Hepatotoxicities Induced by Neoadjuvant Chemotherapy in Colorectal Cancer Liver Metastases: Distinguishing the True From the False.

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 ( = .01), pre-operative platelets <150 g/L ( = .04), and aspartate aminotransferase to platelet ratio index (APRI) score >0.36 ( = .02). Steatohepatitis was observed in 15 patients (10.2%), more frequently after irinotecan (14.8% vs 3.4%,  = .01; odds ratio [OR] = 7.3; 95% confidence interval [CI] = [1.5-34.7]), and for patients with body mass index (BMI) >25 kg/m (= .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.