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To evaluate the efficacy and safety of intravesical electrical stimulation (IVES) performed with a novel device in patients with underactive bladder (UAB).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 (QIn 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, QThe 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.

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/β‐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., lncRNA BCYRN1 is upregulated in urinary exosomes from bladder cancer (BCa) patients and associated with LN metastasis and poor prognosis of patients. BCYRN1 upregulates WNT5A expression to activate WNT/β‐catenin pathway and promotes the secretion of VEGF‐C in BCa. Exosomal BCYRN1 stabilizes VEGFR3 mRNA in HLECs, constituting a feedforward loop to promote lymphangiogenesis and LN metastasis of BCa.

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.

Objective: To report a giant bladder calculi in a 52-year-old man. Methods: The patient was diagnosed as bladder calculi since 1998. Due to the lack of sufficient medical and health conditions in the countryside, he only received the Chinese traditional treatment and did not seek any urologic treatments for more than 20 years. In April 2018, he was referred to our hospital with dysuria. Results: A big bladder calculi (8.0 cm × 10.0 cm × 6.0 cm in size) was revealed by ultrasound and intravenous pyelography and removed by open cystolithotomy. Conclusions: Our case demonstrates the necessity of early treatment for patients with bladder calculi.

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

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.

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-naive, asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC) patients from China, Malaysia, Thailand and Russia. Methods Adult chemotherapy-naive patients with confirmed prostate adenocarcinoma, Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade 0–1, ongoing androgen deprivation (serum testosterone

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.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).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, p0.001).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.

Objective: To compare the short-time complications associated with time-opening suprapubic catheter (SPT) versus intermittent catheter (IC) in male patients with spinal cord injury (above level C5). Methods: A prospective review of records was carried out to identify SCI patients managed with SPT or IC between 2011 and 2016. The complications included renal function (Serum creatinine), urinary tract infection (UTI), bladder stones, urethral complications, scrotal, and gross hematuria. Patients were followed at week 4, 3 and 6 months; the urodynamic assessment was repeated at 6 months. Results: A total of 30 patients (11 SPT, 19 IC) were recruited in this trial. There is no significant difference between the two catheter groups for the entire out-come. Scrotal abscesses and urethral stricture were only seen in patients with IC. Conclusions: SPT has similar urological complication with IC for SCI patients (above level C5) except the incidence of scrotal abscesses and urethral stricture.

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

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

Objective: To assess the safety and efficacy of bladder irrigation for reducing the morbidity of bladder stones in patients with neurological lower urinary tract dysfunction (NLUTD). Methods: From June 2012 to July 2013, patients with NLUTD were prospectively randomized and assigned to either a bladder irrigation group or a no bladder irrigation group. Bladder irrigations were performed twice a week by urologists. Patients were followed up at 6 months respectively. Primary outcomes were Incontinence-Specific Quality-of-Life Instrument (I-QoL), the rate incidences of bladder stone. All adverse events were also noted. Results: A total of 80 eligible patients participated and 78 (97.5%) patients (bladder irrigation, n = 39; no bladder irrigation, n = 39) completed 24 weeks of follow-up. Out of the 78 patients, 19 (24.3%) developed bladder stones. All occurred in no bladder irrigation group. In 8 of the 19 patients (42.1%), stones were only detected by cystoscopy. The bladder stones were mostly thin with an eggshell appearance (78.95% for diameter of stone < 5 mm, 84.21% for volume of bladder stone < 0.2 cm3). Bladder stones were removed by vigorous bladder irrigation guided by ultrasound (73.68%) or endoscopic lithotripsy (26.32%). The I-QOL was significantly better in the bladder irrigation group than in no bladder irrigation group at weeks 6, 12, 18, and 24 of follow-up. Conclusion: Bladder irrigation may be more effective and safer than no bladder irrigation for reducing the morbidity of bladder stone in spinal cord injury patients.

