肝内胆管细胞癌淋巴结转移的预测和治疗

贺康丽; 刘宏; 李星悦

doi:10.3969/j.issn.1001-5256.2021.08.040

肝内胆管细胞癌淋巴结转移的预测和治疗

DOI: 10.3969/j.issn.1001-5256.2021.08.040

1.
山西医科大学第一临床医学院，太原 030000
2.
山西医科大学第一医院肝胆胰外科，太原 030000

基金项目:

山西省回国留学人员科研资助项目 (2017-113)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：贺康丽、李星悦负责收集文献，归纳分析，撰写论文；贺康丽、刘宏、李星悦负责修改论文；贺康丽、刘宏负责课题设计，拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
刘宏，1906386041@qq.com

中图分类号: R735.7
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- 被引次数: 0
出版历程
- 收稿日期: 2021-01-02
- 录用日期: 2021-01-27
- 出版日期: 2021-08-20

Prediction and treatment of lymph node metastasis of intrahepatic cholangiocarcinoma

Kangli HE¹,
Hong LIU^{2
, ,},
Xingyue LI¹

1.
The First Clinical Medical College of Shanxi Medical University, Taiyuan 030000, China
2.
Department of Hepatopancreatobiliary Surgery, The First Hospital of Shanxi Medical University, Taiyuan 030000, China

Research funding:

Shanxi Scholarship Council of China (2017-113)

摘要

摘要: 肝内胆管细胞癌(ICC)是第二大原发性肝癌，极易发生淋巴结转移。淋巴结转移的发生不仅影响患者的预后，还决定患者治疗方案的选择。归纳并总结近年国内外ICC的相关文献，阐述了预测ICC淋巴结转移的血清学指标及影像学指标；可接受根治性手术切除患者的在选择淋巴结切除术及术后辅助治疗方面存在的争议；不可手术的晚期ICC患者接受新辅助治疗的研究进展。以期为ICC患者的治疗及淋巴结转移的预测作好理论支持。
- 胆管上皮癌 /
- 淋巴结转移 /
- 治疗学
Abstract: Intrahepatic cholangiocarcinoma (ICC) is the second largest primary liver cancer, and lymph node metastasis of ICC is commonly observed. Lymph node metastasis not only affects the prognosis of patients, but also determines the choice of treatment regimen. This article summarizes related articles on ICC in China and globally and elaborates on the serological markers and imaging indicators for predicting lymph node metastasis of ICC, the controversy over the selection of lymph node resection and postoperative adjuvant treatment for patients eligible for radical resection, and the research advances in neoadjuvant therapy for patients with advanced ICC who cannot undergo surgery, so as to provide theoretical support for the treatment of ICC patients and the prediction of lymph node metastasis.
- Cholangiocarcinoma /
- Lymph Node Metastasis /
- Therapeutics

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参考文献(57)

