasible tool for disease characterization and monitoring due to its minimally invasive nature. To reduce unwanted variation in biobanks and clinical studies, it is important to determine the effect of external factors on metabolic profiles of biofluids. In this study we examined the effect of sample collection and sample processing procedures on NMR measured serum lipoproteins and small-molecule metabolites in serum and urine, using a cohort of men diagnosed with either prostate cancer or benign prostatic hyperplasia. We determined day-to-day reliability of metabolites by systematic sample collection at two different days, in both fasting and non-fasting conditions. Study participants received prostate massage the first day to assess the differences between urine with and without prostate secretions. Further, metabolic differences between first-void and mid-stream urine samples, and the effect of centrifugation of urine samples before storage were assessed. Our results show that day-to-day reliability is highly variable between metabolites in both serum and urine, while lipoprotein subfractions possess high reliability. Further, fasting status clearly influenced the metabolite concentrations, demonstrating the importance of keeping this condition constant within a study cohort. Day-to-day reliabilities were however comparable in fasting and non-fasting samples. Urine sampling procedures such as sampling of first-void or mid-stream urine, and centrifugation or not before sample storage, were shown to only have minimal effect on the overall metabolic profile, and is thus unlikely to constitute a confounder in clinical studies utilizing NMR derived metabolomics.

Background chronic prostatitis is a common disease that significantly influence on the quality of life. Aim Our aim was to assess the prevalence of particular domains of UPOINT classification and determine the efficiency of prostate-selective cytomedins in complex therapy of chronic prostatitis with the predominance of organic component. Materials and methods a total of 96 patients aged from 24 to 48 years were treated in City clinical hospital named after D.D. Pletnev in 2017-2018 yy. with a previously diagnosed chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). The mean duration of the disease was 18.0+/-6.2 months. The total NIH-CPSI score was 24+/-7.3 (pain score 9+/-4.9, urinary score 7+/-2,7, quality of life 8+/-2.3), Qmax was 16+/-4.2 ml/s, prostate volume - 34+/-12 cc. Leukocyturia in post-massage urine was found in 52 patients (54%). Positive urine culture after prostate massage or positive bacterial semen study were found in 22 patients (23%). Prostate-specific therapy consisted of 20 days of rectal suppositories Vitaprost-forte followed by oral therapy by Vitaprost tablet of the same duration. Results Follow-up examination of 72 patients (75%) was performed after 3 months of therapy. The total NIH-CSPI score decreased to 15.6+/-5.1 (pain score 6.3+/-3.8, urinary score 4.6+/-2.2, quality of life 4.7+/-2), Qmax was 16+/-3.8 ml/s and mean prostate volume was 24+/-6 cc. The normalization of laboratory parameters was achieved in all cases. Conclusion using the UPOINT classification allows to optimize the treatment of patients with chronic prostatitis. Use of prostate-specific cytomedins (Vitaprost) is highly effective in case of prostatic involvement according to the UPOINT classification.

To prospectively examine the changes in microbiota within the urinary tract after transrectal prostate biopsy. Data, urine, and fecal samples prospectively collected from 30 patients before and after transrectal biopsy of the prostate. DNA was extracted from urine collected after a prostate massage before and after prostate biopsy, and from fecal samples collected before the biopsy. We sequenced DNA using the bacterial 16S rRNA high-throughput next-generation sequencing and analyzed changes in microbial profiles for taxonomy comparison between samples. Pre-biopsy urinary microbial profiles contained Lactobacillus and Staphylococcus bacteria. Post-biopsy urinary microbial profiles included lower levels of Lactobacillus and higher levels of Prevotella bacteria. Bacteroides bacteria were predominant in fecal samples. We identified two clustering patterns containing both pre- and post-biopsy urine samples. Cluster 1 had a urine cluster pattern that was distinct from fecal, whereas cluster 2 was similar to fecal. We observed two different modes of microbial changes, 11 patients had both of their urine (pre and post) samples associated with a particular cluster group, whereas others (n = 15) had movement between clusters 1 and 2 following the biopsy procedure. Four patient’s post-biopsy urine microbial profiles clustered very tightly to the fecal microbial profile. We describe two models of change in the urinary tract microbiota after prostate biopsy using 16S RNA gene analysis. Further research to determine what controls changes in the urinary microbiota after prostate biopsy can help us understand why some patients are more susceptible to develop post-biopsy infections.

The aim of the study was to increase the efficiency of complex treatment of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with the combined effect of magnetolaser therapy (MLT) and red light. MATERIALS AND METHODS We examined and included in the study 120 men with a verified diagnosis of CP/CPPS (III B), at the stage of exacerbation. By envelope method, patients were divided into two randomized groups. The main group consisted of 60 patients who received a basic treatment complex, including medicamentous therapy, prostate massage, diet therapy, a complex of therapeutic gymnastics, and the combined effect of MLT and red light of 10 procedures per course. The comparison group consisted of 60 patients who received only a basic therapeutic complex. Evaluation of the effectiveness of treatment was carried out in dynamics before complex treatment, immediately after the course of treatment and 6 months later for analysis of long-term results using the questionnaire "System of summary evaluation of chronic prostatitis symptoms", dopplerography of urethral arteries of the prostate, laser Doppler flowmetry in the prostate. RESULTS AND DISCUSSION In the main group of patients with CP/CPPS immediately after complex treatment and after 6 months, a positive therapeutic effect was noted in the form of relief of pain syndrome, dysuria, improving the quality of life, improvement of blood circulation in the urethral arteries of the prostate and microcirculation. In the comparison group, the positive effects from the complex baseline treatment were less pronounced. Comparative analysis of the results of the study between the main group of patients with CP/CPPS and comparison group showed the presence of statistically significant differences in all indicators of clinical symptoms of the disease, dopplerography in the urethral arteries of the prostate and microcirculation in the prostate, both immediately after treatment and after 6 months of follow-up. CONCLUSION The method of complex treatment of patients with CP/CPPS with the combined effect of MLT and red light has greater immediate and remote efficacy in comparison with baseline treatment.

The main advantage of urinary biomarkers is their noninvasive character and the ability to detect multifocal prostate cancer (CaP). We have previously implemented a quadruplex assay of urinary markers into clinical practice (PCA3, AMACR, TRPM8 and MSMB with KLK3 normalization). In this study, we aimed to validate it in a larger cohort with serum PSA 2.5&ndash, 10 ng/mL and test other selected transcripts and clinical parameters, including the percentage of free prostate-specific antigen (PSA) (% free PSA) and inflammation. In the main cohort of 299 men, we tested the quadruplex transcripts. In a subset of 146 men, we analyzed additional transcripts (CD45, EPCAM, EZH2, Ki67, PA2G4, PSGR, RHOA and TBP). After a prostate massage, the urine was collected, RNA isolated from a cell sediment and qRT-PCR performed. Ct values of KLK3 (i.e., PSA) were strongly correlated with Ct values of other genes which play a role in CaP (i.e., PCA3, AMACR, TRPM8, MSMB and PSGR). AMACR, PCA3, TRPM8 and EZH2 mRNA expression, as well as % free PSA, were significantly different for BPH and CaP. The best combined model (% free PSA plus PCA3 and AMACR) achieved an AUC of 0.728 in the main cohort. In the subset of patients, the best AUC 0.753 was achieved for the combination of PCA3, % free PSA, EPCAM and PSGR. PCA3 mRNA was increased in patients with inflammation, however, this did not affect the stratification of patients indicated for prostate biopsy. In conclusion, the percentage of free PSA and urinary markers contribute to a more accurate indication for prostate biopsy.

