Neoadjuvant versus Perioperative Chemotherapy for Resectable Colorectal Liver Metastases: An International Multicentre Propensity-score Matched Analysis

Abstract

In-situ normothermic regional perfusion (NRP) and ex-situ normothermic machine perfusion (NMP) aim to improve outcomes of liver transplantation (LT) using donors after circulatory death (DCD). However, these two dynamic preservation strategies have not been compared yet. The aim of this study was to compare outcomes of DCD grafts exposed to NRP with subsequent static cold storage (SCS) versus continuous NMP commenced at the donor centre after a short period of SCS. Method: This international multicentre retrospective study included DCD donor livers that had been subjected to either NRP or NMP. The NRP cohort was transplanted in six French centres participating in the national NRP organ retrieval programme. The NMP cohort was enrolled by four UK and one Belgian centres as part of a multinational randomised controlled trial (COPE). Study endpoints were liver utilisation rate, 2-year patient and graft survival, 30day graft loss, incidence of clinically manifest biliary strictures, early allograft dysfunction and peak aspartate aminotransferase (AST) levels. Results: Overall, 157 NRP and 34 NMP livers were transplanted, resulting in organ utilisation rates of 70% vs 85% (p = 0.056). The donor and recipient characteristics were similar, including the donor functional warm ischemic time (22 vs 20 min; p = 0.170), UK-DCD risk score (6 vs 5 points; p = 0.15) and lab-MELD scores (12 vs 12 points; p=0.99). NRP livers were more frequently allocated to recipients suffering from hepatocellular carcinoma (62 vs 21%; p < 0.001). HCC-censored 2-year graft and patient survival were 89% vs 88% (p = 0.78) and 93% vs 94% (p = 0.865) after NRP and NMP, respectively, with similar 30day graft loss (5% vs 9%; p=0.416). The incidence of nonanastomotic biliary strictures (1% vs 3%; p = 0.357) and early allograft dysfunction (20% vs 9%; p = 0.139) were also similar, although peak post-transplant AST levels were lower in the NMP cohort (865 vs 344 IU/l; p < 0.001). Conclusion: Outcomes for both in-situ NRP and continuous ex-situ NMP of DCD grafts appear to match benchmarks expected for DBD livers. This study may inform the appropriate design of a prospective randomised trial comparing the efficacy of both preservation strategies in DCD liver transplantation.