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.

Randomized controlled trial of intravesical electrical stimulation for underactive bladder.

AIM: To evaluate the efficacy and safety of intravesical electrical stimulation (IVES) performed with a novel device in patients with underactive bladder (UAB). PATIENTS AND METHODS: This was a multicentre, prospective, single-blind, randomized controlled clinical trial of patients with UAB in China. Eligible patients were randomly assigned in a 1:1 ratio to receive conventional IVES (n = 38) or IVES with an open circuit (n = 38). The primary efficacy measure was change from baseline in post-void residual urine volume (PVR) after 4 weeks of treatment. Secondary efficacy measures included changes in maximum urinary flow rate (Qmax ), bladder voiding efficiency (BVE), number of 24-h clean intermittent catheterization (CIC) procedures, and Patient Perception of Bladder Condition-Scale (PPBC-S) and American Urological Association Symptom Index Quality of Life (AUA-SI-QoL) scores from baseline after 4 weeks of treatment. Adverse events (AEs) were monitored throughout the trial. RESULTS: In the full analysis set (FAS), the mean (sd) PVR changes in the trial and control groups at 4 weeks were -97.1 (107.5) mL and -10.5 (86.7) mL, respectively (P < 0.01). Similar results were obtained in the per-protocol set (PPS): -102.9 (100.0) mL vs 0.7 (82.5) mL (P < 0.01). In the FAS and PPS, Qmax improved significantly at 4 weeks (P = 0.04 and P = 0.03). In the FAS and PPS, BVE was significantly improved at 4 weeks in the two groups (P < 0.01 and P < 0.01), whereas no significant differences in the number of 24-h CIC procedures, PPBC-S score or AUA-SI-QoL score were observed between the groups. Six possible therapy-related AEs occurred in six patients (four in the trial group and two in the control group; P = 0.67), all of which were urinary tract infections. No severe AEs were reported. CONCLUSIONS: The results of this clinical study strongly demonstrate that UAB patients benefit from this novel IVES device. More research is needed to validate the clinical utility of this device.

Intravesical injection of botulinum toxin type a may be an effective treatment option for autonomic dysreflexia in patients with high-level spinal cord injury.

OBJECTIVE: To evaluate the efficacy of intravesical injection of botulinum toxin type A (BTX-A) for neurogenic detrusor overactivity (DO) in reducing the frequency and severity of autonomic dysreflexia (AD). DESIGN: A cross-sectional nonrandomized trial with before (baseline) and after (follow-up) assessments. SETTING: A single spinal cord injury (SCI) rehabilitation center in China. PARTICIPANTS: Twenty-five patients with SCI at or above T6 and a history of AD who underwent urodynamic studies (UDS) before and 3 months after BTX-A injection. INTERVENTIONS: Received bladder injection treatment wtih 200 U BTX-A. OUTCOME MEASURES: The maximum detrusor pressure(Pdetmax) and voume at first DO(VFIDC), baseline and overall maximum systolic blood pressure (SBP) during UDS, and scores of Incontinence Specific Quality of Life Instrument (IQoL) were recorded before and 3 months after the injection. The change in SBP (ΔSBP) from baseline to maximum SBP during UDS was calculated to assess the severity. The frequency of AD was recorded using ambulatory blood pressure monitoring during a 24 h period before and 3 months after the injection. RESULTS: BTX-A injection decreased the Pdetmax and increased the VFIDC and mean urine volume per catheterization increased. The maximum SBP and the ΔSBP during UDS decreased significantly decreased after the injection (151.44 ± 13.92 vs 133.32 ± 9.20 mmHg and 49.44 ± 12.81 vs 33.08 ± 9.11 mmHg respectively, P < 0.05). The frequency of bladder-related ADs (i.e. performed a clean intermittent catheterization or leakage) during a 24-h period significantly decreased from 11.04 ± 1.81-7.88 ± 2.15 (P < 0.001). CONCLUSIONS: BTX-A decreases the severity of SBP increase and the number of AD episodes 3 months after intravesical injection.