The development of more specific biomarkers for prostate cancer and/or high-risk prostate cancer is necessary, because the prostate-specific antigen test lacks specificity for the detection of prostate cancer and can lead to unnecessary prostate biopsies. Urine is a promising source for the development of new biomarkers of prostate cancer. Biomarkers derived from prostate cancer cells are released into prostatic fluids and then into urine. Urine after manipulation of the prostate is enriched with prostate cancer biomarkers, which include prostate cancer cells, DNAs, RNAs, proteins and other small molecules. The urinary prostate cancer antigen 3 test is the first Food and Drug Administration-approved RNA-based urinary marker, and it helps in the detection of prostate cancer on repeat biopsy. The SelectMDx test is based on messenger RNA detection of DLX1 and HOXC6 in urine after prostate massage, and helps in the detection of high-risk prostate cancer on prostate biopsy. Exosomes are extracellular vesicles with a diameter of 30-200 nm that are secreted from various types of cells. Urinary prostate cancer-derived exosomes also contain RNAs and proteins specific for prostate cancer (e.g. PCA3 and TMPRSS2-ERG), and could be promising sources of novel biomarker discovery. The ExoDx Prostate test is a commercially available test based on the detection of three genes (PCA3, ERG and SPDEF) in urinary exosomes. Advancement of comprehensive analysis (microarray, mass spectrometry and next-generation sequencing) has resulted in the discovery of several urinary biomarkers. Non-invasive urinary markers can help in the decision to carry out prostate biopsy or in the design of a therapeutic strategy.

Prostate cancer is the leading type of cancer diagnosed in men. Serum prostate-specific antigen levels and digital rectal exam are far from perfect when it comes to differentiation of patients with prostate cancer and benign prostatic hyperplasia. In this study, we attempt to determine whether amino acids can be used as prostate cancer biomarkers. Concentrations of derivatized amino acids and amines were quantified by liquid chromatography tandem mass spectrometry. A total of 100 urine samples from the two groups including samples provided before and after prostate massage were examined quantitatively for amino acid and amine concentrations with 50 urine samples collected from cancer patients and 50 samples from patients diagnosed with benign prostatic hyperplasia. Arginine, homoserine, and proline were more abundant in urine samples of cancer patients compared with arginine, homoserine, and proline levels determined in urine collected from patients with benign growth. We also show that sarcosine is not a definitive indicator of prostate cancer when analyzed in urine samples collected either before or after prostate massage.

Introduction: Transrectal ultrasound guided prostate biopsy (TRUS-Bx), according to the literature, can lead to urinary tract infections in up to 11% and sepsis in up to 2% of patients. We evaluate whether an original way to apply povidone-iodine rectal preparation just prior to TRUS-Bx can reduce infectious complications. Material and Methods: Between January 2014 and September 2016, 94 men in private office were prospectively randomized to two groups, before TRUS-Bx: • Rectal cleansing (an original transrectal “prostate massage” for about half a minute with 2.5 mL of betadine dermic solution 100 mg/mL) (n=47) or • No cleansing (n=47). All of the patients received prophylactic antibiotics: levofloxacin 500 mg PO for 7 days, beginning the day before procedure. Patients completed a telephone interview 4 days after undergoing the biopsy and went to the office 2 weeks after biopsy. The primary end point was the rate of infectious complications. An infectious complication when one or more of the following events occurred: 1) fever greater than 38.0Cº, 2) urinary tract infection or 3) sepsis (standardized definition). Student t test and multivariate regression analysis were used for data analysis. Results: Infectious complications developed in 6 cases (12.7%) in the non-rectal preparation group: five patients had fever without sepsis (11%) and one had sepsis (2%). In the povidone-iodine rectal preparation group there were no infectious complications (0.0%). Multivariate analysis did not identify any patient subgroups at significantly higher risk of infection after prostate biopsy. Of the 94 men who underwent TRUS-Bx 45 (47.9%) were diagnosed with prostate cancer and 3 (3.2%) had ASAP in the result. The hospital admission rate for urological complications within 30 days of the procedure was 1%, and only for infection related reasons (sepsis). Conclusion: The administration of quinolone-based prophylactic antibiotics and the simple use of 2.5 mL of povidone-iodine dermic solution in a transrectal prostate massage for Introduction: Transrectal ultrasound guided prostate biopsy (TRUS-Bx), according to the literature, can lead to urinary tract infections in up to 11% and sepsis in up to 2% of patients. We evaluate whether an original way to apply povidone-iodine rectal preparation just prior to TRUS-Bx can reduce infectious complications. Material and Methods: Between January 2014 and September 2016, 94 men in private office were prospectively randomized to two groups, before TRUS-Bx: • Rectal cleansing (an original transrectal “prostate massage” for about half a minute with 2.5 mL of betadine dermic solution 100 mg/mL) (n=47) or • No cleansing (n=47). All of the patients received prophylactic antibiotics: levofloxacin 500 mg PO for 7 days, beginning the day before procedure. Patients completed a telephone interview 4 days after undergoing the biopsy and went to the office 2 weeks after biopsy. The primary end point was the rate of infectious complications. An infectious complication when one or more of the following events occurred: 1) fever greater than 38.0Cº, 2) urinary tract infection or 3) sepsis (standardized definition). Student t test and multivariate regression analysis were used for data analysis. Results: Infectious complications developed in 6 cases (12.7%) in the non-rectal preparation group: five patients had fever without sepsis (11%) and one had sepsis (2%). In the povidone-iodine rectal preparation group there were no infectious complications (0.0%). Multivariate analysis did not identify any patient subgroups at significantly higher risk of infection after prostate biopsy. Of the 94 men who underwent TRUS-Bx 45 (47.9%) were diagnosed with prostate cancer and 3 (3.2%) had ASAP in the result. The hospital admission rate for urological complications within 30 days of the procedure was 1%, and only for infection related reasons (sepsis). Conclusion: The administration of quinolone-based prophylactic antibiotics and the simple use of 2.5 mL of povidone-iodine dermic solution in a transrectal prostate massage for

There is emerging evidence that microRNAs (miRNAs) dysregulation is involved in the genesis and the progression of Prostate Cancer (PCa), thus potentially increasing their use in urological clinical practice. This is the first pilot study which utilizes Illumina Deep Sequencing to examine the entire miRNAs spectrum existent in urine exfoliated prostate cells (UEPCs) of PCa patients. A total of 11 male patients with histological diagnosis of PCa were enrolled in the present study. First-catch urine (30 mL) was collected following a prostate massage. Total RNA was extracted from urine and sequenced using an HiSeq2500 System (Illumina). QPCR assay was used to validate the highest NGS results in PCA patients and in age-matched, caucasian men. Remarkably, PCA let-7 family was down-regulated (P let-7 family. The present research confirmed the potential use of miRNAs as non-invasive biomarkers in the diagnosis of PCa, potentially reducing the invasiveness of actual clinical strategy.

