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Liver and biliary damages following transarterial chemoembolization of hepatocellular carcinoma: comparison between drug-eluting beads and lipiodol emulsion

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Abstract

Objectives

To compare transarterial chemoembolization (TACE)-related hepatic toxicities of conventional TACE (cTACE) and drug-eluting beads TACE (DEB-TACE) in patients with intermediate-stage hepatocellular carcinoma.

Methods

In this retrospective study, 151 consecutive patients undergoing cTACE or DEB-TACE and MRI 3-6 weeks before and after therapy were included. Toxicity was assessed on imaging (global hepatic damages (GHD), overall biliary injuries, biliary cast, bile duct dilatation, intrahepatic biloma, portal thrombosis), and clinico-biological follow-ups. Tumour response, time to progression (TTP), and overall survival were assessed. Factors influencing complication rate were identified by generalized equation logistic regression model.

Results

Biliary injuries and intrahepatic biloma incidence were significantly higher following DEB-TACE (p < 0.001). DEB-TACE showed a significant increased risk of GHD (OR: 3.13 [1.74-5.63], p < 0.001) and biliary injuries (OR: 4.53 [2.37-8.67], p < 0.001). A significant relationship was found between baseline prothrombin value and GHD, biliary injuries and intrahepatic biloma (all p < 0.01), and between the dose of chemotherapy and intrahepatic biloma (p = 0.001). Only TTP was significantly shorter following DEB-TACE compared to cTACE (p = 0.025).

Conclusions

DEB-TACE was associated with increased hepatic toxicities compared to cTACE. GHD, biliary injuries, and intrahepatic biloma were more frequently observed with high baseline prothrombin value, suggesting that cTACE might be more appropriate than DEB-TACE in patients with less advanced cirrhosis.

Key points

DEB-TACE demonstrated more therapy-related hepatic locoregional complications compared to cTACE.

TACE-related hepatic locoregional toxicities occurred more frequently with high baseline PT value.

cTACE may be more appropriate in patients with high baseline PT value.

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Abbreviations

AFP:

Alpha-fetoprotein

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

cTACE:

Conventional transarterial chemoembolization

DEB-TACE:

Drug-eluting beads transarterial chemoembolization

GHD:

Global hepatic damages

HCC:

Hepatocellular carcinoma

PT:

Prothrombin time

PVT:

Portal vein thrombosis

OS:

Overall survival

TR:

Tumour response

TTP:

Time to progression

References

  1. Llovet JM, Bruix J (2003) Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 37:429–442

    Article  CAS  PubMed  Google Scholar 

  2. Ohishi H, Uchida H, Yoshimura H et al (1985) Hepatocellular carcinoma detected by iodized oil. Use of anticancer agents. Radiology 154:25–29

    Article  CAS  PubMed  Google Scholar 

  3. Bhattacharya S, Novell JR, Winslet MC, Hobbs KE (1994) Iodized oil in the treatment of hepatocellular carcinoma. Br J Surg 81:1563–1571

    Article  CAS  PubMed  Google Scholar 

  4. Boulin M, Schmitt A, Delhom E et al (2016) Improved stability of lipiodol-drug emulsion for transarterial chemoembolisation of hepatocellular carcinoma results in improved pharmacokinetic profile: Proof of concept using idarubicin. Eur Radiol 26:601–609

    Article  PubMed  Google Scholar 

  5. 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 30:6–25

    Article  PubMed  Google Scholar 

  6. Lencioni R, de Baere T, Burrel M et al (2012) Transcatheter treatment of hepatocellular carcinoma with Doxorubicin-loaded DC Bead (DEBDOX): technical recommendations. Cardiovasc Intervent Radiol 35:980–985

    Article  PubMed  Google Scholar 

  7. Hong K, Khwaja A, Liapi E, Torbenson MS, Georgiades CS, Geschwind JF (2006) New intra-arterial drug delivery system for the treatment of liver cancer: preclinical assessment in a rabbit model of liver cancer. Clin Cancer Res 12:2563–2567

