From Cell Biology to Tissue Engineering


Immunohistochemical and radiological characterization of wound healing in porcine liver after radiofrequency ablation

Vanessa Stadlbauer1*, Ingrid Lang-Olip2*, Bettina Leber3, Ursula Mayrhauser3, Sonja Koestenbauer3, Monika Tawdrous1, Michael Moche4, Michael Sereinigg3, Daniel Seider4, Florian Iberer3, Iris Wiederstein-Grasser5, Rupert Horst Portugaller6 and Philipp Stiegler3

1Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University Graz, Austria, 2Institute of Cell Biology, Histology and Embryology, Medical University Graz, Austria, 3Department of Surgery, Division of Transplantation Surgery, Medical University Graz, Austria, 4Department of Diagnostic and Interventional Radiology, University of Leipzig, Germany, 5Division of Biomedical Research and Section for Surgical Research, Medical University Graz, Austria and 6Department of Interventional Radiology, Medical University Graz, Austria
* these authors contributed equally to the study

Offprint requests to: Dr. Bettina Leber, Division of Transplantation Surgery, Medical University Graz, Austria, Centre for Medical Research, Stiftingtalstrasse 24, 8010 Graz, Germany. e-mail: bettina.leber@medunigraz.at

Summary. Background: Radiofrequency ablation (RFA) is a minimal invasive therapeutic option for patients with hepatocellular carcinoma or liver metastases. We investigated RFA-induced cellular changes in the liver of pigs. Material and Methods: Healthy pigs (n=18) were sacrificed between day 0 and 3 months after RFA. The wound healing process was evaluated by computed tomography (CT), chromotrope anilinblue (CAB) staining of large-scale and standard tissue sections. Immunohistochemistry (IHC) for heat shock protein 70, Caspase-3, Ki67, Reelin, Vinculin, Vimentin and α-SMA was perfomed. Results: One day after RFA, CAB staining showed cell damage and massive hyperaemia. All IHC markers were predominantly expressed at the outer borders of the lesion, except Reelin, which was mainly detected in untreated liver regions. By staining for Hsp70, the heat stress during RFA was monitored, which was most distinct 1-2 days after RFA. CT revealed decreased lesion size after one week. Development of a Vimentin and α-SMA positive fibrotic capsule was observed. Conclusion: In the early phase signs of cell damage, apoptosis and proliferation are dominant. Reduced expression of Reelin suggests a minor role of hepatic stellate cells in the RFA zone. After one week myofibroblasts become prominent and contribute to the development of the fibrotic capsule. This elucidates the pathophysiology of RFA and could contribute to the future optimization of RFA procedures. Histol Histopathol 31, 115-129 (2016)

Key words: Radiofrequency ablation, Healthy pig, Liver, Immunohistochemistry, Wound healing

DOI: 10.14670/HH-11-667