Biological Substrate of the Rapid Volumetric Changes Observed in the Human Liver During the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Approach

Abstract

BackgroundThe associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) strategy induces rapid future liver remnant (FLR) hypertrophy. Hepatocyte cellular and molecular changes associated with liver hypertrophy during ALPPS remain ill-defined in humans. MethodsPatients undergoing the ALPPS approach between June 2011 and October 2014 were extracted. Biopsies from the FLR were obtained during the first and second stages. Hematoxylin–eosin staining and immunohistochemical analysis for expression of the proliferating cell nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were performed. The proliferative index was defined as: PCNA–TUNEL ratio. ResultsEleven of 34 patients treated were studied during both stages. Median FLR hypertrophy was 104 % in 6 days, with a mean difference between preoperative and postoperative volume of 361 ml (P < 0.001). The mean hepatocyte number increased from 52.7 cells/mm2 in the first stage to 89.6 cells/mm2 in the second stage (P = 0.001). PCNA expression increased by 190 % between stages with a linear correlation (r = 0.58) with macroscopic hypertrophy. The proliferative index increased from −3.78 cells/mm2 in first stage to 2.32 cells/mm2 in the second stage (P = 0.034). ConclusionsThe results of the present study indicate that the rapid FLR volumetric increase observed in ALPPS is accompanied by histological and molecular features of hepatocyte cell proliferation.