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中华肝脏外科手术学电子杂志

中华肝脏外科手术学电子杂志 ›› 2025, Vol. 14 ›› Issue (01) : 53 -59. doi: 10.3877/cma.j.issn.2095-3232.2025012

临床研究

肝内胆管细胞癌术后极早期复发的危险因素
余承澍1, 刘红枝1, 林科灿1, 林起柱1, 黄霆峰1, 周伟平2, 程张军3, 楼健颖4, 郑树国5, 毕新宇6, 王剑明7, 郭伟8, 李富宇9, 王坚10, 郑亚民11, 李敬东12, 程石13, 曾永毅1,†()   
  1. 1.350015 福州，福建医科大学孟超肝胆医院肝胆外科
    2.200438 上海，海军军医大学东方肝胆外科医院肝外三科
    3.210009 南京，东南大学附属中大医院肝胆外科
    4.310009 杭州，浙江大学医学院附属第二医院肝胆胰外科
    5.400038 重庆，陆军军医大学第一附属医院全军肝胆外科研究所
    6.100021 北京，中国医学科学院北京协和医学院肿瘤医院肝胆外科
    7.430030 武汉，华中科技大学同济医学院附属同济医院肝胆胰外科
    8.100050 北京，首都医科大学附属北京友谊医院普通外科
    9.610041 成都，四川大学华西医院胆道外科
    10.200127 上海交通大学医学院附属仁济医院胆胰外科
    11.100053 北京，首都医科大学宣武医院普通外科
    12.617000 四川省南充市，川北医学院附属医院肝胆外科
    13.100070 北京，首都医科大学附属天坛医院普通外科
  • 收稿日期:2024-11-21 出版日期:2025-02-10
  • 通信作者: 曾永毅
  • 基金资助:
    福建省科技重大专项(2021YZ036017)福建省卫生健康委员会中青年科研重大项目(2021ZQNZD013)福州市卫生健康科技创新平台项目(2021-S-wp1)

Risk factors of very early recurrence of intrahepatic cholangiocarcinoma after surgery

Chengshu Yu1, Hongzhi Liu1, Kecan Lin1, Qizhu Lin1, Tingfeng Huang1, Weiping Zhou2, Zhangjun Cheng3, Jianying Lou4, Shuguo Zheng5, Xinyu Bi6, Jianming Wang7, Wei Guo8, Fuyu Li9, Jian Wang10, Yamin Zheng11, Jingdong Li12, Shi Cheng13, Yongyi Zeng1,†()   

  1. 1.Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital, Fujian Medical University, Fuzhou 350015, China
    2.Department of Hepatobiliary Surgery, Oriental Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai 200438, China
    3.Department of Hepatobiliary Surgery,Zhongda Hospital affiliated to Southeast University, Nanjin·g 210009, China
    4.Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China
    5.Institute of Hepatobiliary Surgery of the Whole Army, the First Affiliated Hospital of Army Medical University, Chongqing 400038,China
    6.Department of Hepatobiliary Surgery, Peking Union Medical College Cancer Hospital, Chinese Academy of Medical Sciences, Beijing 100021, China
    7.Department of Hepatobiliary and Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
    8.Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
    9.Department of Hepatobiliary Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
    10.Department of Hepatobiliary and Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
    11.Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
    12.Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 617000, China
    13.Department of General Surgery, Beijing Tiantan Hospital, Capital Medical University,Beijing 100070, China
  • Received:2024-11-21 Published:2025-02-10
  • Corresponding author: Yongyi Zeng
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引用本文：

余承澍, 刘红枝, 林科灿, 林起柱, 黄霆峰, 周伟平, 程张军, 楼健颖, 郑树国, 毕新宇, 王剑明, 郭伟, 李富宇, 王坚, 郑亚民, 李敬东, 程石, 曾永毅. 肝内胆管细胞癌术后极早期复发的危险因素[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(01): 53-59.

