Comparison and trend of perioperative outcomes between robot-assisted radical prostatectomy and open radical prostatectomy: nationwide inpatient sample 2009-2014

ABSTRACT Purpose: To make a further evaluation of perioperative outcomes between the robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP), we conducted a comparison and trend analysis by using the Nationwide Inpatient Sample (NIS) from 2009 to 2014. Materials and Methods: Adult prostate cancer patients with radical prostatectomy were abstracted from the NIS. RARP and ORP were identified according to the International Classification of Diseases, 9th Revision, Clinical Modification procedure codes. The perioperative outcomes included blood transfusion, intraoperative and postoperative complications, prolonged length of stay (pLOS), and in-hospital mortality. Propensity score matching method and multivariable logistic regression model were performed to adjust for the pre-defined covariates. The annual percent change (APC) was used to detect the change trend of rates for outcomes. Results: A total of 77.054 patients were included in our study. According to the results of propensity score matching analyses, RARP outperformed ORP in blood transfusion (1.96% vs. 9.40%), intraoperative complication (0.73% vs. 1.25%), overall postoperative complications (8.87% vs. 11.97%), and pLOS (13.39% vs. 36.70%). We also found that there was a significant decreasing tendency of incidence in blood transfusion (APC=-9.81), intraoperative complication (APC=-12.84), and miscellaneous surgical complications (APC=-14.09) for the RARP group. The results of multivariable analyses were almost consistent with those of propensity score matching analyses. Conclusions: The RARP approach has lower incidence rates of perioperative complications than the ORP approach, and there is a potential decreasing tendency of complication incidence rates for the RARP.

Comparison and trend of perioperative outcomes between robot-assisted radical prostatectomy and open radical prostatectomy: nationwide inpatient sample 2009-2014.

PURPOSE: To make a further evaluation of perioperative outcomes between the robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP), we conducted a comparison and trend analysis by using the Nationwide Inpatient Sample (NIS) from 2009 to 2014. MATERIALS AND METHODS: Adult prostate cancer patients with radical prostatectomy were abstracted from the NIS. RARP and ORP were identified according to the International Classification of Diseases, 9th Revision, Clinical Modification procedure codes. The perioperative outcomes included blood transfusion, intraoperative and postoperative complications, prolonged length of stay (pLOS), and in-hospital mortality. Propensity score matching method and multivariable logistic regression model were performed to adjust for the pre-defined covariates. The annual percent change (APC) was used to detect the change trend of rates for outcomes. RESULTS: A total of 77.054 patients were included in our study. According to the results of propensity score matching analyses, RARP outperformed ORP in blood transfusion (1.96% vs. 9.40%), intraoperative complication (0.73% vs. 1.25%), overall postoperative complications (8.87% vs. 11.97%), and pLOS (13.39% vs. 36.70%). We also found that there was a significant decreasing tendency of incidence in blood transfusion (APC=-9.81), intraoperative complication (APC=-12.84), and miscellaneous surgical complications (APC=-14.09) for the RARP group. The results of multivariable analyses were almost consistent with those of propensity score matching analyses. CONCLUSIONS: The RARP approach has lower incidence rates of perioperative complications than the ORP approach, and there is a potential decreasing tendency of complication incidence rates for the RARP.

Cuprous oxide nanoparticles trigger reactive oxygen species-induced apoptosis through activation of erk-dependent autophagy in bladder cancer.

Cisplatin-based chemotherapy is the first-line treatment for patients with advanced bladder cancer. However, as more than 50% of patients are ineligible for cisplatin-based chemotherapy, there is an urgent need to develop new drugs. Cuprous oxide nanoparticles (CONPs), as a new nano-therapeutic agent, have been proved to be effective in many kinds of tumors. In the present study, CONPs showed dose-dependent and time-dependent inhibitory effects on various bladder cancer cell lines (T24, J82, 5637, and UMUC3) and weak inhibitory effects on non-cancerous epithelial cells (SVHUCs). We found that CONPs induced cell cycle arrest and apoptosis in bladder cancer cells. We further demonstrated that the potential mechanisms of CONP-induced cytotoxicity were apoptosis, which was triggered by reactive oxygen species through activation of ERK signaling pathway, and autophagy. Moreover, the cytotoxic effect of CONPs on bladder cancer was confirmed both in orthotopic xenografts and subcutaneous nude mouse models, indicating that CONPs could significantly suppress the growth of bladder cancer in vivo. In further drug combination experiments, we showed that CONPs had a synergistic drug-drug interaction with cisplatin and gemcitabine in vitro, both of which are commonly used chemotherapy agents for bladder cancer. We further proved that CONPs potentiated the antitumor activity of gemcitabine in vivo without exacerbating the adverse effects, suggesting that CONPs and gemcitabine can be used for combination intravesical chemotherapy. In conclusion, our preclinical data demonstrate that CONPs are a promising nanomedicine against bladder cancer and provide good insights into the application of CONPs and gemcitabine in combination for intravesical bladder cancer treatment.