Proteinases secreted by the prostate gland have a reproductive function in cleaving proteins in the ejaculate and in the female reproductive tract, but some may have a fundamental role in disease and pathological processes including cancer. The purpose of this study was to determine if there were differences in proteinase activities in urine samples collected following prostate massage of men positive (CaP) or negative (no evidence of malignancy, NEM) for biopsy determined prostate cancer. Matrix metalloproteinase (MMP) and serine proteinase activities were detected using protein substrate zymography. There were no differences in activities of MMP-2, proMMP-9, and MMP-9/NGAL (neutrophil gelatinase associated lipocalin) complex (gelatin substrate) in men with detected prostate cancer, although the latter two were somewhat diminished. A caseinolytic activity of about 75 kDa inhibited by calcium did not differ between the NEM and CaP groups. Heparin stimulated calcium sensitive gelatinolytic activities of approximately 22, 42, and 60 kDa, but did not affect activities of MMP-2, MMP-9, or the 75 kDa caseinolytic activity. The 22, 42, and 60 kDa activities appear to be serine proteinases since they were inhibited by benzamidine. There was a significant decrease in the 22 kDa heparin-stimulated serine proteinase activity in urines of men with cancer. Proteinase expression and activities, perhaps in combination with other potential markers, may prove useful in urine for detection and evaluation of prostate cancer.

Prostate cancer antigen 3 (PCA3) is a non-coding RNA fragment that is overexpressed in prostate cancer cells. However, the clinical applications of PCA3 are highly limited due to the instability of RNA and the lack of reliable and efficient RNA extraction and purification methods. Thus, in the present study, we compared three different methods of RNA extraction to further confirm the higher yield of commercial magnetic beads with poly-T functionalization and a capturer strand. The current protocols for RNA extraction of i) the phenol-chloroform method, ii) the affinity column method and iii) magnetic beads with poly-T functionalization and a capturer strand were applied separately for RNA extraction in urine samples. Reverse transcription‑quantitative polymerase chain reaction was performed to evaluate the yield of the three methods of RNA extraction. Furthermore, 52 urine samples after prostate massage from patients suspected of a diagnosis of prostate cancer were collected. The Mag-Cap method and RT-PCR were applied to obtain the PCA3 score. The clinical value of the PCA3 score was investigated by comparison with the pathology of the prostate biopsy. The yield of the Mag-Cap method was higher than that of the phenol‑chloroform method and commercial kits. Thirty‑four patients were pathologically diagnosed with prostate cancer and 18 with benign prostatic hyperplasia (BPH). It was confirmed that the median PCA3 score was higher among the prostate cancer patients than those with benign disease (53.5 vs. 17, p=0.000). A sensitivity of 82.4% and a specificity of 77.8% were obtained when the cut-off value for the PCA3 score was 28.5. The Mag-Cap method was found to be more efficient for RNA extraction. The urinary PCA3 score is a promising method for prostate cancer screening, detection and diagnosis, and has the potential to reduce unnecessary prostate biopsies.

BACKGROUND. Voided urine samples have been shown to contain cells released from prostate tumors. Could good quality RNA from cells in urine be obtained from every donor for multimarker analysis? In addition, could urine donation be as simple as possible, a practical consideration for a lab test, without involving a prostate massage (as indicated for PCA3 testing), which precludes frequent collection; needing it done at a specific time of day (e.g., first or second urine); and requiring prompt processing of samples in clinics with limited molecular biology capability? METHODS. Collected urine samples were pelleted, and the RNA isolated was processed for cDNA synthesis and in vitro transcription to generate amplified sense aRNA. The resultant aRNA was rigorously analyzed for possible introduced changes. DMSO was used as a cell preservative for frozen storage of urine samples. RESULTS. Good quality aRNA was obtained for over 100 samples collected at two different institutions. The process of RNA amplification removed co-isolated DNA in some samples, which did not affect RNA amplification. Amplification did not amplify genes that were absent and produce other expression alterations. The sense aRNA could be used to generate urinary transcriptomes specific to individual patients. No chaotropic agents for RNA preservation were added to the urine samples so that the supernatant could be used for analysis of secreted protein biomarkers. The time of donation was not important since patients were seen during the entire day. DMSO was an effective cell preservative for freezing urine. CONCLUSIONS. Urinary RNA can be readily isolated and amplified for prostate cancer biomarker analysis. Individual patients had unique set of transcripts derived from their tumor. Prostate 75:1886–1895, 2015. # 2015 Wiley Periodicals, Inc.

This study aims to evaluate the effectiveness and clinical performance of a panel of urinary biomarkers to diagnose prostate cancer (PCa) in Chinese men with PSA levels between 4 and 10 ng/mL. A total of 122 patients with PSA levels between 4 and 10 ng/mL who underwent consecutive prostate biopsy at three hospitals in China were recruited. First-catch urine samples were collected after an attentive prostate massage. Urinary mRNA levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The predictive accuracy of these biomarkers and prediction models was assessed by the area under the curve (AUC) of the receiver-operating characteristic (ROC) curve. The diagnostic accuracy of PCA3, PSGR, and MALAT-1 was superior to that of PSA. PCA3 performed best, with an AUC of 0.734 (95% CI: 0.641, 0.828) followed by MALAT-1 with an AUC of 0.727 (95% CI: 0.625, 0.829) and PSGR with an AUC of 0.666 (95% CI: 0.575, 0.749). The diagnostic panel with age, prostate volume, % fPSA, PCA3 score, PSGR score, and MALAT-1 score yielded an AUC of 0.857 (95% CI: 0.780, 0.933). At a threshold probability of 20%, 47.2% of unnecessary biopsies may be avoided whereas only 6.2% of PCa cases may be missed. This urinary panel may improve the current diagnostic modality in Chinese men with PSA levels between 4 and 10 ng/mL.

This study investigated the effects of long-term treatment with rifaximin and the probiotic VSL#3 on uro-genital and gastrointestinal symptoms in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) plus diarrhoea-predominant irritable bowel syndrome (D-IBS) compared with patients with D-IBS alone. Eighty-five patients with CP/CPPS (45 with subtype IIIa and 40 with IIIb) plus D-IBS according to the Rome III criteria and an aged-matched control-group of patients with D-IBS alone (n = 75) received rifaximin and VSL#3. The primary endpoints were the response rates of IBS and CP/CPPS symptoms, assessed respectively through Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) and The National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI), and performed at the start of therapy (V0) and three months after (V3). In IIIa prostatitis patients, the total NIH-CPSI scores significantly (p < 0.05) decreased from a baseline mean value of 21.2 to 14.5 at V3 , as did all subscales, and in the IIIb the total NIH-CPSI score also significantly decreased (from 17.4 to 15.1). Patients with IBS alone showed no significant differences in NIH-CPSI score. At V3, significantly greater improvement in the IBS-SSS and responder rate were found in IIIa patients. Our results were explained through a better individual response at V3 in IIIa prostatitis of urinary and gastrointestinal symptoms, while mean leukocyte counts on expressed prostate secretion (EPS) after prostate massage significantly lowered only in IIIa cases.

