混合细胞型肝癌的临床诊疗进展

肝癌电子杂志 ›› 2021, Vol. 8 ›› Issue (2): 43-46.

混合细胞型肝癌的临床诊疗进展

黄璋侃¹, 黄小准¹, 徐林¹, 张仁杰¹, 车旭^1,2, 孙永琨^3,*

1.国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院深圳医院肝胆外科,广东深圳 518116;
2.国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院胰胃外科,北京 100021;
3.国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院北京协和医学院肿瘤医院肿瘤内科,北京 100021

收稿日期:2021-02-09 发布日期:2021-07-16
通讯作者: *孙永琨,E-mail：yongkun2021@126.com
作者简介:黄璋侃, 主治医师,国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院肿瘤医院深圳医院,肝胆外科
基金资助:
深圳市“医疗卫生三名工程”项目资助（SZSM202011010）

Progress in diagnosis and treatment of combined hepatocellular cholangiocarcinoma

Huang Zhangkan¹, Huang Xiaozhun¹, Xu Lin¹, Zhang Renjie¹, Che Xu^1,2, Sun Yongkun^3,*

1. Department of Hepatobiliary Surgery,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital &Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College,Shenzhen 518116, Guangdong, China;
2. Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021,China;
3. Department of Medical Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021,China

Received:2021-02-09 Published:2021-07-16

摘要/Abstract

摘要： 混合细胞型肝癌是一种少见的原发性肝癌,含有肝细胞和胆管细胞分化的混合成分。因其组织学和表型的多样性给诊断以及治疗方面带来很大困难。随着生物化学方法和肿瘤干细胞理论的发展,混合型肝癌的特殊病理分型、肿瘤生物学和临床表现获得了越来越多的认识。本文将从病理学、临床诊断及治疗等方面对混合型肝癌的最新研究进展进行介绍。

关键词: 混合细胞型肝癌, 肝肿瘤, 病理学, 诊断, 治疗

Abstract: Combined hepatocellular-cholangiocarcinoma is a rare primary liver cancer, which contains a mixture of hepatocytes and cholangiocytes. Because of the diversity of histology and phenotype, it is difficult to diagnose and treat. With the development of biochemical methods and cancer stem cell theory, the special pathological classification, tumor biology and clinical manifestations of Combined hepatocellular-cholangiocarcinoma have been more and more recognized. The thesis summarizes the recent progress in combined hepatocellular-cholangiocarcinoma from the perspective of Pathology, diagnosis, and treatment.

Key words: Combined hepatocellular-cholangiocarcinoma, Liver neoplasms, Pathology, Diagnosis, Treatment

黄璋侃, 黄小准, 徐林, 张仁杰, 车旭, 孙永琨. 混合细胞型肝癌的临床诊疗进展[J]. 肝癌电子杂志, 2021, 8(2): 43-46.

Huang Zhangkan, Huang Xiaozhun, Xu Lin, Zhang Renjie, Che Xu, Sun Yongkun. Progress in diagnosis and treatment of combined hepatocellular cholangiocarcinoma[J]. Electronic Journal of Liver Tumor, 2021, 8(2): 43-46.

