EP200 - A systematic review of rat anal fistula models

Image or Table (Do Not add text here):

Purpose/Background: An anal fistula is a pathological tract connecting the anal canal or rectum to the perianal skin, often causing significant social and daily living difficulties for patients. Establishing animal models for anal fistulas is crucial for understanding disease pathogenesis, evaluating therapeutic approaches, and translating new treatments into clinical practice. Rats, due to their small size, ease of acquisition, and low cost, are ideal for exploratory research. This study aims to comprehensively review the literature on rat models of both simple and Crohn's disease-associated anal fistulas.

Methods/Interventions: A systematic literature review was conducted in July 2024 to identify studies that described or utilized rat models of anal fistula, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was performed using PubMed, EMBASE, and Web of Science, with the following search terms: 'anal fistula', 'animal model', and 'rat'. Studies were considered for inclusion if their titles and abstracts indicated relevance to rat models of anal fistula up to July 14, 2024. The initial search yielded 190 citations. Two independent reviewers screened English-language articles related to both Crohn's disease-associated and general anal fistulas. Articles without full-text availability, reviews, those not describing rat models of anal fistula, and conference papers were excluded. Discrepancies between the two reviewers were resolved by a third reviewer. After reviewing the abstracts and full texts, 181 articles were excluded based on predefined eligibility criteria. Ultimately, 9 studies met the inclusion criteria and were summarized in this review.

Results/Outcomes: Rat models of anal fistula are widely used in research due to their cost-effectiveness, ease of management, and straightforward experimental procedures. Techniques for creating these models include the wire or suture method, which involves surgically implanting a metal wire or suture into the perianal region and produces uniform fistula morphology; the chemical induction method, using trinitrobenzene sulfonic acid (TNBS) combined with thick seton threads, which effectively mimics inflammatory disease-induced fistulas but may cause non-specific inflammation; the surgical creation method, which allows precise control over fistula location and size but requires advanced surgical skills; and the electrolytic aluminum plus dextran sulfate sodium (DSS) method, which rapidly forms fistulas but can cause local chemical irritation.

Conclusion/Discussion: Although rat models offer significant advantages in terms of cost-effectiveness, ease of management, and straightforward experimental procedures, making them suitable for initial drug testing and the exploration of therapeutic approaches, their anatomical and immunological differences from humans pose certain limitations. For instance, the absence of anal glands in rats, a structure that is present in humans, is an important consideration when modeling human anal fistulas. Therefore, the choice of model and species should be carefully tailored to the specific research question at hand. Additionally, there is a need for more studies involving larger animals to develop models that can be effectively utilized for the investigation of diagnostic tests and treatments applicable to actual patients.