Free PSA performs better than total PSA in predicting prostate volume in Chinese men with PSA levels of 2.5-9.9 ng ml-1.

This study investigated whether free prostate-specific antigen (fPSA) performs better than total PSA (tPSA) in predicting prostate volume (PV) in Chinese men with different PSA levels. A total of 5463 men with PSA levels of <10 ng ml-1 and without prostate cancer diagnosis were included in this study. Patients were classified into four groups: PSA <2.5 ng ml-1, 2.5-3.9 ng ml-1, 4.0-9.9 ng ml-1, and 2.5-9.9 ng ml-1. Pearson/Spearman's correlation coefficient (r) and receiver operating characteristic (ROC) curves were used to evaluate the ability of tPSA and fPSA to predict PV. The correlation coefficient between tPSA and PV in the PSA <2.5 ng ml-1 cohort (r = 0.422; P < 0.001) was markedly higher than those of the cohorts with PSA levels of 2.5-3.9 ng ml-1, 4.0-9.9 ng ml-1, and 2.5-9.9 ng ml-1 (r = 0.114, 0.167, and 0.264, respectively; all P ≤ 0.001), while fPSA levels did not differ significantly among different PSA groups. Area under ROC curve (AUC) analyses revealed that the performance of fPSA in predicting PV ≥40 ml (AUC: 0.694, 0.714, and 0.727) was better than that of tPSA (AUC = 0.545, 0.561, and 0.611) in men with PSA levels of 2.5-3.9 ng ml-1, 4.0-9.9 ng ml-1, and 2.5-9.9 ng ml-1, respectively, but not at PSA levels of <2.5 ng ml-1 (AUC: 0.713 vs 0.720). These findings suggest that the relationship between tPSA and PV may vary with PSA level and that fPSA is more powerful at predicting PV only in the ''gray zone'' (PSA levels of 2.5-9.9 ng ml-1), but its performance was similar to that of tPSA at PSA levels of <2.5 ng ml-1.

Successful treatment of encrusted cystitis: A case report and review of literature.

BACKGROUND: Encrusted cystitis (EC) is a chronic inflammation of the bladder associated with mucosal encrustations. Early diagnosis and optimal treatment are not well established. Here, we report a case of EC successfully treated with com-bination therapy. CASE SUMMARY: A 27-year-old man presented with frequency, urgency, dysuria, gross hematuria and suprapubic pain for 2 mo. He was diagnosed with EC based on characteristic calcifications of the bladder wall (most of them were struvite), cystoscopy and histopathological examination. He was cured after combined therapy of elimination of encrustations, bladder instillation of hyaluronic acid and injection of botulinum-A neurotoxin into bladder submucosal tissue. CONCLUSION: Bladder instillation of hyaluronic acid and injection of botulinum-A neurotoxin into the bladder submucosal tissue can be used for treatment of EC.

Prospective Study of CRMP4 Promoter Methylation in Prostate Biopsies as a Predictor For Lymph Node Metastases.

Background: For patients with prostate cancer (PCa), the presence of pelvic lymph node metastasis (LNM) is a strong predictor of poor outcome. However, the approaches with promising sensitivity and specificity to detect LNM are still lacking. We investigated the value of collapsin response mediator protein 4 (CRMP4) promoter methylation in biopsies as a predictor for LNM. Methods: CRMP4 promoter methylation at two previously identified CpG sites was determined in 80 case-matched biopsy samples (the training set) using bisulfite pyrosequencing. The predictive cutoff value was independently validated using cohort I of 339 PCa patients (Southern China) and cohort II of 328 case patients (Germany, across China). Mann-Whitney U test, the receiver operating characteristic curve, McNemar's test, and logistic regression were used to assess data. All statistical tests were two-sided. Results: In the training set, CRMP4 promoter methylation (≥15.0% methylated) was statistically significantly associated with LNM (P < 001). Successful validations were achieved in both cohorts I and II (sensitivity = 92.3%, 95% confidence interval [CI] = 79.3 to 97.9, and sensitivity = 92.2%, 95% CI = 81.1 to 97.8, respectively; specificity = 92.7%, 95% CI = 80.2 to 99.1, and specificity = 91.3%, 95% CI = 87.4 to 94.4, respectively). The sensitivity of CRMP4 promoter methylation is superior to conventional MRI (cohort I: 92.3% vs 26.2%, P < 001; cohort II: 92.2% vs 33.3%, P < 001). CRMP4 promoter methylation is an independent predictor of LNM (cohort I: hazard ratio [HR] = 8.35, 95% CI = 5.64 to 12.35, P < 001; cohort II: HR = 12.46, 95% CI = 5.82 to 26.70, P < 001) in a multivariable analysis model. Conclusion: CRMP4 promoter methylation in diagnostic biopsies could be a robust biomarker for LNM in PCa.