Chronic nonbacterial prostatitis is an ill-defined, painful clinical condition that is characterized by various nonspecific symptoms, some of which are related to urination or the male reproductive organs. Urologists diagnose this particular condition when the symptoms are not associated with urinary bacterial growth before and after transrectal prostate massage. In this review, we describe the recommended and optional tests that can be performed in these cases. There is significant overlap between chronic nonbacterial prostatitis and other unexplained pain conditions, raising the question as to whether the prostate is the culprit. The sources and mediators of pain and the psychological aspects of this complex condition are discussed. Treatments consist of traditional antibiotics and α-blockers. Because the pain relief is often temporary, patients seek other solutions. Various therapeutics have been introduced to satisfy the expectations of patients and physicians. We discuss other pain medications, as well as intraprostatic drug injections and shockwave therapy. Importantly, however, not all of these suggestions have been widely accepted by urologists or pain clinics.

Purpose: The diagnosis of localized prostate cancer is difficult due to a lack of cancer-specific biomarkers. Many patients require repeat prostate biopsies to diagnose the disease. We investigated whether aberrant promoter hypermethylation in prostatic fluid could reliably detect prostate cancer. Experimental Design: Urine samples were collected after prostate massage from 95 patients with localized prostate cancer undergoing radical prostatectomy (63 pT1, 31 pT2, and 1 pT3) and from 38 control patients. Ten genes (GSTP1, RASSF1a, ECDH1, APC, DAPK, MGMT, p14, p16, RARβ2, and TIMP3) were investigated using quantitative real-time methylation-specific PCR. Receiver operator curves were generated. Results: The frequency of gene methylation ranged from 6.3% (p14) to 83.2% (GSTP1) in prostate cancer patients. At least one gene was hypermethylated in 93% of cancer patients. The specificity of methylation was 0.74. Methylation was significantly more frequent (P < 0.05) in cancer than control patients for all genes except p14 and p16. According to receiver operator curve analysis, the four-gene combination of GSTP1 (0.86), RASSF1a (0.85), RARβ2 (0.80), and APC (0.74) best discriminated malignant from nonmalignant cases. The sensitivity and accuracy of this four-gene set were 86% and 89%, respectively. Conclusions: The presence of aberrant methylation in urinary cells obtained after prostate massage is significantly associated with prostate cancer. A panel of four genes could stratify patients into low and high risk of having prostate cancer and optimize the need for repeat prostatic biopsies.

Young men comprise the overwhelming majority of men with spinal cord injury (SCI), the incidence of which has been growing over the years. Due to advances in physical medicine and rehabilitation, remarkable improvements in survival rates have been reported, leading to life expectancies similar to those of the general population. However, many sexual and reproductive functions may be impaired due to erectile or ejaculatory dysfunction and semen abnormalities, characterised by low-sperm motility or viability in SCI males who have not become parents yet. Nevertheless, fatherhood is still possible through the introduction of specialised medical management, by using various medical, technical and surgical methods for sperm retrieval in combination with assisted reproductive techniques. Erectile dysfunction can be managed by the use of phosphodiesterase-5 inhibitors, intracavernosal injections, vacuum devices and penile prostheses. Semen can be obtained from the vast majority of anejaculatory men by medically assisted ejaculation through the use of penile vibratory stimulation or electroejaculation and via prostate massage or surgical procedures. Despite impaired sperm parameters, reasonable pregnancy rates similar to those in able-bodied subfertile cohorts have been reported. However, future research should focus on the optimisation of semen quality in these men and on improving natural ejaculation.

Background Because of the numerous limitations of prostate-specific antigen (PSA), α-methylacyl-CoA racemase (AMACR) and hepsin have recently been suggested as potential biomarkers in prostate cancer (PC). This report presents a comparison study of the presence of AMACR and hepsin in urine collected before and after digital rectal examination (DRE) as a previously suggested diagnostic marker for PC. Methods Seventy-six urine samples (38 before and 38 after prostate massage) from patients with benign prostate hyperplasia (BPH) and 66 urine samples (33 before and 33 after prostate massage) from patients with PC were analyzed. PC was confirmed by prostate biopsy. Urinary levels of AMACR and hepsin were determined by ELISA and related to the tumor stage, Gleason score and PSA level. Results AMACR and hepsin levels in urine collected after prostate massage were higher only in the PC group. There were no correlations between AMACR levels, hepsin levels, tumor stage and Gleason score. AMACR and hepsin did not differentiate between BPH and PC with better true positive and false negative rates than serum PSA. Conclusions AMACR and hepsin were unable to diagnose PC with better true positive and false negative rates than PSA. An additional procedure combined with other markers should be applied for the reliable diagnosis of PC.

PURPOSE: Prostate cancer (PCa) is one of the most commonly diagnosed malignancies in the world. Although PSA utilization as a serum marker has improved prostate cancer detection it still presents some limitations, mainly regarding its specificity. The expression of this marker, along with the detection of PCA3 mRNA in urine samples, has been suggested as a new approach for PCa detection. The goal of this work was to evaluate the efficacy of the urinary detection of PCA3 mRNA and PSA mRNA without performing the somewhat embarrassing prostate massage. It was also intended to optimize and implement a methodological protocol for this kind of sampling. MATERIALS AND METHODS: Urine samples from 57 patients with suspected prostate disease were collected, without undergoing prostate massage. Increased serum PSA levels were confirmed by medical records review. RNA was extracted by different methods and a preamplification step was included in order to improve gene detection by Real-Time PCR. RESULTS: An increase in RNA concentration with the use of TriPure Isolation Reagent. Despite this optimization, only 15.8% of the cases showed expression of PSA mRNA and only 3.8% of prostate cancer patients presented detectable levels of PCA3 mRNA. The use of a preamplification step revealed no improvement in the results obtained. CONCLUSION: This work confirms that prostate massage is important before urine collection for gene expression analysis. Since PSA and PCA3 are prostate specific, it is necessary to promote the passage of cells from prostate to urinary tract, in order to detect these genetic markers in urine samples.

Chronic bacterial prostatitis (CBP) is, usually, caused by uropathogens, especially gram-negative bacilli, although infection is sometimes due to Gram-positive and atypical microorganisms. A recent increasing in prevalence of Gram-positive strains has been reported. The aim of this study was to explore the epidemiological features and resistance rates in uropathogens isolated from CBP outpatients in last 10 years. All consecutive outpatients with demonstrated CBP attending a single Sexually Transmitted Disease centre from January 1997 and December 2008, were enrolled and underwent microbiological cultures in first void early morning urine, midstream urine, expressed prostatic secretion, and post prostate massage urine. Prevalence of different bacterial strains was stratified in four different periods: 1997-1999, 2000-2002, 2003-2005, 2006-2008. Any changes observed in epidemiological features and resistance rates in uropathogens over the whole study period have been analyzed. The present study has been planned, thus, as in vitro study. From 6,221 patients, 4,601 Gram-positive and 1,620 Gram-negative bacterial strains have been isolated. Enterococcus faecalis and Escherichia coli strains are the first and second frequent pathogens found, respectively. Significant differences between E. faecalis prevalence in the 1997-1999 and 2006-2008 periods were found. E. coli showed a significant difference between prevalence in 1997-1999 and 2006-2008 periods. Gram-positive organisms showed a decreasing of susceptibility to ciprofloxacin as well as Gram-negative strains, while a good susceptibility to the levofloxacin was evidenced. E. faecalis prevalence seemed to be raised in 2006-2008 periods. Moreover, a decreasing of activity of ciprofloxacin and a good activity profile of levofloxacin have been reported.

