Time-Dependent Impact of Irreversible Electroporation on Pancreas, Liver, Blood Vessels and Nerves: A Systematic Review of Experimental Studies

PLoS One. 2016 Nov 21;11(11):e0166987. doi: 10.1371/journal.pone.0166987. eCollection 2016.

Abstract

Introduction: Irreversible electroporation (IRE) is a novel ablation technique in the treatment of unresectable cancer. The non-thermal mechanism is thought to cause mostly apoptosis compared to necrosis in thermal techniques. Both in experimental and clinical studies, a waiting time between ablation and tissue or imaging analysis to allow for cell death through apoptosis, is often reported. However, the dynamics of the IRE effect over time remain unknown. Therefore, this study aims to summarize these effects in relation to the time between treatment and evaluation.

Methods: A systematic search was performed in Pubmed, Embase and the Cochrane Library for original articles using IRE on pancreas, liver or surrounding structures in animal or human studies. Data on pathology and time between IRE and evaluation were extracted.

Results: Of 2602 screened studies, 36 could be included, regarding IRE in liver (n = 24), pancreas (n = 4), blood vessels (n = 4) and nerves (n = 4) in over 440 animals (pig, rat, goat and rabbit). No eligible human studies were found. In liver and pancreas, the first signs of apoptosis and haemorrhage were observed 1-2 hours after treatment, and remained visible until 24 hours in liver and 7 days in pancreas after which the damaged tissue was replaced by fibrosis. In solitary blood vessels, the tunica media, intima and lumen remained unchanged for 24 hours. After 7 days, inflammation, fibrosis and loss of smooth muscle cells were demonstrated, which persisted until 35 days. In nerves, the median time until demonstrable histological changes was 7 days.

Conclusions: Tissue damage after IRE is a dynamic process with remarkable time differences between tissues in animals. Whereas pancreas and liver showed the first damages after 1-2 hours, this took 24 hours in blood vessels and 7 days in nerves.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Blood Vessels*
  • Electroporation / methods*
  • Humans
  • Liver*
  • Organ Specificity
  • Pancreas*
  • Peripheral Nerves*
  • Rats

Grants and funding

J. A. Vogel, E. van Veldhuisen, Pierre Agnass, Johannes Crezee; Thomas van Gulik and M. G. Besselink received a grant (no. 2014-7244) from the Dutch Cancer Society (KWF) for studies on irreversible electroporation in pancreatic cancer. M. G. Besselink received a grant (no. 2015-5842) from KWF for studies on pancreatic cancer.