PSA density improves the rate of prostate cancer detection in Chinese men with a PSA between 2.5-10.0 ng ml (-1) and 10.1-20.0 ng ml (-1) : a multicenter study.

Chinese men should have a higher prostate-specific antigen (PSA) "gray zone" than the traditional value of 2.5-10.0 ng ml-1 since the incidence of prostate cancer (PCa) in Chinese men is relative low. We hypothesized that PSA density (PSAD) could improve the rate of PCa detection in Chinese men with a PSA higher than the traditional PSA "gray zone." A total of 461 men with a PSA between 2.5 and 20.0 ng ml-1 , who had undergone prostatic biopsy at two Chinese centers were included in the analysis. The men were then further divided into groups with a PSA between 2.5-10.0 ng ml-1 and 10.1-20.0 ng ml-1 . Receiver operating characteristic (ROC) curve was used to evaluate the efficacy of PSA and PSAD for the diagnosis of PCa. In men with a PSA of 2.5-10.0 ng ml-1 or 10.1-20.0 ng ml-1 , the areas under the ROC curve were higher for PSAD than for PSA. This was consistent across both centers and the cohort overall. When the entire cohort was considered, the optimal PSAD cut-off for predicting PCa in men with a PSA of 2.5-10.0 ng ml-1 was 0.15 ng ml-1 ml-1 , with a sensitivity of 64.4% and specificity of 64.6%. The optimal cut-off for PSAD in men with a PSA of 10.1-20.0 ng ml-1 was 0.33 ng ml-1 ml-1 , with a sensitivity of 60.3% and specificity of 82.7%. PSAD can improve the effectiveness for PCa detection in Chinese men with a PSA of 2.5-10.0 ng ml-1 (traditional Western PSA "gray zone") and 10.1-20.0 ng ml-1 (Chinese PSA "gray zone").

Effectiveness and complication rates of tension-free vaginal tape, transobturator tape, and tension-free vaginal tape-obturator in the treatment of female stress urinary incontinence in a medium- to long-term follow up. Meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness and complications of tension-free vaginal tape (TVT), transobturator tape (TOT), and tension-free vaginal tape-obturator (TVT-O) in a medium- to long-term follow up. METHODS: We searched PubMed, EMBASE, Cochrane database, ClinicalTrials.gov, Google Scholar, and the International Continence Society (ICS) website from August to December 2012 in Guangzhou First People's Hospital, Guangzhou, China. Randomized controlled trials (RCTs) comparing the effectiveness and complications of TVT, TOT, and TVT-O were selected. RESULTS: Forty RCTs were included. The TVT and TOT had similar subjective (risk ratio [RR]: 0.99; 95% confidence interval [CI]: 0.93-1.04), and objective cure rates (RR: 0.96; 95% CI: 0.70-1.32). However, TVT had a reduced risk of groin/thigh pain (RR: 0.33; 95% CI: 0.18-0.59). The subjective (RR: 1.02; 95% CI: 0.97-1.06) and objective cure rates (RR: 1.02; 95% CI: 0.99-1.06) of TVT-O were similar to TVT, but TVT had a higher risk of bladder perforations (RR: 2.29; 95% CI: 1.18-4.45). The TVT-O and TOT had similar subjective (RR: 0.99; 95% CI: 0.93-1.06), and objective cure rates (RR: 1.01; 95% CI: 0.95-1.07). However, TVT-O had a lower risk of vaginal erosion rates (RR: 0.16; 95% CI: 0.03-0.89). CONCLUSION: The subjective and objective cure rates of stress urinary incontinence were similar among TVT, TOT, and TVT-O in a medium- to long-term follow up. The TVT had a higher risk of bladder perforation than TVT-O, and a lower risk of groin/thigh pain than TOT, and TVT-O had a lower risk of vaginal erosion rates than TOT.