Objectives To compare the efficacy and safety of transurethral enucleation and resection of the prostate (TUERP) and transvesical prostatectomy (TVP) for patients with benign prostatic hyperplasia (BPH) and prostate volumes >80 mL. Patients and Methods A total of 100 patients with urodynamic obstruction and prostate volume >80 mL were prospectively randomized and enrolled in the study at a tertiary hospital. Patients underwent TVP or TUERP performed by one of two surgeons with experience of a large number of cases. All patients were preoperatively evaluated using patient age, prostate volume measurement, clinical characteristics of digital rectal examination, self-assessment using the International Prostate Symptom Scores (IPSS) questionnaire, a quality-of-life (QoL) questionnaire, maximum urinary flow rate (Qmax), post-void residual urine volume (PVR), urine analysis, blood sample analysis, including determination of prostate-specific antigen (PSA) and haemoglobin concentration. All patients were assessed peri-operatively and postoperatively at 3 and 12 months. All complications were documented. Results Of 100 patients eligible to participate, 92 patients completed 12 months of follow-up. Patients who underwent TUERP had shorter catheterization times and hospital stays. Operation duration was not significantly different between the two surgical groups (P = 0.107). The resected adenoma weight in the TVP group was more than that in the TUERP group, but the difference was not significant (P = 0.062). There were no significant differences in IPSS, PVR, Qmax or QoL scores between the groups at 3 and 12 months. The patients in the TVP group appeared to have a better Qmax at 3 months, however, the difference was not significant (P = 0.081). Adverse events were similar in the two groups. Conclusion We found that TUERP had efficacy and safety equivalent to that of TVP for patients with BPH and prostate volume >80 mL.

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 (

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.

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.

Objective To compare the safety and efficacy of trigone-including versus trigone-excluding intradetrusor injection of botulinum toxin A (BTX-A) for decreasing detrusor leak point pressure (DLPP) in patients with urinary incontinence (UI) secondary to spinal cord injury (SCI) in China. Methods A prospective, multicenter, single-blind and randomized controlled trial (RCT) was conducted between December 2012 and June 2015. Patients with UI and low compliance bladder secondary to SCI were recruited. At a 1:1 ratio, patients randomly received 200 U BTX-A intradetrusor injections excluding the trigone (control group) or 160 U intradetrusor and 40 U intratrigonal injections (experimental group). Patients were evaluated at baseline, and 4, 12 weeks after injection. The efficacy and safety outcomes included DLPP, detrusor leak point volume (LPV), I-QoL, voiding volume, UI episodes, complete dryness. Vesicoureteral reflux (VUR) and other adverse events were recorded. Results Eighty-six patients were recruited and 80 (41 in experimental group and 39 in the control group) of them completed the trial. There were no significant differences in baseline evaluation items (gender, age, duration of SCI, level of neurological injury, AIS scores) between the two groups. At 12 weeks, the improvement was significantly better in the experimental group than in the control group for DLPP (−25.66 vs. −19.70 cmH2O, P=0.02), DLPV (116.09 vs. 87.34 mL, P=0.03), I-QoL (27.02 vs. 20.32, P=0.02), mean UI episodes (−7.19/d vs. −6.65/d, P=0.01), complete dryness (22 vs. 10, P=0.01),mean voiding volume (142.84 vs. 110.36 mL, P=0.01). In both of two groups, no patients developed VUR. Conclusions Trigone-including intradetrusor injection of BTX-A are more effective than those excluding the trigone to decrease DLPP for patients with UI and poor compliant bladders secondary to SCI. It does not induce VUR.

Objective: To investigate the relationship between surgeon’s experience, tumor characteristics, absent detrusor muscle (DM) tissue in resected specimens, and residual tumor after an initial transurethral resection. Patients and Methods: We conducted an analysis of 216 patients from two centers over a 3-year period. Patients with primary bladder tumors that were judged to have been completely resected were recruited. The data included tumor characteristics, surgeon category, and DM status. Logistic regression multivariate analyses were conducted. Results: Large tumors, lateral/dome/anterior wall tumors, and surgery performed by junior surgeons were independently associated with absent DM. Large tumors, dome/anterior wall tumors, T1 and absent DM were independently associated with residual disease. The absence and presence of the DM were associated with residual tumor rates of 51.8 and 20.9%, respectively (OR 15.537). Resection by senior surgeons was associated with the presence of DM and clean resection (OR 0.274 and 0.141, respectively). Conclusions: Absent DM and residual tumor were more likely to occur in cases involving large tumors that were located in the lateral/dome/anterior wall, especially when the surgery was performed by a junior surgeon. Absent DM appears to be a surrogate marker for residual disease.

