Ruifa Han

Laparoscopic versus open nephroureterectomy for the treatment of upper urinary tract urothelial carcinoma: a systematic review and cumulative analysis of comparative studies.

CONTEXT Laparoscopic nephroureterectomy (LNU) has increasingly been used as a minimally invasive alternative to open nephroureterectomy (ONU), but studies comparing the efficacy and safety of the two surgical procedures are still limited. OBJECTIVE Evaluate the oncologic and perioperative outcomes of LNU versus ONU in the treatment of upper urinary tract urothelial carcinoma. EVIDENCE ACQUISITION A systematic review and cumulative analysis of comparative studies reporting both oncologic and perioperative outcomes of LNU and ONU was performed through a comprehensive search of the Medline, Embase, and the Cochrane Library electronic databases. All analyses were performed using the Review Manager (RevMan) v.5 (Nordic Cochrane Centre, Copenhagen, Denmark) and Meta-analysis In eXcel (MIX) 2.0 Pro (BiostatXL) software packages. EVIDENCE SYNTHESIS Twenty-one eligible studies (1235 cases and 3093 controls) were identified. A significantly higher proportion of pTa/Tis was observed in LNU compared to ONU (27.52% vs 22.59%; p = 0.047), but there were no significant differences in other stages and pathologic grades (all p>0.05). For patients who underwent LNU, the 5-yr cancer-specific survival (CSS) rate was significantly higher, at 9% (p = 0.03), compared to those who underwent ONU, while the overall recurrence rate and bladder recurrence rate were notably lower, at 15% (p = 0.01) and 17% (p = 0.02), respectively. However, there were no statistically significant differences in 2-yr CSS, 5-yr recurrence-free survival (RFS), 5-yr overall survival (OS), 2-yr OS, and metastasis rates between LNU and ONU (all p>0.05). Moreover, there were no significant differences between LNU and ONU in terms of intraoperative complications, postoperative complications, and perioperative mortality (all p>0.05). The results of our study were mainly limited by the retrospective design of most of the individual studies included as well as selection biases based on different management of regional lymph nodes and pathologic characteristics. CONCLUSIONS Our data suggest that LNU offers reliable perioperative safety and comparable oncologic efficacy when compared to ONU. Given that some limitations cannot be overcome, well-designed prospective trials are needed to confirm our findings.

Tubeless Percutaneous Nephrolithotomy is Associated With Less Pain and Shorter Hospitalization Compared with Standard or Small Bore Drainage: A Meta-analysis of Randomized, Controlled Trials

OBJECTIVES To assess the efficacy and safety of tubeless percutaneous nephrolithotomy (PCNL) compared with standard or small-bore PCNL with a meta-analysis of randomized, controlled trials. METHODS All eligible studies were searched on MEDLINE, Embase, and the Cochrane Library databases. Risk ratio (RR), mean difference, or standardized mean difference (SMD), with its 95% CI, was used to evaluate the size effect. RESULTS Ten and 3 trials were identified for comparison I (tubeless PCNL vs standard PCNL, 320 cases and 323 controls) and comparison II (tubeless PCNL vs small-bore PCNL, 55 cases and 54 controls), respectively. Tubeless PCNL required significantly less analgesia relative to standard PCNL (SMD -1.72; 95% CI -2.30 to 1.13; P(heterogeneity) = 0.04) and small-pore PCNL (SMD -0.69; 95% CI -1.13 to 2.05; P(heterogeneity) = 0.94). Furthermore, there was a remarkably shorter hospital stay in comparison I (SMD -1.35; 95% CI -1.40 to 1.30; P(heterogeneity) = 0.60) and comparison II (SMD -0.49; 95% CI -0.76 to 0.21; P(heterogeneity) = 0.15). The return to normal activity days was also significantly decreased in comparison I (SMD -4.34; 95% CI -6.28 to 2.41; P(heterogeneity) = 0.02). However, no significant difference was observed in the analyses concerning stone-free blood transfusion and complications rate in both comparisons. In subgroup analyses by nephrostomy diameter (22-Fr) and drainage methods, most results were consistent with the overall findings except for that to evaluate the operative time in the double-J stent subgroup. CONCLUSIONS Tubeless PCNL is associated with less pain and quicker recovery compared with standard or small-bore PCNL, in the management of uncomplicated renal calculi.

