Skip to main content
Top
Published in: World Journal of Surgical Oncology 1/2019

Open Access 01-12-2019 | Cholangiocarcinoma | Research

Combined hepatocellular-cholangiocarcinoma: a population level analysis of incidence and mortality trends

Authors: Jiakun Wang, Enliang Li, Hao Yang, Junjun Wu, Hong cheng Lu, Chenhao Yi, Jun Lei, Wenjun Liao, Linquan Wu

Published in: World Journal of Surgical Oncology | Issue 1/2019

Login to get access

Abstract

Background

The purpose of this study was to explore trends in incidence, incidence-based (IB) mortality, and survival for combined hepatocellular-cholangiocarcinoma (cHCC-CC) utilizing a population-based database to attract people’s attention to this disease.

Methods

The Surveillance, Epidemiology, and End Results (SEER) database was utilized to investigate the incidence and IB mortality for cHCC-CC from 2000 to 2014. Trends in age-adjusted incidence and IB mortality were characterized by the Joinpoint Regression program. The Kaplan-Meier method and log-rank test were utilized to implement survival analyses. Cox regression was utilized to estimate independent predictors of mortality.

Results

The incidence of cHCC-CC was 0.26 per 1,000,000 individuals in 2000 and 0.59 per 1,000,000 individuals in 2014, with an annual percent change (APC) (i.e., the extent of increase in incidence) of 3.84% (95% confidence interval [CI] 1.7–6.1; P < 0.05). The IB mortality also displayed a sustained increase (APC was 4.59%, 95% CI 1.9–7.4; P < 0.05). Compared to patients not undergoing surgery, patients undergoing surgical treatment experienced a significant increase in median survival (3 vs. 28 months; P < 0.001). However, the median survival decreased in patients with tumor size > 5 cm (20 vs. 9 months; P < 0.001). Based on univariate Cox regression analysis, African-American race, distant stage, regionalized stage, tumor size ≥ 5 cm, and no surgery were risk factors for death.

