Inflammation and tissue remodeling contribute to fibrogenesis in stricturing Crohn’s disease: image processing and analysis study

Abstract

Crohn's disease (CD), a form of idiopathic inflammatory bowel disease (IBD), has an estimated annual incidence of 3.1 to 20.2 per 100,000, and a prevalence of 201 per 100,000 in North America [1,2]. Based on its clinical behavior, CD is classified as B1 (non-stricturing, non-penetrating), B2 (stricturing) and B3 (penetrating) [3][4][5]. While most CD patients initially present as B1, they can have more than one phenotype, and clinical behavior may change over time [4]; i.e., a patient with B1 phenotype may develop strictures and or fistula during the disease course and subsequently be re-classified as having a B2 or B3 phenotype [6,7]. Eventually, about 70% of CD patients develop stenosis or fistula [7]. Stricture is the most common indication for surgery in CD [8].The progression of fibrosis and eventual stricture formation is a significant disease burden requiring escalation of medical treatment or surgical intervention in CD. Although many factors, such as genetic, epigenetic, serological, clinical, environmental, and endoscopic factors are postulated to portend an increased risk for fibrosis progression, its pathogenesis is relatively poorly understood [5,9,10]. Moreover, most of the pathological studies using formalin-fixed paraffin-embedded (FFPE) tissue are limited to morphological evaluation on routine hematoxylin and eosin (H&E)