Abstract

Abstract Background The quantification of fibrosis in Crohn’s disease (CD) still relies on surgical specimens’ pathology. We aimed to correlate quantification of inflammation and fibrosis of CD ileal resection specimens with postoperative progressive disease. Methods All patients (patients) having primary ileal resection for CD complications with a follow-up >3 years (n = 262) were considered. Unavailability of specimen excluded 72 patients and 22 for absence of the three study sections: (1) proximal ileal margin; (2) most affected area (B2: narrower calibre of stricture; B3: area with fistulas/deep ulcers); (3) inflamed area (inflamed bowel, no lesions as in 2). Of the 168 patients with the three studied phenotypes (B2 and B3 with stenosis (B3s) and without stenosis (B3o), we randomly excluded 65 B3s for overrepresentation. We analysed three sections per patient (3 × 103 patients = 309 sections), stained with haematoxylin and eosin and Masson’s trichrome. Chiorean et al. histopathological score grades inflammation 1–3 and fibrosis 0–2. We add a ‘0’ category to inflammation and observed adipose tissue and muscularisation in submucosa. Progressive disease was previously defined as one of eight post-operative outcomes (reoperation, hospitalisation, steroids, start or change of immunosupressives or biologics, new stricturing/penetrating/anal event). Statistics: Continuous variables were described by mean(standard deviation), median(interquartile range), minimum and maximum, and categorical variables by absolute(n) and relative(%) frequencies. Chi-square, Mann–Whitney and Kruskal–Wallis compared groups. Hypotheses were tested at 5% level of significance, using IBM SPSS Statistics for Mac, vs. 24.0. Results We assessed 103 patients (B2–29; B3o–20; B3s–54), 55% males, mean age at diagnosis 30(12) years, followed for a mean time of 10(4) years. Median time from surgery to reoperation was 8.0 (7.0, 12.0) years. B3 patients have significantly more inflammation than B2 patients [score 3: 78%vs.55% and 96%vs.76% in most affected (p = 0.027) and inflamed (p = 0.005) sections, respectively]. B3s patients had significantly more fibrosis than B3o [score 1 + 2: 90%vs.60% in most affected (p = 0.011) and 99%vs.85% in inflamed (p = 0.048) sections] and significantly more inflammation than B2 patients [score 3: 81%vs.55% in most affected (p = 0.020) and 94%vs.76% in inflamed (p = 0.019) sections]. B3s had higher total score than B3o and B2 [score 4–5: 78%vs.45%vs.52%, p = 0.019] and more new penetrating events (p = 0.043). Of the 25 patients changing biologic after surgery, 88% had inflammation at the margins [score 3: 55%vs.12%, p = 0.035]. Conclusion B3s stood out as a distinctive phenotype, with significantly more fibrosis than B3o but significantly more inflammation than B2. It displayed the highest total score and was associated to progressive disease.

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