Elevated Prostate-specific Antigen Levels Research Articles

Effect of obesity on International Prostate Symptom Score and prostate volume.

Aim:The aim of this study was to investigate the relationship between obesity and lower urinary tract symptoms and prostate volume in patients who underwent prostate biopsies.Materials and Methods:Between December 2008 and November 2009, transrectal ultrasound-guided prostate biopsy was performed on patients who had elevated prostate-specific antigen levels or abnormal digital rectal examination findings. A total of 211 patients were included in this study. Prostate volumes, International Prostate Symptom Score (IPSS) values, and the patient's height and weight were all recorded during the biopsy. Body mass index (BMI) <18.5 was determined as underweight, 18.5–23.0 normal, 23.0–27.5 overweight, and >27.5 obese.Results:The mean age of the patients was 68.0 ± 6.3 years, and the mean BMI was 28.0 ± 4.9 kg/m2. The mean prostate volume of the normal, overweight, and obese groups was 30, 50, and 70 ml, respectively. The positive and statistically significant correlation between BMI and prostate volume was determined (P < 0.001). According to BMI, the mean IPSS was 8.0, 16.5, and 20.0 in the groups, respectively. Similarly, a statistically positive correlation between BMI and IPSS was demonstrated (P < 0.001).Conclusions:As the result of a rise in BMI, prostate volumes and IPSS increase in patients. Prostate volume and IPSS decrease due to weight loss, and hence that fewer urinary symptoms occur, and the quality-of-life of patients may increase.

Augmented immunoexpression of survivin correlates with parameters of aggressiveness in prostate cancer.

The clinical significance of the immunoexpression of survivin in prostate cancer and its correlation with the biological aggressiveness of prostate cancer remains unclear. Therefore, the present study was undertaken to compare the immunoexpression of survivin in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) as well as to determine whether this immunoexpression could correlate with Gleason score, proliferation activity and prostate specific antigen (PSA) levels. The prostate needle biopsies from 28 patients with elevated serum PSA levels were studied. As a control, 12 needle biopsies of prostate diagnosed as BPH were used. The immunoexpression of survivin was evaluated semiquantitatively, whereas the Ki-67 index was assessed quantitatively. The immunoexpression of survivin and Ki-67 in epithelial cells in the prostate cancer group was significantly increased as compared to BPH cases. In the prostate cancer group there were positive significant correlations between the immunoexpression of survivin and Gleason score as well as Ki‑67 antigen. The correlation between the immunoexpression of survivin and PSA levels was also positive, but it did not reach statistical significance. In conclusion, we can confirm that in prostate cancer the immunoexpression of survivin is augmented as compared to BPH and positively correlated with parameters of tumor aggressiveness.

Lower Levels of Human MOB3B Are Associated with Prostate Cancer Susceptibility and Aggressive Clinicopathological Characteristics.

Mps one binder (MOB) proteins are integral components of signaling pathways that control important cellular processes, such as mitotic exit, centrosome duplication, apoptosis, and cell proliferation. However, the biochemical and cellular functions of the human MOB (hMOB) protein family remain largely unknown. The present study investigated the association between hMOB3B expression and clinicopathological characteristics of prostate cancer (PCa).Study subjects included 137 PCa patients and 137 age-matched benign prostatic hyperplasia (BPH) patients. hMOB3B expression was estimated using real-time PCR and compared with clinicopathological parameters of PCa. hMOB3B mRNA expression was significantly lower in PCa tissues than in BPH control tissues (P<0.001). According to receiver operating characteristics curve analysis, the sensitivity of hMOB3B expression for PCa diagnosis was 84.7%, with a specificity of 86% (AUC=0.910; 95% CI=0.869-0.941; P<0.001). hMOB3B expression was significantly lower in patients with elevated prostate specific antigen (PSA) levels (≥10 ng/mL), a Gleason score≥8, and metastatic disease (any T, N+/M+) than in those with low PSA levels, a low Gleason score, and non-metastatic disease (each P<0.05). In conclusion, low levels of hMOB3B are closely associated with aggressive clinicopathologic features in patients with PCa. Our results suggest that hMOB3B may act as a tumor suppressor in human PCa.

Effect of taurine on prostate-specific antigen level and migration in human prostate cancer cells.

