title: Time-Dependent Impact of Irreversible Electroporation on Pancreas, Liver, Blood Vessels and Nerves: A Systematic Review of Experimental Studies.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Vogel
authors.affiliation: Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: van Veldhuisen
authors.affiliation: Department of Radiation Therapy, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Agnass
authors.affiliation: Department of Radiation Therapy, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Crezee
authors.affiliation: Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Dijk
authors.affiliation: Department of Pathology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Verheij
authors.affiliation: Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands.|Department of Experimental Surgery, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: T M
authors.initials: TM
authors.lastname: van Gulik
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: M R
authors.initials: MR
authors.lastname: Meijerink
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: L G
authors.initials: LG
authors.lastname: Vroomen
authors.affiliation: Department of Radiology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: K P
authors.initials: KP
authors.lastname: van Lienden
authors.affiliation: Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: M G
authors.initials: MG
authors.lastname: Besselink
mesh_terms: D000818:Animals; D001808:Blood Vessels; D018274:Electroporation / Q000379:methods*; D006801:Humans; D008099:Liver; D009928:Organ Specificity; D010179:Pancreas; D010525:Peripheral Nerves; D051381:Rats