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CardioVascular and Interventional Radiology

, Volume 34, Issue 4, pp 774–785 | Cite as

Safety Profile of Sequential Transcatheter Chemoembolization with DC Bead: Results of 237 Hepatocellular Carcinoma (HCC) Patients

  • Katerina Malagari
  • Mary Pomoni
  • Themistoklis N. Spyridopoulos
  • Hippokratis Moschouris
  • Alexis Kelekis
  • Spyros Dourakis
  • Efthymia Alexopoulou
  • John Koskinas
  • Michalis Angelopoulos
  • John Kornezos
  • Anastasia Pomoni
  • Savvas Tandeles
  • Athanasios Marinis
  • Spyros Rizos
  • Dimitrios Kelekis
Clinical Investigation

Abstract

Introduction

Complications of chemoembolization performed with DC Bead loaded with doxorubicin (DEBDOX) of diameters 100–300 μm and 300–500 μm are presented in this paper. These diameters are currently the smallest available in drug-eluting technology.

Methods

Included are 237 patients who were treated with sequential DEBDOX with doxorubicin loaded at 37.5 mg/ml of DC Bead. The National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0) were used to categorize complications.

Results

Thirty-day mortality was 1.26% (3/237). Incidence of grade 5 complications was 1.26% (3/237). Overall, grade 4 complications resulted in 5.48% (13/237) (irreversible liver failure, cholecystitis). Grade 2 liver function deterioration developed in 10 patients (4.2%). Cholecystitis/grade 2 and 4 incidents were observed in 3.6–5.06% across sessions (overall 13 patients; 5.48%). Postembolization Syndrome (PES) grade 1 or 2 was observed in up to 86.5%; however, grade 2 was observed in 25–42.19% across treatments. Pleural effusion was seen in eight patients (overall 3.37%; grade 1 in 1.8–3.7% across treatments; grade 3 in 0.42%). Grade 1 procedure-related laboratory pancreatitis was seen in 0.45%, and grade 2 gastrointestinal bleeding was seen in 0.84%. Procedure-associated skin erythema/grade 1 was seen in 0.84%. There was no correlation of liver failure or transient liver function deterioration with the diameter of the beads (p = 0.25–0.37 and p = 0.14–0.89, respectively). Stratifying with the diameter of the beads correlation values was: for cholecystitis (p = 0.11–0.96 across treatments), PES (p = 0.35–0.83), temporary/grade 1 elevation of liver enzymes (p = 0.002–0.0001), and bilirubin (p = 0.04–0.99).

Conclusions

DEBDOX chemoembolization is safe and small calibres do not result in increased complication rates compared with results of series using larger diameters of beads.

Keywords

Interventional oncology Endovascular treatment Liver/hepatic 

Notes

Conflict of interest

The authors claim no conflict of interest.