[1]	YEESOONSANG S, MCNEIL E, VIRANI S, et al. Trends in incidence of two major subtypes of liver and bile duct cancer: Hepatocellular carcinoma and cholangiocarcinoma in Songkhla, southern Thailand, 1989-2030[J]. J Cancer Epidemiol, 2018, 2018: 8267059. DOI: 10.1155/2018/8267059.
[2]	MENG ZW, HAN SH, ZHU JH, et al. Risk factors for cholangiocarcinoma after initial hepatectomy for intrahepatic stones[J]. World J Surg, 2017, 41(3): 835-843. DOI: 10.1007/s00268-016-3752-2.
[3]	MORINE Y, SHIMADA M. The value of systematic lymph node dissection for intrahepatic cholangiocarcinoma from the viewpoint of liver lymphatics[J]. J Gastroenterol, 2015, 50(9): 913-927. DOI: 10.1007/s00535-015-1071-2.
[4]	JI GW, ZHU FP, ZHANG YD, et al. A radiomics approach to predict lymph node metastasis and clinical outcome of intrahepatic cholangiocarcinoma[J]. Eur Radiol, 2019, 29(7): 3725-3735. DOI: 10.1007/s00330-019-06142-7.
[5]	CHANG ME, LEI HJ, CHEN MH, et al. Evaluation of prognostic factors and implication of lymph node dissection in intrahepatic cholangiocarcinoma: 10-year experience at a tertiary referral center[J]. J Chin Med Assoc, 2017, 80(3): 140-146. DOI: 10.1016/j.jcma.2016.09.010.
[6]	YOH T, HATANO E, SEO S, et al. Preoperative criterion identifying a low-risk group for lymph node metastasis in intrahepatic cholangiocarcinoma[J]. J Hepatobiliary Pancreat Sci, 2018, 25(6): 299-307. DOI: 10.1002/jhbp.552.
[7]	HAMMAD AY, BERGER NG, EASTWOOD D, et al. Is radiotherapy warranted following intrahepatic cholangiocarcinoma resection? The impact of surgical margins and lymph node status on survival[J]. Ann Surg Oncol, 2016, 23(Suppl 5): 912-920. DOI: 10.1245/s10434-016-5560-1.
[8]	WANG L, LIN ZG, YANG T, et al. A multicenter retrospective study on clinical value of lymph node dissection in the radical resection of intrahepatic cholangiocarcinoma[J]. Chin J Dig Surg, 2020, 19(1): 72-80. DOI: 10.3760/cma.j.issn.1673-9752.2020.01.012. 王垒, 林自国, 杨田, 等. 淋巴结清扫在肝内胆管癌根治术中临床价值的多中心回顾性研究[J]. 中华消化外科杂志, 2020, 19(1): 72-80. DOI: 10.3760/cma.j.issn.1673-9752.2020.01.012.
[9]	BRAUER DG, FIELDS RC, TAN BR Jr, et al. Optimal extent of surgical and pathologic lymph node evaluation for resected intrahepatic cholangiocarcinoma[J]. HPB (Oxford), 2018, 20(5): 470-476. DOI: 10.1016/j.hpb.2017.11.010.
[10]	ZHANG XF, XUE F, DONG DH, et al. Number and station of lymph node metastasis after curative-intent resection of intrahepatic cholangiocarcinoma impact prognosis[J]. Ann Surg, 2020. DOI: 10.1097/SLA.0000000000003788.[Online ahead of print]
[11]	NAVARRO JG, LEE JH, KANG I, et al. Prognostic significance of and risk prediction model for lymph node metastasis in resectable intrahepatic cholangiocarcinoma: Do all require lymph node dissection?[J]. HPB (Oxford), 2020, 22(10): 1411-1419. DOI: 10.1016/j.hpb.2020.01.009.
[12]	ASAOKA T, KOBAYASHI S, HANAKI T, et al. Clinical significance of preoperative CA19-9 and lymph node metastasis in intrahepatic cholangiocarcinoma[J]. Surg Today, 2020, 50(10): 1176-1186. DOI: 10.1007/s00595-020-01992-x.
[13]	SUI Y, GONG P, ZHANG XB, et al. Value of lymph node ratio in prognosis of patients with intrahepatic cholangiocarcinoma[J]. Chin J Hepatobiliary Surg, 2019, 25(4): 268-271. DOI: 10.3760/cma.j.issn.1007-8118.2019.04.007. 隋毅, 巩鹏, 张贤彬, 等. 淋巴结阳性比率对于肝内胆管癌患者预后的价值[J]. 中华肝胆外科杂志, 2019, 25(4): 268-271. DOI: 10.3760/cma.j.issn.1007-8118.2019.04.007.
[14]	ZHU Y, MAO Y, CHEN J, et al. Preoperative computed tomography features of intrahepatic cholangiocarcinoma for predicting lymph node metastasis and overall survival[J]. J Comput Assist Tomogr, 2019, 43(5): 729-735. DOI: 10.1097/RCT.0000000000000922.
