Department of Surgery, Medical University of Vienna, Vienna, Austria.
Ann Surg Oncol. 2011 Feb;18(2):421-30. doi: 10.1245/s10434-010-1317-4. Epub 2010 Sep 16.
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.
化疗引起的肝损伤是接受结直肠肝转移手术患者的一个重要问题,因为术后发病率和死亡率增加。我们研究了肝损伤是否对这些患者的长期预后有进一步的影响。
对 196 例因结直肠肝转移而行切除术的患者的肝标本进行了非肿瘤性肝组织中与化疗相关的肝损伤评估。损伤模式与无复发生存(RFS)和总生存(OS)相关。确定导致窦状损伤的因素。
发生 2 级或 3 级窦状扩张的患者 RFS(风险比 [HR] 2.05;95%置信区间 [95%CI] 1.23-3.39,P =.005)和 OS(HR 2.90;95%CI 1.61-6.19,P <.001)明显缩短,与无此改变的患者相比。这些患者的肝内复发也明显更多(66.7% vs 30.5%,P =.003)。其他与化疗相关的肝损伤模式(非酒精性脂肪性肝炎、纤维化)与生存率降低无关。表明窦状损伤的因素包括奥沙利铂为基础的化疗、肿瘤大小>5cm、碱性磷酸酶或γ-谷氨酰转移酶升高。
奥沙利铂为基础的化疗引起的窦状阻塞综合征不仅可能影响围手术期的结果,而且可能导致早期复发和长期生存降低。显然需要制定预防这种情况的策略。