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Vol. 75, Suppl. 1, 2008
Issue release date: December 2008
Oncology 2008;75:91–98

PIVKA-II Is the Best Prognostic Predictor in Patients with Hepatocellular Carcinoma after Radiofrequency Ablation Therapy

Takahashi S. · Kudo M. · Chung H. · Inoue T. · Ishikawa E. · Kitai S. · Tatsumi C. · Ueda T. · Nagai T. · Minami Y. · Ueshima K.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kinki University School of Medicine, Osaka-Sayama, Japan

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Objective: This study was undertaken to assess the prognostic predictor in patients with hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). Methods: This study retrospectively evaluated clinical outcomes in a cohort of 179 Child-Pugh stage A cirrhotic patients who received curative RFA for naive HCC within Milan criteria. The median follow-up period was 40.5 months. Results: The cumulative survival rate was significantly lower in patients with prothrombin induced by vitamin K absence or antagonist II (PIVKA-II) ≥100 mAU/ml compared with PIVKA-II <100 mAU/ml (58.0 vs. 84.0% at 5 years; p < 0.001). The cumulative recurrence-free survival rates were significantly lower in patients with PIVKA-II ≥100 mAU/ml compared with PIVKA-II <100 mAU/ml (12.1 vs. 16.9% at 5 years; p < 0.032). The cumulative rate of maintaining period within Milan criteria was significantly lower in patients with PIVKA-II ≥100 mAU/ml compared with PIVKA-II <100 mAU/ml (34.1 vs. 55.6% at 5 years; p < 0.001). Cox regression analysis showed that low serum albumin (<3.5 g/dl; p = 0.002, RR 3.75, CI 1.64–8.56), a high level of PIVKA-II (≥100 mAU/ml; p = 0.04, RR 3.15, CI 1.45–6.87), and multiple nodules (p = 0.021, RR 2.61, CI 1.15–5.91) were independently significant mortality risk factors. Conclusion: In patients with Child-Pugh stage A HCC, the PIVKA-II level is the best prognostic predictor after curative RFA.

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  1. Lencioni RA, Allgaier HP, Cioni D, Ol- schewski M, Deibert P, Crocetti L, Frings H, Laubenberger J, Zuber I, Blum HE, Barto- lozzi C: Small hepatocellular carcinoma in cirrhosis: randomized controlled trial of radiofrequency thermal ablation versus percutaneous ethanol injection. Radiology 2003;228:235–240.
  2. Lin SM, Lin CJ, Lin CC, Hsu CW, Chen YC: Radiofrequency ablation improves prognosis compared with ethanol injection for hepatocellular carcinoma of 4 cm or less. Gastroenterology 2004;127:1714–1723.
  3. Shiina S, Teratani T, Obi S, Sato S, Tateishi R, Fujishima T, Ishikawa T, Koike Y, Yoshida H, Kawabe T, Omata M: A randomized controlled trial of radiofrequency ablation with ethanol injection for small hepatocellular carcinoma. Gastroenterology 2005;129:122–130.
  4. 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.
  5. Barnet CC Jr, Curley SA: Ablative techniques for hepatocellular carcinoma. Semin Oncol 2001;28:487–496.
  6. Curley SA, Izzo F, Ellis LM, Nicolas Vauthey J, Vallone P: Radiorequency ablation of hepatocellular cancer in 110 patients with cirrhosis. Ann Surg 2000;232:381–391.
  7. Sala M, Llovet JM, Vilana R, Bianchi L, Sole M, Ayuso C, Bru C, Bruix J; Barcelona Clinic Liver Cancer Group: Initial response to percutaneous ablation predicts survival in patients with hepatocellular carcinoma. Hepatology 2004;40:1352–1360.
  8. Tsukuma H, Hiyama T, Tanaka S, Nakao M, Yabuuchi T, Kitamura T, Nakanishi K, Fujimoto I, Inoue A, Yamazaki H, Kawashima T: Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med 1993;328:1797–1801.
  9. Liebman HA, Furie BC, Tong MJ, Blanchard RA, Lo KJ, Lee SD, Coleman MS, Furie B: Des-gamma-carboxy(abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med 1984;310:1427–1431.
  10. Toyoda H, Kumada T, Kiriyama S, Sone Y, Tanikawa M, Hisanaga Y, Yamaguchi A, Isogai 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.
  11. Imamura H, Matsuyama Y, Miyagawa Y, Ishida K, Shimada R, Miyagawa S, Makuuchi M, Kawasaki S: Prognosic significance of anatomical resection and des-gamma-carboxy prothrombin in patients with hepatocellular carcinoma. Br J Surg 1999;86:1032–1038.
  12. Inoue S, Nakao A, Harada A, Nonami T, Ta- kagi H: Clinical significance of abnormal prothrombin (DCP) in relation to postoperative survival and prognosis in patients with hepatocellular carcinoma. Am J Gastroenterol 1994;89:2222–2226.
  13. Hamamura K, Shiratori Y, Shiina S, Imamura M, Obi S, Sato S, Yoshida H, Omata M: Unique clinical characteristics of patients with high plasma des-gamma-carboxy prothrombin and low serum alpha-fetoprotein. Cancer 2000;88:1557–1564.
  14. Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases: Management of hepatocellular carcinoma. Hepatology 2005;42:1208–1236.
  15. Kudo M, Okanoue T; Japan Society of Hepatology: Management of hepatocellular carcinoma in Japan: consensus-based clinical practice manual proposed by the Japan Society of Hepatology. Oncology 2007;72:S2–S15.
  16. Komorizono Y, Oketani M, Sako K, Yamasaki N, Shibatou T, Maeda M, Kohara K, Shigenobu S, Ishibashi K, Arima T: Risk factors for local recurrence of small hepatocellular carcinoma tumors after a single session, single application of percutaneous radiofrequency ablation. Cancer 2003;97:1253–1262.
  17. Goldberg SN, Charboneau JW, Dodd GD 3rd, Dupuy DE, Gervais DA, Gillams AR, Kane RA, Lee FT Jr, Livraghi T, McGahan JP, Rhim H, Silverman SG, Solbiati L, Vogl TJ, Wood BJ; International Working Group on Image-Guided Tumor Ablation: Image-guided tumor ablation: proposal for standardization of terms and reporting criteria. Radiology 2003;228:335–345.
  18. Livraghi T, Goldberg SN, Lazzaroni S, Meloni F, Solbiati L, Gazelle GS: Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection. Radiology 1999;210:655–661.
  19. Livraghi T, Solbati L, Meloni MF, Gazelle GS, Halpern EF, Goldberg SN: Treatment of focal liver tumors with percutaneous radio-frequency ablation: complications encountered in a multicenter study. Radiology 2003;226:441–451.
  20. De Baere T, Risse O, Kuoch V, Dromain C, Sengel C, Smayra T, Gamal El Din M, Letoublon C, Elias D: Adverse events during radiofrequency treatment of 582 hepatic tumors. AJR Am J Roentgenol 2003;181:695–700.
  21. Sakon M, Umeshita K, Nagano H, Eguchi H, Kishimoto S, Miyamoto A, Ohshima S, Dono K, Nakamori S, Gotoh M, Monden M: Clinical significance of hepatic resection in hepatocellular carcinoma: analysis by disease-free survival curves. Arch Surg 2000;135:1456–1459.
  22. Ikai I, Arii S, Ichida T, Okita K, Omata M, Kojiro M, Takayasu K, Nakamura Y, Makuuchi M, Matsuyama Y, Yamaoka Y: Report of the 16th follow-up survey of primary liver cancer. The Liver Cancer Study Group of Japan. Hepatol Res 2005;32:163–172.
  23. Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, Pagliaro L, Colombo M, Rodés J; EASL Panel of Experts on HCC: Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001;35:421–430.
  24. Shiratori Y, Shiina S, Teratani T, Imamura M, Obi S, Sato S, Koike Y, Yoshida H, Omata M: Interferon therapy after tumor ablation improves prognosis in patients with hepatocellular carcinoma associated with hepatitis C virus. Ann Intern Med 2003;138:299–306.
  25. Yamanaka Y, Shiraki K, Miyashita K, Inoue T, Kawakita T, Yamaguchi Y, Saitou Y, Yamamoto N, Nakano T, Nakatsuka A, Yamakado Y, Takeda K: Risk factors for the recurrence of hepatocellular carcinoma after radiofrequency ablation of hepatocellular carcinoma in patients with hepatitis C. World J Gastroenterol 2005;11:2174–2178.

