Skip to main content
SpringerLink
Log in

First In Vivo Test of Thermoembolization: Turning Tissue Against Itself Using Transcatheter Chemistry in a Porcine Model

  • Laboratory Investigation
  • Published:
CardioVascular and Interventional Radiology Aims and scope Submit manuscript

Abstract

Purpose

Embolotherapies are commonly used for management of primary liver cancer. Explant studies of treated livers, however, reveal an untreated tumor in a high fraction of cases. To improve on this, we propose a new concept referred to as thermoembolization. In this technique, the embolic material reacts in local tissues. Highly localized heat energy is released simultaneously with the generation of acid in the target vascular bed. Combined with ischemia, this should provide a multiplexed attack. We report herein our initial results testing the feasibility of this method in vivo.

Materials and Methods

Institutional approval was obtained, and three outbred swine were treated in a segmental hepatic artery branch (right or left medial lobe) with thermoembolic material (100, 400, or 500 µL). Solutions (2 or 4 mol/L) of an acid chloride were made using ethiodized oil as the vehicle. Animals were housed overnight, scanned by CT, and euthanized. Necropsy samples of treated tissue were obtained for histologic analysis.

Results

All animals survived the procedure. Vascular stasis occurred rapidly in all cases despite the small volumes used. The lower concentration (2 mol/L) penetrated more distally than the 4 mol/L solution. At CT the following day, vascular casts of ethiodized oil were observed, indicating recanalization had not occurred. Histology specimens demonstrated coagulative necrosis centered on the vessel lumen extending for several hundred microns with a peripheral inflammatory infiltrate.

Conclusions

Thermoembolization is a new technique for embolization with initial promise. However, results indicate much work must be done to optimize the technique.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Massarweh NN, El-Serag HB. Epidemiology of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Cancer Control. 2017;24(3):1–11. https://doi.org/10.1177/1073274817729245.

    Article  Google Scholar 

  2. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90. https://doi.org/10.3322/caac.20107.

    Article  PubMed  Google Scholar 

  3. Yang JD, Roberts LR. Hepatocellular carcinoma: a global view. Nat Rev Gastroenterol Hepatol. 2010;7(8):448–58. https://doi.org/10.1038/nrgastro.2010.100.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Richani M, Kolly P, Knoepfli M, Herrmann E, Zweifel M, von Tengg-Kobligk H, et al. Treatment allocation in hepatocellular carcinoma: assessment of the BCLC algorithm. Ann Hepatol. 2016;15(1):82–90.

    Article  PubMed  Google Scholar 

  5. Marrero JA. Staging systems for hepatocellular carcinoma: should we all use the BCLC system? J Hepatol. 2006;44(4):630–2. https://doi.org/10.1016/j.jhep.2006.02.003.

    Article  PubMed  Google Scholar 

  6. Rimassa L, Santoro A. Sorafenib therapy in advanced hepatocellular carcinoma: the SHARP trial. Expert Rev Anticancer Ther. 2009;9(6):739–45. https://doi.org/10.1586/era.09.41.

    Article  PubMed  CAS  Google Scholar 

  7. Lu LC, Chen PJ, Yeh YC, Hsu CH, Chen HM, Lai MS, et al. Prescription patterns of sorafenib and outcomes of patients with advanced hepatocellular carcinoma: a national population study. Anticancer Res. 2017;37(5):2593–9. https://doi.org/10.21873/anticanres.11604.

    Article  PubMed  Google Scholar 

  8. Marin HL, Furth EE, Olthoff K, Shaked A, Soulen MC. Histopathologic outcome of neoadjuvant image-guided therapy of hepatocellular carcinoma. J Gastrointestin Liver Dis. 2009;18(2):169–76.

    PubMed  Google Scholar 

  9. Sheth RA, Sabir S, Krishnamurthy S, Avery RK, Zhang YS, Khademhosseini A, et al. Endovascular embolization by transcatheter delivery of particles: past, present, and future. J Funct Biomater. 2017. https://doi.org/10.3390/jfb8020012.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kishore S, Friedman T, Madoff DC. Update on embolization therapies for hepatocellular carcinoma. Curr Oncol Rep. 2017;19(6):40. https://doi.org/10.1007/s11912-017-0597-2.

