Objective: 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. Methods: 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. Results: 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 (P=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 (P=0.075). No significant difference was found in liver-only recurrence (45.6% in bilobar vs. 53.3% in unilobar, P=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 P<0.05). Multivariate analysis indicated that diameter of largest liver metastases > 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) and RAS gene mutation (HR=1.561, 95% CI: 1.102-2.212, P=0.012) were independent risk factors of poor overall survival after hepatectomy. Conclusions: 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.
目的： 肝脏是结直肠癌远处转移的常见器官，手术是目前治疗结直肠癌肝转移（CRLM）最有效的方法。对于双叶多发CRLM病灶，手术相对复杂，且容易出现阳性切缘，故手术切除的预后较差。为此，本文对双叶与单叶多发性CRLM手术切除的远期疗效进行比较，并分析CRLM预后影响因素。 方法： 采用回顾性队列研究的方法。收集北京肿瘤医院肝胆胰外一科2002年1月至2018年11月期间，手术切除的多发性CRLM患者临床病理资料。病例纳入标准：（1）经术前增强CT/MRI和超声造影检查确诊；（2）肝转移病灶经评估为可切除，或通过转化治疗获得手术机会而考虑手术切除者，同时对于合并的肝外转移灶亦可R(0)切除；（3）保留足够有功能的残余肝，原则上计划残余肝体积应≥30%，化疗后残余肝体积则至少保留40%；（4）病例资料和随访资料完整。排除复发后多次手术者、R(2)切除者和单发病灶者。根据肿瘤的分布将患者分为双叶组和单叶组，通过倾向性评分匹配（PSM）进行1:1匹配，比较匹配后两组患者的远期生存、复发情况及其影响因素。 结果： 多发性CRLM手术切除患者共491例，双叶组344例（69.6%），单叶组147例（30.4%）。PSM法评价后双叶组和单叶组CRLM各纳入143例患者。两组病例基线水平差异无统计学意义（均P>0.05）。双叶组术后1、3、5年生存率分别为91.6%、52.1%和35.3%，单叶组则分别为93.7%、56.8%和43.8%，两组差异无统计学意义（P=0.204）。双叶组术后1、3、5年无复发生存率分别为45.7%、33.7%和33.7%，单叶组则分别为62.5%、44.1%和42.1%，两组差异亦无统计学意义（P=0.075）。双叶组和单叶组患者术后单纯肝内复发率分别为45.6%（52/143）和53.3%（57/143），差异亦无统计学意义（P=0.543）。单因素生存分析结果显示，原发灶N分期、肝转移最大直径、癌胚抗原水平、RAS基因状态和临床危险评分（CRS）与CRLM的预后有关（均P<0.05）。多因素分析结果表明，肝转移最大直径>5 cm（HR=1.888，95% CI：1.251~2.848，P=0.002）、CRS≥3分（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CRLM预后的独立危险因素。 结论： 肝转移的分布不影响多发性CRLM患者手术切除的预后；双叶与单叶多发CRLM手术治疗生存获益相当。.
Keywords: Bilobar; Colorectal neoplasms; Hepatectomy; Liver metastases; Overall survival rates; Propensity score matching.