Perianal fistula and the ileoanal pouch – different aetiologies require distinct evaluation

Restorative proctocolectomy has been widely adopted as the procedure of choice for restoring gastrointestinal continuity following proctocolectomy. It is often associated with improved quality of life and high patient satisfaction; however, the development of a pouch anal fistula can cause significant morbidity. Pouch fistulas are notoriously difficult to treat and there is great heterogeneity in the management reported of these fistulas. A lack of classification, and the assumption that fistulas originating from completely different aetiologies will behave and respond similarly to a particular treatment strategy, precludes meaningful comparison of management outcomes. We aim to introduce consistency in the reporting of pouch fistulas using a novel classification system.


Introduction
The ileoanal pouch was first described 40 years ago [1]. With a greater number of pouches being created, pouch dysfunction and pouch failure are increasingly being reported; the most common causes are pelvic sepsis and pouchitis [2].
'Pouch fistula' comprising either perianal or vaginal fistula (with some publications also including enterocutaneous fistula to the abdominal wall) are commonly seen in inflammatory bowel disease (IBD) referral centres specialized in managing dysfunctional pouches, but discussion in the literature remains limited. There has been an assumption that such fistulas are generally due to either an anastomotic leak, when diagnosed shortly after pouch formation or restoration of intestinal continuity, or Crohn's disease, either newly diagnosed or a previously known diagnosis [3]. Low heterogeneity amongst the patient population in studies reporting pouch fistulas hinders interpretation of findings and meta-analysis.

Method
The classification proposed is based on the collective experience of treating high volumes of complex pouch patients in our two centres.

Comparison with other methods of classification
The (non-pouch) anal fistula literature is littered with mixed series containing various morphologies, duration and complexities of fistula of cryptoglandular and Crohn's origin. These are often analysed together and treated as though they should respond to therapies in a similar way. Even within the Crohn's fistula literature, a lack of adequate classification has led to such heterogeneity that comparison of therapeutic techniques and outcomes is almost impossible. Similarly, series of rectovaginal fistula repairs often group multiple aetiological causes together including those of obstetric, Crohn's related, radiation induced and septic (cryptoglandular, Bartholin's) origin. Mixed case series may produce a success rate which is not true for any of the fistula or cohorts included, and so represents an unhelpful average.
We herein propose a classification that allows separation of pouch fistulas into groups aetiologically distinct from one another and which would therefore, intuitively, benefit from differing treatment strategies.
We have observed four groups of fistulas in the ileoanal pouch.

Group 1 -Anastomotic dehiscence and pelvic sepsis related
These fistulas have two crucial identifying features: (i) anastomoticthey arise from the anastomosis; and (ii) timingthey develop shortly after pouch construction or restoration of intestinal continuity if the pouch construction was diverted (Fig. 1a). Anastomotic dehiscence can occur at the pouch anal anastomosis, at the efferent or afferent seams of the pouch or at the apex of the J-pouch. The internal opening of the fistula is identified at the point of the anastomotic separation and may fistulate into surrounding structures including bladder, prostate, urethra and vagina. Peri-pouch sepsis or a presacral collection may also be present [4]. We have also occasionally seen 'late' anastomotic fistulas with small or previously unrecognized radiological evidence of anastomotic abnormality on early MRI. Efforts to understand the aetiological cause centre around the risk factors associated with anastomotic leakage. Treatment strategies include early diagnosis of anastomotic leak with immediate intervention, such as an Endo-spongeâ [5], or later surgical repair with pouch advancement or reconstruction, given appropriate features such as an adequate distance between the anastomotic opening of the fistula and the dentate line [4].

Group 2 -Inflammatory bowel disease related
These fistulas can appear at any time but will generally appear at least 6 months following pouch construction (Fig. 1b). They may arise from the dentate line, the anastomosis, the cuff (perhaps in the presence of We define two subgroups in this category. Type A fistulas are associated with characteristic features on imaging and/or the histology of Crohn's disease. Crohn's can be confirmed by findings of discontinuous small bowel disease on enterography or typical granulomas on histological evaluation [3]. The presence of a (non-anastomotic) fistula and a history of ulcerative colitis (UC) is not, as has been suggested by some, sufficient to diagnose Crohn's disease in our view [6]. Type B fistulas are a distinct subgroup that are not associated with features consistent with Crohn's disease but are associated with histological characteristics of chronic inflammation in the pouch or cuff.
Aetiological analysis and treatment will mirror those in non-pouch Crohn's perianal fistulas, perhaps including appropriate reparative/reconstructive procedures, medical treatment or palliative loose seton insertion. Defunctioning and pouch excision may be necessary more often in the presence of active inflammatory disease.

Group 3 -Cryptoglandular related
These fistulas arise from the dentate line rather than the anastomosis and in the complete absence of luminal inflammation (e.g. cuffitis or pouchitis) [7] (Fig. 1c). They appear cryptoglandular in origin but seem to arise at a greater frequency than that seen in the healthy population. The cryptoglandular theory may explain origination but persistence, particularly at a higher rate than in the healthy population, may be related to factors seen in IBD more generally. This is consistent with a recent report that demonstrated that perianal fistulas were more common following anorectal abscess in people with UC than in the healthy population, although less common than in those with Crohn's disease [8].
The latter and most fascinating group, like those patients with an anal fistula in the presence of UC, may hold the key to understanding the factors leading to persistence of anal fistulas in IBD, since they may share these with anal fistulas arising in Crohn's disease (and IBD-related fistulas more generally, including those in group 2). This phenotypic overlap probably correlates with a genotypic or perhaps immunological similarity, highlighted previously [9], which predisposes both groups to fistula occurrence and/or persistence.

Group 4 -Malignancy related
Primary malignancy in the ileoanal pouch or cuff may present with a pouch fistula. This should be considered in the absence of an obvious alternative aetiology especially in those with a background of familial adenomatous polyposis or previous dysplasia or cancer in UC. Primary malignancy presenting as a pouch fistula has a poor prognosis if diagnosis is delayed; therefore, imaging, pouchoscopy, examination under anaesthetic and biopsy should be used early and evaluated with a high clinical suspicion in the presence of a new fistula.

Conclusion
Pouch fistulas are an increasingly important topic of investigation. To adequately define optimal treatment practices and investigate aetiological risk factors, a classification system which allows separation of fistulas into cohorts, suitable for further study, is necessary. We herein describe four primary cohorts of fistulas related to pelvic sepsis, IBD, cryptoglandular disease and malignancy in origin as a starting point for consistent investigation in aetiology, risk factors and treatment paradigms. This will strengthen the results of any future investigation.