Shuxiong Zeng

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.

Low-Dose Versus Standard Dose of Bacillus Calmette-Guerin in the Treatment of Nonmuscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis.

AbstractWhether low-dose Bacillus Calmette-Guerin (BCG) treatment can reduce the side effects while maintaining efficacy for patients with nonmuscle invasive bladder cancer (NMIBC) is controversial.To investigate whether low-dose BCG treatment can reduce the side effects while maintaining efficacy for patients with NMIBC when compared with standard-dose BCG treatment.A comprehensive literature search of PubMed, EMBASE, CINAHL, LILACS, and CENTRAL databases was conducted to identify relevant randomized controlled trials (RCT) or quasi-randomized controlled trials (qRCT) that have assessed the efficacy of low- and standard-dose BCG therapy for patients with NMIBC. Systematic review and meta-analysis were performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis Criteria.Six RCTs and 2 qRCTs were eligible for meta-analysis. Low-dose BCG instillation was not inferior to reduce the risk of bladder tumor recurrence (hazard ratio [HR], 1.15; 95% confidence interval [CI], 1.00–1.31; P = 0.05), meanwhile no difference was found regarding tumor progression (HR = 1.08; 95%CI, 0.83–1.42; P = 0.57). However, low-dose BCG provided a significantly lower incidence of overall side effects (RR = 0.75; 95%CI, 0.60–0.94; P = 0.01), systemic side effects (RR = 0.57; 95%CI, 0.34–0.97; P = 0.04), severe side effects (RR = 0.52; 95%CI, 0.36–0.74; P = 0.0003), and withdrawal due to BCG toxicity (RR = 0.49; 95%CI, 0.26–0.91; P = 0.02). In contrast, local side effects were comparable between low- and standard-dose arms (RR = 0.89; 95%CI, 0.73–1.08; P = 0.24).Low-dose BCG instillation significantly reduces the incidence of overall side effects, especially severe and systemic symptoms in patients with NMIBC, while the oncological control efficacy of low-dose BCG is not inferior to standard-dose BCG. Further studies with stratification using different risk factors at randomization are required to assess whether the efficacy of low-dose BCG is comparable to standard dose BCG for different risk of patients.PROSPERO registration No CRD42014014871 (www.crd.york.ac.uk/prospero/).

DAPK Promoter Methylation and Bladder Cancer Risk: A Systematic Review and Meta-Analysis.

Background Methylation of tumor suppressor gene promoter leads to transcription inactivation and is involved in tumorigenesis. Several studies demonstrate a potential association between the Death-Associated Protein Kinase (DAPK) gene promoter methylation and bladder cancer risk, tumor stage and histological grade. Due to inconsistent results of these studies, we performed this meta-analysis to ascertain the association. Methods Studies were retrieved from the PubMed, Embase, Web of Science and the Cochrane Library databases. Study selection and data extraction were executed by two reviewers independently. Meta-analysis was performed using Stata 13.0 and Review Manager 5.3 software. Results A total of 21 articles involving 15 case control and 8 case series studies were included in this meta-analysis. DAPK promoter methylation was associated with bladder cancer risk (OR: 5.81; 95%CI = 3.83–8.82, P<0.00001). The frequency of DAPK promoter methylation was equal in bladder cancer tissue and paired adjacent normal tissue (OR: 0.87; 95%CI = 0.31–2.48, P = 0.794). Furthermore, DAPK promoter methylation was associated with higher histological grade (OR: 1.52; 95%CI = 1.10–2.09, P = 0.011) but not associated with tumor stage (OR: 1.12; 95%CI = 0.67–1.87, P = 0.668). Conclusions The result suggests that DAPK promoter methylation is significantly increased in bladder cancer patients compared to normal controls. DAPK promoter methylation could serve as a biomarker for bladder cancer detection and management.

