Research progress in clinical diagnosis and treatment strategies of combined hepatocellular<b>-</b>cholangiocarcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

XU Zhenying , CHEN Ting , MA Jiaman ,  YANG Yu

Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

YANG Yu, Email: yangyu@wchscu.cn

Keywords：

combined hepatocellular-cholangiocarcinoma; diagnosis; treatment

DOI：

10.7507/1007-9424.202206050

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To summarize the diagnosis and treatment progress of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) in recent years, in order to provide a reference for clinical diagnosis and treatment decision-making. Method The recent literature related to the diagnosis and treatment of cHCC-CCA was reviewed. Results There was no specific guideline or consensus on the diagnosis and management of cHCC-CCA. The diagnosis of the cHCC-CCA was challenging by imaging alone, and the tumor markers such as alpha fetoprotein and carbohydrate antigen 19-9 were of particular value in clinical diagnosis, but it was ultimately relied on the pathological examination results. For the patients with early cHCC-CCA, the radical surgery was recommended to undergo if possible, but there was some controversy regarding the efficacy of liver transplantation and the mode of recurrence and metastasis. For the patients with advanced cHCC-CCA, the systemic therapy was being explored further, and some retrospective analyses of small samples suggested that the gemcitabine and platinum-containing chemotherapy regimens might be beneficial. With the better success of immunotherapy and targeted therapies in hepatocellular carcinoma and cholangiocarcinoma, it might provide some experiences for treatment selection of cHCC-CCA. Conclusions cHCC-CCA has a lower incidence rate and stronger heterogeneity. Its diagnosis mainly relies on surgical pathology, and treatment strategy is lack of high-level evidence-based medical evidence and rigorously designed clinical studies are still needed to explore its efficacy and safety in the future.

Citation： XU Zhenying, CHEN Ting, MA Jiaman, YANG Yu. Research progress in clinical diagnosis and treatment strategies of combined hepatocellular-cholangiocarcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(12): 1667-1673. doi: 10.7507/1007-9424.202206050 Copy

1.	McGlynn KA, Petrick JL, El-Serag HB. Epidemiology of hepatocellular carcinoma. Hepatology, 2021, 73 Suppl 1(Suppl 1): 4-13.
2.	Wakizaka K, Yokoo H, Kamiyama T, et al. Clinical and pathological features of combined hepatocellular-cholangiocarcinoma compared with other liver cancers. J Gastroenterol Hepatol, 2019, 34(6): 1074-1080.
3.	Trikalinos NA, Zhou A, Doyle MBM, et al. Systemic therapy for combined hepatocellular-cholangiocarcinoma: a single-institution experience. J Natl Compr Canc Netw, 2018, 16(10): 1193-1199.
4.	Huang X, Li Y, Long L. Comparison of imaging and clinically relevant features of combined hepatocellular carcinoma and cholangiocarcinoma with hepatocellular carcinoma. Med Sci Monit, 2019, 25: 8595-8601.
5.	Beaufrère A, Calderaro J, Paradis V. Combined hepatocellular-cholangiocarcinoma: an update. J Hepatol, 2021, 74(5): 1212-1224.
6.	Rizvi S, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology, 2013, 145(6): 1215-1229.
7.	Villanueva A. Hepatocellular carcinoma. N Engl J Med, 2019, 380(15): 1450-1462.
8.	Cutolo C, Dell’Aversana F, Fusco R, et al. Combined hepato-cellular-cholangiocarcinoma: what the multidisciplinary team should know. Diagnostics (Basel), 2022, 12(4): 890. doi: 10.3390/diagnostics12040890.
9.	Jarnagin WR, Weber S, Tickoo SK, et al. Combined hepatocellular and cholangiocarcinoma: demographic, clinical, and prognostic factors. Cancer, 2002, 94(7): 2040-2046.
10.	Wachtel MS, Zhang Y, Xu T, et al. Combined hepatocellular cholangiocarcinomas; analysis of a large database. Clin Med Pathol, 2008, 1: 43-47.
