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The Evaluation of the Eighth Edition of the AJCC/UICC Staging System for Intrahepatic Cholangiocarcinoma: a Proposal of a Modified New Staging System

  • Yusuke YamamotoEmail author
  • Teiichi Sugiura
  • Yukiyasu Okamura
  • Takaaki Ito
  • Ryo Ashida
  • Katsuhisa Ohgi
  • Yasuni Nakanuma
  • Katsuhiko Uesaka
Original Article
  • 54 Downloads

Abstract

Background

The objective was to clarify the prognostic impact of the 8th edition of American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) of intrahepatic cholangiocarcinoma (ICC).

Methods

A total of 103 ICC patients who underwent hepatectomy between 2002 and 2016 were enrolled. The survival impact of AJCC/UICC 8th edition was examined.

Results

The 5-year disease-specific survival (DSS) rate was 75.9% in T1a (n = 23), 88.9% in T1b (n = 10), 14.9% in T2 (n = 24), 52.5% in T3 (n = 11), and 15.2% in T4 (n = 35). The DSS was comparable among T2, T3, and T4 (T2 vs. T3; p = 0.345, T3 vs. T4; 0.295). A multivariate analysis identified multiple tumors (hazard ratio [HR] 2.821), periductal infiltrating (HR 2.439), perforation of the visceral peritoneum (HR 1.850), and vascular invasion (HR 1.872) as independent prognostic factors that were associated with the DSS. The optimum tumor size with the greatest difference in the DSS was 2 cm (p = 0.014). The new T classification was developed as follows: T1, size ≤ 2 cm without other factors; T2, size > 2 cm without other factors; T3, vascular invasion or perforation of the visceral peritoneum; and T4, multiple tumors or periductal infiltrating. The 5-year DSS was 100% in T1 (n = 7), 76.6% in T2 (n = 28), 45.1% in T3 (n = 28), and 3.4% in T4 (n = 40). There were differences in the DSS between T2 and T3 (p = 0.035) and between T3 and T4 (p = 0.003).

Conclusions

T2, T3, and T4 of AJCC/UICC overlapped with regard to the DSS. The new staging can classify ICC patients with sufficient prognostic differences.

Keywords

Intrahepatic cholangiocarcinoma AJCC/UICC 8th edition Multiple tumor Vascular invasion Lymph node metastasis 

Abbreviations

ICC

Intrahepatic cholangiocarcinoma

TNM

Tumor-node-metastasis

AJCC

American Joint Committee on Cancer

UICC

International Union Against Cancer

HR

Hazard ratio

LCSGJ

Liver Cancer Study Group of Japan

Notes

Authors’ Contribution

Design of work: Y Yamamoto, T Sugiura, and K Uesaka

Acquisition, analysis, and interpretation of data: Y Yamamoto, T Sugiura, Y Okamura, T Ito, R Ashida, K Ohgi, and Y Nakanuma

Drafting and revising: Y Yamamoto, T Sugiura, Y Okamura, T Ito, R Ashida, K Ohgi, and K Uesaka

Final approval: Y Yamamoto, T Sugiura, Y Okamura, T Ito, R Ashida, K Ohgi, and K Uesaka

Agreement to be accountable for all aspects of the work: Y Yamamoto, T Sugiura, Y Okamura, T Ito, R Ashida, K Ohgi, Y Nakanuma, and K Uesaka

Compliance with Ethical Standards

The Institutional Review Board approved this study.

Conflict of Interest

The authors declare that they have no conflicts of interest.