A Pilot Study of Vela Laser for En Bloc Resection of Papillary Bladder Cancer

Micro‐Abstract Transurethral resection of bladder tumors is associated with perioperative or postoperative complications, and an “incise and scatter” procedure contradicts basic oncologic principles. The present study introduces the Vela laser, a new type of thulium laser with a 1.94‐&mgr;m wavelength, for en bloc resection of bladder tumors. The pilot experience found the Vela laser could preserve the muscle layer and was effective, feasible, and safe for patients with bladder tumors. Introduction: The present study evaluated the safety and efficacy of the Vela laser for en bloc resection of papillary bladder tumors. Materials and Methods: From January 2013 to August 2014, 38 patients underwent en bloc resection with the Vela laser and a 26F continuous flow resectoscope or 18F flexible cystoscope. Random cold forceps biopsy samples were also taken. The total operation time, pathologic result, and intraoperative and postoperative complications were recorded. Each patient was followed up for ≥ 1 year. Results: The average total operation time was 23 minutes. The en bloc resection of all tumors was successful, with 2 cases located at the bladder dome requiring the use of a flexible cystoscope for better management. No complications occurred during or after surgery. All resected tumors were intact with the detrusor muscle layer and architecture available for pathologic evaluation. One patient with stage T2b tumor underwent laparoscopic cystectomy 1 week after the initial surgery. At a median follow‐up period of 21.8 months, the recurrence rate at 12 months was 21.6% (8 of 37). Conclusion: The results of our study have shown that the Vela laser is an effective, feasible, and safe thulium laser for en bloc bladder tumor resection. It was associated with negligible complications and allows accurate pathologic evaluation. The Vela laser can serve as an alternative treatment method for nonmuscle‐invasive bladder cancer or infiltrating tumor.

Whole-exome sequencing of muscle-invasive bladder cancer identifies recurrent copy number variation in IPO11 and prognostic significance of importin-11 overexpression on poor survival

Non-muscle-invasive bladder cancer (NMIBC) often has a worse prognosis following its progression to muscle-invasive bladder cancer (MIBC), despite radical cystectomy with pelvic lymph node dissection combined with chemotherapy. Therefore, the discovery of novel biomarkers for predicting the progression of this disease and of therapeutic targets for preventing it is crucial. We performed whole-exome sequencing to analyze superficial tumor tissues (Tsup) and basal tumor tissues (Tbas) from 3 MIBC patients and identified previously unreported copy number variations in IPO11 that warrants further investigation as a molecular target. In addition, we identified a significant association between the absolute copy number and mRNA expression of IPO11 and found that high importin-11 expression was correlated with poor 3-year overall survival (OS), cancer-specific survival (CSS) and cancer-free survival (CFS) compared with low expression in the BCa patients. Importin-11 overexpression was also an independent risk factor for CSS and CFS in the BCa patients. Our study has revealed that IPO11 copy number amplification contributes to its overexpression and that these changes are unfavorable prognostic factors in NMIBC. Thus, IPO11 copy number amplification and importin-11 overexpression are promising biomarkers for predicting the progression and poor prognosis of patients with NMIBC.

rs1495741 as a tag single nucleotide polymorphism of N-acetyltransferase 2 acetylator phenotype associates bladder cancer risk and interacts with smoking: A systematic review and meta-analysis.

Abstract Rs1495741 has been identified to infer N-acetyltransferase 2 (NAT2) acetylator phenotype, and to decrease the risk of bladder cancer. However, a number of studies conducted in various regions showed controversial results. To quantify the association between rs1495741 and the risk of bladder cancer and to estimate the interaction effect of this genetic variant with smoking, we performed a systematic literature review and meta-analysis involving 14,815 cases and 58,282 controls from 29 studies. Our results indicates rs1495741 significantly associated with bladder cancer risk (OR = 0.85, 95% CI = 0.82–0.89, test for heterogeneity P = 0.36, I 2 = 7.0%). And we verified this association in populations from Europe, America, and Asia. Further, our stratified meta-analysis showed rs1495741s role is typically evident only in ever smokers, which suggests its interaction with smoking. This study may provide new insight into gene-environment study on bladder cancer.

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.

Deceptive muscle invasive bladder cancer recurrence with benign biopsy foci after bladder sparing treatment.