11.	Yamashita YI, Aishima S, Nakao Y, et al. Clinicopathological characteristics of combined hepatocellular cholangiocarcinoma from the viewpoint of patient prognosis after hepatic resection: high rate of early recurrence and its predictors. Hepatol Res, 2020, 50(7): 863-870.
12.	张瑜, 刘秀峰, 秦叔逵, 等. 混合型肝癌的临床特征和预后分析. 临床肿瘤学杂志, 2019, 24(8): 738-742.
13.	Ishii T, Ito T, Sumiyoshi S, et al. Clinicopathological features and recurrence patterns of combined hepatocellular-cholangiocarcinoma. World J Surg Oncol, 2020, 18(1): 319. doi: 10.1186/s12957-020-02099-w.
14.	Gao YX, Yang TW, Yin JM, et al. Progress and prospects of biomarkers in primary liver cancer (Review). Int J Oncol, 2020, 57(1): 54-66.
15.	Zhang H, Yu X, Xu J, et al. Combined hepatocellular-cholangiocarcinoma: an analysis of clinicopathological characteristics after surgery. Medicine (Baltimore), 2019, 98(38): e17102. doi: 10.1097/MD.0000000000017102.
16.	Li R, Yang D, Tang CL, et al. Combined hepatocellular carcinoma and cholangiocarcinoma (biphenotypic) tumors: clinical characteristics, imaging features of contrast-enhanced ultrasound and computed tomography. BMC Cancer, 2016, 16: 158. doi: 10.1186/s12885-016-2156-x.
17.	Sasaki M, Sato Y, Nakanuma Y. Is nestin a diagnostic marker for combined hepatocellular-cholangiocarcinoma? Histopathology, 2022, 80(5): 859-868.
18.	Kono Y, Lyshchik A, Cosgrove D, et al. Contrast Enhanced Ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS^®): the official version by the American College of Radiology (ACR). Ultraschall Med, 2017, 38(1): 85-86.
19.	Yang J, Huang JY, Chen X, et al. Combined hepatocellular-cholangiocarcinoma: can we use contrast-enhanced ultrasound Liver Imaging Reporting and Data System (LI-RADS) to predict the patient’s survival? Eur Radiol, 2021, 31(8): 6397-6405.
20.	Granata V, Fusco R, Venanzio Setola S, et al. Major and ancillary features according to LI-RADS in the assessment of combined hepatocellular-cholangiocarcinoma. Radiol Oncol, 2020, 54(2): 149-158.
21.	Brunt E, Aishima S, Clavien PA, et al. cHCC-CCA: consensus terminology for primary liver carcinomas with both hepatocytic and cholangiocytic differentation. Hepatology, 2018, 68(1): 113-126.
22.	Gigante E, Ronot M, Bertin C, et al. Combining imaging and tumour biopsy improves the diagnosis of combined hepatocellular-cholangiocarcinoma. Liver Int, 2019, 39(12): 2386-2396.
23.	Kudo M, Izumi N, Kubo S, et al. Report of the 20th Nationwide follow-up survey of primary liver cancer in Japan. Hepatol Res, 2020, 50(1): 15-46.
24.	Lee JH, Chung GE, Yu SJ, et al. Long-term prognosis of combined hepatocellular and cholangiocarcinoma after curative resection comparison with hepatocellular carcinoma and cholangiocarcinoma. J Clin Gastroenterol, 2011, 45(1): 69-75.
25.	Lin CW, Wu TC, Lin HY, et al. Clinical features and outcomes of combined hepatocellular carcinoma and cholangiocarcinoma versus hepatocellular carcinoma versus cholangiocarcinoma after surgical resection: a propensity score matching analysis. BMC Gastroenterol, 2021, 21(1): 20. doi: 10.1186/s12876-020-01586-4.
26.	Zhou C, Wang Y, Ma L, et al. Combined hepatocellular carcinoma-cholangiocarcinoma: MRI features correlated with tumor biomarkers and prognosis. Eur Radiol, 2022, 32(1): 78-88.