References

  1. 1.
    Shirabe K, Mano Y, Taketomi A, Soejima Y, Uchiyama H, Aishima S et al. Clinicopathological prognostic factors after hepatectomy for patients with mass-forming type intrahepatic cholangiocarcinoma: relevance of the lymphatic invasion index. Ann Surg Oncol. 2010;17(7):1816–22.CrossRefGoogle Scholar
  2. 2.
    Gurlevik E, Fleischmann-Mundt B, Armbrecht N, Longerich T, Woller N, Kloos A et al. Adjuvant gemcitabine therapy improves survival in a locally induced, R0-resectable model of metastatic intrahepatic cholangiocarcinoma. Hepatology. 2013;58(3):1031–41.CrossRefGoogle Scholar
  3. 3.
    Shen WF, Zhong W, Liu Q, Sui CJ, Huang YQ, Yang JM. Adjuvant transcatheter arterial chemoembolization for intrahepatic cholangiocarcinoma after curative surgery: retrospective control study. World J Surg. 2011;35(9):2083–91.CrossRefGoogle Scholar
  4. 4.
    Cho SY, Park SJ, Kim SH, Han SS, Kim YK, Lee KW et al. Survival analysis of intrahepatic cholangiocarcinoma after resection. Ann Surg Oncol. 2010;17(7):1823–30.CrossRefGoogle Scholar
  5. 5.
    Ariizumi S, Kotera Y, Takahashi Y, Katagiri S, Chen IP, Ota T et al. Mass-forming intrahepatic cholangiocarcinoma with marked enhancement on arterial-phase computed tomography reflects favorable surgical outcomes. J Surg Oncol. 2011;104(2):130–9.CrossRefGoogle Scholar
  6. 6.
    Yamamoto Y, Turkoglu MA, Aramaki T, Sugiura T, Okamura Y, Ito T et al. Vascularity of Intrahepatic Cholangiocarcinoma on Computed Tomography is Predictive of Lymph Node Metastasis. Ann Surg Oncol. 2016;23(Suppl 4):485–93.CrossRefGoogle Scholar
  7. 7.
    Yamamoto Y, Sugiura T, Todaka A, Okamura Y, Ito T, Ashida R et al. Surgical Indication for Advanced Intrahepatic Cholangiocarcinoma According to the Optimal Preoperative Carbohydrate Antigen 19-9 Cutoff Value. World J Surg. 2018. 42(10):3331–40. doi: https://doi.org/10.1007/s00268-018-4605-y.CrossRefGoogle Scholar
  8. 8.
    Yamamoto Y, Shimada K, Sakamoto Y, Esaki M, Nara S, Ban D et al. Clinicopathological characteristics of intrahepatic cholangiocellular carcinoma presenting intrahepatic bile duct growth. J Surg Oncol. 2009;99(3):161–5.CrossRefGoogle Scholar
  9. 9.
    Turkoglu MA, Yamamoto Y, Sugiura T, Okamura Y, Ito T, Ashida R et al. The favorable prognosis after operative resection of hypervascular intrahepatic cholangiocarcinoma: A clinicopathologic and immunohistochemical study. Surgery. 2016;160(3):683–90.CrossRefGoogle Scholar
  10. 10.
    Amin MB ES, Greene F. AJCC Cancer Staging Manual. 8th ed. New York. Springer International Publishing. 2017.CrossRefGoogle Scholar
  11. 11.
    Nathan H, Aloia TA, Vauthey JN, Abdalla EK, Zhu AX, Schulick RD et al. A proposed staging system for intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2009;16(1):14–22. doi: https://doi.org/10.1245/s10434-008-0180-z.CrossRefGoogle Scholar
  12. 12.
    Sobin LH. TNM Classification of Malignant Tumours seventh edition. 2009.Google Scholar
  13. 13.
    Farges O, Fuks D, Le Treut YP, Azoulay D, Laurent A, Bachellier P et al. AJCC 7th edition of TNM staging accurately discriminates outcomes of patients with resectable intrahepatic cholangiocarcinoma: By the AFC-IHCC-2009 study group. Cancer. 2011;117(10):2170–7. doi: https://doi.org/10.1002/cncr.25712.CrossRefGoogle Scholar
  14. 14.
    Sakamoto Y, Kokudo N, Matsuyama Y, Sakamoto M, Izumi N, Kadoya M et al. Proposal of a new staging system for intrahepatic cholangiocarcinoma: Analysis of surgical patients from a nationwide survey of the Liver Cancer Study Group of Japan. Cancer. 2016;122(1):61–70. doi: https://doi.org/10.1002/cncr.29686.CrossRefGoogle Scholar
  15. 15.
    Igami T, Ebata T, Yokoyama Y, Sugawara G, Takahashi Y, Nagino M. Staging of peripheral-type intrahepatic cholangiocarcinoma: appraisal of the new TNM classification and its modifications. World J Surg. 2011;35(11):2501–9. doi: https://doi.org/10.1007/s00268-011-1242-0.CrossRefGoogle Scholar
  16. 16.
    Uenishi T, Ariizumi S, Aoki T, Ebata T, Ohtsuka M, Tanaka E et al. Proposal of a new staging system for mass-forming intrahepatic cholangiocarcinoma: a multicenter analysis by the Study Group for Hepatic Surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. J Hepatobiliary Pancreat Sci. 2014;21(7):499–508. doi: https://doi.org/10.1002/jhbp.92.CrossRefGoogle Scholar
  17. 17.
