Transarterial Therapy for Hepatocellular Carcinoma: Which Technique Is More Effective? A Systematic Review of Cohort and Randomized Studies

  • Laura Marelli
  • Rosa Stigliano
  • Christos Triantos
  • Marco Senzolo
  • Evangelos Cholongitas
  • Neil Davies
  • Jonathan Tibballs
  • Tim Meyer
  • David W. Patch
  • Andrew K. Burroughs



Chemoembolization (TACE) improves survival in cirrhotic patients with hepatocellular carcinoma (HCC). The optimal schedule, or whether embolization (TAE) alone gives the same survival advantage, is not known.


To evaluate whether specific patient characteristics and/or radiological transarterial techniques result in better outcomes.


A PubMed search was carried out for cohort and randomized trials (n = 175) testing transarterial therapies; meta-analysis was performed where appropriate.


Anticancer drugs were used as sole agent in 75% of cases (double 15% and triple 6%): doxorubicin (36%), cisplatin (31%), epirubicin (12%), mitoxantrone (8%), mitomycin (8%), and SMANCS (5%). Embolizing agents used were: gelatin sponge particles (71%), polyvinyl alcohol (PVA) particles (8%), degradable starch microspheres (DSM) (4%), and embospheres (4%). Sessions per patient were 2.5 ± 1.5 (interval: 2 months). Objective response was 40 ± 20%; survival rates at 1, 2, 3, and 5 years were: 62 ± 20%, 42 ± 17%, 30 ± 15%, and 19 ± 16%, respectively, and survival time was 18 ± 9.5 months. The post-TACE complications were: acute liver failure, 7.5% (range 0–49%); acute renal failure, 1.8% (0–13%); encephalopathy, 1.8% (0–16%); ascites, 8.3% (0–52%); upper gastrointestinal bleeding; 3% (0–22%); and hepatic or splenic abscess, 1.3% (0–2.5%). Treatment-related mortality was 2.4% (0–9.5%), mainly due to acute liver failure. Our meta-analysis of nine randomized controlled trials (RCTs) confirmed that TACE improves survival; but a meta-analysis of TACE versus TAE alone (3 RCTs, 412 patients) demonstrated no survival difference.


No chemotherapeutic agent appears better than any other. There is no evidence for benefit with lipiodol. Gelatin sponge is the most used embolic agent, but PVA particles may be better. TAE appears as effective as TACE. New strategies to reduce the risk of post-TACE complications are required.


Chemoembolization Complication Embolization Hepatocellular carcinoma Lipiodol Transarterial therapy 


  1. 1.
    Llovet JM, Burroughs A, Bruix J (2003) Hepatocellular carcinoma. Lancet 362:1907–1917PubMedGoogle Scholar
  2. 2.
    Camma C, Schepis F, Orlando A, Albanese M, Shahied L, Trevisani F, Andreone P, Craxi A, Cottone M (2002) Transarterial chemoembolization for unresectable hepatocellular carcinoma: Meta-analysis of randomized controlled trials. Radiology 224:47–54PubMedGoogle Scholar
  3. 3.
    Llovet JM, Bruix J (2003) Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 37:429–442PubMedGoogle Scholar
  4. 4.
    Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Sola R, Rodes J, Bruix J (2002) Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 359:1734–1739PubMedGoogle Scholar
  5. 5.
    Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, Fan ST, Wong J (2002) Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 35:1164–1171PubMedGoogle Scholar
  6. 6.
    Chang JM, Tzeng WS, Pan HB, Yang CF, Lai KH (1994) Transcatheter arterial embolization with or without cisplatin treatment of hepatocellular carcinoma. A randomized controlled study. Cancer 74:2449–2453PubMedGoogle Scholar
  7. 7.
    Kawai S, Okamura J, Ogawa M, Ohashi Y, Tani M, Inoue J, Kawarada Y, Kusano M, Kubo Y, Kuroda C (1992) Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma: A comparison of lipiodol-transcatheter arterial embolization with and without adriamycin (first cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan. Cancer Chemother Pharmacol 31[Suppl]:S1–S6PubMedGoogle Scholar
  8. 8.
    Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS (1996) Evidence based medicine: What it is and what it isn’t. Br Med J 312:71–72Google Scholar
  9. 9.
    Pincus T (2003) Guidelines for monitoring of methotrexate therapy: “Evidence-based medicine” outside of clinical trials. Arthritis Rheum 48:2706–2709PubMedGoogle Scholar
  10. 10.
    Groupe d’Etude et de Traitement du Carcinome Hepatocellulaire (1995) A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma. N Engl J Med 332:1256–1261Google Scholar
  11. 11.
    Bruix J, Llovet JM, Castells A, Montana X, Bru C, Ayuso MC, Vilana R, Rodes J (1998) Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: Results of a randomized, controlled trial in a single institution. Hepatology 27:1578–1583PubMedGoogle Scholar
  12. 12.
    Hatanaka Y, Yamashita Y, Takahashi M, Koga Y, Saito R, Nakashima K, Urata J, Miyao M (1995) Unresectable hepatocellular carcinoma: Analysis of prognostic factors in transcatheter management. Radiology 195:747–752PubMedGoogle Scholar
  13. 13.
    Lladó L, Virgili J, Figueras J, Valls C, Dominguez J, Rafecas A, Torras J, Fabregat J, Guardiola J, Jaurrieta E (2000) A prognostic index of the survival of patients with unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization. Cancer 88:50–57PubMedGoogle Scholar
  14. 14.
