Sinusoidal Obstruction Syndrome Impairs Long-Term Outcome of Colorectal Liver Metastases Treated with Resection after Neoadjuvant Chemotherapy

Adult Aged, 80 and over Male Liver Neoplasms Hepatic Veno-Occlusive Disease Leucovorin Middle Aged Combined Modality Therapy Deoxycytidine 3. Good health 03 medical and health sciences 0302 clinical medicine Chemotherapy, Adjuvant Lymphatic Metastasis Antineoplastic Combined Chemotherapy Protocols Hepatectomy Humans Female Fluorouracil Colorectal Neoplasms Capecitabine Aged Follow-Up Studies
DOI: 10.1245/s10434-010-1317-4 Publication Date: 2010-09-15T14:28:44Z
ABSTRACT
Chemotherapy-induced liver injury is a considerable problem in patients undergoing surgery for colorectal liver metastases, since an increase in postoperative morbidity and mortality has been observed. We investigated whether liver damage had further implications on long-term outcome in these patients.Liver specimens from 196 patients resected for colorectal liver metastases were evaluated for chemotherapy-associated hepatic damage in the nontumorous liver. Injury patterns were correlated with recurrence free (RFS) and overall survival (OS). Factors leading to sinusoidal injury were identified.Patients who developed grade 2 or 3 sinusoidal dilatation had a significantly shorter RFS (hazard ratio [HR] 2.05; 95% confidence interval [95% CI] 1.23-3.39, P = .005) and OS (HR 2.90; 95% CI 1.61-6.19, P < .001), compared to patients without this alteration. Those patients also had significantly more intrahepatic recurrences (66.7% vs 30.5%, P = .003). Other patterns of chemotherapy-associated liver damage (nonalcoholic steatohepatitis, fibrosis) were not associated with impaired survival. Factors indicating sinusoidal injury were oxaliplatin-based chemotherapy, tumor size >5 cm, and elevated alkaline phosphatase or gamma glutamyltransferase.Sinusoidal obstruction syndrome due to oxaliplatin-based chemotherapy may not only compromise perioperative outcome, but can lead to early recurrence and decreased survival in the long term. Strategies to prevent this condition are clearly needed.
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