Conclusions

We identified an overall steady increase in the incidence of cHCC-CC, which indicates that primary prevention strategies for cHCC-CC have not improved much in recent years and that cHCC-CC needs to be taken seriously.
Literature
2.
go back to reference Goodman ZD, Ishak KG, Langloss JM, Sesterhenn IA, Rabin L. Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study. Cancer. 1985;55(1):124–35.PubMedCrossRef Goodman ZD, Ishak KG, Langloss JM, Sesterhenn IA, Rabin L. Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study. Cancer. 1985;55(1):124–35.PubMedCrossRef
3.
go back to reference Kim KH, Lee SG, Park EH, Hwang S, Ahn CS, Moon DB, Ha TY, Song GW, Jung DH, Kim KM, et al. Surgical treatments and prognoses of patients with combined hepatocellular carcinoma and cholangiocarcinoma. Ann Surg Oncol. 2009;16(3):623–9.PubMedCrossRef Kim KH, Lee SG, Park EH, Hwang S, Ahn CS, Moon DB, Ha TY, Song GW, Jung DH, Kim KM, et al. Surgical treatments and prognoses of patients with combined hepatocellular carcinoma and cholangiocarcinoma. Ann Surg Oncol. 2009;16(3):623–9.PubMedCrossRef
4.
go back to reference Theise ND, Yao JL, Harada K, Hytiroglou P, Portmann B, Thung SN, Tsui W, Ohta H, Nakanuma Y. Hepatic ‘stem cell’ malignancies in adults: four cases. Histopathology. 2003;43(3):263–71.PubMedCrossRef Theise ND, Yao JL, Harada K, Hytiroglou P, Portmann B, Thung SN, Tsui W, Ohta H, Nakanuma Y. Hepatic ‘stem cell’ malignancies in adults: four cases. Histopathology. 2003;43(3):263–71.PubMedCrossRef
5.
go back to reference Cong WM, Wu MC. New insights into molecular diagnostic pathology of primary liver cancer: advances and challenges. Cancer Lett. 2015;368(1):14–9.PubMedCrossRef Cong WM, Wu MC. New insights into molecular diagnostic pathology of primary liver cancer: advances and challenges. Cancer Lett. 2015;368(1):14–9.PubMedCrossRef
6.
go back to reference Itoyama M, Hata M, Yamanegi K, Yamada N, Ohyama H, Hirano H, Terada N, Nakasho K. Expression of both hepatocellular carcinoma and cholangiocarcinoma phenotypes in hepatocellular carcinoma and cholangiocarcinoma components in combined hepatocellular and cholangiocarcinoma. Med Mol Morphol. 2012;45(1):7–13.PubMedCrossRef Itoyama M, Hata M, Yamanegi K, Yamada N, Ohyama H, Hirano H, Terada N, Nakasho K. Expression of both hepatocellular carcinoma and cholangiocarcinoma phenotypes in hepatocellular carcinoma and cholangiocarcinoma components in combined hepatocellular and cholangiocarcinoma. Med Mol Morphol. 2012;45(1):7–13.PubMedCrossRef
7.
go back to reference Gera S, Ettel M, Acosta-Gonzalez G, Xu R. Clinical features, histology, and histogenesis of combined hepatocellular-cholangiocarcinoma. World J Hepatol. 2017;9(6):300–9.PubMedPubMedCentralCrossRef Gera S, Ettel M, Acosta-Gonzalez G, Xu R. Clinical features, histology, and histogenesis of combined hepatocellular-cholangiocarcinoma. World J Hepatol. 2017;9(6):300–9.PubMedPubMedCentralCrossRef
8.
go back to reference Kassahun WT, Hauss J. Management of combined hepatocellular and cholangiocarcinoma. Int J Clin Pract. 2008;62(8):1271–8.PubMedCrossRef Kassahun WT, Hauss J. Management of combined hepatocellular and cholangiocarcinoma. Int J Clin Pract. 2008;62(8):1271–8.PubMedCrossRef
9.
go back to reference Panjala C, Senecal DL, Bridges MD, Kim GP, Nakhleh RE, Nguyen JH, Harnois DM. The diagnostic conundrum and liver transplantation outcome for combined hepatocellular-cholangiocarcinoma. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2010;10(5):1263–7.CrossRef Panjala C, Senecal DL, Bridges MD, Kim GP, Nakhleh RE, Nguyen JH, Harnois DM. The diagnostic conundrum and liver transplantation outcome for combined hepatocellular-cholangiocarcinoma. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2010;10(5):1263–7.CrossRef
10.
go back to reference Portolani N, Baiocchi GL, Coniglio A, Piardi T, Grazioli L, Benetti A, Ferrari Bravo A, Giulini SM. Intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma: a Western experience. Ann Surg Oncol. 2008;15(7):1880–90.PubMedCrossRef Portolani N, Baiocchi GL, Coniglio A, Piardi T, Grazioli L, Benetti A, Ferrari Bravo A, Giulini SM. Intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma: a Western experience. Ann Surg Oncol. 2008;15(7):1880–90.PubMedCrossRef