27.	Sempokuya T, Wien EA, Pattison RJ, et al. Factors associated with 5-year survival of combined hepatocellular and cholangiocarcinoma. World J Hepatol, 2020, 12(11): 1020-1030.
28.	Jiang XX, Huang XT, Huang CS, et al. Long-term outcome and prognostic factors of combined hepatocellular carcinoma and cholangiocarcinoma after curative resection. Gastroenterol Rep (Oxf), 2020, 8(2): 134-142.
29.	Kim JH, Yoon HK, Ko GY, et al. Nonresectable combined hepatocellular carcinoma and cholangiocarcinoma: analysis of the response and prognostic factors after transcatheter arterial chemoembolization. Radiology, 2010, 255(1): 270-277.
30.	Gupta R, Togashi J, Akamatsu N, et al. Impact of incidental/misdiagnosed intrahepatic cholangiocarcinoma and combined hepatocellular cholangiocarcinoma on the outcomes of liver transplantation: an institutional case series and literature review. Surg Today, 2017, 47(8): 908-917.
31.	Groeschl RT, Turaga KK, Gamblin TC. Transplantation versus resection for patients with combined hepatocellular carcinoma-cholangiocarcinoma. J Surg Oncol, 2013, 107(6): 608-612.
32.	De Martin E, Rayar M, Golse N, et al. Analysis of liver resection versus liver transplantation on outcome of small intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma in the setting of cirrhosis. Liver Transpl, 2020, 26(6): 785-798.
33.	Dageforde LA, Vachharajani N, Tabrizian P, et al. Multi-center analysis of liver transplantation for combined hepatocellular carcinoma-cholangiocarcinoma liver tumors. J Am Coll Surg, 2021, 232(4): 361-371.
34.	Wang Z, Ren Z, Chen Y, et al. Adjuvant transarterial chemoembolization for HBV-related hepatocellular carcinoma after resection: a randomized controlled study. Clin Cancer Res, 2018, 24(9): 2074-2081.
35.	Wei W, Jian PE, Li SH, et al. Adjuvant transcatheter arterial chemoembolization after curative resection for hepatocellular carcinoma patients with solitary tumor and microvascular invasion: a randomized clinical trial of efficacy and safety. Cancer Commun (Lond), 2018, 38(1): 61. doi: 10.1186/s40880-018-0331-y.
36.	中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗指南(2022年版). 肿瘤综合治疗电子杂志, 2022, 8(2): 16-53.
37.	Liu WR, Tian MX, Tao CY, et al. Adjuvant transarterial chemoembolization does not influence recurrence-free or overall survival in patients with combined hepatocellular carcinoma and cholangiocarcinoma after curative resection: a propensity score matching analysis. BMC Cancer, 2020, 20(1): 642. doi: 10.1186/s12885-020-07138-z.
38.	Mukund A, V Srinivasan S, Rana S, et al. Response evaluation of locoregional therapies in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma versus hepatocellular carcinoma: a propensity score matched study. Clin Radiol, 2022, 77(2): 121-129.
39.	Huang YH, Park BV, Chen YF, et al. Locoregional therapy of hepatocellular-cholangiocarcinoma versus hepatocellular carcinoma: a propensity score-matched study. J Vasc Interv Radiol, 2019, 30(9): 1317-1324.
40.	Fowler K, Saad NE, Brunt E, et al. Biphenotypic primary liver carcinomas: assessing outcomes of hepatic directed therapy. Ann Surg Oncol, 2015, 22(13): 4130-4137.
41.	Badar W, Van Ha T, Zangan S, et al. Yttrium-90 radioembolization therapy for combined hepatocellular and cholangiocarcinoma. Gastrointest Tumors, 2020, 7(4): 144-150.
42.	Joseph NM, Tsokos CG, Umetsu SE, et al. Genomic profiling of combined hepatocellular-cholangiocarcinoma reveals similar genetics to hepatocellular carcinoma. J Pathol, 2019, 248(2): 164-178.
