Journal of Gastrointestinal Surgery

, Volume 18, Issue 3, pp 562–572

Survival Outcomes and Prognostic Factors of Surgical Therapy for All Potentially Resectable Intrahepatic Cholangiocarcinoma: a Large Single-Center Cohort Study

  • Xianwu Luo
  • Lei Yuan
  • Yi Wang
  • Ruiliang Ge
  • Yanfu Sun
  • Gongtian Wei
Original Article



Surgical resection is currently indicated for all potentially resectable intrahepatic cholangiocarcinoma (ICC), but the survival outcomes and the prognostic factors have not been well-documented due to its rarity. This study aims to assess these in a large, consecutive series of patients with ICC treated surgically.


A retrospective study was conducted on 1,333 ICC patients undergoing surgery between January 2007 and December 2011. Surgical results and survival were evaluated and compared among different subgroups of patients. Univariate and multivariate analyses were performed to identify prognostic factors.


R0, R1, R2 resection and exploratory laparotomy were obtained in 34.8, 44.9, 16.4, and 3.9 % of the patients, respectively. The overall 1-, 3-, and 5-year survival rates for the entire cohort were 58.2, 25.2, and 17.0 %, respectively, with corresponding rates of 79.1, 42.6, and 28.7 % for patients with R0 resection; 60.5, 20.1, and 13.9 % for patients with R1 resection; 20.5, 7.4, and 0 % for patients with R2 resection; and 3.8, 0, and 0 % for patients with an exploratory laparotomy. Independent factors for poor survival included positive resection margin, lymph node metastasis, multiple tumors, vascular invasion, and elevated CA19-9 and/or CEA, whereas hepatitis B virus infection and cirrhosis were independently favorable prognosis indicators.


R0 resection offers the best possibility of long-term survival, but the chance of a R0 resection is low when surgery is performed for potential resectable ICC. Further randomized trials are warranted to refine indications for surgery in the management of ICC.


Intrahepatic cholangiocarcinoma Mass-forming type Hepatic resection Prognosis Survival 


