A prospective study of isolated human hepatocyte function following liver resection for colorectal liver metastases: the effects of prior exposure to chemotherapy.
OBJECTIVE
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 (CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, CYP3A4) and phase II enzymes (UDP-glucuronosyltransferase 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.
Hewes
James C
JC
University Department of Surgery, Division of Surgical and Interventional Sciences, Royal Free and University College Medical School, Hampstead Campus, UCL, London NW3 2QG, UK.
Riddy
Darren
D
Morris
Richard W
RW
Woodrooffe
Amanda J
AJ
Davidson
Brian R
BR
Fuller
Barry
B
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D000077150:Oxaliplatin; D011446:Prospective Studies; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil