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Liver Histology and Surgical Outcomes After Preoperative Chemotherapy With Fluorouracil Plus Oxaliplatin in Colorectal Cancer Liver Metastases

Thomas Aloia, Mylène Sebagh, Marylène Plasse, Vincent Karam, Francis Lévi, Sylvie Giacchetti, Daniel Azoulay, Henri Bismuth, Denis Castaing, René Adam

From the Departments of Hepatobiliary Surgery and Liver Transplantation, Pathology, and the Institut National de la Santé et de la Recherche Médicale, Chronotherapy Unit, Paul-Brousse Hospital, Villejuif, France; and Department of Hepatobiliary Surgery and Liver Transplantation, Hôpital St Luc, Montréal, Québec, Canada

Address reprint requests to René Adam, MD, PhD, Paul-Brousse Hospital, 12 Avenue Paul Vaillant Couturier, Villejuif, France 94800; e-mail: rene.adam{at}pbr.ap-hop-paris.fr

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 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.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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