Analyses of mitochondrial biogenesis and function after Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS)

Abstract

Background: The effect of ALPPS on tumor proliferation, remains a concern. This study investigated the impact of ALPPS on growth of colorectal metastases in mice and human. Methods: The effect of ALPPS and 90% portal vein ligation (PVL) on colorectal liver and lung metastases was investigated in mice. In vivo tumor progression was assessed by magnetic resonance imaging (MRI), histology and survival experiments. The effects of ALPPS, PVL and control sera on colorectal cancer cells (MC38 and CT26) were tested in vitro. Additionally, the international ALPPS registry enabled to identify patients with remaining tumor in the future liver remnant (FLR) after ALPPS stage 1. Results: Two and three weeks after ALPPS stage 1, PVL or sham surgery, liver MRI showed similar intrahepatic tumor numbers ((p=0.14/0.82), sizes (p=0.45/0.98) and growth kinetics (p=0.58/0.68). Tumor growth was not different between ALPPS and PVL groups after completion of stage 2. Survival after tumor cell injection was similar after sham surgery and completion of ALPPS and PVL (36 days (IQR 32-40) vs. 42 days (IQR 36-48) vs. 39 days (IQR 35-42), p=0.237). Pulmonary metastases progression and in vitro cell proliferation were comparable among groups. Observations in humans failed to identify accelerated tumor growth in the FLR within the regenerative phase after ALPPS stage 1. Conclusion:The accelerated regeneration process associated to ALPPS does not enhance the growth of residual colorectal liver metastases.