Is there concordance between the Cellvizio system and pathology in determining microscopic inflammation at the ileal resection margins in Crohn's ileal disease? The CELLVICROHN study

Abstract

BackgroundCrohn's disease is an inflammatory bowel disease for which surgery is required in approximately 80% of cases. However, surgery does not cure Crohn's disease. The type of surgery is important, as there are intraoperative risk factors for recurrence, including microscopic inflammation at the resection margins. This point is crucial, as a too large resection may result in short bowel syndrome and a too short resection (microscopic inflammation at the resection site) a higher risk of postoperative recurrence (75% vs 46% at 18 months). Based on the results of a randomised control trial, surgeons are encouraged to perform a limited resection (2 cm from macroscopic Crohn's disease). However, such a macroscopically non-inflamed resection margin may show microscopic inflammation (up to 80%). Thus, it would be useful to evaluate whether there is microscopic inflammation at the resection margin. Moreover, there is an increasing interest in the role of the mesentery in recurrence, which is still unclear. Thus, it would be informative to also clarify the border between inflamed and non-inflamed mesentery. Cellvizio is a type of confocal laser endomicroscopy system that provides the possibility to obtain high-magnification in-vivo images of the gut epithelium. This allows real-time examination of the gastrointestinal mucosa at the cellular and subcellular level. Cellvizio has never been used during surgery for Crohn's disease. PurposeThe aim of this study is to evaluate the intraoperative use of Cellvizio to determine the optimal ileal resection margins in Crohn's disease. Primary outcomeThe primary outcome is the concordance between the evaluation of microscopic inflammation at the ileal resection margin by the Cellvizio system and pathology. Secondary outcomesThe secondary outcomes are the concordance between the Cellvizio system and pathology in evaluating inflammation of the serosa (transmural inflammation) and mesentery and the length of the ileum (in cm) between the surgical margin and the theoretical resection site to have a resection margin free of microscopic inflammation as determined by the Cellvizio system (for the mucosa and serosa). Study designThis is a prospective, single centre, interventional study. Eligibility criteriainclusion criteria: Patients who require an ileocecal resection for Crohn's disease, regardless of the phenotype. exclusion criteria: Patients who are under 18 years of age, are pregnant or breastfeeding, have had an ileocolic resection for a surgical recurrence of Crohn's disease, have had emergency surgery for peritonitis, and those who have a contra indication for fluoresceine injection or severe allergy to any drug. Arm number or label and arm typeThis is a single-arm study. InterventionsDuring surgery an intravenous injection of fluoresceine will be performed. The surgeon will then evaluate the ileal section margins of the mucosa, serosa, and mesentery to evaluate whether the section margin shows microscopic inflammation. The surgeon will then evaluate (in cm) the length between this section margin and the theorical section margin to be within non-inflamed tissue of the mucosa, serosa, and mesentery. The data will be recorded during surgery, blind from the pathological analysis. The pathological analysis will also be performed blind from the Cellvizio data. A video collection will be performed anonymously. Number of participants41 patients Statistical analysisWe assume an estimated Kappa coefficient of 90%, a lower bound of 70%, and a frequency of microscopic inflammation at the ileal resection margin of 70%. Given this hypothesis and an alpha risk of 5%, the inclusion of 41 patients will be necessary.