DEVELOPMENT OF A NOVEL CHEMICAL DISSOLUTION FORMULATION AND ENDOSCOPIC DELIVERY DEVICE TO FACILITATE THE BREAKDOWN AND DRAINAGE OF PANCREATIC NECROSIS IN A SINGLE SESSION

Background: Around 15% of acute pancreatitis patients develop necrosis of the pancreatic/peri-pancreatic tissue resulting in necrotic debris surrounded by a wall of granulation tissue called “walled-off pancreas necrosis” (WON). Patients with WON have a prolonged clinical course, often associated with infection within the necrotic debris. Direct endoscopic necrosectomy has been developed to remove the necrotic debris but is technically challenging due to the gluey debris and limited endoscopic accessories, requiring a median of 3-6 necrosectomy sessions for complete removal. Here, we aim to develop a chemical dissolution product to facilitate the breaking down and dissolution of the solid necrosome, allowing immediate aspiration in a single session.

Methods: Human pancreas necrosis specimens from endoscopic necrosectomies were collected and characterized using near-infrared spectroscopy to help identify candidate dissolution chemicals. The liquid dissolution chemicals were converted into a foam formulation to improve spreading within the WON cavity and contact with the debris. A novel endoscopic foam generation cap device was developed to deliver the dissolution foam through cyst gastrostomy (Fig.1). Ex-vivo high-throughput dissolution studies were performed on the porcine-pancreas necrosis model to optimize the foam formulation, requiring the lowest concentration of dissolution chemical and ensuring the stability of the foam (Fig.2). In-vivo porcine WON model was developed through implantation of the donor pancreas into the abdominal cavity of the recipient pig, to evaluate efficacy of dissolution foam and foam generation cap device. Safety studies were performed evaluating the effect of dissolution foam on granulation tissue wall, blood vessels, and gastric mucosa.

Results: Human pancreas necrosis debris characterization on spectrometry showed the presence of complex fats and proteins, nearly identical to the debris from the porcine pancreas necrosis model (p < 0.01). Hypochlorite (3.5%) based foam formulation with surfactants and stabilizing polymers showed >90% dissolution of necrotic debris at 10 mins, allowing complete suction through an endoscope (Fig.2). Stability testing of the foam formulation showed >95% intact bubbles at up to 18 hours. The in-vivo porcine study demonstrated adequate foam delivery through cyst gastrostomy opening (Fig. 2D). Safety studies showed no significant damage on gross and histopathological examination.

Conclusion: This novel foam formulation can chemically dissolve the WON necrotic debris in less than 10 minutes without damaging the granulation tissue wall or blood vessels and can be effectively delivered using our endoscopic foam generation cap device. This technology will potentially allow a single procedure complete necrosectomy avoiding the need for repeat interventions.