Division of Pathology, Geneva University Hospital, Geneva, Switzerland.
Histopathology. 2010 Mar;56(4):430-9. doi: 10.1111/j.1365-2559.2010.03511.x.
Because of its efficacy, oxaliplatin (OX) is increasingly used as a chemotherapeutic agent in the treatment of colorectal liver metastases (CRLM). Oxaliplatin-associated liver toxicity has been reported and can affect clinical practice, but studies on its prevalence and a full pathological description are lacking. The aims of this study were to fill this gap by providing, from a pathologist's perspective, a detailed assessment of the spectrum of hepatic lesions associated with OX, to suggest a scoring system to quantify them, and to investigate the protective effect of bevacizumab against OX-associated damage.
The spectrum of oxaliplatin-associated liver lesions was investigated in a multi-institutional series of surgically resected CRLM (n = 385). Among 274 patients treated by OX, 54% had moderate/severe sinusoidal obstruction syndrome (SOS). Peliosis, centrilobular perisinusoidal/venular fibrosis and nodular regenerative hyperplasia (NRH) developed in 10.6%, 47% and 24.5%, respectively. The 111 patients treated by surgery alone had no lesions. Hepatic lesions were less severe in patients treated with OX/bevacizumab (n = 70) compared with the group treated by OX alone (n = 204), with an incidence of moderate/severe SOS (31.4% versus 62.2%), peliosis (4.3% versus 14.6%), NRH (11.4% versus 28.9%, respectively) and centrilobular/venular fibrosis (31.4% versus 52%, respectively) (P < 0.001).
Pathologists should be aware of the distinctive lesions associated with OX and of their high prevalence. OX-related lesions are less frequent in patients treated with bevacizumab, suggesting that this drug has a preventive effect. Uniform criteria for diagnosis and grading of OX-associated lesions should help to include histological data in the optimal multidisciplinary management of CRLM.
奥沙利铂（OX）因其疗效，在结直肠癌肝转移（CRLM）的治疗中越来越多地被用作化疗药物。已有报道称奥沙利铂相关的肝毒性会影响临床实践，但缺乏关于其流行率和全面病理描述的研究。本研究的目的是从病理学家的角度提供对与 OX 相关的肝损伤谱的详细评估，提出量化这些损伤的评分系统，并研究贝伐单抗对 OX 相关损伤的保护作用。
对多机构手术切除的 CRLM （n = 385）系列进行了奥沙利铂相关肝损伤谱的研究。在 274 例接受 OX 治疗的患者中，54%出现中度/重度窦状隙阻塞综合征（SOS）。Peliosis、中央小叶周围窦周/静脉纤维化和结节性再生性增生（NRH）分别在 10.6%、47%和 24.5%的患者中发生。单独接受手术治疗的 111 例患者没有病变。与单独接受 OX 治疗的患者（n = 204）相比，接受 OX/贝伐单抗治疗的患者（n = 70）的肝损伤较轻，中度/重度 SOS（31.4%对 62.2%）、Peliosis（4.3%对 14.6%）、NRH（11.4%对 28.9%）和中央小叶/静脉纤维化（31.4%对 52%）的发生率均较低（P < 0.001）。
病理学家应了解与 OX 相关的独特病变及其高发病率。与接受贝伐单抗治疗的患者相比，接受 OX 治疗的患者发生 OX 相关病变的频率较低，这表明该药物具有预防作用。用于 OX 相关病变诊断和分级的统一标准将有助于在 CRLM 的最佳多学科管理中纳入组织学数据。