    Mondazzi L, Bottelli R, Brambilla G, Rampoldi A, Rezakovic I, Zavaglia C, Alberti A, Ideo G (1994) Transarterial oily chemoembolization for the treatment of hepatocellular carcinoma: A multivariate analysis of prognostic factors. Hepatology 19:1115–1123PubMedGoogle Scholar
  15. 15.
    Poyanli A, Rozanes I, Acunas B, Sencer S (2001) Palliative treatment of hepatocellular carcinoma by chemoembolization. Acta Radiol 42:602–607PubMedGoogle Scholar
  16. 16.
    Tanaka K, Nakamura S, Numata K, Kondo M, Morita K, Kitamura T, Saito S, Kiba T, Okazaki H, Sekihara H (1998) The long term efficacy of combined transcatheter arterial embolization and percutaneous ethanol injection in the treatment of patients with large hepatocellular carcinoma and cirrhosis. Cancer 82:78–85PubMedGoogle Scholar
  17. 17.
    Vogl TJ, Trapp M, Schroeder H, Mack M, Schuster A, Schmitt J, Neuhaus P, Felix R (2000) Transarterial chemoembolization for hepatocellular carcinoma: Volumetric and morphologic CT criteria for assessment of prognosis and therapeutic success-results from a liver transplantation center. Radiology 214:349–357PubMedGoogle Scholar
  18. 18.
    Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, Pagliaro L, Colombo M, Rodes J (2001) Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 35:421–430PubMedGoogle Scholar
  19. 19.
    Fan J, Wu ZQ, Tang ZY, Zhou J, Qiu SJ, Ma ZC, Zhou XD, Ye SL (2001) Multimodality treatment in hepatocellular carcinoma patients with tumor thrombi in portal vein. World J Gastroenterol 7:28–32PubMedGoogle Scholar
  20. 20.
    Gates J, Hartnell GG, Stuart KE, Clouse ME (1999) Chemoembolization of hepatic neoplasms: Safety, complications, and when to worry. Radiographics 19:399–414PubMedGoogle Scholar
  21. 21.
    Pentecost MJ, Daniels JR, Teitelbaum GP, Stanley P (1993) Hepatic chemoembolization: Safety with portal vein thrombosis. J Vasc Interv Radiol 4:347–351PubMedGoogle Scholar
  22. 22.
    Tazawa J, Maeda M (2001) [Radiation therapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma]. Nippon Rinsho 59[Suppl 6]:743–747Google Scholar
  23. 23.
    The Cancer of the Liver Italian Program (CLIP) Investigators (2000) Prospective validation of the CLIP score: A new prognostic system for patients with cirrhosis and hepatocellular carcinoma. Hepatology 31:840–845Google Scholar
  24. 24.
    Llovet JM, Bru C, Bruix J (1999) Prognosis of hepatocellular carcinoma: The BCLC staging classification. Semin Liver Dis 19:329–338PubMedGoogle Scholar
  25. 25.
    Cooper GS, Bellamy P, Dawson NV, Desbiens N, Fulkerson WJ Jr., Goldman L, Quinn LM, Speroff T, Landefeld CS (1997) A prognostic model for patients with end-stage liver disease. Gastroenterology 113:1278–1288PubMedGoogle Scholar
  26. 26.
    Marrero JA, Fontana RJ, Barrat A, Askari F, Conjeevaram HS, Su GL, Lok AS (2005) Prognosis of hepatocellular carcinoma: Comparison of 7 staging systems in an American cohort. Hepatology 41:707–716PubMedGoogle Scholar
  27. 27.
    Abe S, Otsuki M (2002) Styrene maleic acid neocarzinostatin treatment for hepatocellular carcinoma. Curr Med Chem Anti-Canc Agents 2:715–726Google Scholar
  28. 28.
    Kasugai H, Kojima J, Tatsuta M, Okuda S, Sasaki Y, Imaoka S, Fujita M, Ishiguro S (1989) Treatment of hepatocellular carcinoma by transcatheter arterial embolization combined with intraarterial infusion of a mixture of cisplatin and ethiodized oil. Gastroenterology 97:965–971PubMedGoogle Scholar
  29. 29.
    Kawai S, Tani M, Okamura J, Ogawa M, Ohashi Y, Monden M, Hayashi S, Inoue J, Kawarada Y, Kusano M, Kubo Y, Kuroda C, Sakata Y, Shimamura Y, Jinno K, Takahashi A, Takayasu K, Tamura K, Nagasue N, Nakanishi Y, Makino M, Masuzawa M, Yumoto Y, Mori T, Oda T (1997) Prospective and randomized trial of lipiodol-transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma: A comparison of epirubicin and doxorubicin (second cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan. Semin Oncol 24[2Suppl6]:S6Google Scholar
  30. 30.
    Watanabe S, Nishioka M, Ohta Y, Ogawa N, Ito S, Yamamoto Y (1994) Prospective and randomized controlled study of chemoembolization therapy in patients with advanced hepatocellular carcinoma. Cooperative Study Group for Liver Cancer Treatment in Shikoku area. Cancer Chemother Pharmacol 33[Suppl]:S93–S96PubMedGoogle Scholar
  31. 31.
    Ichida T, Kato M, Hayakawa A, Watanabe M, Igarashi K, Hata K, Doya Y, Miura M, Sato H, Asakura H (1992) Treatment of hepatocellular carcinoma with a CDDP-epirubicin-lipiodol suspension: a pilot clinico-pharmacological study. Cancer Chemother Pharmacol 31[Suppl]:S51–S54PubMedGoogle Scholar
  32. 32.
    Ono Y, Yoshimasu T, Ashikaga R, Inoue M, Shindou H, Fuji K, Araki Y, Nishimura Y (2000) Long-term results of lipiodol-transcatheter arterial embolization with cisplatin or doxorubicin for unresectable hepatocellular carcinoma. Am J Clin Oncol 23:564–568PubMedGoogle Scholar
  33. 33.
    Lu W, Li Y, He X, Chen Y (2003) Transcatheter arterial chemoembolization for hepatocellular carcinoma in patients with cirrhosis: Evaluation of two kinds of dosages of anticancer drugs and analysis of prognostic factors. Hepatogastroenterology 50:2079–2083PubMedGoogle Scholar
  34. 34.
    Bhattacharya S, Novell JR, Winslet MC, Hobbs KE (1994) Iodized oil in the treatment of hepatocellular carcinoma. Br J Surg 81:1563–1571PubMedGoogle Scholar
  35. 35.
    Kobayashi S, Narimatsu Y, Ogawa K, Hashimoto S, Nakatsuka S, Miura H, Ohzono H, Ka WJ, Ido K, Hiramatsu K (1992) Transcatheter hepatic arterial chemoembolization using epirubicin-lipiodol: Experimental and pharmacological evaluation. Cancer Chemother Pharmacol 31[Suppl]:S45–S50PubMedGoogle Scholar
  36. 36.
    Johnson PJ, Kalayci C, Dobbs N, Raby N, Metivier EM, Summers L, Harper P, Williams R (1991) Pharmacokinetics and toxicity of intraarterial adriamycin for hepatocellular carcinoma: Effect of coadministration of lipiodol. J Hepatol 13:120–127PubMedGoogle Scholar
  37. 37.
    Dodds HM, Walpole ET, Rivory LP, Strong RW, Pond SM (1996) Disposition of epirubicin after intraarterial administration in Lipiodol to patients with hepatocellular carcinoma. Ther Drug Monit 18:537–543PubMedGoogle Scholar
  38. 38.
    Favoulet P, Cercueil JP, Faure P, Osmak L, Isambert N, Beltramo JL, Cognet F, Krause D, Bedenne L, Chauffert B (2001) Increased cytotoxicity and stability of Lipiodol-pirarubicin emulsion compared to classical doxorubicin-Lipiodol: Potential advantage for chemoembolization of unresectable hepatocellular carcinoma. Anticancer Drugs 12:801–806PubMedGoogle Scholar
  39. 39.
    Fujiyama S, Shibata J, Maeda S, Tanaka M, Noumaru S, Sato K, Tomita K (2003) Phase I clinical study of a novel lipophilic platinum complex (SM-11355) in patients with hepatocellular carcinoma refractory to cisplatin/lipiodol. Br J Cancer 89:1614–1619PubMedGoogle Scholar
  40. 40.
    Chen MS, Li JQ, Zhang YQ, Lu LX, Zhang WZ, Yuan YF, Guo YP, Lin XJ, Li GH (2002) High-dose iodized oil transcatheter arterial chemoembolization for patients with large hepatocellular carcinoma. World J Gastroenterol 8:74–78PubMedGoogle Scholar
  41. 41.
    Matsuo N, Uchida H, Sakaguchi H, Nishimine K, Nishimura Y, Hirohashi S, Ohishi H (1997) Optimal lipiodol volume in transcatheter arterial chemoembolotherapy for hepatocellular carcinoma: Study based on lipiodol accumulation patterns and histopathologic findings. Semin Oncol 24[Suppl 6]:S6PubMedGoogle Scholar
  42. 42.
    Nakashima T, Kojiro M (1986) Pathologic characteristics of hepatocellular carcinoma. Semin Liver Dis 6:259–266PubMedCrossRefGoogle Scholar
  43. 43.
    Coldwell DM, Stokes KR, Yakes WF (1994) Embolotherapy: Agents, clinical applications, and techniques. Radiographics 14:623–643PubMedGoogle Scholar
  44. 44.
    Chung JW (1998) Transcatheter arterial chemoembolization of hepatocellular carcinoma. Hepatogastroenterology 45[Suppl 3]:1236–1241PubMedGoogle Scholar
  45. 45.
    Doppman JL, Dunnick NR, Girton M, Fauci AS, Popovsky MA (1979) Bile duct cysts secondary to liver infarcts: Report of a case and experimental production by small vessel hepatic artery occlusion. Radiology 130:1–5PubMedGoogle Scholar
  46. 46.
    Makuuchi M, Sukigara M, Mori T, Kobayashi J, Yamazaki S, Hasegawa H, Moriyama N, Takayasu K, Hirohashi S (1985) Bile duct necrosis: Complication of transcatheter hepatic arterial embolization. Radiology 156:331–334PubMedGoogle Scholar
  47. 47.
    Nakamura H, Tanaka T, Hori S, Yoshioka H, Kuroda C, Okamura J, Sakurai M (1983) Transcatheter embolization of hepatocellular carcinoma: Assessment of efficacy in cases of resection following embolization. Radiology 147:401–405PubMedGoogle Scholar
  48. 48.
    Forsberg JO (1978) Transient blood flow reduction induced by intra-arterial injection of degradable starch microspheres. Experiments on rats. Acta Chir Scand 144:275–281PubMedGoogle Scholar
  49. 49.
    Lindell B, Aronsen KF, Rothman U (1977) Repeated arterial embolization of rat livers by degradable microspheres. Eur Surg Res 9:347–356PubMedGoogle Scholar
  50. 50.
    Sigurdson ER, Ridge JA, Daly JM (1986) Intra-arterial infusion of doxorubicin with degradable starch microspheres: Improvement of hepatic tumor drug uptake. Arch Surg 121:1277–1281PubMedGoogle Scholar
  51. 51.