Chengshu Yu, Hongzhi Liu, Kecan Lin, Qizhu Lin, Tingfeng Huang, Weiping Zhou, Zhangjun Cheng, Jianying Lou, Shuguo Zheng, Xinyu Bi, Jianming Wang, Wei Guo, Fuyu Li, Jian Wang, Yamin Zheng, Jingdong Li, Shi Cheng, Yongyi Zeng. Risk factors of very early recurrence of intrahepatic cholangiocarcinoma after surgery[J/OL]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2025, 14(01): 53-59.

目的

探讨肝内胆管细胞癌（ICC）患者术后极早期复发（VER）的危险因素。

方法

回顾性分析2011 年12 月至2017 年12 月于福建医科大学孟超肝胆医院、海军军医大学东方肝胆外科医院、东南大学附属中大医院、浙江大学医学院附属第二医院、陆军军医大学第一附属医院、中国医学科学院北京协和医学院肿瘤医院、华中科技大学同济医学院附属同济医院、首都医科大学附属北京友谊医院、四川大学华西医院、上海交通大学医学院附属仁济医院、首都医科大学宣武医院、川北医学院附属医院、首都医科大学附属天坛医院13 家中心接受手术治疗的445 例ICC 患者临床资料。患者均签署知情同意书，符合医学伦理学规定。其中男270 例，女175 例；年龄23～88 岁，中位年龄57 岁。肿瘤直径1.1～20.4 cm，中位直径6.0 cm。以术后6 个月内发生ICC 复发为标准分为VER 组（328 例）和非VER 组（117 例）。采用Logistic 单因素和多因素回归分析术后随访资料，生存分析采用Kaplan-Meier 法和Log-rank 检验。

结果

Logistic 多因素回归分析显示，性别（OR=0.51，95%CI：0.32～0.84）、年龄（OR=0.97，95%CI：0.95～0.99）、肿瘤数目（OR=1.28，95%CI：1.06～1.54）、病理类型（OR=0.40，95%CI：0.16～0.99）、肿瘤最大径（OR=1.10，95%CI：1.02～1.17）是ICC 术后患者VER 的独立影响因素（P＜0.05）。随访6～73 个月，中位随访时间21 个月。随访期间236 例死亡，209 例存活。VER 组和非VER 组术后1、3、5 年生存率分别为60.71%、7.14%、0 和89.90%、54.40%、25.30%，差异有统计学意义（χ2=88.844，P＜0.001）。

结论

病理类型、肿瘤数目、肿瘤最大径等为ICC 术后VER 的独立影响因素，VER 患者生存预后较差。

关键词: 肝内胆管细胞癌, 肝肿瘤, 复发, 极早期, 危险因素

Objective

To investigate the risk factors of very early recurrence (VER) in patients with intrahepatic cholangiocarcinoma (ICC) after surgery.

Methods

Clinicals data of 445 ICC patients undergoing surgery in Mengchao Hepatobiliary Hospital of Fujian Medical University,Oriental Hepatobiliary Surgery Hospital of Naval Medical University, Zhongda Hospital Affiliated to Southeast University, the Second Affiliated Hospital of Zhejiang University School of Medicine, the First Affiliated Hospital of Army Medical University, Peking Union Medical College Cancer Hospital of Chinese Academy of Medical Sciences, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Beijing Friendship Hospital Affiliated to Capital Medical University, West China Hospital of Sichuan University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Xuanwu Hospital of Capital Medical University, Affiliated Hospital of North Sichuan Medical College and Beijing Tiantan Hospital Affiliated to Capital Medical University from December 2011 to December 2017 were retrospectively analyzed.The informed consents of all patients were obtained and the local ethical committee approval was received.Among them, 270 patients were male and 175 female, aged from 23 to 88 years, with a median age of 57 years.The tumor diameter was ranged from 1.1 to 20.4 cm, with a median diameter of 6.0 cm.According to the recurrence of ICC within postoperative 6 months, they were divided into the VER group (n=328) and non-VER group (n=117).Postoperative follow-up data were assessed by univariate and multivariate Logistic regression analyses.Survival analysis was conducted by using Kaplan-Meier method and Log-rank test.

