Skip to main content
Log in

Double- and Triple-Positive Tumor Markers Predict Early Recurrence and Poor Survival in Patients with Hepatocellular Carcinoma within the Milan Criteria and Child-Pugh Class A

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

Abstract

The prognostic implications of the expression patterns of three tumor markers, alpha-fetoprotein (AFP), the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) and des-γ-carboxy prothrombin (DCP), have been evaluated in patients with hepatocellular carcinoma (HCC). From January 1994 to December 2014, 1182 consecutive patients underwent hepatic resection and surgical microwave ablation for HCC at our institution. This study analyzed 475 patients within the Milan criteria and Child–Pugh class A. Cumulative overall survival (OS) and disease-free survival (DFS) rates were analyzed relative to the number of positive tumor markers. OS and DFS at 5 years postoperatively were 85.3 and 44.2% in triple-negative patients, 79.4 and 48.0% in single-positive patients, 56.2 and 32.9% in double-positive patients, and 61.7 and 35.7% in triple-positive patients with statistical significance. OS in triple-negative or single-positive patients was 85.3%, and that in all double- or triple-positive patients was 58.0% (P < 0.0001); DFS at 5 years postoperatively in these two groups was 45.9 and 34.0%, respectively (P < 0.0013). Both double- and triple-positive tumor markers are associated with early recurrence and poor survival in HCC patients within the Milan criteria and Child–Pugh class A.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24:2137–2150.

    Article  PubMed  Google Scholar 

  2. Taura N, Fukushima N, Yastuhashi H, Takami Y, Seike M, Watanabe H, Mizuta T, Sasaki Y, Nagata K, Tabara A, Komorizono Y, Taketomi A, Matsumoto S, Tamai T, Muro T, Nakao K, Fukuizumi K, Maeshiro T, Inoue O, Sata M. The incidence of hepatocellular carcinoma associated with hepatitis C infection decreased in Kyushu area. Med Sci Monit. 2011;17:PH7–11.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Mazzaferro V, Regalia E, Doci R, Andrela S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med. 1996;344:693–700.

    Article  Google Scholar 

  4. Kamiyama T, Nakanishi K, Yokoo H, Kamachi H, Tahara M, Suzuki T, Shimamura T, Furukawa H, Matsushita M, Todo S. Recurrence patterns after hepatectomy of hepatocellular carcinoma: implication of Milan criteria utilization. Ann Surg Oncol. 2009;16:1560–1571.

    Article  PubMed  Google Scholar 

  5. Sakaguchi T, Suzuki S, Morita Y, Oishi K, Suzuki A, Fukumoto K, Inaba K, Nakamura S, Konno H. Impact of the preoperative des-gamma-carboxy prothrombin level on prognosis after hepatectomy for hepatocellular carcinoma meeting the Milan criteria. Surg Today. 2010;40:638–645.

    Article  PubMed  Google Scholar 

  6. Kumada T, Nakano S, Takeda I, Kiriyama S, Sone Y, Hayashi K, Katoh H, Endoh T, Sassa T, Satomura S. Clinical utility of Lens culinaris agglutinin-reactive alpha-fetoprotein in small hepatocellular carcinoma: special reference to imaging diagnosis. J Hepatol. 1999;30:125–130.

    Article  CAS  PubMed  Google Scholar 

  7. Koike Y, Shiratori Y, Sato S, Obi S, Teratani T, Imamura M, Yoshida H, Shiina S, Omata M. Des-γ-carboxy prothrombin as a useful predisposing factor for the development of portal venous invasion in patients with hepatocellular carcinoma: a prospective analysis of 227 patients. Cancer. 2001;91:561–569.

    Article  CAS  PubMed  Google Scholar 

  8. Toyoda H, Kumada T, Kiriyama S, Sone Y, Tanikawa M, Hisanaga Y, Yamaguchi M, Kaneoka Y, Washizu J. Prognostic significance of simultaneous measurement of three tumor markers in patients with hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2006;4:111–117.

    Article  CAS  PubMed  Google Scholar 

  9. Kiriyama S, Uchiyama K, Ueno M, Ozawa S, Hayami S, Tani M, Yamaue H. Triple positive tumor markers for hepatocellular carcinoma are useful predictors of poor survival. Ann Surg. 2011;254:984–991.

    Article  PubMed  Google Scholar 

  10. Nakagawa S, Beppu T, Okabe H, Okabe H, Sakamoto K, Kuroki H, Mima K, Nitta H, Imai K, Hayashi H, Sakamoto Y, Hashimoto D, Chikamoto A, Ishiko T, Watanabe M, Baba H. Triple positive tumor markers predict recurrence and survival in early stage hepatocellular carcinoma. Hepatol Res. 2014;44:964–974.

    Article  CAS  PubMed  Google Scholar 

  11. Takami Y, Ryu T, Wada Y, Saitsu H. Evaluation of intraoperative microwave coagulo-necrotic therapy (MCN) for hepatocellular carcinoma: a single center experience of 719 consecutive cases. J Hepatobiliary Pancreat Sci. 2013;20:332–341.

    Article  PubMed  Google Scholar 

  12. Ryu T, Takami Y, Tsutsumi N, Tateishi M, Mikagi K, Wada Y, Saitsu H. Simultaneous microwave coagulo-necrotic therapy (MCN) and laparoscopic splenectomy for the treatment of hepatocellular carcinoma with cirrhotic hypersplenism. Surg Today. 2016; doi: 10.1007/s00595-016-1411-1418.