Prognostic value of the combined expression of tumor-associated trypsin inhibitor (TATI) and p53 in patients with bladder cancer undergoing radical cystectomy.

BACKGROUND: Urothelial carcinoma of the bladder is a heterogeneous disease for which reliable prognostic molecular biomarkers have not been established. OBJECTIVE: To investigate the prognostic value of tumor-associated trypsin inhibitor (TATI) expression combined with p53 expression in bladder cancer patients who have undergone radical cystectomy. METHODS: Tissue microarrays from 110 patients were analyzed immunohistochemically for TATI and p53 protein expression. Complete clinical-pathological information and follow-up data were collected. Univariable Kaplan-Meier analysis and log-rank test were performed to assess the association between TATI and p53 expression patterns with clinical outcomes. Cox's proportional hazard analysis was performed to identify potential independent risk factors for predicting disease progression and evaluate the prognostic value of combining the expression of TATI and p53 on progression-free survival (PFS) and overall survival (OS). RESULTS: TATI expression was positively correlated with favorable differentiation of bladder cancer, and lower tumor stage. p53 expression was positively related to tumor stage, tumor grade, and lymph-node invasion. Univariate Kaplan-Meier analysis revealed significant differences between TATI-positive vs. TATI-negative and p53-positive vs. p53-negative patients, regarding PFS. Multivariate analysis showed that both TATI and p53 expression were independent factors for predicting disease progression. CONCLUSION: TATI expression patterns could enhance the prognostic value of p53 overexpression on progression.

Dysbiosis signatures of the microbial profile in tissue from bladder cancer.

BACKGROUND: To examine the microbial profiles in parenchyma tissues in bladder cancer. METHODS: Tissue samples of cancerous bladder mucosa were collected from patients diagnosed with bladder cancer (22 carcinoma tissues and 12 adjacent normal tissues). The V3-V4 region of the bacterial 16S rRNA gene was PCR amplified, followed by sequencing on an Illumina MiSeq platform. Bioinformatics analysis for microbial classification and functional assessment was performed to assess bladder microbiome diversity and variations. RESULTS: The predominant phylum in both tissues was Proteobacteria. The cancerous tissues exhibited lower species richness and diversity. Beta diversity significantly differed between the cancerous and normal tissues. Lower relative abundances of the microbial genera Lactobacillus, Prevotella_9, as well as Ruminococcaceae were observed, whereas those of Cupriavidus spp., an unknown genus of family Brucellaceae, and Acinetobacter, Anoxybacillus, Escherichia-Shigella, Geobacillus, Pelomonas, Ralstonia, and Sphingomonas were higher in the cancerous tissues. These findings indicate that these genera may be potentially utilized as biomarkers for bladder cancer. PICRUSt analysis revealed that several pathways involved in the metabolism of harmful chemical compounds were enriched in the cancer tissues, thereby providing evidence that environmental factors are strongly associated with bladder cancer etiology. CONCLUSION: This is the first study that has described and analyzed the dysbiotic motifs of urinary microbiota in the parenchymatous tissues of bladder cancer via 16S rRNA gene sequencing. Our results suggest that changes in the bladder microbiome may serve as biomarkers for bladder cancer, possibly assisting in disease screening and monitoring.

Prognostic value of TOP2A in bladder urothelial carcinoma and potential molecular mechanisms.