In Korea, prostate cancer incidence has significantly increased in recent years. Prostate-specific antigen (PSA) is a marker for prostate cancer, and elevated serum PSA levels have been associated with prostate intraepithelial neoplasms. Meanwhile, metastasis is a process by which cancer spreads from the place at which it first arose as a primary tumor to distant locations in the body. The so-called tissue inhibitors of metalloproteinases (TIMPs), which are naturally occurring inhibitors of matrix metalloproteinases (MMPs), play an important role in the complex regulation of MMPs. They inhibit the catalytic activity of MMPs by binding to activated MMPs and control breakdown of extracellular matrix. Thus, the balance between MMPs and TIMPs plays a vital role in maintaining the integrity of healthy tissues, and MMP inhibitors, as well as TIMP activators, are expected to be useful chemotherapeutic agents for the treatment of malignancies. In addition, vascular endothelial growth factor (VEGF) plays an important role in prostate cancer invasion. VEGF is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. In the present study, therefore, we investigated the anti-prostate cancer metastasis effect of taurine, and proved taurine suppressed PSA and several metastasis-related genes in human prostate cancer cells, LNCaP and PC-3. In addition, taurine inhibited migration of LNCaP and PC-3.

Complete response to ethnylestradiol prolonged for almost two years in patients with castration-resistant prostate cancer

An 80-year-old man with an elevated prostate-specific antigen (PSA) level of 120 ng/mL) presented to the hospital in February 2011. A prostate needle biopsy was performed, and pathological examination revealed prostatic adenocarcinoma. The Gleason score was 4+5=9. Computed tomography revealed metastases of the pelvic lymph nodes. Combined androgen blockade was started. The PSA concentration decreased to 1.68 ng/mL, but started increasing again in August 2012 to 6.08 ng/mL. Although bicalutamide was discontinued due to antiandrogen withdrawal syndrome, the PSA concentration increased even more. The PSA concentration reached 21.62 ng/mL in September 2012, at which time ethnylestradiol was started. The PSA concentration decreased again and has remained below the limit of sensitivity for almost 2 years. To our knowledge, this is first case report describing a complete response to ethnylestradiol that lasted for almost 2 years in a patient with castration-resistant prostate cancer.

The role of transurethral resection of the prostate for patients with an elevated prostate-specific antigen.

PurposeThe aim of this study was to define the clinical significance of transurethral resection of the prostate (TURP) in patients with benign prostate hyperplasia (BPH) and an elevated prostate-specific antigen (PSA) level.MethodsWe retrospectively evaluated patients with BPH, lower urinary tract symptoms (LUTS; International Prostate Symptom Score [IPSS]≥8), an elevated serum PSA level (≥4 ng/mL), and previous negative transrectal ultrasonography (TRUS) guided prostate biopsy. The PSA level after TURP was monitored by long-term follow-up. The tumor detection rate on resected prostate tissue, IPSS, maximal urinary flow rate (Qmax), and postvoid residual urine (PVR) were analyzed.ResultsOne-hundred and eighty-six patients were enrolled. Histological examination of resected tissue by TURP revealed prostate cancer in 12 of these patients (6.5%). Among 174 patients without prostate cancer, the mean PSA level and the PSA normalization rate in 112 patients followed up at postoperative day (POD) 3 months were 1.26±0.13 ng/mL and 94.6%, respectively. The mean PSA level and the PSA normalization rate were 1.28±1.01 ng/mL and 95.7% in 47 patients at 1st year, 1.17±0.82 ng/mL and 97.1% in 34 patients at second years, and 1.34±1.44 ng/mL and 97.2% in 36 patients at third years of TURP. One patient showed a dramatic increase in the PSA level was diagnosed with prostate cancer at 7 years after TURP. IPSS, quality of life, Qmax, and PVR were improved significantly at POD 3 months compared to baseline (P<0.05), respectively.ConclusionsTURP significantly reduced the serum PSA level, which was maintained for at least 3 years. This could be helpful to screen the prostate cancer using PSA value in the patient with previous negative biopsy and elevated PSA. In addition, TURP improves IPSS, Qmax, and PVR in patients with BPH, moderate LUTS, and an elevated PSA level.

Impact of the 2012 United States Preventive Services Task Force statement on prostate-specific antigen screening: analysis of urologic and primary care practices.

