Rongchao Wei

miRNA-100 Inhibits Human Bladder Urothelial Carcinogenesis by Directly Targeting mTOR

miRNAs are involved in cancer development and progression, acting as tumor suppressors or oncogenes. In this study, miRNA profiling was conducted on 10 paired bladder cancer tissues using 20 GeneChip miRNA Array, and 10 differentially expressed miRNAs were identified in bladder cancer and adjacent noncancerous tissues of any disease stage/grade. After being validated on expanded cohort of 67 paired bladder cancer tissues and 10 human bladder cancer cell lines by quantitative real-time PCR (qRT-PCR), it was found that miR-100 was downregulated most significantly in cancer tissues. Ectopic restoration of miR-100 expression in bladder cancer cells suppressed cell proliferation and motility, induced cell-cycle arrest in vitro, and inhibited tumorigenesis in vivo both in subcutaneous and in intravesical passage. Bioinformatic analysis showed that the mTOR gene was a direct target of miR-100. siRNA-mediated mTOR knockdown phenocopied the effect of miR-100 in bladder cancer cell lines. In addition, the cancerous metastatic nude mouse model established on the basis of primary bladder cancer cell lines suggested that miR-100/mTOR regulated cell motility and was associated with tumor metastasis. Both mTOR and p70S6K (downstream messenger) presented higher expression levels in distant metastatic foci such as in liver and kidney metastases than in primary tumor. Taken together, miR-100 may act as a tumor suppressor in bladder cancer, and reintroduction of this mature miRNA into tumor tissue may prove to be a therapeutic strategy by reducing the expression of target genes. Mol Cancer Ther; 12(2); 207–19. ©2012 AACR.

Laparoscopic versus open radical cystectomy for elderly patients over 75-year-old: a single center comparative analysis.

Purpose To explore the morbidity, mortality and oncological results of laparoscopic radical cystectomy (LRC) in the elderly patients over 75-year-old in contrast with open radical cystectomy (ORC). Materials and Methods We analyzed 46 radical cystectomies from January 2009 to December 2013 in patients over 75-year-old in our institute, 21 patients in the LRC group and 25 in the ORC group. Demographic parameters, operative variables and perioperative outcome were retrospectively collected and analyzed between the two groups. Perioperative morbidity and mortality were categorized as early (within 90 days after surgery) or late (more than 90 days) according to the time of occurrence. Results Patients in both groups had comparable preoperative characteristics. A significant longer operative time (418 vs. 337 min, p = 0.018) and less estimated blood loss (400 vs. 500 ml p = 0.038) were observed in LRC group compared with ORC group. Infection and ileus were the most common early complications after surgery. Patients underwent ORC suffered from significantly more postoperative ileus (28.0% vs. 4.8%, P = 0.038) and infection (40% vs. 9.5%, P = 0.019) than LRC group within 90 days after surgery. The mortality rate was 4.7% (1/21) and 4% (1/25) for LRC group and ORC group respectively. At a median follow-up of 21 months (range 2–61 months), the Kaplan-Meier survival curves and log-rank analysis demonstrate that there were no significant differences between the LRC and ORC groups in the 3-year overall, cancer-specific, or recurrence-free survival rates. Conclusions It is suggested that LRC should be recommended as the primary intervention to treat muscle invasive or high risk non-muscle invasive bladder cancer in elderly patients with a relative long life expectancy.

Solifenacin is able to improve the irritative symptoms after transurethral resection of bladder tumors.