Results

Multivariate Logistic regression analysis showed that gender (OR=0.51, 95%CI: 0.32-0.84), age(OR=0.97, 95%CI: 0.95-0.99), tumor number (OR=1.28, 95%CI: 1.06-1.54), pathological type (OR=0.40,95%CI: 0.16-0.99) and maximum tumor diameter (OR=1.10, 95%CI: 1.02-1.17) were the independent risk factors of VER in ICC patients after surgery (all P＜0.05).Postoperative follow-up was ranged from 6 to 73 months, with a median follow-up time of 21 months.During postoperative follow-up, 236 patients died and 209 cases survived.The 1-, 3- and 5-year survival rates in the VER and non-VER groups were 60.71%, 7.14%, 0 and 89.90%, 54.40% and 25.30%, respectively, and the differences were statistically significant (χ2=88.844, P＜0.001).

Conclusions

Pathological type, tumor number and maximum tumor diameter are the independent risk factors of VER in ICC patients after surgery.ICC patients with VER obtain poor prognosis.

Key words: Intrahepatic cholangiocarcinoma, Liver neoplasms, Recurrence, Very early stage, Risk factors
表1 两组ICC 患者术前一般资料比较
指标 非VER组 VER组 统计值 P值
年龄[岁，M（Q1，Q3）] 59（51，65） 55（46，61） Z=-3.402 0.001
性别（例，男/女） 188/140 82/35 χ2=5.369 0.021
肝胆肿瘤家族史（例） 27 11 χ2=0.038 0.845
乙肝史（例） 120 47 χ2=0.332 0.564
肝切除史（例） 12 0 χ2=3.115 0.078
Child-Pugh A级（例） 206 69 χ2=0.386 0.534
术前新辅助治疗 17 10 χ2=2.193 0.334
淋巴结转移（例） 56 11 χ2=3.391 0.066
腹腔镜手术（例） 300 113 χ2=2.661 0.103
淋巴结清扫（例） 109 41 χ2=0.059 0.809
肿块型（例） 223 84 χ2=0.420 0.517
腺癌（例） 287 111 χ2=4.211 0.040
高中分化（例） 256 100 χ2=2.523 0.112
肝外侵犯（例） 37 11 χ2=0.151 0.697
脉管浸润（例） 69 28 χ2=0.271 0.603
神经侵犯（例） 43 15 χ2=0 ＞0.999
术后并发症（例） 62 27 χ2=0.696 0.404
ASA评分≤2分（例） 321 115 χ2=0 ＞0.999
CA19-9＞37 kU/L（例） 116 38 χ2=0.318 0.573
AFP＞25 μg/L（例） 109 48 χ2=2.294 0.130
CEA＞5 μg/L（例） 81 21 χ2=2.222 0.136
切缘距离＞2 cm（例） 146 44 χ2=1.410 0.235
阳性淋巴结（例） 52 24 χ2=1.013 0.314
肿瘤最大径[cm，M（Q1，Q3）] 6.5（4.0，8.1） 7.3（5.0，9.0） Z=-3.107 0.002
肿瘤数目[个，M（Q1，Q3）] 1.0（1.0，1.0） 1.0（1.0，2.0） Z=-3.037 0.002
手术时间[min，M（Q1，Q3）] 208（51，324） 166（44，275） Z=-2.604 0.009
术中出血量[ml，M（Q1，Q3）] 3 42（143，400） 316（150，400） Z=-0.484 0.628
表2 ICC 患者术后VER 危险因素的Logistic 单因素及多因素回归分析
参数 单因素分析 多因素分析
OR 95%CI P值 OR 95%CI P值
性别女 0.57 0.36～0.9 0.016 0.51 0.32～0.84 0.007
年龄 0.97 0.95～0.99 0.002 0.97 0.95～0.99 0.009
手术时间 1.00 1.00～1.00 0.010 1.00 1.00～1.00 0.119
肿瘤多发 1.31 1.10～1.56 0.003 1.28 1.06～1.54 0.009
肿瘤最大径 1.08 1.01～1.15 0.018 1.10 1.02～1.17 0.007
腺癌 0.38 0.16～0.92 0.031 0.40 0.16～0.99 0.047
图1 ICC 患者术后不同复发情况的Kaplan-Meier 生存曲线 注：ICC 为肝内胆管细胞癌
[1]
Massarweh NN, El-Serag HB.Epidemiology of hepatocellular carcinoma and intrahepatic cholangiocarcinoma[J].Cancer Control,2017, 24(3):1073274817729245.
[2]