43.	Murugesan K, Sharaf R, Montesion M, et al. Genomic profiling of combined hepatocellular cholangiocarcinoma reveals genomics similar to either hepatocellular carcinoma or cholangiocarcinoma. JCO Precis Oncol, 2021, 5: PO. 20.00397. doi: 10.1200/PO.20.00397.
44.	Xue R, Chen L, Zhang C, et al. Genomic and transcriptomic profiling of combined hepatocellular and intrahepatic cholangiocarcinoma reveals distinct molecular subtypes. Cancer Cell, 2019, 35(6): 932-947.
45.	Kobayashi S, Terashima T, Shiba S, et al. Multicenter retrospective analysis of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma. Cancer Sci, 2018, 109(8): 2549-2557.
46.	Salimon M, Prieux-Klotz C, Tougeron D, et al. Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study. Br J Cancer, 2018, 118(3): 325-330.
47.	Ren Z, Xu J, Bai Y, et al. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study. Lancet Oncol, 2021, 22(7): 977-990.
48.	Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med, 2020, 382(20): 1894-1905.
49.	Finn RS, Ikeda M, Zhu AX, et al. Phase Ⅰb study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma. J Clin Oncol, 2020, 38(26): 2960-2970.
50.	Xu J, Shen J, Gu S, et al. Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE): a nonrandomized, open-label, phase Ⅱ trial. Clin Cancer Res, 2021, 27(4): 1003-1011.
51.	Zhou J, Fan J, Shi G, et al. 56P anti-PD1 antibody toripalimab, lenvatinib and gemox chemotherapy as first-line treatment of advanced and unresectable intrahepatic cholangiocarcinoma: a phase Ⅱ clinical trial. Ann Oncol, 2020, 31: S262-S263. doi: 10.1016/j.annonc.2020.08.034.
52.	Villanueva L, Lwin Z, Chung HC, et al. Lenvatinib plus pembrolizumab for patients with previously treated biliary tract cancers in the multicohort phase Ⅱ LEAP-005 study. 2021 Gastrointestinal Cancers Symposium. San Francisco, California, United States, 2021, 39: 321-321.
53.	OH DY, HE AR, QIN SK, et al. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1. J Clin Oncol, 2022, 40(4_suppl): 378-378.
54.	Nguyen CT, Caruso S, Maille P, et al. Immune profiling of combined hepatocellular-cholangiocarcinoma reveals distinct subtypes and activation of gene signatures predictive of response to immunotherapy. Clin Cancer Res, 2022, 28(3): 540-551.
55.	Sun W, Patel A, Normolle D, et al. A phase 2 trial of regorafenib as a single agent in patients with chemotherapy-refractory, advanced, and metastatic biliary tract adenocarcinoma. Cancer, 2019, 125(6): 902-909.
56.	Kim RD, Chung V, Alese OB, et al. A phase 2 multi-institutional study of nivolumab for patients with advanced refractory biliary tract cancer. JAMA Oncol, 2020, 6(6): 888-894.

1. McGlynn KA, Petrick JL, El-Serag HB. Epidemiology of hepatocellular carcinoma. Hepatology, 2021, 73 Suppl 1(Suppl 1): 4-13.
2. Wakizaka K, Yokoo H, Kamiyama T, et al. Clinical and pathological features of combined hepatocellular-cholangiocarcinoma compared with other liver cancers. J Gastroenterol Hepatol, 2019, 34(6): 1074-1080.
3. Trikalinos NA, Zhou A, Doyle MBM, et al. Systemic therapy for combined hepatocellular-cholangiocarcinoma: a single-institution experience. J Natl Compr Canc Netw, 2018, 16(10): 1193-1199.
4. Huang X, Li Y, Long L. Comparison of imaging and clinically relevant features of combined hepatocellular carcinoma and cholangiocarcinoma with hepatocellular carcinoma. Med Sci Monit, 2019, 25: 8595-8601.
