Skip to main content
SpringerLink
Log in

A New Scoring Method for Personalized Prognostic Prediction in Patients with Combined Hepatocellular and Cholangiocarcinoma After Surgery

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background and Aim

Combined hepatocellular and cholangiocarcinoma (cHCC-CCA) is a rare but aggressive primary liver cancer with dismal prognosis. We aim to develop a new scoring method for personalized prognostic prediction in patients with cHCC-CCA undergoing surgical resection.

Methods

Between January 1993 and December 2015, a total of 296 Allen type C cHCC-CCA patients who had received surgical resection in Liver Cancer Institute, Zhongshan Hospital were retrospectively enrolled. A novel prognostic scoring method for cHCC-CCA (PSM-CHCC model) was established and validated. The predictive value of the new model was compared with current prognostic staging systems.

Results

The scoring model was developed based on the independent prognostic variables identified by Cox regression model. Based on the PSM-CHCC model, patients were stratified into three prognostic subgroups according to their individual score: A (scoring 0–2), B (scoring 3–5), and C (scoring > 5). The prediction performance of the PSM-CHCC model outperformed the widely accepted TNM staging system and other staging systems in both training and validation cohorts. Subgroup analysis also verified the discrimination efficacy of the PSM-CHCC model.

Conclusions

The newly established PSM-CHCC model may facilitate prognostic stratification and clinical decision-making in patients with cHCC-CCA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Brunt E, Aishima S, Clavien PA, Fowler K, Goodman Z, Gores G et al. cHCC-CCA: Consensus terminology for primary liver carcinomas with both hepatocytic and cholangiocytic differentation. Hepatology. 2018;68(1):113-26. doi:https://doi.org/10.1002/hep.29789.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Allen RA, Lisa JR. Combined liver cell and bile duct carcinoma. Am J Pathol. 1949;25(4):647-55.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Bosman FT, Carneiro F, Hruban RH, Theise N, D. WHO classification of tumours of the digestive system. 4th ed. Lyon: International Agency for Research on Cancer; 2010.

    Google Scholar 

  4. Wakizaka K, Yokoo H, Kamiyama T, Ohira M, Kato K, Fujii Y et al. Clinical and pathological features of combined hepatocellular-cholangiocarcinoma compared with other liver cancers. Journal of gastroenterology and hepatology. 2019;34(6):1074-80. doi:https://doi.org/10.1111/jgh.14547.

    Article  CAS  PubMed  Google Scholar 

  5. Rogers JE, Bolonesi RM, Rashid A, Elsayes KM, Elbanan MG, Law L et al. Systemic therapy for unresectable, mixed hepatocellular-cholangiocarcinoma: treatment of a rare malignancy. J Gastrointest Oncol. 2017;8(2):347-51. doi:https://doi.org/10.21037/jgo.2017.03.03.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Chun YS, Pawlik TM, Vauthey JN. 8th Edition of the AJCC Cancer Staging Manual: Pancreas and Hepatobiliary Cancers. Ann Surg Oncol. 2018;25(4):845-7. doi:https://doi.org/10.1245/s10434-017-6025-x.

    Article  PubMed  Google Scholar 

  7. Llovet JM, Brú C, Bruix J. Prognosis of hepatocellular carcinoma: the BCLC staging classification. Seminars in liver disease. 1999;19(3):329-38. doi:https://doi.org/10.1055/s-2007-1007122.

    Article  CAS  PubMed  Google Scholar 

  8. Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N, Hasegawa H et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer. 1985;56(4):918-28. doi:https://doi.org/10.1002/1097-0142(19850815)56:4<918::aid-cncr2820560437>3.0.co;2-e.

    Article  CAS  PubMed  Google Scholar 

  9. Farinati F, Vitale A, Spolverato G, Pawlik TM, Huo TL, Lee YH et al. Development and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma. PLoS Med. 2016;13(4):e1002006. doi:https://doi.org/10.1371/journal.pmed.1002006.

    Article  PubMed  PubMed Central  Google Scholar 

  10. None. A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology. 1998;28(3):751-5. doi:https://doi.org/10.1002/hep.510280322.

  11. He C, Mao Y, Wang J, Song Y, Huang X, Lin X et al. The Predictive Value of Staging Systems and Inflammation Scores for Patients with Combined Hepatocellular Cholangiocarcinoma After Surgical Resection: a Retrospective Study. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2018;22(7):1239-50. doi:https://doi.org/10.1007/s11605-018-3756-3.

    Article  Google Scholar 

  12. Liu CL, Fan ST, Lo CM, Ng IO, Lam CM, Poon RT et al. Hepatic resection for combined hepatocellular and cholangiocarcinoma. Archives of surgery (Chicago, Ill : 1960). 2003;138(1):86-90. doi:https://doi.org/10.1001/archsurg.138.10.1106.

    Article  Google Scholar 

  13. Chantajitr S, Wilasrusmee C, Lertsitichai P, Phromsopha N. Combined hepatocellular and cholangiocarcinoma: clinical features and prognostic study in a Thai population. Journal of hepato-biliary-pancreatic surgery. 2006;13(6):537-42. doi:https://doi.org/10.1007/s00534-006-1117-1.