Prostate volume as an independent predictor of prostate cancer in men with PSA of 10-50 ng ml(-1).

Prostate volume (PV) has been shown to be associated with prostate cancer (PCa) detection rates in men with a prostate-specific antigen (PSA) in the 'grey zone' (2.0-10.0 ng ml(-1)). However, the PSA 'grey zone' in Asian men should be higher because the incidence of PCa in Asian men is relatively low. Therefore, we evaluated the association between PV and PCa detection rates in men with PSAs measuring 10-50 ng ml(-1). Men who underwent a 13-core prostatic biopsy with PV documentation participated in the study. A multivariate stepwise regression was used to evaluate whether the PV at time of prostate biopsy could predict the risk of PCa. The rates of PCa among men in different PSA ranges, stratified by PV medians (<60 and ≥60 ml), were calculated. There were 261 men included in the final analysis. PV was the strongest predictor of PCa risk (odds ratio, 0.02; P<0.001) compared to other variables. The PCa rates in men with PVs measuring <60 and ≥60 ml in the 10-19.9 ng ml(-1) PSA group were 40.6% and 15.1%, respectively, while the rates for men with PSAs measuring 20-50 ng ml(-1) were 65.1% and 26.8%. PV is an independent predictor of PCa in men with PSA measuring 10-50 ng ml(-1). In clinical practice, particularly for those countries with lower incidences of PCa, PV should be considered when counselling patients with PSAs measuring 10-50 ng ml(-1) regarding their PCa risks.

A nomogram based on age, prostate-specific antigen level, prostate volume and digital rectal examination for predicting risk of prostate cancer.

Nomograms for predicting the risk of prostate cancer developed using other populations may introduce sizable bias when applied to a Chinese cohort. In the present study, we sought to develop a nomogram for predicting the probability of a positive initial prostate biopsy in a Chinese population. A total of 535 Chinese men who underwent a prostatic biopsy for the detection of prostate cancer in the past decade with complete biopsy data were included. Stepwise logistic regression was used to determine the independent predictors of a positive initial biopsy. Age, prostate-specific antigen (PSA), prostate volume (PV), digital rectal examination (DRE) status, % free PSA and transrectal ultrasound (TRUS) findings were included in the analysis. A nomogram model was developed that was based on these independent predictors to calculate the probability of a positive initial prostate biopsy. A receiver-operating characteristic curve was used to assess the accuracy of using the nomogram and PSA levels alone for predicting positive prostate biopsy. The rate for positive initial prostate biopsy was 41.7% (223/535). The independent variables used to predict a positive initial prostate biopsy were age, PSA, PV and DRE status. The areas under the receiver-operating characteristic curve for a positive initial prostate biopsy for PSA alone and the nomogram were 79.7% and 84.8%, respectively. Our results indicate that the risk of a positive initial prostate biopsy can be predicted to a satisfactory level in a Chinese population using our nomogram. The nomogram can be used to identify and counsel patients who should consider a prostate biopsy, ultimately enhancing accuracy in diagnosing prostate cancer.

[2-deoxyglucose enhances chemosensitivity of androgen-independent prostate cancer cells to docetaxel].