  1. 1.
    Patel T. Cholangiocarcinoma--controversies and challenges. Nat Rev Gastroenterol Hepatol 2011;8:189–200.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Khan SA, Thomas HC, Davidson BR, Taylor-Robinson SD. Cholangiocarcinoma. Lancet 2005;366:1303–14.PubMedCrossRefGoogle Scholar
  3. 3.
    Poultsides GA, Zhu AX, Choti MA, Pawlik TM. Intrahepatic cholangiocarcinoma. Surg Clin North Am 2010;90:817–37.PubMedCrossRefGoogle Scholar
  4. 4.
    Sempoux C, Jibara G, Ward S, Fan C, Qin L, Roayaie S et al. Intrahepatic Cholangiocarcinoma: New Insights in Pathology. Seminars in Liver Disease 2011;31:049–60.CrossRefGoogle Scholar
  5. 5.
    Lang H, Sotiropoulos GC, Fruhauf NR, Domland M, Paul A, Kind EM et al. Extended hepatectomy for intrahepatic cholangiocellular carcinoma (ICC): when is it worthwhile? Single center experience with 27 resections in 50 patients over a 5-year period. Ann Surg 2005;241:134–43.PubMedGoogle Scholar
  6. 6.
    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;248:84–96.PubMedCrossRefGoogle Scholar
  7. 7.
    Tan JC, Coburn NG, Baxter NN, Kiss A, Law CH. Surgical management of intrahepatic cholangiocarcinoma--a population-based study. Ann Surg Oncol 2008;15:600–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Jonas S, Thelen A, Benckert C, Biskup W, Neumann U, Rudolph B et al. Extended liver resection for intrahepatic cholangiocarcinoma: A comparison of the prognostic accuracy of the fifth and sixth editions of the TNM classification. Ann Surg 2009;249:303–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Roayaie S, Guarrera JV, Ye MQ, Thung SN, Emre S, Fishbein TM et al. Aggressive surgical treatment of intrahepatic cholangiocarcinoma: predictors of outcomes. J Am Coll Surg 1998;187:365–72.PubMedCrossRefGoogle Scholar
  10. 10.
    Meyer CG, Penn I, James L. Liver transplantation for cholangiocarcinoma: results in 207 patients. Transplantation 2000;69:1633–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Weimann A, Varnholt H, Schlitt HJ, Lang H, Flemming P, Hustedt C et al. Retrospective analysis of prognostic factors after liver resection and transplantation for cholangiocellular carcinoma. Br J Surg 2000;87:1182–7.PubMedCrossRefGoogle Scholar
  12. 12.
    DeOliveira ML, Cunningham SC, Cameron JL, Kamangar F, Winter JM, Lillemoe KD et al. Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg 2007;245:755–62.PubMedCrossRefGoogle Scholar
  13. 13.
    Farges O, Fuks D, Boleslawski E, Le Treut YP, Castaing D, Laurent A et al. Influence of surgical margins on outcome in patients with intrahepatic cholangiocarcinoma: a multicenter study by the AFC-IHCC-2009 study group. Ann Surg 2011;254:824–9.PubMedCrossRefGoogle Scholar
  14. 14.
    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;12:479–83.PubMedCrossRefGoogle Scholar
  15. 15.
    Shimada K, Sano T, Sakamoto Y, Esaki M, Kosuge T, Ojima H. Clinical impact of the surgical margin status in hepatectomy for solitary mass-forming type intrahepatic cholangiocarcinoma without lymph node metastases. J Surg Oncol 2007;96:160–5.PubMedCrossRefGoogle Scholar
  16. 16.
    Konstadoulakis MM, Roayaie S, Gomatos IP, Labow D, Fiel MI, Miller CM et al. Fifteen-year, single-center experience with the surgical management of intrahepatic cholangiocarcinoma: operative results and long-term outcome. Surgery 2008;143:366–74.PubMedCrossRefGoogle Scholar
  17. 17.
    Tamandl D, Herberger B, Gruenberger B, Puhalla H, Klinger M, Gruenberger T. Influence of hepatic resection margin on recurrence and survival in intrahepatic cholangiocarcinoma. Ann Surg Oncol 2008;15:2787–94.PubMedCrossRefGoogle Scholar
  18. 18.
    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;17:1816–22.PubMedCrossRefGoogle Scholar
  19. 19.
    de Jong MC, Nathan H, Sotiropoulos GC, Paul A, Alexandrescu S, Marques H et al. Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of prognostic factors and lymph node assessment. J Clin Oncol 2011;29:3140–5.PubMedCrossRefGoogle Scholar
  20. 20.
    Uchiyama K, Yamamoto M, Yamaue H, Ariizumi S, Aoki T, Kokudo N et al. Impact of nodal involvement on surgical outcomes of 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 2011;18:443–52.PubMedCrossRefGoogle Scholar
  21. 21.
    Li YY, Li H, Lv P, Liu G, Li XR, Tian BN et al. Prognostic value of cirrhosis for intrahepatic cholangiocarcinoma after surgical treatment. J Gastrointest Surg 2011;15:608–13.PubMedCrossRefGoogle Scholar
  22. 22.
    Nanashima A, Sumida Y, Abo T, Nagasaki T, Takeshita H, Fukuoka H et al. Patient outcome and prognostic factors in intrahepatic cholangiocarcinoma after hepatectomy. Hepatogastroenterology. 2007;54(80):2337–42.PubMedGoogle Scholar
  23. 23.
    Jan YY, Yeh CN, Yeh TS, Chen TC. Prognostic analysis of surgical treatment of peripheral cholangiocarcinoma: two decades of experience at Chang Gung Memorial Hospital. World J Gastroenterol. 2005;11(12):1779–84.PubMedGoogle Scholar
  24. 24.
    Nathan H, Pawlik TM, Wolfgang CL, Choti MA, Cameron JL, Schulick RD. Trends in survival after surgery for cholangiocarcinoma: a 30-year population-based SEER database analysis. J Gastrointest Surg 2007;11:1488–96.PubMedCrossRefGoogle Scholar
  25. 25.
    Dhanasekaran R, Hemming AW, Zendejas I, Treatment outcomes and prognostic factors of intrahepatic cholangiocarcinoma. Oncol Rep. 2013;29(4):1259–67.PubMedGoogle Scholar
  26. 26.
    Wang Y, Li J, Xia Y, Gong R, Wang K, Yan Z et al. Prognostic nomogram for intrahepatic cholangiocarcinoma after partial hepatectomy. J Clin Oncol 2013;31:1188–95.PubMedCrossRefGoogle Scholar
