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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

冯子夜, 李松岩, 滕达, 胡时栋, 刘帛岩, 杨星朋, 杜晓辉. 结直肠癌肝转移患者的临床表现及预后关联因素研究[J]. 解放军医学院学报, 2023, 44(4): 333-338. doi: 10.3969/j.issn.2095-5227.2023.04.003
引用本文: 冯子夜, 李松岩, 滕达, 胡时栋, 刘帛岩, 杨星朋, 杜晓辉. 结直肠癌肝转移患者的临床表现及预后关联因素研究[J]. 解放军医学院学报, 2023, 44(4): 333-338. doi: 10.3969/j.issn.2095-5227.2023.04.003
FENG Ziye, LI Songyan, TENG Da, HU Shidong, LIU Boyan, YANG Xingpeng, DU Xiaohui. Clinical manifestations and prognostic factors in patients with liver metastasis of colorectal cancer[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2023, 44(4): 333-338. doi: 10.3969/j.issn.2095-5227.2023.04.003
Citation: FENG Ziye, LI Songyan, TENG Da, HU Shidong, LIU Boyan, YANG Xingpeng, DU Xiaohui. Clinical manifestations and prognostic factors in patients with liver metastasis of colorectal cancer[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2023, 44(4): 333-338. 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
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

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

More Information
  • 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。

     

  • 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

    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/UP
    性别(女/男)/例11/2014/170.6030.437
    年龄/岁58.16 ± 12.157.16 ± 8.9450.1370.713
    手术时间/[min,Md(IQR)]250.00
    (200.0,355.0)
    270.00
    (210.0,365.0)
    0.0090.925
    出血量/[mL,Md(IQR)]200.00
    (100.0,300.0)
    200.00
    (100.0,300.0)
    0.6410.426
    新辅助治疗/(例,%)0.0650.799
     否17(54.8)16(51.6)
     是14(45.2)15(48.4)
    术后化疗/(例,%)0.0970.755
     否7(22.6)6(19.4)
     是24(77.4)25(80.6)
    原发灶位置/(例,%)0.9950.319
     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,%)0.0760.783
     <5 cm22(71.0)21(67.7)
     ≥5 cm9(29.0)10(32.3)
    分化程度/(例,%)0.0820.960
     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,%)0.0760.783
     T2 ~ T322(71.0)21(67.7)
     T49(29.0)10(32.3)
    淋巴结转移/(例,%)0.6320.729
     N08(25.8)9(29.0)
     N113(41.9)10(32.3)
     N210(32.3)12(38.7)
    癌栓/(例,%)2.0800.149
     否24(77.4)29(93.5)
     存在7(22.6)2(6.5)
    癌结节/(例,%)1.6530.199
     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
     ≤328(90.3)15(48.4)
     >33(9.7)16(51.6)
    转移灶直径/(例,%)2.1990.138
     <5 cm26(83.9)21(67.7)
     ≥5 cm5(16.1)10(32.3)
    转移灶切除术式/(例,%)2.3230.316
     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,%)0.0690.793
     ≤10 ng·mL-111(35.5)12(38.7)
     >10 ng·mL-120(64.5)19(61.3)
    CA199/(例,%)1.6400.200
     ≤27 ng·mL-111(35.5)16(51.6)
     >27 ng·mL-120(64.5)15(48.4)
    总生存期/[月,Md(IQR)]38.00
    (20.0,48.0)
    19.00
    (13.0,37.0)
    11.1950.001
    3年生存/(例,%)4.2390.039
     否14(45.2)22(71.0)
     是17(54.8)9(29.0)
    下载: 导出CSV

