肝门部胆管癌的诊断及不可切除肝门部胆管癌的治疗研究进展

摘要/Abstract

摘要： 肝门部胆管癌（hilar cholangiocarcinoma,HCCA）在亚洲的发病率较高,我国是发病率及死亡率最高的国家之一。HCCA早期症状隐匿,临床诊断较为困难,患者就诊时多处于癌症晚期,失去手术机会;对于不可切除HCCA,不同治疗方法的疗效不尽相同。本文基于一些现有的临床试验,对HCCA的诊断及不可切除HCCA的治疗研究进展进行综述,旨在为HCCA的临床诊断及治疗提供参考。

关键词: 肝门部胆管癌, 诊断, 不可切除肝门部胆管癌, 治疗

Abstract: Hilar cholangiocarcinoma (HCCA) has a high incidence in Asia, among which China has one of the highest morbidity and mortality. The early symptoms of HCCA are hidden and the clinical diagnosis is more difficult. Most of the patients are in the late stage and lose the opportunity of operation. For unresectable HCCA, the curative effect of different treatment methods is different. Based on some existing clinical trials, this paper reviews the diagnosis of HCCA and the treatment of unresectable HCCA, in order to provide reference for clinical diagnosis and treatment.

Key words: Hilar cholangiocarcinoma, Diagnosis, Unresectable hilar cholangiocarcinoma, Treatment

岳子鹏, 石宝琪. 肝门部胆管癌的诊断及不可切除肝门部胆管癌的治疗研究进展[J]. 肝癌电子杂志, 2023, 10(2): 45-50.

Yue Zipeng, Shi Baoqi. Diagnosis of hilar cholangiocarcinoma and advances in the treatment of unresectable hilar cholangiocarcinoma[J]. Electronic Journal of Liver Tumor, 2023, 10(2): 45-50.