BACKGROUND: The prognosis of bladder urothelial carcinoma (BLCA) varies greatly among patients, and conventional pathological predictors are generally inadequate and often inaccurate to predict the heterogeneous behavior of BLCA. This study aims to investigate the prognostic value and function of TOP2A in BLCA. METHODS: TOP2A expression level was examined by RNA-sequencing, quantitative real time polymerase chain reaction and immunohistochemistry from 10, 40 and 209 BLCA samples, respectively. Public databases were analyzed for validation. Cell proliferation, migration, invasion assays were performed to explore potential functions of TOP2A in BLCA. Flow cytometry was performed for cell cycle and apoptosis analysis. Univariable and multivariable Cox regression models were performed to identify independent risk factors for the prognosis of BLCA. RESULTS: We found TOP2A was significantly upregulated in BLCA samples, especially for high-grade and advanced stage tumors, compared with matched normal epithelial tissue. Univariable COX regression analysis revealed high TOP2A expression was significantly associated with poorer cancer-specific, progression-free and recurrence-free survival, but not independently of clinical characteristics in the multivariable models. Knockdown of TOP2A remarkably inhibited the proliferation of BLCA cells and non-cancerous urothelial cells. Furthermore, migration and invasion capacity of BLCA cells were strongly suppressed after TOP2A knockdown. Moreover, flow cytometry suggested TOP2A had anti-apoptotic function, and knockdown of TOP2A could induce resistance to doxorubicin in J82 cells. CONCLUSIONS: In our study, TOP2A was overexpressed in BLCA and could serve as a prognostic biomarker for BLCA. Moreover, TOP2A is functionally important for the proliferation, invasion and survival of BLCA cells.

Tumor­infiltrating M2 macrophages driven by specific genomic alterations are associated with prognosis in bladder cancer.

The present study aimed to explore the mechanism by which the immune landscape of the tumor microenvironment influences bladder cancer. CIBERSORT and ssGSEA analyses revealed that M2 macrophages accounted for the highest proportion from 22 subsets of tumor­infiltrating immune cells and were enriched in higher histologic grade and higher pathologic stage bladder cancer and 'basal' subtype of muscle invasive bladder cancer (MIBC). Kaplan­Meier survival curve analysis indicated that patients with high numbers of infiltrating M2 macrophages had worse overall and disease­specific survival rates. RNA sequencing and immunohistochemistry results indicated that M2 macrophages were enriched in MIBC and promoted angiogenesis. M2 macrophage infiltration was higher in bladder cancer tissues with mutant TP53, RB transcriptional corepressor 1, phosphatidylinositol­4,5­bisphosphate 3­kinase catalytic subunit α, lysine methyltransferase 2A, lysine demethylase 6A and apolipoprotein B mRNA editing enzyme catalytic­polypeptide­like, but lower in tissues with mutant fibroblast growth factor receptor 3 (FGFR3), E74­like ETS transcription factor 3, PC4 and SFRS1 interacting protein 1 and transmembrane and coiled­coil domains 4. In addition, M2 macrophage infiltration was lower in the tissues with amplified FGFR3, erb­b2 receptor tyrosine kinase 2, BCL2­like 1, telomerase reverse transcriptase and tyrosine­3­monooxygenase/tryptophan­5­monooxygenase activation protein ζ, as well as in the tissues with deleted cyclin­dependent kinase inhibitor 2A, CREB binding protein, AT­rich interaction domain 1A, fragile histidine triad diadenosine triphosphatase, phosphodiesterase 4D, RAD51 paralog B, nuclear receptor corepressor 1 and protein tyrosine phosphatase receptor type D. Finally, seven micro (mi) RNAs (miR­214­5p, miR­223­3p, miR­155­5p, miR­199a­3p, miR­199b­3P, miR­146b­5p, miR­142­5p) which were expressed differentially in at least three mutant genes and were positively correlated with M2 macrophage infiltration as well as expressed highly in high grade bladder cancer were identified. Overall, the present study concluded that M2 macrophages are the predominant tumor­infiltrating immune cell in bladder cancer and differentially expressed miRNAs due to cancer­specific genomic alterations may be important drivers of M2 macrophage infiltration. These findings suggested that M2 macrophage infiltration may serve as a potential immunotherapy target in bladder cancer.

Prognostic value of differentially methylated gene profiles in bladder cancer.

DNA methylation can regulate gene expression and is pivotal in the occurrence and development of bladder cancer. In this study, we analyzed whole-genome DNA methylation on the basis of data from The Cancer Genome Atlas to select epigenetic biomarkers predictive of survival and further understand the molecular mechanisms underlying methylation patterns in bladder cancer. We identified 540 differentially methylated genes between tumor and normal tissues, including a number of independent prognostic factors based on univariate analysis. Genes (MIR6732, SOWAHC, SERPINI1, OR10W1, OR7G3, AIM1, and ZFAND5) were integrated to establish a risk model for prognostic assessment based on multivariate Cox analysis. The methylation of SOWAHC was negatively correlated with its messenger RNA expression, and together these were significantly correlated with prognosis. This study took advantage of high-throughput data mining to provide new bioinformatics evidence and ideas for further study into the pathogenesis and prognosis of bladder cancer.