Hengli® Chinese Botulinum Toxin Type A for Treatment of Patients With Overactive Bladder: A Multicenter, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: To evaluate the efficacy and safety of Hengli® Chinese botulinum toxin type A (BTX-A; 100 U) in Chinese patients with overactive bladder. Methods: This study was a multicenter, randomized, double-blind, placebo-controlled trial in Chinese patients who were inadequately managed with anticholinergic medications. Eligible patients were randomized 2:1 to receive intradetrusor injections of Hengli® BTX-A (n = 144) or placebo (n = 72). The primary endpoint was the change in the number of daily micturition episodes at week 6 from baseline. The secondary efficacy endpoints included the average frequency of urgency and urinary incontinence (UI) episodes per day, urgency score, average micturition volume per day, OABSS, and QoL score. Results: In the Hengli® BTX-A group, there was a significantly greater reduction in the average number of micturition episodes per 24 h compared with the placebo group (3.28 vs. 1.43; p = 0.003). Moreover, there was a significantly greater improvement in the daily number of urgency episodes, micturition volume and OABSS score. An increased post-void residual urine volume, dysuria, and urinary tract infection represented adverse events (AEs) in the Hengli® BTX-A group. Most AEs were mild or moderate in severity. One patient in the BTX-A group initiated clean intermittent catheterization (CIC) during treatment. Conclusion: Hengli® BTX-A treatment was well-tolerated and resulted in significant improvements in OAB symptoms among Chinese patients inadequately managed by anticholinergics. Clinical Trial Registration: http://www.chinadrugtrials.org.cn/clinicaltrials.prosearch.dhtml, Identifier: CTR20131190.

Tumor-derived exosomal BCYRN1 activates WNT5A/VEGF-C/VEGFR3 feedforward loop to drive lymphatic metastasis of bladder cancer.

BACKGROUND: Patients with lymph node (LN) metastatic bladder cancer (BCa) present with extremely poor prognosis. BCa-derived exosomes function as crucial bioactive cargo carriers to mediate the signal transduction in tumor microenvironment triggering tumor metastasis. However, the mechanisms underlying exosome-mediated LN metastasis in BCa are unclear. METHODS: We conducted the high-throughput sequencing to explore the expression profile of long noncoding RNA (lncRNA) in urinary exosomes (urinary-EXO) from patients with BCa and further evaluated the clinical relevance of exosomal lncRNA BCYRN1 in a larger 210-case cohort. The functional role of exosomal BCYRN1 was evaluated through the migration and tube formation assays in vitro and the footpad-popliteal LN metastasis model in vivo. RNA pull-down assays, luciferase assays, and actinomycin assays were conducted to detect the regulatory mechanism of exosomal BCYRN1. RESULTS: LncRNA BCYRN1 was substantially upregulated in urinary-EXO from patients with BCa, and associated with the LN metastasis of BCa. We demonstrated that exosomal BCYRN1 markedly promoted tube formation and migration of human lymphatic endothelial cells (HLECs) in vitro and lymphangiogenesis and LN metastasis of BCa in vivo. Mechanistically, BCYRN1 epigenetically upregulated WNT5A expression by inducing hnRNPA1-associated H3K4 trimethylation in WNT5A promoter, which activated Wnt/ß-catenin signaling to facilitate the secretion of VEGF-C in BCa. Moreover, exosomal BCYRN1 was transmitted to HLECs to stabilize the VEGFR3 mRNA and thus formed an hnRNPA1/WNT5A/VEGFR3 feedforward regulatory loop, ultimately promoting the lymphatic metastasis of BCa. Importantly, blocking VEGFR3 with specific inhibitor, SAR131675 significantly impaired exosomal BCYRN1-induced the LN metastasis in vivo. Clinically, exosomal BCYRN1 was positively associated with the shorter survival of BCa patients and identified as a poor prognostic factor of patients. CONCLUSION: Our results uncover a novel mechanism by which exosomal BCYRN1 synergistically enhances VEGF-C/VEGFR3 signaling-induced lymphatic metastasis of BCa, indicating that BCYRN1 may serve as an encouraging therapeutic target for patients with BCa.

