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Oncolytic virus therapy has shown benefits for multiple cancers, while limitations remain for traditional treatment. However, few studies have concentrated on comparing whether oncolytic virus combined with traditional treatment is better than traditional treatment alone in patients with cancer. We conducted a meta-analysis of the curative effect and safety of oncolytic virus combination therapy. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases comprehensively for articles comparing oncolytic virus combined with traditional treatment to traditional treatment alone in patients with cancer. A meta-analysis and trial sequential analysis were performed. A total of 12 studies involving 1494 patients (combination therapy group, 820 patients; traditional treatment group, 674 patients) were included in the study. Compared with traditional treatment alone, combination therapy was significantly associated with high objective response rate [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.01–1.82, p = 0.04]. There were no significant differences for other outcomes such as 1- and 2-year survival rate, and 4- and 12-month progression-free survival rate. Combination therapy was significantly associated with high incidence of grade ≥ 3 adverse effects (OR 1.47, 95% CI 1.06–2.05, p = 0.02) and high incidence of grade ≥ 3 neutropenia (OR 1.65, 95% CI 1.13–2.43, p = 0.01). There were no significant differences for other grade ≥ 3 adverse effects, e.g., gastrointestinal adverse effects, influenza-like illness, fatigue, anemia, and thrombocytopenia. Despite partially increased toxicity, the combination therapy improves the effectiveness of cancer treatment. However, high-quality, large-scale studies are needed to evaluate its effectiveness and safety.

Background and Aims: This study aimed at comparing the efficacy and safety of eltrombopag (EPAG) plus immunosuppressive therapies (ISTs) and haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in the frontline treatment for severe aplastic anemia (SAA) patients.Methods: Four electronic databases and Clinicaltrials.gov were comprehensively searched from January 2010 to August 2020. Studies that aimed at evaluating the efficacy and safety of EPAG+IST or haplo-HSCT in SAA patients were included. One-/2-year overall survival (OS), complete response (CR), and overall response rates (ORRs) were indirectly compared between EPAG+IST and haplo-HSCT.Results: A total of 447 patients involved in 10 cohort studies were found to be eligible for this study. A narrative synthesis was performed due to lack of data directly comparing the outcome of EPAG+IST and haplo-HSCT. Consistent with the analysis results in the whole population, subgroup analyses in the age-matched population showed that there was no significant difference in ORR between EPAG+IST and haplo-HSCT groups. However, the CR rate was lower in the EPAG+IST group when compared with the haplo-HSCT group. The incidence rate of clonal evolution/SAA relapse ranged at 8–14 and 19–31% in the EPAG+IST group but not reported in the haplo-HSCT group. The incidence rate for acute graft vs. host disease (aGVHD) and chronic graft vs. host disease (cGVHD) ranged at 52–57 and 12–67%, respectively, for the haplo-HSCT group. The main causes of deaths were infections in the EPAG+IST group, and GVHD and infections in the haplo-HSCT group.Conclusion: EPAG+IST has a comparable ORR and 1-/2-year OS but lower CR rate when indirectly compared with haplo-HSCT in the frontline treatment of patients with SAA. Patients treated with haplo-HSCT may exhibit a high incidence of GVHD, whereas patients treated with EPAG+IST may experience more relapses or clone evolution.

Among hundreds of thousands of signal receptors contributing to oncogenic activation, tumorigenesis, and metastasis, the hepatocyte growth factor (HGF) receptor – also called tyrosine kinase MET – is a promising target in cancer therapy as its axis is involved in several different cancer types. It is also associated with poor outcomes and is involved in the development of therapeutic resistance. Several HGF/MET-neutralizing antibodies and MET kinase-specific small molecule inhibitors have been developed, resulting in some context-dependent progress in multiple cancer treatments. Nevertheless, the concomitant therapeutic resistance largely inhibits the translation of such targeted drug candidates into clinical application. Until now, numerous studies have been performed to understand the molecular, cellular, and upstream mechanisms that regulate HGF/MET-targeted drug resistance, further explore novel strategies to reduce the occurrence of resistance, and improve therapeutic efficacy after resistance. Intriguingly, emerging evidence has revealed that, in addition to its conventional function as an oncogene, the HGF/MET axis stands at the crossroads of tumor autophagy, immunity, and microenvironment. Based on current progress, this review summarizes the current challenges and simultaneously proposes future opportunities for HGF/MET targeting for therapeutic cancer interventions.

