Annals of Surgical Oncology

, Volume 15, Issue 2, pp 618–629 | Cite as

Prognostic Factors and Optimal Treatment Strategy for Intrahepatic Nodular Recurrence After Curative Resection of Hepatocellular Carcinoma

  • Gi-Hong Choi
  • Dong-Hyun Kim
  • Chang-Moo Kang
  • Kyung-Sik Kim
  • Jin-Sub Choi
  • Woo-Jung Lee
  • Byong-Ro Kim
Hepatic and Pancreatic Tumors



Intrahepatic recurrence is a major problem after curative resection of hepatocellular carcinoma. However, the most effective treatments for patients with intrahepatic recurrence still remain unclear. In addition, the selection of various treatment modalities such as repeat resection, local ablation therapy, and transarterial chemoembolization is only applicable to patients with intrahepatic nodular recurrence.


Of 353 patients who underwent curative resection, 97 patients with intrahepatic nodular recurrence were retrospectively studied. The prognostic factors for survival after recurrence and treatment modalities were analyzed. The patients were divided into two groups, a control group and a progression group, according to their response to initial treatment for recurrent tumors.


The 1-, 3-, and 5-year overall survival rates after recurrence in patients with intrahepatic nodular recurrence were 91.0%, 71.0%, and 37.5%, respectively. Multivariate analysis revealed that early recurrence (≤12 months), Child-Pugh class B or C at diagnosis of recurrence, and serum albumin level of ≤3.5 g/dL at diagnosis of recurrence were poor prognostic factors for survival after recurrence. With regard to the response to the initial treatment, time to recurrence of ≤12 months was found to be the only statistically significant risk factor for progression of disease in multivariate analysis.


Time to recurrence, which usually corresponds with the cellular origin of recurrence, seems to be more important when determining the prognosis of patients with recurrent disease and treatment response than treatment modality. Therefore, different treatment methods should be selected according to the time to recurrence of intrahepatic nodular recurrence.


Hepatocellular carcinoma Intrahepatic nodular recurrence Prognosis–Treatment modalities 


  1. 1.
    Poon RT, Fan ST, Lo CM, et al. Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors. Ann Surg 1999;229:216–22PubMedCrossRefGoogle Scholar
  2. 2.
    Cha C, Fong Y, Jarnagin WR, et al. Predictors and patterns of recurrence after resection of hepatocellular carcinoma. J Am Coll Surg 2003;197:753–8PubMedCrossRefGoogle Scholar
  3. 3.
    Chen WT, Chau GY, Lui WY, et al. Recurrent hepatocellular carcinoma after hepatic resection: prognostic factors and long-term outcome. Eur J Surg Oncol 2004;30:414–20PubMedCrossRefGoogle Scholar
  4. 4.
    Taura K, Ikai I, Hatano E, et al. Implication of frequent local ablation therapy for intrahepatic recurrence in prolonged survival of patients with hepatocellular carcinoma undergoing hepatic resection: an analysis of 610 patients over 16 years old. Ann Surg 2006;244:265–73PubMedCrossRefGoogle Scholar
  5. 5.
    Poon RT, Fan ST, Ng IO, et al. Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer 2000;89:500–7PubMedCrossRefGoogle Scholar
  6. 6.
    Shimada K, Sakamoto Y, Esaki M, et al. Analysis of prognostic factors affecting survival after initial recurrence and treatment efficacy for recurrence in patients undergoing potentially curative hepatectomy for hepatocellular carcinoma. Ann Surg Oncol 2007;14:2319–29CrossRefGoogle Scholar
  7. 7.
    Shimada M, Takenaka K, Gion T, et al. Prognosis of recurrent hepatocellular carcinoma: a 10-year surgical experience in Japan. Gastroenterology 1996;111:720–6PubMedCrossRefGoogle Scholar
  8. 8.
    Portolani N, Coniglio A, Ghidoni S, et al. Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg 2006;243:229–35PubMedCrossRefGoogle Scholar
  9. 9.
    Tralhao JG, Dagher I, Lino T, et al. Treatment of tumour recurrence after resection of hepatocellular carcinoma. Analysis of 97 consecutive patients. Eur J Surg Oncol 2006Google Scholar
  10. 10.
    Minagawa M, Makuuchi M, Takayama T, Kokudo N. Selection criteria for repeat hepatectomy in patients with recurrent hepatocellular carcinoma. Ann Surg 2003;238:703–10PubMedCrossRefGoogle Scholar
  11. 11.
    Yamamoto J, Okada S, Shimada K, et al. Treatment strategy for small hepatocellular carcinoma: comparison of long-term results after percutaneous ethanol injection therapy and surgical resection. Hepatology 2001;34:707–13PubMedCrossRefGoogle Scholar
  12. 12.
    Lu MD, Yin XY, Xie XY, et al. Percutaneous thermal ablation for recurrent hepatocellular carcinoma after hepatectomy. Br J Surg 2005;92:1393–8PubMedCrossRefGoogle Scholar
  13. 13.
    Choi D, Lim HK, Rhim H, et al. Percutaneous radiofrequency ablation for recurrent hepatocellular carcinoma after hepatectomy: long-term results and prognostic factors. Ann Surg Oncol 2007;14:2337–47CrossRefGoogle Scholar
  14. 14.
    Poon RT, Fan ST, Lo CM, et al. Long-term survival and pattern of recurrence after resection of small hepatocellular carcinoma in patients with preserved liver function: implications for a strategy of salvage transplantation. Ann Surg 2002;235:373–82PubMedCrossRefGoogle Scholar
  15. 15.
    Belghiti J, Cortes A, Abdalla EK, et al. Resection prior to liver transplantation for hepatocellular carcinoma. Ann Surg 2003;238:885–92PubMedCrossRefGoogle Scholar
  16. 16.
    Matsumata T, Kanematsu T, Takenaka K, et al. Patterns of intrahepatic recurrence after curative resection of hepatocellular carcinoma. Hepatology 1989;9:457–60PubMedCrossRefGoogle Scholar
  17. 17.
    Liver Cancer Study Group of Japan. The General Rules for the Clinical and Pathological Study of Primary Liver Cancer. 4th ed. Tokyo, Japan: Kanehara, 2000Google Scholar
  18. 18.
    Poon RT, Fan ST, Ng IO, Wong J. Significance of resection margin in hepatectomy for hepatocellular carcinoma: a critical reappraisal. Ann Surg 2000;231:544–51PubMedCrossRefGoogle Scholar
  19. 19.
    Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003;362:1907–17PubMedCrossRefGoogle Scholar
  20. 20.
    Kim JK, Han KH, Lee JT, et al. Long-term clinical outcome of phase IIb clinical trial of percutaneous injection with holmium-166/chitosan complex (Milican) for the treatment of small hepatocellular carcinoma. Clin Cancer Res 2006;12:543–8PubMedCrossRefGoogle Scholar
  21. 21.
