The Warsaw Proposal for the Use of Extended Selection Criteria in Liver Transplantation for Hepatocellular Cancer

Abstract

BackgroundCombination of the University of California, San Francisco (UCSF) and the up-to-7 criteria with alpha-fetoprotein (AFP) cutoff of 100 ng/ml was proposed as the Warsaw expansion of the Milan criteria in selection of hepatocellular cancer (HCC) patients for liver transplantation. The purpose of this retrospective study was to validate this proposal.MethodsA total of 240 HCC patients after liver transplantation were included. Recurrence-free survival and overall survival at 5 years were set as the primary and secondary outcome measures, respectively.ResultsThe Warsaw expansion increased transplant eligibility rate by 20.3 %. AFP >100 ng/ml significantly increased the recurrence risk in patients within the Milan criteria (p = 0.025) and in those beyond, yet within either the UCSF or the up-to-7 criteria (p < 0.001). Recurrence-free survival at 5 years was 90.8 % for patients within the Milan criteria, 100.0 % in patients within the Warsaw expansion, 54.9 % in patients beyond the Warsaw expansion but within either the UCSF or the up-to-7 criteria, and 45.1 % in patients beyond both the UCSF and the up-to-7 criteria (p < 0.001). The corresponding overall survival rates were 71.6, 82.4, 64.3, and 55.3 %, respectively (p = 0.027).ConclusionsThe Warsaw expansion of the Milan criteria substantially increases the recipient pool without compromising outcomes.

Challenging the principle of utility as a barrier for wider use of liver transplantation for hepatocellular cancer

“…While division of HCC patients into subgroups was based on total tumor volume and alpha-fetoprotein, the two well-known predictors of HCC recurrence, division of non-HCC patients was based solely on laboratory MELD score, commonly used for prioritization purposes and also known to influence negatively posttransplant outcomes. 8 , 9 , 11 , 12 , 24 The presented survival outcomes of high-risk HCC patients are even lower than that reported in the literature for patients beyond the Milan criteria, presumably due to more liberal selection policy applied in the authors department reducing selection bias. 5 , 7 , 12 , 25 , 26 The outcomes of high-MELD non-HCC patients seem comparable to that previously reported.…”

Ischemia-reperfusion injury and the risk of hepatocellular carcinoma recurrence after deceased donor liver transplantation

“…Importantly, initial analyses performed in all patients failed to reveal any significant associations between post-reperfusion AST, ALT, and LDH levels and HCC recurrence risk, irrespective whether the factors were analysed as continuous or categorical variables. However, the study cohort comprised patients with a wide range of tumour burden due to a liberal selection policy utilised in the authors’ department before establishment of precise criteria 5 . Nevertheless, a major significant negative effect of post-reperfusion AST and LDH levels was observed for patients within the Milan criteria, which still determine the majority of liver transplant recipients 28 .…”

8u, a pro-apoptosis/cell cycle arrest compound, suppresses invasion and metastasis through HSP90α downregulating and PI3K/Akt inactivation in hepatocellular carcinoma cells

“…So far, HCC is still an incurable disease, because it has strong abilities of invasion and metastasis 2 . Currently, therapies for HCC include chemical therapy, surgical resection, partial ablation therapy, and liver transplantation 3 – 6 . However, recurrence and metastasis after surgery, as well as drug resistance are major barriers to successful therapy, thus leading to a poor outcome in HCC patients 7 .…”