结直肠癌肝转移患者的临床表现及预后关联因素研究

冯子夜; 李松岩; 滕达; 胡时栋; 刘帛岩; 杨星朋; 杜晓辉

doi:10.3969/j.issn.2095-5227.2023.04.003

结直肠癌肝转移患者的临床表现及预后关联因素研究

doi: 10.3969/j.issn.2095-5227.2023.04.003

解放军总医院第一医学中心普通外科，北京　100853

基金项目: 国家自然科学基金项目(81871317)

详细信息

作者简介:
冯子夜，男，在读硕士，医师。研究方向：胃肠道肿瘤。Email: fzy18019090102@163.com

通讯作者:
杜晓辉，男，博士，主任医师，博士生导师。Email: duxiaohui301@sina.com

中图分类号: R735.34
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出版历程
- 收稿日期: 2022-07-15
- 网络出版日期: 2023-03-23
- 刊出日期: 2023-04-28

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

Department of General Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing 100853, China

More Information

Corresponding author: DU Xiaohui. Email: duxiaohui301@sina.com

摘要

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。
- 结直肠癌 /
- 肝转移 /
- 肝切除术 /
- 位置 /
- 预后
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 (19.00[13.0-37.0] vs 38.00[20.0-48.0]) 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.
- colorectal cancer /
- liver metastasis /
- hepatectomy /
- location /
- prognosis

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图 1 根据独立危险因素比较肝切除术后总生存期的Kaplan-Meier曲线

A：原发肿瘤位置；B：分化程度；C：肝转移灶分布位置；D：CEA水平；E：CA199水平

Figure 1. Kaplan Meier curve for comparing overall survival after hepatectomy based on independent risk factors

A: Location of primary tumor; B: Differentiated; C: Location of metastases; D: CEA level; E: CA199 level

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表 1 两组患者基本资料及临床资料比较

Table 1. Comparison of basic and clinical data between the two groups

指标	单侧	双侧	χ²/t/U值	P值
性别(女/男)/例	11/20	14/17	0.603	0.437
年龄/岁	58.16 ± 12.1	57.16 ± 8.945	0.137	0.713
手术时间/[min，Md(IQR)]	250.00 (200.0，355.0)	270.00 (210.0，365.0)	0.009	0.925
出血量/[mL，Md(IQR)]	200.00 (100.0，300.0)	200.00 (100.0，300.0)	0.641	0.426
新辅助治疗/(例，%)			0.065	0.799
否	17(54.8)	16(51.6)
是	14(45.2)	15(48.4)
术后化疗/(例，%)			0.097	0.755
否	7(22.6)	6(19.4)
是	24(77.4)	25(80.6)
原发灶位置/(例，%)			0.995	0.319
右半结肠	4(12.9)	7(22.6)
左半结肠	27(87.1)	24(77.4)
原发肿瘤直径/(例，%)			0.076	0.783
＜5 cm	22(71.0)	21(67.7)
≥5 cm	9(29.0)	10(32.3)
分化程度/(例，%)			0.082	0.960
低分化	8(25.8)	9(29.0)
中分化	22(71.0)	21(67.7)
高分化	1(3.2)	1(3.3)
T分期/(例，%)			0.076	0.783
T2 ~ T3	22(71.0)	21(67.7)
T4	9(29.0)	10(32.3)
淋巴结转移/(例，%)			0.632	0.729
N0	8(25.8)	9(29.0)
N1	13(41.9)	10(32.3)
N2	10(32.3)	12(38.7)
癌栓/(例，%)			2.080	0.149
否	24(77.4)	29(93.5)
存在	7(22.6)	2(6.5)
癌结节/(例，%)			1.653	0.199
否	23(74.2)	27(87.1)
存在	8(25.8)	4(12.9)
转移灶数目/(例，%)			12.825	＜0.001
≤3	28(90.3)	15(48.4)
＞3	3(9.7)	16(51.6)
转移灶直径/(例，%)			2.199	0.138
＜5 cm	26(83.9)	21(67.7)
≥5 cm	5(16.1)	10(32.3)
转移灶切除术式/(例，%)			2.323	0.316
挖除	21(67.7)	26(83.9)
段切除	7(22.6)	3(9.6)
半肝切除	3(9.7)	2(6.5)
CEA/(例，%)			0.069	0.793
≤10 ng·mL^-1	11(35.5)	12(38.7)
＞10 ng·mL^-1	20(64.5)	19(61.3)
CA199/(例，%)			1.640	0.200
≤27 ng·mL^-1	11(35.5)	16(51.6)
＞27 ng·mL^-1	20(64.5)	15(48.4)
总生存期/[月，Md(IQR)]	38.00 (20.0，48.0)	19.00 (13.0，37.0)	11.195	0.001
3年生存/(例，%)			4.239	0.039
否	14(45.2)	22(71.0)
是	17(54.8)	9(29.0)