Targeting WD repeat domain 5 enhances chemosensitivity and inhibits proliferation and programmed death-ligand 1 expression in bladder cancer.

BACKGROUND: Chemotherapy and/or immunotherapy are first-line treatments for advanced muscle-invasive bladder cancer (BCa), but the unsatisfactory objective response rate to these treatments yields poor 5-year patient survival. Discovery of therapeutic targets essential for BCa maintenance is critical to improve therapy response in clinic. This study evaluated the role of targeting WD repeat domain 5 (WDR5) with the small molecule compound OICR-9429 and whether it could be used to treat bladder cancer. METHODS: We analysed the expression and clinical prognosis of WDR5 in a TCGA cohort. The pharmacological role of OICR-9429 was further investigated in vitro and in vivo. RNA sequencing, western blot, and chromatin immunoprecipitation (ChIP) were utilized to explored the mechanism underlying OICR-9429-induced WDR5 inhibition. RESULTS: First, we found that WDR5 expression was upregulated in BCa and was associated with histologic grade, metastasis status, histologic subtype, and molecular subtype. High WDR5 expression level was also correlated with shorter overall survival (OS) in BCa. The WDR5 inhibitor OICR-9429 reduced cell viability by decreasing H3K4me3 levels but not WDR5 levels in T24, UM-UC-3, and TCCSUP BCa cells. OICR-9429 suppressed the proliferation of BCa cells by blocking the G1/S phase transition. Next, OICR-9429 enhanced apoptosis and chemosensitivity to cisplatin in BCa cells. In addition, OICR-9429 independently inhibited the motility and metastatic behaviour of BCa cells. In vivo experiments further revealed that OICR-9429 suppressed tumour growth, enhanced chemosensitivity, and reduced the toxicity of cisplatin in BCa. Notably, WDR5 was positively correlated with programmed death-ligand 1 (PD-L1) expression, and OICR-9429 suppressed immune evasion by blocking PD-L1 induced by IFN-γ. Mechanistically, some cell cycle-, antiapoptosis-, DNA repair-, metastasis-, and immune evasion-related genes, including BIRC5, XRCC2, CCNB1, CCNE2, PLK1, AURKA, FOXM1, and PD-L1 were identified to be directly regulated by OICR-9429 in a H3K4me3-dependent manner. CONCLUSIONS: Our novel finding is that the WDR5 inhibitor, OICR-9429, suppressed proliferation, metastasis and PD-L1-based immune evasion while enhancing apoptosis and chemosensitivity to cisplatin in BCa by blocking the WDR5-MLL complex mediating H3K4me3 in target genes. Hence, our findings offer insight into a multipotential anticancer compound, OICR-9429, which enhances the antitumour effect of cisplatin or immunotherapy in BCa.

A single-blind randomized control trial of trigonal versus nontrigonal Botulinum toxin-A injections for patients with urinary incontinence and poor bladder compliance secondary to spinal cord injury.

Objective: To evaluate the effect of trigonal Botulinum toxin-A (BTX-A) injections on patients with urinary incontinence (UI) and poor bladder compliance (BC) secondary to spinal cord injury (SCI).Design: A single-blind randomized control trial.Setting: Department of urology in three hospitals.Participants: SCI patients with UI and poor BC were randomly assigned to either the experimental group or the control group.Interventions: The experimental group received an injection of 240 U BTX-A into the detrusor plus 60 U BTX-A into the trigone, while the control group received 300 U BTX-A into the detrusor sparing the trigone.Outcome Measures: Video urodynamic outcomes, including vesicoureteric reflux (VUR), detrusor leak point pressure (DLPP), and detrusor leak point volume (DLPV), were measured at baseline and week 12. UI episodes, voiding volume, and Incontinence Quality of Life (I-QoL) were assessed at baseline, week 2, 4, 8 and 12.Results: No patient reported new-onset VUR. Compared with baseline data, a significant improvement was achieved in both groups, whereas compared with DLPP and DLPV, a significant difference was noted between the two groups 12 weeks after injection. In the experimental group, the improvement of mean weekly UI episodes, voiding volume, and I-QoL were significantly better than those in the control group at 4, 8, and 12 weeks, respectively (all P < 0.05). Systemic complications of BTX-A injection were not reported.Conclusion: Trigonal BTX-A injection is more effective and safer than nontrigonal BTX-A injection for SCI patients with UI secondary to neurogenic-poor BC and does not result in VUR.

