Evaluation of Electrochemotherapy with Bleomycin in the Treatment of Colorectal Hepatic Metastases in a Rat Model

Antonios E Spiliotis; Sebastian Holländer; Jeannette Rudzitis-Auth; Gudrun Wagenpfeil; Robert Eisele; Spyridon Nika; Orestis Mallis Kyriakides; Matthias W Laschke; Michael D Menger; Matthias Glanemann; Gereon Gäbelein

doi:10.3390/cancers15051598

Evaluation of Electrochemotherapy with Bleomycin in the Treatment of Colorectal Hepatic Metastases in a Rat Model

Cancers (Basel). 2023 Mar 4;15(5):1598. doi: 10.3390/cancers15051598.

Affiliations

¹ Department of Surgery, Campus Charité Mitte, Campus Virchow Klinikum, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
² Department of General Surgery, Vascular-, Visceral- and Pediatric Surgery, Saarland University Medical Center, 66421 Homburg, Germany.
³ Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg, Germany.
⁴ Institute for Medical Biometry, Epidemiology and Medical Informatics, Saarland University Medical Center, 66421 Homburg, Germany.
⁵ Department of Urology and Pediatric Urology, Saarland University Medical Center, 66421 Homburg, Germany.

Abstract

Background: The available ablative procedures for the treatment of hepatic cancer have contraindications due to the heat-sink effect and the risk of thermal injuries. Electrochemotherapy (ECT) as a nonthermal approach may be utilized for the treatment of tumors adjacent to high-risk regions. We evaluated the effectiveness of ECT in a rat model.

Methods: WAG/Rij rats were randomized to four groups and underwent ECT, reversible electroporation (rEP), or intravenous injection of bleomycin (BLM) eight days after subcapsular hepatic tumor implantation. The fourth group served as Sham. Tumor volume and oxygenation were measured before and five days after the treatment using ultrasound and photoacoustic imaging; thereafter, liver and tumor tissue were additionally analysed by histology and immunohistochemistry.

Results: The ECT group showed a stronger reduction in tumor oxygenation compared to the rEP and BLM groups; moreover, ECT-treated tumors exhibited the lowest levels of hemoglobin concentration compared to the other groups. Histological analyses further revealed a significantly increased tumor necrosis of >85% and a reduced tumor vascularization in the ECT group compared to the rEP, BLM, and Sham groups.

Conclusion: ECT is an effective approach for the treatment of hepatic tumors with necrosis rates >85% five days following treatment.

Keywords: bleomycin; electrochemotherapy; electroporation; liver neoplasms; rats.

Grants and funding

The research program was funded by the Homburg Research Funding Program (HOMFOR, Funding Number: T201000872). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We acknowledge support by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) and Saarland University within the ‘Open Access Publication Funding’ program.