Evaluation of Safety and Feasibility of Endoscopic Ultrasound (EUS)-Guided Radiofrequency Ablation (RFA) for Solid Pancreatic Neoplasms

RFA causes tissue destruction through the application of a high frequency alternating current, generating local temperatures above 60°C and leading to coagulative necrosis. The technique has been widely used in many solid organ tumours and has been shown to result in 5-year survival rates comparable to surgery. The technique is currently the standard therapy in hepatocellular carcinoma and colorectal pulmonary metastasis particular in patients that are not suitable for surgery.

The application of RFA in the pancreas was first described in 1999. Thereafter, several studies performed in the porcine model demonstrated the feasibility of RFA under EUS guidance. In the first porcine study by Goldberg et al, RFA was applied through a modified 19 gauge Vilmann-type needle (GIP/MediGlobe, Grassau, Germany). The needles were electrically insulated with shrink tubing for all but the distal 1 to 1.5cm. 16 ablations were performed and the procedure resulted in hypodense foci of non-enhancing pancreas 1 to 2 days after ablation. Pathologic examination showed well demarcated spherical foci of coagulation necrosis measuring 8 to 12mm in size. One swine developed hyperlipasemia, a focal zone of pancreatitis and another with pancreatic fluid collection. 4 swine also suffered from thermal injury to the gastrointestinal wall caused by improper electrode placement.

Thereafter, 4 subsequent porcine studies also demonstrated the feasibility of RFA under EUS guidance with proprietary radiofrequency electrodes. In the most recent study, EUS-guided RFA was delivered by a novel 18-gauge RFA electrode and a VIVA RF generator (STARmed, Korea). RFA was applied to both the ex-vivo and in-vivo models to determine the optimum power settings and efficacy of the device. A power setting of 50 W for 6 minutes was shown to result in the most effective depth and size of ablation zone, whilst a higher power setting resulted in tissue charring and reduced the conductive coagulative necrosis effect. 10 swine then received EUS-guided RFA to the pancreas and the mean size of the ablated lesions were 23 +/- 6.9mm. None of the swine suffered from any adverse events and there were no significant changes in the serum levels of amylase and lipase, both before and after the procedures.

On the other hand, the experience of RFA in human pancreas is accumulating. Earlier studies using first generation percutaneous RFA probes applied intra-operatively to pancreatic carcinomas were associated with unacceptably high rates of mortality (0% - 25%) and morbidity (0% - 40%). Subsequently, human data on new generation EUS-guided RFA probes with improved design and outcomes have become available. 22 patients with locally advanced pancreatic ductal adenocarcinoma were treated the cryotherm probe (CTP) (ERBE Elektromedizin GmbH, Tübingen, Germany). The CTP was successfully applied in 16 patients (72.8%), amylase rose in 3 of 16 patients but none had clinical signs of pancreatitis. The median post ablation survival time was 6 months. In another 2 studies, the Habib RFA catheter was used (EMcision, United Kingdom). 7 patients with unresectable pancreatic ductal carcinoma and 8 patients with pancreatic neuroendocrine tumour and cystic tumours were treated with EUS-guided RFA. In patients suffering from pancreatic ductal carcinoma, post procedural imaging showed a decrease in size of the lesions in 2 patients and 1 patient suffered from mild pancreatitis. Whilst in patients with cystic neoplasms and neuroendocrine tumours, all showed complete resolution or reduction in size of the lesions. Only 2 patients suffered from abdominal pain that resolved spontaneously. On the other hand, RFA with the VIVA generator was applied in 6 patients with unresectable pancreatic adenocarcinoma. Two patients suffered from mild abdominal pain but no serious adverse events reported.

Thus, based on these preliminary results, we conclude that the new generation EUS-guided RFA probe is safe and feasible. The next stage in development with conduction of this study would involve recruitment of larger patient cohorts to further establish the efficacy and risk profile of the procedure.