参考文献

[1] DELACRUZ D, SALOMON J, ROBINE S, et al.Plasticity of the brush border-the yin and yang of intestinal homeostasis[J]. Nat Rev Gastroenterol Hepatol, 2016, 13(3): 161-174.
[2] CAPOBIANCO I, ROLINGER J, NADALIN S.Resection for Klatskin tumors: technical complexities and results[J]. Transl Gastroenterol Hepatol, 2018, 3: 69.
[3] 张东, 李起, 张健, 等. 从病理学角度探讨肝门部胆管癌的治疗与预后[J/OL]. 中华肝脏外科手术学电子杂志, 2021, 10(1): 10-14.
[4] 于泓, 缪林. 胆管癌支架治疗的现状及进展[J]. 世界华人消化杂志, 2014, 22(5): 648-653.
[5] 苏德望, 付先东, 于佳楠, 等. 血清糖类抗原19-9、癌胚抗原在胆管癌诊断中的应用价值[J]. 中国实验诊断学, 2017, 21(10): 1693-1695.
[6] WANG J, HU H, SHRESTHA A, et al.Can preoperative and postoperative CA19-9 levels predict survival and early recurrence in patients with resectable hilar cholangiocarcinoma?[J]. Oncotarget, 2017, 8(28): 45335-45344.
[7] 王石, 夏医君, 胡志伟, 等. 波形蛋白表达与联合检测血清CA19-9在肝门部胆管癌的临床意义[J]. 中国实验诊断学, 2022, 26(2): 265-269.
[8] 付赵虎, 王卓. 彩色多普勒超声诊断肝门部胆管癌的临床价值[J]. 现代肿瘤医学, 2016, 24(16): 2591-2593.
[9] 周莹, 向言平, 关彩平. 超声诊断肝门部胆管癌的临床价值[J]. 临床医学, 2018, 38(8): 24-25.
[10] 戴磊, 卢庆凯, 董刚, 等. 影像学技术在肝门部胆管癌诊断和治疗中的价值评估[J]. 中国临床新医学, 2013, 6(4): 330-332.
[11] 刘晖, 王军平, 闫建峰, 等. CT联合MRI检查对肝门部胆管癌的诊断价值分析[J]. 中国CT和MRI杂志, 2021, 19(7): 112-113, 117.
[12] RUYS A T, BEEM B E, ENGELBRECHT M R W, et al. Radiological staging in patients with hilar cholangiocarcinoma: a systematic review and meta-analysis[J]. Br J Radiol, 2012, 85(1017): 1255-1262.
[13] XIN Y, LIU Q, ZHANG J, et al.Hilar cholangiocarcinoma: Value of high-resolution enhanced magnetic resonance imaging for preoperative evaluation[J]. J Cancer Res Ther, 2020, 16(7): 1634-1640.
[14] YOO J, KIM J H, BAE J S, et al.Prediction of prognosis and resectability using MR imaging, clinical, and histopathological findings in patients with perihilar cholangiocarcinoma[J]. Abdom Radiol (NY), 2021, 46(9): 4159-4169.
[15] 黄德干, 李俊. MRI联合MRCP在肝门部胆管癌诊断中的价值分析[J]. 现代医用影像学, 2021, 30(8): 1457-1460.
[16] 丁薇, 成友华, 李俊余, 等. MRCP联合DWI序列诊断肝门胆管癌的应用价值[J]. 临床和实验医学杂志, 2022, 21(15): 1671-1674.
[17] HUANG X, YANG J, LI J, et al.Comparison of magnetic resonance imaging and 18-fludeoxyglucose positron emission tomography/computed tomography in the diagnostic accuracy of staging in patients with cholangiocarcinoma: A meta-analysis[J]. Medicine (Baltimore), 2020, 99(35): e20932.
[18] 中国抗癌协会. 肝门部胆管癌规范化诊治专家共识(2015)[J]. 中华肝胆外科杂志, 2015, 21(8): 505-511.
[19] TSALIS K, PARPOUDI S, KYZIRIDIS D, et al.Klatskin tumors and "Klatskin-mimicking lesions": our 22-year experience[J]. Rev Esp Enferm Dig, 2019, 111(2): 121-128.
[20] DONDOSSOLA D, GHIDINI M, GROSSI F, et al.Practical review for diagnosis and clinical management of perihilar cholangiocarcinoma[J] .World J Gastroenterol, 2020, 26(25): 3542-3561.
[21] NAGAKAWA Y, KASUYA K, BUNSO K, et al.Usefulness of multi-3-dimensional computed tomograms fused with multiplanar reconstruction images and peroral cholangioscopy findings in hilar cholangiocarcinoma[J]. J Hepatobiliary Pancreat Sci, 2014, 21(4): 256-262.
[22] ISHII Y, SERIKAWA M, TSUBOI T, et al.Usefulness of peroral cholangioscopy in the differential diagnosis of IgG4-related sclerosing cholangitis and extrahepatic cholangiocarcinoma: a single-center retrospective study[J]. BMC Gastroenterol, 2020, 20(1): 287.
[23] MOHAMADNEJAD M, DeWitt J M, SHERMAN S, et al. Role of EUS for preoperative evaluation of cholangiocarcinoma: a large single-center experience[J]. Gastrointest Endosc, 2011, 73(1): 71-78.
[24] 邢铃, 王田田, 孙波, 等. 内镜超声检查在肝门部胆管癌诊断和术前评价中的作用[J]. 中华消化内镜杂志, 2021, 38(8): 624-627.
