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Elevated Serum Carcinoembryonic Antigen Is Associated with a Worse Survival Outcome of Patients After Liver Resection for Hepatocellular Carcinoma: a Propensity Score Matching Analysis

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery

Abstract

Background

The relationship between serum carcinoembryonic antigen (CEA) and postoperative prognosis in hepatocellular carcinoma (HCC) has not been reported.

Methods

Data of 5410 consecutive HCC patients who underwent hepatectomy was retrospectively reviewed. Survival curves for overall survival (OS) and tumor recurrence (TR) were depicted using the Kaplan-Meier method and compared using the log-rank test. Independent risk factors of OS and TR were analyzed with Cox hazard regression model. Besides, a one-to-one propensity score-matched (PSM) subset was performed to reduce selection bias. Subgroup analysis was done according to hepatitis B virus (HBV) infection or not.

Results

Serum CEA ≥5.1 μg/L was an independent risk factor of OS and TR in the entire cohort and PSM subset (OS—hazard ratio = 1.218, 95 % confidence interval = 1.060–1.400; 1.383, 1.133–1.688, respectively; TR—1.256, 1.114–1.417; 1.258, 1.067–1.484, respectively). Subgroup analysis showed that CEA ≥5.1 μg/L was an independent risk factor of OS and TR in the HBV infection group (OS—1.234, 1.065–1.429; TR—1.231, 1.083–1.399) but not in the non-HBV infection group (OS—1.376, 0.895–2.117; TR—1.437, 0.989–2.088).

Conclusion

Serum CEA ≥5.1 μg/L was an independent risk factor of OS and TR of HCC patients, and patients with CEA ≥5.1 μg/L had poorer prognosis, especially for HCC patients with HBV infection.

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References

  1. Ferenci P, Fried M, Labrecque D, et al. Hepatocellular carcinoma (HCC): a global perspective. J Clin Gastroenterol. Apr 2010;44(4):239–245.

  2. Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. Mar 31 2012;379(9822):1245–1255.

  3. Yuen MF, Hou JL, Chutaputti A. Hepatocellular carcinoma in the Asia Pacific region. J Gastroenterol Hepatol. Mar 2009;24(3):346–353.

  4. Lai CL, Yuen MF. Prevention of hepatitis B virus-related hepatocellular carcinoma with antiviral therapy. Hepatology. Jan 2013;57(1):399–408.

  5. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. Mar 2011;53(3):1020–1022.

  6. Rahbari NN, Mehrabi A, Mollberg NM, et al. Hepatocellular carcinoma: current management and perspectives for the future. Ann Surg. Mar 2011;253(3):453–469.

  7. Ho CM, Lee PH, Shau WY, Ho MC, Wu YM, Hu RH. Survival in patients with recurrent hepatocellular carcinoma after primary hepatectomy: comparative effectiveness of treatment modalities. Surgery. May 2012;151(5):700–709.

  8. Earl TM, Chapman WC. Hepatocellular carcinoma: resection versus transplantation. Semin Liver Dis. Aug 2013;33(3):282–292.

  9. Shah SA, Cleary SP, Wei AC, et al. Recurrence after liver resection for hepatocellular carcinoma: risk factors, treatment, and outcomes. Surgery. Mar 2007;141(3):330–339.

  10. Roayaie S, Blume IN, Thung SN, et al. A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma. Gastroenterology. Sep 2009;137(3):850–855.

  11. Hung IF, Poon RT, Lai CL, Fung J, Fan ST, Yuen MF. Recurrence of hepatitis B-related hepatocellular carcinoma is associated with high viral load at the time of resection. Am J Gastroenterol. Jul 2008;103(7):1663–1673.

  12. 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. Feb 2003;38(2):200–207.

  13. Shi M, Guo RP, Lin XJ, et al. Partial hepatectomy with wide versus narrow resection margin for solitary hepatocellular carcinoma: a prospective randomized trial. Ann Surg. Jan 2007;245(1):36–43.

  14. Li T, Fan J, Qin LX, et al. Risk factors, prognosis, and management of early and late intrahepatic recurrence after resection of primary clear cell carcinoma of the liver. Ann Surg Oncol. Jul 2011;18(7):1955–1963.

  15. Su CW, Lei HJ, Chau GY, et al. The effect of age on the long-term prognosis of patients with hepatocellular carcinoma after resection surgery: a propensity score matching analysis. Arch Surg. Feb 2012;147(2):137–144.

  16. Sempoux C, Jibara G, Ward SC, et al. Intrahepatic cholangiocarcinoma: new insights in pathology. Semin Liver Dis. Feb 2011;31(1):49–60.

  17. Sakamoto Y, Kokudo N, Matsuyama Y, 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. Jan 1 2016;122(1):61–70.

  18. Austin PC. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res. May 2011;46(3):399–424.

  19. D’Agostino RB, Jr. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. Oct 15 1998;17(19):2265–2281.

  20. Gold P, Freedman SO. Specific carcinoembryonic antigens of the human digestive system. J Exp Med. Sep 1 1965;122(3):467–481.