    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% CIχ2P
    性别1.7390.187
     男3745.929.7 ~ 45.6
     女2536.020.7 ~ 39.0
    年龄0.1630.686
     <60岁3542.925.8 ~ 38.6
     ≥60岁2740.726.4 ~ 49.3
    新辅助治疗0.0200.886
     是2937.925.6 ~ 44.7
     否3345.525.8 ~ 42.2
    术后化疗0.5480.459
     是4942.928.9 ~ 43.8
     否1338.517.9 ~ 35.6
    原发肿瘤位置4.4820.034
     左半结肠5147.130.6 ~ 44.7
     右半结肠1118.29.6 ~ 31.5
    原发肿瘤直径0.6490.420
     <5 cm4346.528.9 ~ 42.0
     ≥5 cm1931.618.5 ~ 45.8
    分化程度6.8610.009
     低分化1723.514.1 ~ 32.0
     中-高分化4548.932.1 ~ 48.6
    T分期0.0070.934
     T2 ~ T34443.226.7 ~ 41.9
     T41838.922.7 ~ 45.3
    淋巴结转移0.1610.688
     N01747.124.3 ~ 46.4
     N1 ~ N24540.027.1 ~ 42.7
    癌栓0.6080.435
     存在922.212.9 ~ 42.6
     否5345.328.8 ~ 42.8
    癌结节0.1460.702
     存在1241.722.7 ~ 48.8
     否5042.026.7 ~ 40.9
    肝转移灶分布位置7.7830.005
     双侧3129.018.8 ~ 29.7
     单侧3154.834.2 ~ 53.8
    肝转移灶数目14.108<0.001
     ≤34353.533.4 ~ 50.2
     >31915.814.7 ~ 24.0
    肝转移灶直径0.1860.666
     <5 cm4740.427.3 ~ 42.1
     ≥5 cm1546.722.4 ~ 41.4
    CEA5.3620.021
     ≤10 ng·mL-12360.934.0 ~ 56.1
     >10 ng·mL-13930.821.4 ~ 35.1
    CA1993.6390.056
     ≤27 ng·mL-12755.631.2 ~ 50.2
     >27 ng·mL-13531.421.9 ~ 36.8
    下载: 导出CSV