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.

Self-Care and Quality of Life in Elderly Chinese Patients with Benign Prostatic Hyperplasia.

The authors in this study explored the relationship between self-care agency and quality of life in patients with benign prostatic hyperplasia. A convenience sample of 157 patients was interviewed. The levels of both self-care agency and quality of life were close to the mean. Pearson correlation analysis demonstrated that quality of life was positively correlated with self-care agency and the self-care subgroups of abilities, responsibility, esteem, and evaluation. Improved self-care agency and the four subscale items could enhance quality of life. Intervention programs for benign prostatic hyperplasia patients must emphasize self-care agency so as to improve their health behavior and quality of life.

Distributions and characteristics of initial PSA and PSA velocity in Chinese men aged 50 years and younger without prostate cancer: a multi-center study.

PURPOSE: To analyze the distributions and characteristics of initial prostate-specific antigen (PSA) and PSA velocity in Chinese men aged 50 years and younger without prostate cancer. METHODS: The initial PSA test of men aged 50 years and younger, taken from January 2008 to December 2018 in two medical centers, was retrospectively analyzed. Cases with prostate cancer were excluded. The distributions of initial PSA and PSA velocity, and the correlations between these two values were estimated. Kaplan-Meier and log-rank test were used to estimate significant difference on the risk of PSA≥2.5 ng/mL after initial PSA measurement, stratified by median initial PSA (0.6 ng/mL). RESULTS: A total of 9461 men with non-prostate cancer were included in this study. The median initial PSA value was 0.7 ng/mL. A total of 853 men had their PSA measured two times or more and the median PSA velocity was 0.026 ng·mL-1·yr-1. There was no two-two direct correlation between initial PSA testing age, initial PSA, and PSA velocity. After a follow-up of up to 10 years from the baseline PSA test, the risk of PSA ≥ 2.5 ng/mL, stratified by median initial PSA (0.7 ng/mL), was significantly different (log-rank test, p<0.001). CONCLUSION: More than 25% of the men aged ≤ 50 years should have regularly PSA screening based on current guidelines. However, the subsequent risk of being diagnosed with prostate cancer in these men is unknown. Men aged 50 years and younger with an initial PSA higher than the median (0.7 ng/mL) have a subsequent higher risk of abnormal PSA value.

Repeat periods of electrical stimulation prolong the modulation of the micturition reflex in the rat.

AIMS: The aim of this study was to determine if the duration of the micturition reflex modulation could be prolonged by repeated periods of afferent stimulation in the decorticated rat. METHODS: Eighteen female Sprague-Dawley rats were used for the study, 10 for intravesical electrical stimulation (IVES), and 8 for Ano-genital pudendal afferents stimulation. Repeated constant flow cystometries were performed with body-warm saline (0.06-0.1 mL/min) at about 10 min interval. The selected afferents were stimulated continuously for 5 min at maximal intensity. The same stimulation was repeated six times with a pause of 5 min between the stimulations. The mean threshold volume of cystometries performed during one hour before and each hour after the stimulation were compared. RESULTS: After six periods of IVES, the micturition threshold volume decreased to its lowest value (62% of control) during the first hour and remained at 80% 4 h later (n = 10, P < 0.01). Ano-genital afferent stimulation produced a corresponding increase in the micturition threshold volume. The long-lasting poststimulation effect was again observed for more than 5 h. During the first hour the mean threshold volume increased to 211% of controls and it remained at about this level for the entire observation period (n = 8, P < 0.01). CONCLUSIONS: Repeated short periods of stimulation prolonged the modulatory effect well beyond the stimulation period. The findings provide experimental evidence supporting the clinical application of IVES and ano-genital stimulation for treatment of neurogenic urinary bladder dysfunction.