参考文献

[1] TAGUCHI J, NAKASHIMA O, TANAKA M, et al.A clinicopathological study on combined hepatocellular and cholangiocarcinoma[J]. J Gastroenterol Hepatol, 1996, 11(8): 758-764.
[2] KOMUTA M, SPEE B, BORGHT SV, et al.Clinicopathological study on cholangiolocellular carcinoma suggesting hepatic progenitor cell origin[J]. Hepatology, 2008, 47(5): 1544-1556.
[3] 蔡雄. 混合型肝细胞—胆管细胞癌发生机制及临床意义的研究[D].上海:第二军医大学,2012.
[4] SASAKI M, SATO H, KAKUDA Y, et al.Clinicopathological significance of subtypes with stem-cell feature' in combined hepatocellular-cholangiocarcinoma[J]. Liver Int, 2015, 35(3): 1024-1035.
[5] 孙丽萍,周燕,曹敏,等.混合型肝癌的免疫组织化学分析[J].中华消化杂志,2002,22(11):671-673.
[6] 徐菁,张翠明,乔爱秀,等.混合型肝癌伴干细胞特征(细胆管癌型)26例临床病理学观察[J].中华病理学杂志,2016,45(3):175-179.
[7] KLEIN W M, MOLMENTI E P, COLOMBANI P M, et al.Primary liver carcinoma arising in people younger than 30 years[J]. Am J Clin Pathol, 2005, 124(4): 512-518.
[8] WU P, FANG J, LAU V, et al.Classification of hepatocellular carcinoma according to hepatocellular and biliary differentiation markers. Clinical and biological implications[J]. Am J Pathol, 1996, 149(4): 1167-1175.
[9] KOMUTA M, GOVAERE O, VANDECAVEYE V, et al.Histological diversity in cholangiocellular carcinoma reflects the different cholangiocyte phenotypes[J]. Hepatology, 2012, 55(6): 1876-1888.
[10] AKIBA J, NAKASHIMA O, HATTORI S, et al.Clinicopathologic analysis of combined hepatocellular-cholangiocarcinoma according to the latest WHO classification[J]. Am J Surg Pathol, 2013, 37(4): 496-505.
[11] PIERRE‐ALAIN C, MICHIIE S, HIROHISA Y, et al. cHCC‐CCA: Consensus terminology for primary liver carcinomas with both hepatocytic and cholangiocyticdifferentation[J]. Hepatology, 2018, 68(1): 113-126.
[12] 杨新伟,傅晓辉,张永杰.细胆管癌的临床病理特征[J].世界华人消化杂志,2019,27(18):1114-1117.
[13] MOEINI A, SIA D, ZHANG Z, et al.Mixed hepatocellular cholangiocarcinoma tumors: Cholangiolocellular carcinoma is a distinct molecular entity[J]. J Hepatol, 2017, 66(5): 952-961.
[14] CHEN J, HE J, DENG M, et al.Clinicopathological, radiologic, and molecular study of 23 combined hepatocellular-cholangiocarcinomas with stem cell features, cholangiolocellular type[J]. Human Pathology, 2017, 64: 118-127.
[15] SASAKI M, SATO Y, NAKANUMA Y.Mutational landscape of combined hepatocellular carcinoma and cholangiocarcinoma, and its clinicopathological significance[J]. Histopathology, 2017, 70(3): 423-434.
[16] CHANTAJITR S, WILASRUSMEE C, LERTSITICHAI P, et al.Combined hepatocellular and cholangiocarcinoma: clinical features and prognostic study in a Thai population[J]. J Hepatobiliary Pancreat Surg, 2006, 13(6): 537-542.
[17] JARNAGIN W R, WEBER S, TICKOO S K, et al.Combined hepatocellular and cholangiocarcinoma: demographic, clinical, and prognostic factors[J]. Cancer, 2010, 94(7): 2040-2046.
[18] KASSAHUN WT, HAUSS J.Management of combined hepatocellular and cholangiocarcinoma[J]. Int J Clin Pract, 2008, 62(8): 1271-1278.
[19] LI R, YANG D, TANG C L, et al.Combined hepatocellular carcinoma and cholangiocarcinoma (biphenotypic) tumors: clinical characteristics, imaging features of contrast-enhanced ultrasound and computed tomography[J]. BMC Cancer, 2016,16(1): 1-11.
[20] GRANATA V, FUSCO R, SETOLA SV, et al.Major and ancillary features according to LI-RADS in the assessment of combined hepatocellular-cholangiocarcinoma[J]. Radiol Oncol, 2020, 54(2): 149-158.
[21] LEE HS, KIM MJ, AN C.How to utilize LR-M features of the LI-RADS to improve the diagnosis of combined hepatocellular-cholangiocarcinoma on gadoxetate-enhanced MRI?[J]. Eur Radiol, 2019, 29(5): 2408-2416.
[22] ZHANG HC, ZHU T, HU RF, et al.Contrast-enhanced ultrasound imaging features and clinical characteristics of combined hepatocellular cholangiocarcinoma: comparison with hepatocellular carcinoma and cholangiocarcinoma[J]. Ultrasonography, 2020, 39(4): 356-366.
[23] KIM KH, LEE SG, PARK EH, et al.Surgical Treatments and Prognoses of Patients with Combined Hepatocellular Carcinoma and Cholangiocarcinoma[J]. Ann Surg Oncol, 2009, 16(3): 623-629.
[24] SASAKI A, KAWANO K, ARAMAKI M, et al.Clinicopathologic study of mixed hepatocellular and cholangiocellular carcinoma: modes of spreading and choice of surgical treatment by reference to macroscopic type[J]. J Surg Oncol, 2015, 76(1): 37-46.