Background: Intrahepatic cholangiocarcinoma (iCCA) patients have poor outcomes due to the lack of biomarkers for the selection of treatment options. The present study was conducted to find biomarkers with independent prognostic vaule in iCCA patients. Methods: Gene transcriptome profiles of E-MTAB-6389, TCGA-CHOL and GSE26566 were obtained from ArrayExpress, The Cancer Genome Atlas and the Gene Expression Omnibus databases, respectively. Bioinformatic analyses were performed to screen novel biomarkers for predicting the prognosis of iCCA patients. Using multivariate Cox regression analyses, a 3-gene signature (BTD-FER-COL12A1) with potential prognostic value was identified and validated in both a training cohort and two validation cohorts. Results: A total of 177 iCCA patients were included in this study. From the key gene modules significantly associated with liver cirrhosis and overall survival (OS) of iCCA patients, we identified 89 hub genes for functional analyses. Cox-regression analyses in both the training and validation cohort indicate that FER, COL12A1 and BTD were independent risk factors for iCCA patients. A 3-gene signature (BTD-FER-COL12A1) with independent prognostic value in iCCA patients was validated in the training cohort, as well as in two validation cohorts. In terms of predicting the prognosis of iCCA patients, the receiver operating characteristics (ROC) curves showed that this 3-gene signature had superior prediction power to BTD, FER, and COL12A1 alone, as well as known biomarkers (MUC1, MUC13) of iCCA. Immunohistochemical staining of samples from The Human Protein Atlas showed that FER and COL12A1 were positively expressed in iCCA tissue, although BTD was not, while none of these genes was detected in normal tissue. These findings were consistent with the expression status of BTD, FER and COL12A1 at the transcriptional level. In addition, we found that FER and COL12A1 were significantly associated with the degree of infiltration by tumor-infiltrating immune cells. Conclusion: We discovered a three-gene signature with independent prognostic value as a novel biomarker for prediction prognosis of iCCA patients. Our findings may help to find novel therapeutic targets for precision treatment of iCCA.

Supplemental Digital Content is available in the text, Serum ferritin (SF) has been identified as a potential prognostic factor for patients undergoing stem cell transplantation, but the prognostic value of SF in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients and the impact of iron chelation therapy (ICT) on MDS patients are controversial. The present meta-analysis aimed to better elucidate these relationships. Three electronic databases were searched systematically to identify reports on the prognostic role of SF in MDS and AML patients, and those investigating the impact of ICT on prognosis of MDS patients. The hazard ratios (HRs) and its 95% confidence interval (95%CI) were extracted from the identified studies using Cox proportional hazard regression model for overall survival (OS) and progression of MDS to AML. Twenty reports including 1066 AML patients and 4054 MDS patients were included in present study. The overall pooled HRs for OS of AML and MDS patients with elevated SF prior to transplantation was 1.73 (1.40–2.14), subgroup analyses stratified by the cut-off value of SF ≥1400/1000 ng/mL showed that the pooled HRs were 1.45 (0.98–2.15) and 1.65 (1.30–2.10), respectively. The pooled HRs for ICT in MDS patients was 0.30 (0.23–0.40). For ICT, the pooled HRs for the progression of MDS to AML was 0.84 (0.61–1.61). SF has a negative impact on the OS of AML and MDS patients when it is higher than 1000 ng/mL. ICT can improve the OS of MDS patients with iron overload but it is not associated with the progression of MDS to AML.