OBJECTIVE: To explore the antitumor effects of 2-deoxyglucose (2-DG) plus docetaxel (Doc) on PC3 and DU145 cells and its mechanism. METHODS: The proliferation of cells was detected by methyl thiazolyl tetrazolium (MTT) assay. Then propidium iodide (PI) staining measured apoptotic cells on flow cytometry. ATP assay kit was used to detect ATP content. The expressions of proteins ubiquitinated protein (Ub) and Hsp70 were measured by Western blot. RESULTS: 2-DG could inhibit proliferation of PC3 and DU145 cells in a dose- and time-dependent manner. However, it could not induce apoptosis in PC3 or DU145. The inhibition rates for PC3 proliferation at 48 h by Doc with concentrations of 0.1, 0.5, 2.5 nmol/L were 10.71%, 25.32% and 56.46% respectively. The inhibition rates for DU145 cell proliferation at 48h by Doc with concentrations of 0.1, 0.5, 2.5 nmol/L were 12.28%, 23.94% and 63.43% respectively. The inhibition rates for PC3 cell proliferation by Doc plus 2-DG with a concentration of 1.0 g/L were 27.15%, 58.74% and 87.95% respectively and 29.53%, 59.41%, and 90.48% for DU145 respectively. 2-DG could enhance the effectiveness of inhibition to PC3 and DU145 proliferation by Doc with a synergistic manner (all q>1.15). The apoptotic rates for PC3 and DU145 induced by Doc 0.5 nmol/L plus 2-DG 1.0 g/L at 48 h were 46.49% and 53.64% respectively. The apoptotic rates were significantly higher than Doc 0.5 nmol/L alone (21.30% for PC3 and 18.92% for DU145 respectively) (P < 0.05). The ATP relative concentration for PC3 in 2-DG 1.0 g/L at 0, 12, 24, 48, and 72 h were 13.75, 11.23, 10.19, 9.81 and 9.02 and for DU145 15.00, 12.59, 11.38, 10.54 and 10.37 respectively. Simultaneously, Western blot showed that Ub and Hsp70 protein were expressed intensively. CONCLUSIONS: 2-DG can enhance the sensitivity of androgen-independent prostate cancer cells to docetaxel. Its mechanism may be associated with the decrease of proteasome function.

ERG rearrangement for predicting subsequent cancer diagnosis in high-grade prostatic intraepithelial neoplasia and lymph node metastasis.

PURPOSE: We aimed to analyze whether ERG rearrangement in biopsies could be used to assess subsequent cancer diagnosis in high-grade prostatic intraepithelial neoplasia (HGPIN) and the risk of lymph node metastasis in early prostate cancer. EXPERIMENTAL DESIGN: Samples from 523 patients (361 with early prostate cancer and 162 with HGPIN) were collected prospectively. On the basis of the cutoff value established previously, the 162 patients with HGPIN were stratified to two groups: one with an ERG rearrangements rate ≥1.6% (n = 59) and the other with an ERG rearrangements rate <1.6% (n = 103). For the 361 prostate cancer cases undergoing radical prostatectomy, 143 had pelvic lymph node dissection (node-positive, n = 56 and node-negative, n = 87). All ERG rearrangement FISH data were validated with ERG immunohistochemistry. RESULTS: A total of 56 (of 59, 94.9%) HGPIN cases with an ERG rearrangements rate ≥1.6% and 5 (of 103, 4.9%) HGPIN cases with an ERG rearrangements rate <1.6% were diagnosed with prostate cancer during repeat biopsy follow-ups (P < 0.001). There were significant differences in ERG rearrangement rates between lymph node-positive and -negative prostate cancer (P < 0.001). The optimal cutoff value to predict lymph node metastasis by ERG rearrangement was established, being 2.6% with a sensitivity at 80.4% [95% confidence interval (CI), 67.6-89.8] and a specificity at 85.1% (95% CI, 75.8-91.8). ERG protein expression by immunohistochemistry was highly concordant with ERG rearrangement by FISH. CONCLUSIONS: The presence of ERG rearrangement in HGPIN lesions detected on initial biopsy warrants repeat biopsies and measuring ERG rearrangement could be used for assessing the risk of lymph node metastasis in early prostate cancer.

[The effect of prostatectomy on nocturia in patients with benign prostatic hyperplasia].