    Article  CAS  PubMed  Google Scholar 

  8. Johnson PJ, Kalayci C, Dobbs N et al (1991) Pharmacokinetics and toxicity of intraarterial adriamycin for hepatocellular carcinoma: effect of coadministration of lipiodol. J Hepatol 13:120–127

    Article  CAS  PubMed  Google Scholar 

  9. Lammer J, Malagari K, Vogl T et al (2010) Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol 33:41–52

    Article  PubMed  Google Scholar 

  10. Varela M, Real MI, Burrel M et al (2007) Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 46:474–481

    Article  CAS  PubMed  Google Scholar 

  11. Malagari K, Pomoni M, Spyridopoulos TN et al (2011) Safety profile of sequential transcatheter chemoembolization with DC Bead: results of 237 hepatocellular carcinoma (HCC) patients. Cardiovasc Intervent Radiol 34:774–785

    Article  PubMed  Google Scholar 

  12. Guiu B, Deschamps F, Aho S et al (2012) Liver/biliary injuries following chemoembolisation of endocrine tumours and hepatocellular carcinoma: lipiodol vs. drug-eluting beads. J Hepatol 56:609–617

    Article  CAS  PubMed  Google Scholar 

  13. Bhagat N, Reyes DK, Lin M et al (2013) Phase II study of chemoembolization with drug-eluting beads in patients with hepatic neuroendocrine metastases: high incidence of biliary injury. Cardiovasc Intervent Radiol 36:449–459

    Article  PubMed  Google Scholar 

  14. Brandsaeter B, Schrumpf E, Clausen OP, Abildgaard A, Hafsahl G, Bjoro K (2004) Recurrent sclerosing cholangitis or ischemic bile duct lesions--a diagnostic challenge? Liver Transpl 10:1073–1074

    Article  PubMed  Google Scholar 

  15. Pfau PR, Kochman ML, Lewis JD et al (2000) Endoscopic management of postoperative biliary complications in orthotopic liver transplantation. Gastrointest Endosc 52:55–63

    Article  CAS  PubMed  Google Scholar 

  16. Clermonts SH, van Dam RM (2014) Obstructive putty-like cast of the biliary tree. Hepatobiliary Surg Nutr 3:47–49

    PubMed  PubMed Central  Google Scholar 

  17. Benninger J, Grobholz R, Oeztuerk Y et al (2005) Sclerosing cholangitis following severe trauma: description of a remarkable disease entity with emphasis on possible pathophysiologic mechanisms. World J Gastroenterol 11:4199–4205

    Article  PubMed  PubMed Central  Google Scholar 

  18. Gelbmann CM, Rummele P, Wimmer M et al (2007) Ischemic-like cholangiopathy with secondary sclerosing cholangitis in critically ill patients. Am J Gastroenterol 102:1221–1229

    Article  PubMed  Google Scholar 

  19. Kwon ON, Cho SH, Park CK, Mun SH (2012) Biliary cast formation with sclerosing cholangitis in critically ill patient: case report and literature review. Korean J Radiol 13:358–362

    Article  PubMed  PubMed Central  Google Scholar 

  20. Chung J, Yu JS, Chung JJ, Kim JH, Kim KW (2010) Haemodynamic events and localised parenchymal changes following transcatheter arterial chemoembolisation for hepatic malignancy: interpretation of imaging findings. Br J Radiol 83:71–81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gillmore R, Stuart S, Kirkwood A et al (2011) EASL and mRECIST responses are independent prognostic factors for survival in hepatocellular cancer patients treated with transarterial embolization. J Hepatol 55:1309–1316