Moris D, Palta M, Kim C, et al.Advances in the treatment of intrahepatic cholangiocarcinoma: an overview of the current and future therapeutic landscape for clinicians[J].CA Cancer J Clin, 2023,73(2):198-222.
[3]
Krenzien F, Nevermann N, Krombholz A, et al.Treatment of intrahepatic cholangiocarcinoma-a multidisciplinary approach[J].Cancers, 2022, 14(2):362.
[4]
Bekki Y, Von Ahrens D, Takahashi H, et al.Recurrent intrahepatic cholangiocarcinoma - review[J].Front Oncol, 2021, 11:776863.
[5]
Tsilimigras DI, Sahara K, Wu L, et al.Very early recurrence after liver resection for intrahepatic cholangiocarcinoma: considering alternative treatment approaches[J].JAMA Surg, 2020, 155(9):823-831.
[6]
Yousaf A, Kim JU, Eliahoo J, et al.Ablative therapy for unresectable intrahepatic cholangiocarcinoma: a systematic review and metaanalysis[J].J Clin Exp Hepatol, 2019, 9(6):740-748.
[7]
Choi WJ, Williams PJ, Claasen MPAW, et al.Systematic review and meta-analysis of prognostic factors for early recurrence in intrahepatic cholangiocarcinoma after curative-intent resection[J].Ann Surg Oncol,2022, DOI:10.1245/s10434-022-11463-x[Epub ahead of print].
[8]
崔广飞, 高凌.肝内胆管癌术后复发和生存的危险因素研究[J].癌症进展, 2017, 15(5):589-591, 595.
[9]
Martin SP, Ruff S, Diggs LP, et al.Tumor grade and sex should influence the utilization of portal lymphadenectomy for early stage intrahepatic cholangiocarcinoma[J].HPB, 2019, 21(4):419-424.
[10]
Yeh CN, Jan YY, Chen MF.Influence of age on surgical treatment of peripheral cholangiocarcinoma[J].Am J Surg, 2004, 187(4):559-563.
[11]
Addeo P, Jedidi I, Locicero A, et al.Prognostic impact of tumor multinodularity in intrahepatic cholangiocarcinoma[J].J Gastrointest Surg, 2019, 23(9):1801-1809.
[12]
Hyder O, Hatzaras I, Sotiropoulos GC, et al.Recurrence after operative management of intrahepatic cholangiocarcinoma[J].Surgery,2013, 153(6):811-818.
[13]
陈青, 王征, 周俭.肿瘤负荷评分在获得根治性切除肝内胆管癌患者预后预测中的价值[J].肝胆胰外科杂志, 2022, 34(7):399-405.
[14]
Mazzaferro V, Gorgen A, Roayaie S, et al.Liver resection and transplantation for intrahepatic cholangiocarcinoma[J].J Hepatol,2020, 72(2):364-377.
[15]
Song P, Midorikawa Y, Nakayama H, et al.Patients' prognosis of intrahepatic cholangiocarcinoma and combined hepatocellularcholangiocarcinoma after resection[J].Cancer Med, 2019, 8(13):5862-5871.
[16]
Lee AJ, Chun YS.Intrahepatic cholangiocarcinoma: the AJCC/UICC 8th edition updates[J].Chin Clin Oncol, 2018, 7(5):52.
[17]
Lurje G, Bednarsch J, Czigany Z, et al.The prognostic role of lymphovascular invasion and lymph node metastasis in perihilar and intrahepatic cholangiocarcinoma[J].Eur J Surg Oncol, 2019, 45(8):1468-1478.
[18]