    Brierley JD. TNM Classification of Malignant Tumours eight edition. 2017.Google Scholar
  18. 18.
    Ebata T, Kosuge T, Hirano S, Unno M, Yamamoto M, Miyazaki M et al. Proposal to modify the International Union Against Cancer staging system for perihilar cholangiocarcinomas. Br J Surg. 2014;101(2):79–88.CrossRefGoogle Scholar
  19. 19.
    Uenishi T, Kubo S, Yamazaki O, Yamada T, Sasaki Y, Nagano H et al. Indications for surgical treatment of intrahepatic cholangiocarcinoma with lymph node metastases. J Hepatobiliary Pancreat Surg. 2008;15(4):417–22. doi: https://doi.org/10.1007/s00534-007-1315-5.CrossRefGoogle Scholar
  20. 20.
    Nakagohri T, Kinoshita T, Konishi M, Takahashi S, Gotohda N. Surgical outcome and prognostic factors in intrahepatic cholangiocarcinoma. World J Surg. 2008;32(12):2675–80. doi: https://doi.org/10.1007/s00268-008-9778-3.CrossRefGoogle Scholar
  21. 21.
    Endo I, Gonen M, Yopp AC, Dalal KM, Zhou Q, Klimstra D et al. Intrahepatic cholangiocarcinoma: rising frequency, improved survival, and determinants of outcome after resection. Ann Surg. 2008;248(1):84–96. doi: https://doi.org/10.1097/SLA.0b013e318176c4d3.CrossRefGoogle Scholar
  22. 22.
    Spolverato G, Bagante F, Weiss M, Alexandrescu S, Marques HP, Aldrighetti L et al. Comparative performances of the 7th and the 8th editions of the American Joint Committee on Cancer staging systems for intrahepatic cholangiocarcinoma. J Surg Oncol. 2017;115(6):696–703. doi: https://doi.org/10.1002/jso.24569.CrossRefGoogle Scholar
  23. 23.
    Sasaki K, Margonis GA, Andreatos N, Bagante F, Weiss M, Barbon C et al. Preoperative Risk Score and Prediction of Long-Term Outcomes after Hepatectomy for Intrahepatic Cholangiocarcinoma. J Am Coll Surg. 2018;226(4):393–403. doi:  https://doi.org/10.1016/j.jamcollsurg.2017.12.011 CrossRefGoogle Scholar
  24. 24.
    Ohtsuka M, Ito H, Kimura F, Shimizu H, Togawa A, Yoshidome H et al. Results of surgical treatment for intrahepatic cholangiocarcinoma and clinicopathological factors influencing survival. Br J Surg. 2002;89(12):1525–31. doi: https://doi.org/10.1046/j.1365-2168.2002.02268.x.CrossRefGoogle Scholar
  25. 25.
    Yamasaki S. Intrahepatic cholangiocarcinoma: macroscopic type and stage classification. J Hepatobiliary Pancreat Surg. 2003;10(4):288–91. doi: https://doi.org/10.1007/s00534-002-0732-8.CrossRefGoogle Scholar
  26. 26.
    Uenishi T, Yamazaki O, Yamamoto T, Hirohashi K, Tanaka H, Tanaka S et al. Serosal invasion in TNM staging of mass-forming intrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Surg. 2005;12(6):479–83. doi: https://doi.org/10.1007/s00534-005-1026-8.CrossRefGoogle Scholar
  27. 27.
    Bridgewater J, Galle PR, Khan SA, Llovet JM, Park JW, Patel T et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol. 2014;60(6):1268–89.CrossRefGoogle Scholar
  28. 28.
    Shimada K, Sano T, Sakamoto Y, Esaki M, Kosuge T, Ojima H. Surgical outcomes of the mass-forming plus periductal infiltrating types of intrahepatic cholangiocarcinoma: a comparative study with the typical mass-forming type of intrahepatic cholangiocarcinoma. World J Surg. 2007;31(10):2016–22.CrossRefGoogle Scholar
  29. 29.
    Yamamoto M, Takasaki K, Yoshikawa T, Ueno K, Nakano M. Does gross appearance indicate prognosis in intrahepatic cholangiocarcinoma? J Surg Oncol. 1998;69(3):162–7.CrossRefGoogle Scholar
  30. 30.
    Uenishi T, Yamazaki O, Horii K, Yamamoto T, Kubo S. A long-term survivor of intrahepatic cholangiocarcinoma with paraaortic lymph node metastasis. J Gastroenterol 2006;41(4):391–2.CrossRefGoogle Scholar
  31. 31.
    Miura JT, Johnston FM, Tsai S, George B, Thomas J, Eastwood D, et al. Chemotherapy for Surgically Resected Intrahepatic Cholangiocarcinoma. Ann Surg Oncol. 2015;22(11):3716–23.CrossRefGoogle Scholar
  32. 32.
    Reames BN, Bagante F, Ejaz A, Spolverato G, Ruzzenente A, Weiss M, et al. Impact of adjuvant chemotherapy on survival in patients with intrahepatic cholangiocarcinoma: a multi-institutional analysis. HPB (Oxford) 2017;19(10):901–9.CrossRefGoogle Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2019

Authors and Affiliations

  1. 1.Division of Hepato-Biliary-Pancreatic SurgeryShizuoka Cancer CenterShizuokaJapan
  2. 2.Division of PathologyShizuoka Cancer CenterShizuokaJapan

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