title: Inclusion of tumor markers improves the correlation of the Milan criteria with vascular invasion and tumor cell differentiation in patients with hepatocellular carcinoma undergoing liver resection (#JGSU-D-07-00462).
abstract: The currently used criteria, such as the Milan criteria, to select a candidate of liver transplantation for HCC consists of size and number of tumors because vascular invasion and poor differentiation, the strongest prognostic factors, are difficult to be assessed preoperatively. We hypothesized that inclusion of two tumor markers (alpha-fetoprotein and des-gamma-carboxy prothrombin) into the criteria would increase the prediction accuracy of these factors. Our hypothesis was tested in 478 HCC patients undergoing liver resection. The models with or without markers, constructed at predicting vascular invasion (n=150) or poor differentiation (n=49), were compared. The model including markers was superior at predicting the absence of vascular invasion to either the Milan criteria alone [at 81.2% sensitivity; specificity, 52.4 vs 43.3%; difference, 9.1%(95% CI, 1.3-14.2%)] or a model in which size and number varied freely [AUCs of receiver operating characteristic curves, 75.2 vs 69.1%; difference, 6.1%(2.33-10.7%)]. The model incorporating markers was also superior at predicting well to moderate differentiation to either the Milan criteria [at 74.5% sensitivity; specificity, 57.1 vs 38.8%; difference, 18.3%(2.4-32.7%)] or a model with size and number [AUCs, 71.5 vs 59.0%; difference, 12.5%(5.84-21.4%)]. In conclusion, the tumor marker levels should be considered when selecting patients with HCC for liver transplantation.
authors.affiliation: Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imamura
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Ijichi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Matsuyama
authors.forename: Keiji
authors.initials: K
authors.lastname: Sano
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sugawara
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kokudo
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Makuuchi
mesh_terms: D000328:Adult; D000368:Aged; D001652:Bile Ducts / Q000473:pathology; D015415:Biomarkers / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D005260:Female; D006498:Hepatectomy; D006503:Hepatic Veins / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009361:Neoplasm Invasiveness; D011169:Portal Vein / Q000473:pathology*; D011379:Prognosis; D011498:Protein Precursors / Q000097:blood*; D011516:Prothrombin; D012372:ROC Curve; D012680:Sensitivity and Specificity; D000509:alpha-Fetoproteins / Q000032:analysis*
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C008208:acarboxyprothrombin; D011516:Prothrombin