    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HR95% CIP
    原发灶位置1=右半结肠,0=左半结肠4.0671.738 ~ 9.5160.001
    分化程度1=低分化,0=中-高分化2.4821.280 ~ 4.8120.007
    肝转移灶分布位置1=双侧,0=单侧2.2631.008 ~ 5.0790.048
    转移灶数目1=>3,0=≤31.4110.607 ~ 3.2810.424
    CEA1=>10 ng·mL-1,0=≤10 ng·mL-12.2301.048 ~ 4.7470.037
    CA1991=>27 ng·mL-1,0=≤27 ng·mL-12.0491.008 ~ 4.1660.048
    下载: 导出CSV
  • [1] Baidoun F,Elshiwy K,Elkeraie Y,et al. Colorectal cancer epidemiology:recent trends and impact on outcomes[J]. Curr Drug Targets,2021,22(9): 998-1009. doi: 10.2174/18735592MTEx9NTk2y
    [2] Stewart CL,Warner S,Ito K,et al. Cytoreduction for colorectal metastases:liver,lung,peritoneum,lymph nodes,bone,brain. When does it palliate,prolong survival,and potentially cure?[J]. Curr Probl Surg,2018,55(9): 330-379. doi: 10.1067/j.cpsurg.2018.08.004
    [3] Chandra R,Karalis JD,Liu C,et al. The colorectal cancer tumor microenvironment and its impact on liver and lung metastasis[J]. Cancers (Basel),2021,13(24): 6206. doi: 10.3390/cancers13246206
    [4] Ren L,Zhu DX,Benson AB 3rd,et al. Shanghai international consensus on diagnosis and comprehensive treatment of colorectal liver metastases (version 2019)[J]. Eur J Surg Oncol,2020,46(6): 955-966. doi: 10.1016/j.ejso.2020.02.019
    [5] Frankel TL,D'Angelica MI. Hepatic resection for colorectal metastases[J]. J Surg Oncol,2014,109(1): 2-7. doi: 10.1002/jso.23371
    [6] Kow AWC. Hepatic metastasis from colorectal cancer[J]. J Gastrointest Oncol,2019,10(6): 1274-1298. doi: 10.21037/jgo.2019.08.06
    [7] Chakedis J,Schmidt CR. Surgical treatment of metastatic colorectal cancer[J]. Surg Oncol Clin N Am,2018,27(2): 377-399. doi: 10.1016/j.soc.2017.11.010
    [8] She WH,Cheung TT,Ma KW,et al. Relevance of chemotherapy and margin status in colorectal liver metastasis[J]. Langenbecks Arch Surg,2021,406(8): 2725-2737. doi: 10.1007/s00423-021-02205-w
    [9] Solaini L,Gardini A,Passardi A,et al. Preoperative chemotherapy and resection margin status in colorectal liver metastasis patients:a propensity score-matched analysis[J]. Am Surg,2019,85(5): 488-493. doi: 10.1177/000313481908500525
    [10] Benedetti Cacciaguerra A,Görgec B,Cipriani F,et al. Risk factors of positive resection margin in laparoscopic and open liver surgery for colorectal liver metastases:a new perspective in the perioperative assessment:a European multicenter study[J]. Ann Surg,2022,275(1): e213-e221. doi: 10.1097/SLA.0000000000004077
    [11] Akgül Ö,Çetinkaya E,Ersöz Ş,et al. Role of surgery in colorectal cancer liver metastases[J]. World J Gastroenterol,2014,20(20): 6113-6122. doi: 10.3748/wjg.v20.i20.6113
    [12] Bong JW,Ju Y,Seo J,et al. Effects of the proximity of metastasis to the central vessels of the liver on surgical outcomes and survival in colorectal cancer with liver metastasis[J]. ANZ J Surg,2021,91(4): E183-E189.
    [13] Shen H,Yang J,Huang Q,et al. Different treatment strategies and molecular features between right-sided and left-sided colon cancers[J]. World J Gastroenterol,2015,21(21): 6470-6478. doi: 10.3748/wjg.v21.i21.6470
    [14] Yang SY,Cho MS,Kim NK. Difference between right-sided and left-sided colorectal cancers:from embryology to molecular subtype[J]. Expert Rev Anticancer Ther,2018,18(4): 351-358. doi: 10.1080/14737140.2018.1442217
    [15] Ninomiya M,Emi Y,Motomura T,et al. Efficacy of neoadjuvant chemotherapy in patients with high-risk resectable colorectal liver metastases[J]. Int J Clin Oncol,2021,26(12): 2255-2264. doi: 10.1007/s10147-021-02024-5
    [16] Chow FCL,Chok KSH. Colorectal liver metastases:an update on multidisciplinary approach[J]. World J Hepatol,2019,11(2): 150-172. doi: 10.4254/wjh.v11.i2.150
    [17] Saad AM,Abdel-Rahman O. Initial systemic chemotherapeutic and targeted therapy strategies for the treatment of colorectal cancer patients with liver metastases[J]. Expert Opin Pharmacother,2019,20(14): 1767-1775. doi: 10.1080/14656566.2019.1642324
    [18] Benson AB,Venook AP,Al-Hawary MM,et al. Colon cancer,version 2.2021,NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw,2021,19(3): 329-359. doi: 10.6004/jnccn.2021.0012
    [19] Liu W,Zhou JG,Sun Y,et al. The role of neoadjuvant chemotherapy for resectable colorectal liver metastases:a systematic review and meta-analysis[J]. Oncotarget,2016,7(24): 37277-37287. doi: 10.18632/oncotarget.8671
    [20] Ishizuka D,Shirai Y,Sakai Y,et al. Colorectal carcinoma liver metastases:clinical significance of preoperative measurement of serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels[J]. Int J Colorectal Dis,2001,16(1): 32-37. doi: 10.1007/s003840000268
    [21] Jelski W,Mroczko B. Biochemical markers of colorectal cancer - present and future[J]. Cancer Manag Res,2020,12: 4789-4797. doi: 10.2147/CMAR.S253369
    [22] Ye YJ,Wang S,Wu J,et al. Clinicopathological analysis of synchronous hepatic metastases from colorectal cancer[J]. Chin J Gastrointest Surg,2008,11(3): 208-212.
    [23] Zhang S,Gao F,Luo J,et al. Prognostic factors in survival of colorectal cancer patients with synchronous liver metastasis[J]. Colorectal Dis,2010,12(8): 754-761.
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  • 收稿日期:  2022-07-15
  • 网络出版日期:  2023-03-23
  • 刊出日期:  2023-04-28

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