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Ablation of colorectal liver metastases by irreversible electroporation: results of the COLDFIRE-I ablate-and-resect study

  • Hepatobiliary-Pancreas
  • Published:
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Abstract

Objectives

Irreversible electroporation (IRE) is a new ablation technique that relies on high-voltage electrical pulses. This clinical study evaluates the pathological response of colorectal liver metastases (CRLM) treated with IRE and the clinical safety and feasibility.

Methods

Ten patients with resectable CRLM were included. During laparotomy, the metastases were treated with IRE and resected 60 min later. Safety and feasibility were assessed based on adverse events, laboratory values, technical success and intra-operative ultrasound findings. Tissue response was assessed using triphenyl tetrazolium chloride (TTC) vitality staining and (immuno)histochemical stainings (HE, complement-3d and caspase-3).

Results

Ten lesions with a mean diameter of 2.4 cm were successfully electroporated and resected, on average, 84 min later (range 51–153 min). One minor transient cardiac arrhythmia occurred during IRE. Ultrasound showed a sharply demarcated hypoechoic ablation zone around the tumour. TTC showed avitality of all lesions, covering the complete tumour in 8/10 lesions. Although immunohistochemistry proved heterogeneous and difficult to interpret within the tumours, it confirmed irreversible cell damage in the tumour-free margin of all specimens.

Conclusions

This ablate-and-resect study demonstrated avitality caused by IRE of CRLM in humans. Further characterisation of tissue- and tumour-specific electrical properties is warranted to improve ablation protocols for maximised tissue ablation.

Key Points

• Irreversible electroporation induces cell death in colorectal liver metastases within 1 h.

• The ablation zone shows a sharp demarcation between avital and vital tissue.

• Apoptosis is involved in cell death of colorectal liver metastases after IRE.

• Effects of IRE can be monitored real-time using intraoperative ultrasound.

• Local electrical heterogeneities of tumour tissue may require tumour-specific ablation protocols.

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Abbreviations

ASA:

American Society of Anesthesiologists

CRLM:

Colorectal liver metastases

IOUS:

Intraoperative ultrasound

IRE:

Irreversible electroporation

RFA:

Radiofrequency ablation

TTC:

5-triphenyl tetrazolium chloride

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Acknowledgements

The authors thank Dr. P.A.J. Krijnen, assistant professor at the Department of Pathology, M.P.V. Begieneman and H.I. Korkmaz, respectively PhD candidate/research assistant at the Department of Pathology, for their assistance with the immunohistochemical staining, and Dr. E.C. Eringa, assistant professor at the Laboratory for Physiology, VU University Medical Centre, for his help with preparing the TTC staining.

The scientific guarantor of this publication is Dr. MR Meijerink. 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. Dr. E.S.M. de Lange- de Klerk kindly provided statistical advice for this manuscript. Institutional Review Board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study. Methodology: prospective, experimental, performed at one institution.

H. J. Scheffer and K. Nielsen contributed equally to this work.

Author information

Authors and Affiliations

  1. Department of Radiology and Nuclear Medicine, VU University Medical Centre, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

    H. J. Scheffer, A. A. J. M. van Tilborg, C. van Kuijk & M. R. Meijerink

  2. Department of Surgery, VU University Medical Centre, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

    K. Nielsen, G. Kazemier, S. Meijer & M. P. van den Tol

  3. Department of Anaesthesiology, VU University Medical Centre, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

    J. M. Vieveen & R. A. Bouwman

  4. Department of Pathology and Cardiac Surgery, ICaR-VU, VU University Medical Centre, de Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

    H. W. M. Niessen

Authors
  1. H. J. Scheffer
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  2. K. Nielsen
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  3. A. A. J. M. van Tilborg
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  4. J. M. Vieveen
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  5. R. A. Bouwman
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  6. G. Kazemier
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  7. H. W. M. Niessen
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  8. S. Meijer
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  9. C. van Kuijk
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  10. M. P. van den Tol
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  11. M. R. Meijerink
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Corresponding author

Correspondence to H. J. Scheffer.

Additional information

HJ Scheffer and K Nielsen contributed equally to this manuscript.

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Scheffer, H.J., Nielsen, K., van Tilborg, A.A.J.M. et al. Ablation of colorectal liver metastases by irreversible electroporation: results of the COLDFIRE-I ablate-and-resect study. Eur Radiol 24, 2467–2475 (2014). https://doi.org/10.1007/s00330-014-3259-x

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  • DOI: https://doi.org/10.1007/s00330-014-3259-x

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