[15]	HARADA N, YOSHIZUMI T, YAMASHITA YI, et al. Impact and prediction of lymph node involvement in patients with intrahepatic cholangiocarcinoma after curative resection[J]. Anticancer Res, 2017, 37(7): 3763-3769. DOI: 10.21873/anticanres.11751.
[16]	XIA L, XIE YJ, ZHANG L, et al. Diagnosis and treatment of intrahepatic cholangiocarcinoma: Current status and thoughts[J]. J Clin Hepatol, 2020, 36(10): 2380-2385. DOI: 10.3969/j.issn.1001-5256.2020.10.048. 夏龙, 夏医君, 张磊, 等. 肝内胆管细胞癌的诊疗现状与思考[J]. 临床肝胆病杂志, 2020, 36(10): 2380-2385. DOI: 10.3969/j.issn.1001-5256.2020.10.048.
[17]	HAN C, JIN LY, ZHAI TY, et al. Predictive value of preoperative serum tumor markers test for lymph node metastasis of intrahepatic cholangiocarcinoma[J]. Chin J Dig Surg, 2017, 16(5): 503-507. DOI: 10.3760/cma.j.issn.1673-9752.2017.05.013. 韩超, 靳龙洋, 翟天宇, 等. 术前肿瘤标志物检测对肝内胆管细胞癌淋巴结转移的预测价值[J]. 中华消化外科杂志, 2017, 16(5): 503-507. DOI: 10.3760/cma.j.issn.1673-9752.2017.05.013.
[18]	YAMADA T, NAKANISHI Y, OKAMURA K, et al. Impact of serum carbohydrate antigen 19-9 level on prognosis and prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma[J]. J Gastroenterol Hepatol, 2018, 33(9): 1626-1633. DOI: 10.1111/jgh.14124.
[19]	CHEN Q, ZHENG Y, ZHAO H, et al. The combination of preoperative D-dimer and CA19-9 predicts lymph node metastasis and survival in intrahepatic cholangiocarcinoma patients after curative resection[J]. Ann Transl Med, 2020, 8(5): 192. DOI: 10.21037/atm.2020.01.72.
[20]	WEI MY, ZHANG YY, GENG ZM, et al. Clinicopathological features and lymph node metastases characteristics of intrahepatic cholangiocarcinoma: A multicenter retrospective study (A report of 1321 cases)[J]. Chin J Dig Surg, 2018, 17(3): 257-265. DOI: 10.3760/cma.j.issn.1673-9752.2018.03.009. 魏妙艳, 张园园, 耿智敏, 等. 肝内胆管癌临床病理特征及淋巴结转移特点的多中心回顾性研究(附1321例报告)[J]. 中华消化外科杂志, 2018, 17(3): 257-265. DOI: 10.3760/cma.j.issn.1673-9752.2018.03.009.
[21]	YAMAMOTO Y, TÜRKOǦLU MA, ARAMAKI T, et al. Vascularity of intrahepatic cholangiocarcinoma on computed tomography is predictive of lymph node metastasis[J]. Ann Surg Oncol, 2016, 23(Suppl 4): 485-493. DOI: 10.1245/s10434-016-5382-1.
[22]	ZHOU Y, ZHOU G, GAO X, et al. Apparent diffusion coefficient value of mass-forming intrahepatic cholangiocarcinoma: A potential imaging biomarker for prediction of lymph node metastasis[J]. Abdom Radiol (NY), 2020, 45(10): 3109-3118. DOI: 10.1007/s00261-020-02458-x.
[23]	TSILIMIGRAS DI, SAHARA K, PAREDES AZ, et al. Predicting lymph node metastasis in intrahepatic cholangiocarcinoma[J]. J Gastrointest Surg, 2021, 25(5): 1156-1163. DOI: 10.1007/s11605-020-04720-5.
[24]	MENG ZW, LIN XQ, ZHU JH, et al. A nomogram to predict lymph node metastasis before resection in intrahepatic cholangiocarcinoma[J]. J Surg Res, 2018, 226: 56-63. DOI: 10.1016/j.jss.2018.01.024.
[25]	XU L, YANG P, LIANG W, et al. A radiomics approach based on support vector machine using MR images for preoperative lymph node status evaluation in intrahepatic cholangiocarcinoma[J]. Theranostics, 2019, 9(18): 5374-5385. DOI: 10.7150/thno.34149.
[26]	HE K, HU ZM, RUAN JH, et al. Correlation of extracellular matrix protein 1 with primary intrahepatic cholangiocarcinoma and; lymph node metastasis[J]. Chin J Biomed Eng, 2015, 21(1): 40-44. DOI: 10.3760/cma.j.issn.1674-1927.2015.01.008. 何坤, 胡泽民, 阮嘉后, 等. 细胞外基质蛋白1与原发性肝内胆管细胞癌及淋巴结转移的相关性分析[J]. 中华生物医学工程杂志, 2015, 21(1): 40-44. DOI: 10.3760/cma.j.issn.1674-1927.2015.01.008.
[27]	YAMAOKA R, ISHⅡ T, KAWAI T, et al. CD90 expression in human intrahepatic cholangiocarcinoma is associated with lymph node metastasis and poor prognosis[J]. J Surg Oncol, 2018, 118(4): 664-674. DOI: 10.1002/jso.25192.