To identify the effect of the 2012 United States Preventive Services Task Force (USPSTF) prostate-specific antigen (PSA) recommendation statement on primary care referral patterns and urologists' decision making. Men referred to our institution for newly elevated PSA level from June 2011 to June 2013 were identified. Patients with a prior history of prostate cancer or biopsy were excluded. Clinical and management parameters were compared between those presenting in the year before vs the year after the USPSTF statement. Factors predictive of receiving a prostate biopsy were identified using multivariate regression analysis. A total of 201 men were identified in the pre-USPSTF period and 212 men, thereafter. The groups were comparable in age, race, prostate cancer family history, PSA values, and digital rectal examination findings. At the initial evaluation, patients presenting after the statement were more likely to undergo PCA3 testing (27% vs 11%; P <.01) and repeat PSA testing (82% vs 72%; P = .02) and less likely to undergo immediate biopsy (16% vs 24%; P = .03). The proportion of patients ultimately receiving a biopsy was equivalent. The groups were similar in the percentage of positive biopsies, Gleason distribution, and D'Amico risk. African American race and family history were predictors for receiving a biopsy in the post-USPSTF group but not in the pre-USPSTF group. The 2012 USPSTF recommendation statement has not affected the number or clinical characteristics of patients referred to a tertiary center for elevated PSA level. After recommendation, urologists ordered significantly more PCA3 and repeat PSA tests and recommended fewer biopsies at the initial visit. The fraction of patients ultimately receiving a biopsy remained the same.

Clinical Presentation and Outcomes of Prostate Cancer in an Urban Cohort of Predominantly African American, Human Immunodeficiency Virus–infected Patients

To determine the clinical presentation and outcomes of prostate cancer in human immunodeficiency virus (HIV)-infected men compared with HIV-uninfected men in an urban setting. A retrospective cohort study of prostate cancer stage at diagnosis and mortality comparing HIV-infected patients with HIV-uninfected patients from 2000 to 2011 was carried out. Clinical features, HIV history, cancer presentation, and outcomes were reviewed. Cox proportional hazards analysis was performed to estimate the association between HIV status and mortality. A total of 54 HIV-infected subjects were identified and reviewed, and 49 of them had complete data available; they were compared with 1496 HIV-uninfected subjects with prostate cancer. HIV-infected subjects were younger (median age, 60.7 vs 64 years) and had a higher proportion of African Americans (92% vs. 45%). An elevated prostate-specific antigen (PSA) level (76%) was the predominant indication for biopsy; 10 patients (27%) with an elevated PSA level had normal findings on digital rectal examination. Eighteen men (37%) presented with stage III and IV disease compared with 14% in the general population (P <.001). Eight patients (16%) died of prostate cancer. Subjects with HIV progressed to death at a significantly faster rate than those in the general population (adjusted hazard ratio, 2.02; 95% confidence interval, 1.14-3.58). HIV-infected patients in this cohort presented with more advanced stage disease compared with the general population even though the majority were detected by screening PSA. The overall mortality rate was higher for HIV-infected patients with prostate cancer after controlling for race, tumor stage at diagnosis, and age. Prostate cancer screening methods may need to be individualized for HIV-infected men.

The impact of the use of aspirin and other nonsteroidal anti-inflammatory drugs on the risk of prostate cancer detection on biopsy.

To evaluate the association between nonsteroidal anti-inflammatory drug (NSAID) use and the risk of prostate cancer (PC) detection in men undergoing biopsy. Men were identified using our academic institution's prospectively maintained prostate biopsy database. Patients were classified as aspirin (ASA) users, users of other NSAIDs, or nonusers. The primary outcome was any PC on biopsy, and the secondary outcome was clinically significant PC (CSPC; Gleason sum ≥7). Multivariate logistic regression analyses were performed to adjust for a priori defined clinical confounders. Of 839 patients, 408 (48.6%) were diagnosed with PC and 201 (24.0%) had CSPC. A higher proportion of ASA users (63.5%) and other NSAID users (61.2%) had PC compared with nonusers (41.9%; P <.001). CSPC was more common among ASA users (34.9%; P <.001) compared with other NSAID users (20.0%) and nonusers (20.9%). In multivariate regression analyses, ASA use (odds ratio [OR] = 2.04; 95% confidence interval [CI] = 1.32-3.13; P = .001) and other NSAID use (OR = 2.42; 95% CI = 1.36-431; P = .003) were associated with higher odds of PC detection, whereas ASA use was associated with higher odds of CSPC (OR = 1.62; 95% CI = 1.00-2.62; P = .048). In men undergoing biopsy, ASA and other NSAID use were associated with increased probability of detecting PC, whereas ASA use was associated with the risk of detecting CSPC. Although NSAID use might have a protective biological effect against PC, men who develop elevated prostate-specific antigen levels while on NSAIDs may nonetheless be less likely to have an inflammatory etiology and more likely to harbor PC. It may be warranted for clinicians to consider the influence of NSAIDs when evaluating patients being considered for biopsy.

