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Poster presentations: Basic Science 2020

P051 Quantifying inflammation and fibrosis through a surgical histopathological score can differentiate ileal Crohn’s disease phenotypes and predict postoperative progressive disease

H. Tavares de Sousa1,2, I. Gullo3,4,5, C. Castelli6, C.C. Dias7,8, F. Magro9,10,11

1Algarve University Hospital Centre, Gastroenterology Department – Portimão Unit, Portimão, Portugal, 2ABC – Algarve Biomedical Centre, University of Algarve, Faro, Portugal, 3São João University Hospital and Faculty of Medicine, Department of Pathology, Porto, Portugal, 4University of Porto, Institute of Investigation and Inovation in Health i3S, Porto, Portugal, 5Institute of Molecular Pathology and Immunology of the University of Porto Ipatimup, Institute of Molecular Pathology and Immunology of the University of Porto Ipatimup, Porto, Portugal, 6University and Hospital Trust of Verona, Department of Diagnostics and Public Health- section of Pathology, Verona, Italy, 7Faculty of Medicine, University of Porto, Portugal, Department of Community Medicine, Information and Decision in Health, Porto, Portugal, 8University of Porto, Centre for Health Technology and Services Research, Porto, Portugal, 9Faculty of Medicine, University of Porto, Department of Biomedicine, Unit of Pharmacology and Therapeutics, Porto, Portugal, 10MedInUP, Centre for Drug Discovery and Innovative Medicines, MedInUP, Centre for Drug Discovery and Innovative Medicines, Porto, Portugal, 11São João University Hospital, Department of Gastroenterology, Porto, Portugal

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.