[25] 郭享, 王宏光, 王曼彤, 等. SpyGlass DS胆道镜联合射频消融在肝外胆管癌诊治中的应用[J]. 中国内镜杂志, 2019, 25(8): 75-79.
[26] 夏明星, 吴军, 叶馨, 等. 新型SpyGlass经口胆道镜对性质不明胆管狭窄的诊断价值[J]. 中华消化内镜杂志, 2020, 37(10): 722-726.
[27] 倪其泓, 王坚. 肝门部胆管癌诊断和治疗指南(2013版)的解读与思考[J]. 肝胆胰外科杂志, 2015, 27(6): 450-454.
[28] 环韵峰, 刘立鑫, 张小文. 晚期局部肝门部胆管癌应用新辅助治疗进行术前降期的研究现状[J]. 腹部外科, 2022, 35(6): 452-456, 464.
[29] LIN J, WU A L, TENG F, et al.Stent insertion for inoperable hilar cholangiocarcinoma: Comparison of radioactive and normal stenting[J]. Medicine (Baltimore), 2021, 100(21): e26192.
[30] KEULEN A M, GASPERSZ M P, VAN VUGT J L A, et al. Success, complication, and mortality rates of initial biliary drainage in patients with unresectable perihilar cholangiocarcinoma[J]. Surgery, 2022, 172(6): 1606-1613.
[31] 张燚. 经皮肝穿刺胆道引流术在肝门部胆管癌治疗中的应用研究[J]. 中国校医, 2022, 36(1): 35-37, 40.
[32] 秦亚鹏, 商中华. 微创胆道引流对肝门部胆管癌的临床疗效及预后[J]. 实用癌症杂志, 2020, 35(7): 1149-1152.
[33] CELOTTI A, SOLAINI L, MONTORI G, et al.Preoperative biliary drainage in hilar cholangiocarcinoma: Systematic review and meta-analysis[J]. Eur J Surg Oncol, 2017, 43(9): 1628-1635.
[34] TAKAHASHI Y, NAGINO M, NISHIO H, et al.Percutaneous transhepatic biliary drainage catheter tract recurrence in cholangiocarcinoma[J]. Br J Surg, 2010, 97(12): 1860-1866.
[35] 沈洪哲, 贺鸣, 杨浩, 等. 术前PTCD在肝门部胆管癌围术期中的价值[J]. 肝胆外科杂志, 2022, 30(4): 262-265.
[36] NEHLS O, KLUMP B, ARKENAU H T, et al.Oxaliplatin, fluorouracil and leucovorin for advanced biliary system adenocarcinomas: a prospective phase Ⅱ trial[J]. Br J Cancer, 2002, 87(7): 702-704.
[37] VALLE J, WASAN H, PALMER D H, et al.Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer[J]. N Engl J Med, 2010, 362(14): 1273-1281.
[38] LI H, ZHANG Z Y, ZHOU Z Q, et al.Combined gemcitabine and S-1 chemotherapy for treating unresectable hilar cholangiocarcinoma: a randomized open-label clinical trial[J]. Oncotarget, 2016, 7(18): 26888-26897.
[39] SHROFF R T, JAVLE M M, XIAO L, et al.Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial[J]. JAMA Oncol, 2019, 5(6): 824-830.
[40] LAMARCA A, PALMER D H, WASAN H S, et al.Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial[J]. Lancet Oncol, 2021, 22(5): 690-701.
[41] CHEN Y, LI H Q, JIANG X Y, et al.Regional thermochemotherapy versus hepatic arterial infusion chemotherapy for palliative treatment of advanced hilar cholangiocarcinoma: a retrospective controlled study[J]. Eur Radiol, 2016, 26(10): 3500-3509.
[42] WANG X, HU J, CAO G, et al.Phase Ⅱ Study of Hepatic Arterial Infusion Chemotherapy with Oxaliplatin and 5-Fluorouracil for Advanced Perihilar Cholangiocarcinoma[J]. Radiology, 2017, 283(2): 580-589.
[43] MOMM F, SCHUBERT E, HENNE K, et al.Stereotactic fractionated radiotherapy for Klatskin tumours[J]. Radiother Oncol, 2010, 95(1): 99-102.
[44] KOPEK N, HOLT M I, HANSEN A T, et al.Stereotactic body radiotherapy for unresectable cholangiocarcinoma[J]. Radiother Oncol, 2010, 94(1): 47-52.
[45] HASHIMOTO Y, KOMATSU S, TERASHIMA K, et al.Space-Making Particle Therapy for Unresectable Hilar Cholangiocarcinoma[J]. Dig Surg, 2022, 39(2-3): 99-108.
[46] 符誉, 翁杰, 韩霖, 等. 经皮胆道支架置入联合¹²⁵I粒子腔内照射治疗肝门部胆管癌的疗效观察[J]. 广西医科大学学报, 2018, 35(11): 1503-1507.
[47] ZHOU C, LI H, HUANG Q, et al.Biliary self-expandable metallic stent combined with Iodine-125 seeds strand in the treatment of hilar malignant biliary obstruction[J]. J Int Med Res, 2020, 48(4): 300060519887843.
[48] CHEN G, ZHANG M, SHENG Y G, et al.Stent with radioactive seeds strand insertion for malignant hilar biliary obstruction[J]. Minim Invasive Ther Allied Technol, 2021, 30(6): 356-362.
