Liver histology and surgical outcomes after preoperative chemotherapy with fluorouracil plus oxaliplatin in colorectal cancer liver metastases.
OBJECTIVE
Preoperative chemotherapy for colorectal liver metastases (CLM) can produce histologic changes in the nontumor-bearing liver (NTBL) that may impact on surgical outcomes.


METHODS
From a cohort of 303 patients treated for CLM with liver resection, 92 patients (75 received preoperative chemotherapy: group C+; and 17 were chemotherapy naïve: group C-) were randomly selected for detailed pathologic analysis. Preoperative chemotherapy consisted of fluorouracil (FU)/leucovorin alone (23 patients, the majority chronomodulated) or in combination with oxaliplatin (52 patients, all chronomodulated). To determine associations between study factors, clinical and operative variables were compared with pathology data and surgical outcomes.


RESULTS
Although clinical and operative factors were similarly distributed, C+ patients, compared with C- patients, were more likely to receive intraoperative RBC transfusions (mean units: 1.9 v 0.5, respectively; P = .03) and to have vascular abnormalities in the NTBL (52% v 18%, respectively; P = .01). Presence of the most severe forms of vascular alterations was closely associated with RBC transfusion requirements (P = .04). In contrast, moderate to severe steatosis was similarly distributed (C- group, 12%; C+ group, 13%). Although perioperative mortality and morbidity rates were similar in all groups, more than 12 courses of chemotherapy, compared with < or = 12 courses, predisposed patients to reoperation (11% v 0%, respectively; P = .04) and to longer hospitalization (15 v 11 days, respectively; P = .02).


CONCLUSIONS
The main hepatic lesion induced by preoperative FU/oxaliplatin chemotherapy in patients with CLM is vascular and not steatosis. Detailed pathologic analysis determined that the most severe vascular lesions are associated with increased intraoperative transfusions. The risk for other postoperative complications is related to the duration of preoperative chemotherapy administration.
Aloia
Thomas
T
Department of Hepatobiliary Surgery and Liver Transplantation, Paul-Brousse Hospital, Villejuif, France.
Sebagh
Mylène
M
Plasse
Marylène
M
Karam
Vincent
V
Lévi
Francis
F
Giacchetti
Sylvie
S
Azoulay
Daniel
D
Bismuth
Henri
H
Castaing
Denis
D
Adam
René
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000473:pathology*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006498:Hepatectomy; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy / Q000379:methods; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil