Skip to main content
SpringerLink
Log in

Adjuvant Chemolipiodolization Reduces Early Recurrence Derived from Intrahepatic Metastasis of Hepatocellular Carcinoma After Hepatectomy

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The recurrence of hepatocellular carcinoma is still high even after surgery. Two general recurrence patterns occur: intrahepatic metastasis (IM) and multicentric carcinogenesis (MC). The aim of this study was to investigate the effectiveness of adjuvant chemolipiodolization for reducing IM or MC recurrences after surgery.

Methods

A retrospective case-control study was carried out. From April 2005, adjuvant chemolipiodolization was performed in 63 initial hepatocellular carcinoma patients 3 months after surgery. Sixty-four patients who underwent surgery between April 2001 and March 2005 were analyzed as the control group. Recurrence-free and overall survival as well as prognostic factors were analyzed univariately and multivariately.

Results

The 2-year recurrence-free survival was 57% in the chemolipiodolization group and 37% in the control group (P = 0.02). However, there was no significant difference at 5 years after surgery (P = 0.09). The 5-year overall survival rates in the chemolipiodolization and the control groups were 82.4 and 55.7%, respectively (P = 0.04). Cox proportional multivariate analysis revealed that adjuvant chemolipiodolization was an independent favorable prognostic factor for 2-year recurrence-free survival, and the odds ratio [95% confidential interval] was 0.55 [0.34–0.90] (P = 0.02). However, adjuvant chemolipiodolization was not an independent favorable prognostic factor for 5-year overall survival.

Conclusions

Adjuvant chemolipiodolization can reduce the risk of early recurrences, which would be mainly IM derived. However, chemolipiodolization did not reduce late phase recurrences after surgery, which would be mainly MC derived. To prevent late phase recurrences, another novel strategy would be needed.

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

Similar content being viewed by others

References

  1. 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;38:200–7.

    Article  PubMed  Google Scholar 

  2. Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology. 1999;30:1434–40.

    Article  PubMed  CAS  Google Scholar 

  3. Poon RT, Fan ST, Ng IO, Lo CM, Liu CL, Wong J. Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma. Cancer. 2000;89:500–7.

    Article  PubMed  CAS  Google Scholar 

  4. Takenaka K, Adachi E, Nishizaki T, et al. Possible multicentric occurrence of hepatocellular carcinoma: a clinicopathological study. Hepatology. 1994;19:889–94.

    Article  PubMed  CAS  Google Scholar 

  5. Chen PJ, Chen DS, Lai MY, et al. Clonal origin of recurrent hepatocellular carcinomas. Gastroenterology. 1989;96:527–9.

    PubMed  CAS  Google Scholar 

  6. 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;243:229–35.

    Article  PubMed  Google Scholar 

  7. Sakon M, Umeshita K, Nagano H, et al. Clinical significance of hepatic resection in hepatocellular carcinoma: analysis by disease-free survival curves. Arch Surg. 2000;135:1456–9.

    Article  PubMed  CAS  Google Scholar 

  8. A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology. 1998;28:751–5.

  9. Tateishi R, Yoshida H, Shiina S, et al. Proposal of a new prognostic model for hepatocellular carcinoma: an analysis of 403 patients. Gut. 2005;54:419–25.

    Article  PubMed  CAS  Google Scholar 

  10. Yamamoto J, Kosuge T, Takayama T, et al. Perioperative blood transfusion promotes recurrence of hepatocellular carcinoma after hepatectomy. Surgery. 1994;115:303–9.

    PubMed  CAS  Google Scholar 

  11. Eguchi S, Kanematsu T, Arii S, et al. Comparison of the outcomes between an anatomical subsegmentectomy and a non-anatomical minor hepatectomy for single hepatocellular carcinomas based on a japanese nationwide survey. Surgery. 2008;143:469–75.

    Article  PubMed  Google Scholar 

  12. Katz SC, Shia J, Liau KH, et al. Operative blood loss independently predicts recurrence and survival after resection of hepatocellular carcinoma. Ann Surg. 2009;249:617–23.

    Article  PubMed  Google Scholar 

  13. Yamamoto M, Arii S, Sugahara K, Tobe T. Adjuvant oral chemotherapy to prevent recurrence after curative resection for hepatocellular carcinoma. Br J Surg. 1996;83:336–40.

    Article  PubMed  CAS  Google Scholar 

  14. Lau WY, Leung TW, Ho SK, et al. Adjuvant intra-arterial iodine-131-labelled lipiodol for resectable hepatocellular carcinoma: a prospective randomised trial. Lancet. 1999;353:797–801.

    Article  PubMed  CAS  Google Scholar 

  15. Izumi R, Shimizu K, Iyobe T, et al. Postoperative adjuvant hepatic arterial infusion of lipiodol containing anticancer drugs in patients with hepatocellular carcinoma. Hepatology. 1994;20:295–301.

    Article  PubMed  CAS  Google Scholar 

  16. Takenaka K, Yoshida K, Nishizaki T, et al. Postoperative prophylactic lipiodolization reduces the intrahepatic recurrence of hepatocellular carcinoma. Am J Surg. 1995;169:400–4.

    Article  PubMed  CAS  Google Scholar 

  17. Li JQ, Zhang YQ, Zhang WZ, Yuan YF, Li GH. Randomized study of chemoembolization as an adjuvant therapy for primary liver carcinoma after hepatectomy. J Cancer Res Clin Oncol. 1995;121:364–6.

