Pathologic and Radiographic Studies of Intrahepatic Metastasis Hepatocellular Carcinoma; The Role of Efferent Vessels

The efferent vessel of hepatocellular carcinoma (HCC) and the mechanism and pathogenesis of the high frequency of intrahepatic metastasis in HCC has not yet been clarified. Three hundred ninety-three resected specimens of HCC were examined for tumor thrombosis in the portal vein and the hepatic vein: 231 tumors ≤5 cm in diameter were examined for the relationship between mode of tumor spread and tumor size. Efferent vessels in HCC were identified by direct injection of radiopaque material into the tumor in 23 resected liver specimens and by percutaneous infusion of radiopaque media into tumor nodules in 8 patients. The mode of tumor spread in HCC progressed from capsular invasion to extracapsular invasion, then to vascular invasion, and finally to intrahepatic metastasis. There was a strong statistical correlation between the presence of intrahepatic metastasis and portal vein thrombosis (p<0.05, R=0.998). Radiopaque material injected directly into 23 resected tumors entered only the portal vein in 17 tumors and into both the portal and hepatic veins in 6 tumors. In all 8 patients with unresectable lesions, radiopaque media injected percutaneously into tumor nodules flowed only into the portal vein. These findings suggest that intrahepatic invasion by HCC may occur through the portal vein as an efferent tumor vessel

CPM Is a Useful Cell Surface Marker to Isolate Expandable Bi-Potential Liver Progenitor Cells Derived from Human iPS Cells

To develop a culture system for large-scale production of mature hepatocytes, liver progenitor cells (LPCs) with a high proliferation potential would be advantageous. We have found that carboxypeptidase M (CPM) is highly expressed in embryonic LPCs, hepatoblasts, while its expression is decreased along with hepatic maturation. Consistently, CPM expression was transiently induced during hepatic specification from human-induced pluripotent stem cells (hiPSCs). CPM+ cells isolated from differentiated hiPSCs at the immature hepatocyte stage proliferated extensively in vitro and expressed a set of genes that were typical of hepatoblasts. Moreover, the CPM+ cells exhibited a mature hepatocyte phenotype after induction of hepatic maturation and also underwent cholangiocytic differentiation in a three-dimensional culture system. These results indicated that hiPSC-derived CPM+ cells share the characteristics of LPCs, with the potential to proliferate and differentiate bi-directionally. Thus, CPM is a useful marker for isolating hiPSC-derived LPCs, which allows development of a large-scale culture system for producing hepatocytes and cholangiocytes