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[双侧多发性结直肠癌肝转移患者肝切除术后的长期结局——倾向评分匹配分析]

[Long-term outcomes of patients undergoing hepatectomy for bilateral multiple colorectal liver metastases-a propensity score matching analysis].

作者信息

Bao Q, Wang K, Wang H W, Jin K M, Xing B C

机构信息

Key Laboratory of Carcinogenesis & Translational Research(Ministry of Education), First Department of Hepatopanereatobiliary Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China.

出版信息

Zhonghua Wei Chang Wai Ke Za Zhi. 2020 Oct 25;23(10):976-983. doi: 10.3760/cma.j.cn.441530-20200414-00204.

Abstract

Liver is the most common site of distant metastasis in colorectal cancer patients. Currently, surgical resection of colorectal liver metastasis (CRLM) still remains the most curative therapeutic option which is associated with long-term survival. However, the outcome of CRLM patients with bilobar multiple lesions has been reported to be extremely poor due to the complex techniques of the surgery and the difficulties to achieve a negative resection margin. In this study, postoperative long-term outcome in patients with bilobar versus unilobar multiple CRLM undergoing surgical resection were compared and the prognostic factors of CRLM were analyzed. A retrospective cohort study was performed. The clinicopathological data were collected retrospectively from patients with multiple CRLM who received liver resection between January 2002 and November 2018 at our department. Inclusion criteria: (1) All CRLM lesions were confirmed by preoperative enhanced CT or MRI and enhanced ultrasonography. (2) All CRLM lesions were resectable either initially or converted by systemic treatments. The CRLM patients were considered as resectable, if their extrahepatic diseases were able to be completely removed. (3) Sufficient remnant liver volume was required to maintain normal liver function, which was defined by the ratio of remnant liver volume to total liver volume (RLV-TLV), of greater than 30% in general or 40% for the patients undergoing chemotherapy. (4) Medical records and follow-up information were intact. Those undergoing multiple operations after recurrence, with R2 resection, or with a single CRLM lesion were excluded. Patients were divided into bilobar and unilobar group according to tumor distribution. One-to-one propensity score matching (PSM) was performed to balance the covariates between the bilobar group and unilobar group. After PSM, the differences in long-term outcomes between the two groups were compared. A total of 491 patients met the inclusion criteria, 344 (69.6%) with bilobar and 147 (30.4%) with unilobar CRLM. In the propensity-score-matched population (bilobar, 143; unilobar, 143), baseline characteristics were similar between the two groups. The 1-, 3-, and 5-year overall survival rates in the bilobar group were 91.6%, 52.1%, and 35.3% respectively, compared with 93.7%, 56.8%, and 43.8% in the unilobar group, and the difference was not statistically significant (=0.204). The 1-, 3-, and 5-year recurrence-free survival rates in the bilobar group were 45.7%, 33.7%, and 33.7% respectively, compared with 62.5%, 44.1%, and 42.1% in the unilobar group, and the difference was not statistically significant (=0.075). No significant difference was found in liver-only recurrence (45.6% in bilobar vs. 53.3% in unilobar, =0.543). Univariate analysis showed that N stage of primary tumor, diameter of the largest liver metastases, carcinoembyonic antigen level, RAS gene status and clinical risk score (CRS) were significantly associated with the prognosis of CRLM (all <0.05). Multivariate analysis indicated that diameter of largest liver metastases > 5 cm (HR=1.888, 95% CI: 1.251-2.848, =0.002), CRS≥3 (HR=1.552,95% CI:1.050-2.294, =0.027) and RAS gene mutation (HR=1.561, 95% CI: 1.102-2.212, =0.012) were independent risk factors of poor overall survival after hepatectomy. Tumor distribution may not affect the prognosis of multiple CRLM after resection. Surgical removal in patients with bilobar multiple CRLM provides comparable long-term survival to unilobar multiple CRLM.

摘要

肝脏是结直肠癌患者远处转移最常见的部位。目前,结直肠癌肝转移(CRLM)的手术切除仍然是最具治愈性的治疗选择,与长期生存相关。然而,据报道,由于手术技术复杂且难以实现阴性切缘,双叶多发CRLM患者的预后极差。在本研究中,比较了接受手术切除的双叶与单叶多发CRLM患者的术后长期预后,并分析了CRLM的预后因素。进行了一项回顾性队列研究。回顾性收集2002年1月至2018年11月在我科接受肝切除的多发CRLM患者的临床病理资料。纳入标准:(1)所有CRLM病灶均经术前增强CT或MRI及增强超声检查确诊。(2)所有CRLM病灶最初均可切除或经全身治疗后可转化为可切除。如果肝外疾病能够完全切除,则CRLM患者被认为是可切除的。(3)需要足够的残余肝体积以维持正常肝功能,残余肝体积与全肝体积之比(RLV-TLV)一般大于30%,接受化疗的患者大于40%。(4)病历和随访信息完整。排除复发后接受多次手术、R2切除或单发CRLM病灶的患者。根据肿瘤分布将患者分为双叶组和单叶组。进行一对一倾向评分匹配(PSM)以平衡双叶组和单叶组之间的协变量。PSM后,比较两组的长期预后差异。共有491例患者符合纳入标准,其中双叶CRLM患者344例(69.6%),单叶CRLM患者147例(30.4%)。在倾向评分匹配人群中(双叶组143例,单叶组143例),两组的基线特征相似。双叶组的1年、3年和5年总生存率分别为91.6%、52.1%和35.3%,单叶组分别为93.7%、56.8%和43.8%,差异无统计学意义(P=0.204)。双叶组的1年、3年和5年无复发生存率分别为45.7%、33.7%和33.7%,单叶组分别为62.5%、44.1%和42.1%,差异无统计学意义(P=0.075)。仅肝内复发方面未发现显著差异(双叶组为45.6%,单叶组为53.3%,P=0.543)。单因素分析显示,原发肿瘤的N分期、最大肝转移灶直径、癌胚抗原水平、RAS基因状态和临床风险评分(CRS)与CRLM的预后显著相关(均P<0.05)。多因素分析表明,最大肝转移灶直径>5 cm(HR=1.888,95%CI:1.251-2.848,P=0.002)、CRS≥3(HR=1.552,95%CI:1.050-2.294,P=0.027)和RAS基因突变(HR=1.561,95%CI:1.102-2.212,P=0.012)是肝切除术后总体生存不良的独立危险因素。肿瘤分布可能不影响多发CRLM切除术后的预后。双叶多发CRLM患者的手术切除与单叶多发CRLM患者具有相当的长期生存率。

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