Metabolic syndrome-like components and prostate cancer risk: results from the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study.

To evaluate the relationship between number of metabolic syndrome (MetS)-like components and prostate cancer diagnosis in a group of men where nearly all biopsies were taken independent of prostate-specific antigen (PSA) level, thus minimising any confounding from how the various MetS-like components may influence PSA levels. We analysed data from 6426 men in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study with at least one on-study biopsy. REDUCE compared dutasteride vs placebo on prostate cancer risk among men with an elevated PSA level and negative pre-study biopsy and included two on-study biopsies regardless of PSA level at 2 and 4 years. Available data for MetS-like components included data on diabetes, hypertension, hypercholesterolaemia, and body mass index. The association between number of these MetS-like components and prostate cancer risk and low-grade (Gleason sum <7) or high-grade (Gleason sum >7) vs no prostate cancer was evaluated using logistic regression. In all, 2171 men (34%) had one MetS-like component, 724 (11%) had two, and 163 (3%) had three or four. Men with more MetS-like components had lower PSA levels (P = 0.029). One vs no MetS-like components was protective for overall prostate cancer (P = 0.041) and low-grade prostate cancer (P = 0.010). Two (P = 0.69) or three to four (P = 0.15) MetS-like components were not significantly related to prostate cancer. While one MetS-like component was unrelated to high-grade prostate cancer (P = 0.97), two (P = 0.059) or three to four MetS-like components (P = 0.02) were associated with increased high-grade prostate cancer risk, although only the latter was significant. When biopsies are largely PSA level independent, men with an initial elevated PSA level and a previous negative biopsy, and multiple MetS-like components were at an increased risk of high-grade prostate cancer, suggesting the link between MetS-like components and high-grade prostate cancer is unrelated to a lowered PSA level.

Multiparametric magnetic resonance imaging (MRI) and subsequent MRI/ultrasonography fusion‐guided biopsy increase the detection of anteriorly located prostate cancers

To describe the detection rate of anteriorly located prostate cancer (PCa) with the addition of magnetic resonance imaging (MRI)/ultrasonography (US) fusion-guided biopsy (FGB) to the standard transrectal ultrasonography (TRUS)-guided biopsy. All patients, regardless of their biopsy history, who were referred for clinical suspicion of PCa (i.e elevated prostate-specific antigen (PSA) level and abnormal digital rectal examination) underwent 3T multiparametric-MRI (mpMRI) screening; and those with suspicious lesions in the anterior region of the prostate were identified. Patients then received a FGB of all suspicious lesions in addition to a systematic 12-core extended sextant TRUS-guided biopsy. We conducted a lesion-based analysis comparing cancer detection rates of anterior targets using FGB vs systematic cores taken from the same anatomic sextant within the prostate. Lengths of cancer in the most involved core were also compared between the two biopsy techniques used. Patients with only anterior targets were analysed separately. Of 499 patients undergoing FGB, 162 had a total of 241 anterior lesions. The mean age, PSA level and prostate volume in this group were 62 years, 12.7 ng/dL, and 57 mL, respectively. In total, PCa was diagnosed in 121 anterior lesions (50.2%) identified on mpMRI. Sixty-two (25.7%) of these anterior lesions were documented as positive for cancer on systematic 12-core TRUS-guided biopsy cores, while 97 (40.2%) were positive on the targeted FGB cores (P = 0.001). In lesions that were positive on both FGB and TRUS biopsy, the most involved core was 112% longer on FGB (3.7 vs 1.6 mm, P ≤ 0.01). Forty-two patients had only anterior lesions on mpMRI; of these, 24 (57.1%) were found to have cancer on the FGB + TRUS biopsy platform. Six patients were positive on FGB only and 13 were positive on both biopsy techniques; however, 7/13 patients were upgraded to a higher Gleason score after FGB. All five patients positive on TRUS biopsy only were candidates for active surveillance. The results showed that FGB detects significantly more anteriorly located PCa than does TRUS-guided biopsy alone and it may serve as an effective tool for the subset of patients with such tumours.

