No abstract

BackgroundRobot-assisted partial nephrectomy (RAPN) has been widely used worldwide, to determine whether RAPN is a safe and effective alternative to open partial nephrectomy (OPN) via the comparison of RANP and OPN.MethodsA comprehensive literature search was performed within the databases including PubMed, Cochrane Library, and Embase updated on 30 September 2015. Summary data with their corresponding 95 % confidence intervals (CIs) were calculated using a random effects or fixed effects model. Heterogeneity and publication bias were also evaluated.ResultsA total of 16 comparative studies including 3024 cases were used for this meta-analysis. There are no significant differences in the demographic characteristic between the two groups, but the age was lower and the tumor size was smaller for the RAPN group. RAPN had a longer operative time and warm ischemia time but which showed less estimated blood loss, hospital stay, and perioperative complications. No differences existed in the margin status, the change of glomerular filtration rate, transfusion rate, and conversion rate between the two groups. There was no significant publication bias.ConclusionsRAPN offered a lower rate of perioperative complications, less estimated blood loss, and shorter length of hospital stay than OPN, suggesting that RAPN can be an effective alternative to OPN. Well-designed prospective randomized controlled trials will be helpful in validating our findings.

Growing evidence has indicated that circular RNAs (circRNAs) play crucial roles in multiple biological processes. However, alterations in circRNA profiles during bladder cancer progression and the clinical significance thereof remain unclear.Therefore, high-throughput RNA sequencing was conducted to identify circRNA and mRNA profiles in five pairs of bladder cancer tissues and adjacent noncancerous tissues. A total of 87 differentially expressed circRNAs and 2756 mRNAs were detected in above bladder cancer samples compared with paired noncancerous samples.Functional enrichment analyses, circRNA-microRNA-mRNA, and protein-protein interaction networks revealed that these dysregulated circRNAs were potentially involved in carcinogenesis and evolution of bladder cancer. Subsequently, the differential expression of eight circRNAs was detected by real-time qPCR. Hsa_circ_0003141 and hsa_circ_0008039 were significantly upregulated as well as hsa_circ_0026782, hsa_circ_0077837, hsa_circ_0004826, and hsa_circ_0001946 were significantly downregulated among validation of 70 matched bladder cancer tissues (≥75%).Moreover, hsa_circ_0077837 and hsa_circ_0004826 were also verified as markedly downregulated in four bladder cancer cells (100%). Naturally, hsa_circ_0077837 and hsa_circ_0004826 were also demonstrated using RNase-R+ resistance experiments. In addition, Fisherʹs exact test, Kaplan-Meier plots, Cox regression analyses, and receiver operating characteristic curve was performed to assess their clinical value. Downregulation of hsa_circ_0077837 and hsa_circ_0004826 all was significantly correlated with worse clinicopathological features and poor prognosis of bladder cancer patients. The area under the receiver operating characteristic curve of them was 0.775 (P < .0001) and 0.790 (P < .0001), respectively. Not surprisingly, in vitro functional experiments also demonstrated that the overexpression of hsa_circ_0077837 and hsa_circ_0004826 significantly weakened the proliferation, migration, and invasion of bladder cancer cells. Overall, hsa_circ_0077837 and 3886 | SHEN Et al hsa_circ_0004826 might act as tumor suppressors in the bladder cancer progression and serve as a potential biomarker for the diagnosis, prognosis, and therapy of bladder cancer. K E Y W O R D S bioinformatic analysis, Bladder cancer, circular RNAs, high-throughput RNA sequencing, invasion, prognosis