11.
go back to reference Ng IO, Shek TW, Nicholls J, Ma LT. Combined hepatocellular-cholangiocarcinoma: a clinicopathological study. J Gastroenterol Hepatol. 1998;13(1):34–40.PubMedCrossRef Ng IO, Shek TW, Nicholls J, Ma LT. Combined hepatocellular-cholangiocarcinoma: a clinicopathological study. J Gastroenterol Hepatol. 1998;13(1):34–40.PubMedCrossRef
12.
go back to reference Kim H, Park C, Han KH, Choi J, Kim YB, Kim JK, Park YN. Primary liver carcinoma of intermediate (hepatocyte-cholangiocyte) phenotype. J Hepatol. 2004;40(2):298–304.PubMedCrossRef Kim H, Park C, Han KH, Choi J, Kim YB, Kim JK, Park YN. Primary liver carcinoma of intermediate (hepatocyte-cholangiocyte) phenotype. J Hepatol. 2004;40(2):298–304.PubMedCrossRef
13.
go back to reference Zhang F, Chen XP, Zhang W, Dong HH, Xiang S, Zhang WG, Zhang BX. Combined hepatocellular cholangiocarcinoma originating from hepatic progenitor cells: immunohistochemical and double-fluorescence immunostaining evidence. Histopathology. 2008;52(2):224–32.PubMedCrossRef Zhang F, Chen XP, Zhang W, Dong HH, Xiang S, Zhang WG, Zhang BX. Combined hepatocellular cholangiocarcinoma originating from hepatic progenitor cells: immunohistochemical and double-fluorescence immunostaining evidence. Histopathology. 2008;52(2):224–32.PubMedCrossRef
14.
go back to reference Maeda T, Adachi E, Kajiyama K, Sugimachi K, Tsuneyoshi M. Combined hepatocellular and cholangiocarcinoma: proposed criteria according to cytokeratin expression and analysis of clinicopathologic features. Hum Pathol. 1995;26(9):956–64.PubMedCrossRef Maeda T, Adachi E, Kajiyama K, Sugimachi K, Tsuneyoshi M. Combined hepatocellular and cholangiocarcinoma: proposed criteria according to cytokeratin expression and analysis of clinicopathologic features. Hum Pathol. 1995;26(9):956–64.PubMedCrossRef
15.
go back to reference Imai Y, Oda H, Arai M, Shimizu S, Nakatsuru Y, Inoue T, Ishikawa T. Mutational analysis of the p53 and K-ras genes and allelotype study of the Rb-1 gene for investigating the pathogenesis of combined hapatocellular-cholangiocellular carcinomas. Jpn J Cancer Res. 1996;87(10):1056–62.PubMedPubMedCentralCrossRef Imai Y, Oda H, Arai M, Shimizu S, Nakatsuru Y, Inoue T, Ishikawa T. Mutational analysis of the p53 and K-ras genes and allelotype study of the Rb-1 gene for investigating the pathogenesis of combined hapatocellular-cholangiocellular carcinomas. Jpn J Cancer Res. 1996;87(10):1056–62.PubMedPubMedCentralCrossRef
16.
go back to reference Wakasa T, Wakasa K, Shutou T, Hai S, Kubo S, Hirohashi K, Umeshita K, Monden M. A histopathological study on combined hepatocellular and cholangiocarcinoma: cholangiocarcinoma component is originated from hepatocellular carcinoma. Hepato-Gastroenterology. 2007;54(74):508–13.PubMed Wakasa T, Wakasa K, Shutou T, Hai S, Kubo S, Hirohashi K, Umeshita K, Monden M. A histopathological study on combined hepatocellular and cholangiocarcinoma: cholangiocarcinoma component is originated from hepatocellular carcinoma. Hepato-Gastroenterology. 2007;54(74):508–13.PubMed
17.
go back to reference Zuo HQ, Yan LN, Zeng Y, Yang JY, Luo HZ, Liu JW, Zhou LX. Clinicopathological characteristics of 15 patients with combined hepatocellular carcinoma and cholangiocarcinoma. Hepatobiliary Pancreat Dis Int. 2007;6(2):161–5.PubMed Zuo HQ, Yan LN, Zeng Y, Yang JY, Luo HZ, Liu JW, Zhou LX. Clinicopathological characteristics of 15 patients with combined hepatocellular carcinoma and cholangiocarcinoma. Hepatobiliary Pancreat Dis Int. 2007;6(2):161–5.PubMed
18.
go back to reference Chantajitr S, Wilasrusmee C, Lertsitichai P, Phromsopha N. Combined hepatocellular and cholangiocarcinoma: clinical features and prognostic study in a Thai population. J Hepato-Biliary-Pancreat Surg. 2006;13(6):537–42.CrossRef Chantajitr S, Wilasrusmee C, Lertsitichai P, Phromsopha N. Combined hepatocellular and cholangiocarcinoma: clinical features and prognostic study in a Thai population. J Hepato-Biliary-Pancreat Surg. 2006;13(6):537–42.CrossRef
19.
