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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)

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Journal of Gastrointestinal Surgery Aims and scope

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-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.

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Abbreviations

HCC:

hepatocellular carcinoma

UCSF:

University of California at San Francisco

AFP:

alpha-fetoprotein

DCP:

des-γ-carboxy prothrombin

ROC:

receiver operating characteristic

AUC:

area under the curve

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Acknowledgment

This work was supported by a grant from the Mitsui Life Social Welfare Foundation, a grant from the Kanae Foundation for Life and Socio-Medical Science, and a grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (grant no. 18790955) in Japan.

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  1. Masayoshi Ijichi

    Present address: Social Insurance Chuo General Hospital, 3-22-1, Hyakunincho, Shinjuku-ku, Tokyo, 169-0073, Japan

Authors and Affiliations

  1. 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

    Kiyoshi Hasegawa, Hiroshi Imamura, Masayoshi Ijichi, Keiji Sano, Yasuhiko Sugawara, Norihiro Kokudo & Masatoshi Makuuchi

  2. Department of Biostatistics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

    Yutaka Matsuyama

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  1. Kiyoshi Hasegawa
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Hasegawa, K., Imamura, H., Ijichi, M. et al. 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). J Gastrointest Surg 12, 858–866 (2008). https://doi.org/10.1007/s11605-007-0464-9

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