    Dakhil S, Ensminger W, Cho K, Niederhuber J, Doan K, Wheeler R (1982) Improved regional selectivity of hepatic arterial BCNU with degradable microspheres. Cancer 50:631–635PubMedGoogle Scholar
  52. 52.
    Gunji T, Kawauchi N, Ohnishi S, Ishikawa T, Nakagama H, Kaneko T, Moriyama T, Matsuhashi N, Yazaki Y, Imawari M (1992) Treatment of hepatocellular carcinoma associated with advanced cirrhosis by transcatheter arterial chemoembolization using autologous blood clot: A preliminary report. Hepatology 15:252–257PubMedGoogle Scholar
  53. 53.
    Gunji T, Kawauchi N, Akahane M, Watanabe K, Kanamori H, Ohnishi S (2002) Long-term outcomes of transcatheter arterial chemoembolization with autologous blood clot for unresectable hepatocellular carcinoma. Int J Oncol 21:427–432PubMedGoogle Scholar
  54. 54.
    Kwok PC, Lam TW, Chan SC, Chung CP, Wong WK, Chan MK, Lo HY, Lam WM (2000) A randomized clinical trial comparing autologous blood clot and gelfoam in transarterial chemoembolization for inoperable hepatocellular carcinoma. J Hepatol 32:955–964PubMedGoogle Scholar
  55. 55.
    Zheng C, Feng G, Liang H (1998) Bletilla striata as a vascular embolizing agent in interventional treatment of primary hepatic carcinoma. Chin Med J (Engl ) 111:1060–1063Google Scholar
  56. 56.
    Brown DB, Pilgram TK, Darcy MD, Fundakowski CE, Lisker-Melman M, Chapman WC, Crippin JS (2005) Hepatic arterial chemoembolization for hepatocellular carcinoma: Comparison of survival rates with different embolic agents. J Vasc Interv Radiol 16:1661–1666PubMedGoogle Scholar
  57. 57.
    Varela M, Real MI, Brunet M, Sala M, Burrel M, Forner A, Llovet JM, Bruix J (2005) Chemoembolization of hepatocellular carcinoma with drug eluting beads reduces the systemic availability of doxorubicin: A pharmacokinetic assessment. Hepatology 42[Suppl 1]abstractGoogle Scholar
  58. 58.
    Rand T, Loewe C, Schoder M, Schmook MT, Peck-Radosavljevic M, Kettenbach J, Wolf F, Schneider B, Lammer J (2005) Arterial embolization of unresectable hepatocellular carcinoma with use of microspheres, lipiodol, and cyanoacrylate. Cardiovasc Intervent Radiol 28:313–318PubMedGoogle Scholar
  59. 59.
    Georgiades CS, Hong K, D’Angelo M, Geschwind JF (2005) Safety and efficacy of transarterial chemoembolization in patients with unresectable hepatocellular carcinoma and portal vein thrombosis. J Vasc Interv Radiol 16:1653–1659PubMedGoogle Scholar
  60. 60.
    Horiguchi Y, Itoh M, Takagawa H, Imai H, Kamei A, Sekoguchi B, Nagamura Y (1992) Assessment of chemoembolization therapy for primary liver cancer using a stabilized adriamycin-lipiodol suspension. Cancer Chemother Pharmacol 31[Suppl]:S60–S64PubMedGoogle Scholar
  61. 61.
    Geschwind JF, Ramsey DE, van der Wal BC, Kobeiter H, Juluru K, Hartnell GG, Choti MA (2003) Transcatheter arterial chemoembolization of liver tumors: Effects of embolization protocol on injectable volume of chemotherapy and subsequent arterial patency. Cardiovasc Intervent Radiol 26:111–117PubMedGoogle Scholar
  62. 62.
    Takayasu K, Shima Y, Muramatsu Y, Moriyama N, Yamada T, Makuuchi M, Hasegawa H, Hirohashi S (1987) Hepatocellular carcinoma: treatment with intraarterial iodized oil with and without chemotherapeutic agents. Radiology 163:345–351PubMedGoogle Scholar
  63. 63.
    Ernst O, Sergent G, Mizrahi D, Delemazure O, Paris JC, L’Hermine C (1999) Treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization: Comparison of planned periodic chemoembolization and chemoembolization based on tumor response. AJR Am J Roentgenol 172:59–64PubMedGoogle Scholar
  64. 64.
    Matsui O, Kadoya M, Yoshikawa J, Gabata T, Takashima T, Demachi H (1994) Subsegmental transcatheter arterial embolization for small hepatocellular carcinomas: Local therapeutic effect and 5-year survival rate. Cancer Chemother Pharmacol 33[Suppl]:S84–S88PubMedGoogle Scholar
  65. 65.
    Nishimine K, Uchida H, Matsuo N, Sakaguchi H, Hirohashi S, Nishimura Y, Guo Q, Ohishi H, Nagano N, Yoshioka T (1994) Segmental transarterial chemoembolization with Lipiodol mixed with anticancer drugs for nonresectable hepatocellular carcinoma: Follow-up CT and therapeutic results. Cancer Chemother Pharmacol 33[Suppl]:S60–S68PubMedGoogle Scholar
  66. 66.
    Jaeger HJ, Mehring UM, Castaneda F, Hasse F, Blumhardt G, Loehlein D, Mathias KD (1996) Sequential transarterial chemoembolization for unresectable advanced hepatocellular carcinoma. Cardiovasc Intervent Radiol 19:388–396PubMedGoogle Scholar
  67. 67.