    Article  PubMed  Google Scholar 

  14. Song P, Midorikawa Y, Nakayama H, Higaki T, Moriguchi M, Aramaki O et al. Patients’ prognosis of intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma after resection. Cancer medicine. 2019;8(13):5862-71. doi:https://doi.org/10.1002/cam4.2495.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ramai D, Ofosu A, Lai JK, Reddy M, Adler DG. Combined Hepatocellular Cholangiocarcinoma: A Population-Based Retrospective Study. The American Journal of Gastroenterology. 2019;114(9):1496-501. doi:https://doi.org/10.14309/ajg.0000000000000326.

    Article  PubMed  Google Scholar 

  16. He C, Zhang Y, Cai Z, Lin X. Competing risk analyses of overall survival and cancer-specific survival in patients with combined hepatocellular cholangiocarcinoma after surgery. BMC Cancer. 2019;19(1):178. doi:https://doi.org/10.1186/s12885-019-5398-6.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Kostadinova L, Shive CL, Zebrowski E, Fuller B, Rife K, Hirsch A et al. Soluble Markers of Immune Activation Differentially Normalize and Selectively Associate with Improvement in AST, ALT, Albumin, and Transient Elastography During IFN-Free HCV Therapy. Pathogens & Immunity. 2018;3(1):149-63. doi:https://doi.org/10.20411/pai.v3i1.242.

    Article  Google Scholar 

  18. Maximin S, Ganeshan DM, Shanbhogue AK, Dighe MK, Yeh MM, Kolokythas O et al. Current update on combined hepatocellular-cholangiocarcinoma. Eur J Radiol Open. 2014;1:40-8. doi:https://doi.org/10.1016/j.ejro.2014.07.001.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kassahun WT, Hauss J. Management of combined hepatocellular and cholangiocarcinoma. Int J Clin Pract. 2008;62(8):1271-8. doi:https://doi.org/10.1111/j.1742-1241.2007.01694.x.

    Article  CAS  PubMed  Google Scholar 

  20. Yamashita S, Passot G, Aloia TA, Chun YS, Javle M, Lee JE et al. Prognostic value of carbohydrate antigen 19-9 in patients undergoing resection of biliary tract cancer. The British journal of surgery. 2017;104(3):267-77. doi:https://doi.org/10.1002/bjs.10415.

    Article  CAS  PubMed  Google Scholar 

  21. Tella SH, Kommalapati A, Yadav S, Bergquist JR, Goyal G, Durgin L et al. Novel staging system using carbohydrate antigen (CA) 19-9 in extra-hepatic cholangiocarcinoma and its implications on overall survival. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2020. doi:https://doi.org/10.1016/j.ejso.2020.01.016.

  22. Ohta S, Morine Y, Imura S, Ikemoto T, Arakawa Y, Iwahashi S et al. Carbohydrate Antigen 19-9 Is a Prognostic Factor Which Correlates With HDAC1 and HIF-1α for Intrahepatic Cholangiocarcinoma. Anticancer Research. 2019;39(11):6025-33. doi:https://doi.org/10.21873/anticanres.13808.

    Article  CAS  PubMed  Google Scholar 

  23. Huang SH, Tsai WS, You JF, Hung HY, Yeh CY, Hsieh PS et al. Preoperative Carcinoembryonic Antigen as a Poor Prognostic Factor in Stage I-III Colorectal Cancer After Curative-Intent Resection: A Propensity Score Matching Analysis. Annals of surgical oncology. 2019;26(6):1685-94. doi:https://doi.org/10.1245/s10434-019-07184-3.

    Article  PubMed  Google Scholar 

  24. Wang W, Seeruttun SR, Fang C, Chen J, Li Y, Liu Z et al. Prognostic Significance of Carcinoembryonic Antigen Staining in Cancer Tissues of Gastric Cancer Patients. Annals of surgical oncology. 2016;23(4):1244-51. doi:https://doi.org/10.1245/s10434-015-4981-6.

    Article  CAS  PubMed  Google Scholar 

  25. Wang M, Gao Y, Feng H, Warner E, An M, Jia J et al. A nomogram incorporating six easily obtained parameters to discriminate intrahepatic cholangiocarcinoma and hepatocellular carcinoma. Cancer medicine. 2018;7(3):646-54. doi:https://doi.org/10.1002/cam4.1341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Yoshikawa M, Morine Y, Ikemoto T, Imura S, Higashijima J, Iwahashi S et al. Elevated Preoperative Serum CEA Level Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma Through the Epithelial-Mesenchymal Transition. Anticancer Research. 2017;37(3):1169-75. doi:https://doi.org/10.21873/anticanres.11430.

    Article  CAS  PubMed  Google Scholar 

  27. Kobayashi S, Terashima T, Shiba S, Yoshida Y, Yamada I, Iwadou S et al. Multicenter retrospective analysis of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma. Cancer science. 2018;109(8):2549-57. doi:https://doi.org/10.1111/cas.13656.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Lim JS, Yang JH, Chun BY, Kam S, Jacobs DR, Lee DH. Is serum gamma-glutamyltransferase inversely associated with serum antioxidants as a marker of oxidative stress? Free radical biology & medicine. 2004;37(7):1018-23.

    Article  CAS  Google Scholar 

  29. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free radical biology & medicine. 2010;49(11):1603-16.

    Article  CAS  Google Scholar 

  30. Yano Y, Yamamoto J, Kosuge T, Sakamoto Y, Yamasaki S, Shimada K et al. Combined hepatocellular and cholangiocarcinoma: a clinicopathologic study of 26 resected cases. Jpn J Clin Oncol. 2003;33(6):283-7. doi:https://doi.org/10.1093/jjco/hyg056.

    Article  PubMed  Google Scholar 

  31. Lin G, Toh CH, Wu RC, Ko SF, Ng SH, Chou WC et al. Combined hepatocellular cholangiocarcinoma: prognostic factors investigated by computed tomography/magnetic resonance imaging. Int J Clin Pract. 2008;62(8):1199-205. doi:https://doi.org/10.1111/j.1742-1241.2007.01291.x.

    Article  CAS  PubMed  Google Scholar 

  32. Fowler K, Saad NE, Brunt E, Doyle MB, Amin M, Vachharajani N et al. Biphenotypic Primary Liver Carcinomas: Assessing Outcomes of Hepatic Directed Therapy. Ann Surg Oncol. 2015;22(13):4130-7. doi:https://doi.org/10.1245/s10434-015-4774-y.

    Article  PubMed  Google Scholar 

  33. Morizono S, Fukutomi M, Yokota M, Iguchi H, Funakoshi A, Wakasugi H et al. [A case of combined liver cell and bile duct carcinoma detected 6 years after interferon therapy for chronic hepatitis C, in spite of showing complete response]. Nihon Shokakibyo Gakkai Zasshi. 2002;99(5):505-10.

    PubMed  Google Scholar 

  34. Hayashi H, Beppu T, Ishiko T, Mizumoto T, Masuda T, Okabe K et al. [A 42-month disease free survival case of combined hepatocellular-cholangiocarcinoma with lymph node metastases treated with multimodal therapy]. Gan To Kagaku Ryoho. 2006;33(12):1941-3.

    PubMed  Google Scholar 

  35. Tani S, Murata S, Tamura M, Fukunaga K, Morita M, Hirata Y et al. Effectiveness of systemic chemotherapy of GEM+CBDCA+5-FU/LV and hepatic arterial infusion of CDDP in a case of advanced, combined hepatocellular-cholangiocarcinoma with multiple lung metastases. The Japanese journal of gastroenterology. 2011;108(11):1892-901. doi:undefined.

  36. Wakizaka K, Yokoo H, Kamiyama T, Ohira M, Kato K, Fujii Y et al. Clinical and pathological features of combined hepatocellular-cholangiocarcinoma compared with other liver cancers. J Gastroenterol Hepatol. 2019;34(6):1074-80. doi:https://doi.org/10.1111/jgh.14547.

    Article  CAS  PubMed  Google Scholar 

  37. Kim G, Jeung H, Kim D, Kim J, Yoon S, Jung E et al. A case of combined hepatocellular-cholangiocarcinoma with favorable response to systemic chemotherapy. Cancer research and treatment : official journal of Korean Cancer Association. 2010;42(4):235-8. doi:https://doi.org/10.4143/crt.2010.42.4.235.

    Article  Google Scholar 

  38. Chi M, Mikhitarian K, Shi C, Goff LW. Management of combined hepatocellular-cholangiocarcinoma: a case report and literature review. Gastrointest Cancer Res. 2012;5(6):199-202.

    PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (No. 81672331; No. 81972889).

Author information

Authors and Affiliations

  1. Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 136 Yi Xue Yuan Road, Shanghai, 200032, China

    Feng Zhang, Keshu Hu, Bei Tang, Mengxin Tian, Shenxin Lu, Jia Yuan, Miao Li, Rongxin Chen, Zhenggang Ren, Yinghong Shi & Xin Yin

Authors
  1. Feng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Keshu Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bei Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mengxin Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shenxin Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jia Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Miao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rongxin Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Zhenggang Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yinghong Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Xin Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XY and YHS conceived the study, and participated in its design and coordination. FZ, BT, ML, and KSH participated in data acquisition. MXT, SXL, JY, and RXC contributed to collecting all the cases. FZ and KSH contributed to statistical analysis. XY, YHS, FZ, and ZGR drafted and revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xin Yin.

Ethics declarations

Conflict of Interest

None of the authors has any conflict of interest related to the manuscript.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Yinghong Shi and Xin Yin contributed equally in guiding this study, therefore, they should be considered as co-corresponding authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, F., Hu, K., Tang, B. et al. A New Scoring Method for Personalized Prognostic Prediction in Patients with Combined Hepatocellular and Cholangiocarcinoma After Surgery. J Gastrointest Surg 25, 971–982 (2021). https://doi.org/10.1007/s11605-020-04618-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-020-04618-2

Keywords

Search

Navigation