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表 2 总生存期预后因素的单因素分析

Table 2. Univariate analysis of prognostic factors on overall survival

指标	例数	3年总生存率/%	95% CI	χ²值	P值
性别				1.739	0.187
男	37	45.9	29.7 ~ 45.6
女	25	36.0	20.7 ~ 39.0
年龄				0.163	0.686
＜60岁	35	42.9	25.8 ~ 38.6
≥60岁	27	40.7	26.4 ~ 49.3
新辅助治疗				0.020	0.886
是	29	37.9	25.6 ~ 44.7
否	33	45.5	25.8 ~ 42.2
术后化疗				0.548	0.459
是	49	42.9	28.9 ~ 43.8
否	13	38.5	17.9 ~ 35.6
原发肿瘤位置				4.482	0.034
左半结肠	51	47.1	30.6 ~ 44.7
右半结肠	11	18.2	9.6 ~ 31.5
原发肿瘤直径				0.649	0.420
＜5 cm	43	46.5	28.9 ~ 42.0
≥5 cm	19	31.6	18.5 ~ 45.8
分化程度				6.861	0.009
低分化	17	23.5	14.1 ~ 32.0
中-高分化	45	48.9	32.1 ~ 48.6
T分期				0.007	0.934
T2 ~ T3	44	43.2	26.7 ~ 41.9
T4	18	38.9	22.7 ~ 45.3
淋巴结转移				0.161	0.688
N0	17	47.1	24.3 ~ 46.4
N1 ~ N2	45	40.0	27.1 ~ 42.7
癌栓				0.608	0.435
存在	9	22.2	12.9 ~ 42.6
否	53	45.3	28.8 ~ 42.8
癌结节				0.146	0.702
存在	12	41.7	22.7 ~ 48.8
否	50	42.0	26.7 ~ 40.9
肝转移灶分布位置				7.783	0.005
双侧	31	29.0	18.8 ~ 29.7
单侧	31	54.8	34.2 ~ 53.8
肝转移灶数目				14.108	＜0.001
≤3	43	53.5	33.4 ~ 50.2
＞3	19	15.8	14.7 ~ 24.0
肝转移灶直径				0.186	0.666
＜5 cm	47	40.4	27.3 ~ 42.1
≥5 cm	15	46.7	22.4 ~ 41.4
CEA				5.362	0.021
≤10 ng·mL^-1	23	60.9	34.0 ~ 56.1
＞10 ng·mL^-1	39	30.8	21.4 ~ 35.1
CA199				3.639	0.056
≤27 ng·mL^-1	27	55.6	31.2 ~ 50.2
＞27 ng·mL^-1	35	31.4	21.9 ~ 36.8

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表 3 总生存期预后因素的多因素分析

Table 3. Multivariate analysis of prognostic factors on overall survival

关联因素	赋值	HR	95% CI	P值
原发灶位置	1=右半结肠，0=左半结肠	4.067	1.738 ~ 9.516	0.001
分化程度	1=低分化，0=中-高分化	2.482	1.280 ~ 4.812	0.007
肝转移灶分布位置	1=双侧，0=单侧	2.263	1.008 ~ 5.079	0.048
转移灶数目	1=＞3，0=≤3	1.411	0.607 ~ 3.281	0.424
CEA	1=＞10 ng·mL^-1，0=≤10 ng·mL^-1	2.230	1.048 ~ 4.747	0.037
CA199	1=＞27 ng·mL^-1，0=≤27 ng·mL^-1	2.049	1.008 ~ 4.166	0.048

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