    Lin DY, Liaw YF, Lee TY, Lai CM (1988) Hepatic arterial embolization in patients with unresectable hepatocellular carcinoma: A randomized controlled trial. Gastroenterology 94:453–456PubMedGoogle Scholar
  68. 68.
    Monna T, Kanno T, Marumo T, Harihara S, Kuroki T, Yamamoto S, Kobayashi N, Sato M, Nakamura K, Nakatsuka H, Onoyama Y, Yamada R (1982) A comparison of transcatheter arterial embolization with one shot therapy for the patients with hepatic cell carcinoma. Gastroenterol Jpn 17:542–549PubMedGoogle Scholar
  69. 69.
    Yamashita Y, Torashima M, Oguni T, Yamamoto A, Harada M, Miyazaki T, Takahashi M (1993) Liver parenchymal changes after transcatheter arterial embolization therapy for hepatoma: CT evaluation. Abdom Imaging 18:352–356PubMedGoogle Scholar
  70. 70.
    Bismuth H, Morino M, Sherlock D, Castaing D, Miglietta C, Cauquil P, Roche A (1992) Primary treatment of hepatocellular carcinoma by arterial chemoembolization. Am J Surg 163:387–394PubMedGoogle Scholar
  71. 71.
    Liem MS, Poon RT, Lo CM, Tso WK, Fan ST (2005) Outcome of transarterial chemoembolization in patients with inoperable hepatocellular carcinoma eligible for radiofrequency ablation. World J Gastroenterol 11:4465–4471PubMedGoogle Scholar
  72. 72.
    Yang CF, Ho YJ (1992) Transcatheter arterial chemoembolization for hepatocellular carcinoma. Cancer Chemother Pharmacol 31[Suppl]:S86–S88PubMedGoogle Scholar
  73. 73.
    Plentz RR, Lankisch TO, Basturk M, Muller CC, Kirchhoff T, Gebel M, Bleck JS, Kubicka S, Manns MP, Meier PN, Rudolph KL (2005) Prospective analysis of German patients with hepatocellular carcinoma undergoing transcatheter arterial chemoembolization with or without prophylactic antibiotic therapy. J Gastroenterol Hepatol 20:1134–1136PubMedGoogle Scholar
  74. 74.
    Ramsey DE, Kernagis LY, Soulen MC, Geschwind JF (2002) Chemoembolization of hepatocellular carcinoma. J Vasc Interv Radiol 13:S211–S221PubMedGoogle Scholar
  75. 75.
    Kobayashi N, Ishii M, Ueno Y, Kisara N, Chida N, Iwasaki T, Toyota T (1999) Co-expression of Bcl-2 protein and vascular endothelial growth factor in hepatocellular carcinomas treated by chemoembolization. Liver 19:25–31PubMedGoogle Scholar
  76. 76.
    Liou TC, Shih SC, Kao CR, Chou SY, Lin SC, Wang HY (1995) Pulmonary metastasis of hepatocellular carcinoma associated with transarterial chemoembolization. J Hepatol 23:563–568PubMedGoogle Scholar
  77. 77.
    Louha M, Poussin K, Ganne N, Zylberberg H, Nalpas B, Nicolet J, Capron F, Soubrane O, Vons C, Pol S, Beaugrand M, Berthelot P, Franco D, Trinchet JC, Brechot C, Paterlini P (1997) Spontaneous and iatrogenic spreading of liver-derived cells into peripheral blood of patients with primary liver cancer. Hepatology 26:998–1005PubMedGoogle Scholar
  78. 78.
    Ikeda K, Saitoh S, Koida I, Tsubota A, Arase Y, Chayama K, Kumada H (1995) A prospective randomized evaluation of a compound of tegafur and uracil as an adjuvant chemotherapy for hepatocellular carcinoma treated with transcatheter arterial chemoembolization. Am J Clin Oncol 18:204–210PubMedGoogle Scholar
  79. 79.
    Ikeda K, Saitoh S, Suzuki Y, Koida I, Tsubota A, Kobayashi M, Arase Y, Chayama K, Murashima N, Kumada H (1997) A prospective randomized administration of 5’-deoxy-5-fluorouridine as adjuvant chemotherapy for hepatocellular carcinoma treated with transcatheter arterial chemoembolization. Am J Clin Oncol 20:202–208PubMedGoogle Scholar
  80. 80.
    Kawata S, Yamasaki E, Nagase T, Inui Y, Ito N, Matsuda Y, Inada M, Tamura S, Noda S, Imai Y, Matsuzawa Y (2001) Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial. Br J Cancer 84:886–891PubMedGoogle Scholar
  81. 81.
    Yan JJ, Shen F, Wang K, Wu MC (2002) Patients with advanced primary hepatocellular carcinoma treated by melatonin and transcatheter arterial chemoembolization: A prospective study. Hepatobiliary Pancreat Dis Int 1:183–186PubMedGoogle Scholar
  82. 82.
    Stefanini GF, Foschi FG, Castelli E, Marsigli L, Biselli M, Mucci F, Bernardi M, Van Thiel DH, Gasbarrini G (1998) Alpha-1-thymosin and transcatheter arterial chemoembolization in hepatocellular carcinoma patients: A preliminary experience. Hepatogastroenterology 45:209–215PubMedGoogle Scholar
  83. 83.
    Poon RT, Yu WC, Fan ST, Wong J (2004) Long-term oral branched chain amino acids in patients undergoing chemoembolization for hepatocellular carcinoma: a randomized trial. Aliment Pharmacol Ther 19:779–788PubMedGoogle Scholar
  84. 84.
    Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216PubMedGoogle Scholar
  85. 85.
    Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207–214PubMedGoogle Scholar
  86. 86.
