Effect of steatohepatitis associated with irinotecan or oxaliplatin pretreatment on resectability of hepatic colorectal metastases.
BACKGROUND
The objective was to evaluate the effect of preoperative administration of newer chemotherapeutic agents (irinotecan and oxaliplatin) on development of steatohepatitis, which could limit surgical options.


METHODS
Thirty-seven patients were referred for resection of hepatic colorectal metastases. Thirteen patients received no neoadjuvant therapy (NO CHEMO group); 10 received neoadjuvant 5-fluorouracil only (5-FU group), and 14 received neoadjuvant irinotecan (n = 12), or oxaliplatin, or both (n = 4), in conjunction with 5-FU (IRI-OXALI group). Specimens were graded for the presence of nonalcoholic steatohepatitis (NASH) according to established criteria. Specimens were also evaluated by a nine-criteria liver injury score (LIS).


RESULTS
Mean biopsy scores were: NO CHEMO: NASH, 1.2, LIS, 5.2; 5-FU only: NASH, 1.1, LIS 5.7; and IRI-OXALI: NASH, 1.9, LIS, 9.4. Biopsy scores were significantly worse for IRI-OXALI compared with NO CHEMO or 5-FU only for NASH score, p = 0.003, and close to significantly worse for LIS score, p = 0.057. A multivariate analysis showed that both being in the IRI-OXALI group and body mass index were independent risk factors for developing this type of steatohepatitis.


CONCLUSIONS
Severe steatohepatitis can be associated with preoperative administration of irinotecan or oxaliplatin, especially in the obese. It can affect the ability to perform large liver resections. Consideration should be given to performing resections before commencing these agents and to obtaining preoperative biopsy in those who have received these agents.
Fernandez
Felix G
FG
Section of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Ritter
John
J
Goodwin
J Wendell
JW
Linehan
David C
DC
Hawkins
William G
WG
Strasberg
Steven M
SM
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001706:Biopsy; D002166:Camptothecin / Q000008:administration & dosage* / Q000009:adverse effects* / Q000031:analogs & derivatives*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000473:pathology*; D005234:Fatty Liver / Q000139:chemically induced* / Q000150:complications / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006498:Hepatectomy; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000556:secondary* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects*; D000077150:Oxaliplatin; D011300:Preoperative Care; D011446:Prospective Studies; D012307:Risk Factors; D059004:Topoisomerase I Inhibitors
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D009944:Organoplatinum Compounds; D059004:Topoisomerase I Inhibitors; D000077150:Oxaliplatin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin