肝外胆管癌的介入治疗现状与展望

doi:10.19401/j.cnki.1007-3639.2022.02.003

中国癌症杂志 ›› 2022, Vol. 32 ›› Issue (2): 118-124.doi: 10.19401/j.cnki.1007-3639.2022.02.003

肝外胆管癌的介入治疗现状与展望

王宏博, 杨业发, 葛乃建()

海军军医大学第三附属医院东方肝胆微创介入中心,上海201805

收稿日期:2021-10-15 修回日期:2022-11-27 出版日期:2022-02-28 发布日期:2022-03-08
通信作者: 葛乃建 E-mail:gelarge@163.com
作者简介:杨业发,海军军医大学第三附属医院东方肝胆微创介入中心主任,主任医师,教授,博士研究生导师。1998年博士毕业于第二军医大学,师从著名肝胆外科学家、国家最高科技奖获得者吴孟超院士。现任中国研究型医院协会介入学分会主任委员,中国医师协会肿瘤介入与靶向治疗专业委员会主任委员,上海市抗癌协会理事,上海市抗癌协会肿瘤介入专业委员会主任委员,国际肝胆胰协会中国分会委员,中国抗癌协会肿瘤介入专业委员会委员,国家自然科学基金评审委员库成员,《抗癌动态》高级编委等职。先后承担国家“863”计划、国家重大传染病专项、国家自然科学基金及军队、省部级科研课题11项,基金总额达500 余万元。发表论文40余篇, 其中SCI收录6篇。申请专利3项。参加编写《肝脏外科学》、《实用肝脏外科学》、《肝癌》、《肝癌治疗学》、《放射介入临床应用进展》、《普通外科手术学》等专著 6部。获2010国际抗癌联盟（UICC）二等奖1项,李瑞麟医学教育奖1项,省部级科技进步二等奖 1项,军队医疗成果和科技进步三等奖各1项。擅长肝脏特殊部位肿瘤、恶性梗阻性黄疸、门脉高压消化道出血、Budd-Chiari综合征及肝胆胰脾术后并发症等的微创介入治疗。
葛乃建,副主任医师,副教授,研究生导师。第二军医大学肝胆外科学博士。现任中国研究型医院学会介入医学专委会秘书长兼常务委员、国际肝胆胰协会中国分会微创介入专委会常务委员、中国生物材料学会生物材料表界面工程分会委员。获首届东方肝胆外科医院吴孟超式优秀青年人才称号。主持国家自然科学基金、部级基金等6项,主持上海市科委课题2项。参编专著3部,担任Journal of Interventional Medicine编委。获专利5项,荣获国家级、部级奖项3项。近5年第一作者在SCI收录期刊上发表论文7篇,其中影响因子>5分4篇。
基金资助:
国家自然科学基金(319711249)

Progress in interventional therapy of extrahepatic cholangiocarcinoma

WANG Hongbo, YANG Yefa, GE Naijian()

Eastern Hepatobiliary Intervention Center, the Third Affiliated Hospital of Naval Medical University, Shanghai 201805, China

Received:2021-10-15 Revised:2022-11-27 Published:2022-02-28 Online:2022-03-08
Contact: GE Naijian E-mail:gelarge@163.com