XRCC1 Genetic Polymorphisms and Bladder Cancer Susceptibility: A Meta-analysis

OBJECTIVES To examine the association between three x-ray repair cross-complementing group 1 (XRCC1) genetic polymorphisms (Arg(194)Trp, Arg(280)His, and Arg(399)Gln) and bladder cancer susceptibility. METHODS A comprehensive search was conducted to identify all case-control studies of XRCC1 polymorphisms and bladder cancer risk. Statistical analysis was performed with the software program Review Manage, version 4.2. RESULTS A total of 10 eligible reports, including 3749 cases and 3947 controls, were identified. For Arg(194)Trp (six studies, 3091 cases, 3219 controls), no evidence indicated that individuals carrying the variant genotypes (Trp/Trp + Arg/Trp), relative to those carrying the wild homozygote Arg/Arg genotype, had a decreased risk of bladder cancer (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.77 to 1.05; P = 0.17). For Arg(280)His (three studies, 2547 cases, 1784 controls), individuals with His/His+Arg/His genotypes had no significant risk of bladder cancer, compared with those with the Arg/Arg genotype (OR 0.99, 95% CI 0.55 to 1.77; P = 0.97). For Arg(399)Gln (10 studies, 3729 cases, 3927 controls), the Gln/Gln genotype carriers did not have a decreased cancer risk compared with those individuals with the Arg/Arg genotype (OR 0.95, 95% CI 0.82 to 1.10; P = 0.48). Similarly, no associations were found in the recessive and dominant modeling (Gln/Gln versus Arg/Gln+Arg/Arg: OR 0.92, 95% CI 0.80 to 1.05; P = 0.23; Arg/Gln+Gln/Gln versus Arg/Arg: OR 1.04, 95% CI 0.95 to 1.14; P = 0.36). CONCLUSIONS No association was found between the polymorphisms in XRCC1 (Arg(194)Trp, Arg(280)His, Arg(399)Gln) and bladder cancer susceptibility.

Metastasis-associated in colon cancer 1 is a novel survival-related biomarker for human patients with renal pelvis carcinoma.

Metastasis-associated in colon cancer 1 (MACC1) has recently been identified as a novel independent prognostic indicator for metastasis occurrence, overall survival and cancer-free survival for patients with colon cancer and other solid tumors. In this study, we investigated the role of MACC1 in the development and progression of renal pelvis carcinoma, a form of upper tract urothelial carcinomas. MACC1 protein has been found in the cytoplasm as well as in the nucleus of the transitional epithelial cells of the normal renal pelvis in immunohistochemical (IHC) assays. Quantitative IHC examinations revealed that MACC1 abnormal abundance in cancerous tissues might represent a biological indicator clinically suggestive of tumor malignancy in the renal pelvis. Furthermore, investigation of the association of MACC1 protein levels with clinicopathological parameters in this study has suggested a correlation of MACC1 expression with tumor-node-metastasis stage and histopathological grade of patients with renal pelvis carcinoma, with elevated MACC1 protein levels frequently associated with higher aggressiveness of the disease. Moreover, both disease-free survival and overall survival for the patients in the high MACC1 expression group were significantly lower than those in the low expression group. Multivariate analysis with a Cox proportional-hazards model suggested that MACC1 is indeed an independent prognostic indicator of overall survival and cancer-free survival for patients with renal pelvis carcinoma. Thus, MACC1 may represent a promising prognostic biomarker candidate, as well as a potential therapeutic target for this disease.