ObjectiveSerum carbohydrate antigen 19–9 (CA19-9) is a widely used tumour marker for cholangiocarcinoma (CCA). However, it is not a necessarily good CCA marker in terms of diagnostic accuracy. The purpose of this study is to evaluate the diagnostic value ofWisteria floribundaagglutinin-sialylated Mucin1 (WFA-MUC1) and the prognostic role of Mucin1 (MUC1) in human CCA.DesignMeta-analysis.Data sourcesStudies published in PubMed, Web of Science, The Cochrane Library and the China National Knowledge Infrastructure up to 11 October 2017.Eligibility criteriaWe included reports assessing the diagnostic capacity of WFA-MUC1 and the prognostic role of MUC1 in CCA. The receiver operating characteristic curve (ROC) of WFA-MUC1 and/or CA19-9 was described, and the HRs including 95% CI and the corresponding p value for MUC1 can be extracted.Data extraction and synthesisTwo independent researchers extracted data and assessed risk of bias. The diagnostic sensitivity and specificity data of WFA-MUC1 were extracted and analysed as bivariate data. Pooled HRs and its 95% CI for MUC1 were calculated with a random-effects meta-analysis model on overall survival of resectable CCA.ResultsSixteen reports were included in this study. The pooled sensitivity and specificity of WFA-MUC1 were 0.76 (95% CI 0.71 to 0.81) and 0.72 (95% CI 0.59 to 0.83) in serum, 0.85 (95% CI 0.81 to 0.89) and 0.72 (95% CI 0.64 to 0.80) in bile and 0.72 (95% CI 0.50 to 0.87) and 0.85 (95% CI 0.70 to 0.93) in tissue, respectively. The summary ROC (SROC) were 0.77 (95% CI 0.73 to 0.81) in serum, 0.88 (95% CI 0.85 to 0.90) in bile and 0.86 (95% CI 0.83 to 0.89) in tissue, respectively. Furthermore, the pooled sensitivity and specificity and the SROC of CA19-9 in serum were 0.67 (95% CI 0.61 to 0.72), 0.86 (95% CI 0.75 to 0.93) and 0.75 (95% CI 0.71 to 0.79), respectively. The pooled HRs for MUC1 was 2.20 (95% CI 1.57 to 3.01) in CCA and 4.17 (95% CI 1.71 to 10.17) in mass-forming intrahepatic CCA.ConclusionsCompared with CA19-9, WFA-MUC1 was shown to possess stronger diagnostic capability. MUC1 could serve as a prognosis factor for poor outcomes of CCA, particularly, mass-forming intrahepatic CCA.

Supplemental Digital Content is available in the text, The operative treatment combined with preoperative biliary drainage (PBD) has been established as a safe Klatskin tumor (KT) treatment strategy. However, there has always been a dispute for the preferred technique for PBD technique. This meta-analysis was conducted to compare the biliary drainage-related cholangitis, pancreatitis, hemorrhage, and the success rates of palliative relief of cholestasis between percutaneous transhepatic biliary drainage (PTBD) and endoscopic biliary drainage (EBD), to identify the best technique in the management of KT. PubMed, EMBASE, and Web of Science were searched systematically for prospective or retrospective studies reporting the biliary drainage-related cholangitis, pancreatitis, hemorrhage, and the success rates of palliative relief of cholestasis in patients with KT. A meta-analysis was performed, using the fixed or random-effect model, with Review Manager 5.3. PTBD was associated with lower risk of cholangitis (risk ratio [RR] = 0.49, 95% confidence interval [CI]: 0.36–0.67; P