Aims Experimental animal models of bladder outlet obstruction (BOO) have reproduced several features of BOO in man, i.e., detrusor hypertrophy, instability, frequency, and residual urine. This stud ...

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.

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").

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

Patients undergoing androgen blockade therapy develop castration-resistant prostate cancer (CRPC), which is associated with Bcl-2 upregulation and results in disease progression and death. In recent years, promising therapeutic agents, such as the BH3-only mimetic ABT-263 and proteasome inhibitors, have been developed and widely evaluated against a broad spectrum of cancer types, including prostate cancer, alone or in combination with other chemotherapeutic agents. In this study, the antitumor efficacy of ABT-263 and MLN2238 were evaluated as single agents and in combination in four CRPC cell lines: PC3, C4-2B, C4-2, and DU145. The viability of the treated cells and markers of apoptosis were assayed. Protein-protein interactions were analyzed by co-immunoprecipitation in drug-treated cells. Lentivirus-mediated short hairpin RNA was used to knockdown Bax, Mcl-1, and NOXA expressions. We found that ABT-263 and MLN2238 alone exhibited a mild cytotoxicity, and in combination, they elicited a synergistic cytotoxic effect in CRPC cells. The cell apoptosis induced by the combination drug treatment was evidenced by enhanced caspase-3 and Poly (ADP-ribose) polymerase (PARP) cleavage, and annexin-V-positive staining was significantly depleted by Bax knockdown. MLN2238 treatment upregulated NOXA and Mcl-1 expression, leading NOXA/Mcl-1 complexes to disassociate Bak from its complexes with Mcl-1 and enhancing ABT263-triggered Bax activation. NOXA knockdown by short hairpin RNA significantly attenuated the cytotoxicity of ABT-263 and MLN2238 co-administration. In conclusion, MLN2238 and ABT-263 synergistically triggered apoptosis in CRPC cells by upregulating NOXA and activating Bax, indicating a promising therapeutic strategy for the treatment of CRPC.

The prostate-specific antigen (PSA) “gray zone” in Chinese men is likely higher than the traditional value (2.5–10.0 ng/ml) since the incidence of prostate cancer in Chinese men is relative low. The utility of percent free PSA in predicting prostate cancer is based on Western populations and may introduce sizable bias when applied to a Chinese cohort. We assessed the efficacy of percent free PSA in predicting prostate cancer in Chinese men with a PSA of 2.5–10.0 and 10.1–20.0 ng/ml. A total of 558 men with a PSA of 2.5–20.0 ng/ml who had undergone prostatic biopsy to detect prostate cancer from two Chinese centers were included. The rates of prostate cancer in different percent free PSA ranges were evaluated. Receiver operating characteristic curve (ROC) was used to evaluate and compare the efficiency of PSA and percent free PSA in the diagnosis of prostate cancer. The areas under ROC (AUCs) for percent free PSA for predicting prostate cancer were not higher than those for PSA, although prostate cancer detection rates increased with decreased percent free PSA in men with a PSA of 2.5–10.0, 10.1–20.0, and 2.5–20.0 ng/ml. Similarly, for men aged

