A prospective study of isolated human hepatocyte function following liver resection for colorectal liver metastases: The effects of prior exposure to chemotherapy

James C. Hewes, Darren Riddy, Richard W. Morris, Amanda J. Woodrooffe, Brian R. Davidson, Barry Fuller*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

22 Citations (Scopus)

Abstract

Background/Aims: Chemotherapy is increasingly used prior to resection of colorectal liver metastases, yet few studies have addressed its effect on the viability and function of hepatocytes. This study evaluated the effect of pre-operative chemotherapy on human hepatocytes.

Methods: Studies were carried out on isolated hepatocytes from 47 patients undergoing hepatectomy for colorectal metastases. The function of drug metabolising enzymes in hepatocytes was assessed in vitro, as well as hepatocyte integrity and culture longevity. These results were compared between patients undergoing no pre-operative chemotherapy (N = 8), 5 fluorouracil (5FU) post-bowel resection (N = 20), and neo-adjuvant 5FU alone (N = 7) or in a combination with oxaliplatin (N = 12).

Results: Average cell viability at isolation determined by trypan blue dye exclusion was 71% with no significant difference between the no chemotherapy or pre-resection chemotherapy groups. There was no significant difference in LDH leakage and cellular ATP content over a 96-h time course between the patient treatment groups. The function of cytochromes P450 (CYPIA2, CYP2A6, CYP2C9, CYP2D6, CYP2EI, CYP3A4) and phase 11 enzymes (UDP-glucuronosyl-transferase and sulphotransferase) was not adversely affected by pre-operative chemotherapy.

Conclusions: Pre-resection chemotherapy does not impair the function or culture integrity of hepatocytes isolated at the time of liver resection. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)263-270
Number of pages8
JournalJournal of Hepatology
Volume45
Issue number2
DOIs
Publication statusPublished - Aug 2006
Event6th World Congress of the International-Hepato-Pancreatico-Biliary-Association - Washington, United Kingdom
Duration: 3 Jun 20045 Jun 2004

Keywords

  • neo-adjuvant chemotherapy
  • liver cell culture
  • isolated human hepatocytes
  • oxaliplatin
  • hepatectomy
  • NEOADJUVANT CHEMOTHERAPY
  • ARTERIAL INFUSION
  • HEPATIC TOXICITY
  • DRUG-METABOLISM
  • IN-VITRO
  • CANCER
  • OXALIPLATIN
  • 5-FLUOROURACIL
  • FLOXURIDINE
  • STRATEGIES

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