    Article  PubMed  Google Scholar 

  22. Golfieri R, Giampalma E, Renzulli M et al (2014) Randomised controlled trial of doxorubicin-eluting beads vs conventional chemoembolisation for hepatocellular carcinoma. Br J Cancer 111:255–264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Joskin J, de Baere T, Auperin A et al (2015) Predisposing factors of liver necrosis after transcatheter arterial chemoembolization in liver metastases from neuroendocrine tumor. Cardiovasc Intervent Radiol 38:372–380

    Article  PubMed  Google Scholar 

  24. Katabathina VS, Dasyam AK, Dasyam N, Hosseinzadeh K (2014) Adult bile duct strictures: role of MR imaging and MR cholangiopancreatography in characterization. Radiographics 34:565–586

    Article  PubMed  Google Scholar 

  25. Yu JS, Kim KW, Jeong MG, Lee DH, Park MS, Yoon SW (2002) Predisposing factors of bile duct injury after transcatheter arterial chemoembolization (TACE) for hepatic malignancy. Cardiovasc Intervent Radiol 25:270–274

    Article  PubMed  Google Scholar 

  26. Demachi H, Matsui O, Kawamori Y, Ueda K, Takashima T (1995) The protective effect of portoarterial shunts after experimental hepatic artery embolization in rats with liver cirrhosis. Cardiovasc Intervent Radiol 18:97–101

    Article  CAS  PubMed  Google Scholar 

  27. Kobayashi S, Nakanuma Y, Matsui O (1994) Intrahepatic peribiliary vascular plexus in various hepatobiliary diseases: a histological survey. Hum Pathol 25:940–946

    Article  CAS  PubMed  Google Scholar 

  28. Itai Y, Matsui O (1997) Blood flow and liver imaging. Radiology 202:306–314

    Article  CAS  PubMed  Google Scholar 

  29. Sakamoto I, Iwanaga S, Nagaoki K et al (2003) Intrahepatic biloma formation (bile duct necrosis) after transcatheter arterial chemoembolization. AJR Am J Roentgenol 181:79–87

    Article  PubMed  Google Scholar 

  30. Van Beers BE, Leconte I, Materne R, Smith AM, Jamart J, Horsmans Y (2001) Hepatic perfusion parameters in chronic liver disease: dynamic CT measurements correlated with disease severity. AJR Am J Roentgenol 176:667–673

    Article  PubMed  Google Scholar 

  31. Gulberg V, Haag K, Rossle M, Gerbes AL (2002) Hepatic arterial buffer response in patients with advanced cirrhosis. Hepatology 35:630–634

    Article  PubMed  Google Scholar 

  32. Duran R, Chapiro J, Schernthaner RE, Geschwind JF (2015) Systematic review of catheter-based intra-arterial therapies in hepatocellular carcinoma: state of the art and future directions. Br J Radiol 88:20140564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lewis AL, Taylor RR, Hall B, Gonzalez MV, Willis SL, Stratford PW (2006) Pharmacokinetic and safety study of doxorubicin-eluting beads in a porcine model of hepatic arterial embolization. J Vasc Interv Radiol 17:1335–1343

    Article  PubMed  Google Scholar 

  34. Gao J, Qian F, Szymanski-Exner A, Stowe N, Haaga J (2002) In vivo drug distribution dynamics in thermoablated and normal rabbit livers from biodegradable polymers. J Biomed Mater Res 62:308–314

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The scientific guarantor of this publication is Alban Denys. The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. The authors state that this work has not received any funding. One of the authors has significant statistical expertise. Institutional Review Board approval was obtained. Written informed consent was waived by the Institutional Review Board. Methodology: retrospective, observational, performed at one institution.

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Correspondence to Alban Denys.

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Monier, A., Guiu, B., Duran, R. et al. Liver and biliary damages following transarterial chemoembolization of hepatocellular carcinoma: comparison between drug-eluting beads and lipiodol emulsion. Eur Radiol 27, 1431–1439 (2017). https://doi.org/10.1007/s00330-016-4488-y

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  • DOI: https://doi.org/10.1007/s00330-016-4488-y

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