结直肠癌肝转移患者的临床表现及预后关联因素研究

Clinical manifestations and prognostic factors in patients with liver metastasis of colorectal cancer

  • 摘要:
      背景  在结直肠癌患者中,约50%患者在疾病发展过程中发生结直肠癌肝转移(colorectal liver metastases,CLM)且预后往往较差。肝转移灶同步切除可提高CLM患者预后水平。
      目的  探讨CLM患者临床特征及预后的关联因素。
      方法  回顾性分析2015年4月 - 2019年3月就诊于解放军总医院第一医学中心,诊断为同时性结直肠癌肝转移并行同期根治性切除术的患者,收集相关临床、原发灶及肝转移灶病理等资料,并对患者进行随访。根据患者肝转移灶分布位置,将患者分为单侧肝转移组及双侧肝转移组。通过单因素分析及Cox回归分析CLM患者术后预后的独立影响因素,并绘制Kaplan-Meier曲线比较患者术后总生存期(overall survival,OS)。
      结果  共纳入符合条件患者157例,其中男性100例,女性57例,年龄31 ~ 82岁。按照转移灶位置分为单侧肝转移组和双侧肝转移组,利用倾向评分匹配方法对两组患者进行匹配,共成功匹配31组。双侧肝转移组患者肝转移灶数目>3的比例显著高于单侧肝转移组(51.6% vs 9.7%,P<0.05),而OS 19.00(13.0,37.0)个月 vs 38.00(20.0,48.0)个月、3年生存率(29.0% vs 54.8%)显著低于单侧肝转移组(P<0.05)。单因素分析显示,原发肿瘤位于右半结肠、原发肿瘤低分化、双侧肝转移、肝转移灶数目>3、术前癌胚抗原(carcinoembryonic antigen,CEA)>10 ng/mL对CLM患者术后预后的影响差异显著(P<0.05)。多因素分析显示,原发肿瘤位于右半结肠(HR=4.067, 95% CI:1.738 ~ 9.516,P=0.001)、分化程度为低分化(HR=2.482,95% CI:1.280 ~ 4.812,P=0.007)、双侧肝转移(HR=2.263,95% CI:1.008 ~ 5.079,P=0.048)、术前CEA>10 ng/mL (HR=2.230,95% CI:1.048 ~ 4.747,P=0.037)、术前CA199>27 ng/mL (HR=2.049,95% CI:1.008 ~ 4.166,P=0.048)均为影响患者预后的相关危险因素。
      结论  双侧肝转移的CLM患者肝转移灶数量相对更多、OS及3年生存率相对较低。原发肿瘤位于右半结肠、原发肿瘤低分化、双侧肝转移、术前CEA>10 ng/mL、术前CA199>27 ng/mL是影响CLM患者预后的相关危险因素。

     

    Abstract:
      Background   About 50% of patients with colorectal cancer may develop colorectal liver metastases (CLM) during the course of the disease, and their prognosis are often poor. Simultaneous liver resection according to the anatomical location of liver metastases can improve the prognosis of CLM patients.
      Objective   To investigate the clinical features and prognostic factors of CLM patients.
      Methods   A retrospective analysis was performed on patients diagnosed with synchronous liver metastasis of colorectal cancer and underwent simultaneous radical resection surgery in the First Medical Center of Chinese PLA General Hospital from April 2015 to March 2019. Relevant clinical, pathological data of primary and metastatic tumor were collected, and patients with CLM were followed up. According to the location of liver metastasis, patients were divided into unilateral liver metastasis group and bilateral liver metastasis group. Univariate analysis and Cox regression were used to analyze the independent factors influencing postoperative prognosis of patients with CLM, and Kaplan-Meier curves were drawn to compare the overall survival (OS) of patients.
      Results   A total of 157 eligible patients were included, including 100 males and 57 females, with age ranging from 31 to 82 years. According to the location of metastasis, patients were divided into unilateral liver metastasis group and bilateral liver metastasis group. Propensity score matching method was used to match the two groups, and a total of 31 groups were successfully matched. The proportion of liver metastases > 3 in bilateral liver metastasis group was significantly higher than that in unilateral liver metastasis group (51.6% vs 9.7%, P < 0.05), the OS (19.0013.0-37.0 vs 38.0020.0-48.0) and 3-year survival rate (29.0% vs 54.8%) were significantly lower than those in unilateral liver metastasis group (P < 0.05). Univariate analysis showed that primary tumor located in the right colon, poorly differentiated primary tumor, bilateral liver metastasis, the number of liver metastases > 3, preoperative CEA > 10 ng/mL had significant effects on the prognosis of CLM patients (P < 0.05). Multivariate analysis showed that primary tumor located in the right colon (HR=4.067, 95% CI: 1.738-9.516, P=0.001), poorly differentiated (HR=2.482, 95% CI: 1.280-4.812, P=0.007), bilateral liver metastases (HR=2.263, 95% CI: 1.008-5.079, P=0.048), preoperative CEA > 10 ng/mL (HR=2.230, 95% CI: 1.048-4.747, P=0.037) and preoperative CA199 > 27 ng/mL (HR=2.049, 95% CI: 1.008-4.166, P=0.048) were all risk factors affecting prognosis.
      Conclusion   CLM patients with bilateral liver metastases have more liver metastases, lower OS and 3-year survival. The primary tumor located in the right colon, poorly differentiated of primary tumor, bilateral liver metastasis, preoperative CEA > 10 ng/mL, and preoperative CA199 > 27 ng/mL are related risk factors affecting the prognosis of CLM patients.

     

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