Chen Y, Liu H, Zhang J, et al.Prognostic value and predication model of microvascular invasion in patients with intrahepatic cholangiocarcinoma: a multicenter study from China[J].BMC Cancer,2021, 21(1):1299.
[19]
Park HM, Yun SP, Lee EC, et al.Outcomes for patients with recurrent intrahepatic cholangiocarcinoma after surgery[J].Ann Surg Oncol,2016, 23(13):4392-4400.Park HM, Yun SP, Lee EC, et al.Outcomes for patients with recurrent intrahepatic cholangiocarcinoma after surgery[J].Ann Surg Oncol,2016, 13:4392-4400.
[20]
Xu Y, Li Z, Zhou Y, et al.Using immunovascular characteristics to predict very early recurrence and prognosis of resectable intrahepatic cholangiocarcinoma[J].BMC Cancer, 2023, 23(1):1009.
[21]
Hu LS, Zhang XF, Weiss M, et al.Recurrence patterns and timing courses following curative-intent resection for intrahepatic cholangiocarcinoma[J].Ann Surg Oncol, 2019, 26(8):2549-2557.
[22]
Veenhof AA, Vlug MS, van der Pas MH, et al.Surgical stress response and postoperative immune function after laparoscopy or open surgery with fast track or standard perioperative care: a randomized trial[J].Ann Surg, 2012, 255(2):216-221.
[23]
Ratti F, Maina C, Clocchiatti L, et al.Minimally invasive approach provides oncological benefit in patients with high risk of very early recurrence (VER) after surgery for intrahepatic cholangiocarcinoma(iCCA)[J].Ann Surg Oncol, 2024, DOI:10.1245/s10434-023-14807-3[Epub ahead of print].
[24]
Zhang Y, Shi SM, Yang H, et al.Systemic inflammation score predicts survival in patients with intrahepatic cholangiocarcinoma undergoing curative resection[J].J Cancer, 2019, 10(2):494-503.
[25]
马炳奇, 孟慧娟, 张伟, 等.多种免疫炎症指标对肝内胆管癌患者根治性切除术后预后的预测价值[J].临床肝胆病杂志, 2022,38(9):2061-2066.
[26]
Chen S, Wan L, Zhao R, et al.Preoperative MRI features predicting very early recurrence of intrahepatic mass-forming cholangiocarcinoma after R0 resection: a comparison with the AJCC 8th edition staging system[J].Abdom Radiol, 2024, 49(1):21-33.
[27]
Chen B, Mao Y, Li J, et al.Predicting very early recurrence in intrahepatic cholangiocarcinoma after curative hepatectomy using machine learning radiomics based on CECT: a multi-institutional study[J].Comput Biol Med, 2023, 167:107612.
[28]
Le Roy B, Gelli M, Pittau G, et al.Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma[J].Br J Surg,2018, 105(7):839-847.
[29]
Chen X, Du J, Huang J, et al.Neoadjuvant and adjuvant therapy in intrahepatic cholangiocarcinoma[J].J Clin Transl Hepatol, 2022,10(3):553-563.
[30]
Benson AB, D'Angelica MI, Abbott DE, et al.Hepatobiliary cancers,version 2.2021, NCCN clinical practice guidelines in oncology[J].J Natl Compr Canc Netw, 2021, 19(5):541-565.
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