Overexpression of G2 and S phase-expressed-1 contributes to cell proliferation, migration, and invasion via regulating p53/FoxM1/CCNB1 pathway and predicts poor prognosis in bladder cancer.

Bladder cancer is one of the most common urogenital tumors worldwide. The specific function and molecular mechanism of GTSE1 in bladder cancer remain unknown. In the present study, real-time quantitative polymerase chain reaction and Western blotting were used to identify GTSE1 expression in bladder cancer tissues and cells, and immunohistochemical assays were conducted to investigate GTSE1 expression in tissue microarray. Regression analyses explored the relationship between GTSE1 expression and pathological characteristics. A series of functional tests were performed to observe the effects of GTSE1 knockdown or overexpression, and the related mechanism was also performed. GTSE1 expression was significantly higher in bladder cancer tissues; overexpression of GTSE1 was positively associated with disease recurrence history, lymph node invasion, and progression. Patients with higher GTSE1 expression were more likely to experience shorter survival time, and GTSE1 expression served as a prognostic factor for the disease progression. Knockdown of GTSE1 obviously suppressed the proliferation, migration, and invasion capacity whereas increasing GTSE1 led to the opposite trend, which suggested that GTSE1 could serve as a potential therapeutic target for bladder cancer. GTSE1 overexpression in bladder cancer might participate in the regulation of FoxM1/CCNB1 expression via the induction of the transfer of p53 to cytoplasm.

Total parenteral nutrition versus early enteral nutrition after cystectomy: a meta-analysis of postoperative outcomes.

BACKGROUND: This study aimed to systematically summarize and analyze the current evidence regarding the effect of total parenteral nutrition (TPN) versus early enteral nutrition (EEN) on postoperative outcomes of cystectomy. METHODS: A comprehensive search of online databases was conducted to identify comparative studies on the postoperative outcomes of patients receiving TPN and EEN after cystectomy. Our subsequent meta-analysis followed the PRISMA Protocol and the Cochrane Handbook. RESULTS: Five studies with 556 participants were included for meta-analysis. EEN was shown to have a significant effect on reducing the overall complications (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.37-0.75, P < 0.01) and infectious complications (OR 0.32, 95% CI 0.21-0.49, P < 0.01) compared with TPN. Additionally, EEN saved €614-€3120 in costs compared to TPN. There were no significant differences between TPN and EEN groups regarding mortality rate (OR 0.47, 95% CI 0.06-3.51, P = 0.46), the incidence of postoperative ileus (OR 0.90, 95% CI 0.55-1.47, P = 0.68), length of hospital stay (mean difference (MD) 2.12, 95% CI - 0.15 to 4.40, P = 0.07), or time to resume a full diet (MD 1.31, 95% CI - 1.15 to 3.77, P = 0.30). CONCLUSION: EEN was found to have a significant effect on reducing infectious complications and costs compared with TPN treatment after cystectomy. Remarkably, EEN had no significant impact on mortality incidence, postoperative ileus, length of hospital stay, or the time to resumption of full diet.

[Inlaid labial versus bladder mucosal graft repair for complex urethral skin fistula].

OBJECTIVE: To compare the effect of inlaid labial mucosal graft repair (LMGR) with that of bladder mucosal graft repair (BMGR) in the treatment of complex urethral skin fistula after hypospadias repair. METHODS: This study included 55 cases of complex urethral skin fistula following hypospadias repair. We randomly assigned them to receive inlaid LMGR (n=36) or BMGR (n=19). After surgery, we compared the incidence of complications and recurrence rate of urinary fistula between the two groups of patients. RESULTS: The success rates of operation were 91.7% and 84.2% in the LMGR and BMGR groups, respectively, and the penile appearance was desirable in both groups. Postoperative complications included 2 cases of urinary fistula and 1 case of urethral stricture in each group. There were no statistically significant differences between the two groups in the success rate of operation (P>0.05) or the incidence rate of postoperative complications (P>0.05). CONCLUSIONS: Both inlaid LMGR and BMGR yield satisfactory results in the treatment of complex urethral skin fistula. However, LMGR involves less injury in mucosa collection and is easier to perform and therefore deserves more clinical attention.