OBJECTIVE To evaluate the efficacy and safety of solifenacin in the management of irritative symptoms after transurethral resection of bladder tumors (TURBTs) with subsequent intravesical chemotherapy. METHODS A total of 116 patients undergoing TURBT were randomly allocated into 2 groups, 58 patients in each group. Group 1 patients received solifenacin 5 mg, 6 hours before surgery and 5 mg per day, after surgery for 2 weeks, whereas group 2 patients received a placebo. Patients with low-risk non-muscle-invasive bladder cancer received immediate postoperative instillation of epirubicin. Patients with medium- or high-risk non-muscle-invasive bladder cancer received postoperative instillation twice within 2 weeks, once immediately following the operation and once on the eighth postoperative day. All patients completed bladder diaries before surgery, on the 1st, 7th, and 14th days after removal of the catheter with overactive bladder symptom scores completed preoperatively, and on the 7th and 14th days. Additionally, the incidence and severity of catheter-related bladder discomfort were recorded at 6, 12, 24, 48, and 72 hours after the surgery. RESULTS The incidence and the severity of catheter-related bladder discomfort in group 1, compared with group 2, were significantly reduced (P<.05). There was a significant difference in overactive bladder symptom scores between the 2 groups (5.67 vs 7.86; P<.001). Episodes of daytime, frequency, nocturia, urgency, and urge urinary incontinence in group 1 were also significantly lower than in group 2 (P<.05). CONCLUSION This study demonstrates that solifenacin can be beneficial for the management of irritative symptoms after TURBT with subsequent intravesical chemotherapy.

A New Tool for Distinguishing Muscle Invasive and Non-Muscle Invasive Bladder Cancer: The Initial Application of Flexible Ultrasound Bronchoscope in Bladder Tumor Staging

Objectives To validate the flexible ultrasound bronchoscope (FUB) as a tool in distinguishing muscle invasive and non-muscle invasive bladder tumors. Materials and Methods From June 2010 to April 2012, 62 patients (11 female and 51 male) with 92 bladder urothelial carcinoma were treated in our study. The mean (±SD) patient age was 64.0±12.5 years old (ranged from 22 to 87). Clinical T stage was assessed by FUB at first in operating room, then immediately initial diagnostic transurethral resection (TUR) was performed. A second TUR would be done 2–4 weeks after initial TUR when the latter was incomplete (in large and multiple tumours, no muscle in the specimen) or when an exophytic high-grade and/or T1 tumour was detected. And radical cystectomy would be performed for the patients who were diagnosed with muscle-invasive tumors. FUB staging and initial TUR staging, final pathological results were compared. Results In ultrasonic images, the normal muscle layer of bladder wall could be clearly distinguished into three layers, which were hyperechogenic mucosa, hypoechogenic muscle and hyperechogenic serosal. For non-muscle invasive tumors, the muscle layers were continuous. And distorted or discontinuous muscle layers could be seen in muscle-invasive case. The overall accuracy (95.7%) and the specificity of muscle invasion detection of FUB (98.8%) were comparable to TUR (overall accuracy 90.2% and specificity 100%), but sensitivity of muscle invasion detection of FUB was significantly higher than initial TUR (72.7%VS18.2%). Moreover, the tumors diameter could not affect the FUBs accuracy of muscle invasion detection. For tumors near the bladder neck, FUB also showed the similar validity as those far from bladder neck. Conclusions To conclude, the flexible ultrasound bronchoscope is an effective tool for muscle invasion detection of bladder tumor with ideal ultrasonic images. It is an alternative option for bladder tumor staging besides TUR. It might have the potentiality to change the bladder diagnostic strategy.

Imaging diagnosis and endoscopic treatment for ureteral fibroepithelial polyp prolapsing into the bladder

OBJECTIVE Fibroepithelial polyps of ureter prolapsing into the bladder are a rare urological condition. We report the imaging findings and our experience with endoscopic treatment for ureteral fibroepithelial polyps prolapsing into the bladder. PATIENTS AND RESULTS Four patients with frank pain and hematuria were enrolled. Intravenous urography and computed tomography revealed a ureteral mass with filling defects in affected ureter and mild hydronephrosis. Endoscopic examination showed ureteral polyps prolapsing in the bladder. The histopathologic diagnosis on 4 cases was benign fibroepithelial polyps of ureter. The largest polyps (from 4-10 cm in length) were successfully resected and vaporized by Holmium: YAG laser. A double-pigtail ureteral stent at 7F was placed and left for 6 weeks after the procedure. Neither recurrence nor ureter stricture was observed after up to 12 years of follow-up. CONCLUSIONS Ureteral malignancy must be excluded in cases where a ureteral mass is detected. Endoscopic management is recommended to minimize morbidity and complications in treatment of ureteral fibroepithelial polyps that prolapse into the bladder.