摘要/Abstract

摘要：

肝外胆管癌是指源于肝外胆管包括肝门区至胆总管下端胆管的恶性肿瘤。在美国癌症联合会（American Joint Committee on Cancer,AJCC）第8版指南中,肝外胆管癌被分类分为肝门胆管癌和远端胆管癌两部分。近年来,肝外胆管癌的发病率逐渐升高,且预后较差,手术切除在治疗中的局限性逐渐体现。在胆管癌的诊断方面,癌胚抗原（carcinoembryonic antigen,CEA）和糖类抗原19-9（carbohydrate antigen 19-9,CA19-9）均无特异性,仅作为提示患者病情改变的标志,便于及时调整治疗。影像学检查如计算机体层成像（computed tomography,CT）或磁共振成像（magnetic resonance imaging,MRI）可以用来进行多期对比,磁共振胰胆管造影（magnetic resonance cholangiopancreatography,MRCP）在肝外胆管癌的诊断中也具有重要的作用。目前,肝部分切除或胆管切除是肝门部胆管癌的常规外科治疗方式,而针对远端胆管癌可以行胰十二指肠切除术,但对于有转移的肝外胆管癌,手术不能达到根治的效果。随着介入治疗技术的发展,针对不可切除的肝外胆管癌的介入治疗将成为新的趋势。近年来,胆道引流、胆道腔内射频消融术（radio frequency ablation,RFA）、胆道支架、放射性粒子植入以及经肝动脉介入治疗等方法在胆管癌治疗中已广泛应用,研究的热点包括胆管癌的胆道引流以及改善胆汁淤积等,目前临床常用的介入治疗方法包括胆管引流术、RFA以及局部放化疗,其中胆道引流术包括经皮穿肝胆管引流术（percutaneous transhepatic biliary drainage,PTBD）、内镜下鼻胆管引流术（endoscopic nasobiliary drainage,ENBD）以及经皮胆道内支架植入术（percutaneous transhepatic biliary stenting,PTBS）,对于缓解病情、治疗胆道梗阻均具有较好的效果。RFA通过高频电流产生热量,达到杀死肿瘤细胞的目的。经动脉化疗栓塞术（transarterial chemoembolization,TACE）已成为肝脏肿瘤主要的治疗方式之一,许多学者在TACE联合放射性粒子植入、TACE联合经动脉灌注化疗（hepatic arterial infusion chemotherapy,HAIC）方面进行尝试,并取得了不同程度的成果; ¹²⁵I粒子近距离放射治疗、立体定向放疗、光动力疗法等在一些小样本的临床试验中也取得了一定的效果,但目前仍旧缺乏大样本的临床数据支持。因此,未来在胆管癌的介入治疗方面,放射性粒子或放射性支架置入病变部位以进行局部放疗,或采用TACE联合HAIC,以及采用分子靶向治疗药物和免疫疗法与介入技术的结合等,有望为肝外胆管癌患者提供更多选择。

关键词: 胆管癌, 介入治疗, 胆道引流术, 射频消融术

Abstract:

Extrahepatic cholangiocarcinoma refers to a malignant tumor originating from the extrahepatic bile duct, including the bile duct from the hilar area to the lower end of the common bile duct. In the 8th edition of American Joint Committee on Cancer (AJCC) guideline, extrahepatic cholangiocarcinoma is classified into two parts: hilar and distal parts. In recent years, the incidence of extrahepatic cholangiocarcinoma has gradually increased, and the prognosis has been poor. The limitations of traditional surgical resection in treatment have gradually manifested. In the diagnosis of cholangiocarcinoma, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are not specific and are only used as a reminder of changes in the condition for patients, which facilitates timely adjustment of treatment. Imaging examinations such as computed tomography (CT)/magnetic resonance imagining (MRI) can be used for multi-phase comparison to achieve the purpose of diagnosis. MRCP also plays an important role in the diagnosis of extrahepatic cholangiocarcinoma. At present, hepatectomy or cholangioectomy is the conventional surgical treatment for hilar cholangiocarcinoma. For distal cholangiocarcinoma, pancreaticoduodenectomy can be performed to achieve the purpose of treatment. However, due to the limitations of traditional surgery, extrahepatic cholangiocarcinoma with metastasis can not be effectively controlled. Therefore, with the development of interventional technology, interventional therapy for unresectable extrahepatic cholangiocarcinoma will become a new trend. In recent years, biliary drainage, radiofrequency ablation of the biliary tract, biliary stents, radioactive particles implantation and transhepatic artery intervention have become more and more mature in the treatment of cholangiocarcinoma. Recent research hotspots include biliary drainage of cholangiocarcinoma and improving cholestasis. The current commonly used interventional treatment methods include bile duct drainage, radiofrequency ablation and local radiotherapy and chemotherapy. Among them, biliary drainage includes percutaneous transhepatic biliary drainage (PTBD), endoscopic nasobiliary drainage (ENBD) and percutaneous transhepatic biliary stenting (PTBS) are effective in relieving the condition and treating biliary obstruction; in addition, radiofrequency ablation generates heat through high-frequency current, which can achieve the purpose of killing tumors. In recent years, transarterial chemoembolization (TACE) has become one of the main treatment options for liver cancer. Many attempts have been made, and various results have been achieved. In addition, ¹²⁵I particle brachytherapy, stereotactic radiotherapy, photodynamic therapy, etc. have also achieved certain effects in some small-sample clinical trials, but they are still lack of sufficient clinical data to support. Therefore, in the future interventional treatment of cholangiocarcinoma, radioactive particles or radioactive stents placed in the lesion for local radiotherapy, TACE combined with hepatic arterial infusion chemotherapy (HAIC), as well as molecular targeted drugs and immunotherapy with combination of interventional technology are hopeful to be effective treatment options for patients with extrahepatic cholangiocarcinoma.