ObjectiveTo investigate the prognostic role of hematological biomarkers, especially hemoglobin-platelet ratio (HPR) in the oncological outcomes in stage 1 and grade 3 (T1G3) bladder cancer.Materials and MethodsWe identified 457 T1G3 bladder cancer patients who underwent transurethral resection of the bladder (TURB) between 2009 and 2014. Based on hematological parameters (hemoglobin-platelet ratio (HPR), hemoglobin, and platelet counts), recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) and cancer-specific survival (CSS) were analyzed by using Kaplan-Meier analysis. Multivariate Cox regression model was adopted to identify the predictors of oncological outcomes.ResultsKaplan-Meier survival analysis showed that low HPR (< 0.615), low hemoglobin (< 125g/l) and elevated platelet counts (> 240 × 103/μl) were correlated with poor OS. Low HPR, but not low hemoglobin and high platelet counts, is associated with worse PFS. Low HPR and low hemoglobin, but not elevated platelet counts, are associated with worse CSS. However, no significant difference was observed in RFS according to any of these hematological markers. On multivariate analysis, low HPR (HR = 1.27, 95% CI = 0.81–1.75, P = 0.030), low hemoglobin (HR = 1.20, 95% CI = 0.79–1.84, P = 0.028) and elevated platelet counts (HR = 1.07, 95% CI = 0.72–1.32, P = 0.038) were significantly associated with OS. Low hemoglobin (HR = 1.08, 95% CI = 0.68–1.82, P = 0.041) was significantly linked with CSS. Particularly, low HPR was identified as an independent predictor of PFS (HR = 1.16, 95% CI = 0.97–1.49, P = 0.033) and CSS (HR = 1.14, 95% CI = 0.87–1.78, P = 0.029).ConclusionsPreoperative HPR can be taken into account as a factor predictive of oncological outcomes for T1G3 bladder cancer, particularly disease progression and mortality outcomes.

The aim of the present study was to investigate the impact of squamous and/or glandular differentiation on the recurrence and progression in patients with nonmuscle invasive urothelial carcinoma of bladder (NMIUCB) following transurethral resection (TURBT). A total of 869 patients with NMIUCB who had been treated with TURBT at The Second Hospital of Tianjin Medical University (Tianjin, China) between January 2006 and January 2011 were retrospectively selected for the present analysis. Associations among squamous and/or glandular differentiation with other clinical and pathological features were assessed by the χ2 test. Recurrence-free survival (RFS) and progression-free survival (PFS) curves were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed through a Cox's proportional hazards regression model. Among the 869 patients, 232 (26.7%) patients had squamous and/or glandular differentiation. High grade tumors were more common in patients with squamous and/or glandular differentiation compared with those with pure urothelial carcinoma of bladder (P<0.001). Associations between age (P=0.115), sex (P=0.184), tumor size (P=0.223), tumor multiplicity (P=0.108), pathological tumor stage (P=0.909) and squamous and/or glandular differentiation were not observed to be statistically significant. There was a significant tendency towards higher recurrence rate and shorter RFS time in patients with squamous and/or glandular differentiation. However, no statistically significant differences were observed in progression rate and PFS between the two groups. The multivariate Cox regression analysis, identified squamous and/or glandular differentiation as an independent prognostic predictor of recurrence (hazard ratio =1.46, 95% confidence interval=1.10–1.92, P=0.008). In the present study, the presence of squamous and/or glandular differentiation was associated with a higher recurrence rate and shorter RFS time in patients with NMIUCB. Squamous and/or glandular differentiation is therefore an independent prognostic predictor of recurrence.

Neddylation has been researched in many different human carcinomas. However, the roles of neural precursor cell expressed, developmentally downregulated 8 (NEDD8) in bladder cancer are still unknown. Our study was the first study which systematically investigated the possible functions of NEDD8 in bladder cancer (BC) progression. We carried out immunohistochemistry to explore associations between the expression of NEDD8 in tumor tissues and clinical outcomes of patients. RT‐qPCR and western blot were used to detect the expressional levels of genes. The biological abilities of cell proliferation, migration and invasion were researched by in vitro and in vivo experiments. Results were as follows: Data from The Cancer Genome Atlas (TCGA) database showed that NEDD8 was overexpressed in BC tissues and was associated with poor patient survival. Results of immunohistochemistry found that NEDD8 was significantly associated with poor clinical outcomes of BC patients. Suppression of NEDD8 could inhibit the proliferation, migration and invasion of tumor cells. Knocking down NEDD8 could induce apoptosis and G2 phase arrest of cell cycle progression. In vivo, suppression of NEDD8 restricted growth and metastasis of tumors in mice. In conclusion, NEDD8 has important roles in regulating the progression of BC cells and was associated with poor prognosis of patients; hence, it may become a potential therapeutic target of BC.