RETRACTED ARTICLE: Down-regulation of Sphk2 suppresses bladder cancer progression

Bladder cancer is the second most common urological malignancy around the world and is by far the most frequent urological malignancy in China. The abnormal expression of sphingosine kinase 2 (SphK2) is associated with tumor progression and a poor patient survival rate, however, the effect of SphK2 on the bladder cancer cells remains unclear. The aim of the paper was to study the expression of SphK2 in bladder cancer and the role of SphK2 on the cell proliferation, metastasis, and apoptosis in bladder cancer in vitro. Our results showed that SphK2 is up-regulated in bladder cancer tissues compared with the corresponding adjacent non-neoplastic tissues, and the expression level of SphK2 was significantly higher in human bladder cancer cells in comparison with normal bladder epithelial cells. Silencing of SphK2 could inhibit the proliferation ability of T24 cells in vitro. In addition, SphK2 knockdown could induce a significant increase in the number of apoptotic cells. Furthermore, the transwell assay also showed significant cell migration inhibition in SphK2 siRNA transfectant compared with cell lines transfected with NC. Thus, this study suggested that SphK2 inhibition may provide a promising treatment for bladder cancer patients.

Polymorphism in IGFBP3 gene is associated with prostate cancer risk: an updated meta-analysis

Objective Insulin-like growth factor-binding protein-3 (IGFBP3) is the major protein that binds with insulin-like growth factor-1 (IGF-1) and is considered to be involved in the development and progression of various cancers. We aimed to examine the association between prostate cancer (PCa) and the IGFBP3 gene-202A/C polymorphism. Methods A comprehensive search within PubMed, EMBASE, and Cochrane Library was conducted to identify all case–control studies up to October 30, 2015, for a meta-analysis. Pooled odds ratios (ORs) and the 95% confidence intervals (CIs) were calculated using the fixed or random effects model. Results Eighteen studies including 10,538 cases and 10,078 controls were identified. Overall, the CC genotype of IGFBP3-202A/C polymorphism was associated with increased risk of PCa in homozygote comparison (CC vs AA − OR =1.16, 95% CI: 1.08–1.25) and in recessive model (CC vs AA+AC − OR =1.11, 95% CI: 1.04–1.17). In dominant model, the CC/AC genotypes also implicated an increased risk of PCa (CC+AC vs AA − OR =1.11, 95% CI: 1.05–1.19). The C allele of IGFBP3-202A/C polymorphism was the risk allele for PCa relative to the A allele (OR =1.09, 95% CI: 1.05–1.14). Further stratification analysis revealed that the association between –202A/C polymorphism and PCa risk among Caucasians, but not in other ethnicities, was statistically significant (recessive model, OR =1.10, 95% CI: 1.02–1.19). In addition, the IGFBP3-202A/C polymorphism was associated with PCa risk in both population-based and hospital-based studies in homozygote comparison, recessive model, and allele model. Conclusion Our meta-analysis indicates that the IGFBP3-202A/C polymorphism is associated with the risk of PCa, particularly in Caucasians, with the C allele being the risk allele for PCa.

Graphene oxide/DNA-decorated electrode for the fabrication of microRNA biosensor

We fabricate a sensitive biosensor for miRNA quantification using a graphene oxide/DNA-decorated electrode. AgNPs are modified on DNA probe, which is the complementary sequence of target miRNA. Since the hybridization between DNA and miRNA releases DNA, electrochemical signals from AgNPs are declined, which indicates the concentration of miRNA.

Human telomerase reverse-transcriptase promoter-controlled and herpes simplex virus thymidine kinase-armed adenoviruses for renal cell carcinoma treatment

