Haitao Yu

Despite a rising trend in intrahepatic cholangiocarcinoma (ICC) incidence in the elderly population worldwide, the benefit of surgery for those patients is still controversial. Data from 811 elderly patients diagnosed with non-metastatic ICC were obtained from the US surveillance, epidemiology, and end results (SEER) program database. Propensity score matched (PSM) was conducted for the better balance of baseline. The associations between tumor characteristics and surgery with overall survival (OS) and cancer specific survival (CSS) were estimated using hazard ratios (HR) and 95% confidence intervals (CI). The results showed that ICC patients above 60 years old taking surgery had better OS (hazard ratio [HR], 0.258; 95% CI, 0.205–0.324) and CSS (hazard ratio [HR], 0.239; 95% CI, 0.188–0.303) than patients without surgery. Similar trends in patients above 65 years old, above 70 years old, above 75 years old, and above 80 years old were observed, separately. This benefit was also showed in lymph node-negative (N0) and lymph node-positive (N1) subgroups and N0 patients are more likely to take an advantage from surgery than N1 patients. The different outcomes between surgery and non-surgery suggest that surgical treatment may be recommended for elderly ICC if the tumor is resectable to ensure optimal treatment.

Background: Although sarcopenia has been reported as a negative prognostic factor in patients with hepatocellular carcinoma (HCC), the lack of studies with a prospective design utilizing comprehensive sarcopenia assessment with composite endpoints is an important gap in understanding the impact of sarcopenia in patients with HCC. The aim of this study was to investigate the relationship between sarcopenia and postoperative 1-year mortality and health-related quality of life (HRQOL) based on sarcopenia assessment. Methods: The study cohort, who received resection surgery for HCC between May 2020 and August 2021, was assessed for sarcopenia based on grip strength, the chair stand test, skeletal muscle mass, and gait speed. The primary outcome measures were 1-year mortality and HRQOL determined using the QLQ-C30 questionnaire. In addition, we collected hospital costs, postoperative hospital stays, complications, 30-day and 90-day mortality, and 90- and 180-day readmission rates. Univariate and multivariate linear regression analyses were conducted to examine factors associated with global health status. Results: A total of 153 eligible patients were included in the cohort. One-year mortality was higher in patients with sarcopenia than in those without sarcopenia (p = 0.043). There was a correlation between sarcopenia and the surgical approach to global health status (p = 0.025) and diarrhea (p = 0.003). Conclusions: Preoperative sarcopenia reduces postoperative survival and health-related quality of life in patients with HCC.

Endothelial progenitor cells (EPCs) can migrate to the tumor tissue and enhance the angiogenesis of hepatocellular carcinoma (HCC); thus, they are associated with a poor prognosis. However, the specific molecular mechanism underlying the homing of EPCs to the HCC neovasculature remains unrevealed. Co-culture experiments of endothelial progenitor cells with HCC cells with modulation of EphA1 were performed in vitro. Using EPCs as angiogenic promoters by injecting them into HCC xenograft-bearing nude mice via their tail veins to test homing ability of EPCs changed according to different EphA1 level in HCC xenograft. In this study, we found that the up-regulation of EphA1 expression in HCC cells could affect not only the chemotaxis of EPCs to tumor cells and endothelial cells (ECs) but also the tube formation ability of EPCs in a paracrine fashion. Further, we revealed that the increased expression of EphA1 in HCC cells led to an increased SDF-1 concentration in the tumor microenvironment, which in turn activated the SDF-1/CXCR4 axis and enhanced the recruitment of EPCs to HCC. In addition, the EphA1-activated SDF-1 expression and secretion was partially mediated by the PI3K and mTOR pathways. In vivo experiments demonstrated that blocking EphA1/SDF-1/CXCR4 signaling significantly inhibited the growth of HCC xenografts. Using immunohistochemistry and immunofluorescence assays, we verified that the inhibition of tumor angiogenesis was at least partially caused by the decreased number of EPCs homing to tumor tissue. Our findings indicate that targeting the EphA1/SDF-1 signaling pathway might be a therapeutic anti-angiogenesis approach for treating HCC.