Min-Guang Zhang

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.

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.

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.

Vasoactive intestinal polypeptide, an erectile neurotransmitter, improves erectile function more significantly in castrated rats than in normal rats

What’s known on the subject? and What does the study add?

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.

Lymphovascular Invasion and the Presence of More Than Three Tumors Are Associated With Poor Outcomes of Muscle-invasive Bladder Cancer After Bladder-conserving Therapies

OBJECTIVES To identify the predictive factors for survival and recurrence of patients with muscle-invasive bladder cancer (MIBC) (urothelial carcinoma) after bladder-conserving therapies and to determine the efficacy of partial cystectomy plus chemotherapy and radiotherapy in the treatment of MIBC. METHODS From 2002 through 2007, 100 patients with MIBC (pT2 74%, pT3-4 26%) underwent partial cystectomy (PC). Subjects who had stage pT3-4 disease received adjuvant chemotherapy and radiotherapy. Univariate and multivariate analyses were performed to determine the predictive factors. RESULTS At median follow-up of 31.5 months (range 6-66 months), 46% patients experienced superficial local recurrence and 14% developed muscle-invasive local recurrence. At the end of follow-up, 24 patients died of bladder cancer, and 71 patients (71%) survived with intact bladders. The 5-year bladder-intact survival rate was 63%. The 5-year cancer-specific survival (CSS) rate was 68%. By multivariate analysis, the presence of more than 3 tumors (P = .002, RR 2.718, 95% CI 1.455-5.079) and nonpapillary growth patterns (P = .005, RR 4.537, 95% CI 1.573-13.081) were predictive factors for local cancer recurrence; the presence of more than 3 tumors (P = .002, RR 4.109, 95% CI 1.676-10.072), lymphovascular invasion (P = .001, RR 6.098, 95% CI 2.038-18.246), and partial cystectomy plus ureteral reimplantation (PC plus UR) (P = .011, RR 0.129, 95% CI .027-0.627) were significantly associated with 5-year CSS, and PC plus UR promoted survival. CONCLUSIONS PC plus chemotherapy and radiotherapy is a rational alternative to radical cystectomy for the treatment of MIBC. Lymphovascular invasion and the presence of more than 3 tumors predict poor outcomes in MIBC after bladder-sparing therapy.

Engagement of Integrinβ1 Induces Resistance of Bladder Cancer Cells to Mitomycin-C

OBJECTIVE To identify whether integrinβ1 subunit is responsible for the resistance of bladder cancer cell to the therapeutic drug mitomycin-C (MMC), when grown on fibronectin (FN). MATERIALS AND METHODS The expression of integrinβ1 on bladder cancer T24 and 5637 cells was examined by the flow cytometer. The adhesion of cells to plates with the absence or presence of FN was determined. Analysis of apoptosis induced by MMC was assessed using the flow cytometer in combination with an integrinβ1-blocking antibody or siRNA targeting the coding region of integrinβ1. Western blot was used to study the expression change of integrinβ1 and its downstream molecules. RESULTS Bladder cancer T24 and 5637 cells express high level of integrinβ1 (87.3% ± 2.3 and 90.1% ± 1.9, respectively). Cellular adhesion to FN was significantly reduced by the blocking of integrinβ1. Blocking or silencing of integrinβ1 significantly abolished the drug resistance of cells grown on FN to MMC (P <.05) and inhibited the activation of survival signals phosphoinositide-3 kinase (PI3-K)/Akt. CONCLUSION Integrinβ1-mediated cellular adhesion to FN confers drug resistance to MMC on bladder cancer cells. Knockdown of integrinβ1 may abolish the drug resistance phenotype and sensitize bladder cancer cells to MMC.

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.

Theranostic Studies of Human Sodium Iodide Symporter Imaging and Therapy Using 188Re: A Human Glioma Study in Mice

Objective To investigate the role of 188Re in human sodium iodide symporter (hNIS) theranostic gene-mediated human glioma imaging and therapy in model mice. Methods The human glioma cell line U87 was transfected with recombinant lentivirus encoding the hNIS gene under the control of cytomegalovirus promoter (U87-hNIS). The uptake and efflux of 188Re were determined after incubating the cells with 188Re. 188Re uptake experiments in the presence of various concentrations of sodium perchlorate were carried out. In vitro cell killing tests with 188Re were performed. U87-hNIS mediated 188Re distribution, imaging and therapy in nude mice were also tested. Results U87-hNIS cell line was successfully established. The uptake of 188Re in U87-hNIS cells increased up to 26-fold compared to control cells, but was released rapidly with a half-life of approximately 4 minutes. Sodium perchlorate reduced hNIS-mediated 188Re uptake to levels of control cell lines. U87-hNIS cells were selectively killed following exposure to 188Re, with a survival of 21.4%, while control cells had a survival of 92.1%. Unlike in vitro studies, U87-hNIS tumor showed a markedly increased 188Re retention even 48 hours after 188Re injection. In the therapy study, there was a significant difference in tumor size between U87-hNIS mice (317±67 mm3) and control mice (861±153 mm3) treated with 188Re for 4 weeks (P<0.01). Conclusion The results indicate that inserting the hNIS gene into U87 cells is sufficient to induce specific 188Re uptake, which has a cell killing effect both in vitro and in vivo. Moreover, our study, based on the function of hNIS as a theranostic gene allowing noninvasive imaging of hNIS expression by 188Re scintigraphy, provides detailed characterization of in vivo vector biodistribution and level, localization, essential prerequisites for precise planning and monitoring of clinical gene therapy that aims to individualize gene therapy concept.

Histopathological classification criteria of rat model of chronic prostatitis/chronic pelvic pain syndrome

ObjectiveA variety of murine models of experimental prostatitis that mimic the phenotype of human chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have been developed. However, there is still a lack of explicit diagnosis criteria about those animal model. Our study is to establish histopathological classification criteria, which will be conducive to evaluate the animal models.MethodsWe firstly established a rat model of experimental autoimmune prostatitis that is considered a valid model for CP/CPPS. For modelling, male Sprague–Dawley rats were immunized with autologous prostate tissue homogenate supernatant emulsified with complete Freund’s adjuvant by subcutaneous injection into abdominal flank and simultaneously immunized with pertussis–diphtheria–tetanus vaccine by intraperitoneal injection. Three immunizations were administered semimonthly. At the 45th day, animals were killed, and prostate tissues were examined for morphology.ResultsHistologically, the prostate tissues were characterized by lymphoproliferation, atrophy of acini, and chronic inflammatory cells infiltration in the stromal connective tissue around the acini or ducts. Finally, we built histopathological classification criteria incorporating inflammation locations (mesenchyme, glands, periglandular tissues), ranges (focal, multifocal, diffuse), and grades (grade I–IV). To verify the effectiveness and practicability of the histopathological classification criteria, we conducted the treatment study with one of the alpha blockers, tamsulosin.ConclusionThe histopathological classification criteria of rat model of CP/CPPS will serve for further research of the pathogenesis and treatment strategies of the disease.