New treatment strategies are required for renal cell carcinoma (RCC) due to its relative insensitivity to conventional radio- and chemotherapies. The promising strategy of tumor inhibition using human telomerase reverse transcriptase (hTERT)-controlled herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) in the hTERT promoter-driven HSV-TK/GCV suicide gene system was investigated. Tumor volume, weight, relative proliferation rate, and cell-apoptosis levels were examined in mice injected with adenovirus (Ad)-hTERT-HSV-TK and GCV. Increased cell death occurred following treatment with Ads carrying hTERT-HSV-TK/GCV or cytomegalovirus promoter-controlled (CMV)-HSV-TK/GCV for human RCC 786-0 and fibroblast MRC-5 cells. In mice, Ad-hTERT-HSV-TK/GCV more specifically inhibited tumor and RCC xenograft growth than Ad-CMV-HSV-TK/GCV (P < 0.05). Furthermore, Ad-hTERT-HSV-TK/GCV did not significantly damage normal fibroblasts or organ systems (heart, lung, liver, brain, kidney, and spleen). Thus, Ad-hTERT-HSV-TK/GCV is an effective RCC inhibitor in human cells in vitro and in vivo mouse models, indicating potential usefulness in RCC-targeted gene therapy.

Association between MDM2 SNP309 T>G polymorphism and the risk of bladder cancer: new data in a Chinese population and an updated meta-analysis

Objective Human murine double minute 2 protein (MDM2) is mainly a negative regulator of p53 tumor suppressor pathway. We aimed to investigate the association between MDM2 SNP309 polymorphism and bladder cancer risk. Methods A total of 535 bladder cancer patients and 649 health controls were recruited for our study. MDM2 SNP309 T>G polymorphism was genotyped by polymerase chain reaction-ligase detection reaction method. Logistic regression was used to analyze the relationship between the genotype and susceptibility of bladder cancer. Kaplan–Meier estimates and log-rank test were obtained to analyze the association between the genotype and risk of recrudesce in nonmuscle-invasive bladder cancer patients. A multivariable Cox proportional hazards model was fitted to identify independent prognostic factors. To further investigate the association, we conducted a meta-analysis including six studies. Results The frequency of the MDM2 SNP309 T>G polymorphism showed no significant difference between cases and controls (all P>0.05). In the stratification analysis, the results showed that G allele carriers were prone to have a significant decrease in risk of low-grade bladder cancer (adjusted odds ratio: 0.613, 95% confidence interval: 0.427–0.881), and G variant was associated with a significantly reduced risk of recurrence in nonmuscle-invasive bladder cancer patients with or without chemotherapy (P<0.05). The results of the meta-analysis showed that G allele and GG genotype of MDM2 SNP309 polymorphism were significantly associated with increased risk of bladder cancer in Caucasians (both P<0.05), and no association was observed in total populations and Asians (P>0.05). Conclusion MDM2 SNP309 T>G polymorphism has no influence on bladder cancer risk in Asians, but this single nucleotide polymorphism may be associated with genetic susceptibility of bladder cancer among Caucasians.

Expression of brain‑specific angiogenesis inhibitor‑1 and association with p53, microvessel density and vascular endothelial growth factor in the tissue of human bladder transitional cell carcinoma

The aim of the present study was to investigate the expression levels of brain‑specific angiogenesis inhibitor‑1 (BAI‑1) in bladder transitional cell carcinoma (BTCC) at different stages and the mechanism by which it inhibits tumor endothelial cell proliferation. Normal bladder mucosa biopsy specimens were obtained as the control group, and human BTCC biopsy specimens were used as the study group. Immunohistochemical assays were used to detect the expression levels of BAI‑1, vascular endothelial growth factor (VEGF) and mutant p53, in addition to microvessel density (MVD) in the tissues. Western blotting was used to analyze the differential expression of BAI‑1 in the two samples. Statistical analysis was performed, which indicated that BAI‑1 expression levels in the normal bladder mucosa group were significantly higher than those in the BTCC group and were associated with clinical staging. BAI‑1 levels in the T1 stage BTCC tissues were higher than those in the T2‑4 stage BTCC tissues (P<0.05). BAI‑1 expression levels were negatively correlated with those of VEGF (r=‑0.661, P<0.001), mutant p53 (r=‑0.406, P=0.002) and with the MVD (r=‑0.675, P<0.001). BAI‑1 may be involved in the negative regulation of BTCC microvascular proliferation, and its expression may be associated with a reduction in p53 mutations.