    Imamura H, Matsuyama Y, Tanaka E, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol 2003;38:200–7PubMedCrossRefGoogle Scholar
  22. 22.
    Arii S, Teramoto K, Kawamura T, et al. Characteristics of recurrent hepatocellular carcinoma in Japan and our surgical experience. J Hepatobiliary Pancreat Surg 2001;8:397–403PubMedCrossRefGoogle Scholar
  23. 23.
    Matsuda M, Fujii H, Kono H, Matsumoto Y. Surgical treatment of recurrent hepatocellular carcinoma based on the mode of recurrence: repeat hepatic resection or ablation are good choices for patients with recurrent multicentric cancer. J Hepatobiliary Pancreat Surg 2001;8:353–9PubMedCrossRefGoogle Scholar
  24. 24.
    Govindarajan S, Craig JR, Valinluck B. Clonal origin of hepatitis B virus–associated hepatocellular carcinoma. Hum Pathol 1988;19:403–5PubMedCrossRefGoogle Scholar
  25. 25.
    Chen PJ, Chen DS, Lai MY, et al. Clonal origin of recurrent hepatocellular carcinomas. Gastroenterology 1989;96:527–9PubMedGoogle Scholar
  26. 26.
    Yamamoto T, Kajino K, Kudo M, et al. Determination of the clonal origin of multiple human hepatocellular carcinomas by cloning and polymerase chain reaction of the integrated hepatitis B virus DNA. Hepatology 1999;29:1446–52PubMedCrossRefGoogle Scholar
  27. 27.
    Mas VR, Maluf DG, Dumur CI, et al. Molecular techniques for identifying HCC origin and biology after orthotopic liver transplantation. Diagn Mol Pathol 2006;15:90–4PubMedCrossRefGoogle Scholar
  28. 28.
    Altimari A, Gruppioni E, Fiorentino M, et al. Genomic allelotyping for distinction of recurrent and de novo hepatocellular carcinoma after orthotopic liver transplantation. Diagn Mol Pathol 2005;14:34–8PubMedCrossRefGoogle Scholar
  29. 29.
    Shimada M, Takenaka K, Taguchi K, et al. Prognostic factors after repeat hepatectomy for recurrent hepatocellular carcinoma. Ann Surg 1998;227:80–5PubMedCrossRefGoogle Scholar
  30. 30.
    Yang W, Chen MH, Yin SS, et al. Radiofrequency ablation of recurrent hepatocellular carcinoma after hepatectomy: therapeutic efficacy on early- and late-phase recurrence. AJR Am J Roentgenol 2006;186:S275–83PubMedCrossRefGoogle Scholar
  31. 31.
    Hwang S, Lee SG, Moon DB, et al. Salvage living donor liver transplantation after prior liver resection for hepatocellular carcinoma. Liver Transpl 2007;13:741–6PubMedCrossRefGoogle Scholar
  32. 32.
    Margarit C, Escartin A, Castells L, et al. Resection for hepatocellular carcinoma is a good option in Child-Turcotte-Pugh class A patients with cirrhosis who are eligible for liver transplantation. Liver Transpl 2005;11:1242–51PubMedCrossRefGoogle Scholar
  33. 33.
    Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996;334:693–9PubMedCrossRefGoogle Scholar
  34. 34.
    Itamoto T, Nakahara H, Amano H, et al. Repeat hepatectomy for recurrent hepatocellular carcinoma. Surgery 2007;141:589–97PubMedCrossRefGoogle Scholar
  35. 35.
    Sasaki Y, Yamada T, Tanaka H, et al. Risk of recurrence in a long-term follow-up after surgery in 417 patients with hepatitis B– or hepatitis C–related hepatocellular carcinoma. Ann Surg 2006;244:771–80PubMedCrossRefGoogle Scholar
  36. 36.
    Nagasue N, Ono T, Yamanoi A, et al. Prognostic factors and survival after hepatic resection for hepatocellular carcinoma without cirrhosis. Br J Surg 2001;88:515–22PubMedCrossRefGoogle Scholar
  37. 37.
    Sasaki A, Iwashita Y, Shibata K, et al. Preoperative transcatheter arterial chemoembolization reduces long-term survival rate after hepatic resection for resectable hepatocellular carcinoma. Eur J Surg Oncol 2006;32:773–9PubMedCrossRefGoogle Scholar
  38. 38.
    Huang YS, Chiang JH, Wu JC, et al. Risk of hepatic failure after transcatheter arterial chemoembolization for hepatocellular carcinoma: predictive value of the monoethylglycinexylidide test. Am J Gastroenterol 2002;97:1223–7PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2007

Authors and Affiliations

  • Gi-Hong Choi
    • 1
  • Dong-Hyun Kim
    • 1
  • Chang-Moo Kang
    • 1
  • Kyung-Sik Kim
    • 1
  • Jin-Sub Choi
    • 1
  • Woo-Jung Lee
    • 1
  • Byong-Ro Kim
    • 1
  1. 1.Department of SurgeryYonsei University College of MedicineSeodaemun-KuKorea

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