Commentary on “Asymptomatic prostatic inflammation in men with clinical BPH and erectile dysfunction affects the positive predictive value of prostate-specific antigen.” Agnihotri S, Mittal RD, Kapoor R, Mandhani A, Department of Urology & Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.: Urol Oncol 2014; [Epub ahead of print]. doi: 10.1016/j.urolonc.2014.03.004.

ObjectiveTo test the hypothesis that sexual dysfunction in elderly men with benign prostatic hyperplasia leads to prostatic inflammation, diagnosed by prostatic fluid interleukin-8 (IL-8), which lowers the positive predictive value of prostate-specific antigen (PSA). MethodsOverall, 160 men with lower urinary tract symptoms between 50 and 75 years of age with an elevated PSA level of more than 4ng/ml with normal digital rectal examination and 50 age-matched controls with normal PSA level were prospectively evaluated for prostatic fluid IL-8 levels. Erectile dysfunction was measured by self-administered questionnaire of the Sexual Health Inventory for Men. Total and free serum PSA levels and IL-8 in prostatic fluid were measured 6 to 8 weeks after a course of 400mg of ofloxacin and 20mg of piroxicam given daily for 2 weeks. Transrectal ultrasonography-guided biopsy was done only when PSA level did not decrease less than 4ng/ml. ResultsMean ages of patients and controls were 63.18 (standard deviation [SD]±7.10) and 60.18 (SD+6.02) years, respectively. Mean concentration of IL-8 in prostatic fluid of the patients was significantly higher, i.e., 6,678pg/ml (SD±1,985.7) than in control, i.e., 1,543pg/ml (SD±375.7) (P<0.001). Following anti-inflammatory treatment, there was a significant decrease in the mean level of IL-8 from baseline to 5,622pg/ml (SD±1,870.66) (P<0.001). Corresponding to this, a significant decrease was noted in total PSA levels to less than 4ng/ml in 105 (65.62%) patients. Men with the highest levels of IL-8 had a greater degree of erectile dysfunction. ConclusionMen with symptomatic benign prostatic hyperplasia and erectile dysfunction had significant inflammation of the prostate to cause spurious rise in PSA level resulting in an unnecessary biopsy.

Cumulative probability of prostate cancer detection using the international prostate symptom score in a prostate-specific antigen-based population screening program in Japan.

The International Prostate Symptom Score (IPSS) is often used as an interview sheet for assessing lower urinary tract symptoms (LUTS) at the time of prostate-specific antigen (PSA) testing during population-based screening for prostate cancer. However, the relationship between prostate cancer detection and LUTS status remains controversial. To elucidate this relationship, the cumulative probability of prostate cancer detection using IPSS in biopsy samples from patients categorized by serum PSA levels was investigated. The clinical characteristics of prostate cancer detected using IPSS during screening were also investigated. A total of 1,739 men aged 54-75 years with elevated serum PSA levels who completed the IPSS questionnaire during the initial population screening in Kanazawa City, Japan and underwent systematic transrectal ultrasonography-guided prostate biopsy between 2000 and 2013 were enrolled in the present study. Of the 1,739 men, 544 (31.3%) were diagnosed with prostate cancer during the observation period. The probability of cancer detection at 3 years in the entire study population was 27.4% and 32.7% for men with IPSS ≤ 7 and those with IPSS ≥ 8, respectively; there was no statistically significant difference between groups. In men with serum PSA levels of 6.1 to 12.0 ng/ mL at initial screening, the probability of cancer detection was significantly higher in men with IPSS ≤ 7 than in those with IPSS ≥ 8. There were no significant differences in clinical characteristics between groups of patients stratified by IPSS. These findings indicate that the use of IPSS for LUTS status evaluation may be useful for prostate cancer detection in the limited range of serum PSA levels.

Outcomes of men with an elevated prostate-specific antigen (PSA) level as their sole preoperative intermediate- or high-risk feature.