[28]	ZHU T, RAO JF, LIU CY, et al. Expression of CD90 in intrahepatic cholangiocellular carcinoma and its association with poor prognosis[J]. J Clin Hepatol, 2020, 36(2): 354-357. DOI: 10.3969/j.issn.1001-5256.2020.02.024. 朱彤, 饶井芬, 刘承一, 等. CD90在肝内胆管细胞癌中的表达及其与患者预后不良的关系[J]. 临床肝胆病杂志, 2020, 36(2): 354-357. DOI: 10.3969/j.issn.1001-5256.2020.02.024.
[29]	YOH T, CAUCHY F, LE ROY B, et al. Prognostic value of lymphadenectomy for long-term outcomes in node-negative intrahepatic cholangiocarcinoma: A multicenter study[J]. Surgery, 2019, 166(6): 975-982. DOI: 10.1016/j.surg.2019.06.025.
[30]	KIM SH, HAN DH, CHOI GH, et al. Oncologic impact of lymph node dissection for intrahepatic cholangiocarcinoma: A propensity score-matched study[J]. J Gastrointest Surg, 2019, 23(3): 538-544. DOI: 10.1007/s11605-018-3899-2.
[31]	ZENG YY, LI YT, ZHANG X. Effect of abdominal lymphadenectomy on prognosis of intrahepatic cholangiocarcinoma: A systematic review and Meta analysis[J]. Chin J Dig Surg, 2016, 15(4): 339-345. DOI: 10.3760/cma.j.issn.1673-9752.2016.04.007. 曾永毅, 黎蕴通, 张翔. 腹腔淋巴结清扫对肝内胆管细胞癌预后影响的系统评价[J]. 中华消化外科杂志, 2016, 15(4): 339-345. DOI: 10.3760/cma.j.issn.1673-9752.2016.04.007.
[32]	ZHU MH, ZHANG XZ, HAN F, et al. Prognostic factors of radical resection on patients with intrahepatic cholangiocarcinoma and impact of abdominal lymph node dissection on prognosis[J]. Chin J Hepatobiliary Surg, 2020, 26(1): 48-52. DOI: 10.3760/cma.j.issn.1007-8118.2020.01.011. 朱明辉, 张先舟, 韩风, 等. 腹腔淋巴结清扫范围对肝内胆管细胞癌患者根治性切除术预后的影响[J]. 中华肝胆外科杂志, 2020, 26(1): 48-52. DOI: 10.3760/cma.j.issn.1007-8118.2020.01.011.
[33]	ZHOU R, LU D, LI W, et al. Is lymph node dissection necessary for resectable intrahepatic cholangiocarcinoma? A systematic review and meta-analysis[J]. HPB (Oxford), 2019, 21(7): 784-792. DOI: 10.1016/j.hpb.2018.12.011.
[34]	HU J, CHEN FY, ZHOU KQ, et al. Intrahepatic cholangiocarcinoma patients without indications of lymph node metastasis not benefit from lymph node dissection[J]. Oncotarget, 2017, 8(69): 113817-113827. DOI: 10.18632/oncotarget.22852.
[35]	MIYATA T, YAMASHITA YI, YAMAO T, et al. Clinical benefits of lymph node dissection in intrahepatic cholangiocarcinoma: A retrospective single-institution study[J]. Anticancer Res, 2017, 37(5): 2673-2677. DOI: 10.21873/anticanres.11615.
[36]	KIZY S, ALTMAN AM, MARMOR S, et al. Surgical resection of lymph node positive intrahepatic cholangiocarcinoma may not improve survival[J]. HPB (Oxford), 2019, 21(2): 235-241. DOI: 10.1016/j.hpb.2018.08.006.
[37]	AMIN MB, GREENE FL, EDGE SB, et al. The eighth edition AJCC cancer staging manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging[J]. CA Cancer J Clin, 2017, 67(2): 93-99. DOI: 10.3322/caac.21388.
[38]	KIM SH, HAN DH, CHOI GH, et al. Recommended minimal number of harvested lymph nodes for intrahepatic cholangiocarcinoma[J]. J Gastrointest Surg, 2021, 25(5): 1164-1171. DOI: 10.1007/s11605-020-04622-6.
[39]	JUTRIC Z, JOHNSTON WC, HOEN HM, et al. Impact of lymph node status in patients with intrahepatic cholangiocarcinoma treated by major hepatectomy: A review of the National Cancer Database[J]. HPB (Oxford), 2016, 18(1): 79-87. DOI: 10.1016/j.hpb.2015.07.006.
[40]	ERVIN TJ, WEICHSELBAUM RR, FABIAN RL, et al. Advanced squamous carcinoma of the head and neck. A preliminary report of neoadjuvant chemotherapy with cisplatin, bleomycin, and methotrexate[J]. Arch Otolaryngol, 1984, 110(4): 241-245. DOI: 10.1001/archotol.1984.00800300033007.