AbstractMost of recurrent bladder carcinoma after partial cystectomy did not cause diagnostic difficulties for urologists, because of the appearance of typical papillary in ultrasonography or cystoscopy, and could be easily confirmed by tumor biopsy. Three patients, ages from 35 to 62 years, had undergone bladder sparing treatment for muscle invasive bladder cancer, all of them had biopsy revealed benign bladder lesion at surveillance cystoscopy. However, transurethral resection of bladder tumor showed high-grade muscle invasive urothelial bladder carcinoma for these patients. Two patients were thus delayed for timely cystectomy and consequently resulted in local or distal metastasis.As a result, we recommended that timely pelvic enhanced computed tomography and transurethral resection of bladder tumor were necessary when bladder lesion occurred after partial cystectomy, avoiding the possibility of missing muscle invasive urothelial bladder carcinoma recurrence and delaying timely cystectomy.

Importin-11 overexpression promotes the migration, invasion, and progression of bladder cancer associated with the deregulation of CDKN1A and THBS1

OBJECTIVES We recently determined that a novel oncogene, IPO11 from 5q12, participates in bladder cancer (BCa) progression. However, the biological function of IPO11 and the molecular mechanisms through which it contributes to BCa progression remain unclear. The aim of this study was to investigate the role of IPO11 in BCa aggressiveness and elucidate the molecular mechanisms underlying its effects in BCa. MATERIALS AND METHODS The mRNA expression levels of IPO11 in BIU-87, RT4, UMUC3, EJ, 5637, T24, J82, and HT-1376 cell lines were determined using quantitative real-time polymerase chain reaction. Expression of importin-11 was detected in 134 formalin-fixed and paraffin-embedded (FFPE) BCa tissues and 10 paired nonneoplastic bladder tissue specimens by immunohistochemistry. The copy number of IPO11 was examined in 25 FFPE BCa specimens using fluorescent in situ hybridization. The effects of IPO11 on migration, invasion, and cell proliferation were investigated in EJ and 5637 cell lines using RNA interference. Potential molecular mechanisms were investigated using whole transcriptome sequencing and bioinformatic approaches in EJ cells and IPO11-silenced EJ cells and verified using quantitative real-time polymerase chain reaction. RESULTS Endogenous IPO11 mRNA was highly expressed in 6 invasive BCa cell lines (EJ, HT-1376, UMUC3, 5637, J82, and T24) but had a low expression in the noninvasive BCa cell line BIU-87 and the papillary BCa cell line RT4. Immunohistochemical staining revealed that 87 (64.9%) of 134 FFPE BCa tissues displayed importin-11 overexpression. Moreover, importin-11 overexpression was positively associated with increased tumor stages and tumor grades, lymphatic invasion, and lymph node metastasis. Furthermore, importin-11 overexpression was detected in 100% (14/14) of BCa tissues with IPO11 amplification, and IPO11 amplification was not observed in 2 additional BCa tissues with importin-11 overexpression. Small interfering RNA-mediated knockdown of IPO11 is sufficient to inhibit the motility and invasiveness of EJ and 5637 cells. IPO11 knockdown also inhibited cell proliferation in EJ cells, whereas this was not observed in 5637 cells or the in vivo experiments. Using whole transcriptome sequencing, we found that 22 genes (including IPO11) were differentially expressed in IPO11-silenced EJ cells compared with wild-type EJ cells, 4 of which were upregulated, and 18 of which were downregulated. KEGG pathway enrichment analysis of the significantly differentially expressed genes showed that the proteoglycans in cancer pathway (pathway Id: hsa05205) was most significantly enriched among 10 genetically altered pathways and referred to 6 significantly altered genes (CDKN1A, HBEGF, PTK2, THBS1, CCNG2, and EGR1). The next 3 most significantly enriched pathways in order were the p53, ErbB, and BCa pathways. CDKN1A and THBS1 were the most 2 frequently covered genes and were involved in 9 and 6 pathways, respectively. They were also 2 key proteins in the BCa pathway (pathway Id: hsa05219) that were downregulated in IPO11-knockdown EJ cells compared with wild-type EJ cells. CONCLUSIONS Importin-11 overexpression can promote BCa cell invasiveness, probably associated with the deregulation of CDKN1A and THBS1 primarily through the activation of the proteoglycans in cancer pathway and the classical BCa pathway. Importin-11 may be a useful target through which the progression of noninvasive BCa to invasive BCa can be blocked.