Transcriptome sequencing identifies ANLN as a promising prognostic biomarker in bladder urothelial carcinoma

The prognosis of bladder urothelial carcinoma (BLCA) varies greatly even for patients with similar pathological characteristics. We conducted transcriptome sequencing on ten pairs of BLCA samples and adjacent normal tissues to identify differentially expressed genes. Anillin (ANLN) was identified as a transcript that was significantly up-regulated in BLCA samples compared with normal tissues. Prognostic power of candidate gene was studied using qRT-PCR and immunohistochemistry on 40 and 209 patients, respectively. Patients with elevated ANLN expression level was correlated with poorer cancer-specific (median, 22.4 vs. 37.3 months, p = 0.001), progression-free (median, 19.7 vs. 27.9 months, p = 0.001) and recurrence-free survival (median, 17.1 vs. 25.2 months, p = 0.011) compared with low ANLN expression. Public datasets TCGA and NCBI-GEO were analyzed for external validation. Knockdown of ANLN in J82 and 5637 cells using small interfering RNA significantly inhibited cell proliferation, migration, and invasion ability. Moreover, knockdown of ANLN resulted in G2/M phase arrest and decreased expression of cyclin B1 and D1. Microarray analysis suggested that ANLN played a major role in cell migration and was closely associated with several cancer-related signaling pathways. In conclusion, ANLN was identified as a promising prognostic biomarker which could be used to stratify different risks of BLCA.

AB100. Laparoscopic ureteral reimplantation underneath broad ligament tunnel for female vesicoureteral stenosis: a technical innovation

Purpose In order to anatomically reconstruct the ureteral stenosis, we present a novel technique for laparoscopic ureteral reimplantation. Patients and methods Three young females, who were diagnosed as hydroureteronephrosis caused by congenital vesicoureteral junction obstruction, were treated by laparoscopic ureteral reimplantation with a tunnel underneath the broad ligament. Results Surgery was performed successfully without conversion to open surgery. No major intraoperative or postoperative complications occurred. The mean postoperative follow-up was 38, 33 and 26 months respectively. The operative time was between 220 and 260 minutes. The mean estimated blood loss was less than 20 mL. Subsequent imaging performed 3 months after surgery revealed relief of hydroureteronephrosis for all patients. Patients all gave birth to healthy neonates and showed normal urinary tract sonogram and urine analysis during gestation period. Conclusion Laparoscopic ureteral reimplantation with a tunnel underneath the broad ligament tunnel is safe, effective, allowing for anatomical reconstruction of ureter defects, however. A larger clinical sample and longer follow-up period will be needed for fully validation of this technique.

Expression of transglutaminase 4 in prostate cancer and its clinical significance

Objective To investigate the value of transglutaminase 4 in diagnosis and prognosis prediction of prostate cancer.Methods Transglutaminase 4 immunostaining was performed with paraffin sections from 159 prostate cancer patients receiving radical prostatectomy,and the staining results were divided into 4 levels:negative staining,weak staining,moderate staining,and strong staining.The clinical and pathological information of the patients were obtained by reviewing the medical records.The follow-up data were collected by reviewing medical records,prostate cancer database of our department,and telephoning the patients or their family members.Expression of transglutaminase 4 and clinical,prognosis data of patients were subjected to statistical analysis.Results The expression of transglutaminase 4 in the prostatic cancer tissue was significantly higher than that in the adjacent normal tissue(P0.001);and the expressions were significantly different in patients with different Gleason grades(P0.001)and different prostate specific antigen levels(P=0.005).Univariate Cox regression analysis indicated that high transglutaminase 4 expression was a risk factor of biochemical recurrence of prostatic cancer(P=0.020),but multivariate Cox regression analysis did not support this finding(P=0.139).Conclusion Transglutaminase 4 expression is increased in prostate cancer tissues,and the expression is stronger in malignant tissues with higher Gleason grade and prostate specific antigen level.