Cold plasma endoscopy applied to biliary ducts: feasibility risk assessment on human-like and porcine models for the treatment of cholangiocarcinoma

Abstract

Abstract For the past 12 years, cold plasmas (i.e. weakly ionized gas) have been positioned as a breakthrough technology for treating cancer thanks to their antitumor properties. The innovation of ad hoc plasma sources and personalized protocols appears crucial to treat cancers with a very poor prognosis. This is the case for cholangiocarcinoma (CCA), a biliary tract cancer, whose treatment with cold plasma is envisioned but requires the innovation of catheters and endoscopic devices for local therapies. Before conducting clinical trials, the performances and limitations of cold plasma endoscopy (CPE) must be evaluated in terms of safety for both the patient and clinician as well as in terms of therapeutic efficacy. These objectives are pursued in the present work, in which a transferred plasma catheter is used, powered by 8–10 kV, 1–2 µs wide, 5–10 kHz repeated pulses, allowing guided streamers to be transferred over lengths of at least 2 m. In a first step, the catheter is utilized without the duodenoscope and directly inserted into an artificial model reproducing the topography and the electrical response of the biliary tree. This model allows to validate the technical feasibility of the technology and to demonstrate the absence of electrical and thermal risks. Indeed, the voltage and current deposited are as low as 3.98 V and 1.19 mA (RMS values) respectively, while the temperature locally increases from 23 °C to 27 °C. In a second step, the catheter is inserted into the duodenoscope, the whole being applied to a porcine anatomical model. After passing through the esophagus, stomach and duodenum, the distal part of the duodenoscope is placed at the entrance to the papilla so that the catheter can easily enter the choledoc and then the common bile duct. Interestingly, the electrical power values deposited are of the order of 100 mW especially because the current values are at least ten times higher. These more elevated values of electrical parameters but also electromagnetic effects are discussed considering physical aspects like eddy currents. The absence of electrical and thermal risks is demonstrated and consolidated by the medical devices standards fixed by the International Electrotechnical Commission (IEC). In a third time, we demonstrate that the cold plasma catheter can induce antitumor effects on in vitro experimental models of human CCA. The methodology proposed in this article validates the relevance of CPE as a potential local treatment for CCA and allows bridging cognitive and patient-oriented research.