To compare the efficacy and safety of transurethral enucleation and resection of the prostate (TUERP) and transvesical prostatectomy (TVP) for patients with benign prostatic hyperplasia (BPH) and prostate volumes80 mL.A total of 100 patients with urodynamic obstruction and prostate volume80 mL were prospectively randomized and enrolled in the study at a tertiary hospital. Patients underwent TVP or TUERP performed by one of two surgeons with experience of a large number of cases. All patients were preoperatively evaluated using patient age, prostate volume measurement, clinical characteristics of digital rectal examination, self-assessment using the International Prostate Symptom Scores (IPSS) questionnaire, a quality-of-life (QoL) questionnaire, maximum urinary flow rate (Qmax ), post-void residual urine volume (PVR), urine analysis, blood sample analysis, including determination of prostate-specific antigen (PSA) and haemoglobin concentration. All patients were assessed peri-operatively and postoperatively at 3 and 12 months. All complications were documented.Of 100 patients eligible to participate, 92 patients completed 12 months of follow-up. Patients who underwent TUERP had shorter catheterization times and hospital stays. Operation duration was not significantly different between the two surgical groups (P = 0.107). The resected adenoma weight in the TVP group was more than that in the TUERP group, but the difference was not significant (P = 0.062). There were no significant differences in IPSS, PVR, Qmax or QoL scores between the groups at 3 and 12 months. The patients in the TVP group appeared to have a better Qmax at 3 months, however, the difference was not significant (P = 0.081). Adverse events were similar in the two groups.We found that TUERP had efficacy and safety equivalent to that of TVP for patients with BPH and prostate volume80 mL.

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.

Objective To evaluate the effect and safety of trigonal injection of botulinum toxin A (BTX-A) for patients with neurological detrusor overactivity (NDO) with incontinence. Methods A prospective, multicenter, single-blind and randomized controlled trial (RCT) was conducted between June 2011 and June 2014. Spinal cord injury patients with urinary incontinence secondary to NDO were recruited. At a 1:1 ratio, patients randomly received 200 U BTX-A intradetrusor injections excluding the trigone (control group) or 160 U intradetrusor and 40 U intratrigonal injections (experimental group). Patients were evaluated at baseline, and 4, 12 weeks after injection. The efficacy and safety outcomes included I-QoL, voiding volume, urinary incontinence episodes, complete dryness, maximum detrusor pressure (Pdetmax), volume at first involuntary detrusor contraction (VFIDC). Vesicoureteral reflux (VUR) and other adverse events were recorded. Results Ninety-six patients were recruited and 91 of them completed the trial. Among the 91 patients, 47 were randomized to experimental group and 44 to the control group. There were no significant differences in baseline evaluation items (gender, age, duration of spinal cord injury, level of neurological injury, AIS scores) between the two groups. At 12 weeks, the improvement was significantly better in the experimental group than in the control group for I-QoL (26.01 vs. 18.75, P=0.01), mean urinary incontinence episodes (−5.22/d vs. −4.68/d, P=0.01), complete dryness (13 vs. 5, P=0.03), mean voiding volume (159.72 vs. 139.07 mL, P=0.02), Pdetmax (−33.34 vs. −28.02 cmH2O, P=0.04), and VFIDC (106.81 vs. 97.86 mL, P=0.02), duration of first detrusor contraction (−41.54 vs. −18.65 s, P=0.03) and the number of patients with detrusor contraction (−20 vs. −9, P=0.02). In both of two groups, no patients developed VUR. Conclusions BTX-A intradetrusor and intratrigonal injections are more effective than those excluding the trigone for patients with NDO with incontinence. Intratrigonal injections do not induce VUR.

Objective To assess the safety and efficacy of bladder irrigation for reducing the morbidity of bladder stones in spinal cord injury (SCI) patients. Methods From December 2011 to July 2013, SCI patients were prospectively randomized and assigned to either a bladder irrigation group or a no bladder irrigation group. Bladder irrigations were performed twice a week by urologists. The primary outcomes were incidences of bladder stones and Incontinence-Specific Quality-of-Life Instrument (I-QoL). Secondary outcomes were related adverse events. Results A total of 80 eligible patients participated and 78 (97.5%) patients (bladder irrigation, n=39; no bladder irrigation, n=39) completed 24 weeks of follow-up. Out of the 78 patients, 19 (24.3%) developed bladder stones. All occurred in no bladder irrigation group. In 8 of the 19 patients (42.1%), stones were only detected by cystoscopy .The bladder stones were mostly thin with an eggshell appearance (78.95% for diameter of stone

