## 1 Introduction  
Pancreatic cancer remains one of the most difficult-to-treat cancers, and the overall survival of patients with an advanced stage is low [1]. Pancreatic cancer is often diagnosed to be unresectableand the available therapeutic methods, including chemo- and radiotherapy, are not effective. Thus, alternative methods such as electroporation (EP)-based treatments could be considered here. EP is a physical method in which electrodes are placed within tissue, and short electrical impulses (from picosecond up to milliseconds) with an electric field intensity in the range of 1000 to 3000 V/cm are administered, which causes permeabilization of the cell membrane through lipid rearrangement [2]. Consequently, new transport pathways termed \"nanopores\" for ions and other hydrophilic particles, including drugs, are created. Changes in the concentration of electrolytes such as potassium and sodium lead to rapid changes in cell membrane potential. Destabilization of the cell membrane causes disturbance in cell homeostasis, the relocation of calcium ions to inside of the cell, and death due to the depletion of energy sources [3; 4]. Disturbances in calcium metabolism and homeostasis, mitochondrial damage, and depletion of ATP sources lead to a rapid necrotic type of cell death. However, overloading cells with a subthreshold concentration of calcium ions may induce the apoptotic pathway wherein a large number of damaged cells are removed by macrophages [5; 6]. The changes induced in cells by electrical pulses can be reversible (Reversible Electroporation [RE]) or irreversible (Irreversible Electroporation [IRE]) depending on the voltage and number of pulses affecting the cell membrane. The effectiveness of this method for treating various types of cancers was proved by several in vivo and in vitro preclinical studies [7; 8; 9; 10; 11]. The protocol of its application has also been developed and described, in combination with chemotherapy (CTH), in ESOPE (The European Standard Operating Procedures of Electrochemotherapy) for the treatment of cutaneous and subcutaneous lesions [12; 13]. Electrotherapy is an ablation method with low thermal effect, and it is used for treating head and neck cancer, brain cancer, sarcoma, metastatic cancer, or primary cancer of liver, lungs, breast, pancreatic, and prostate cancer [14; 15; 16; 17; 18; 19; 20; 21; 22; 23]. The combination of these two methods, established as electrochemotherapy (ECT), was applied the most to treat different solid tumors and with different chemotherapeutic in in vitro studies. The simultaneous conduction of EP and administration of a chemotherapeutic agent increase the cytotoxicity of a given drug against cancer cells and decrease the dose of a drug necessary for intravenous administration, which in turn decreases the drug toxicity affecting a patient. This leads to a higher \"effectiveness' of chemotherapeutics [24; 25; 26; 27; 28; 29]. Some ECT research has been conducted on patients with pancreatic cancer who showed metastatic changes. The studies were conducted using bleomycin, cisplatin, and doxorubicin [29; 30; 31; 32; 33; 34; 35; 36]. ECT using bleomycin was found to be most \"effective\"; this agent is 700 to 1000 times more toxic when administered simultaneously with IRE application [24; 36; 37; 38]. The effectiveness of ECT using bleomycin was demonstrated only in an animal model with pancreatic cancer [39] or melanoma [26]. In studies, patients with nonresectable pancreatic cancer first received Folfrinox or Gemox CTH, and when the tumor was stabilized according to RECIST (i.e. response evaluation criteria in solid tumors) criteria, IRE alone was applied. Positive results were obtained, and the changes in the tumor mass were not visible in computer tomography but only in MRI [40]. Another novel approach is the combination of EP with intratumoral (IT) administration of calcium ions.