Abstract
Perianal Crohn’s disease (PCD) is associated with worse outcomes including poor quality of life and higher medical costs. PCD is notoriously difficult to treat despite advancements in biologic therapies for luminal disease. In order to test innovative therapies for PCD, an animal model that closely mimics human perianal disease is warranted. Previous efforts were successful in creating perianal fistulas in swine, however, these closed after removal of the seton. A chronic model that maintains the fistula open and replicates the inflammatory component found in clinic is necessary.
Under general anesthesia, 4 female pigs underwent creation of surgical perianal fistulas using basic surgical technique with scalpel and hemostat. Size 24 French silicone foley catheter setons were placed to maintain patency of the fistula tract. Each pig had 3 fistulas created – 1 rectovaginal and 2 perianal. The setons were left in place for 4 weeks. After removal of the setons, Trinitrobenzenesulfonic acid (TNBS) was administered into the fistula tract twice a week to create local inflammation. After 2 weeks of TNBS, an MRI was obtained to assess the fistula tracts and the pigs were sacrificed to review histopathology.
MRI showed successful creation of chronic fistula tracts, and maintenance of these tracts 2 weeks after removal of setons. We noted a transsphincteric fistula with supralevator component as well as an associated abscess 3.3 x 1.0 cm containing fluid and gas (Fig 1). Gross specimen revealed patent fistula tracts. Histopathology found significant chronic active inflammation on standard H&E staining (Fig 2).
A chronic perianal fistula model in pigs was successfully created using large bore rubber setons and TNBS stimulation that strongly resembles that seen in humans. Further studies are needed to standardize the conditions required to have a reproducible model with well-defined levels of inflammation, fistula patency, and other parameters.