Objective To compare laparoscopic prostatectomy with open prostatectomy for benign prostatic hyperplasia with large volume. Methods The literature was identified systematically using Medline, Embase. Meta-analysis was performed by Review Manager 5.0. Results Three CCTs were included. There was no difference between LP and OP in terms of IPSS, Qmax. LP was associated with significantly less blood loss, a shorter irrigation, catheterization and hospital stay time except longer operating time. LP and OP were similar in terms of urethral stricture, incontinence, transfusion requirement and rate of reintervention. Conclusions LP served a significant improvement in IPSS, Qmax as well as OP. Although more operating time and less resected tissue, LP has several advantages over OP. It was as safe as OP in terms of adverse events.

Objective: To assess effective outcomes following repeated treatment with intradetrusor botulinum toxin type an in patients with neurogenic detrusor overactivity (NDO). Methods: Patients with NDO secondary to spinal cord injury (SCI) were enrolled. Botulinum toxin type A 200 U detrusor injections by a rigid cystoscope were repeated. Primary outcomes were urodynamic variables including maximum detrusor pressure during first involuntary detrusor contraction (P detmaxIDC) filling cystometry, detrusor compliance (DC). Secondary outcomes were improvement of the patient’s QoL measured by Incontinence-Specific Qualityof-Life Instrument (I-QoL), the validated short forms of Urogenital Distress Inventory (UDI-6) and the Incontinence Impact Questionnaire (IIQ-7). Related adverse events were recorded. Results: From 2012 to 2014, 159 injections were performed in 52 patients (44 male, 8 female). The mean age was 36.67 years. The maximum number of repeated injections was five. BC increased from (4.03-7.45) to (6.96-10.86) ml/cm H2O, Pdetmax in bladder storage decreased from (42.80-79.52) to (26.40-43.33) cm H 2 O, respectively. The I-QoL, UDI-6 and IIQ-7 showed a consistent improvement after repeated injections. Conclusion: Repeated intradetrusor botulinum toxin type A injections remain improve Quality of Life in patients with NDO secondary to spinal cord injury.

To compare holmium laser enucleation (HoLEP) versus open prostatectomy (OP) for large volume benign prostatic hyperplasia.The randomized controlled trials (RCTs) pertaining to HoLEP and OP for management of large volume benign prostatic hyperplasia were retrieved from Medline and Embase. Meta-analysis was performed using Review Manager 5.0 software.Three RCTs were included in the analysis. No significant differences were found in IPSS or Qmax between HoLEP and OP (P0.05). Compared with OP, HoLEP was associated with significantly less blood loss, a shorter catheterization time and a shorter hospital stay, but a longer operating time. HoLEP and OP were similar in terms of urethral stricture, stress incontinence, transfusion requirement and the rate of reintervention.HoLEP and OP have similar therapeutic effects in the management of large volume benign prostatic hyperplasia. Although with a longer operating time and less resected tissue, HoLEP causes less blood loss and requires a shorter catheterization time and a shorter hospital stay. HoLEP has a comparable safety to OP in terms of the adverse events.

Objectives We hypothesized the prostate-specific antigen (PSA) “grey zone” in Chinese men was higher than the traditional value (4.0–10.0 ng/ml) since incidence of prostate cancer (CaP) in Chinese men was relative low. We then assessed the efficiencies of transition zone PSA density (TZPSAD) in the diagnosis of CaP in Chinese men with a PSA of both 4.0–10.0 and 10.1–20.0 ng/ml. Materials and methods Men had a prostatic biopsy for detecting CaP from November 1999 to August 2009 were retrospectively retrieved from our computer center. Those had a document of transrectal ultrasound transition zone measurement with a PSA of 4.0–20.0 ng/ml were included. Receiver-operating characteristic (ROC) curve was used to analyze the efficiencies of PSA and TZPSAD in the diagnosis of CaP. Results A total of 189 men were included in the study. Of these men, 78 and 111 had a PSA of 4.0–10.0 and 10.1–20.0 ng/ml, respectively. The rate of CaP in men with a PSA of 4.0–10.0 ng/ml was not statistically significantly different compared with those with a PSA of 10.1–20.0 ng/ml (20.5% vs. 21.6%, P = 0.854). The areas under the ROC curve (AUCs) in diagnosis of CaP for PSA and TZPSAD were 0.569 and 0.702 in men with a PSA of 4.0–10.0 ng/ml and 0.463 and 0.730 in men with a PSA of 10.1–20.0 ng/ml, respectively. The best cut-off of TZPSAD in predicting CaP in men with a PSA of 4.0–10.0 ng/ml was 0.370 ng/ml/ml, the sensitivity of which equaled 68.8%, specificity 72.6%. The best cut-off of TZPSAD in predicting CaP in men with a PSA of 10.1–20.0 ng/ml was 0.500 ng/ml/ml. Its sensitivity equaled 70.8%, specificity 70.1%. Conclusions Using TZPSAD can improve the efficiency of PSA in diagnosis of CaP and decreases the unnecessary prostatic biopsy in men with a PSA of both 4.0–10.0 and 10.1–20.0 ng/ml in Chinese men.

BACKGROUND Baseline prostate specific antigen (PSA) and PSA velocity used to stratify subsequent prostate cancer risk in young men may not directly applicable to all populations. We sought to compare the baseline PSA and PSA velocity among ethnic groups. PATIENTS AND METHODS Chinese, African-American (AA), and Caucasian-American (CA) men aged ≤50 years old without prostate cancer were used to identify baseline PSA and PSA velocity. The differences of baseline PSA and PSA velocity between races were assessed. The important cutoffs of baseline PSA and PSA velocity were used to stratify patients among races. RESULTS Four thousand two hundred six Chinese, 997 AA, and 2,030 CA were included. The rates of baseline PSA of ≥1.0, ≥2.5, and ≥4.0 ng/ml was 24.4%, 4.2%, and 2.1% in Chinese, 30.7%, 5.2%, and 1.8% in AA, 29.7%, 5.3%, and 2.8% in CA, respectively. The rates of PSA velocity of ≥0.35, ≥0.75, and ≥1.0 ng/ml/year was 6.0%, 3.1%, and 2.6% in Chinese, 5.3%, 2.3%, and 1.7% in AA, 5.4%, 3.5%, and 3.3% in CA, respectively. Chinese had a lower baseline PSA and higher PSA velocity as compared to AA and CA. Baseline PSA and PSA velocity in AA had no statistical differences as compared to CA. CONCLUSIONS The distributions of baseline PSA and PSA velocity in young men among Chinese, AA, and CA races are different. These characteristics shall be taken into account when using these variables to stratify risk of prostate cancer in young men. Prostate 72:173–180, 2012. © 2011 Wiley Periodicals, Inc.

Patients with benign prostatic hyperplasia (BPH) suffering from hypocontractile detrusor were generally regarded unsuitable for surgery. This prospective study is to evaluate the efficacy of transurethral resection of the prostate (TURP) on BPH patients diagnosed detrusor hypocontractility on urodynamic study (UDs).Twenty patients were included in the study with mean age of 74.20 ± 7.93 years (range: 57-88). Outcomes were determined by patients' self-assessment questionnaires, International Prostate Symptom Score (IPSS) and Quality of Life (QoL), and UDs parameters including maximum uroflow rate (Qmax), postvoid urine volume (PVR), bladder compliance, maximal cystometric capacity (MCC), and maximum detrusor pressure (Pdetmax).Median follow-up duration was 12 months (range: 10-16). After TURP, IPSS/QoL, Qmax, PVR, and Pdetmax were significantly improved and there were no significant differences with regard to bladder compliance and MCC.UDs may play a very limited role in detecting bladder outlet obstruction (BOO) in BPH patients with hypocontractile detrusor. TURP may obtain a promising effect on such patients with unidentified BOO. These patients should not be arbitrarily excluded from surgical indications simply based on UDs findings.

To improve prostate cancer (PC) detection accuracy among patients with a prostate-specific antigen (PSA) above 4.0 ng/ml and asymptomatic prostate inflammation.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.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 (P0.01). 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 were0.01).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.