Scientific background: Pancreatic cancer is the fourth leading cause of cancer-related death in the Western world. At the time of diagnosis approximately 40% of patients present with locally advanced disease , unsuitable for surgical treatment. The success of chemotherapy and radiotherapy therapy in these patients is limited, with a short survival (<12 months) despite therapy. Local ablative methods could represent a new treatment option for these patients. Electrochemotherapy (ECT) is an ablative procedure based on the local use of reversible electroporation. The procedure facilitates the transport of intravenously administered chemotherapeutic agents that do not cross the cell membrane directly into the cell. The method has already been established in the treatment of skin and liver tumors. To date, the safety and efficacy of pancreatic ECT has not been systematically studied.
Aim and hypothesis: The purpose of the doctoral thesis is to investigate the safety of pancreatic ECT with bleomycin on a survival model of a pig. Our hypothesis is that normal pancreatic electrochemotherapy does not cause clinically relevant local or systemic side effects, and that normal pancreatic electrochemotherapy causes cell necrosis in the ablative region.
Methods: Permission to conduct the experiments was granted by the Ethical Commission for Animal Experimentation at the Administration of the Republic of Slovenia for Food Safety, Veterinary and Plant Protection (permission number U34401-1/2017/4). All procedures were compliant with national and European legislation. The study was conducted on eight (8) pigs. The pigs were divided into two groups. In the first group, ECT of pancreatic tail was performed percutaneously under computed tomography (CT) guidance. In the second group, ECT of pancreatic head and pancreatic tail was performed with surgical laparatomy. Electroporation was carried out through 2 needle electrodes (1.2 mm thick) with a 3 cm long active part. The two groups of animals were followed for 7 days after the procedure. The clinical status of the animals and laboratory parameters were monitored to evaluate potential complications. CT scan was performed Immediately after the procedure and 7 days after the procedure. Animals were euthanized on the 7th day after the procedure and a pathological examination of the pancreas was performed to assess histological changes.
Results: All pigs survived the ECT procedure and none of them developed clinical signs of acute pancreatitis or related complications. There were no signs of acute pancreatitis or damage to the large vessels present in the follow-up CT scans. No significant change in laboratory parameters was obtained after procedure.
Conclusions: This study shows that ECT causes in necrosis and apoptosis in the ablative field, but these changes do not result in the formation of local and systemic side effects. Electrochemotherapy of pancreatic parenchyma is therefore safe local ablative method. The results of our study will contribute to further developement of pancreatic ECT.
|