  27. 27.
    Shaib YH, Davila JA, McGlynn K, El-Serag HB. Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase? J Hepatol 2004;40:472–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010;17:1471–4.PubMedCrossRefGoogle Scholar
  29. 29.
    Nathan H, Pawlik TM. Staging of intrahepatic cholangiocarcinoma. Curr Opin Gastroenterol 2010;26:269–73.PubMedCrossRefGoogle Scholar
  30. 30.
    The general rules for the clinical and pathological study of primary liver cancer. Liver Cancer Study Group of Japan. Jpn J Surg 1989; 19:98–129.Google Scholar
  31. 31.
    Zhou XD, Tang ZY, Fan J, Zhou J, Wu ZQ, Qin LX et al. Intrahepatic cholangiocarcinoma: report of 272 patients compared with 5,829 patients with hepatocellular carcinoma. J Cancer Res Clin Oncol 2009;135:1073–80.PubMedCrossRefGoogle Scholar
  32. 32.
    Tamandl D, Kaczirek K, Gruenberger B, Koelblinger C, Maresch J, Jakesz R et al. Lymph node ratio after curative surgery for intrahepatic cholangiocarcinoma. Br J Surg 2009;96:919–25.PubMedCrossRefGoogle Scholar
  33. 33.
    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;89:1525–31.PubMedCrossRefGoogle Scholar
  34. 34.
    Sotiropoulos GC, Bockhorn M, Sgourakis G, Brokalaki EI, Molmenti EP, Neuhäuser M et al. R0 liver resections for primary malignant liver tumors in the noncirrhotic liver: a diagnosis-related analysis. Dig Dis Sci. 2009;54(4):887–94.PubMedCrossRefGoogle Scholar
  35. 35.
    Zhou HB, Wang H, Li YQ, Li SX, Zhou DX, Tu QQ et al. Hepatitis B virus infection: a favorable prognostic factor for intrahepatic cholangiocarcinoma after resection. World J Gastroenterol 2011;17:1292–1303.PubMedCrossRefGoogle Scholar
  36. 36.
    Puhalla H, Schuell B, Pokorny H, Kornek GV, Scheithauer W, Gruenberger T. Treatment and outcome of intrahepatic cholangiocellular carcinoma. Am J Surg 2005;189:173–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Nakagawa T, Kamiyama T, Kurauchi N, Matsushita M, Nakanishi K, Kamachi H et al. Number of lymph node metastases is a significant prognostic factor in intrahepatic cholangiocarcinoma. World J Surg 2005;29:728–33.PubMedCrossRefGoogle Scholar
  38. 38.
    Paik KY, Jung JC, Heo JS, Choi SH, Choi DW, Kim YI. What prognostic factors are important for resected intrahepatic cholangiocarcinoma? J Gastroenterol Hepatol 2008;23:766–70.PubMedCrossRefGoogle Scholar
  39. 39.
    Miwa S, Miyagawa S, Kobayashi A, Akahane Y, Nakata T, Mihara M et al. Predictive factors for intrahepatic cholangiocarcinoma recurrence in the liver following surgery. J Gastroenterol 2006;41:893–900.PubMedCrossRefGoogle Scholar
  40. 40.
    Lang H, Sotiropoulos GC, Sgourakis G, Schmitz KJ, Paul A, Hilgard P et al. Operations for intrahepatic cholangiocarcinoma: single-institution experience of 158 patients. J Am Coll Surg 2009;208:218–28.PubMedCrossRefGoogle Scholar
  41. 41.
    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;16:14–22.PubMedCrossRefGoogle Scholar
  42. 42.
    Morimoto Y, Tanaka Y, Ito T, Nakahara M, Nakaba H, Nishida T et al. Long-term survival and prognostic factors in the surgical treatment for intrahepatic cholangiocarcinoma. J Hepatobiliary Pancreat Surg 2003;10:432–40.PubMedCrossRefGoogle Scholar
  43. 43.
    Okabayashi T, Yamamoto J, Kosuge T, Shimada K, Yamasaki S, Takayama T et al. A new staging system for mass-forming intrahepatic cholangiocarcinoma: analysis of preoperative and postoperative variables. Cancer 2001;92:2374–83.PubMedCrossRefGoogle Scholar
  44. 44.
    Patel T. Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology. 2001;33:1353–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Grobmyer SR, Wang L, Gonen M, Fong Y, Klimstra D, D’Angelica M et al. Perihepatic lymph node assessment in patients undergoing partial hepatectomy for malignancy. Ann Surg. 2006;244(2):260–4.PubMedCrossRefGoogle Scholar
  46. 46.
    Shimada M, Yamashita Y, Aishima S, Shirabe K, Takenaka K, Sugimachi K. Value of lymph node dissection during resection of intrahepatic cholangiocarcinoma. Br J Surg 2001;88:1463–6.PubMedCrossRefGoogle Scholar
  47. 47.
    Uenishi T, Hirohashi K, Kubo S, Yamamoto T, Yamazaki O, Shuto T et al. Clinicopathologic features in patients with long-term survival following resection for intrahepatic cholangiocarcinoma. Hepatogastroenterology 2003;50:1069–72.PubMedGoogle Scholar
  48. 48.
    Inoue K, Makuuchi M, Takayama T, Torzilli G, Yamamoto J, Shimada K et al. Long-term survival and prognostic factors in the surgical treatment of mass-forming type cholangiocarcinoma. Surgery 2000;127:498–505.PubMedCrossRefGoogle Scholar
  49. 49.
    Rana A, Hong JC. Orthotopic liver transplantation in combination with neoadjuvant therapy: a new paradigm in the treatment of unresectable intrahepatic cholangiocarcinoma. Curr Opin Gastroenterol 2012;28:258–65.PubMedCrossRefGoogle Scholar
  50. 50.
    Zeng ZC, Tang ZY, Fan J, Zhou J, Qin LX, Ye SL et al. Consideration of the role of radiotherapy for unresectable intrahepatic cholangiocarcinoma: a retrospective analysis of 75 patients. Cancer J 2006;12:113-22.PubMedGoogle Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2014

Authors and Affiliations

  • Xianwu Luo
    • 1
  • Lei Yuan
    • 1
  • Yi Wang
    • 1
  • Ruiliang Ge
    • 1
  • Yanfu Sun
    • 1
  • Gongtian Wei
    • 1
  1. 1.Second Department of Hepatic Surgery, Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghaiPeople’s Republic of China

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