References

  1. 1.
    Lo CM, Ngan H, Tso WK et al (2002) Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 35:1164–1171PubMedCrossRefGoogle Scholar
  2. 2.
    Llovet JM, Real MI, Montana X et al (2002) Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomized controlled trial. Lancet 359:1734–1739PubMedCrossRefGoogle Scholar
  3. 3.
    Cammà C, Schepis F, Orlando A et al (2002) Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology 224(1):47–54PubMedCrossRefGoogle Scholar
  4. 4.
    Varela M, Real MI, Burrel M et al (2007) Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 46(3):474–481PubMedCrossRefGoogle Scholar
  5. 5.
    Poon RN, Tso WK, Pang RWC et al (2007) A phase I/II trial of chemoembolization for hepatocellular carcinoma using a novel intra-arterial drug-eluting bead. Clin Gastroenterol Hepatol 5:1100–1108PubMedCrossRefGoogle Scholar
  6. 6.
    Malagari K, Chatzimichael K, Alexopoulou E et al (2008) Transarterial chemoembolisation of unresectable hepatocellular carcinoma (HCC) with drug eluting beads (DEB); results of an open label study of 62 patients. Cardiovasc Intervent Radiol 31:269–280PubMedCrossRefGoogle Scholar
  7. 7.
    Malagari K, Alexopoulou E, Chatzimichail K et al (2008) Transcatheter chemoembolization in the treatment of HCC in patients not eligible for curative treatments: midterm results of doxorubicin-loaded DC Bead. Abdom Imaging 33(5):512–519PubMedCrossRefGoogle Scholar
  8. 8.
    Kettenbach J, Stadler A, Katzler I et al (2008) Drug-loaded microspheres for the treatment of liver cancer: review of current results. Cardiovasc Intervent Radiol 31:468–476PubMedCrossRefGoogle Scholar
  9. 9.
    Malagari K, Pomoni M, Kelekis A et al (2010) Prospective randomized comparison of chemoembolization with doxorubicin-eluting beads and bland embolization with BeadBlock for hepatocellular carcinoma. Cardiovasc Intervent Radiol 33(3):541–551PubMedCrossRefGoogle Scholar
  10. 10.
    Lammer J, Malagari K, Vogl T et al (2010) PRECISION V Investigators Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol 33(1):41–52PubMedCrossRefGoogle Scholar
  11. 11.
    National Cancer Institute (2003) Common terminology criteria for adverse events, version 3.0. National Cancer Institute, Bethesda, MDGoogle Scholar
  12. 12.
    Common Terminology Criteria for Adverse Events (CTCAE) v3.0, Publish Date: June 10, 2003, Notice of Modifications (March 31, 2003–June 10, 2003)Google Scholar
  13. 13.
    Vogl TJ, Lee C, Lencioni R et al (2010) Liver, gastrointestinal and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads: results from the PRECISION V randomized trial ECR 2010-B241, p 311Google Scholar
  14. 14.
    Kim W, Clark TW, Baum RA et al (2001) Risk factors for liver abscess formation after hepatic chemoembolization. J Vasc Interv Radiol 12:965–968PubMedCrossRefGoogle Scholar
  15. 15.
    Del Poggio P, Maddeo A, Zabbialini G et al (2007) Chemoembolization of hepatocellular carcinoma with drug eluting beads. J Hepatol 47:157–159PubMedCrossRefGoogle Scholar
  16. 16.
    Song SY, Chung J, Han KW et al (2001) Liver abscess after transcatheter oily chemoembolization for hepatic tumors: Incidence, predisposing factors, and clinical outcome. J Vasc Interv Radiol 12(3):313–320PubMedCrossRefGoogle Scholar
  17. 17.
    Poon RT, Ngan H, Lo CM et al (2000) Transarterial chemoembolization for inoperable hepatocellular carcinoma and postresection intrahepatic recurrence. J Surg Oncol 73:109–114PubMedCrossRefGoogle Scholar
  18. 18.
    de Baere T, Roche A, Amenabar JM et al (1996) Liver abscess formation after local treatment of liver tumors. Hepatology 23:1436–1440PubMedCrossRefGoogle Scholar
  19. 19.
    Tarazov PG, Polysalov VN, Prozorovskij KV et al (2000) Ischemic complications of transcatheter arterial chemoembolization in liver malignancies. Acta Radiol 41:156–160PubMedCrossRefGoogle Scholar
  20. 20.
    Chan AO, Yuen MF, Hui CK et al (2002) A prospective study regarding the complications of transcatheter intraarterial lipiodol chemoembolization in patients with hepatocellular carcinoma. Cancer 94:1747–1752PubMedCrossRefGoogle Scholar
  21. 21.
    Groupe d’Étude et de Traitment du Carcinome Hépatocellulaire (1995) A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma. N Engl J Med 332:1256–1261CrossRefGoogle Scholar
  22. 22.
    Chung JW, Park JH, Han JK et al (1996) Hepatic tumors: predisposing factors for complications of transcatheter oily chemoembolization. Radiology 198:33–40PubMedGoogle Scholar
  23. 23.
    Chang JM, Tzeng WS, Pan HB et al (1994) Transcatheter arterial embolization with or without cisplatin treatment of hepatocellular carcinoma. A randomized controlled study. Cancer 74:2449–2453PubMedCrossRefGoogle Scholar
  24. 24.
    Katsushima S, Inokuma T, Oi H et al (1997) Acute hepatic failure following transcatheter arterial embolization for the treatment of hepatocellular carcinoma. Digestion 58(2):189–195PubMedCrossRefGoogle Scholar
  25. 25.
    Jeon SH, Park KS, Kim YH et al (2007) Incidence and risk factors of acute hepatic failure after transcatheter arterial chemoembolization for hepatocellular carcinoma. Korean J Gastroenterol 50(3):176–182PubMedGoogle Scholar
  26. 26.
    Marelli L, Stigliano R, Triantos C et al (2007) Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol 30:6–25PubMedCrossRefGoogle Scholar
