Background: Platelets contain several growth factors, including platelet-derived growth factor and hepatocyte growth factor. Materials and methods: We examined the effects of platelet increment on liver regeneration after 70% hepatectomy. Hepatectomies were carried out in male BALB/c mice, and subsequently divided into three groups: (i) untreated mice, (ii) thrombocytotic mice induced with thrombopoietin, and (iii) thrombocytopenic mice induced with anti-platelet antibody. Growth kinetics in the liver were analyzed as a function of the liver/body weight ratio, the mitotic index, the proliferating cell nuclear antigen labeling index and Ki-67 labeling index. Activation of signal transduction pathways relating to cell proliferation were examined, including the STAT3, Akt, and ERK1/2 pathways. Platelet accumulation in the residual liver was quantified by immunohistochemistry and transmission electron microscopy. Results: In thrombocytotic and thrombocytopenic mice, liver/body weight ratios and Ki-67 labeling indices were significantly increased and significantly decreased, respectively, compared with untreated mice 48 hours post-hepatectomy. The Akt pathway was strongly activated, and platelet accumulation was significantly increased in thrombocytotic group 5 minutes post-hepatectomy compared with normal and thrombocytopenic groups. After hepatectomy platelets accumulated in the sinusoids of liver and promoted hepatocyte proliferation in early period after hepatectomy. Conclusion: By increasing or decreasing the platelet, marked changes in liver regeneration can occur, due to differences in cellular signaling and mitosis.

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Among patients undergoing surgical resection for extrahepatic cholangiocarcinoma, invasive carcinoma at the ductal resection margins appears to have a significant relation to local recurrence and also a significant negative impact on survival, whereas residual carcinoma in situ does not. Discrimination whether carcinoma in situ or invasive carcinoma is present is important in clinical setting in which the resection margin at the ductal stump is positive.

Cholangiocarcinoma (CC) is an aggressive malignant tumor for which useful markers are not presently available for early and precise diagnosis. The aim of this study was therefore to identify a high-performance diagnostic marker with a special focus on glyco-alteration of glycoproteins. In the course of study, we found that Wisteria floribunda agglutinin (WFA) is the best probe to differentiate intrahepatic cholangiocarcinoma (ICC) lesions from normal bile duct epithelia (BDE) (P < 0.0001). The subsequent histochemical study confirmed ICC-specific WFA staining on 165 tissue specimens. On the other hand, the WFA staining was shown to be closely associated with that of MY.1E12 established previously against sialylated mucin 1 (MUC1) by double-staining experiments. Moreover, glyco-alteration of MUC1 could be verified by western blotting of WFA-captured bile samples from patients with CC patients. Thus, we attempted to construct an enzyme-linked immunosorbent assay system for more convenient CC diagnosis, where WFA-coated plates, the specific monoclonal antibody MY.1E12, and the bile specimens from CC including ICC (n 5 30) and benign diseases (n 5 38) were combined. As a result, CC was clearly distinguished from benign diseases with statistical scores (sensitivity 5 90.0%, specificity 5 76.3%, and area under the curve 5 0.85). As a particular note, the obtained sensitivity is the highest score among those having been so far reported. Conclusion: Our approach focusing significant glyco-alteration of a particular glycoprotein yielded a novel diagnostic system for CC with satisfactory clinical scores. (HEPATOLOGY 2010;52:174-182) C holangiocarcinoma (CC) is an aggressive malignant tumor arising from the epithelial lining of the intrahepatic biliary tract. Although it contributes to only 15% of the total incidence of primary liver cancer, 1 recent epidemiological reports show that the CC incidence has increased significantly in Abbreviations: AFP, alpha-fetoprotein; AUC, area under the curve; BDE, bile duct epithelia; BSA, bovine serum albumin; CA19-9, carbohydrate antigen 19-9;