    Yang WT, Johnson PJ (1999) Monitoring response to treatment in liver tumours. Baillieres Best Pract Res Clin Gastroenterol 13:637–654PubMedGoogle Scholar
  87. 87.
    Filmus J, Capurro M (2004) Glypican-3 and alphafetoprotein as diagnostic tests for hepatocellular carcinoma. Mol Diagn 8:207–212PubMedGoogle Scholar
  88. 88.
    Hosoki T, Yosioka Y, Matsubara T, Minamitani K, Higashi M, Ohtani M, Choi S, Mitomo M, Tono T (1999) Power Doppler sonography of hepatocellular carcinoma treated by transcatheter arterial chemoembolization: Assessment of the therapeutic effect. Acta Radiol 40:639–643PubMedGoogle Scholar
  89. 89.
    Ito K, Honjo K, Fujita T, Matsui M, Awaya H, Matsumoto T, Matsunaga N, Nakanishi T (1995) Therapeutic efficacy of transcatheter arterial chemoembolization for hepatocellular carcinoma: MRI and pathology. J Comput Assist Tomogr 19:198–203PubMedGoogle Scholar
  90. 90.
    Yamashita Y, Yoshimatsu S, Sumi M, Harada M, Takahashi M (1993) Dynamic MR imaging of hepatoma treated by transcatheter arterial embolization therapy: Assessment of treatment effect. Acta Radiol 34:303–308PubMedCrossRefGoogle Scholar
  91. 91.
    Pelletier G, Ducreux M, Gay F, Luboinski M, Hagege H, Dao T, Van Steenbergen W, Buffet C, Rougier P, Adler M, Pignon JP, Roche A (1998) Treatment of unresectable hepatocellular carcinoma with lipiodol chemoembolization: A multicenter randomized trial. Groupe CHC. J Hepatol 29:129–134PubMedGoogle Scholar
  92. 92.
    Pelletier G, Roche A, Ink O, Anciaux ML, Derhy S, Rougier P, Lenoir C, Attali P, Etienne JP (1990) A randomized trial of hepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma. J Hepatol 11:181–184PubMedGoogle Scholar
  93. 93.
    Madden MV, Krige JE, Bailey S, Beningfield SJ, Geddes C, Werner ID, Terblanche J (1993) Randomised trial of targeted chemotherapy with lipiodol and 5-epidoxorubicin compared with symptomatic treatment for hepatoma. Gut 34:1598–1600PubMedGoogle Scholar
  94. 94.
    Yoshikawa M, Saisho H, Ebara M, Iijima T, Iwama S, Endo F, Kimura M, Shimamura Y, Suzuki Y, Nakano T (1994) A randomized trial of intrahepatic arterial infusion of 4’-epidoxorubicin with Lipiodol versus 4’-epidoxorubicin alone in the treatment of hepatocellular carcinoma. Cancer Chemother Pharmacol 33[Suppl]:S149–S152PubMedGoogle Scholar
  95. 95.
    Castells A, Bruix J, Ayuso C, Bru C, Montanya X, Boix L, Rodes J (1995) Transarterial embolization for hepatocellular carcinoma: Antibiotic prophylaxis and clinical meaning of postembolization fever. J Hepatol 22:410–415PubMedGoogle Scholar
  96. 96.
    Hwang TL, Chen MF, Lee TY, Chen TJ, Lin DY, Liaw YF (1987) Resection of hepatocellular carcinoma after transcatheter arterial embolization: Reevaluation of the advantages and disadvantages of preoperative embolization. Arch Surg 122:756–759PubMedGoogle Scholar
  97. 97.
    Takenaka K, Yoshida K, Nishizaki T, Korenaga D, Hiroshige K, Ikeda T, Sugimachi K (1995) Postoperative prophylactic lipiodolization reduces the intrahepatic recurrence of hepatocellular carcinoma. Am J Surg 169:400–404PubMedGoogle Scholar
  98. 98.
    Paye F, Farges O, Dahmane M, Vilgrain V, Flejou JF, Belghiti J (1999) Cytolysis following chemoembolization for hepatocellular carcinoma. Br J Surg 86:176–180PubMedGoogle Scholar
  99. 99.
    Wigmore SJ, Redhead DN, Thomson BN, Currie EJ, Parks RW, Madhavan KK, Garden OJ (2003) Postchemoembolisation syndrome: tumour necrosis or hepatocyte injury? Br J Cancer 89:1423–1427PubMedGoogle Scholar
  100. 100.
    Chan AO, Yuen MF, Hui CK, Tso WK, Lai CL (2002) A prospective study regarding the complications of transcatheter intraarterial lipiodol chemoembolization in patients with hepatocellular carcinoma. Cancer 94:1747–1752PubMedGoogle Scholar
  101. 101.
    Chung JW, Park JH, Han JK, Choi BI, Han MC, Lee HS, Kim CY (1996) Hepatic tumors: Predisposing factors for complications of transcatheter oily chemoembolization. Radiology 198:33–40PubMedGoogle Scholar
  102. 102.
    Tarazov PG, Polysalov VN, Prozorovskij KV, Grishchenkova IV, Rozengauz EV (2000) Ischemic complications of transcatheter arterial chemoembolization in liver malignancies. Acta Radiol 41:156–160PubMedGoogle Scholar
  103. 103.
    Chen C, Chen PJ, Yang PM, Huang GT, Lai MY, Tsang YM, Chen DS (1997) Clinical and microbiological features of liver abscess after transarterial embolization for hepatocellular carcinoma. Am J Gastroenterol 92:2257–2259PubMedGoogle Scholar
  104. 104.