[25] WANG J, LI E, YANG H, et al.Combined hepatocellular-cholangiocarcinoma: a population level analysis of incidence and mortality trends[J]. World J Surg Oncol, 2019, 17(1): 43.
[26] JUNG DH, HWANG S, SONG GW, et al.Longterm prognosis of combined hepatocellular carcinoma-cholangiocarcinoma following liver transplantation and resection[J]. Liver Transpl, 2017, 23(3): 330-341.
[27] SONG S, MOON H H, LEE S, et al.Comparison between resection and transplantation in combined hepatocellular and cholangiocarcinoma[J]. Transplant Proc, 2013, 45(8): 3041-3046.
[28] BERGQUIST JR, GROESCHL RT, IVANICS T, et al.Mixed hepatocellular and cholangiocarcinoma: a rare tumor with a mix of parent phenotypic characteristics[J]. HPB (Oxford), 2016, 18(11): 886-892.
[29] ANTWI SO, HABBOUSH YY, CHASE LA, et al.Response to loco-regional therapy predicts outcomes after liver transplantation for combined hepatocellular-cholangiocarcinoma[J]. Ann Hepatol, 2018, 17(6): 969-979.
[30] MAGISTRI P, TARANTINO G, SERRA V, et al.Liver transplantation and combined hepatocellular-cholangiocarcinoma: Feasibility and outcomes[J]. Dig Liver Dis, 2017, 49(5): 467-470.
[31] JARADAT D, BAGIAS G, LORF T, et al.Liver transplantation for combined hepatocellular-cholangiocarcinoma: outcomes and prognostic factors for mortality. A multicenter analysis[J]. Clin Transplant, 2020, 35(2): e14094.
[32] FOWLER K, SAAD N E, BRUNT E, et al.Biphenotypic primary liver carcinomas: assessing outcomes of hepatic directed therapy[J]. Ann Surg Oncol, 2015, 22(13): 4130-4137.
[33] KYUN N S, HYEON C G, CHU L H, et al.The effectiveness of transarterial chemoembolization in recurrent hepatocellular-cholangiocarcinoma after resection[J]. Plos One, 2018, 13(6): e0198138
[34] BADAR W, VAN HA T, ZANGAN S, et al.Yttrium-90 radioembolization therapy for combined hepatocellular and cholangiocarcinoma[J]. Gastrointestinal Tumors, 2020, 7(4): 144-150.
[35] MALONE CD, GIBBY W, TSAI R, et al.Outcomes of Yttrium-90 radioembolization for unresectable combined biphenotypic hepatocellular-cholangiocarcinoma[J]. J Vasc Interv Radiol, 2020, 31(5): 701-709.
[36] SATOSHI K, TAKESHI T, SATOSHI S, et al.Multicenter retrospective analysis of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma[J]. Cancer Science, 2018, 109(8): 2549-2557.
[37] ROGERS JE, BOLONESI RM, RASHID A, et al.Systemic therapy for unresectable, mixed hepatocellular-cholangiocarcinoma: treatment of a rare malignancy[J]. J Gastrointest Oncol, 2017, 8(2): 347-351.
[38] YANO Y, YAMAMOTO J, KOSUGE T, et al.Combined hepatocellular and cholangiocarcinoma: a clinicopathologic study of 26 resected cases[J]. Jpn J Clin Oncol, 2003, 33(6): 283-287.
[39] LEE WS, LEE KW, HEO JS, et al.Comparison of combined hepatocellular and cholangiocarcinoma with hepatocellular carcinoma and intrahepatic cholangiocarcinoma[J]. Surgery Today, 2006, 36(10): 892-897.
[40] ARIIZUMI S I, KOTERA Y, KATAGIRI S, et al.Combined hepatocellular-cholangiocarcinoma had poor outcomes after hepatectomy regardless of allen and lisa class or the predominance of intrahepatic cholangiocarcinoma cells within the tumor[J]. Ann Surg Oncol, 2012, 19(5): 1628-1636.
[41] KIM SH,PARK YN, LIM JH, et al.Characteristics of combined hepatocelluar-cholangiocarcinoma and comparison with intrahepatic cholangiocarcinoma[J]. Eur J Surg Oncol, 2014, 40(8): 976-981.
[42] FUTSUKAICHI Y, TAJIRI K, KOBAYASHI S, et al.Combined hepatocellular-cholangiocarcinoma successfully treated with sorafenib: case report and review of the literature[J]. Clin J Gastroenterol, 2019, 12(2): 128-134.
[43] LIU ZH, LIAN BF, DONG QZ, et al.Whole-exome mutational and transcriptional landscapes of combined hepatocellular cholangiocarcinoma and intrahepatic cholangiocarcinoma reveal molecular diversity[J]. Biochim Biophys Acta Mol Basis Dis, 2018, 1864(6B): 2360-2368.
[44] CHENG AL, HSU C, CHAN SL, et al.Challenges of combination therapy with immune checkpoint inhibitors for hepatocellular carcinoma[J]. J Hepatol, 2020, 72(2): 307-319.
[45] BROUTIERL, MASTROGIOVANNI G, VERSTEGEN M M, et al.Human primary liver cancer-derived organoid cultures for disease modeling and drug screening[J]. Nat Med, 2017, 23(12): 1424-1435.