Key words: Cholangiocarcinoma, Interventional therapy, Biliary drainage, Radiofrequency ablation

中图分类号:

R735.8

王宏博, 杨业发, 葛乃建. 肝外胆管癌的介入治疗现状与展望[J]. 中国癌症杂志, 2022, 32(2): 118-124.

WANG Hongbo, YANG Yefa, GE Naijian. Progress in interventional therapy of extrahepatic cholangiocarcinoma[J]. China Oncology, 2022, 32(2): 118-124.

参考文献 43

[1]	李年丰,, 冯思佳. NCCN肝胆肿瘤临床实践指南(2021.V1)胆管肿瘤诊治的解读[J]. 肝胆胰外科杂志, 2021,33(9):513-518.
	LI N F,, FENG S J. Interpretation of NCCN clinical practice guidelines in hepatoliliary cancers (2021, version) for diagnosis and treatment of cholangiocarcinoma[J]. J Hepatopancreatobiliary Surg, 2021,33(9):513-518.
[2]	BANALES J M,, MARIN J J G,, LAMARCA A, et al. Cholangiocarcinoma 2020: the next horizon in mechanisms and management[J]. Nat Rev Gastroenterol Hepatol, 2020,17(9):557-588.
[3]	CHEN P D,, CHEN L J,, CHANG Y J, et al. Long-term survival of combined hepatocellular-cholangiocarcinoma: a nationwide study[J]. Oncologist, 2021,26(10):e1774-e1785.
[4]	RIZVI S,, KHAN S A,, HALLEMEIER C L, et al. Cholangiocarcinoma-evolving concepts and therapeutic strategies[J]. Nat Rev Clin Oncol, 2018,15(2):95-111.
[5]	FERRONE C,, GOYAL L,, QADAN M, et al. Management implications of fluorodeoxyglucose positron emission tomography/magnetic resonance in untreated intrahepatic cholangiocarcinoma[J]. Eur J Nucl Med Mol Imaging, 2020,47(8):1871-1884.
[6]	RIBERO D,, ZIMMITTI G,, ALOIA T A, et al. Preoperative cholangitis and future liver remnant volume determine the risk of liver failure in patients undergoing resection for hilar cholangiocarcinoma[J]. J Am Coll Surg, 2016,223(1):87-97.
[7]	CAI Z Y,, HE C B,, ZHAO C Y, et al. Survival comparisons of hepatic arterial infusion chemotherapy with mFOLFOX and transarterial chemoembolization in patients with unresectable intrahepatic cholangiocarcinoma[J]. Front Oncol, 2021,11:611118.
[8]	KAWAKAMI H,, KUWATANI M,, ONODERA M, et al. Endoscopic nasobiliary drainage is the most suitable preoperative biliary drainage method in the management of patients with hilar cholangiocarcinoma[J]. J Gastroenterol, 2011,46(2):242-248.
[9]	COELEN R J S,, ROOS E,, WIGGERS J K, et al. Endoscopic versus percutaneous biliary drainage in patients with resectable perihilar cholangiocarcinoma: a multicentre, randomised controlled trial[J]. Lancet Gastroenterol Hepatol, 2018,3(10):681-690.
[10]	MAEDA T,, EBATA T,, YOKOYAMA Y, et al. Preoperative course of patients undergoing endoscopic nasobiliary drainage during the management of resectable perihilar cholangiocarcinoma[J]. J Hepatobiliary Pancreat Sci, 2019,26(8):341-347.
[11]	KAWASHIMA H,, HIROOKA Y,, OHNO E, et al. Effectiveness of a modified 6-Fr endoscopic nasobiliary drainage catheter for patients with preoperative perihilar cholangiocarcinoma[J]. Endosc Int Open, 2018,6(8):E1020-E1030.
[12]	NAKAMURA S,, ISHII Y,, SERIKAWA M, et al. Utility of the inside stent as a preoperative biliary drainage method for patients with malignant perihilar biliary stricture[J]. J Hepatobiliary Pancreat Sci, 2021,28(10):864-873.
[13]	KHAN S A,, DAVIDSON B R,, GOLDIN R D, et al. Guidelines for the diagnosis and treatment of cholangiocarcinoma: an update[J]. Gut, 2012,61(12):1657-1669.
[14]	ANDERLONI A,, FUGAZZA A,, TRONCONE E, et al. Single-stage EUS-guided choledochoduodenostomy using a lumen-apposing metal stent for malignant distal biliary obstruction[J]. Gastrointest Endosc, 2019,89(1):69-76.
[15]	中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范(2019年版)[J]. 肝癌电子杂志, 2020,7(1):5-23.
	Medical Administration of the State Health Commission of the People’s Republic of China. Standard for diagnosis and treatment of primary liver cancer (2019 edition)[J]. Electron J Liver Cancer, 2020,7(1):5-23.
[16]	HAN K,, KO H K,, KIM K W, et al. Radiofrequency ablation in the treatment of unresectable intrahepatic cholangiocarcinoma: systematic review and meta-analysis[J]. J Vasc Interv Radiol, 2015,26(7):943-948.
[17]	GAO D J,, YANG J F,, MA S R, et al. Endoscopic radiofrequency ablation plus plastic stent placement versus stent placement alone for unresectable extrahepatic biliary cancer: a multicenter randomized controlled trial[J]. Gastrointest Endosc, 2021, 94(1): 91-100.e2.
[18]	QI S,, YAN H. Effect of percutaneous transhepatic cholangial drainag + radiofrequency ablation combined with biliary stent implantation on the liver function of patients with cholangiocarcinoma complicated with malignant obstructive jaundice[J]. Am J Transl Res, 2021,13(3):1817-1824.
[19]	XIA M X,, WANG S P,, YUAN J G, et al. Effect of endoscopic radiofrequency ablation on the survival of patients with inoperable malignant biliary strictures: a large cohort study[J]. J Hepatobiliary Pancreat Sci, 2021.[Online ahead of print].
[20]	PEREIRA P,, SANTOS A L,, MORAIS R, et al. Endoscopic radiofrequency ablation for palliative treatment of hilar cholangiocarcinoma[J]. VideoGIE, 2021,6(4):195-198.
[21]	INOUE T,, ITO K,, YONEDA M. Novel balloon catheter-based endobiliary radiofrequency ablation system: ex-vivo experimental study[J]. Dig Endosc, 2020,32(6):974-978.
[22]	CILLO U,, FONDEVILA C,, DONADON M, et al. Surgery for cholangiocarcinoma[J]. Liver Int, 2019: 143-155.
[23]	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.
[24]	何湛. PTCD途径胆道金属支架置入术联合放疗在胆管癌患者中的应用效果分析[J]. 浙江创伤外科, 2019,24(1):176-177.
	HE Z. Effect of PTCD biliary metallic stent implantation combined with radiotherapy in patients with cholangiocarcinoma[J]. Zhejiang J Trauma Surg, 2019,24(1):176-177.
[25]	WANG Y,, MAN Z R,, HU X S, et al. Percutaneous biliary stent with intraluminal brachytherapy versus palliative surgery in the management of extrahepatic cholangiocarcinoma[J]. Int J Clin Oncol, 2021,26(5):933-940.
[26]	侯喜山. 胆管支架联合碘( ¹²⁵I)粒子植入介入治疗恶性梗阻性黄疸的临床分析 [J]. 基层医学论坛, 2019,23(32):4637-4638.
	HOU X S. Clinical analysis of biliary stent combined with iodine ( ¹²⁵I) seed implantation in interventional treatment of malignant obstructive jaundice [J]. Med Forum, 2019,23(32):4637-4638.
[27]	LEE J,, YOON W S,, KOOM W S, et al. Efficacy of stereotactic body radiotherapy for unresectable or recurrent cholangiocarcinoma: a meta-analysis and systematic review[J]. Strahlenther Onkol, 2019,195(2):93-102.
