Patterns of chemotherapy-induced hepatic injury and their implications for patients undergoing liver resection for colorectal liver metastases.
OBJECTIVE
Neoadjuvant chemotherapy is increasingly being used to enlarge the cohort of patients who can be offered hepatic resection for malignancy. However, the impact of these agents on the liver parenchyma itself, and their effects on clinical outcomes following hepatic resection remain unclear. This review identifies patterns of regimen-specific chemotherapy-induced hepatic injury and assesses their impact on outcomes following hepatic resection for colorectal liver metastases (CLM).


METHODS
An electronic search was performed using the MEDLINE (US Library of Congress) database from 1966 to May 2007 to identify relevant articles related to chemotherapy-induced hepatic injury and subsequent outcome following hepatic resection.


RESULTS
The use of the combination of 5-flourouracil and leucovorin is linked to the development of hepatic steatosis, and translates into increased postoperative infection rates. A form of non-alcoholic steatohepatitis (NASH) related to chemotherapy and otherwise known as chemotherapy-associated steatohepatitis (CASH) is closely linked to irinotecan-based therapy and is associated with inferior outcomes following hepatic surgery mainly due to hepatic insufficiency and poor regeneration. Data on sinusoidal obstruction syndrome (SOS) following treatment with oxaliplatin are less convincing, but there appears to be an increased risk for intra-operative bleeding and decreased hepatic reserve associated with the presence of SOS. Intra-arterial floxuridine therapy damages the extrahepatic biliary tree in addition to causing parenchymal liver damage, and has been shown to be associated with increased morbidity after hepatic resection.


CONCLUSIONS
Agent-specific patterns of damage are now being recognized with increasing use of neoadjuvant chemotherapy prior to surgery. The potential benefits and risks of these should be considered on an individual patient basis prior to hepatic resection.
Khan
Aamir Z
AZ
Royal Marsden Hospital, Fulham Road, London, UK. aamirzkhan@yahoo.com
Morris-Stiff
Gareth
G
Makuuchi
Masatoshi
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000473:pathology*; D003131:Combined Modality Therapy; D005234:Fatty Liver / Q000139:chemically induced*; D005467:Floxuridine / Q000009:adverse effects; D005472:Fluorouracil / Q000009:adverse effects; D006498:Hepatectomy; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced*; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000009:adverse effects; D008099:Liver / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary* / Q000601:surgery; D020360:Neoadjuvant Therapy / Q000009:adverse effects*; D009944:Organoplatinum Compounds / Q000009:adverse effects; D000077150:Oxaliplatin; D012307:Risk Factors
D009944:Organoplatinum Compounds; D005467:Floxuridine; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin