Recurrence of HCC when transplanted outside milan criteria

Hepatocellular carcinoma (HCC) is a cancer with global significance being the fifth most common cancer in men worldwide and seventh among women, with over half a million new cases diagnosed annually. It is presently the second leading cause of cancer-related mortality in the world; the disease burden is highest in Eastern Asian and in sub-Saharan areas with endemic HBV infection. With respect to any available treatment for liver cancer, liver transplantation (LT) retains the potential to cure the disease per se as well as the underlying chronic liver disease. The “Milan criteria” proposed by Mazzaferro et al. in 1996 (a single tumor of 5 cm or less in size or up to a maximum of three HCC, each 3 cm or less in size, with no macroscopic vascular invasion) have been proven to be reliable and easily applicable for the selection of patients with small unresectable hepatocellular carcinomas for LT. The main disadvantage of this set of criteria is that it is relatively restrictive. Several attempts have been made to expand these criteria to include tumors of greater number and size. The model for end-stage liver disease (MELD) prioritization system has utilized the Milan criteria since adopted by UNOS in 2002 and by Eurotransplant in 2006. The current MELD priority score for T2 HCC (1 lesion of 2-5 cm or 2-3 lesions, each 1-3 cm) is 22 points, and there are quarterly increases corresponding to a 10 % increase in pre-transplant mortality. This system has decreased wait-list time from 1.3 to 0.6 years, and the dropout rate from 25.9 to 6.7 %. The number of LT performed for HCC has risen to 26 %; however, in some UNOS regions the percentage is much higher, as well as there being a parallel increase in the wait-list dropout rate. Any macro-morphologic tumor progression beyond the Milan size limits results in loss of MELD prioritization. In such situations, LT centers have looked at downsizing the HCC prior to deceased donor LT (DDLT) or live donor liver transplant (LDLT). Tumor recurrence is a strong predictor for reduced overall post-LT survival. Multiple factors have been looked at in selecting patients to avoid post-transplant recurrence including tumor biology, microvascular invasion, tumor staging, total tumor volume, age, and AFP levels. Careful selection of patients outside of Milan criteria disease allows LT of more patients without compromising long-term disease-free and patient survival. What follows is a review of several of the other HCC staging systems that LT centers use to list and prioritize their patients, an outline of specific prognostic variables that may impact post-LT recurrence of HCC, and then data on surveillance strategies to detect post-LT HCC recurrence as well as its treatment.