BACKGROUND Several studies have demonstrated the usefulness of monitoring an RNA transcript in urine, such as PCA3, for prostate cancer (PCa) diagnosis. PCa screening would benefit from additional biomarkers of higher specificity and could be used in conjunction with prostate-specific antigen (PSA) testing, in order to better determine biopsy candidates. METHODS We used urine sediments after prostate massage (PM) from 215 consecutive patients, who presented for prostate biopsy. We tested whether prostate-specific G-protein coupled receptor (PSGR), a biomarker previously described to be over-expressed in PCa tissue, could also be detected by quantitative real-time PCR in post-PM urine sediment. We combined these findings with prostate cancer gene 3 (PCA3), the current gold standard for PCa diagnosis in urine, to test if a combination of both biomarkers could improve the sensitivity of PCA3 alone. RESULTS By univariate analysis we found that PSGR and PCA3 were significant predictors of PCa. Receiver operator characteristic curve analysis and its multivariate extension, multivariate ROC (MultiROC), were used to assess the outcome predictive values of the individual and the paired biomarkers. We obtained the following area under the curve values: PSA (0.602), PSGR (0.681), PCA3 (0.656), and PSGRvPCA3 (0.729). Then, we tested whether a combination of PSGR and PCA3 could improve specificity by fixing the sensitivity at 95%. We obtained specificities of 15% (PSGR), 17% (PCA3), and 34% (PSGRvPCA3). CONCLUSIONS A multiplexed model including PSGR and PCA3 improves the specificity for the detection of PCa, especially in the area of high sensitivity. This could be clinically useful for determining which patients should undergo biopsy. Prostate 70: 1760–1767, 2010. © 2010 Wiley-Liss, Inc.

The prostate gland secretes many proteins in a prostatic fluid that combines with seminal vesicle derived fluids to promote sperm activation and function. Proximal fluids of the prostate that can be collected clinically are seminal plasma and expressed-prostatic secretion (EPS) fluids. EPS represents the fluid being secreted by the prostate following a digital rectal prostate massage, which in turn can be collected in voided urine post-exam. This collection is not disruptive to a standard urological exam, and it can be repeatedly collected from men across all prostatic disease states. A direct EPS fluid can also be collected under anesthesia prior to prostatectomy. While multiple genetic assays for prostate cancer detection are being developed for the shed epithelial cell fraction of EPS urines, the remaining fluid that contains many prostate-derived proteins has been minimally characterized. Approaches to optimization and standardization of EPS collection consistent with current urological exam and surgical practices are described, and initial proteomic and glycomic evaluations of the of EPS fluid are summarized for prostate specific antigen and prostatic acid phosphatase. Continued characterization of the prostate specific protein components of EPS urine combined with optimization of clinical collection procedures should facilitate discovery of new biomarkers for prostate cancer.

Introduction: Treatment of lower urinary tract symptoms (LUTS) in men due to benign prostatic hyperplasia (BPH) or chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are difficult for both the patient and the clinician. In office prostatic massage has been documented to provide symptom relief but use of at-home massage has not been determined. We performed a retrospective analysis of data from men utilizing an at-home-use prostate device to examine disease, treatment characteristics, and symptom relief in order to ascertain whether evidence exists to perform a clinical trial. Methods: Data on 154 consecutive men was reviewed and subjects evaluated in two Groups, BPH w/ LUTS (Group 1) and CP/CPPS w/ LUTS (Group 2). All subjects completed the National Institutes of Health, Chronic Prostatitis Symptom Index (CPSI) at baseline and follow-up. Demographics, scores on the CPSI, duration of device use, self-reported symptom assessment, and comments were analyzed. Results: Of 154 men, 115 were analyzed. Of the 115, 90 (78.3%) were in Group 1 (BPH w/LUTS) and 25 (21.7%) were in Group 2 (CP/CPPS w/LUTS). The average age was 64.48 years ± 10.86 (average ± SD) vs 46.68 ± 12.5 (Group 1 - 2, respectively). In Group 1 total CPSI score from baseline to follow-up were (11.61 ± 7.07 (mean ± SD) - 6.63 ± 5.20, p = 0.0001). In Group 2 total scores from baseline to follow-up were (16.67 ± 7.0 vs 11.48 ± 5.84 (5.20, p = 0.0127). Other self-reported comments included 16/115 (13.9%) of subjects unsure about proper use/application and 10/115 (8.6%) reporting rectal soreness. Conclusions: The preliminary findings suggest that a clinical trial of a novel at-home-use prostatic massage device is warranted.

This study was designed to compare and evaluate the presence of engrailed-2 (EN2) protein in urine collected before and after prostate massage as a diagnostic marker for prostate cancer (PCa). We analysed and compared 76 urine samples (38 before and 38 after prostate massage) from the benign group (BPH) and 66 urine samples (33 before and 33 after prostate massage) from patients with PCa confirmed by prostate biopsy. EN2 levels from the PCa and men with BPH (age range 50-82) were related to the tumour stage, Gleason score and prostate-specific antigen. EN2 levels were determined by enzyme-linked immunosorbent assay in urine. The median EN2 levels in urine after prostate massage were significantly different from those determined in urine before prostate massage (1.25 ng/ml in the PCa group and 0.34 ng/ml in the BPH). The mean EN2 levels in PCa patients were 3.76-fold higher than those in non-PCa patients after prostate massage. The distinct influence of prostate massage on EN2 levels was found to be related to the Gleason score and tumour stage. EN2 may be considered a marker of PCa with certain limitations, such as those related to tumour staging. The specificity and sensitivity of the protocol are highly dependent on prostate massage.