Muscarinic cholinergic signaling and overactive bladder-like symptoms associated with invasive bladder cancer.

The objective of the present study was to explore the association between muscarinic cholinergic signaling and urothelial bladder tumors. Possible associations among overactive bladder (OAB) symptoms and bladder tumors were retrospectively investigated using a multicenter Chinese database with prospectively collected data since 2010. Firstly, it was demonstrated that OAB symptoms, such as urgency, were more severe in patients with invasive bladder cancer and were associated with a reduced prognosis. Following this, muscarinic cholinergic receptor 3 (M3R) expression in urothelium was determined to be lower in invasive cancer tissue than in adjacent non-cancerous tissue, yet M3R upregulation was associated with a reduced progression free survival (PFS) time. Additionally, it was also demonstrated that muscarinic cholinergic receptor 2 (M2R) was upregulated in the sub-urothelium, and this was also associated with a reduced PFS time. Furthermore, it was determined that cholinesterase and acetylcholinesterase were lower in invasive cancer than in non-invasive cancer. In conclusion, the results indicated that M3R expression was downregulated in invasive bladder cancer, which may have a role as a protective anti-oncogene, in contrast to its oncogenic role in numerous other cancer types. Therefore, muscarinic cholinergic signaling may be a novel therapeutic target for treating bladder cancer.

Potential use of chymotrypsin-like proteasomal activity as a biomarker for prostate cancer.

Although it is the most widely used biomarker for prostate cancer, the use of prostate specific antigen (PSA) is controversial due to its limitations in specificity and sensitivity. The proteasome is a complex associated with cell proliferation and apoptosis, and the abnormity of these processes may lead to tumor occurrence. Previous studies have reported that proteasomal activity is associated with cancer progression and can be used in risk stratification. The purpose of the present study was thus to investigate the feasibility of proteasome activity as a biomarker for prostate cancer. Proteasome activity in vitro and in vivo was detected, along with the expression of the substrate proteins NF-κB inhibitor-α (IκB-α), Bcl-2-associated X (Bax) and p27. Chymotrypsin-like proteasomal activity was elevated by 70% in vitro and 23% in vivo, and the expression levels of the proteasome substrate proteins IκB-α, Bax and p27 were decreased in prostate cancer cells and prostate tumor xenografts compared with normal mouse prostate tissue. In conclusion, proteasomal chymotrypsin-like activity maybe a potential biomarker for prostate cancer, and may be suitable to supplement PSA in clinical application for prostate cancer diagnosis.

A phase 3, double-blind, randomized placebo-controlled efficacy and safety study of abiraterone acetate in chemotherapy-naïve patients with mCRPC in China, Malaysia, Thailand and Russia.