OBJECTIVE: To explore the effect of prostatectomy on nocturia in patients with benign prostatic hyperplasia (BPH). METHODS: The data of patients who had received prostatectomy for BPH between June 2006 and December 2007 were collected. Nocturia severity was assessed preoperatively and 3 to 6 months after prostatectomy by the number of nocturia events, the time from falling sleep to the first awakening to void (hours of undisturbed sleep, HUS), the score of the nocturia quality of life (N-QOL) questionnaire, the International Prostatic Symptom Score (IPSS) and the quality of life (QOL) score. RESULTS: One hundred and twenty five cases were included. Of them, 73 patients finished the follow-up completely. There were 62 patients whose number of nocturia events before the operation was equal or more than 2. The data from these 62 patients were analyzed. Of them, 56 patients underwent transurethral resection of prostate, the remaining 11 patients suprapubic prostatectomy. Significant improvement (P < 0.01) was noted in all the following parameters after treatment: the number of nocturia events decreased from 4.2 ± 2.4 to 2.2 ± 1.0, HUS increased from (1.8 ± 0.7) h to (3.0 ± 1.4) h, N-QOL score raised from 30 ± 10 to 40 ± 7, IPSS decreased from 23 ± 5 to 8 ± 5, and QOL score fell down from 4.4 ± 0.7 to 1.5 ± 1.0. CONCLUSION: The prostatectomy can markedly improve the symptoms of nocturia, sleep and life quality in the BPH patients who accompanied with nocturia.

Antibacterial therapy improves the effectiveness of prostate cancer detection using prostate-specific antigen in patients with asymptomatic prostatitis.

OBJECTIVES: To improve prostate cancer (PC) detection accuracy among patients with a prostate-specific antigen (PSA) above 4.0 ng/ml and asymptomatic prostate inflammation. MATERIALS AND METHODS: A total of 136 patients with PSA ranging from 4.0 to 50.0 ng/ml with asymptomatic prostatitis were included in the study cohort. All these patients underwent antibacterial therapy for 2 weeks followed by repeat PSA determination and transrectal ultrasound-guided needle prostate biopsy. The PSA, PSAD (PSA density), and f/t PSA (free/total PSA) before and after antibacterial therapy were compared using t-test. The receiver-operating characteristic (ROC) technique was used to evaluate the effectiveness of PSA, PSAD, f/t PSA, and their changes after antibacterial therapy (DeltaPSA, DeltaPSAD, and Deltaf/t PSA) on PC detection. RESULTS: Among the 136 patients, 33 had PC and the other 103 histologically confirmed benign prostatic disease. After antibacterial therapy for 2 weeks, the PSA (mean +/- standard deviation) decreased from 14.0 +/- 7.8 ng/ml to 10.4 +/- 7.7 ng/ml (P < 0.01). The DeltaPSA, DeltaPSAD, and Deltaf/tPSA were -3.60 +/- 4.3 ng/ml, -0.1 +/- 0.1 ng/ml/ml, and -0.1 +/- 0.1 respectively. The areas under ROC curve were 0.29 for PSA, 0.64 for PSAD, and 0.50 for f/t PSA. The areas under ROC curve were 0.91 for DeltaPSA, 0.96 for DeltaPSAD, and 0.98 for Deltaf/t PSA. These values were increased significantly when compared with those for the PSA-related parameters before antibacterial therapy (P value, DeltaPSA, DeltaPSAD, and Deltaf/t PSA were <0.01). CONCLUSIONS: Using the changes in PSA-related parameters after antibacterial therapy DeltaPSA, DeltaPSAD, and Deltaf/t PSA improve the PC detection rate and decrease unnecessary prostate biopsies in patients with asymptomatic prostatitis.

[Nephrotoxicity of tacrolimus and preventive effect of diltiazem: experiment with rats].