5. Beaufrère A, Calderaro J, Paradis V. Combined hepatocellular-cholangiocarcinoma: an update. J Hepatol, 2021, 74(5): 1212-1224.
6. Rizvi S, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology, 2013, 145(6): 1215-1229.
7. Villanueva A. Hepatocellular carcinoma. N Engl J Med, 2019, 380(15): 1450-1462.
8. Cutolo C, Dell’Aversana F, Fusco R, et al. Combined hepato-cellular-cholangiocarcinoma: what the multidisciplinary team should know. Diagnostics (Basel), 2022, 12(4): 890. doi: 10.3390/diagnostics12040890.
9. Jarnagin WR, Weber S, Tickoo SK, et al. Combined hepatocellular and cholangiocarcinoma: demographic, clinical, and prognostic factors. Cancer, 2002, 94(7): 2040-2046.
10. Wachtel MS, Zhang Y, Xu T, et al. Combined hepatocellular cholangiocarcinomas; analysis of a large database. Clin Med Pathol, 2008, 1: 43-47.
11. Yamashita YI, Aishima S, Nakao Y, et al. Clinicopathological characteristics of combined hepatocellular cholangiocarcinoma from the viewpoint of patient prognosis after hepatic resection: high rate of early recurrence and its predictors. Hepatol Res, 2020, 50(7): 863-870.
12. 张瑜, 刘秀峰, 秦叔逵, 等. 混合型肝癌的临床特征和预后分析. 临床肿瘤学杂志, 2019, 24(8): 738-742.
13. Ishii T, Ito T, Sumiyoshi S, et al. Clinicopathological features and recurrence patterns of combined hepatocellular-cholangiocarcinoma. World J Surg Oncol, 2020, 18(1): 319. doi: 10.1186/s12957-020-02099-w.
14. Gao YX, Yang TW, Yin JM, et al. Progress and prospects of biomarkers in primary liver cancer (Review). Int J Oncol, 2020, 57(1): 54-66.
15. Zhang H, Yu X, Xu J, et al. Combined hepatocellular-cholangiocarcinoma: an analysis of clinicopathological characteristics after surgery. Medicine (Baltimore), 2019, 98(38): e17102. doi: 10.1097/MD.0000000000017102.
16. Li R, Yang D, Tang CL, et al. Combined hepatocellular carcinoma and cholangiocarcinoma (biphenotypic) tumors: clinical characteristics, imaging features of contrast-enhanced ultrasound and computed tomography. BMC Cancer, 2016, 16: 158. doi: 10.1186/s12885-016-2156-x.
17. Sasaki M, Sato Y, Nakanuma Y. Is nestin a diagnostic marker for combined hepatocellular-cholangiocarcinoma? Histopathology, 2022, 80(5): 859-868.
18. Kono Y, Lyshchik A, Cosgrove D, et al. Contrast Enhanced Ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS^®): the official version by the American College of Radiology (ACR). Ultraschall Med, 2017, 38(1): 85-86.
19. Yang J, Huang JY, Chen X, et al. Combined hepatocellular-cholangiocarcinoma: can we use contrast-enhanced ultrasound Liver Imaging Reporting and Data System (LI-RADS) to predict the patient’s survival? Eur Radiol, 2021, 31(8): 6397-6405.
20. Granata V, Fusco R, Venanzio Setola S, et al. Major and ancillary features according to LI-RADS in the assessment of combined hepatocellular-cholangiocarcinoma. Radiol Oncol, 2020, 54(2): 149-158.
21. Brunt E, Aishima S, Clavien PA, et al. cHCC-CCA: consensus terminology for primary liver carcinomas with both hepatocytic and cholangiocytic differentation. Hepatology, 2018, 68(1): 113-126.
22. Gigante E, Ronot M, Bertin C, et al. Combining imaging and tumour biopsy improves the diagnosis of combined hepatocellular-cholangiocarcinoma. Liver Int, 2019, 39(12): 2386-2396.
