目的结直肠癌肝转移(colorectal liver metastases,CRLM)常见,半数患者在病程不同阶段会合并肝脏转移。外科手术切除仍然是让患者可能获得长期生存的唯一手段(5年生存率可达40%~67%),但仅有20%~30%的患者获得切除机会。对于那些肝内多发转移并且联合化疗、门静脉栓塞(portal vein embolization,PVE)和局部消融等治疗方案仍难以单次手术切除的患者,可考虑两步肝切除(2-stage hepatectomy,TSH)。本研究组2000年首先提出了TSH的手术方式。经过10余年的发展,该手术联合围手术期化疗和PVE,患者5年生存率可达32%~64%。然而,仍有1/3准备行TSH治疗的患者最终未能完成二期手术。其主要原因是两次手术期间出现肿瘤进展。这类患者的5年生存率显著低于完成二期手术的患者。本研究目的在于确认导致两步肝切除失败的预测因素,以更好地筛选两叶存在广泛CRLM进行TSH干预的适应证。方法自2000年至2012年,接受手术的845例CRLM患者中,125例(14.8%)准备接受TSH治疗。分析所有可能导致TSH失败的危险因素,并建立预测模型。多数患者都先行化疗,每隔4个化疗周期以CT评估病情。术中常规超声检查以确定切缘,并评估肿瘤和肝脏血管关系。消融治疗仅在肿瘤较深无法切除时才联合使用。常规进行PVE以保证可安全进行二期肝切除术。一期手术后3周恢复化疗。若肿瘤无进展且预期残存的肝再生体积达到安全性肝切除范围,可二期切除PVE栓塞的肝叶。二期手术结束后继续接受化疗。结果 44例(35.2%)患者未能接受二期手术,5年总体生存率显著低于完成TSH的患者(0%比44.2%;P<0.0001)。通过多变量回归分析发现,癌胚抗原(arcinoembryonic antigen,CEA)>30ng/m L(RR:2.73,P=0.03);肿瘤大小>40 mm(RR:2.89,P=0.04);化疗周期>12次(RR:3.46,P=0.01)以及一线化疗进展(RR:6.56,P=0.01)是TSH失败的独立危险因素。无任何危险因素的患者TSH治疗失败的比例为10.5%,5年生存率可达41.9%。具备以上1~4个危险因素且每增加1种危险因素,TSH失败可能性分别为43.5%、72.7%、88.5%及95.5%。对应的5年生存率则分别递减至38.8%、29.2%、0%和0%。结论患者血清CEA水平、肿瘤大小、化疗次数和一期化疗反应等4个危险因素有助于筛选合适的两部肝切除患者。当患者存在超过2个危险因素时,应视为TSH的禁忌证。由于联合肝脏分割和门静脉结扎的分阶段肝切除术(associating liver partition and portal ligation for staged hepatectomy,ALPPS)可避免二期肝切除失败,当患者存在2个以上危险因素时,是否应进行ALPPS需要进一步验证。 Purpose Colorectal cancer metastasis (colorectal liver metastases, CRLM) common, half of patients in different stages of disease will be associated with liver metastases. Surgical resection is still the only way for patients to obtain long-term survival (5-year survival rate of 40% to 67%), but only 20% to 30% of patients get the chance of resection. Two-stage hepatectomy (TSH) may be considered for patients with multiple intrahepatic metastases who may not have a single surgically treated regimen such as combined chemotherapy, portal vein embolization (PVE), and local ablation. This research group first proposed the operation way of TSH in 2000. After more than 10 years of development, the operation combined with perioperative chemotherapy and PVE, the 5-year survival rate of patients up to 32% to 64%. However, one third of patients who are scheduled for TSH have failed to complete the second phase of surgery. The main reason is the tumor progression during the two surgeries. The 5-year survival rates of these patients were significantly lower than those who completed the second phase of surgery. The aim of this study was to identify predictors of failed two-step hepatectomy to better screen for indications of TSH intervention with extensive CRLM in both leaves. Methods From 2000 to 2012, out of 845 CRLM patients undergoing surgery, 125 (14.8%) were scheduled for TSH. Analyze all possible risk factors for TSH failure and establish predictive models. Most patients are treated with chemotherapy, CT every four cycles of chemotherapy to assess the condition. Intraoperative routine ultrasound to determine the margins and to assess tumor and liver vascular relationships. Ablation therapy is only used when the tumor can not be removed. PVE routine to ensure safe for two hepatectomy. Three weeks after surgery, chemotherapy was resumed. If the tumor is not progressing and the expected residual liver regeneration volume reaches the range of safe hepatic resection, the hepatic lobe of PVE embolization can be resected in two phases. After the second phase of surgery continue to receive chemotherapy. RESULTS: Forty-four patients (35.2%) were unable to undergo stage II surgery and had a 5-year overall survival significantly lower than those who completed TSH (0% vs 44.2%; P <0.0001). Multivariate regression analysis showed that CEA> 30ng / m L (RR: 2.73, P = 0.03), tumor size> 40 mm (RR: 2.89, P = 0.04) (RR: 3.46, P = 0.01) and progression of first-line chemotherapy (RR: 6.56, P = 0.01) were independent risk factors for TSH failure. In patients without any risk factor, the rate of TSH failure was 10.5% and the 5-year survival rate was 41.9%. With more than 1 to 4 risk factors and one additional risk factor for each, the probability of TSH failure is 43.5%, 72.7%, 88.5% and 95.5%, respectively. The corresponding 5-year survival rates decreased to 38.8%, 29.2%, 0% and 0% respectively. Conclusions The four risk factors of serum CEA level, tumor size, the number of chemotherapy and the first-stage chemotherapy response are helpful to screen the suitable two-stage hepatectomy patients. When patients have more than two risk factors, TSH should be considered a contraindication. Due to the association of liver partition and portal ligation for staged hepatectomy (ALPPS) to avoid failed secondary hepatectomy, whether patients should have ALPPS need further if patients have more than two risk factors verification.