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Do We Need to Be Limited by Matching Milan Criteria for Survival in Living Donor Liver Transplantation?

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Abstract

Purpose

Hepatocellular carcinoma (HCC) is the second leading cause of cancer deaths and the 7th most common cancer. It has two characteristic features: being advanced stage at diagnosis and association with liver cirrhosis. Liver transplantation (LT) offers the only curative option to treat both components of the disease. The Milan criteria have been extensively used for selecting patients with HCC for LT. However, using Milan criteria, we can only transplant 30% of the patients. The aim of the present review is to evaluate the role of LT in HCC beyond the Milan criteria.

Methods

We evaluated the studies that have introduced extended criteria to select patients with HCC beyond the Milan criteria. We evaluated the outcomes in terms of disease-free survival rates and HCC recurrences.

Results

There are patients with tumors that are beyond Milan criteria that could benefit from LT. Selection of these patients has paramount importance in the era of living donor liver transplantation. Current expanded criteria depend on either the bulk of the tumor or the additional surrogate markers of tumor biology such as alpha-fetoprotein (AFP) and des-gamma carboxyprothrombin (DCP).

Conclusion

There is no ideal marker or an extended criterion for selecting patients with HCC beyond the Milan criteria and it needs further research to find an effective biomarker that has prognostic significance to select patients with advanced tumors.

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Abbreviations

AFP:

Alpha-Feto-Protein

CRP:

C-reactive protein

CUN:

Clinica Universitaria de Navarra

DCP/PIVKA-II:

Des-carboxyprothrombin/protein induced by vitamin K absence or antagonist II

EpCAM:

Epithelial Cell Adhesion Molecules

DDLT :

Deceased donor liver transplantation

GGT:

Gamma-Glutamyl Transferase

GGT-II:

GGT Isozyme 2

HCC:

Hepatocellular carcinoma

K19:

Keratin 19

LDLT:

Living donor liver transplantation

LRT:

Locoregional therapy

LT:

Liver transplantation

MC:

Milan criteria

UNOS:

United Organ Sharing Network

NLR:

Neutrophil to lymphocyte ratio

MMP2/9:

Matrix Metalloproteinase 2/9

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Acknowledgements

The article defining the Hangzhou Criteria was retracted by the editors of the Transplantation in 2019 [47]. Unless this issue is clarified by the authors of the article, it is not appropriate to use these criteria in new studies.

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Authors and Affiliations

  1. Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Elazig Yolu 10. Km, 244280, Malatya, Turkey

    Sami Akbulut & Cemalettin Koc

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  1. Sami Akbulut
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All authors contributed equally to the manuscript.

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Correspondence to Sami Akbulut.

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Akbulut, S., Koc, C. Do We Need to Be Limited by Matching Milan Criteria for Survival in Living Donor Liver Transplantation?. J Gastrointest Canc 51, 1107–1113 (2020). https://doi.org/10.1007/s12029-020-00482-0

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