OBJECTIVE To investigate the features of chronic prostatitis (CP) during puberty and the effects of biofeedback on young males with this disease. PATIENTS AND METHODS In all, 40 patients were divided into two groups; group 1 included 25 pubertal patients with CP (mean age 16.5 years, sd 1.1) and group 2 was a control group including 15 patients (mean age 16.2 years, sd 1.2) with a normal lower urinary tract. National Institute of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) scores (three parts) were assessed individually in both groups. Expressed prostatic secretions and urine samples after prostate massage from group 1 were cultured to determine whether patients were infected with bacteria, and group 1 was categorized into various NIH types. Each patients in the two groups underwent urodynamics and group 1 were treated with biofeedback. RESULTS In group 1, there were one, three and 21 patients with type II, IIIA and IIIB prostatitis. The incidence of staccato voiding and detrusor-sphincter dyssynergia (DSD), and the maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), maximum detrusor pressure (Pdetmax) and maximum urethral closure pressure (MUCP) between the groups were significantly different (P

Purpose. We performed a case-control study in which we tested the ability of a non-invasive assay to detect telomerase activity and to distinguish between prostatic cancer (Pca) and benign prostatic hyperplasia (BPH) on samples of epithelial cells obtained after prostatic massage. Methods. Telomerase activity was determined by a telomeric repeat amplification protocol (TRAP) assay. We selected 60 patients with histologically proven Pca (30 cases) or BPH (30 cases). Specimens included in this study were from patients who had no suspicious findings on digital rectal examination for cancer, had clinical evidence of lower urinary tract symptoms, had no sonographic signs of Pca at the transrectal ultrasound evaluation, had total PSA values moderately elevated (2.6-15 ng/ml), and had no evidence of other urological cancers. The whole procedure was conducted in double blind between pathologists and molecular biology operators. Results. Telomerase activity was detected in 90% of Pca cases and in 13% of BPH cases. The sensitivity (90%) and specificity (76%) of this method were calculated. The positive predictive value, negative predictive value, and diagnostic efficiency were 87%, 90%, and 88% respectively. Conclusion. Our data indicate that telomerase activity detected by TRAP assay on prostate epithelial cells collected by prostate massage can substantially improve the distinction between Pca and BPH conditions. One of the clinical benefits resulting from the use of this new assay would be to refine the biopsy indication and to avoid for several patients without Pca the unnecessary cost and the complications of prostate biopsy.

Recurrent urinary tract infections (UTI) are a major problem affecting spinal cord injury (SCI) patients and may stem from chronic bacterial prostatitis. We have therefore investigated the presence of chronic bacterial prostatitis and its role in the development of recurrent symptomatic UTI in SCI men. This study is a prospective cross-sectional investigation of bacterial prostatitis in SCI men in a single SCI rehabilitation center. In 50 men with chronic SCI presenting for a routine urologic examination, urine samples before and after prostate massage were taken for microbiologic investigation and white blood cell counting. Furthermore, patient characteristics, bladder diary details, and the annual rate of symptomatic UTI were collected retrospectively. No participant reported current symptoms of UTI or prostatitis. In most men (39/50, 78 %), the microbiologic analysis of the post-massage urine sample revealed growth of pathogenic bacteria. The majority of these men (32/39, 82 %) also presented with mostly (27/39, 69 %) the same pathogenic bacteria in the pre-massage sample. There was no significant (p = 0.48) difference in the number of symptomatic UTI in men with a positive post-massage culture compared with those with a negative culture. No significant (p = 0.67) difference in the frequency distribution of positive versus negative post-massage cultures was detected between men with recurrent and sporadic UTI. Most SCI men are affected by asymptomatic bacterial prostatitis; however, bacterial prostatitis does not play a major role in the development of recurrent UTI. The indication for antibiotic treatment of chronic bacterial prostatitis in asymptomatic SCI men with recurrent UTI is questionable.

dom urine samples (without prostate massage) were collected from 163 men who were stratified into 4 groups: TRUS prostate biopsy negative (Bx Neg, n 39), TRUS biopsy positive (Bx Pos, n 47), post-radical prostatectomy (RP, n 37) and controls (males 35 yrs, n 40). Additionally, whole-mount paraffin embedded prostate sections were obtained from 11 patients who underwent RP and had pre-RP urine specimens available (7 T:E positive, 4 T:E negative in pre-RP urine). Urine samples were stored at 4°C and 0.8 m filtration was used to remove whole cells and debris. Urinary exosomal RNA and tissue RNA were isolated using an in-house technique (Exosome Diagnostics, NY) and analyzed using RP-qPCR. RESULTS: Mean serum PSA levels were similar in the Bx Neg and Bx Pos groups. All groups except the control (males 35 yrs) were age matched. T:E fusion events were found to occur in 68% of Bx Pos and 44% of Bx Neg patients. Only 5% of controls expressed T:E and no patient in the post RP group had positive T:E detection. Furthermore, T:E expression was lost in the 4 Bx Pos patients that underwent prostatectomy and were retested following surgery. Tissue analysis revealed positive T:E in 8 of 11 prostates. T:E expression concordance between urine and tissue occurred in 10 of 11 (91%) patients with a sensitivity and specificity of 89% and 100%, respectively. CONCLUSIONS: The detection rate of the T:E fusion in the Bx Pos group using urinary exosomal RNA was consistent with previous reports using tissue analyses. Our study exhibited near perfect concordance between urinary exosomal mRNA with matched prostate tissue analysis. The detection of T:E expression in the urine of patients with a negative TRUS biopsy may be due to false negative biopsy results or assay detection of T:E expression in premalignant lesions. The unique stability and yield of urinary exosomal RNA will broaden the role of exosomes in future diagnostic testing and simplify sample handing without the variability and patient discomfort inherent to prostate massage.

Objective To provide preliminary clinical performance evaluation of a novel prostate cancer (CaP) assay, prostate-specific antigen/solvent interaction analysis (PSA/SIA) that focused on changes to the structure of PSA. Methods Two-hundred twenty-two men undergoing prostate biopsy for accepted clinical criteria at 3 sites (University Hospitals Case Medical Center in Cleveland, Cleveland Clinic, and Veterans Administration Boston Healthcare System) were enrolled in institutional review board–approved study. Before transrectal ultrasound–guided biopsy, patients received digital rectal examination with systematic prostate massage followed by collection of urine. The PSA/SIA assay determined the relative partitioning of heterogeneous PSA isoform populations in urine between 2 aqueous phases. A structural index, K, whose numerical value is defined as the ratio of the concentration of all PSA isoforms, was determined by total PSA enzyme-linked immunosorbent assay and used to set a diagnostic threshold for CaP. Performance was assessed using receiver operating characteristic (ROC) analysis with biopsy as the gold standard. Results Biopsies were pathologically classified as case (malignant, n = 100) or control (benign, n = 122). ROC performance demonstrated area under the curve = 0.90 for PSA/SIA and 0.58 for serum total PSA. At a cutoff value of k = 1.73, PSA/SIA displayed sensitivity = 100%, specificity = 80.3%, positive predictive value = 80.6%, and negative predictive value = 100%. No attempt was made in this preliminary study to further control patient population or selection criteria for biopsy, nor did we analytically investigate the type of structural differences in PSA that led to changes in k value. Conclusion PSA/SIA provides ratiometric information independently of PSA concentration. In this preliminary study, analysis of the overall structurally heterogeneous PSA isoform population using the SIA assay showed promising results to be further evaluated in future studies.

