Liver histology and surgical outcomes after preoperative chemotherapy with fluorouracil plus oxaliplatin in colorectal cancer liver metastases

Abstract

Purpose: Preoperative chemotherapy for colorectal liver metastases (CLM) can produce histologic changes in the nontumor-bearing liver (NTBL) that may impact on surgical outcomes.

Patients and 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).

Conclusion: 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.