Calprotectin in patients with perianal fistulas: the CANALS study

Rationale: Cryptoglandular (CG) and Crohn’s disease (CD) perianal fistulas represent separate entities, both with regard to etiopathogenesis as well as treatment strategy. Differentiating both entities on clinical grounds can be difficult and in a considerable number of patients endoscopy is required to rule tout CD. Still, diagnostic accuracy is limited by the fact that perianal fistulas may be the first manifestations of CD. In a retrospective observational study, we recently demonstrated that faecal calprotectin (FC) – a non-invasive surrogate marker of inflammation – can discriminate between CG and CD perianal fistulas. Furthermore, the diagnostic accuracy of FC to detect luminal inflammation CD patients with an active perianal fistula appeared to be decreased. Especially specificity of FC was low, as one-third of patients with an elevated FC value (>250mcg/g) had endoscopically quiescent disease.
Objective: Determine the diagnostic accuracy of FC for (i) differentiating between active CD perianal fistulas and CG perianal fistulas and (ii) predicting the presence of intestinal inflammation in CD patients with an active perianal fistula
Study design: Prospective single center cross-sectional study
Study population: 70 patients with an active perianal fistula who require surgical examination under anesthesia at the outpatient surgery center; 35 patients with a CD perianal fistula and 35 with a CG perianal fistula
Main study parameters/endpoints:
Primary objectives
• Determine the diagnostic accuracy of faecal calprotectin for differentiating between active Crohn’s disease perianal fistulas and cryptoglandular perianal fistulas
Secondary objective
• Determine the diagnostic accuracy of faecal calprotectin for the presence of active intestinal inflammation in CD patients with an active perianal fistula
• Determine local calprotectin production in an active fistula tract determined by fistula fluid and scrapings calprotectin concentration
• Determine the association between the anatomical nature of the fistula tract (simple vs complex) and faecal calprotectin and fistula fluid and scrapings calprotectin concentrations
• Determine the association between the epithelialization status of the fistula tract and faecal calprotectin and fistula fluid calprotectin concentrations
• Determine the correlation between the Perianal Disease Activity Index (PDAI) and faecal calprotectin concentration
• Determine the correlation between calprotectin concentration in faeces and fistula fluid
• Determine the correlation between calprotectin concentration in fistula fluid and fistula scraping
• Determine the correlation between calprotectin concentration in faeces and fistula scraping

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: For this study patients only undergo procedures as part of standard clinical care. During examination under anesthetics, additional biomaterial will be collected: faeces, fistula fluid and fistula tract scraping. To acquire this biomaterial rinsing of the fistula tract is followed by scraping of the fistula tract using a curette surgical instrument (to create a fresh tract). Both procedures are part of general clinical practice. A scoop of faeces will be collected from the rectum which does not burden the patient. In the CD group, intestinal inflammation is assessed in all patients with an abdominal ultrasound which will only focus at the gastrointestinal tract. This procedure is non-invasive, painless, quick and without risks. We therefore consider this procedure not to burden the patient.

We recently published a retrospective observation study in which we showed that:
• Faecal calprotectin can discriminate between cryptoglandular and Crohn’s perianala fistulas, even in the absence of endoscopic inflammation and
• In Crohn’s disease patients with an actively draining perianal fistula, specificity of faecal calprotectin to predict intestinal ulcers is low and faecal calprotectin values should be interpreted with caution. The underlying hypothesis for the aforementioned results comes down to the loss of calprotectin via the fistula tract into the faeces. Due to distinct underlying etiopathogenesis, active CG fistulas might not produce calprotectin in a similar amount as active CD fistulas. Hence FC could be used to discriminate these two entities. Furthermore due to the loss of calprotectin from within the fistula tract towards the intestinal lumen, the diagnostic accuracy of FC for the presence of intestinal inflammation might be decreased.

cross sectional.

N/A