ABSTRACT
BACKGROUND: Recombinant human soluble thrombomodulin (rTM) protects against disseminated intravascular coagulopathy by inhibiting coagulation, inflammation, and apoptosis. This study tests the hypothesis that rTM is hepatoprotective after extensive hepatectomy (Hx) and investigates the mechanisms underlying this effect. MATERIALS AND METHODS: Experiment 1: rats (15 per group) were injected with rTM (1.0 or 2.0 mg/kg) or saline just before 95% Hx and their 7-d survival assessed. Experiment 2: rats were assigned to either a treated (2.0 mg/kg rTM just before Hx) or control group (n = 5 per group). Five rats per group were euthanized immediately after surgery, and at 1, 3, 6, 12, and 24 h postoperatively; serum and liver remnant samples were collected for biochemical and histologic analysis, as well as reverse-transcription polymerase chain reaction and Western blotting. RESULTS: All saline-injected rats died within 52 h of Hx, whereas injection of 2.0 mg/kg rTM prolonged survival (P = 0.003). rTM increased the number of Ki67-positive cells and reduced the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells. The number of myeloperoxidase-positive cells and the expression of high-mobility group box 1 protein did not differ. Reverse-transcription polymerase chain reaction revealed that rTM significantly enhanced protease-activated receptor-1 and sphingosine kinase 1 messenger RNA expression and significantly reduced plasminogen activator inhibitor-1 and Bax messenger RNA expression. Immunohistochemistry and Western blotting demonstrated that protease-activated receptor-1 expression 24 h after Hx was significantly higher in rTM-treated than in control rats. CONCLUSIONS: rTM may improve survival after extensive Hx by inhibiting apoptosis and promoting liver regeneration.
Subject(s)
Hepatectomy/adverse effects , Liver Failure/prevention & control , Liver Regeneration/drug effects , Postoperative Complications/prevention & control , Thrombomodulin/therapeutic use , Alanine Transaminase/blood , Animals , Apoptosis/drug effects , Blotting, Western , Drug Evaluation, Preclinical , Hepatectomy/mortality , Hepatocytes/drug effects , Immunohistochemistry , Liver Failure/etiology , Male , Postoperative Complications/etiology , Rats, Wistar , Receptor, PAR-1/metabolism , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
BACKGROUND AND AIM: The aim of the present study was to evaluate the efficacy of liver resection for multinodular hepatocellular carcinoma (MNHCC). PATIENTS AND METHODS: A total of 399 patients who underwent R0 resection for HCC from 1992 to 2011 were subjected to analysis. Out of these 399 patients, 107 patients had multinodular HCC, while 292 had a single tumor. RESULTS: The 3- and 5-year overall survival rates of patients with MNHCC were 62.0% and 38.1% respectively. By a multivariate analysis of the survival of the 107 patients after liver resection for MNHCC, it was shown that the presence of four or more tumors and a lower serum albumin level were unfavorable prognostic factors for long-term survival. With respect to the patients with four or more HCCs, portal vein invasion was an independent unfavorable prognostic factor for long-term survival. However, in patients with four or more HCCs without portal vein invasion, overall survival rates of those with preoperative serum albumin level >4.0 mg/dl and a platelet count >10(5)/mm(3) were significantly higher than those of patients with albumin <4.0mg/dl or platelet count <10(5)/mm(3) (p=0.049). CONCLUSION: Liver resection can provide a survival benefit, even for patients with multiple HCCs. Even if patients have four or more tumors without portal vein invasion and with well-preserved liver function, resection for HCC may be the treatment of choice.