    Google Scholar 

  13. Wada Y, Takami Y, Tateishi M, Ryu T, Mikagi K, Saitsu H. Efficacy of surgical treatment using microwave coagulo-necrotic therapy for unresectable multiple colorectal liver metastases. OncoTargets Ther. 2016;9:937–943.

    Article  Google Scholar 

  14. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60:646–649.

    Article  CAS  PubMed  Google Scholar 

  15. Liver Cancer Study Group of Japan. General rules for the clinical and pathological study of primary liver cancer, 3rd English edn. Tokyo: Kanehara Shuppan, 2010.

    Google Scholar 

  16. Tateyama M, Yatsuhashi H, Taura N, Motoyoshi Y, Nagaoka S, Yanagi K, Abiru S, Yano K, Komori A, Migita K, Nakamura M, Nagahara H, Sasaki Y, Miyakawa Y, Ishibashi H. Alpha-fetoprotein above normal levels as a risk factor for the development of hepatocellular carcinoma in patients infected with hepatitis C virus. J Gastroenterol 2011;46:92–100.

    Article  CAS  PubMed  Google Scholar 

  17. Farinati F, Marino D, De Giorgio M, Baldan A, Cantarini M, Cursaro C, Rapaccini G, Del Poggio P, Di Nolfo MA, Benvegnu L, Zoli M, Borzio F, Bernardi M, Trevisani F. Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither. Am J Gastroenterol 2006;101:524–532.

    Article  CAS  PubMed  Google Scholar 

  18. Kobayashi M, Hosaka T, Ikeda K, Seko Y, Kawamura Y, Sezaki H, Akuta N, Suzuki F, Suzuki Y, Saitoh S, Arase Y, Kumada H. Highly sensitive AFP-L3% assay is useful for predicting recurrence of hepatocellular carcinoma after curative treatment pre- and postoperatively. Hepatol Res 2011;41:1036–1045.

    Article  CAS  PubMed  Google Scholar 

  19. Takayama T, Makuuchi M, Hirohashi S, Sakamoto M, Yamamoto J, Shimada K, Kosuge T, Okada S, Takayasu K, Yamasaki S. Early hepatocellular carcinoma as an entity with a high cure rate of surgical cure. Hepatology. 1998;28:1241–1246.

    Article  CAS  PubMed  Google Scholar 

  20. Belghiti J, Hiramatsu K, Benoist S, Massault PP, Sauvanet A, Farges O. Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection. J Am Coll Surg. 2000;191:38–46.

    Article  CAS  PubMed  Google Scholar 

  21. Liang P, Wang Y. Microwave ablation of hepatocellular carcinoma. Oncology. 2007;72:124–131.

    Article  PubMed  Google Scholar 

  22. Tateishi R, Shiina S, Teratani T, Obi S, Sato S, Koike Y, Fujishima T, Yoshida H, Kawabe T, Omata M. Percutaneous radiofrequency ablation for hepatocellular carcinoma. An analysis of 1000 cases. Cancer. 2005;103:1201–1209.

    Article  PubMed  Google Scholar 

  23. Saitsu H, Yoshida M, Taniwaki S, Sato H, Okami N, Matsumoto A, Shigetomi K, Sugiyama T, Okuda Y, Nakayama K. Laparoscopic coagulo-necrotic therapy using microtase for small hepatocellular carcinoma. Jpn J Gastroenterol. 1991;88:2727.

    CAS  Google Scholar 

  24. Takenaka K, Kawahara N, Yamamoto K, Kajiyama K, Maeda T, Itasaka H, Shirabe K, Nishizaki T, Yanaga K, Sugimachi K. Results of 280 liver resections for hepatocellular carcinoma. Arch Surg 1996;131:71–76.

    Article  CAS  PubMed  Google Scholar 

  25. Kobayashi A, Miyagawa S, Miwa S, Nakata T. Prognostic impact of anatomical resection on early and late intrahepatic recurrence in patients with hepatocellular carcinoma. J Hepatobiliary Pancreat Surg 2008;15:515–1521.

    Article  PubMed  Google Scholar 

  26. Yamamoto J, Kosuge T, Takayama T, Shimada K, Yamasaki S, Ozaki H, Yamaguchi N, Makuuchi M. Recurrence of hepatocellular carcinoma after surgery. Br J Surg 1996;83:1219–1222.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Study conception and design: Ryu, Takami, and Saitsu Acquisition of data: Ryu, Wada, Tateishi, Matsushima, and Mikagi Analysis and interpretation of data: Ryu, Takami, and Saitsu Drafting of manuscript: Ryu Critical revision: Saitsu

Corresponding author

Correspondence to Tomoki Ryu.

Ethics declarations

This retrospective study was conducted in accordance with the Declaration of Helsinki and the ethical guidelines for clinical studies of the Ministry of Health, Labor and Welfare in Japan. The study protocol was approved by the Ethics Committee on Clinical Investigations of Kyushu Medical Center.

Conflict of Interest

The authors declare that they have no conflicts of interest.

Grant Support

None

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ryu, T., Takami, Y., Wada, Y. et al. Double- and Triple-Positive Tumor Markers Predict Early Recurrence and Poor Survival in Patients with Hepatocellular Carcinoma within the Milan Criteria and Child-Pugh Class A. J Gastrointest Surg 21, 957–966 (2017). https://doi.org/10.1007/s11605-017-3394-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-017-3394-1

Keywords

Navigation