Clinical and experimental studies in idiopathic and Crohn's-related anal fistula

Abstract

The factors leading to the creation and persistence of anal fistula in Crohn’s disease are poorly understood. As with luminal Crohn’s disease genetic, microbiological and immunological factors are implicated but the immunological and microbiological composition of Crohn’s and idiopathic anal fistulae have been obscure. My data demonstrate a lack of clinically relevant organisms within fistula tracts, a luminally driven immune response and subtle differences in this response between Crohn’s and idiopathic fistulae which may provide the basis for diagnostic tests, interventions and further research. Surgical treatment of anal fistula is characterised by a compromise between risk of recurrence and impairment of continence. In complex, recurrent and multiply operated anal fistulae, fistulotomy can still provide a high success rate with low additional risk of impairment of continence. Rectovaginal fistulae are also difficult to manage both surgically and medically. In the infliximab era, successful healing of Crohn’s RVF remains disappointingly rare. Surgery for RVF requires a variety of approaches but remains a valuable tool in the treatment of both Crohn’s and non-Crohn’s tracts. Medical treatment of Crohn’s anal fistulae with combination thiopurine and anti-TNFα agents has demonstrated good short term results. Clinical and radiological data to 3 years follow up demonstrate that around a third of patients maintain healing on infliximab, radiological healing lags behind clinical remission by around a year, and cessation may lead to recurrence in spite of a healed tract on MRI. A treatment for anal fistula with high success and low risk of impairment of continence in complex anal fistulae eludes colorectal surgeons and gastroenterologists. A treatment combining the best aspects of current fistula management with novel elements prompted by improved aetiological understanding must be the goal for fistula surgeons and is the inspiration behind this thesis.