  21. Hammarstrom S. The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol. Apr 1999;9(2):67–81.

  22. Gores GJ. Early detection and treatment of cholangiocarcinoma. Liver Transpl. Nov 2000;6(6 Suppl 2):S30–34.

  23. Duffy MJ. Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful? Clin Chem. Apr 2001;47(4):624–630.

  24. Wichmann MW, Muller C, Lau-Werner U, et al. The role of carcinoembryonic antigen for the detection of recurrent disease following curative resection of large-bowel cancer. Langenbecks Arch Surg. Jul 2000;385(4):271–275.

  25. Chau I, Allen MJ, Cunningham D, et al. The value of routine serum carcino-embryonic antigen measurement and computed tomography in the surveillance of patients after adjuvant chemotherapy for colorectal cancer. J Clin Oncol. Apr 15 2004;22(8):1420–1429.

  26. Kievit J. Follow-up of patients with colorectal cancer: numbers needed to test and treat. Eur J Cancer. May 2002;38(7):986–999.

  27. Fora A, Patta A, Attwood K, Wilding G, Fakih M. Intensive radiographic and biomarker surveillance in stage II and III colorectal cancer. Oncology. 2012;82(1):41–47.

    Article  CAS  PubMed  Google Scholar 

  28. Chen CH, Hsieh MC, Lai CC, et al. Lead time of carcinoembryonic antigen elevation in the postoperative follow-up of colorectal cancer did not affect the survival rate after recurrence. Int J Colorectal Dis. May 2010;25(5):567–571.

  29. Holt A, Nelson RA, Lai L. Surveillance with serial serum carcinoembryonic levels detect colorectal cancer recurrences in patients who are initial nonsecretors. Am Surg. Oct 2010;76(10):1100–1103.

  30. Engaras B. Individual cutoff levels of carcinoembryonic antigen and CA 242 indicate recurrence of colorectal cancer with high sensitivity. Dis Colon Rectum. Mar 2003;46(3):313–321.

  31. Park IJ, Choi GS, Lim KH, Kang BM, Jun SH. Serum carcinoembryonic antigen monitoring after curative resection for colorectal cancer: clinical significance of the preoperative level. Ann Surg Oncol. Nov 2009;16(11):3087–3093.

  32. Irvine T, Scott M, Clark CI. A small rise in CEA is sensitive for recurrence after surgery for colorectal cancer. Colorectal Dis. Jul 2007;9(6):527–531.

  33. Korner H, Soreide K, Stokkeland PJ, Soreide JA. Diagnostic accuracy of serum-carcinoembryonic antigen in recurrent colorectal cancer: a receiver operating characteristic curve analysis. Ann Surg Oncol. Feb 2007;14(2):417–423.

  34. El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. May 2012;142(6):1264–1273.e1261.

  35. Benchimol S, Fuks A, Jothy S, Beauchemin N, Shirota K, Stanners CP. Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. Cell. Apr 21 1989;57(2):327–334.

  36. Sanders DS, Kerr MA. Lewis blood group and CEA related antigens; coexpressed cell-cell adhesion molecules with roles in the biological progression and dissemination of tumours. Mol Pathol. Aug 1999;52(4):174–178.

  37. Juntermanns B, Radunz S, Heuer M, et al. Tumor markers as a diagnostic key for hilar cholangiocarcinoma. Eur J Med Res. Aug 20 2010;15(8):357–361.

  38. Ni XG, Bai XF, Mao YL, et al. The clinical value of serum CEA, CA19-9, and CA242 in the diagnosis and prognosis of pancreatic cancer. Eur J Surg Oncol. Mar 2005;31(2):164–169.

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Authors’ Contributions

Dr Yan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Liu, Xia, and Yan were responsible for the study concept and design; all authors for the acquisition, analysis, or interpretation of data; Liu and Xia for the drafting of the manuscript; all authors for the critical revision of the manuscript for important intellectual content; Liu, Xia, and Yan for statistical analysis; Shi and Yan for administrative, technical, or material support; and Yan for study supervision.

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    Authors and Affiliations

    1. Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China

      Jianwei Liu, Yong Xia, Lehua Shi, Xifeng Li, Lu Wu & Zhenlin Yan

    2. The First Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China

      Jianwei Liu

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    1. Jianwei Liu
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    Correspondence to Zhenlin Yan.

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    Jianwei Liu and Yong Xia contributed equally to this work.

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    Liu, J., Xia, Y., Shi, L. et al. Elevated Serum Carcinoembryonic Antigen Is Associated with a Worse Survival Outcome of Patients After Liver Resection for Hepatocellular Carcinoma: a Propensity Score Matching Analysis. J Gastrointest Surg 20, 2063–2073 (2016). https://doi.org/10.1007/s11605-016-3295-8

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