[49] LI Z, JIANG X, XIAO H, et al.Long-term results of ERCP- or PTCS-directed photodynamic therapy for unresectable hilar cholangiocarcinoma[J]. Surg Endosc, 2021, 35(10): 5655-5664.
[50] CHEN P C, YANG T, SHI P, et al.Benefits and safety of photodynamic therapy in patients with hilar cholangiocarcinoma: A meta-analysis[J]. Photodiagnosis Photodyn Ther, 2022, 37: 102712.
[51] GONZALEZ-CARMONA M A, BOLCH M, JANSEN C, et al. Combined photodynamic therapy with systemic chemotherapy for unresectable cholangiocarcinoma[J]. Aliment Pharmacol Ther, 2019, 49(4): 437-447.
[52] FENG Q, CHI Y, LIU Y, et al.Efficacy and safety of percutaneous radiofrequency ablation versus surgical resection for small hepatocellular carcinoma: a meta-analysis of 23 studies[J]. J Cancer Res Clin Oncol, 2015, 141(1): 1-9.
[53] 谢应海, 王琦, 李瑞, 等. 经皮肝穿刺胆管腔内射频消融联合植入支架治疗肝门胆管癌伴恶性梗阻临床疗效研究[J]. 临床军医杂志, 2017, 45(9): 894-897.
[54] WANG Y, CUI W, FAN W Z, et al.Percutaneous intraductal radiofrequency ablation in the management of unresectable Bismuth types Ⅲ and Ⅳ hilar cholangiocarcinoma[J]. Oncotarget, 2016, 7(33): 53911-53920.
[55] WAHIDA A, BUSCHHORN L, FRÖHLING S, et al. The coming decade in precision oncology: six riddles[J]. Nat Rev Cancer, 2023, 23(1): 43-54.
[56] CHAKRABARTI S, KAMGAR M, MAHIPAL A.Targeted Therapies in Advanced Biliary Tract Cancer: An Evolving Paradigm[J]. Cancers (Basel), 2020, 12(8): 2039.
[57] ABOU-ALFA G K, SAHAI V, HOLLEBECQUE A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study[J]. Lancet Oncol, 2020, 21(5): 671-684.
[58] JAVLE M, ROYCHOWDHURY S, KELLEY R K, et al.Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study[J]. Lancet Gastroenterol Hepatol, 2021, 6(10): 803-815.
[59] CHONG D Q, ZHU A X.The landscape of targeted therapies for cholangiocarcinoma: current status and emerging targets[J]. Oncotarget, 2016, 7(29): 46750-46767.
[60] XU Y F, YANG X Q, LU X F, et al.Fibroblast growth factor receptor 4 promotes progression and correlates to poor prognosis in cholangiocarcinoma[J]. Biochem Biophys Res Commun, 2014, 446(1): 54-60.
[61] YAMAMOTO Y, MATSUI J, MATSUSHIMA T, et al.Lenvatinib, an angiogenesis inhibitor targeting VEGFR/FGFR, shows broad antitumor activity in human tumor xenograft models associated with microvessel density and pericyte coverage[J]. Vasc Cell, 2014, 6: 18.
[62] 黄娜, 刘强, 周晓琳. 仑伐替尼在原发性肝癌治疗中的研究进展[J]. 巴楚医学, 2021, 4(2): 111-115.
[63] JAVLE M, BEKAII-SAAB T, JAIN A, et al.Biliary cancer: Utility of next-generation sequencing for clinical management[J]. Cancer, 2016, 122(24): 3838-3847.
[64] WALTER D, HARTMANN S, WAIDMANN O.Update on cholangiocarcinoma: potential impact of genomic studies on clinical management[J]. Z Gastroenterol, 2017, 55(6): 575-581.
[65] PIHA-PAUL S A, OH D Y, UENO M, et al. Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE-158 and KEYNOTE-028 studies[J]. Int J Cancer, 2020, 147(8): 2190-2198.
[66] SUN D, MA J, WANG J, et al.Anti-PD-1 therapy combined with chemotherapy in patients with advanced biliary tract cancer[J]. Cancer Immunol Immunother, 2019, 68(9): 1527-1535.
[67] KLEIN O, KEE D, NAGRIAL A, et al.Evaluation of Combination Nivolumab and Ipilimumab Immunotherapy in Patients With Advanced Biliary Tract Cancers: Subgroup Analysis of a Phase 2 Nonrandomized Clinical Trial[J]. JAMA Oncol, 2020, 6(9): 1405-1409.
[68] 王敬晗, 李炜, 马文聪, 等. 程序性细胞死亡蛋白-1抑制剂治疗晚期胆道恶性肿瘤疗效和预后因素分析[J]. 中国实用外科杂志, 2021, 41(5): 559-564, 569.