OBJECTIVE: This double-blind, placebo-controlled phase 3 study was designed to compare efficacy and safety of abiraterone acetate + prednisone (abiraterone) to prednisone alone in chemotherapy-naïve, asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC) patients from China, Malaysia, Thailand and Russia. METHODS: Adult chemotherapy-naïve patients with confirmed prostate adenocarcinoma, Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade 0-1, ongoing androgen deprivation (serum testosterone <50 ng/dL) with prostate specific antigen (PSA) or radiographic progression were randomized to receive abiraterone acetate (1000 mg, QD) + prednisone (5 mg, BID) or placebo + prednisone (5 mg, BID), until disease progression, unacceptable toxicity or consent withdrawal. Primary endpoint was improvements in time to PSA progression (TTPP). RESULTS: Totally, 313 patients were randomized (abiraterone: n = 157; prednisone: n = 156); and baseline characteristics were balanced. At clinical cut-off (median follow-up time: 3.9 months), 80% patients received treatment (abiraterone: n = 138, prednisone: n = 112). Median time to PSA progression was not reached with abiraterone versus 3.8 months for prednisone, attaining 58% reduction in PSA progression risk (HR = 0.418; p < 0.0001). Abiraterone-treated patients had higher confirmed PSA response rate (50% vs. 21%; relative odds = 2.4; p < 0.0001) and were 5 times more likely to achieve radiographic response than prednisone-treated patients (22.9% vs. 4.8%, p = 0.0369). Median survival was not reached. Most common (≥10% abiraterone vs. prednisone-treated) adverse events: bone pain (7% vs. 14%), pain in extremity (6% vs. 12%), arthralgia (10% vs. 8%), back pain (7% vs. 11%), and hypertension (15% vs. 14%). CONCLUSION: Interim analysis confirmed favorable benefit-to-risk ratio of abiraterone in chemotherapy-naïve men with mCRPC, consistent with global study, thus supporting use of abiraterone in this patient population.

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.

Results of a randomized, double-blind, active-controlled clinical trial with propiverine extended release 30 mg in patients with overactive bladder.

OBJECTIVE: To compare the efficacy and safety of the 30 mg extended release (ER) formulation of propiverine hydrochloride with the 4 mg ER formulation of tolterodine tartrate in patients with overactive bladder (OAB) in a non-inferiority trial. PATIENTS AND METHODS: Eligible patients, aged 18-75 years and with symptoms of OAB, were enrolled in this multicentre, randomized, double-blind, parallel-group, active-controlled study. After a 2-week screening period, patients were randomized at a 1:1 ratio to receive either propiverine ER 30 mg or tolterodine ER 4 mg daily during the 8-week treatment period. Efficacy was assessed using a 3-day voiding diary and patient's self-reported assessment of treatment effect. Safety assessment included recording of adverse events, laboratory test results, measurement of post-void residual urine and electrocardiograms. RESULTS: A total of 324 patients (244 female and 80 male) were included in the study. Both active treatments improved the variables included in the voiding diary and in the patient's self-reported assessment. The change from baseline in the number of voidings per 24 h was significantly greater in the propiverine ER 30 mg group compared with the tolterodine ER 4 mg group after 8 weeks of treatment (full analysis set [FAS] -4.6 ± 4.1 vs -3.8 ± 5.1; P = 0.005). Significant improvements were also observed for the change of urgency incontinence episodes after 2 weeks (P = 0.026) and 8 weeks (P = 0.028) of treatment when comparing propiverine ER 30 mg with tolterodine ER 4 mg. Both treatments were well tolerated, with a similar frequency of adverse drug reactions in both the propiverine ER 30 mg and tolterodine ER 4 mg groups (FAS 40.7 vs 39.5%; P = 0.8). More patients treated with tolterodine ER 4 mg discontinued the treatment because of adverse drug reactions compared with propiverine ER 30 mg (7.4 vs 3.1%). CONCLUSIONS: Propiverine ER 30 mg was confirmed to be an effective and well-tolerated treatment option for patients with OAB symptoms. This first head-to-head study showed non-inferiority of propiverine ER 30 mg compared with tolterodine ER 4 mg.

Effects of botulinum toxin A injections in spinal cord injury patients with detrusor overactivity and detrusor sphincter dyssynergia.

