title: Effect of steatohepatitis associated with irinotecan or oxaliplatin pretreatment on resectability of hepatic colorectal metastases.
abstract: 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.
authors.affiliation: Section of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Felix G
authors.initials: FG
authors.lastname: Fernandez
authors.forename: John
authors.initials: J
authors.lastname: Ritter
authors.forename: J Wendell
authors.initials: JW
authors.lastname: Goodwin
authors.forename: David C
authors.initials: DC
authors.lastname: Linehan
authors.forename: William G
authors.initials: WG
authors.lastname: Hawkins
authors.forename: Steven M
authors.initials: SM
authors.lastname: Strasberg
mesh_terms: 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
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D009944:Organoplatinum Compounds; D059004:Topoisomerase I Inhibitors; D000077150:Oxaliplatin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin