Xianjin Wang

Diabetes Mellitus and Risk of Bladder Cancer: A Meta-Analysis of Cohort Studies

Background Increasing evidence suggests that diabetes mellitus (DM) may be associated with an increased risk of bladder cancer. To provide a quantitative assessment of this association, we evaluated the relation between DM and incidence and mortality of bladder cancer in an updated meta-analysis of cohort studies. Methods We identified cohort studies by searching the EMBASE and MEDLINE databases, through 31 March 2012. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated with random-effects models. Results A total of 29 cohort studies (27 articles) were included in this meta-analysis. DM was associated with an increased incidence of bladder cancer (RR 1.29, 95% CI: 1.08–1.54), with significant evidence of heterogeneity among these studies (p<0.001, I2 = 94.9%). In stratified analysis, the RRs of bladder cancer were 1.36 (1.05–1.77) for diabetic men and 1.28 (0.75–2.19) for diabetic women, respectively. DM was also positively associated with bladder cancer mortality (RR 1.33, 95% CI: 1.14–1.55), with evident heterogeneity between studies (p = 0.002, I2 = 63.3%). The positive association was observed for both men (RR 1.54, 95% CI: 1.30–1.82) and women (RR 1.50, 95% CI: 1.05–2.14). Conclusion These findings suggest that compared to non-diabetic individuals, diabetic individuals have an increased incidence and mortality of bladder cancer.

Robotic versus open radical cystectomy: an updated systematic review and meta-analysis.

Objective To critically review the currently available evidence of studies comparing robot-assisted radical cystectomy (RARC) with open radical cystectomy (ORC). Methods A comprehensive review of the literature from Pubmed, Web of Science and Scopus was performed in April 2014. All relevant studies comparing RARC with ORC were included for further screening. A pooled meta-analysis of all comparative studies was performed and publication bias was assessed by a funnel plot. Results Nineteen studies were included for the analysis, including a total of 1779 patients (787 patients in the RARC group and 992 patients in the ORC group). Although RARC was associated with longer operative time (p <0.0001), patients in this group might benefit from significantly lower overall perioperative complication rates within 30 days and 90 days (p = 0.005 and 0.0002, respectively), more lymph node yields (p = 0.009), less estimated blood loss (p <0.00001), lower need for perioperative and intraoperative transfusions (p <0.0001 and <0.0001, respectively), and shorter postoperative length of stay (p = 0.0002). There was no difference between two groups regarding positive surgical margin rates (p = 0.19). Conclusions RARC appears to be an efficient alternative to ORC with advantages of less perioperative complications, more lymph node yields, less estimated blood loss, lower need for transfusions, and shorter postoperative length of stay. Further studies should be performed to compare the long-term oncologic outcomes between RARC and ORC.

Risk of bladder cancer in patients with diabetes mellitus: an updated meta-analysis of 36 observational studies

BackgroundIncreasing evidence suggests that a history of diabetes mellitus (DM) may be associated with an increased risk of bladder cancer. We performed a systematic review with meta-analysis to explore this relationship.MethodsWe identified studies by a literature search of Medline (from 1 January 1966) and EMBASE (from 1 January 1974), through 29 February 2012, and by searching the reference lists of pertinent articles. Summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated with a random-effects model.ResultsA total of 36 studies (9 case–control studies, 19 cohort studies and 8 cohort studies of patients with diabetes) fulfilled the inclusion criteria. Analysis of all studies showed that DM was associated with an increased risk of bladder cancer (the summary RR = 1.35, 95% CI 1.17–1.56, p < 0.001, I2 = 94.7%). In analysis stratified by study design, diabetes was positively associated with risk of bladder cancer in case–control studies (RR = 1.45, 95% CI 1.13-1.86, p = 0.005, I2 = 63.8%) and cohort studies (RR = 1.35, 95% CI 1.12-1.62, p < 0.001, I2 = 94.3%), but not in cohort studies of diabetic patients (RR = 1.25, 95% CI 0.86–1.81, p < 0.001, I2 = 97.4%). The RRs of bladder cancer were 1.38 (1.08-1.78) for men and 1.38 (0.90-2.10) for women with diabetes, respectively. Noteworthy, the relative risk of bladder cancer was negatively correlated with the duration of DM, with the higher risk of bladder cancer found among patients diagnosed within less than 5 years.ConclusionsThese findings support the hypothesis that men with diabetes have a modestly increased risk of bladder cancer, while women with diabetes were not the case.

Effects of oral finasteride on erectile function in a rat model.

INTRODUCTION Many clinical studies reported finasteride-related erectile dysfunction, but to date, few animal experiments have focused on it. AIM To investigate the effects of oral finasteride on erectile function in a rat model. MAIN OUTCOME MEASURES Erectile responses and morphological changes. METHODS Adult, male Sprague-Dawley rats were divided into four groups (25/group): (i) control; (ii) castration; (iii) castration with testosterone (T) replacement; and (iv) oral finasteride treatment. Four weeks later, erectile function was measured by the ratio of intracavernosal pressure and mean arterial blood pressure upon electrical stimulation of the cavernous nerve. Serum T and dihydrotestosterone (DHT) and intraprostatic DHT were measured. The weights and histopathological features of the penile corpus cavernosum and prostate were examined. RESULTS Serum T and DHT and intraprostatic DHT concentrations, erectile function, and mean weights of the corpus cavernosum and prostate were lowest in group 2. There was no significant difference in the serum T concentration and erectile function between groups 4 and 1. However, the serum and intraprostatic DHT concentrations were significantly lower in group 4 than in group 1 (both P < 0.001). The tissue weights of the corpus cavernosum and prostate were reduced by 25.9% and 92.3% in group 4 compared with group 1 (both P < 0.001). Histopathology revealed a significant atrophy of the prostate in groups 2 and 4. There was a significant decrease in the smooth muscle content in group 2, but not in groups 3 and 4. CONCLUSIONS In a rat model, finasteride treatment for 4 weeks reduces the weight of the corpus cavernosum but appears not to affect the erectile responses to electrical stimulation of the cavernous nerve. As erection is a complex process involving important signaling in the brain, further studies are necessary to demonstrate the long-term effects of finasteride on both central and peripheral neural pathways of erection.

MicroRNA-145 directly targets the insulin-like growth factor receptor I in human bladder cancer cells

The insulin‐like growth factor receptor I (IGF‐IR) is a proto‐oncogene with potent mitogenic and antiapoptotic activities. It has been reported that expression of IGF‐IR is up‐regulated in bladder cancer. Here, we assessed whether microRNA‐145 (miR‐145) regulates IGF‐IR expression in bladder cancer. In our study, miR‐145 was shown to directly target IGF‐IR 3′‐untranslated region (UTR) in human bladder cancer cells. Small interfering RNA (siRNA)‐ and miR‐145‐mediated IGF‐IR knockdown experiments revealed that miR‐145 promotes cell apoptosis, and suppresses cell proliferation and migration through suppression of IGF‐IR expression. Taken together, our data suggest that miR‐145 may inhibit bladder cancer initiation by affecting IGF‐IR signaling.

Predicting Recurrence and Progression in Chinese Patients With Nonmuscle-invasive Bladder Cancer Using EORTC and CUETO Scoring Models

OBJECTIVE To validate the European Organization for Research and Treatment of Cancer (EORTC) model and the Spanish Urological Club for Oncological Treatment (CUETO) model in Chinese patients with nonmuscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS A retrospective study was performed of 363 Chinese patients with NMIBC treated at our hospital from January 2003 to September 2010. Most of these patients had undergone intravesical chemotherapy after transurethral resection of the bladder tumor. The scores for recurrence and progression were calculated using the 2 models. Next, all the patients were divided into 4 risk groups according to their scores. The Kaplan-Meier method was used to estimate the probabilities of recurrence and progression according to both models. Discrimination was assessed using the concordance index. RESULTS The EORTC model successfully stratified our patients into 4 groups with statistically significant different probabilities of recurrence. For progression, only the intermediate- and high-risk groups could be reasonably distinguished using the EORTC model. The CUETO model stratified neither the recurrence nor the progression risks. The concordance index using the EORTC and CUETO model was 0.711 and 0.663 for recurrence and 0.768 and 0.741 for progression, respectively. CONCLUSION Compared with the CUETO risk tables, the EORTC model showed more value in predicting recurrence and progression in Chinese patients with NMIBC, most of whom received intravesical chemotherapy after transurethral resection of the bladder tumor. Prospective multicenter studies should be performed of large cohorts to construct an ideal prognostic model for Chinese patients with NMIBC.

