Therapeutic Advances
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jul 28, 2016; 8(21): 874-880
Published online Jul 28, 2016. doi: 10.4254/wjh.v8.i21.874
Hepatocellular carcinoma beyond Milan criteria: Management and transplant selection criteria
Mohammed Elshamy, Federico Aucejo, K V Narayanan Menon, Bijan Eghtesad
Mohammed Elshamy, Federico Aucejo, Bijan Eghtesad, Hepato-biliary and Transplant Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, United States
KV Narayanan Menon, Gastroenterology and Hepatology, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, United States
Author contributions: This manuscript was written completely by the stated authors.
Conflict-of-interest statement: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Bijan Eghtesad, MD, Hepato-biliary and Transplant Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue/A100, Cleveland, OH 44195, United States. eghtesb@ccf.org
Telephone: +1-216-4445914 Fax: +1-216-4449375
Received: March 30, 2016
Peer-review started: April 6, 2016
First decision: June 7, 2016
Revised: June 17, 2016
Accepted: July 11, 2016
Article in press: July 13, 2016
Published online: July 28, 2016
Processing time: 113 Days and 11.9 Hours
Abstract

Liver transplantation (LT) for hepatocellular carcinoma (HCC) has been established as a standard treatment in selected patients for the last two and a half decades. After initially dismal outcomes, the Milan criteria (MC) (single HCC ≤ 5 cm or up to 3 HCCs ≤ 3 cm) have been adopted worldwide to select HCC patients for LT, however cumulative experience has shown that MC can be too strict. This has led to the development of numerous expanded criteria worldwide. Morphometric expansions on MC as well as various criteria which incorporate biomarkers as surrogates of tumor biology have been described. HCC that presents beyond MC initially can be downstaged with locoregional therapy (LRT). Post-LRT monitoring aims to identify candidates with favorable tumor behavior. Similarly, tumor marker levels as response to LRT has been utilized as surrogate of tumor biology. Molecular signatures of HCC have also been correlated to outcomes; these have yet to be incorporated into HCC-LT selection criteria formally. The ongoing discrepancy between organ demand and supply makes patient selection the most challenging element of organ allocation. Further validation of extended HCC-LT criteria models and pre-LT treatment strategies are required.

Keywords: Hepatocellular carcinoma; Milan criteria; Liver transplantation; Expanded criteria; Locoregional therapy; Down staging

Core tip: Numerous expanded selection criteria for hepatocellular carcinoma (HCC)-liver transplantation (LT) have been proposed worldwide. Surrogates of favorable tumor biology such as Post-locoregional therapy strategies which observe tumor behavior, and the addition of HCC biomarkers to selection criteria have been explored. Further investigation is encouraged to identify patients beyond MC with the most favorable tumor biology for LT.