    Cohen SE, Safadi R, Verstandig A, Eid A, Sasson T, Symmer L, Shouval D (1997) Liver-spleen infarcts following transcatheter chemoembolization: A case report and review of the literature on adverse effects. Dig Dis Sci 42:938–943PubMedGoogle Scholar
  105. 105.
    Song SY, Chung JW, Han JK, Lim HG, Koh YH, Park JH, Lee HS, Kim CY (2001) Liver abscess after transcatheter oily chemoembolization for hepatic tumors: Incidence, predisposing factors, and clinical outcome. J Vasc Interv Radiol 12:313–320PubMedGoogle Scholar
  106. 106.
    Kim HK, Chung YH, Song BC, Yang SH, Yoon HK, Yu E, Sung KB, Lee YS, Lee SG, Suh DJ (2001) Ischemic bile duct injury as a serious complication after transarterial chemoembolization in patients with hepatocellular carcinoma. J Clin Gastroenterol 32:423–427PubMedGoogle Scholar
  107. 107.
    Wang MQ, Shao RH, Ye HY, Wang ZQ, Wang ZP, Liu FY (2005) [Investigation of bile duct injury after transcatheter arterial chemoembolization]. Zhonghua Zhong Liu Za Zhi 27:609–612PubMedGoogle Scholar
  108. 108.
    Leung TK, Lee CM, Chen HC (2005) Anatomic and technical skill factor of gastroduodenal complication in post-transarterial embolization for hepatocellular carcinoma: A retrospective study of 280 cases. World J Gastroenterol 11:1554–1557PubMedGoogle Scholar
  109. 109.
    Morante A, Romano M, Cuomo A, de S, I, Cozzolino A, Mucherino C, Salerno R, Blanco C, V, Romano M (2006) Massive gastric ulceration after transarterial chemoembolization for hepatocellular carcinoma. Gastrointest Endosc 63:718–720PubMedGoogle Scholar
  110. 110.
    Huo TI, Wu JC, Lee PC, Chang FY, Lee SD (2004) Incidence and risk factors for acute renal failure in patients with hepatocellular carcinoma undergoing transarterial chemoembolization: A prospective study. Liver Int 24:210–215PubMedGoogle Scholar
  111. 111.
    Guevara M, Fernandez-Esparrach G, Alessandria C, Torre A, Terra C, Montana X, Piera C, Alvarez ML, Jimenez W, Gines P, Arroyo V (2004) Effects of contrast media on renal function in patients with cirrhosis: A prospective study. Hepatology 40:646–651PubMedGoogle Scholar
  112. 112.
    Burroughs A, Hochhauser D, Meyer T (2004) Systemic treatment and liver transplantation for hepatocellular carcinoma: Two ends of the therapeutic spectrum. Lancet Oncol 5:409–418PubMedGoogle Scholar
  113. 113.
    Nakamura H, Murakami T, Tomoda K, Nakanishi K, Hori S, Oi H, Tsukaguchi I, Watanabe H, Masuike M, Inoue Y (1994) [Doses of epirubicin used in oily chemoembolization of hepatocellular carcinoma]. Gan To Kagaku Ryoho 21(3):2218–2221PubMedGoogle Scholar
  114. 114.
    Higashi S, Shimizu M, Nakashima T, Iwata K, Uchiyama F, Tateno S, Tamura S, Setoguchi T (1995) Arterial-injection chemotlierapy for hepatocellular carcinoma using monodispcrscd poppy-seed oil roicrodroplets containing fine aqueous vesicles of epirubicin. Initial medical application of a membrane-emulsiflcation technique. Cancer 75(6):1245–1254PubMedGoogle Scholar
  115. 115.
    Lu CD, Qi YG, Peng SY (1994) Lipiodolization with or without gelatin sponge in hepatic arterial chemoembolization for hepatocellular carcinoma. Chin Med J (Engl) 107(3):209–1SGoogle Scholar
  116. 116.
    Takayasu K, Shima Y, Muramatsu Y, Moriyama N, Yamada T, Makuuchi M, Hascgawa H, Hirohashi S (1987) Hepatocellular carcinoma: treatment with intraarterial iodized oil with and without chemotherapeutic agents. Radiology 163(2):345–351PubMedGoogle Scholar
  117. 117.
    Li CR, Jiang WH, Feng XM, Guo YJ, Shi ZH, Zhou CW (2005) [Value of mixed embolus transarterial chemoembolization in the treatment of hepatocellular carcinoma], Zhonghua Zhong Liu Za Zhi 27(9):557–560PubMedGoogle Scholar
  118. 118.
    Ikeda M, Maeda S, Shibata J, Muta R, Ashihara H, Tanaka M, Fujiyama S, Tomita K (2004) Transcatheter arterial chemotherapy with and without embolization in patients with hepatocellular carcinoma. Oncology 66(l):24–31PubMedGoogle Scholar
  119. 119.
    Aoyama K, Tsukishiro T, Okada K, Tsuchida T, Aiba N, Nambu S, Miyabayashi C, Yasuyama T, Higuchi K, Watanabe A (1992) Evaluation of transcatheter arterial embolization with epirubicin-lipiodol emulsion for hepatocellular carcinoma. Cancer Chemother Pharmacol 31(Suppl):S55–S59PubMedGoogle Scholar
  120. 120.
    Nakao N, Uchida H, Kamino K, Nishimura Y, Ohishi H, Takayasu Y, Nakamura H, Kuroda C, Fujita M, Yoshioka H (1992) Effectiveness of Lipiodol in transcatheter arterial embolization of hepatocellular carcinoma. Cancer Chemother Phartnacol 31(Suppl):S72–S76PubMedGoogle Scholar
  121. 121.