MicroRNA-31 functions as a tumor suppressor and increases sensitivity to mitomycin-C in urothelial bladder cancer by targeting integrin α5

Urothelial bladder cancer (UBC) is a common genitourinary malignancy. MiR-31, a well-identified miRNA, exhibits diverse properties in different cancers. However, the specific functions and mechanisms of miR-31 in UBC have not been investigated. In this study, tumor samples, especially invasive UBC, showed significantly reduced level of miR-31, as compared with normal urothelium. Prognostic analysis using the EORTC model showed that down-regulation of miR-31 correlated with higher risks of recurrence and progression in noninvasive UBC cases. Remarkably, overexpression of miR-31 mimics in UBC cell lines inhibited cell proliferation, migration and invasion. Integrin α5 (ITGA5), an integrin family member, was subsequently identified as a direct target of miR-31 in UBC cells. When treated with mitomycin-C (MMC), miR-31-expressing UBC cells displayed lower survival and higher apoptotic rates, and deactivated Akt and ERK. These effects arising from miR-31 overexpression were abrogated by ITGA5 restoration. Furthermore, miR-31 markedly inhibited tumor growth and increased the effectiveness of MMC in UBC xenografts. In summary, our data suggest that miR-31 is a prognostic predictor and can serve as a potential therapeutic target of UBC.

Castration impairs erectile organ structure and function by inhibiting autophagy and promoting apoptosis of corpus cavernosum smooth muscle cells in rats

ObjectiveThe aim of this study was to determine the changes and underlying mechanisms of erectile organ structure and function in castrated rats. In addition, the regulatory effects of an androgen on autophagy and apoptosis in corpus cavernosum smooth muscle cells (CCSMCs), especially the regulatory effect of androgen on the BECN 1–Bcl-2 interaction, were investigated.MethodsMale Sprague–Dawley rats were divided into three groups (30/group): control group, castration group, and castration with testosterone supplementation group. The erectile function was examined both in vivo and in vitro, by electric stimulation of the cavernous nerve and corpus cavernosum strip bath test, respectively. Transmission electron microscopy, TUNEL assay, Masson’s trichrome staining, immunohistochemistry, and western blotting were performed to determine the levels of autophagy and apoptosis, and the structural changes in corpus cavernosum.ResultsCompared with control group, the castration group showed (1) lower erectile function: lower intracavernosal pressure/mean arterial pressure ratio, lower systolic and diastolic capability of corporal strips, and reduced expressions of eNOS and nNOS; (2) greater fibrosis: decreased smooth muscle/collagen ratio, lower expression of α-SMA, and higher expression of TGF-β1; (3) inhibited autophagy: decreased autophagosomes, lower expressions of BECN1 and LC3-II; and (4) enhanced apoptosis: higher apoptotic index and decreased Bcl-2/Bax ratio. Testosterone supplementation partially improved the effects of castration.ConclusionsCastration attenuates erectile function and induces corporeal fibrosis by inhibiting autophagy and promoting apoptosis of CCSMCs in rats. Therefore, our study highlights the important role of androgens in maintaining the integrity of the structure and function of corpus cavernosum in rats through counter-regulation of autophagy and apoptosis, mainly by regulating BECN 1–Bcl-2 interaction.