OBJECTIVE: To study the nephrotoxicity tacrolimus (FK506) at the therapeutic dose the preventive effect of diltiazem (Dil), a calcium antagonist against the FK506-induced pathological changes. METHODS: 24 Sprague-Dawley male rats were randomly divided into 4 equal groups: cyclosporine A (CsA) group, undergoing treatment of CsA at the therapeutic dose after kidney transplantation (25 mg x kg(-1) x d(-1)) for 4 weeks, FK506 group treated with FK506 (0.8 mg x kg(-1) x d(-1)), FK506 + Dil group treated with FK506 (0.8 mg x kg(-1) x d(-1)) and Dil at the dose of 8 mg x kg(-1) x d(-1), and control group. Four weeks later body weight was measured and 24 h urine sample was collected. Then the rats were killed. Their kidneys underwent light and transmission electron microscopy. RESULTS: The body weight ad weight gain, and the weights of both kidney of the CsA group were all significantly lower than those of the other 3 groups (all P < 0.05), and there were not significant differences in there parameters among the other 3 groups. The serum creatinine levels of the FK506 and CsA groups were (36.0 +/- 2.6) and (34.2 +/- 4.5) micromol/L respectively, both significantly higher than those of the FK506 + Dil and control groups [(28.5 +/- 2.1) and (29.2 +/- 3.428) micromol/L respectively, all P < 0.05], however, there was no significant difference between the FK506 + Dil and control groups. The creatinine clearance rate of the FK506 and CsA groups were (0.63 +/- 0.45) and (0.58 +/- 0.39) ml x min(-1) x 100 g(-1) respectively, significantly lower than those of the FK506 + Dil and control groups [(1.55 +/- 0.91) and (1.02 +/- 0.62) mlxmin(-1) x 100 g(-1) respectively, all P < 0.05]. Pathological examination showed epithelial cell cloudy swelling and vacuolization and interstitial fibrosis in the renal tubules, mitochondria swelling and vacuolization in renal tubular epithelial cells, renal arteriole hyalinization, and foot cell conjugation glomerulus, mitochondria swelling and vacuolization in the FK506 and CsA groups, and such changes were relatively mild in the FK506 + Dil group. CONCLUSION: FK506 at renal transplantation therapeutic dose, as well as CsA, induces pathological changes in renal tissues and ultrastructural organization. Dil is able to prevent FK506-induced these pathological changes.

[Prevention of diltiazem in tacrolimus-induced nephrotoxicity: experiment with rats].

OBJECTIVE: To study the nephrotoxicity induced by first oral administration of tacrolimus (FK506) and the prevention of diltiazem (Dil). METHODS: 24 Sprague-Dawley male rats were randomly divided into 4 equal groups: control (n = 6), cyclosporine A (CsA) group (receiving CsA 25 mg.kg(-1).d(-1) so as to develop CsA-induced nephropathy model), FK506 group (receiving FK506 0.8 mg.kg(-1).d(-1), the common renal transplantation therapeutic dose, so as to develop FK506-induced nephropathy model), FK506 + Dil group (receiving CsA 0.8 mg.kg(-1).d(-1) and Dil 8 mg.kg(-1).d(-1)), and control group. Four weeks later body weight was measured, blood samples were collected to examine the creatinine, urea nitrogen, and uric acid, and urine samples were collected to examine the 24 h urine protein, uric acid, and creatinine. Then the rats were killed with their kidneys taken out to undergo histopathological examination. RESULTS: The urine creatinine levels of the CsA and FK506 groups were significantly lower than that of the control group (both P < 0.05), however, there was no significant difference in urine creatinine between the FK506 + Dil group and control group. The blood creatinine levels of both CsA and FK506 groups were significantly higher than those of the FK506 + Dil group and control group (all P < 0.05), however, there was no significant difference in blood creatinine between the FK506 + Dil group and control group. The urea nitrogen level of the CsA group was significantly higher than those of the other 3 groups (all P < 0.05). The creatinine clearance rates of the CsA and FK506 groups were both significantly lower than that of the control group (both P < 0.05), and the creatinine clearance rate of the FK506 + Dil group was between those of the FK506 group and control group, however, with significant differences with both of them. Histopathology examination showed cloudy swelling and vacuolization of the renal tubular epithelial cells in the CsA and FK506 groups. However, the pathological changes of the FK506 + Dil group were remarkably milder in comparison with these 2 groups. CONCLUSION: FK506 and CsA at the renal transplantation therapeutic dose induce nephrotoxicity. Diltiazem prevents FK506-induced nephrotoxicity.