    Article  PubMed  Google Scholar 

  11. Gunn AJ, Sheth RA, Luber B, Huynh MH, Rachamreddy NR, Kalva SP. Predicting outcomes after chemo-embolization in patients with advanced-stage hepatocellular carcinoma: an evaluation of different radiologic response criteria. Cardiovasc Intervent Radiol. 2017;40(1):61–8. https://doi.org/10.1007/s00270-016-1451-x.

    Article  PubMed  Google Scholar 

  12. Llovet JM, Real MI, Montaña X, Planas R, Coll S, Aponte J, et al. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002;359(9319):1734–9. https://doi.org/10.1016/s0140-6736(02)08649-x.

    Article  PubMed  Google Scholar 

  13. Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002;35(5):1164–71. https://doi.org/10.1053/jhep.2002.33156.

    Article  PubMed  CAS  Google Scholar 

  14. Brown KT, Do RK, Gonen M, Covey AM, Getrajdman GI, Sofocleous CT, et al. Randomized trial of hepatic artery embolization for hepatocellular carcinoma using doxorubicin-eluting microspheres compared with embolization with microspheres alone. J Clin Oncol. 2016;34(17):2046–53. https://doi.org/10.1200/JCO.2015.64.0821.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Massani M, Stecca T, Ruffolo C, Bassi N. Should we routinely use DEBTACE for unresectable HCC? cTACE versus DEBTACE: a single-center survival analysis. Updates Surg. 2017;69(1):67–73. https://doi.org/10.1007/s13304-017-0414-3.

    Article  PubMed  CAS  Google Scholar 

  16. Cressman EN, Jahangir DA. Dual mode single agent thermochemical ablation by simultaneous release of heat energy and acid: hydrolysis of electrophiles. Int J Hyperthermia. 2013;29(1):71–8. https://doi.org/10.3109/02656736.2012.756124.

    Article  PubMed  CAS  Google Scholar 

  17. Devore JA, O’Neal HE. Heats of formation of the acetyl halides and of the acetyl radical. J Phys Chem. 1969;73:2644–8.

    Article  CAS  Google Scholar 

  18. Cressman EN, Geeslin MG, Shenoi MM, Hennings LJ, Zhang Y, Iaizzo PA, et al. Concentration and volume effects in thermochemical ablation in vivo: results in a porcine model. Int J Hyperthermia. 2012;28(2):113–21. https://doi.org/10.3109/02656736.2011.644621.

    Article  PubMed  CAS  Google Scholar 

  19. Cressman EN, Shenoi MM, Edelman TL, Geeslin MG, Hennings LJ, Zhang Y, et al. In vivo comparison of simultaneous versus sequential injection technique for thermochemical ablation in a porcine model. Int J Hyperthermia. 2012;28(2):105–12. https://doi.org/10.3109/02656736.2011.644620.

    Article  PubMed  CAS  Google Scholar 

  20. Cressman ENK, IEEE. Image-guided thermochemical ablation: theoretical and practical considerations. In: 2009 annual international conference of the IEEE engineering in medicine and biology society, vols 1–20. IEEE Engineering in Medicine and Biology Society Conference Proceedings. New York: IEEE; 2009. p. 4291–4.

  21. Stacpoole PW. Therapeutic targeting of the pyruvate dehydrogenase complex/pyruvate dehydrogenase kinase (pdc/pdk) axis in cancer. J Natl Cancer Inst. 2017. https://doi.org/10.1093/jnci/djx071.

    Article  PubMed  Google Scholar 

  22. Ngo H, Tortorella SM, Ververis K, Karagiannis TC. The Warburg effect: molecular aspects and therapeutic possibilities. Mol Biol Rep. 2015;42(4):825–34. https://doi.org/10.1007/s11033-014-3764-7.

    Article  PubMed  CAS  Google Scholar 

  23. Mitchell J, Tinkey PT, Avritscher R, Van Pelt C, Eskandari G, Konnath George S, et al. Validation of a preclinical model of diethylnitrosamine-induced hepatic neoplasia in yucatan miniature pigs. Oncology. 2016. https://doi.org/10.1159/000446074.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Cao W, Wan Y, Liang ZH, Duan YY, Liu X, Wang ZM, et al. Heated lipiodol as an embolization agent for transhepatic arterial embolization in VX2 rabbit liver cancer model. Eur J Radiol. 2010;73(2):412–9. https://doi.org/10.1016/j.ejrad.2008.11.001.