go back to reference Lee WS, Lee KW, Heo JS, Kim SJ, Choi SH, Kim YI, Joh JW. Comparison of combined hepatocellular and cholangiocarcinoma with hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Surg Today. 2006;36(10):892–7.PubMedCrossRef Lee WS, Lee KW, Heo JS, Kim SJ, Choi SH, Kim YI, Joh JW. Comparison of combined hepatocellular and cholangiocarcinoma with hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Surg Today. 2006;36(10):892–7.PubMedCrossRef
20.
go back to reference Poon RT, Fan ST, Lo CM, Liu CL, Lam CM, Yuen WK, Yeung C, Wong J. Improving perioperative outcome expands the role of hepatectomy in management of benign and malignant hepatobiliary diseases: analysis of 1222 consecutive patients from a prospective database. Ann Surg. 2004;240(4):698–708 discussion 708-610.PubMedPubMedCentral Poon RT, Fan ST, Lo CM, Liu CL, Lam CM, Yuen WK, Yeung C, Wong J. Improving perioperative outcome expands the role of hepatectomy in management of benign and malignant hepatobiliary diseases: analysis of 1222 consecutive patients from a prospective database. Ann Surg. 2004;240(4):698–708 discussion 708-610.PubMedPubMedCentral
22.
go back to reference Hur C, Miller M, Kong CY, Dowling EC, Nattinger KJ, Dunn M, Feuer EJ. Trends in esophageal adenocarcinoma incidence and mortality. Cancer. 2013;119(6):1149–58.PubMedCrossRef Hur C, Miller M, Kong CY, Dowling EC, Nattinger KJ, Dunn M, Feuer EJ. Trends in esophageal adenocarcinoma incidence and mortality. Cancer. 2013;119(6):1149–58.PubMedCrossRef
23.
go back to reference Njei B, Rotman Y, Ditah I, Lim JK. Emerging trends in hepatocellular carcinoma incidence and mortality. Hepatology. 2015;61(1):191–9.PubMedCrossRef Njei B, Rotman Y, Ditah I, Lim JK. Emerging trends in hepatocellular carcinoma incidence and mortality. Hepatology. 2015;61(1):191–9.PubMedCrossRef
24.
go back to reference Kaplan EL. Nonparametric estimation for incomplete observation. J Am Stat Assoc. 1958;53:457–81.CrossRef Kaplan EL. Nonparametric estimation for incomplete observation. J Am Stat Assoc. 1958;53:457–81.CrossRef
25.
go back to reference Koh KC, Lee H, Choi MS, Lee JH, Paik SW, Yoo BC, Rhee JC, Cho JW, Park CK, Kim HJ. Clinicopathologic features and prognosis of combined hepatocellular cholangiocarcinoma. Am J Surg. 2005;189(1):120–5.PubMedCrossRef Koh KC, Lee H, Choi MS, Lee JH, Paik SW, Yoo BC, Rhee JC, Cho JW, Park CK, Kim HJ. Clinicopathologic features and prognosis of combined hepatocellular cholangiocarcinoma. Am J Surg. 2005;189(1):120–5.PubMedCrossRef
26.
go back to reference Taguchi J, Nakashima O, Tanaka M, Hisaka T, Takazawa T, Kojiro M. A clinicopathological study on combined hepatocellular and cholangiocarcinoma. J Gastroenterol Hepatol. 1996;11(8):758–64.PubMedCrossRef Taguchi J, Nakashima O, Tanaka M, Hisaka T, Takazawa T, Kojiro M. A clinicopathological study on combined hepatocellular and cholangiocarcinoma. J Gastroenterol Hepatol. 1996;11(8):758–64.PubMedCrossRef
27.
go back to reference Liu CL, Fan ST, Lo CM, Ng IO, Lam CM, Poon RT, Wong J. Hepatic resection for combined hepatocellular and cholangiocarcinoma. Arch Surg. 2003;138(1):86–90.PubMedCrossRef Liu CL, Fan ST, Lo CM, Ng IO, Lam CM, Poon RT, Wong J. Hepatic resection for combined hepatocellular and cholangiocarcinoma. Arch Surg. 2003;138(1):86–90.PubMedCrossRef
28.
go back to reference Jarnagin WR, Weber S, Tickoo SK, Koea JB, Obiekwe S, Fong Y, DeMatteo RP, Blumgart LH, Klimstra D. Combined hepatocellular and cholangiocarcinoma: demographic, clinical, and prognostic factors. Cancer. 2002;94(7):2040–6.PubMedCrossRef Jarnagin WR, Weber S, Tickoo SK, Koea JB, Obiekwe S, Fong Y, DeMatteo RP, Blumgart LH, Klimstra D. Combined hepatocellular and cholangiocarcinoma: demographic, clinical, and prognostic factors. Cancer. 2002;94(7):2040–6.PubMedCrossRef
29.
go back to reference Kim W, Lee JH, Kim YJ, Yoon JH, Suh KS, Lee KU, Jang JJ, Lee HS. Analysis of prognostic factors after curative resection for combined hepatocellular and cholangiocarcinoma. Korean J Gastroenterol. 2007;49(3):158–65.PubMed Kim W, Lee JH, Kim YJ, Yoon JH, Suh KS, Lee KU, Jang JJ, Lee HS. Analysis of prognostic factors after curative resection for combined hepatocellular and cholangiocarcinoma. Korean J Gastroenterol. 2007;49(3):158–65.PubMed