  27. 27.
    Lewis AL, Taylor RR, Hall B et al (2006) Pharmacokinetic and safety study of doxorubicin-eluting beads in a porcine model of hepatic arterial embolization. J Vasc Interv Radiol 17(8):1335–1343PubMedCrossRefGoogle Scholar
  28. 28.
    Li X, Feng GS, Zheng CS et al (2003) Influence of transarterial chemoembolization on angiogenesis and expression of vascular endothelial growth factor and vasic fibroblast growth factor in rat with Walker-256 transplanted hepatoma: an experimental study. World J Gastroenterol 9:2445–2449PubMedGoogle Scholar
  29. 29.
    Pelletier G, Ducreux M, Gay F et al (1998) Treatment of unresectable hepatocellular carcinoma with lipiodol chemoembolization: a multicenter randomized trial. J Hepatol 29:129–134PubMedCrossRefGoogle Scholar
  30. 30.
    Chen MS, Li J-Q, Zhang Y-Q et al (2002) High-dose iodized oil transcatheter arterial chemoembolization for patients with large hepatocellular carcinoma. World J Gastroenterol 8(1):74–78PubMedGoogle Scholar
  31. 31.
    Bronowicki JP, Vetter D, Dumas F et al (1994) Transcatheter oily chemoembolization for hepatocellular carcinoma: a 4-year study of 127 French patients. Cancer 74:16–24PubMedCrossRefGoogle Scholar
  32. 32.
    Stefanini GF, Amorati P, Biselli M et al (1995) Efficacy of transarterial targeted treatments on survival of patients with hepatocellular carcinoma. An Italian experience. Cancer 75:2427–2434PubMedCrossRefGoogle Scholar
  33. 33.
    Takenaka K, Yoshida K, Nishizaki T et al (1995) Postoperative prophylactic lipiodolization reduces the intrahepatic recurrence of hepatocellular carcinoma. Am J Surg 169:400–404PubMedCrossRefGoogle Scholar
  34. 34.
    Paye F, Farges O, Dahmane M et al (1999) Cytolysis following chemoembolization for hepatocellular carcinoma. Br J Surg 86:176–180PubMedCrossRefGoogle Scholar
  35. 35.
    Wigmore SJ, Redhead DN, Thomson BN et al (2003) Postchemoembolisation syndrome: tumour necrosis or hepatocyte injury? Br J Cancer 89:1423–1427PubMedCrossRefGoogle Scholar
  36. 36.
    Sakamoto I, Aso N, Nagaoki K et al (1998) Complications associated with transcatheter arterial embolization for hepatic tumors. Radiographics 18(3):605–619PubMedGoogle Scholar
  37. 37.
    Nakamura H, Kondoh H (1986) Emphysematous cholecystitis: complication of hepatic arterial embolization. Cardiovasc Intervent Radiol 9:152–153PubMedCrossRefGoogle Scholar
  38. 38.
    Kim HK, Chung YH, Song BC et al (2001) Ischemic bile duct injury as a serious complication after transarterial chemoembolization in patients with hepatocellular carcinoma. J Clin Gastroenterol 32:423–427PubMedCrossRefGoogle Scholar
  39. 39.
    Wang MQ, Shao RH, Ye HY et al (2005) Investigation of bile duct injury after transcatheter arterial chemoembolization. Zhonghua Zhong Liu Za Zhi 27:609–612PubMedGoogle Scholar
  40. 40.
    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
  41. 41.
    Brennan DDB, Farrelly CB, Cooney RB et al (2005) Abdominal rash after transarterial chemoembolization via the right inferior phrenic artery. J Vasc Interv Radiol 16(9):1269PubMedGoogle Scholar
  42. 42.
    Arora BR, Soulen BMC, Haskal ZJ (1999) Cutaneous complications of hepatic chemoembolization via extrahepatic collaterals. J Vasc Interv Radiol 10:1351–1356PubMedCrossRefGoogle Scholar
  43. 43.
    Brown KT (2004) Fatal pulmonary complications after arterial embolization with 40- to 120-micro m tris-acryl gelatine microspheres. J Vasc Interv Radiol 15(21):197–200PubMedGoogle Scholar
  44. 44.
    Maluccio MA, Covey AM, Ben Porat L et al (2008) Transcatheter arterial embolization with only particles for the treatment of unresectable hepatocellular carcinoma. J Vasc Interv Radiol 19(6):862–869PubMedCrossRefGoogle Scholar
  45. 45.
    Liu CL, Ngan H, Lo CM et al (1998) Ruptured hepatocellular carcinoma as a complication of transarterial oily chemoembolization. Br J Surg 85:512–514PubMedCrossRefGoogle Scholar
  46. 46.
    Battula N, Madanur M, Priest O et al (2009) Spontaneous rupture of hepatocellular carcinoma: a Western experience. Am J Surg 197(2):164–167PubMedCrossRefGoogle Scholar
  47. 47.
    Shin SW, Do YS, Choo SW et al (2006) Diaphragmatic weakness after transcatheter arterial chemoembolization of inferior phrenic artery for treatment of hepatocellular carcinoma. Radiology 241(2):581–583PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2010

Authors and Affiliations

  • Katerina Malagari
    • 1
    • 2
  • Mary Pomoni
    • 1
  • Themistoklis N. Spyridopoulos
    • 1
    • 2
  • Hippokratis Moschouris
    • 3
  • Alexis Kelekis
    • 1
    • 2
  • Spyros Dourakis
    • 4
  • Efthymia Alexopoulou
    • 2
  • John Koskinas
    • 4
  • Michalis Angelopoulos
    • 1
  • John Kornezos
    • 3
  • Anastasia Pomoni
    • 5
  • Savvas Tandeles
    • 1
  • Athanasios Marinis
    • 6
  • Spyros Rizos
    • 6
  • Dimitrios Kelekis
    • 1
  1. 1.Imaging and Research Unit, Evgenidion University HospitalAthensGreece
  2. 2.2nd Department of RadiologyAttikon University HospitalAthensGreece
  3. 3.Department of RadiologyTzanion HospitalAthensGreece
  4. 4.Department of Internal MedicineUniversity of AthensAthensGreece
  5. 5.LauzaneSwitzerland
  6. 6.Department of SurgeryTzanion HospitalAthensGreece

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