[28]	HORGAN A M,, KNOX J J. Adjuvant therapy for biliary tract cancers[J]. J Oncol Pract, 2018,14(12):701-708.
[29]	BAAK R,, WILLEMSSEN F E J A,, VAN NORDEN Y, et al. Stereotactic body radiation therapy after chemotherapy for unresectable perihilar cholangiocarcinoma: the STRONG trial, a phase Ⅰ safety and feasibility study[J]. Cancers (Basel), 2021,13(16):3991.
[30]	WANG Y B,, RONG P H,, FU Y F, et al. Stent with radioactive strand insertion for inoperable hilar cholangiocarcinoma: comparison of unilateral and bilateral insertion[J]. Scand J Gastroenterol, 2021,56(12):1473-1479.
[31]	KIM J Y,, LEE S G,, KANG D, et al. The comparison of endoscopic biliary drainage in malignant hilar obstruction by cholangiocarcinoma: bilateral metal stents versus multiple plastic stents[J]. Gut Liver, 2021,15(6):922-929.
[32]	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.
[33]	PAPROTTKA K J,, GALIÈ F,, INGRISCH M, et al. Outcome and safety after 103 radioembolizations with yttrium-90 resin microspheres in 73 patients with unresectable intrahepatic cholangiocarcinoma-an evaluation of predictors[J]. Cancers (Basel), 2021,13(21):5399.
[34]	GAIRING S J,, THOL F,, MÜLLER L, et al. The addition of transarterial chemoembolization to palliative chemotherapy extends survival in intrahepatic cholangiocarcinoma[J]. J Clin Med, 2021,10(12):2732.
[35]	YANG L D,, SHAN J,, SHAN L, et al. Trans-arterial embolisation therapies for unresectable intrahepatic cholangiocarcinoma: a systematic review[J]. J Gastrointest Oncol, 2015,6(5):570-588.
[36]	MA K W,, CHEUNG T T,, LEUNG B, et al. Adjuvant chemotherapy improves oncological outcomes of resectable intrahepatic cholangiocarcinoma: a meta-analysis[J]. Medicine (Baltimore), 2019,98(5):e14013.
[37]	FULLER C D,, WANG S J,, CHOI M, et al. Multimodality therapy for locoregional extrahepatic cholangiocarcinoma: a population-based analysis[J]. Cancer, 2009,115(22):5175-5183.
[38]	CHOI J H,, OH D,, LEE J H, et al. Initial human experience of endoscopic ultrasound-guided photodynamic therapy with a novel photosensitizer and a flexible laser-light catheter[J]. Endoscopy, 2015,47(11):1035-1038.
[39]	LI Z Y,, JIANG X F,, 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.
[40]	MOHAN B P,, CHANDAN S,, KHAN S R, et al. Photodynamic therapy (PDT), radiofrequency ablation (RFA) with biliary stents in palliative treatment of unresectable extrahepatic cholangiocarcinoma: a systematic review and meta-analysis[J]. J Clin Gastroenterol, 2021.[Online ahead of print].
[41]	LI T,, XU W H,, LIU C, et al. Anticancer effect of biodegradable magnesium on hepatobiliary carcinoma: an in vitro and in vivo study[J]. ACS Biomater Sci Eng, 2021,7(6):2774-2782.
[42]	BATEMAN A C. Immune checkpoint inhibitor therapy in colorectal cancer-the role of cellular pathology[J]. Int J Surg Pathol, 2021,29(6):584-591.
[43]	BARTSCH F,, EBERHARD J,, RÜCKERT F, et al. Repeated resection for recurrent intrahepatic cholangiocarcinoma: a retrospective German multicentre study[J]. Liver Int, 2021,41(1):180-191.

肝外胆管癌的介入治疗现状与展望

Progress in interventional therapy of extrahepatic cholangiocarcinoma

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