Objective The present study was conducted to investigate whether early precut sphincterotomy (EPS) itself increases the incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), bleeding, and perforation, or improves the overall success rates of biliary cannulation. Methods Four electronical databases were searched systematically for randomized controlled trials (RCTs) reporting the incidence of adverse events for difficult biliary access (DBA) between EPS groups and persistent cannulation attempts (PCA). The primary endpoint was the incidence of PEP. Secondary outcomes were the incidence of bleeding and perforation, and the overall success rates of biliary cannulation. The Mantel-Haenszel method was used to pool data on the outcomes into random-effect models. Heterogeneity, sensitivity, and stratified analyses were performed with Review Manager 5.3. Furthermore, we performed trial sequential analysis (TSA) to evaluate the reliability of the primary endpoint and secondary outcomes. Results Seven RCTs (999 patients with DBA of 10450, 9.5%) were included. The incidence of PEP was significantly lower in EPS groups than PCA (risk ratio [RR] = 0.57, 95% confidence interval [CI] 0.36, 0.92, P = .02). Furthermore, TSA (TSA-adjusted 95% CI 0.30-0.82, P = .0061) and subgroup analysis stratified by the fellow involvement in initial cannulation before randomization, technique of precut, and the definition of DBA confirmed this finding. Success rates of overall cannulation (RR = 1.00, P = .94), bleeding (RR = 1.22, P = .58), and perforation (RR = 1.59, P = .32) were similar in both groups; however, the results of TSA could not confirm these findings. Conclusion Both the quality and the quantity of evidence supporting, compared with PCA, EPS itself do not increase the risk of PEP for DBA patients. Moreover, subgroup analysis demonstrated that EPS can significantly decrease the risk of PEP when it is performed by qualified staff endoscopists with using needle-knife fistulutomy earlier for patients with DBA.

Supplemental Digital Content is available in the text, The refinement in surgical techniques combined with the preoperative management has improved the resectability rate of perihilar cholangiocarcinoma (pCCA). However, the prognosis of pCCA with curative resection is still dismal. This meta-analysis was performed to investigate the prognostic clinicopathological factors in resectable pCCA. PubMed, the Cochran Library, ScienceDirect, and Web of Science were searched systematically to identify reports focusing on studying the prognostic clinicopathological factors in resectable pCCA. The hazard ratios (HRs) and its 95% confidence interval (95%CI) from the identified studies using Cox proportional hazard regression model were extracted for overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) analysis. Three prospective and 35 retrospective cohort studies including 5681 resectable pCCA were included in the pooled analysis. Among more than 20 clinicopathological factors associated with negative survival of pCCA, only 6 were included in quantitative analysis which showed that lymph node involvement was associated with a reduced OS (HR = 2.04; 95%CI: 2.10–2.62), DSS (HR = 1.80; 95%CI: 1.39–2.34), DFS (HR = 4.38; 95%CI: 1.89–10.14), negative resection margin (HR = 2.04; 95%CI:1.73–2.41), operative transfusion (HR = 1.82; 95%CI: 1.06–3.11), and T3 or T4-stage (HR = 2.04; 95%CI: 2.04–2.53) were poor prognostic factors of OS, and poor or moderate differentiation was also an adverse prognostic factor of OS (HR = 2.71; 95%CI: 1.80–4.07) and DSS (HR = 1.74; 95%CI: 1.25–2.44). The overall median resectability rate (95CI%), R0 resection (95CI%), and 5-year OS (95CI%) in Eastern and Western countries were 74.9 (66.4–78.4) % and 41.3 (32.6–80.8) %, 70.7 (65.6–80.8) % and 75.9 (64.0–80.4) %, and 33.0 (29.7–39.7) % and 25.5 (20.0–31.6) %, respectively. Negative resection margin, lymph node involvement, poor or moderate differentiation grade was identified as the negative predictor factors of resectable pCCA. Operative transfusion and T3/T4 stage were also associated with a reduced survival of resectable pCCA.

Background:The aim of this study was to compare the clinical outcomes between patients with preoperative cholangitis and noncholangitis patients to determine whether the preoperative cholangitis would be able to serve as an independent predictive factor on hilar cholangiocarcinoma (HCC) outc