Measurement of serum prostate specific antigen (PSA) is commonly used to evaluate the prostate gland in a variety of clinical settings. We examined the effects of prostatic manipulations, including digital rectal examination, prostate massage, transrectal ultrasonography and transrectal needle biopsy, on serum PSA levels in 199 men. We detected no clinically significant difference between serum PSA levels obtained immediately before and at 5 or 90 minutes after rectal examination in 43 men. We observed falsely increased PSA levels (to greater than 4 ng./ml., Tandem-R) in 1 of 17 men (6%) following prostatic massage and in 3 of 27 men (11%) following ultrasonography. Transrectal needle biopsy caused an immediate increase in serum PSA in 92 of 100 men. In 29 of these 92 men (32%) when followed weekly serum PSA levels did not return to baseline as expected according to the published serum PSA half-life of 2 to 3 days. Biopsies taking 3 or fewer cores (7 patients) resulted in a smaller increase in serum PSA (mean 1.63 +/- 1.12 times the baseline level versus 6.24 +/- 1.10 times baseline, p less than 0.03) and a proportionally shorter duration of PSA elevation (mean 1.43 +/- 0.48 weeks versus 2.13 +/- 0.14 weeks, p = 0.20) than those taking 4 or more cores (93 patients). Prostate size and the presence of cancer had no influence on the duration of PSA elevation following biopsy. We conclude that digital rectal examination, prostatic massage and ultrasonography have minimal effects on serum PSA levels in most patients. However, prostatic needle biopsy usually causes marked elevations of serum PSA levels with a persistent PSA leak into the blood stream lasting longer than expected from the serum half-life of PSA in approximately 25% of the patients.

In only about 10% of men with symptoms of chronic prostatitis/chronic pelvic pain syndrome can bacterial infection of the prostate be demonstrated by the Meares & Stamey 4-glass or the pre and post prostate massage (PPM) 2-glass test. Chronic bacterial prostatitis is mainly caused by Gram-negative uropathogens. The role of Gram-positives, such as staphylococci and enterococci, and atypicals, such as chlamydia, ureaplasmas, mycoplasmas, are still debatable. For treatment, fluoroquinolones are considered the drugs of choice because of their favorable pharmacokinetic properties and their antimicrobial spectrum. Because relapse and reinfection are major problems in chronic bacterial prostatitis, only the results of studies with a follow-up period of at least 6 months are meaningful. Analyzing the concentrations of various fluoroquinolones in prostatic and seminal fluid as well as in prostatic tissue, however, it becomes obvious that the fluoroquinolones differ not only in plasma concentrations but also in their penetration ability to these sites. Nevertheless, overall the concentrations at the site of infection of most of the fluoroquinolones with this indication should be sufficient for the treatment of chronic bacterial prostatitis and vesiculitis caused by highly susceptible pathogens. However, the increasing resistance of Escherichia coli, the most frequent uropathogens, against fluoroquinolones in many countries is of great concern.

MicroRNAs constitute a class of small cellular RNAs (typically 19-23 nt) that function as post-transcriptional regulators of gene expression. Current estimates indicate that more than one third of the human cellular transcriptome is regulated by this small class of RNA (∼2000 miRNA). MicroRNAs have been shown to be actively exported from tissues into the circulation through a variety of mechanisms including complexing with RNA binding proteins or HDL and through active exosome transport. Exosomes are nanovesicles secreted into the extracellular environment by a wide range of cell types under normal and pathological conditions. As the profile of exosomal microRNAs may be a fingerprint of the releasing cell type and because they are released in easily accessible body fluids such as blood and urine, their microRNA content holds potential as biomarkers for early detection of malignancy. Cell free urine samples are an obvious liquid biopsy source for microRNA markers in prostate cancer and could serve as diagnostic tools as well as treatment response markers. Yet microRNA levels in urine samples are extremely sparse and cannot be detected reliable by conventional sample preparation methods. It has been reported that tumour derived exosomes carrying genetic information specific for prostate cancer can be measured in urine samples following prostate massage. However, a methodology eliminating the need for prostate massage of every patient to be tested in a clinical setting is highly desirable. The purpose of this study was to combine a simple exosomal enrichment method with our highly sensitive LNA™-based qPCR platform for detection of microRNAs and apply this to a cohort consisting of more than 300 cell free urine samples from prostate cancer cases and controls. In conclusion, cell free urine samples holds potential as a liquid biopsy source for exosomal microRNA markers in prostate cancer, showing miRNA signatures of strong diagnostic potential. Analysis is pending and data will be presented. Citation Format: Thorarinn Blondal, Anni R. Thomsen, Jörg Krummheuer, Michael Borre, Jacob Fredsøe, Christa Haldrup, Ditte Andreasen, Maria W. Teilum, Niels Tolstrup, Karina D. Sørensen, Torben F. Ørntoft, Peter Mouritzen. Exosomal microRNA in cell-free urine samples as a source for liquid prostate cancer biopsy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3987. doi:10.1158/1538-7445.AM2015-3987

INTRODUCTION: The exact mechanism of chronic nonbacterial prostatitis has not been yet elucidated and the outcome with the current management is dismal. In this trial, we studied the effect of allopurinol in the treatment of this disease. MATERIALS AND METHODS: In this randomized double blind controlled trial, a calculated sample size of 56 were grouped into "intervention group" who received allopurinol (100 mg tds for 3 months) with ofloxacin (200 mg tds) for 3 weeks (n = 29) and "control group" who received placebo tablets with ofloxacin (n = 27). Patients’ scores based on the National Institute of Health Chronic Prostatitis Symptom Score were recorded before therapy and then every month during the study. A four-glass study was performed before intervention and after 3 months. RESULTS: The 2 groups were similar regarding outcome variables. In the first month of study, a significant but similar improvement in symptom scores was observed in both groups. Microscopic examination of prostate massage and post-massage samples were also similar in both groups. No side effects due to allopurinol were observed in patients. CONCLUSION: We did not find any advantage for allopurinol in the management of chronic prostatitis versus placebo in patients receiving routine antibacterial treatment.

Male genital tract inflammations constitute an important factor of male subfertility in which different mediators are discussed damaging sperm membranes. As acrosome reaction (AR) is ultimately a membrane function, this study aimed at investigating the effects of the chronic pelvic pain syndrome on AR. In a total of 56 patients with chronic pelvic pain syndrome NIH IIIA and NIH IIIB, AR, concentration of leucocytes in ejaculate and urine after prostate massage, sperm concentration, motility, vitality and morphology were determined. The control group (n=95) consisted of patients with normozoospermia and proven absence of signs of inflammation. Compared to the control, both patients groups showed poorer sperm morphology (P

As the prostate can harbor bacterial and fungal pathogens, it was investigated as a reservoir for HIV. Nine men chronically infected with HIV participated in a crossover trial in which weekly semen samples were collected with and without previous prostate massage (PM). Six of the nine participants had undetectable seminal plasma(SP) HIV RNA in all samples without previous PM, but had detectable SP HIV RNA (> 25 copies/ml) in one to three samples collected after PM.

A total of 388 patients with symptoms of chronic prostatitis and inflammatory findings in expressed prostatic secretion (EPS) or in a urine sample collected immediately after prostate massage, were examined over a 2 year period at the Outpatient Department for Urogenital Infections, University Hospital for Infectious Diseases 'Dr Fran Mihaljevic', Zagreb, Croatia. The infective aetiology was determined in 276 (71.13%) patients. Chlamydia trachomatis was the causative pathogen in 109 patients, Trichomonas vaginalis in 52, Escherichia coli in 26, enterococci in 25, Proteus mirabilis in 14, Klebsiella pneumoniae in six, Streptococcus agalactiae in eight, Ureaplasma urealyticum in seven patients with chronic prostatitis. Other patients had a mixed infection.

