Studies on mechanisms of enterocutaneous fistula healing

Abstract

This thesis reviewed and investigated several aspects of the management of enterocutaneous fistula (ECF). The best management of ECF, particularly complex fistulas, is in specialist units where there is a multidisciplinary structured approach. Surgical management of ECF at St. Mark’s National Intestinal Failure Unit is safe and improving over time. The highest incidence of ECF development occurs following abdominal surgery particularly in the presence of Crohn’s disease. The audit confirmed this in our unit. A retrospective audit of our unit revealed the majority of patients underwent definitive surgery. There were improved overall healing rates following both surgery and conservative management in the current cohort, with also improvement in the 30 day post fistula resection mortality compared with a previous series at our unit. Multivariate analysis revealed co-morbidity, source of referral and aetiology had significant associations with ECF healing. This thesis has included the first study and design of a scoring system for predicting ECF healing. The scoring systems devised were both validated. They can provide further information to aid clinical management and decision making for the multidisciplinary team and predict the possible long term outcome for patients at external institutions. Meta-analyses of randomised control trials has revealed somatostatin and octreotide increase the likelihood of fistula closure, reducing the time to fistula closure, and neither has an effect on mortality. 5 Immunological studies revealed an increased on-going production of cytokines, in particular TNF-α, in non-IBD ECF compared with control terminal ileum tissue. The data may provide evidence for the potential use of anti-TNF-α agents in the treatment of non-IBD ECF. A future pilot study has been designed with the aim to identify a potential novel therapy for patients with persistent enterocutaneous fistula not associated with inflammatory bowel disease. Any positive findings would equate to a major medical advance with a new use for anti-TNF-α agents.