Influencing factors for the prognosis of patients with early-stage intrahepatic cholangiocarcinoma after radical resection / 临床肝胆病杂志

ObjectiveTo investigate the influencing factors for the prognosis of patients with early-stage intrahepatic cholangiocarcinoma (ICC) after surgical treatment. MethodsA total of 155 patients with early-stage ICC who underwent radical resection in The Third Affiliated Hospital of Second Military Medical University from January 2013 to December 2014 were enrolled in this study. Clinicopathological features and 1-, 2-, and 3-year overall survival rates and disease-free survival rates after surgery were analyzed. The Cox forward stepwise regression was used for the univariate and multivariate analyses of the influencing factors for the prognosis of early-stage ICC. ResultsMost patients with early-stage ICC were middle-aged men, with an average tumor diameter of 5.8±2.5 cm. Most patients had normal liver function, but there were varying degrees of increase in carbohydrate antigen 19-9 (CA19-9) level. Postoperative pathological examination revealed highly or moderately differentiated adenocarcinoma in most patients. The 1-, 2-, and 3-year overall survival rates after surgery were 76.1%, 43.9%, and 34.1%, respectively, and the 1-, 2-, and 3-year disease-free survival rates were 50.3%, 250%, and 18.1%, respectively. The Cox multivariate analysis showed that high CA19-9 level before surgery (hazard ratio ［HR］=1705, 95% confidence interval ［CI］: 1.096-2.652, P=0.018), liver cirrhosis (HR=2.399, 95%CI: 1.108-5.196, P=0.026), satellite nodules (HR=1.918, 95%CI: 1.124-3.272, P=0.017), and degree of tumor cell differentiation (HR=5.568, 95%CI: 2591-11.965, P＜0.0001) were independent risk factors for overall survival of patients early-stage ICC. Liver cirrhosis (HR=2.142, 95%CI: 1.054-4.353, P=0.035), satellite nodules (HR=2.045, 95%CI: 1.250-3.343, P=0.004), and degree of tumor cell differentiation (HR=2.748, 95%CI: 1.340-5.638, P=0.006) were independent risk factors for disease-free survival of patients early-stage ICC. ConclusionRadical resection is the preferred treatment for patients with early-stage ICC. Preoperative CA19-9 ≥200 U/ml, liver cirrhosis, satellite nodules, and degree of tumor cell differentiation are independent risk factors for the prognosis of early-stage ICC.

Lineage conversion of mouse fibroblasts to pancreatic α-cells

α-cells, which synthesize glucagon, also support β-cell survival and have the capacity to transdifferentiate into β-cells. However, the role of α-cells in pathological conditions and their putative clinical applications remain elusive due in large part to the lack of mature α-cells. Here, we present a new technique to generate functional α-like cells. α-like cells (iAlpha cells) were generated from mouse fibroblasts by transduction of transcription factors, including Hhex, Foxa3, Gata4, Pdx1 and Pax4, which induce α-cell-specific gene expression and glucagon secretion in response to KCl and Arg stimulation. The cell functions in vivo and in vitro were evaluated. Lineage-specific and functional-related gene expression was tested by realtime PCR, insulin tolerance test (ITT), glucose tolerance test (GTT), Ki67 and glucagon immunohistochemistry analysis were done in iAlpha cells transplanted nude mice. iAlpha cells possess α-cell function in vitro and alter blood glucose levels in vivo. Transplantation of iAlpha cells into nude mice resulted in insulin resistance and increased β-cell proliferation. Taken together, we present a novel strategy to generate functional α-like cells for the purposes of disease modeling and regenerative medicine.