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

SIMPLE SUMMARY: 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) represents an ablative procedure that combines the administration of chemotherapeutic agents with well-dosed electric pulses for cell membrane reversible electroporation (rEP). In ECT, the enhanced cellular permeability facilitates the transportation of chemotherapeutic agents into tumor cells. In our study, ECT was compared with rEP and chemotherapy in a rat liver metastasis model. The ECT group showed a stronger reduction in tumor oxygenation compared to the rEP and chemotherapy groups. Histological analyses revealed a significantly increased tumor necrosis of >85% and a reduced tumor vascularization in the ECT group. Consequently, ECT is an effective treatment of hepatic tumors and may be utilized for the treatment of tumors adjacent to high-risk regions, where other ablative procedures are contraindicated. 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.