    Article  PubMed  Google Scholar 

  25. Moroz P, Pardoe H, Jones SK, St Pierre TG, Song S, Gray BN. Arterial embolization hyperthermia: hepatic iron particle distribution and its potential determination by magnetic resonance imaging. Phys Med Biol. 2002;47(9):1591–602.

    Article  PubMed  Google Scholar 

  26. Harada M, Yamashita Y, Hirai T, Yamamoto H, Miyazaki T, Takahashi M. Intravascular hyperthermia: experimental study of transcatheter treatment. Acad Radiol. 1995;2(6):475–83.

    Article  PubMed  CAS  Google Scholar 

  27. Boddie AW Jr, Wright K, Stephens LC, Yamanashi WS, Frazer J, McBride CM, et al. An animal model of occlusion-hyperthermia of the liver. Invest Radiol. 1985;20(2):159–65.

    Article  PubMed  Google Scholar 

  28. Doyon D. Therapeutic arterial embolization and hyperthermia (author’s transl). Bull Cancer. 1981;68(3):295.

    PubMed  CAS  Google Scholar 

  29. Attaluri A, Seshadri M, Mirpour S, Wabler M, Marinho T, Furqan M, et al. Image-guided thermal therapy with a dual-contrast magnetic nanoparticle formulation: a feasibility study. Int J Hyperthermia. 2016;32(5):543–57. https://doi.org/10.3109/02656736.2016.1159737.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Liang YJ, Yu H, Feng G, Zhuang L, Xi W, Ma M, et al. High-performance poly(lactic-co-glycolic acid)-magnetic microspheres prepared by rotating membrane emulsification for transcatheter arterial embolization and magnetic ablation in VX2 liver tumors. ACS Appl Mater Interfaces. 2017;9(50):43478–89. https://doi.org/10.1021/acsami.7b14330.

    Article  PubMed  CAS  Google Scholar 

  31. Cressman E, Guo C. Feasibility study using tissue as reagent for cancer therapy: endovascular ablation via thermochemistry. Converg Sci Phys Oncol. 2018. https://doi.org/10.1088/2057-1739/aab905.

    Article  Google Scholar 

  32. Gholamrezanezhad A, Mirpour S, Geschwind JF, Rao P, Loffroy R, Pellerin O, et al. Evaluation of 70-150-mum doxorubicin-eluting beads for transcatheter arterial chemoembolization in the rabbit liver VX2 tumour model. Eur Radiol. 2016;26(10):3474–82. https://doi.org/10.1007/s00330-015-4197-y.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Laurent A. Microspheres and nonspherical particles for embolization. Tech Vasc Interv Radiol. 2007;10(4):248–56. https://doi.org/10.1053/j.tvir.2008.03.010.

    Article  PubMed  CAS  Google Scholar 

  34. Salamon S, Podbregar E, Kubatka P, Busselberg D, Caprnda M, Opatrilova R, et al. Glucose metabolism in cancer and ischemia: possible therapeutic consequences of the Warburg effect. Nutr Cancer. 2017;69(2):177–83. https://doi.org/10.1080/01635581.2017.1263751.

    Article  PubMed  CAS  Google Scholar 

  35. Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, et al. A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell. 2007;11(1):37–51. https://doi.org/10.1016/j.ccr.2006.10.020.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Funding from the M.D. Anderson Cancer Center Institutional Research Grant program is gratefully acknowledged. We also thank Katherine Dixon and Amanda McWatters for their assistance in performing the experiments.

Author information

Authors and Affiliations

  1. Department of Interventional Radiology, University of Texas MD Anderson Cancer Center, 1400 Pressler St Unit 1471, Houston, TX, 77030, USA

    Erik N. K. Cressman & Chunxiao Guo

Authors
  1. Erik N. K. Cressman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chunxiao Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Erik N. K. Cressman.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Human and animal rights

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cressman, E.N.K., Guo, C. First In Vivo Test of Thermoembolization: Turning Tissue Against Itself Using Transcatheter Chemistry in a Porcine Model. Cardiovasc Intervent Radiol 41, 1611–1617 (2018). https://doi.org/10.1007/s00270-018-2003-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00270-018-2003-3

Keywords

Search

Navigation