OBJECTIVE: To evaluate the safety and effect of botulinum toxin A injection in the detrusor and external urethral sphincter in male patients with detrusor overactivity (DO) and detrusor external sphincter dyssynergia (DESD) secondary to spinal cord injury. METHODS: A multicentre trial was conducted from June 2012 to August 2015. A total of 65 spinal cord injury patients with DO and DESD participated in the study. Of these, 59 received 200 U botulinum toxin Aintradetrusor and 100 U external urethral sphincter injections. The effective outcomes included maximum detrusor pressure at first DO and DESD, VDO-DESD, maximum urethral closure pressure, duration of first DO and DESD, Incontinence-Specific Quality-of-Life Instrument, voiding volume, urinary incontinence episodes and complete dryness. Adverse events were recorded. RESULTS: All patients experienced a significant mean reduction in PdetmaxDO -DESD (46.60%), maximum urethral closure pressure (29.61%), duration of first DO and DESD (42.93%) and a significant mean increase in VDO-DESD (38.11%) 12-weeks post-injection. Significant (p < 0.001) improvement in mean Incontinence-Specific Quality-of-Life Instrument, voiding volume, urinary incontinence episodes and complete dryness were found in all patients at 2 weeks and were sustained at 8 weeks and 16 weeks. CONCLUSION: Botulinum toxin A injection in the detrusor and external urethral sphincter is an effective treatment to protect the upper urinary tract and improve quality of life for patients with DO and DESD secondary to spinal cord injury.

Plasma proteasomal chymotrypsin-like activity correlates with prostate cancer progression.

Previously, we demonstrated that inhibition of proteasomal chymotrypsin-like (CT-like) activity in human prostate cancer (PCa) PC-3 cultures and PC-3 xenografts results in accumulation of ubiquitinated proteins, followed by induction of cell death. Studies have shown that plasma CT-like proteasomal activity may be a powerful biomarker for risk stratification in hematologic malignancies. We hypothesized that circulating proteasomes could also be used to stratify risk for patients with PCa. A total of 109 patients with suspected PCa underwent prostatic biopsies were enrolled. Subjects were divided into non-cancer, low-risk PCa, and high-risk PCa groups. Three different proteasomal activity markers (CT-like, caspase-like, and trypsin-like) were measured and compared among the three groups. The proteasomal target proteins, Ub-prs, Hsp70, Bax, and P27 in plasma and prostate tissues were also evaluated. Multivariate analysis was used to assess whether CT-like activity was a predictor of PCa progression. Only proteasomal CT-like activity in the high-risk group was statistically higher than in the non-cancer group (P < 0.05). The expression of Ub-prs, Hsp70, Bax, and P27 protein was decreased in both plasma and PCa tissue of high-risk patients. CT-like activity was found to be an independent predictor of high-risk PCa. Subjects with CT-like activity ≥55 had a 2.15-fold higher risk of having high-risk PCa as compared to those with a CT-like activity of <55 (P = 0.021). We found CT-like activity to be an independent predictor of high-risk PCa, and as such, it may be a good candidate as a biomarker for high-risk PCa detection and stratification.

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").

Cystitis glandularis: A controversial premalignant lesion.

Cystitis glandularis (CG) has been hypothesized as a potential precursor of adenocarcinoma, although this remains controversial. The present study reports data accumulated from 166 cases of cystitis glandularis with follow-up periods ranging between 0.5 and 17 years. The association between intestinal and typical CG and bladder carcinoma was retrospectively evaluated. The patients included in the present study had presented with typical (n=155) or intestinal (n=11) CG between 1994 and 2010. Of those patients, concurrent carcinoma of the bladder was identified in 15 (9.0%) patients, including two cases of squamous cell carcinoma and 1 case of sarcoma. The cases of carcinoma were identified either prior to or concurrently with the diagnosis of CG. Follow-up was available for 9/11 (81.8%) patients with intestinal CG. Nine months following transurethral fulguration, 8/11 (72.7%) patients were in complete remission and 1/11 (9.1%) complained of urgency and dysuria; two patients were lost to follow-up. The follow-up of the patients ranged from 0.7 to 4.5 years (median, 2.67 years; mean, 2.82 years). No evidence of subsequent carcinoma was identified in any of the patients during the follow-up of the intestinal and typical CG groups. In addition, there was no evidence of carcinoma subsequent to CG in either of the typical or intestinal CG groups. The results did not support that CG increases the future risk of malignancy in the short term and repeated cystoscopies over a short period of time are not recommended.