Angiogenesis is important in the development of solid tumors. Vasohibin-1 (VASH-1) is an endothelium-derived protein that acts as an inhibitor of angiogenesis in many different types of cancer. However, the expression of VASH-1 and its clinical value in bladder cancer remain unknown. The current study analyzed the expression of VASH-1, as well as the expression of the angiogenesis-related factors vascular endothelial growth factor-A, hypoxia inducible factor-1α and cluster of differentiation 34 in bladder cancer tissues from 50 patients using immunohistochemistry. The associations between the expression of these factors and the clinicopathological characteristics of the patients were assessed. The current study demonstrated that VASH-1 is primarily expressed in the cytoplasm of bladder cancer cells and in a fraction of vascular endothelial cells. Furthermore, the expression of VASH-1 was positively associated with the tumor stage (P<0.01), pathological grade (P<0.01) and distant metastasis (P<0.05) but not with patient age or sex (P>0.05). Spearman rank correlation tests indicated that levels of those four factors were positively correlated with each other. Kaplan-Meier analysis indicated that high expression of these four factors was significantly associated with lower 5-year overall survival and progression-free survival rates. Collectively, the results of the current study suggest that VASH-1 is clinically significant in bladder cancer and its high expression may predict the progression and prognosis of patients with bladder cancer. The present study also implies that VASH-1 may be a novel target for vascular targeting therapy.

ObjectiveThe management of stage 1 and grade 3 (T1G3) bladder cancer continues to be controversial. Although the transurethral resection of bladder tumor (TURBT) followed by intravesical chemotherapy is a conservative strategy for treatment of T1G3 bladder cancer, a relatively high risk of tumor recurrence and progression remains regarding the therapy. This study aimed to compare the efficacy of intravenous chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder cancer after TURBT surgery.MethodsWe retrospectively reviewed the cases of 457 patients who were newly diagnosed with T1G3 bladder urothelial carcinoma between January 2009 and March 2014. After TURBT, 281 patients received intravesical chemotherapy alone, whereas 176 patients underwent intravesical chemotherapy in combination with intravenous chemotherapy. Tumor recurrence and progression were monitored periodically by urine cytology and cystoscopy in follow-up. Recurrence-free survival and progression-free survival of the two chemotherapy strategies following TURBT were analyzed. Univariable and multivariable Cox hazards analyses were performed to predict the prognostic factors for tumor recurrence and progression.ResultsThe tumor recurrence rate was 36.7% for patients who received intravesical chemotherapy alone after TURBT, compared with 19.9% for patients who received intravenous chemotherapy combined with intravesical chemotherapy after TURBT (P<0.001). The progression rate was 10.6% for patients who underwent intravesical chemotherapy alone and 2.3% for patients who underwent the combined chemotherapies (P=0.003). Kaplan–Meier curves showed significant differences in recurrence-free survival and progression-free survival between the two treatment strategies, with a log-rank P-value of <0.001 and 0.003, respectively. Multivariable analyses revealed that intravenous chemotherapy was the independent prognostic factor for tumor recurrence and progression in the cohort.ConclusionIntravenous chemotherapy combined with intravesical chemotherapy offers a better oncologic outcome than the intravesical chemotherapy alone for patients with T1G3 bladder urothelial carcinoma after TURBT, and it may be considered as a new therapy strategy for T1G3 bladder cancer.