Background: Targeted drug therapy and transcatheter arterial chemoembolization (TACE) is the most effective control method for middle and late-stage hepatocellular carcinoma (HCC). Regorafenib as the second-line treatment of patients with advanced HCC, combined with TACE treatment still achieved good results in clinic. However, there is no relevant research at present. However, there is no relevant research at present. This study was to investigate the efficacy and safety of regorafenib combined with TACE in the treatment of patients with advanced HCC after the failure of first-line targeted treatment.Methods: Fifty-nine patients with advanced HCC received second-line regorafenib treatment between October 2019 and September 2021 were enrolled in the study. Patients were treated with routine TACE.Oral administration of regorafenib was started 1 week after the operation for 3 weeks and then stopped for 1 week. Objective response rate (ORR), disease control rate (DCR), median progression-free survival (m-PFS), and safety were evaluated according to the modified Response Evaluation Criteria in Solid Tumors (m-RECIST). In our study, most of the analyses are descriptive.Results: One patient achieved complete response (CR), and 24 patients achieved partial response (PR). stable disease (SD) was observed in 14 patients, while progression disease (PD) was observed in 20 patients.The ORR was 42.3% (25/59), and the DCR was 66.1% (39/59). The longest follow-up was 23 months, and the shortest was 1 month. Disease progression was found in 45 patients during follow-up. Among these patients, the longest interval before the detection of disease progression was 16 months, and the shortest was 1 month. Among patients who had disease progression, the median PFS was 8 months. Adverse events (AEs) were observed in 59 patients. These included hand-foot reaction (n=50, 84.7%), weight decrease (n=18, 30.5%), hypertension (n=8, 13.6%), proteinuria (n=1, 1.7%), weakness (n=12, 20.3%), diarrhea (n=1, 1.7%), and hoarseness (n=9, 15.3%). No treatment-related death occurred.Conclusions: Regorafenib combined with TACE achieved a good ORR and DCR among patients with advanced HCC receiving second-line targeted therapy, with only 9 patients experiencing grade 3 or 4 adverse reactions. Therefore, regorafenib combined with TACE is effective and safe in the treatment of advanced HCC.

Background: At present, there is no standard for the posterior treatment of hepatocellular carcinoma (HCC). This study isTo evaluate and compare the safety and efficacy of transcatheter arterial chemoembolization (TACE) combined with regorafenib and anti-PD-1 antibody with continued TACE combined with regorafenib in patients with HCC after the failure of second-line treatment with regorafenib. Methods:We enrolled patients with advanced HCC who were treated with sorafenib and sequential regorafenib. All patients were treated with TACE and found to have tumor progression in 2021. After tumor progression, patients were treated with TACE combined with regorafenib and PD-1 antibody or with continued TACE combined with regorafenib according to the wishes of the patient. Efficacy was evaluated after 1 month of treatment. The objective response rate (ORR), disease-control rate (DCR), and safety were evaluated according to adverse reactions of patients.Results: Nine patients were treated with TACE combined with regorafenib and PD-1 antibody, and the 9 patients continued to receive TACE combined with regorafenib. There was no significant difference in baseline data between the 2 groups. In the PD-1 group five patients achieved a partial response (PR), three achieved stable disease (SD), and one patient had progressive disease (PD) after 1 month of treatment.The ORR was 55.6% and the DCR was 88.9%. In the continued TACE-regorafenib group, four patients achieved PR, one achieved SD, and four patients achieved PD after 1 month of treatment, while the ORR was 44.4% and the DCR was 55.6%. There was a significant difference in the DCR between the two groups (P=0.012), while adverse events were similar in both.Conclusions: TACE combined with regorafenib and PD-1 antibody had a higher DCR and was more effective than continued TACE combined with regorafenib in patients with HCC who failed second-line treatment with regorafenib. However, PD-1 antibody therapy might increase the risk of death by causing an uncontrollable immune response. Given the risk of an immune response, patients may choose to continue TACE combined with regorafenib, given the similar ORR of the two treatments.

Background: Previous observational studies have suggested that circulating adipokine concentrations are related to a greater risk of venous thromboembolism (VTE). However, it remained unclear whether these observations reflect causality.Objective: This study aimed to investigate the causal relationship between circulating adipokine concentrations (including adiponectin, leptin, PAI-1, MCP-1, leptin receptor, and RETN) and the risk of VTE and its subtypes (DVT and PE) and to determine whether circulating adipokine concentrations are a mediator of venous thromboembolic events in obese patients.Methods: We used Mendelian randomization (MR) analyses to determine the effects of the body mass index (BMI), adiponectin, leptin, PAI-1, MCP-1, leptin receptor, and RETN levels on VTE, DVT, and PE in a cohort of 11,288 VTE cases, 5,632 DVT cases, 5,130 PE cases, and 254,771 controls. We then assessed the proportion of the effect of obesity on VTE, DVT, and PE explained by circulating leptin levels.Result: Genetically predicted higher BMI was related to increased VTE (OR = 1.45, p < 0.001), DVT (OR = 1.63, p < 0.001), and PE (OR = 1.37, p < 0.001) risk, and higher circulating leptin levels increase odds of VTE (OR = 1.96, q < 0.001), DVT (OR = 2.52, q < 0.001), and PE (OR = 2.26, q = 0.005). In addition, we found that the causal effect between elevated serum adiponectin and the decreased risk of VTE (OR = 0.85, p = 0.013, q = 0.053) and PE (OR = 0.81, p = 0.032, q = 0.083) and between MCP-1 and the reduced risk of VTE (OR = 0.88, p = 0.048, q = 0.143) is no longer significant after FDR adjustment. In MR mediation analysis, the mediation effect of circulating leptin levels in the causal pathway from BMI to PE was estimated to be 1.28 (0.95–1.71, p = 0.10), accounting for 39.14% of the total effect.Conclusion: The circulating leptin level is a risk factor for VTE, DVT, and PE, but it might be a potential mediator of BMI on the risk of PE, and thus, interventions on the circulating leptin level in obesity might reduce the risk of PE. Adiponectin is a potential protective factor for both VTE and PE.