30.
go back to reference Yin X, Zhang B-H, Qiu S-J, Ren Z-G, Zhou J, Chen X-H, Zhou Y, Fan J. Combined hepatocellular carcinoma and cholangiocarcinoma: clinical features, treatment modalities, and prognosis. Ann Surg Oncol. 2012;19(9):2869–76.PubMedCrossRef Yin X, Zhang B-H, Qiu S-J, Ren Z-G, Zhou J, Chen X-H, Zhou Y, Fan J. Combined hepatocellular carcinoma and cholangiocarcinoma: clinical features, treatment modalities, and prognosis. Ann Surg Oncol. 2012;19(9):2869–76.PubMedCrossRef
31.
go back to reference Wachtel MS, Zhang Y, Xu T, Chiriva-Internati M, Frezza EE. Combined hepatocellular cholangiocarcinomas; analysis of a large database. Clin Med Pathol. 2008;1:43–7.PubMedPubMedCentralCrossRef Wachtel MS, Zhang Y, Xu T, Chiriva-Internati M, Frezza EE. Combined hepatocellular cholangiocarcinomas; analysis of a large database. Clin Med Pathol. 2008;1:43–7.PubMedPubMedCentralCrossRef
32.
go back to reference Garancini M, Goffredo P, Pagni F, Romano F, Roman S, Sosa JA, Giardini V. Combined hepatocellular-cholangiocarcinoma: a population-level analysis of an uncommon primary liver tumor. Liver Transpl. 2014;20(8):952–9.PubMedCrossRef Garancini M, Goffredo P, Pagni F, Romano F, Roman S, Sosa JA, Giardini V. Combined hepatocellular-cholangiocarcinoma: a population-level analysis of an uncommon primary liver tumor. Liver Transpl. 2014;20(8):952–9.PubMedCrossRef
33.
go back to reference Wang J, Wang F, Kessinger A. Outcome of combined hepatocellular and cholangiocarcinoma of the liver. J Oncol. 2010;2010:770–4. Wang J, Wang F, Kessinger A. Outcome of combined hepatocellular and cholangiocarcinoma of the liver. J Oncol. 2010;2010:770–4.
34.
go back to reference Groeschl RT, Turaga KK, Gamblin TC. Transplantation versus resection for patients with combined hepatocellular carcinoma-cholangiocarcinoma. J Surg Oncol. 2013;107(6):608–12.PubMedCrossRef Groeschl RT, Turaga KK, Gamblin TC. Transplantation versus resection for patients with combined hepatocellular carcinoma-cholangiocarcinoma. J Surg Oncol. 2013;107(6):608–12.PubMedCrossRef
35.
go back to reference Greten TF, Papendorf F, Bleck JS, Kirchhoff T, Wohlberedt T, Kubicka S, Klempnauer J, Galanski M, Manns MP. Survival rate in patients with hepatocellular carcinoma: a retrospective analysis of 389 patients. Br J Cancer. 2005;92(10):1862–8.PubMedPubMedCentralCrossRef Greten TF, Papendorf F, Bleck JS, Kirchhoff T, Wohlberedt T, Kubicka S, Klempnauer J, Galanski M, Manns MP. Survival rate in patients with hepatocellular carcinoma: a retrospective analysis of 389 patients. Br J Cancer. 2005;92(10):1862–8.PubMedPubMedCentralCrossRef
36.
go back to reference Shaib Y, El-Serag HB. The epidemiology of cholangiocarcinoma. Semin Liver Dis. 2004;24(2):115–25.PubMedCrossRef Shaib Y, El-Serag HB. The epidemiology of cholangiocarcinoma. Semin Liver Dis. 2004;24(2):115–25.PubMedCrossRef
37.
go back to reference Zeng ZC, Tang ZY, Fan J, Zhou J, Qin LX, Ye SL, Sun HC, Wang BL, Li D, Wang JH, et al. Consideration of the role of radiotherapy for unresectable intrahepatic cholangiocarcinoma: a retrospective analysis of 75 patients. Cancer J. 2006;12(2):113–22.PubMed Zeng ZC, Tang ZY, Fan J, Zhou J, Qin LX, Ye SL, Sun HC, Wang BL, Li D, Wang JH, et al. Consideration of the role of radiotherapy for unresectable intrahepatic cholangiocarcinoma: a retrospective analysis of 75 patients. Cancer J. 2006;12(2):113–22.PubMed
38.
go back to reference Nathan H, Pawlik TM. Limitations of claims and registry data in surgical oncology research. Ann Surg Oncol. 2008;15(2):415–23.PubMedCrossRef Nathan H, Pawlik TM. Limitations of claims and registry data in surgical oncology research. Ann Surg Oncol. 2008;15(2):415–23.PubMedCrossRef
Metadata
Title
Combined hepatocellular-cholangiocarcinoma: a population level analysis of incidence and mortality trends
Authors
Jiakun Wang
Enliang Li
Hao Yang
Junjun Wu
Hong cheng Lu
Chenhao Yi
Jun Lei
Wenjun Liao
Linquan Wu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2019
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/s12957-019-1586-8

Other articles of this Issue 1/2019

World Journal of Surgical Oncology 1/2019 Go to the issue