To investigate the post-prostatectomy and long-term outcomes of men presenting with an elevated pretreatment prostate-specific antigen (PSA) level (>10 ng/mL), but otherwise low-risk features (biopsy Gleason score ≤6 and clinical stage ≤T2a). PSA-incongruent intermediate-risk (PII) cases were defined as those patients with preoperative PSA >10 and ≤20 ng/mL but otherwise low-risk features, and PSA-incongruent high-risk (PIH) cases were defined as men with PSA >20 ng/mL but otherwise low-risk features. Our institutional radical prostatectomy database (1992-2012) was queried and the results were stratified into D'Amico low-, intermediate- and high risk, PSA-incongruent intermediate-risk and PSA-incongruent high-risk cases. Prostate cancer (PCa) features and outcomes were evaluated using appropriate comparative tests. Multivariable analyses were adjusted for age, race and year of surgery. Of the total cohort of 17 608 men, 1132 (6.4%) had PII-risk disease and 183 (1.0%) had PIH-risk disease. Compared with the low-risk group, the odds of upgrading at radical prostatectomy (RP) were 2.20 (95% CI 1.93-2.52; P < 0.001) for the PII group and 3.58 (95% CI 2.64-4.85; P < 0.001) for the PIH group, the odds of extraprostatic disease at RP were 2.35 (95% CI 2.05-2.68; P < 0.001) for the PII group and 6.68 (95% CI 4.89-9.15; P < 0.001) for the PIH group, and the odds of positive surgical margins were 1.97 (95% CI 1.67-2.33; P < 0.001) for the PII group and 3.54 (95% CI 2.50-4.95, P < 0.001) for the PIH group. Compared with low-risk disease, PII-risk disease was associated with a 2.85-, 2.99- and 3.32-fold greater risk of biochemical recurrence (BCR), metastasis and PCa-specific mortality, respectively, and PIH-risk disease was associated with a 5.32-, 6.14- and 7.07-fold greater risk of BCR, metastasis and PCa-specific mortality, respectively (P ≤ 0.001 for all comparisons). For the PII group, the higher risks of positive surgical margins, upgrading, upstaging and BCR were dependent on PSA density (PSAD): men in the PII group who had a PSAD <0.15 ng/mL/g were not at higher risk compared with those in the low-risk group. Men in the PII group with a PSAD ≥0.15 ng/mL/g and men in the PIH group were more likely to have an anterior component of the dominant tumour (59 and 64%, respectively) compared with those in the low- (35%) and intermediate-risk group (39%) and those in the PII-risk group with PSAD <0.15 ng/mL/g (29%). Men with PSA >20 ng/mL or men with PSA >10 and ≤20 ng/mL with a PSAD ≥0.15 ng/mL/g, but otherwise low-risk PCa, are at greater risk of adverse pathological and oncological outcomes and may be inappropriate candidates for active surveillance. These men are at greater risk of having anterior tumours that are undersampled at biopsy, so if treatment is deferred, ancillary testing such as anterior zone sampling or magnetic resonance imaging should be strongly encouraged. Men with elevated PSA levels >10 and ≤20 ng/mL but low PSAD have outcomes similar to those in the low-risk group, and consideration of surveillance is appropriate in these cases.

Correlation between frequencies of blood monocytic myeloid-derived suppressor cells, regulatory T cells and negative prognostic markers in patients with castration-resistant metastatic prostate cancer.

Myeloid-derived suppressor cells (MDSC) are believed to play a role in immune suppression and subsequent failure of T cells to mount an efficient anti-tumor response, by employing both direct T-cell inhibition as well as induction of regulatory T cells (Tregs). Investigating the frequency and function of immune suppressive cell subsets in the peripheral blood of 41 patients with prostate cancer (PC) and 36 healthy donors (HD) showed a significant increase in circulating CD14(+) HLA-DR(low/neg) monocytic MDSC (M-MDSC) and Tregs in patients with PC compared to HD. Furthermore, M-MDSC frequencies correlated positively with Treg levels. In vitro proliferation assay with autologous T cells confirmed M-MDSC-mediated T-cell suppression, and intracellular staining of immune suppressive enzyme iNOS revealed a higher expression in M-MDSC from patients with PC. Increased frequencies of M-MDSC correlated with known negative prognostic markers in patients with PC including elevated levels of lactate dehydrogenase and prostate-specific antigen. Accordingly, high levels of M-MDSC were associated with a shorter median overall survival. Our data strongly suggest that M-MDSC, possibly along with Tregs, play a role in establishing an immune suppressive environment in patients with PC. Moreover, correlation of M-MDSC frequency with known prognostic markers and the observed impact on OS could reflect a possible role in tumor progression. Further insight into the generation and function of MDSC and their interplay with Tregs and other cell types may suggest ways to tackle their induction and/or function to improve immunological tumor control.

