Introduction: There is a pressing need for the development of new devices facilitating advanced minimally invasive approaches for the in situ treatment of pancreatic cancer (PaCa). To this end, a new endoscopic ultrasound (EUS) compatible cryocatheter (Frostbite) has been developed. When paired with the novel Pressurized Subcooled Nitrogen (PSN) cryoconsole, a cryogen is circulated within EUS cryocatheter delivering ultracold ablative temperatures to a targeted tissue in a closed loop manner. In this study, we evaluated cryocatheter performance for its potential use in transesophageal in situ ablation of PaCa and liver cancer.
Methods: A ~1m cryocatheter with a 13cm long 17 gauge needle with a 3cm ablation tip, was connected to PSN and then passed through the working channel of a EUS endoscope. Performance evaluations included a 37°C ultrasound gel model, ex vivo tissue engineered PaCa model and an acute porcine study wherein 6 lesions were created within the liver (under IACUC Approval). Performance assessment included measurement of ice ball size, isotherm profile in real time and destruction area created. A single 5 minute freeze protocol was employed for all evaluations.
Results: Bench studies demonstrated the generation of a 2.4cm diameter iceball with a tip temperature of < -170°C and penetration of the -40 and -20°C isotherms to 1.5cm and 2.1cm (respectively) following 5mins. Analysis of tissue destruction using PaCa tumor model revealed the creation of a 2.1cm ablation area 1 day post freeze. The porcine study demonstrated the consistent generation of a 2cm x 3.1cm (diameter x length) ablation zone following a single 5 minute freeze protocol. The porcine study also demonstrated the ability to deliver targeted destruction of tissue in close proximity to major vasculature without damaging the blood vessel.
Discussion: The results of this study demonstrated that the cryocatheter was able to rapidly and effectively freeze targeted tissue via a EUS approach. The results showed the device was able to consistently ablate a 2cm x 3cm area using a single 5 minute freeze protocol across all models. Analysis of the ablation efficacy revealed ~70% destruction within the overall frozen mass compared to < 40% attained with current percutaneous based cryodevices. Although further testing and refinement are needed, these studies demonstrated the potential of this new approach to provide a next-generation strategy for the treatment of PaCa.
