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Chemotherapy Regimen Predicts Steatohepatitis and an Increase in 90-Day Mortality After Surgery for Hepatic Colorectal Metastases

Jean-Nicolas Vauthey, Timothy M. Pawlik, Dario Ribero, Tsung-Teh Wu, Daria Zorzi, Paulo M. Hoff, Henry Q. Xiong, Cathy Eng, Gregory Y. Lauwers, Mari Mino-Kenudson, Mauro Risio, Andrea Muratore, Lorenzo Capussotti, Steven A. Curley, Eddie K. Abdalla

From the Departments of Surgical Oncology, Pathology, and Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX; Department of Pathology; Massachusetts General Hospital, Boston, MA; and Departments of Pathology and Surgical Oncology, Istituto per la Ricerca e la Cura del Cancro, Torino, Italy.

Address reprint requests to Jean-Nicolas Vauthey, MD, Department of Surgical Oncology, Unit 444, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030-4009; e-mail: jvauthey{at}mdanderson.org

PURPOSE: Chemotherapy before resection of hepatic colorectal metastases (CRM) may cause hepatic injury and affect postoperative outcome.

PATIENTS AND METHODS: Four hundred six patients underwent hepatic resection of CRM between 1992 and 2005. Pathologic review of the nontumorous liver was performed using established criteria for steatosis, steatohepatitis, and sinusoidal injury. The effect of chemotherapy and liver injury on perioperative outcome was analyzed.

RESULTS: One hundred fifty-eight patients (38.9%) received no preoperative chemotherapy, whereas 248 patients (61.1%) did. The median duration of chemotherapy was 16 weeks (range, 2 to 70 weeks). Chemotherapy consisted of fluoropyrimidine-based regimens (fluorouracil [FU] alone, 15.5%; irinotecan plus FU, 23.1%; and oxaliplatin plus FU, 19.5%) and other therapy (3.0%). On pathologic analysis, 36 patients (8.9%) had steatosis, 34 (8.4%) had steatohepatitis, and 22 (5.4%) had sinusoidal dilation. Oxaliplatin was associated with sinusoidal dilation compared with no chemotherapy (18.9% v 1.9%, respectively; P < .001; odds ratio [OR] = 8.3; 95% CI, 2.9 to 23.6). In contrast, irinotecan was associated with steatohepatitis compared with no chemotherapy (20.2% v 4.4%, respectively; P < .001; OR = 5.4; 95% CI, 2.2 to 13.5). Patients with steatohepatitis had an increased 90-day mortality compared with patients who did not have steatohepatitis (14.7% v 1.6%, respectively; P = .001; OR = 10.5; 95% CI, 2.0 to 36.4).

CONCLUSION: Steatohepatitis is associated with an increased 90-day mortality after hepatic surgery. In patients with hepatic CRM, the chemotherapy regimen should be carefully considered because the risk of hepatotoxicity is significant.

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

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