Advertisement

Single-needle electroporation and interstitial electrochemotherapy: in vivo safety and efficacy evaluation of a new system

  • Federico PedersoliEmail author
  • Andreas Ritter
  • Markus Zimmermann
  • Maximilian Schulze-Hagen
  • Martin Liebl
  • Ebba Dethlefsen
  • Saskia von Stillfried
  • Joachim Pfeffer
  • Christiane K. Kuhl
  • Philipp Bruners
  • Peter Isfort
Interventional
  • 41 Downloads

Abstract

Objectives

We conducted an in vivo trial to investigate the safety and efficacy of a newly developed system for the application of a combined therapy consisting of irreversible electroporation (IRE) and electrochemotherapy (IRECT) in the liver. The system is conceived as a single-needle multitined applicator with expandable electrodes that allow interstitial injection of fluids, e.g., chemotherapy.

Methods

Experiments were conducted in ten domestic pigs. The applicator was placed in different liver lobes under CT guidance. In one lobe, the applicator was used for conventional IRE (1500 V, 120 pulses, pulse length 100 μs). In the other lobe, the same procedure was performed preceded by the injection of a doxorubicin mixture through the expandable electrodes (IRECT). Contrast-enhanced CT and MRI were performed on days 1, 3, and 7 after the procedure. Accordingly, three animals were sacrificed on days 1, 3, and 7 after the imaging and ablation volumes were evaluated histopathologically. Related t test was used to compare the groups.

Results

Technical success was achieved in 9/10 experiments. One animal deceased during the intervention because of ventricular fibrillation. Follow-up CT 1 and 3 days after intervention showed a significant (p < 0.05) difference in the ablation volumes of IRECT vs IRE, respectively, of 4.47 ± 1.78 ml vs 2.51 ± 0.93 ml and of 3.39 ± 1.05 vs 1.53 ± 0.78 ml.

Conclusions

IRECT using the newly developed system proved to be effective and provided significantly larger ablation volumes compared with IRE alone. However, ECG triggering is a necessary prerequisite to allow a safe application of the system.

Key Points

• Working on the geometry of the IRE applicator in terms of expandable electrodes may overcome the current limitations of IRE resulting from the placement of multiple electrodes.

• Efficacy of IRE ablations can be enhanced by the interstitial application of chemotherapy in the periphery of ablation areas.

Keywords

Electroporation Electrochemotherapy Electrodes 

Abbreviations

ECT

Electrochemotherapy

IRE

Irreversible electroporation

IRECT

Irreversible electroporation and electrochemotherapy

Notes

Funding

This work was funded by the German Research Foundation (DFG) under project number 116510359.

Compliance with ethical standards

Guarantor

The scientific guarantor of this publication is Prof. Philipp Bruners.

Conflict of interest

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.

Statistics and biometry

One of the authors has significant statistical expertise; moreover, no complex statistical methods were necessary for this paper.

Informed consent

Approval from the institutional animal care committee was obtained.

Ethical approval

Institutional Review Board approval was not required because it was not necessary after the approval from the institutional animal care committee.

