Hypoxia induces chemoresistance of esophageal cancer cells to cisplatin through regulating the lncRNA-EMS/miR-758-3p/WTAP axis.

Hypoxia contributes significantly to the development of chemoresistance of many malignancies including esophageal cancer (EC). Accumulating studies have indicated that long non-coding RNAs play important roles in chemotherapy resistance. Here, we identified a novel lncRNA-EMS/miR-758-3p/WTAP axis that was involved in hypoxia-mediated chemoresistance to cisplatin in human EC. Hypoxia induced the expressions of lncRNA EMS and WTAP, and reduced the expression of miR-758-3p in EC cell line ECA-109. In addition, the expressions of EMS and WTAP were required for the hypoxia-induced drug resistance to cisplatin in EC cells, while overexpression of miR-758-3p reversed such chemoresistance. The targeting relationships between EMS and miR-758-3p, as well as miR-758-3p and WTAP, were verified by luciferase-based reporter assays and multiple quantitative assays after gene overexpression/knockdown. Moreover, we found significant correlations between tumor expressions of these molecules. Notably, higher levels of EMS/WTAP, or lower levels of miR-758-3p in tumors predicted worse survivals of EC patients. Furthermore, in a xenograft mouse model, targeted knockdown of EMS and WTAP in ECA-109 cells markedly attenuated the resistance of tumors to cisplatin treatments. Our study uncovers a critical lncRNA-EMS/miR-758-3p/WTAP axis in regulating hypoxia-mediated drug resistance to cisplatin in EC.

Comparative Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Advanced Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Combination therapy with immune checkpoint inhibitors (ICIs) has been applied in the clinic to achieve synergistic effects and to improve clinical efficacy. Compared with monotherapy, combination therapy has promising efficacy against various advanced cancers. To further verify the effectiveness of combination therapy, we conducted a meta-analysis of the efficacy and safety of nivolumab (NIVO) and NIVO plus ipilimumab (IPI) in advanced cancer. METHODS: Electronic databases (PubMed, EMbase, and The Cochrane Library) were systematically searched for applicable studies published in English between January 1990 and June 2019. Relevant outcomes included objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and grade 3-4 adverse events (AEs). RESULTS: A total of 1,297 patients from six studies were included. Compared with NIVO alone, NIVO + IPI was more efficacious for advanced tumors. Pooled outcome values were: ORR, 1.73 (95% CI: 1.34-2.23); DCR, 1.80 (95% CI: 1.21-2.69); mPFS, 0.22 (95% CI: 0.03-0.41); mOS, 0.03 (95% CI: -0.20-0.26); and grade 3-4 AEs, 3.64 (95% CI: 2.86-4.62). CONCLUSION: NIVO + IPI is more effective than NIVO alone for the treatment of advanced cancer and can significantly improve ORR and DCR and prolong mPFS. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to validate the above conclusions.

The diagnostic accuracy of artificial intelligence in thoracic diseases: A protocol for systematic review and meta-analysis.

INTRODUCTION: Thoracic diseases include a variety of common human primary malignant tumors, among which lung cancer and esophageal cancer are among the top 10 in cancer incidence and mortality. Early diagnosis is an important part of cancer treatment, so artificial intelligence (AI) systems have been developed for the accurate and automated detection and diagnosis of thoracic tumors. However, the complicated AI structure and image processing made the diagnosis result of AI-based system unstable. The purpose of this study is to systematically review published evidence to explore the accuracy of AI systems in diagnosing thoracic cancers. METHODS AND ANALYSIS: We will conduct a systematic review and meta-analysis of the diagnostic accuracy of AI systems for the prediction of thoracic diseases. The primary objective is to assess the diagnostic accuracy of thoracic cancers, including assessing potential biases and calculating combined estimates of sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). The secondary objective is to evaluate the factors associated with different models, classifiers, and radiomics information. We will search databases such as PubMed/MEDLINE, Embase (via OVID), and the Cochrane Library. Two reviewers will independently screen titles and abstracts, perform full article reviews and extract study data. We will report study characteristics and assess methodological quality using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. RevMan 5.3 and Meta-disc 1.4 software will be used for data synthesis. If pooling is appropriate, we will produce summary receiver operating characteristic (SROC) curves, summary operating points (pooled sensitivity and specificity), and 95% confidence intervals around the summary operating points. Methodological subgroup and sensitivity analyses will be performed to explore heterogeneity. PROSPERO REGISTRATION NUMBER: CRD42019135247.

Omentoplasty Decreases Leak Rate After Esophagectomy: a Meta-analysis.

OBJECTIVE: To compare the efficacy of omentoplasty with non-omentoplasty in the prevention of postoperative anastomotic leakage, and to investigate the safety of omentoplasty. METHODS: Literature searches were performed of the Medline, EMBASE, and Cochrane Library databases. Studies that compared the efficacy of omentoplasty and non-omentoplasty after esophagectomy were selected. A meta-analysis was performed on anastomotic leakage, anastomotic stenosis, hospital mortality, and length of hospital stay. Results were reported as odds ratio (OR), weighted mean difference (WMD), or relative risk (RR), with 95% confidence intervals. RESULTS: Six studies involving a total of 1608 patients met inclusion criteria. Compared with the non-omentoplasty group, the incidence of anastomotic leakage in the omentoplasty group (OR, 0.37; 95% CI, 0.23-0.60; P < 0.0001) was significantly reduced and the length of hospital stay (WMD, 2.13; 95% CI, 3.57-0.69; P = 0.004) was significantly shortened. However, there was no significant difference in the incidence of anastomotic strictures (OR, 0.82; 95% CI, 0.37-1.80; P = 0.61) or in-hospital mortality (OR, 0.61; 95% CI, 0.25-1.51; P = 0.29). CONCLUSIONS: Omentoplasty after esophagectomy is a safe and effective method to prevent anastomotic leakage.

Comparison of safety between manual and mechanical anastomosis of esophageal carcinoma after esophagectomy: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective     To compare the safety of manual anastomosis and mechanical anastomosis after esophagectomy by meta-analysis. Methods    The randomized controlled trials (RCTs) about manual anastomosis and mechanical anastomosis after esophagectomy were searched from PubMed, EMbase and The Cochrane Library from inception to January 2018 by computer, without language restrictions. Two authors according to the inclusion and exclusion criteria independently researched literature, extracted data, evaluated bias risk and used R software meta package for meta-analysis. Results     Seventeen RCTs were enrolled, including 2 159 patients (1 230 by manual anastomosis and 1 289 by mechanical anastomosis). The results of meta-analysis showed that: (1) there was no significant difference in the incidence of anastomotic leakage between mechanical and manual anastomosis (RR=1.00, 95%CI 0.67–1.48, P=0.181); (2) no significant difference was found in the 30-day mortality (RR=0.95, 95%CI 0.61–1.49, P=0.631);(3) compared with manual anastomosis, the mechanical anastomosis group may increase the risk of anastomotic stenosis (RR=0.74, 95%CI 0.48-1.14, P<0.001). Conclusion     Esophageal cancer surgery using a linear or circular stapler can increase the incidence of anastomotic stenosis after surgery. There is no significant difference in the anastomotic leakage and 30-day mortality between manual anastomosis, linear stapler and circular stapler.