    External Resources

  26. Koike Y, Shiratori Y, Sato S, Obi S, Teratani T, Imamura M, Yoshida H, Shiina S, Omata M: Des-gamma-carboxy prothorombin 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.
  27. Shimada M, Yamashita Y, Hamastu T, Ha- segawa H, Utsunomiya T, Aishima S, Sugimachi K: The role of des-gamma-carboxy prothrombin levels in hepatocellular carcinoma and liver tissues. Cancer Lett 2000;159:87–94.
  28. Yamagata H, Nakanishi T, Furukawa M, Okuda H, Obata H: Levels of vitamin K, immunoreactive prothrombin, des-gamma-carboxy prothrombin and gamma-glutamyl carboxylase activity in hepatocellular carcinoma tissue. J Gastroenterol Hepatol 1995;10:8–13.
  29. Wang Z, Wang M, Finn F, Carr BI: The growth inhibitory effects of vitamin K and their actions on gene expression. Hepatology 1995;22:876–882.
  30. Li ZQ, He FY, Stehle CJ, Wang Z, Kar S, Finn FM, Carr BI: Vitamin K uptake in hepatocytes and hepatoma cells. Life Sci 2002;70:2085–2100.
  31. Kasahara A, Hayashi N, Fusamoto H, Kawada Y, Yamamoto H, Hayashi E, Ogihara T, Kamada T: Clinical evaluation of plasma des-g-carboxy prothrombin as a marker protein of hepatocellular carcinoma in patients with tumors of various sizes. Dig Dis Sci 1993;38:2170–2176.
  32. Suehiro T, Matsumura T, Itasaka H, Taketomi A, Yamamoto K, Sugimachi K: Des-gamma-carboxy prothrombin and proliferative activity of hepatocellular carcinoma. Surgery 1995;117:682–691.
  33. Khan KN, Yatsuhashi H, Yamasaki K, Yamasaki M, Inoue O, Koga M, Yano M: Prospective analysis of risk factors for early intrahepatic recurrence of hepatocellular carcinoma following ethanol injection. J Hepatol 2000;32:269–278.
  34. Grazi GL, Mazziotti A, Lengnani C, Jovine E, Miniero R, Gallucci A, Palareti G, Gozzetti G: The role of tumor markers in the diagnosis of hepatocellular carcinoma, with special reference to the des-gamma-carboxy prothrombin. Liver Transpl Surg 1995;1:249–255.
  35. Sugimoto H, Takeda S, Inoue S, Kaneko T, Watanabe K, Nakao A: Des-gamma-carboxy prothrombin (DCP) ratio, a novel parameter measured by monoclonal antibodies MU-3 and 19B7, as a new prognostic indicator for hepatocellular carcinoma. Liver Int 2003;23:38–44.
  36. Nanashima A, Morino S, Yamaguchi H, Tanaka K, Shibasaki S, Tsuji T, Hidaka S, Sawai T, Yasutake T, Nakagoe T: Modified CLIP using PIVKA-II for evaluating prognosis after hepatoctomy for hepatocellular carcinoma. Eur J Surg Oncol 2003;29:735–742.
  37. Shimada M, Yonemura Y, Ijichi H, Harada N, Shiotani S, Ninomiya M, Terashi T, Yoshizumi T, Soejima Y, Maehara Y: Living donor liver transplantation for hepatocellular carcinoma: a special reference to a preoperative des-gamma-carboxy prothrombin value. Transplant Proc 2005;37:1177–1179.
  38. Nagasue N, Uchida M, Makino Y, Takemoto Y, Yamanoi A, Hayashi T, Chang YC, Kohno H, Nakamura T, Yukaya H: Incidence and factors associated with intrahepatic recurrence following resection of hepatocellular carcinoma. Gastroenterology 1993;105:488–494.
  39. Okada S, Shimada K, Yamamoto J, Takayama T, Kosuge T, Yamasaki S, Sakamoto M, Hirohashi S: Predictive factors for postoperative recurrence of hepatocellular carcinoma. Gastroenterology 1994;106:1618–1624.
  40. Izumi R, Shimizu K, Ii T, Yagi M, Matsui O, Nonomura A, Miyazaki I: Prognostic factors of hepatocellular carcinoma in patients undergoing hepatic resection. Gastroenterology 1994;106:720–727.
  41. Kudo M, Sakaguchi Y, Chung H, Hatanaka K, Hagiwara S, Ishikawa E, Takahashi S, Kitai S, Inoue T, Minami Y, Ueshima K: Long-term interferon maintenance therapy improves survival in patients with HCV-related hepatocellular carcinoma after curative radiofrequency ablation. A matched case-control study. Oncology 2007;72:S132–S138.
  42. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group: Sora- fenib in advanced hepatocellular carcino- ma. N Engl J Med 2008;359:378–390.

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