Methodology

• prospective

• experimental

• performed at one institution

References

  1. 1.
    Rubinsky B (2007) Irreversible electroporation in medicine. Technol Cancer Res Treat 6:255–260CrossRefGoogle Scholar
  2. 2.
    Miklavčič D, Mali B, Kos B, Heller R, Serša G (2014) Electrochemotherapy: from the drawing board into medical practice. Biomed Eng Online 13.  https://doi.org/10.1186/1475-925X-13-29
  3. 3.
    Gehl J, Sersa G, Matthiessen LW et al (2018) Updated standard operating procedures for electrochemotherapy of cutaneous tumours and skin metastases. Acta Oncol 25:874–882CrossRefGoogle Scholar
  4. 4.
    Tarantino L, Busto G, Nasto A et al (2017) Percutaneous electrochemotherapy in the treatment of portal vein tumor thrombosis at hepatic hilum in patients with hepatocellular carcinoma in cirrhosis: a feasibility study. World J Gastroenterol 23:906–918CrossRefGoogle Scholar
  5. 5.
    Wichtowski M, Murawa D, Kulcenty K, Zaleska K (2017) Electrochemotherapy in breast cancer - discussion of the method and literature review. Breast Care (Basel) 12:409–414CrossRefGoogle Scholar
  6. 6.
    Plaschke CC, Bertino G, McCaul JA et al (2017) European Research on electrochemotherapy in Head and Neck Cancer (EURECA) project: results from the treatment of mucosal cancers. Eur J Cancer 87:172–181CrossRefGoogle Scholar
  7. 7.
    Bertaccini C, Margotti PM, Bergamini E, Lodi A, Ronchetti M, Cadossi R (2007) Design of an irreversible electroporation system for clinical use. Technol Cancer Res Treat 6:313–320CrossRefGoogle Scholar
  8. 8.
    Nault JC, Sutter O, Nahon P, Ganne-Carrié N, Séror O (2017) Percutaneous treatment of hepatocellular carcinoma: state of the art and innovations. J Hepatol 68:783–797CrossRefGoogle Scholar
  9. 9.
    Venkat S, Hosein PJ, Narayanan G (2015) Percutaneous approach to irreversible electroporation of the pancreas: Miami protocol. Tech Vasc Interv Radiol 18:153–158CrossRefGoogle Scholar
  10. 10.
    Vroomena LGPH, Petrea EN, Cornelis FH, Solomona SB, Srimathveeravalli G (2017) Irreversible electroporation and thermal ablation of tumors in the liver, lung, kidney and bone: what are the differences? Diagn Interv Imaging 98:609–617CrossRefGoogle Scholar
  11. 11.
    Marty M, Sersa G, Garbay JR et al (2006) Electrochemotherapy – an easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study. EJC Suppl 4:3–13CrossRefGoogle Scholar
  12. 12.
    Ritter A, Bruners P, Isfort P et al (2018) Electroporation of the liver: more than 2 concurrently active, curved electrodes allow new concepts for irreversible electroporation and electrochemotherapy. Technol Cancer Res Treat 1(17).  https://doi.org/10.1177/1533033818809994
  13. 13.
    Ritter A (2017) Strategies and electrode design for the patient-customized application of electroporation in tumor therapy  https://doi.org/10.18154/RWTH-2017-08074
  14. 14.
    Mahmood F, Gehl J (2011) Optimizing clinical performance and geometrical robustness of a new electrode device for intracranial tumor electroporation. Bioelectrochemistry 81.  https://doi.org/10.1016/j.bioelechem.2010.12.002
  15. 15.
    Agerholm-Larsen B, Iversen HK, Ibsen P et al (2011) Preclinical validation of electrochemotherapy as an effective treatment for brain tumors. Cancer Res 71:3753–3762CrossRefGoogle Scholar
  16. 16.
    Distelmaier M, Barabasch A, Heil P et al (2017) Midterm safety and efficacy of irreversible electroporation of malignant liver tumors located close to major portal or hepatic veins. Radiology 285:1023–1031CrossRefGoogle Scholar
  17. 17.
    Tarantino L, Busto G, Nasto A et al (2018) Electrochemotherapy of cholangiocellular carcinoma at hepatic hilum: a feasibility study. Eur J Surg Oncol 44:1603–1609CrossRefGoogle Scholar
  18. 18.
    Neal RE 2nd, Rossmeisl JH Jr, D'Alfonso V et al (2014) In vitro and numerical support for combinatorial irreversible electroporation and electrochemotherapy glioma treatment. Ann Biomed Eng 42:375–487Google Scholar
  19. 19.
    Klein N, Zapf S, Gunther E, Stehling M (2017) Treatment of lymph node metastases from gastric cancer with a combination of irreversible electroporation and electrochemotherapy: a case report. Clin Case Rep 5:1389–1394CrossRefGoogle Scholar
  20. 20.
    Deodhar A, Dickfeld T, Single GW et al (2011) Irreversible electroporation near the heart: ventricular arrhythmias can be prevented with ECG synchronization. AJR Am J Roentgenol 196.  https://doi.org/10.2214/AJR.10.4490
  21. 21.
    Tewes F, Munnier E, Antoon B et al (2007) Comparative study of doxorubicin-loaded poly(lactide-co-glycolide) nanoparticles prepared by single and double emulsion methods. Eur J Pharm Biopharm 66:488–492CrossRefGoogle Scholar
  22. 22.
    Miao Y, Ni Y, Mulier S et al (1997) Ex vivo experiment on radiofrequency liver ablation with saline infusion through a screw-tip cannulated electrode. J Surg Res 71(1):19–24CrossRefGoogle Scholar
  23. 23.
    Ahmed M, Lukyanov AN, Torchilin V, Tournier H, Schneider AN, Goldberg SN (2005) Combined radiofrequency ablation and adjuvant liposomal chemotherapy: effect of chemotherapeutic agent, nanoparticle size, and circulation time. J Vasc Interv Radiol 16(10):1365–1371CrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2019

Authors and Affiliations

  • Federico Pedersoli
    • 1
    Email author
  • Andreas Ritter
    • 1
    • 2
  • Markus Zimmermann
    • 1
  • Maximilian Schulze-Hagen
    • 1
  • Martin Liebl
    • 1
  • Ebba Dethlefsen
    • 1
  • Saskia von Stillfried
    • 3
  • Joachim Pfeffer
    • 1
  • Christiane K. Kuhl
    • 1
  • Philipp Bruners
    • 1
  • Peter Isfort
    • 1
  1. 1.Department of Diagnostic and Interventional RadiologyRWTH University Hospital AachenAachenGermany
  2. 2.Helmholtz-Institute for Biomedical EngineeringRWTH Aachen UniversityAachenGermany
  3. 3.Pathology InstituteRWTH University Hospital AachenAachenGermany

Personalised recommendations