Asymptomatic prostatic inflammation in men with clinical BPH and erectile dysfunction affects the positive predictive value of prostate-specific antigen

ObjectiveTo test the hypothesis that sexual dysfunction in elderly men with benign prostatic hyperplasia leads to prostatic inflammation, diagnosed by prostatic fluid interleukin-8 (IL-8), which lowers the positive predictive value of prostate-specific antigen (PSA). MethodsOverall, 160 men with lower urinary tract symptoms between 50 and 75 years of age with an elevated PSA level of more than 4ng/ml with normal digital rectal examination and 50 age-matched controls with normal PSA level were prospectively evaluated for prostatic fluid IL-8 levels. Erectile dysfunction was measured by self-administered questionnaire of the Sexual Health Inventory for Men. Total and free serum PSA levels and IL-8 in prostatic fluid were measured 6 to 8 weeks after a course of 400mg of ofloxacin and 20mg of piroxicam given daily for 2 weeks. Transrectal ultrasonography–guided biopsy was done only when PSA level did not decrease less than 4ng/ml. ResultsMean ages of patients and controls were 63.18 (standard deviation [SD]±7.10) and 60.18 (SD+6.02) years, respectively. Mean concentration of IL-8 in prostatic fluid of the patients was significantly higher, i.e., 6678pg/ml (SD±1985.7) than in control, i.e., 1543pg/ml (SD±375.7) (P<0.001). Following anti-inflammatory treatment, there was a significant decrease in the mean level of IL-8 from baseline to 5622pg/ml (SD±1870.66) (P<0.001). Corresponding to this, a significant decrease was noted in total PSA levels to less than 4ng/ml in 105 (65.62%) patients. Men with the highest levels of IL-8 had a greater degree of erectile dysfunction. ConclusionMen with symptomatic benign prostatic hyperplasia and erectile dysfunction had significant inflammation of the prostate to cause spurious rise in PSA level resulting in an unnecessary biopsy.

MiR-1 and miR-133b are differentially expressed in patients with recurrent prostate cancer.

Prostate cancer (PCa) is currently the most frequently diagnosed malignancy in the western countries. It is more prevalent in older men with 75% of the incident cases above 65 years old. After radical prostatectomy, approximately 30% of men develop clinical recurrence with elevated serum prostate-specific antigen levels. Therefore, it is important to unravel the molecular mechanisms underlying PCa progression to develop novel diagnostic/therapeutic approaches. In this study, it is aimed to compare the microRNA (miRNA) profile of recurrent and non-recurrent prostate tumor tissues to explore the possible involvement of miRNAs in PCa progression. Total RNA from 41 recurrent and 41 non-recurrent PCa tissue samples were used to investigate the miRNA signature in PCa specimens. First of all, 20 recurrent and 20 non-recurrent PCa samples were profiled using miRNA microarray chips. Of the differentially expressed miRNAs, miR-1, miR-133b and miR-145* were selected for further validation with qRT-PCR in a different set of 21 recurrent and 21 non-recurrent PCa samples. Data were statistically analyzed using two-sided Student's t-test, Pearson Correlation test, Receiver operating characteristic analysis. Our results demonstrated that miR-1 and mir-133b have been significantly downregulated in recurrent PCa specimens in comparison to non-recurrent PCa samples and have sufficient power to distinguish recurrent specimens from non-recurrent ones on their own. Here, we report that the relative expression of miR-1 and mir-133b have been significantly reduced in recurrent PCa specimens in comparison to non-recurrent PCa samples, which can serve as novel biomarkers for prediction of PCa progression.

Combination of lidocaine suppository and periprostatic nerve block during transrectal prostate biopsy: a prospective randomized trial.

To assess the most effective local analgesia during transrectal ultrasound-guided prostate biopsy. A total of 123 consecutive patients undergoing transrectal ultrasound-guided prostate biopsy for elevated prostate-specific antigen levels and/or a suspicious digital rectal examination were randomized to three groups. Patients received a 60-mg lidocaine suppository (group 1, n = 41), a periprostatic nerve block (10-mL injection of lidocaine hydrochloride; group 2, n = 41) or a combination of both (group 3, n = 41) before a 10-core transrectal ultrasound-guided biopsy. A total of 80.5% (n = 99) of the patients underwent their first biopsy, 27.1% (n = 22) their second and 2.4% (n = 2) the third. Pain was evaluated on a 10-point visual analog scale for each step of the procedure. Prostate-specific antigen values ranged from 0.39 to 90.1 (mean [SD] 8.76 ng/mL [11.08 ng/mL]). Comparison of the median visual analog scale scores between groups 1 and 2 showed a significant difference (P = 0.004). The differences in the outcomes between groups 1 and 3 (P = 0.001), and groups 2 and 3 (P = 0.001) were also significant. Patients of group 3 had the best output corresponding to the pain sensations and therefore the lowest visual analog scale scores. The combination of lidocaine suppository and periprostatic lidocaine infiltration is more effective for pain control than either lidocaine suppository or periprostatic lidocaine infiltration alone in patients undergoing transrectal ultrasound-guided prostate biopsy.