    Article  PubMed  CAS  Google Scholar 

  18. Takayama T, Sekine T, Makuuchi M, et al. Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial. Lancet. 2000;356:802–7.

    Article  PubMed  CAS  Google Scholar 

  19. Mathurin P, Raynard B, Dharancy S, et al. Meta-analysis: evaluation of adjuvant therapy after curative liver resection for hepatocellular carcinoma. Aliment Pharmacol Ther. 2003;17:1247–61.

    Article  PubMed  CAS  Google Scholar 

  20. Samuel M, Chow PK, Chan Shih-Yen E, Machin D, Soo KC. Neoadjuvant and adjuvant therapy for surgical resection of hepatocellular carcinoma. Cochrane Database Syst Rev. 2009;1:CD001199.

  21. Boucher E, Corbinais S, Rolland Y, et al. Adjuvant intra-arterial injection of iodine-131-labeled lipiodol after resection of hepatocellular carcinoma. Hepatology. 2003;38:1237–41.

    Article  PubMed  CAS  Google Scholar 

  22. Tabone M, Vigano L, Ferrero A, Pellerito R, Carbonatto P, Capussotti L. Prevention of intrahepatic recurrence by adjuvant (131)iodine-labeled lipiodol after resection for hepatocellular carcinoma in HCV-related cirrhosis. Eur J Surg Oncol. 2007;33:61–6.

    Article  PubMed  CAS  Google Scholar 

  23. Shimoda M, Bando T, Nagata T, Shirosaki I, Sakamoto T, Tsukada K. Prophylactic chemolipiodolization for postoperative hepatoma patients. Hepatogastroenterology. 2001;48:493–7.

    PubMed  CAS  Google Scholar 

  24. Tanaka K, Shimada H, Togo S, et al. Use of transcatheter arterial infusion of anticancer agents with lipiodol to prevent recurrence of hepatocellular carcinoma after hepatic resection. Hepatogastroenterology. 1999;46:1083–8.

    PubMed  CAS  Google Scholar 

  25. Shimada M, Takenaka K, Gion T, et al. Prognosis of recurrent hepatocellular carcinoma: a 10-year surgical experience in Japan. Gastroenterology. 1996;111:720–6.

    Article  PubMed  CAS  Google Scholar 

  26. Lau WY, Lai EC, Leung TW, Yu SC. Adjuvant intra-arterial iodine-131-labeled lipiodol for resectable hepatocellular carcinoma: a prospective randomized trial-update on 5-year and 10-year survival. Ann Surg. 2008;247:43–8.

    Article  PubMed  Google Scholar 

  27. Boucher E, Bouguen G, Garin E, Guillygomarch A, Boudjema K, Raoul JL. Adjuvant intraarterial injection of 131i-labeled lipiodol after resection of hepatocellular carcinoma: progress report of a case-control study with a 5-year minimal follow-up. J Nucl Med. 2008;49:362–6.

    Article  PubMed  Google Scholar 

  28. Chevret S, Trinchet JC, Mathieu D, Rached AA, Beaugrand M, Chastang C. A new prognostic classification for predicting survival in patients with hepatocellular carcinoma. Groupe d’etude et de traitement du carcinome hepatocellulaire. J Hepatol. 1999;31:133–41.

    Article  PubMed  CAS  Google Scholar 

  29. Damdinsuren B, Nagano H, Sakon M, et al. Interferon-beta is more potent than interferon-alpha in inhibition of human hepatocellular carcinoma cell growth when used alone and in combination with anticancer drugs. Ann Surg Oncol. 2003;10:1184–90.

    Article  PubMed  Google Scholar 

  30. Ikeda K, Arase Y, Saitoh S, et al. Interferon beta prevents recurrence of hepatocellular carcinoma after complete resection or ablation of the primary tumor—a prospective randomized study of hepatitis C virus-related liver cancer. Hepatology. 2000;32:228–32.

    Article  PubMed  CAS  Google Scholar 

  31. Kubo S, Nishiguchi S, Hirohashi K, et al. Effects of long-term postoperative interferon-alpha therapy on intrahepatic recurrence after resection of hepatitis C virus-related hepatocellular carcinoma. A randomized, controlled trial. Ann Intern Med. 2001;134:963–7.

    PubMed  CAS  Google Scholar 

  32. Mazzaferro V, Romito R, Schiavo M, et al. Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis. Hepatology. 2006;44:1543–54.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Second Department of Surgery, School of Medicine, Wakayama Medical University, Wakayama City, Japan

    Masaki Ueno MD, Kazuhisa Uchiyama MD, Satoru Ozawa MD, Shinya Hayami MD, Yoshinobu Shigekawa MD, Masaji Tani MD & Hiroki Yamaue MD, PhD

Authors
  1. Masaki Ueno MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kazuhisa Uchiyama MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Satoru Ozawa MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shinya Hayami MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoshinobu Shigekawa MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Masaji Tani MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hiroki Yamaue MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroki Yamaue MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ueno, M., Uchiyama, K., Ozawa, S. et al. Adjuvant Chemolipiodolization Reduces Early Recurrence Derived from Intrahepatic Metastasis of Hepatocellular Carcinoma After Hepatectomy. Ann Surg Oncol 18, 3624–3631 (2011). https://doi.org/10.1245/s10434-011-1800-6

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-011-1800-6

Keywords

Search

Navigation