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- Title
Hepatotoxicities Induced by Neoadjuvant Chemotherapy in Colorectal Cancer Liver Metastases: Distinguishing the True From the False.
- Authors
Desjardin, Marie; Bonhomme, Benjamin; Le Bail, Brigitte; Evrard, Serge; Brouste, Véronique; Desolneux, Gregoire; Fonck, Marianne; Bécouarn, Yves; Béchade, Dominique
- Abstract
Background: Pre-operative chemotherapy for colorectal liver metastasis (CRLM) is thought to be the cause of hepatotoxicity of non-tumoural parenchyma. Studies on hepatotoxicity are contradictory. We investigated the impact of a single-line pre-operative chemotherapy on non-tumoural liver analysed by an expert hepatico-pancreatico-biliary pathologist, and the consequences on surgical outcomes. Patients and methods: Patients operated for CRLM, after a pure first-line pre-operative chemotherapy, were retrospectively included. Two comparative histopathological analyses were performed for vascular toxicity and steatohepatitis. Results: Between 2003 and 2015, 147 patients were included. Chemotherapy was based on oxaliplatin (40.1%), irinotecan (55.8%), or both (4.1%). The expert pathologist described 38.8% of vascular lesions including dilation, nodular regeneration, and peliosis. In multivariate analysis, vascular lesions correlated to male sex (P =.01), pre-operative platelets <150 g/L (P =.04), and aspartate aminotransferase to platelet ratio index (APRI) score >0.36 (P =.02). Steatohepatitis was observed in 15 patients (10.2%), more frequently after irinotecan (14.8% vs 3.4%, P =.01; odds ratio [OR] = 7.3; 95% confidence interval [CI] = [1.5-34.7]), and for patients with body mass index (BMI) >25 kg/m2 (P =.004; OR = 10.0; 95% CI = [2.1-47.5]). A total of 29 patients (19.7%) developed major complications with 2 risk factors: portal vein obstruction (PVO) and septic surgery. Reproducibility assessment of steatohepatitis and dilated lesions by 2 pathologists showed moderate agreement (Kappa score 0.53 and 0.54, respectively). Conclusions: There is a probable association between non-alcoholic steatohepatitis (NASH) and irinotecan. Oxaliplatin seems to lead to higher vascular lesions. Except in the presence of pre-existent comorbidities, liver toxicities should not restrain the use of pre-operative chemotherapy prior to parenchymal-sparing surgery.
- Subjects
HEPATOTOXICOLOGY -- Risk factors; ASPARTATE aminotransferase; BLOOD platelets; VASCULAR diseases; CHI-squared test; COLON tumors; COMBINED modality therapy; CONFIDENCE intervals; DRUG toxicity; FATTY liver; FISHER exact test; LIVER diseases; METASTASIS; MULTIVARIATE analysis; PORTAL vein; RECTUM tumors; RESEARCH evaluation; SEPTIC shock; STATISTICS; BODY mass index; OXALIPLATIN; RETROSPECTIVE studies; PREOPERATIVE period; DATA analysis software; DESCRIPTIVE statistics; IRINOTECAN; ODDS ratio; MANN Whitney U Test
- Publication
Clinical Medicine Insights: Oncology, 2019, Vol 13, pN.PAG
- ISSN
1179-5549
- Publication type
Article
- DOI
10.1177/1179554918825450