Journal of Gastrointestinal Surgery

, Volume 12, Issue 5, pp 858–866 | Cite as

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)

  • Kiyoshi Hasegawa
  • Hiroshi Imamura
  • Masayoshi Ijichi
  • Yutaka Matsuyama
  • Keiji Sano
  • Yasuhiko Sugawara
  • Norihiro Kokudo
  • Masatoshi Makuuchi
original article


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-γ-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.


Hepatocellular carcinoma Alpha-fetoprotein Des-γ-carboxy prothrombin Liver transplantation Milan criteria Vascular invasion Tumor differentiation 



hepatocellular carcinoma


University of California at San Francisco




des-γ-carboxy prothrombin


receiver operating characteristic


area under the curve


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Copyright information

© The Society for Surgery of the Alimentary Tract 2007

Authors and Affiliations

  • Kiyoshi Hasegawa
    • 1
  • Hiroshi Imamura
    • 1
  • Masayoshi Ijichi
    • 1
    • 3
  • Yutaka Matsuyama
    • 2
  • Keiji Sano
    • 1
  • Yasuhiko Sugawara
    • 1
  • Norihiro Kokudo
    • 1
  • Masatoshi Makuuchi
    • 1
  1. 1.Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of MedicineUniversity of TokyoTokyoJapan
  2. 2.Department of Biostatistics, Graduate School of MedicineUniversity of TokyoTokyoJapan
  3. 3.Social Insurance Chuo General HospitalTokyoJapan

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