Objectives In men ascending Chlamydia trachomatis (CT) infection may result in the inflammatory process in the prostate. It has been suggested that chronic inflammation and infectious agents related to prostatitis may be involved in prostate cancer (PrCa) susceptibility. Nevertheless, the role of CT in the pathogenesis of this common among sexually active men morbidity is still not clear. Better understanding of the host9s response to CT and the precise pathways in the PrCa development are of great interest. Up to now prostate biopsy (PBx) remains the only test that can confirm the diagnosis of PrCa. Serum prostate-specific antigen (PSA) test has been used worldwide to screen men for PrCa but can results in a significant proportion of negative PBx and prostate cancer antigen 3 (PCA3, first catch of the urine collected after prostate massage) test may be of valuable help in some PSA quandary situations. We present a clinical case with symptomatic CT infection affecting the PrCa diagnosis. Methods In October 2010, a white man 38 y.o. with a history of unprotected sex and followed lower urinary tract symptoms (LUTS) and erectile dysfunction for more than 3 months was applying for STIs and PrCa testing. CT infection was detected by RT-PCR. Physical and digital rectal examinations (DRE) were performed and the number of WBC in the prostate secretion was counted. The results of PSA and PCA3 tests resulted in PBx. Results The results are presented in the Abstract P3-S1.04 table 1. CT positivity was assessed in St. Petersburg by in-house RT-PCR test that was confirmed by an internationally validated molecular test as it has been described elsewhere. No other STIs were detected. The prescribed treatment succeeded: LUTS were released, no CT infection was detected. Interestingly, serum PSA tests showed abnormal results before and 1 month after antibacterial treatment. A cut-off score was exceeded in an additionally prescribed PCA3 test. PBx was performed but histological examination revealed no evidence of PCa but prostate inflammation. Conclusions Further studies to evaluate the time course of prostatitis/STIs on PrCa risk, particularly among a young cohort of men, have been warranted. New diagnostic markers are needed to investigate the pathways between the acquisition of CT and its impact on the prostate. This is the first report on detection of abnormal PSA and PCA3 tests in a Chlamydia-infected man suffering from LUTS, while no PrCa was histologically detected.

Background Methylation-specific polymerase chain reaction (MSP) targeting promoter hypermethylation of the glutathione S transferase P1 gene (GSTP1), as the most frequent DNA alteration in prostatic carcinoma, was used for the molecular detection of cell-bound and cell-free prostate tumor DNA in various human bodily fluids. Materials and methods We investigated GSTP1 promoter hypermethylation in DNA isolated from plasma, serum, nucleated blood cells, ejaculates, urines after prostate massage, and prostate tissue from 33 patients with prostate cancer and 26 control patients with benign prostatic hyperplasia (BPH). Using a viral DNA extraction kit specifically recommended for DNA isolation from urine samples, GSTP1 promoter hypermethylation in urine sediments after prostatic massage was investigated in a cohort of 29 patients with prostate cancer and 40 controls with BPH. Fluorescently labeled MSP products were analyzed on an automated gene sequencer. Results GSTP1 promoter hypermethylation was found in 90% of tumors (18 of 20), 72% of plasma or serum samples (23 of 32), 50% of ejaculates (4 of 8), and between 36% (4 of 11; normal DNA isolation kit) and 76% (22 of 29; viral kit) of exprimated urines from patients with prostate cancer. Also, MSP identified circulating tumor cells in 30% (10 out of 33) of prostate cancer patients. Except for one urine sample, GSTP1 promoter hypermethylation was not found in tissue and body fluids from patients with BPH. Conclusion GSTP1 promoter methylation analysis provides a highly specific tool for DNA-based diagnosis of prostate cancer in body fluids.

Purpose : To determine the value of prostate bed massage as a means to determine whether a rising prostate specific antigen (PSA) after radical prostatectomy is due to local recurrence or distant metastases. Methods and Materials : Eighteen patients referred for pelvic radiotherapy because of a rising PSA after radical prostatectomy had PSA levels measured immediately before and 5 minutes after a vigorous 30-second massage ofthe prostate bed. Results : Only one ofthe 18 (5%) patients experienced a rise in their PSA following vigorous prostate bed massage. Fifteen of the 18 (83%) patients' PSA levels declined after radiotherapy, suggesting that recurrent prostate cancer had been present in the prostate bed at the time of prostate massage in these patients. Only I of these 15 patients (7%) had a rise in their PSA after massage. Conclusion: Prostate bed massage, as performed in this study, was not helpful to determine whether a rise in PSA after radical prostatectomy was due to local or distant recurrence.

We report a case in which a regular prostate massage (chronic prostatitis) turned into a life-threatening event. After the prostate massage, an enormous periprostatic hemorrhage developed. During hospitalization the patient developed an embolic insult to the lungs. To our knowledge no ther cases have been published. This report shows the potentially serious consequences, and we conclude that any pain after prostate massage needs further diagnostic steps (ultrasound, CT scan).

PSA is a 34-kDa 240-amino-acid glycoprotein produced exclusively by prostatic epithelial cells. PSA is a serine protease, is a member of the kallikrein gene family, and has a high sequence homology with human glandular kallikrein. It has chymotrypsin-, trypsin-, and esterase-like activities. In the serum it is present mainly in a complex form with alpha 1-antichymotrypsin. It is secreted in the seminal plasma and is responsible for liquefaction of the seminal coagulum. The production of PSA proteins appears to be under the control of circulating androgens acting through the androgen receptors. The PSA gene is up-regulated predominantly by androgens at both the protein and mRNA levels. DRE causes minimal changes in the PSA level, while prostate massage, ultrasonography, systoscopic examination, and prostate biopsy can all cause clinically significant elevations. Other conditions, such as prostatitis, prostate intraepithelial neoplasia, acute urinary retention, and renal failure can also elevate the PSA level. The value of PSA as a screening tool is questionable because of the great deal of overlap in PSA levels between BPH and prostate cancer. However, if used in men over 50, in conjunction with DRE and/or ultrasonography, it may become a vital part of the early detection program. PSA's role in determining the clinical and pathological stage is also limited, in spite of the direct correlation between the pathological stage and the PSA level, because of great overlap in the PSA levels in various stages. The most important clinical utility of PSA is in monitoring patients after definitive therapy. PSA is most sensitive and reliable in the detection of a residual tumor, possibly recurrence, or disease progression following treatment, irrespective of the treatment modality. PSA can accurately predict the tumor status and can detect recurrence several months before its detection by any other method. PSA is also a very sensitive and specific immunohistochemical marker for tumors of prostatic origin. Compared to PAP, PSA is a more precise and meaningful marker in all clinical situations. With the development of ultrasensitive assays and the adoption of an international standard PSA calibrator, so that results from multicenter studies can be compared, PSA could become one of the most useful tumor marker in cancer biology.