Systematic Review and Meta-Analysis of Comparative Studies Reporting Perioperative Outcomes of Robot-Assisted Partial Nephrectomy Versus Open Partial Nephrectomy

BACKGROUND Robot-assisted partial nephrectomy (RAPN) is increasingly being used for the surgical management of renal masses. The comparison of RAPN with open partial nephrectomy (OPN) has not yet led to a unified conclusion with regard to perioperative outcomes. PURPOSE To conduct a systematic review and meta-analysis of the literature on the perioperative outcomes of RAPN compared with OPN. METHODS We searched PubMed and EMBASE through January 31, 2016, to identify randomized controlled trials (RCTs) and observational comparative studies assessing the comparison of the two approaches (RAPN vs OPN). Primary outcomes were intraoperative complication rate and postoperative complication rate (including minor and major). Secondary outcomes were perioperative transfusion rate, positive surgical margin (PSM) rate, operative time (OT), warm ischemia time (WIT), estimated blood loss (EBL), length of hospital stay (LOS), and estimated glomerular filtration rate (eGFR) change. RESULTS A total of 19 cohort studies with at least 3551 patients (RAPN, 1216; OPN, 2335) were included. Compared with OPN, RAPN had the advantages of (a) lower rates of postoperative complication (risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.46, 0.78, p = 0.0002), postoperative minor complication (RR = 0.73, 95% CI = 0.56, 0.96, p = 0.02), and postoperative major complication (RR = 0.50, 95% CI = 0.30, 0.84, p = 0.01); (b) lower need for transfusion (RR = 0.64, 95% CI = 0.41, 0.98, p = 0.04); (c) less EBL (weighted mean difference [WMD] = -98.82, 95% CI = -125.64, -72.01, p < 0.00001); and (d) shorter LOS (WMD = -2.64, 95% CI = -3.27, -2.00, p < 0.00001). Sensitivity analyses excluding studies with obvious selection bias based on tumor complexity confirmed all these advantages. RAPN had longer OT (WMD = 18.56, 95% CI = 2.13, 35.00, p = 0.03) and WIT (WMD = 3.65, 95% CI = 0.75, 6.56, p = 0.01) in the primary analyses. Sensitivity analyses, however, showed no differences between RAPN and OPN regarding OT and WIT. Intraoperative complication rate (RR = 0.61, 95% CI = 0.29, 1.27, p = 0.19), PSM rate (RR = 0.87, 95% CI = 0.56, 1.34, p = 0.52), and short-term eGFR change, including absolute eGFR change (WMD = -1.56, 95% CI = -3.41, 0.28, p = 0.10) and percentage eGFR change (WMD = 0.99, 95% CI = -0.52, 2.50), did not differ between the two approaches. CONCLUSIONS Compared with OPN, RAPN appears to have lower morbidity and achieves similar short-term functional outcomes. However, evidence is limited regarding the long-term oncologic outcomes even though the PSM rate is similar between the two groups. Well-designed RCTs with large sample sizes and long-term follow-up are needed to confirm and update the findings of our study.

Changes in erectile organ structure and function in a rat model of chronic prostatitis/chronic pelvic pain syndrome

There is a growing recognition of the association between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED); however, most of the reports are based on questionnaires which cannot distinguish between organic and functional ED. The purpose of this study was to determine the exact relationship between CP/CPPS and ED, and to investigate the changes in erectile organ structure and function in a rat model of CP/CPPS. We established a rat model of experimental autoimmune prostatitis (EAP), which is a valid model for CP/CPPS. Erectile function in EAP and normal rats was comparable after cavernous nerve electrostimulation. The serum testosterone and oestradiol levels, ultrastructure of the corpus cavernosum and expression of endothelial nitric oxide synthase and neuronal nitric oxide synthase in the two groups were similar; however, there was a decrease in smooth muscle‐to‐collagen ratio and alpha‐smooth muscle actin expression and an increase in transforming growth factor‐beta 1 expression was observed in EAP rats. Thus, organic ED may not exist in EAP rats. We speculate that ED complained by patients with CP/CPPS may be psychological, which could be caused by impairment in the quality of life; however, further studies are needed to fully understand the potential mechanisms underlying the penile fibrosis in EAP rats.