23. Kudo M, Izumi N, Kubo S, et al. Report of the 20th Nationwide follow-up survey of primary liver cancer in Japan. Hepatol Res, 2020, 50(1): 15-46.
24. Lee JH, Chung GE, Yu SJ, et al. Long-term prognosis of combined hepatocellular and cholangiocarcinoma after curative resection comparison with hepatocellular carcinoma and cholangiocarcinoma. J Clin Gastroenterol, 2011, 45(1): 69-75.
25. Lin CW, Wu TC, Lin HY, et al. Clinical features and outcomes of combined hepatocellular carcinoma and cholangiocarcinoma versus hepatocellular carcinoma versus cholangiocarcinoma after surgical resection: a propensity score matching analysis. BMC Gastroenterol, 2021, 21(1): 20. doi: 10.1186/s12876-020-01586-4.
26. Zhou C, Wang Y, Ma L, et al. Combined hepatocellular carcinoma-cholangiocarcinoma: MRI features correlated with tumor biomarkers and prognosis. Eur Radiol, 2022, 32(1): 78-88.
27. Sempokuya T, Wien EA, Pattison RJ, et al. Factors associated with 5-year survival of combined hepatocellular and cholangiocarcinoma. World J Hepatol, 2020, 12(11): 1020-1030.
28. Jiang XX, Huang XT, Huang CS, et al. Long-term outcome and prognostic factors of combined hepatocellular carcinoma and cholangiocarcinoma after curative resection. Gastroenterol Rep (Oxf), 2020, 8(2): 134-142.
29. Kim JH, Yoon HK, Ko GY, et al. Nonresectable combined hepatocellular carcinoma and cholangiocarcinoma: analysis of the response and prognostic factors after transcatheter arterial chemoembolization. Radiology, 2010, 255(1): 270-277.
30. Gupta R, Togashi J, Akamatsu N, et al. Impact of incidental/misdiagnosed intrahepatic cholangiocarcinoma and combined hepatocellular cholangiocarcinoma on the outcomes of liver transplantation: an institutional case series and literature review. Surg Today, 2017, 47(8): 908-917.
31. Groeschl RT, Turaga KK, Gamblin TC. Transplantation versus resection for patients with combined hepatocellular carcinoma-cholangiocarcinoma. J Surg Oncol, 2013, 107(6): 608-612.
32. De Martin E, Rayar M, Golse N, et al. Analysis of liver resection versus liver transplantation on outcome of small intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma in the setting of cirrhosis. Liver Transpl, 2020, 26(6): 785-798.
33. Dageforde LA, Vachharajani N, Tabrizian P, et al. Multi-center analysis of liver transplantation for combined hepatocellular carcinoma-cholangiocarcinoma liver tumors. J Am Coll Surg, 2021, 232(4): 361-371.
34. Wang Z, Ren Z, Chen Y, et al. Adjuvant transarterial chemoembolization for HBV-related hepatocellular carcinoma after resection: a randomized controlled study. Clin Cancer Res, 2018, 24(9): 2074-2081.
35. Wei W, Jian PE, Li SH, et al. Adjuvant transcatheter arterial chemoembolization after curative resection for hepatocellular carcinoma patients with solitary tumor and microvascular invasion: a randomized clinical trial of efficacy and safety. Cancer Commun (Lond), 2018, 38(1): 61. doi: 10.1186/s40880-018-0331-y.
36. 中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗指南(2022年版). 肿瘤综合治疗电子杂志, 2022, 8(2): 16-53.
37. Liu WR, Tian MX, Tao CY, et al. Adjuvant transarterial chemoembolization does not influence recurrence-free or overall survival in patients with combined hepatocellular carcinoma and cholangiocarcinoma after curative resection: a propensity score matching analysis. BMC Cancer, 2020, 20(1): 642. doi: 10.1186/s12885-020-07138-z.
38. Mukund A, V Srinivasan S, Rana S, et al. Response evaluation of locoregional therapies in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma versus hepatocellular carcinoma: a propensity score matched study. Clin Radiol, 2022, 77(2): 121-129.