Histopathologic characterization of prostate diseases in Madinah, Saudi Arabia.

To delineate the histopathological pattern of prostate diseases and to highlight age variations in prostate specific antigen (PSA) values and histopathological features. A retrospective review was made of all prostate biopsy reports seen between January 2006 and December 2013 at the King Fahad Hospital, Madinah, Saudi Arabia. Prostate lesions were tabulated and classified into benign and malignant groups. Histological scoring of adenocarcinomas was accomplished using the Gleason system. PSA values were correlated with Gleason scores. Of 417 prostate lesions reviewed, 343 (82.3%) were benign and 74 (17.7%) were malignant, giving a benign to malignant ratio of 4.6:1. Benign prostatic hyperplasia (both with and without inflammation) was the commonest prostatic lesion and accounted for 80.3% of all cases and 97.6% of all benign cases. The age range was 20 to 97 years with a mean of 69.2 years and a peak age group at 70-79 years. Seventy one cases of adenocarcinoma accounted for 95.9% of the total of 74 malignant tumors. It showed an age range of 44 to 95 years, a mean age of 70.9 years and peak prevalence in the 80-89 year age group. Gleason score seven was the most frequent (39.4%) in occurrence. Most adenocarcinomas, 41 cases (57.7%), were moderately differentiated (Gleason score of 5-7). PSA values ranged widely between 16-1,865 ng/ml with a mean of 363.4 ng/ml. Elevated PSA (>100 ng/ml) levels were found in 53 (81.6%) patients. There was a statistically significant positive correlation between serum PSA level and Gleason score (p=0.0304). Prostatic lesions constitute a significant source of morbidity among adult males in Madinah. Benign prostatic hyperplasia was the commonest benign prostatic lesion and adenocarcinoma was the commonest histological subtype of prostatic cancer.

Biopsia de próstata en pacientes con diagnóstico clínico de hiperplasia prostática benigna y relación con el antígeno prostático específico

BackgroundBenign prostatic hyperplasia (BPH) is the most frequent benign tumor in men above 50 years of age. Initial suspicion of prostate cancer is based on a digital rectal examination with abnormal findings or elevated serum levels of prostate-specific antigen (PSA) (≥ 4ng/mL); these patients must be evaluated in order to rule out prostate cancer. AimsThe aim of the present study was to determine the association of ultrasound-guided prostate biopsy with prostate cancer diagnosis in patients presenting with clinical BPH diagnosis. Material and methodsA descriptive analytic study was conducted within the time frame of January to July 2012. Patients diagnosed with BPH that underwent ultrasound-guided prostate biopsy were included. Data were analyzed through descriptive statistics, categorical variables were compared using the chi-square test, and odds ratio was used to determine association. ResultsThe mean age of the BPH patients was 68.5 ± 9.9 years (39-93) and the mean PSA (standard deviation, SD) was 5.9 ± 6.4ng/mL. Of these patients, 166 (47.8%) had normal PSA and in 181 (52.2%) it was abnormal. The patients with BPH had an odds ratio (OR) of 1.8 (95% CI = 1.5- 2.6); ultrasound-guided prostate biopsy was performed if they had an abnormal PSA, regardless of digital rectal examination findings and age. ConclusionsIn our study, the patients clinically diagnosed with BPH underwent ultrasoundguided prostate biopsy based on PSA levels in the majority of the cases, to rule out prostate cancer. The patients that underwent the biopsy presented with significantly higher PSA levels (10.9 ± 6.6 vs. 4.6 ± 5.4ng/mL, p=0.0001), but only 28 (32%) of them had a digital rectal examination, and free PSA and PSA density or velocity were not determined. The ultrasound-guided prostate biopsy requested by the urologists in the majority of the cases was not based on the recommendations of the clinical practice guidelines (CPG).