[41]	VALLE J, WASAN H, PALMER DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer[J]. N Engl J Med, 2010, 362(14): 1273-1281. DOI: 10.1056/NEJMoa0908721.
[42]	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. DOI: 10.1002/bjs.10641.
[43]	OTANI T, SAKATA J, KAMEYAMA H, et al. Surgical resection after gemcitabine plus cisplatin chemotherapy for intrahepatic cholangiocarcinoma with multiple lymph node metastases - Report of a case[J]. Gan To Kagaku Ryoho, 2016, 43(12): 1764-1766.
[44]	KONSTANTINIDIS IT, GROOT KOERKAMP B, DO RK, et al. Unresectable intrahepatic cholangiocarcinoma: Systemic plus hepatic arterial infusion chemotherapy is associated with longer survival in comparison with systemic chemotherapy alone[J]. Cancer, 2016, 122(5): 758-765. DOI: 10.1002/cncr.29824.
[45]	SUMIYOSHI T, SHIMA Y, OKABAYASHI T, et al. Chemoradiotherapy for initially unresectable locally advanced cholangiocarcinoma[J]. World J Surg, 2018, 42(9): 2910-2918. DOI: 10.1007/s00268-018-4558-1.
[46]	EDELINE J, TOUCHEFEU Y, GUIU B, et al. Radioembolization plus chemotherapy for first-line treatment of locally advanced intrahepatic cholangiocarcinoma: A phase 2 clinical trial[J]. JAMA Oncol, 2020, 6(1): 51-59. DOI: 10.1001/jamaoncol.2019.3702.
[47]	JAVLE M, LOWERY M, SHROFF RT, et al. Phase Ⅱ study of BGJ398 in patients with FGFR-altered advanced cholangiocarcinoma[J]. J Clin Oncol, 2018, 36(3): 276-282. DOI: 10.1200/JCO.2017.75.5009.
[48]	PAN TT, WANG W, JIA WD, et al. A single-center experience of sorafenib monotherapy in patients with advanced intrahepatic cholangiocarcinoma[J]. Oncol Lett, 2017, 13(5): 2957-2964. DOI: 10.3892/ol.2017.5847.
[49]	HUANG M, HUANG B, LI G, et al. Apatinib affect VEGF-mediated cell proliferation, migration, invasion via blocking VEGFR2/RAF/MEK/ERK and PI3K/AKT pathways in cholangiocarcinoma cell[J]. BMC Gastroenterol, 2018, 18(1): 169. DOI: 10.1186/s12876-018-0870-3.
[50]	FARIA J, de ANDRADE C, GOES AM, et al. Effects of different ligands on epidermal growth factor receptor (EGFR) nuclear translocation[J]. Biochem Biophys Res Commun, 2016, 478(1): 39-45. DOI: 10.1016/j.bbrc.2016.07.097.
[51]	SAEED A, PARK R, AL-JUMAYLI M, et al. Biologics, immunotherapy, and future directions in the treatment of advanced cholangiocarcinoma[J]. Clin Colorectal Cancer, 2019, 18(2): 81-90. DOI: 10.1016/j.clcc.2019.02.005.
[52]	ZHANG J, WU L, LIU J, et al. A metastatic intrahepatic cholangiocarcinoma treated with programmed cell death 1 inhibitor: A case report and literature review[J]. Immunotherapy, 2020, 12(8): 555-561. DOI: 10.2217/imt-2019-0100.
[53]	LIU Z, LI S, ZENG J, et al. LKB1 inhibits intrahepatic cholangiocarcinoma by repressing the transcriptional activity of the immune checkpoint PD-L1[J]. Life Sci, 2020, 257: 118068. DOI: 10.1016/j.lfs.2020.118068.
[54]	MOU H, YU L, LIAO Q, et al. Successful response to the combination of immunotherapy and chemotherapy in cholangiocarcinoma with high tumour mutational burden and PD-L1 expression: A case report[J]. BMC Cancer, 2018, 18(1): 1105. DOI: 10.1186/s12885-018-5021-2.
[55]	JING CY, FU YP, YI Y, et al. HHLA2 in intrahepatic cholangiocarcinoma: An immune checkpoint with prognostic significance and wider expression compared with PD-L1[J]. J Immunother Cancer, 2019, 7(1): 77. DOI: 10.1186/s40425-019-0554-8.
[56]	BANALES JM, CARDINALE V, CARPINO G, et al. Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)[J]. Nat Rev Gastroenterol Hepatol, 2016, 13(5): 261-280. DOI: 10.1038/nrgastro.2016.51.
[57]	ZHAO Z, MA J, WU K, et al. SATB1 is a potential therapeutic target in intrahepatic cholangiocarcinoma[J]. Clin Transl Oncol, 2016, 18(9): 878-883. DOI: 10.1007/s12094-015-1449-x.