39. Huang YH, Park BV, Chen YF, et al. Locoregional therapy of hepatocellular-cholangiocarcinoma versus hepatocellular carcinoma: a propensity score-matched study. J Vasc Interv Radiol, 2019, 30(9): 1317-1324.
40. Fowler K, Saad NE, Brunt E, et al. Biphenotypic primary liver carcinomas: assessing outcomes of hepatic directed therapy. Ann Surg Oncol, 2015, 22(13): 4130-4137.
41. Badar W, Van Ha T, Zangan S, et al. Yttrium-90 radioembolization therapy for combined hepatocellular and cholangiocarcinoma. Gastrointest Tumors, 2020, 7(4): 144-150.
42. Joseph NM, Tsokos CG, Umetsu SE, et al. Genomic profiling of combined hepatocellular-cholangiocarcinoma reveals similar genetics to hepatocellular carcinoma. J Pathol, 2019, 248(2): 164-178.
43. Murugesan K, Sharaf R, Montesion M, et al. Genomic profiling of combined hepatocellular cholangiocarcinoma reveals genomics similar to either hepatocellular carcinoma or cholangiocarcinoma. JCO Precis Oncol, 2021, 5: PO. 20.00397. doi: 10.1200/PO.20.00397.
44. Xue R, Chen L, Zhang C, et al. Genomic and transcriptomic profiling of combined hepatocellular and intrahepatic cholangiocarcinoma reveals distinct molecular subtypes. Cancer Cell, 2019, 35(6): 932-947.
45. Kobayashi S, Terashima T, Shiba S, et al. Multicenter retrospective analysis of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma. Cancer Sci, 2018, 109(8): 2549-2557.
46. Salimon M, Prieux-Klotz C, Tougeron D, et al. Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study. Br J Cancer, 2018, 118(3): 325-330.
47. Ren Z, Xu J, Bai Y, et al. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study. Lancet Oncol, 2021, 22(7): 977-990.
48. Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med, 2020, 382(20): 1894-1905.
49. Finn RS, Ikeda M, Zhu AX, et al. Phase Ⅰb study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma. J Clin Oncol, 2020, 38(26): 2960-2970.
50. Xu J, Shen J, Gu S, et al. Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE): a nonrandomized, open-label, phase Ⅱ trial. Clin Cancer Res, 2021, 27(4): 1003-1011.
51. Zhou J, Fan J, Shi G, et al. 56P anti-PD1 antibody toripalimab, lenvatinib and gemox chemotherapy as first-line treatment of advanced and unresectable intrahepatic cholangiocarcinoma: a phase Ⅱ clinical trial. Ann Oncol, 2020, 31: S262-S263. doi: 10.1016/j.annonc.2020.08.034.
52. Villanueva L, Lwin Z, Chung HC, et al. Lenvatinib plus pembrolizumab for patients with previously treated biliary tract cancers in the multicohort phase Ⅱ LEAP-005 study. 2021 Gastrointestinal Cancers Symposium. San Francisco, California, United States, 2021, 39: 321-321.
53. OH DY, HE AR, QIN SK, et al. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1. J Clin Oncol, 2022, 40(4_suppl): 378-378.
54. Nguyen CT, Caruso S, Maille P, et al. Immune profiling of combined hepatocellular-cholangiocarcinoma reveals distinct subtypes and activation of gene signatures predictive of response to immunotherapy. Clin Cancer Res, 2022, 28(3): 540-551.
55. Sun W, Patel A, Normolle D, et al. A phase 2 trial of regorafenib as a single agent in patients with chemotherapy-refractory, advanced, and metastatic biliary tract adenocarcinoma. Cancer, 2019, 125(6): 902-909.
56. Kim RD, Chung V, Alese OB, et al. A phase 2 multi-institutional study of nivolumab for patients with advanced refractory biliary tract cancer. JAMA Oncol, 2020, 6(6): 888-894.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research progress in clinical diagnosis and treatment strategies of combined hepatocellular-cholangiocarcinoma

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content