Desjardin Marie, Bonhomme Benjamin, Le Bail Brigitte, Evrard Serge, Brouste Véronique, Desolneux Gregoire, Fonck Marianne, Bécouarn Yves, Béchade Dominique
Digestive Tumours Unit, Institut Bergonié, Bordeaux, France.
Department of Anatomopathology, Institut Bergonié, Bordeaux, France.
Clin Med Insights Oncol. 2019 Jan 22;13:1179554918825450. doi: 10.1177/1179554918825450. eCollection 2019.
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 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.
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).
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.
结直肠癌肝转移（CRLM）的术前化疗被认为是非肿瘤实质肝毒性的原因。关于肝毒性的研究结果相互矛盾。我们研究了由一位肝脏胰腺胆管病理专家分析的一线术前化疗对非肿瘤肝脏的影响，以及对手术结果的影响。
回顾性纳入接受CRLM手术且仅接受一线术前化疗的患者。进行了两项比较性组织病理学分析，以评估血管毒性和脂肪性肝炎。
2003年至2015年期间，共纳入147例患者。化疗方案以奥沙利铂（40.）、伊立替康（55.8%）或两者联合（4.1%）为主。专家病理学家描述了38.8%的血管病变，包括扩张、结节状再生和紫癜。多因素分析显示，血管病变与男性（P = 0.01）、术前血小板<150 g/L（P = 0.04）以及天冬氨酸转氨酶与血小板比值指数（APRI）评分>0.36（P = 0.02）相关。15例患者（10.2%）出现脂肪性肝炎，伊立替康治疗后更为常见（14.8%对3.4%，P = 0.01；比值比[OR]=7.3；95%置信区间[CI]=[1.5 - 34.7]），且体重指数（BMI）>25 kg/m²的患者更易发生（P = 0.004；OR = 10.0；95% CI = [2.1 - 47.5]）。共有29例患者（19.7%）发生严重并发症，有两个危险因素：门静脉阻塞（PVO）和感染性手术。两位病理学家对脂肪性肝炎和扩张性病变的重复性评估显示一致性中等（Kappa评分分别为0.53和0.54）。
非酒精性脂肪性肝炎（NASH）与伊立替康之间可能存在关联。奥沙利铂似乎会导致更高的血管病变发生率。除了存在既往合并症外，肝毒性不应限制在保留实质的手术前使用术前化疗。