    Poon RT, Fan ST, Lo CM, Liu CL, Ngan H, Ng IO, Wong J (1999) Hepatocellular carcinoma in the elderly: results of surgical and nonsurgical management. Am J Gtistroenterol 94(9):2460–2466Google Scholar
  122. 122.
    Shah SR, Riordan SM, Karani J, Williams R (1998) Tumour ablation and hepatic decompensation rates in multi-agent chemoembolization of hepatocellular carcinoma. QJM 91(12):821–828PubMedGoogle Scholar
  123. 123.
    Sacchori S, Lovaria A, Sangiovanni A, Nicolini A, De Fazio C, Ronchi G, Fasani P, Del Ninno E, Colombo M (2002) Segmental transcatheter arterial chemoembolization treatment in patients with cirrhosis and inoperable hepatocellular carcinomas. J Vase Interv Radiol 13(10):995–999Google Scholar
  124. 124.
    Sasaki Y, Imaoka S, Kasugai H, Fujita M, Kawamoto S, Ishiguro S, Kojima J, Ishikawa O, Ohigashi H, Furukawa H (1987) A new approach to chemoembolization therapy for hepatoma using ethiodized oil, cisplatin, and gelatin sponge. Cancer 60(6): 1194–1203PubMedGoogle Scholar
  125. 125.
    Inoue H, Miyazono N, Kanetsuki I, Hori A, Tanaka D, Fukukura Y, Matsumoto Y, Nishida H, Ueno K, Nakajo M (1993) [Anticancer and side effect of arterial subsegmental chemoembolization using cisplatinum/pirarubicin lipiodol suspension (CTLS) for hepatocellular carcinoma]. Gan To Kagaku Ryoho 20(13):1973–1975PubMedGoogle Scholar
  126. 126.
    Venook AP, Stagg RJ, Lewis BJ, Chase JL, Ring EJ, Maroncy TP, Hohn DC (1990) Chemoembolization for hepatocellular carcinoma. J Clin Oncol 8(6): 1108–1114PubMedGoogle Scholar
  127. 127.
    Marchiori L, Mansuoto GC, Nifosi F, Bortolasi L, Dal DI, Facci E, Perus G, Nicoli N (1994) [The treatment, of hepatocellular carcinoma by chemoembolization]. Chir Ital 46(l):17–22PubMedGoogle Scholar
  128. 128.
    Colleoni M, Liessi G, Mastrapasqua G, Nelli P, Vicario G, Sgarbossa G, Pancheri F, Manente P (1997) Intra-arterial chemotherapy followed by chemo-embolisation in unresectable hepatocellular carcinoma. Eur J Cancer 33(l): 56–60PubMedGoogle Scholar
  129. 129.
    Brown KT, Nevins AB, Getrajdman GI, Brody LA, Kurtz RC, Fong Y, Blumgart LH (1998) Particle embolization for hepatocellular carcinoma. J Vase Interv Radiol 9(5):822–888CrossRefGoogle Scholar
  130. 130.
    Solomon B, Soulen MC, Baum RA, Haskal ZJ, Shlansky-Goldberg RD, Cope C (1999) Chemoembolization of hepatocellular carcinoma with cisplatin, doxorubicin, mitomycin-C, ethiodol, and polyvinyl alcohol: prospective evaluation of response and survival in a U.S. population. J Vasc .Interv Radiol 10(6):793–798PubMedGoogle Scholar
  131. 131.
    Hsieh CB, Chang HM, Chen TW, Chen CJ, Chan DC, Yu JC, Liu YC, Chang TM, Shen KL (2004) Comparison of transcatheter arterial chemoembolization, laparoscopic radiofrequency ablation) and conservative treatment for decompensated cirrhotic patients with hepalocellular carcinoma. World J Gastroenterol 10(4):505–508PubMedGoogle Scholar
  132. 132.
    Ohnishi K, Sugita S, Nomura F, lida S, Tanabe Y (1987) Arterial chemoembolization with mitomycin C microcapsules followed by transcatheter hepatic artery embolization for hepatocellular carcinoma. Am J Gastroenterol 82(9): 876–879PubMedGoogle Scholar
  133. 133.
    Raoul JL, Guyader D, Bretagne JF, Heautot JF, Duvauferrier R, Bourguet P, Bekhechi D, Deugnier YM, Gosselin M (1997) Prospective randomized trial of chemoembolization versus intra-arterial injection of 1311-labeled-iodized oil in the treatment of hepatocellular carcinoma. Hepatology 26(5): 1156–1161PubMedGoogle Scholar
  134. 134.
    Bhattacharya S, Novell JR, Dusheiko GM, Hilson AJ, Dick R, Hobbs KE (1995) Epirubicin-Lipiodol chemotherapy versus 131iodine-Lipiodol radiotherapy in the treatment of unresectable hepatocellular carcinoma. Cancer 76(11):2202–2210PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Laura Marelli
    • 1
  • Rosa Stigliano
    • 1
  • Christos Triantos
    • 1
  • Marco Senzolo
    • 1
  • Evangelos Cholongitas
    • 1
  • Neil Davies
    • 2
  • Jonathan Tibballs
    • 3
  • Tim Meyer
    • 3
  • David W. Patch
    • 1
  • Andrew K. Burroughs
    • 1
  1. 1.Liver Transplantation and Hepatobiliary Medicine UnitRoyal Free HospitalLondonUK
  2. 2.Department of RadiologyRoyal Free HospitalLondonUK
  3. 3.Department of OncologyRoyal Free HospitalLondonUK

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