Wenqian Chen1, Cathy Lu2, Christina Hirota3, Marietta Iacucci3, Subrata Ghosh3, Xianyong Gui4,5. 1. Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada. 2. Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB, Canada. 3. Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, AB, Canada. 4. Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada xsean.gui@cls.ab.ca. 5. Calgary Laboratory Services, Calgary, AB, Canada.
Abstract
BACKGROUND: The simplistically and ambiguously termed 'fibrostenosis' of bowel is a hallmark of severe Crohn's disease [CD] and a major contributor to medical treatment failure. Non-invasive imaging assessment and novel medical therapy targeting this condition are under investigation, which particularly requires a better understanding of the underlying histological basis. METHODS: We analysed 48 patients with stricturing Crohn's ileitis or/and colitis that required surgical resection. The most representative sections of the fibrostenotic, non-stenotic and uninvolved regions were reviewed for histological analysis. For each layer of bowel wall (mucosa including muscularis mucosae [MU], submucosa [SM], muscularis propria [MP], subserosal adventitia [SS]), histological abnormalities were evaluated individually, including active and chronic inflammation, fibrosis, smooth muscle hyperplasia or hypertrophy, neuronal hypertrophy and adipocyte proliferation. A novel semiquantitative histological grading scheme was created. RESULTS: The most significant histopathological features characterizing the stricturing intestines were smooth muscle hyperplasia of SM, hypertrophy of MP and chronic inflammation. The muscular alteration was predominant in all layers. The overall muscular hyperplasia/hypertrophy was positively correlated with chronic inflammation and negatively correlated with fibrosis, whereas SM muscular hyperplasia was also associated with MU active inflammation. Similar changes, to a lesser extent, occurred in the adjacent non-stenotic inflamed bowel as well. CONCLUSIONS: In CD-associated 'fibrostenosis', it is the smooth muscle hyperplasia/hypertrophy that contributes most to the stricturing phenotype, whereas fibrosis is less significant. The 'inflammation-smooth muscle hyperplasia axis' may be the most important in the pathogenesis of Crohn's strictures.
BACKGROUND: The simplistically and ambiguously termed 'fibrostenosis' of bowel is a hallmark of severe Crohn's disease [CD] and a major contributor to medical treatment failure. Non-invasive imaging assessment and novel medical therapy targeting this condition are under investigation, which particularly requires a better understanding of the underlying histological basis. METHODS: We analysed 48 patients with stricturing Crohn's ileitis or/and colitis that required surgical resection. The most representative sections of the fibrostenotic, non-stenotic and uninvolved regions were reviewed for histological analysis. For each layer of bowel wall (mucosa including muscularis mucosae [MU], submucosa [SM], muscularis propria [MP], subserosal adventitia [SS]), histological abnormalities were evaluated individually, including active and chronic inflammation, fibrosis, smooth muscle hyperplasia or hypertrophy, neuronal hypertrophy and adipocyte proliferation. A novel semiquantitative histological grading scheme was created. RESULTS: The most significant histopathological features characterizing the stricturing intestines were smooth muscle hyperplasia of SM, hypertrophy of MP and chronic inflammation. The muscular alteration was predominant in all layers. The overall muscular hyperplasia/hypertrophy was positively correlated with chronic inflammation and negatively correlated with fibrosis, whereas SM muscular hyperplasia was also associated with MU active inflammation. Similar changes, to a lesser extent, occurred in the adjacent non-stenotic inflamed bowel as well. CONCLUSIONS: In CD-associated 'fibrostenosis', it is the smooth muscle hyperplasia/hypertrophy that contributes most to the stricturing phenotype, whereas fibrosis is less significant. The 'inflammation-smooth muscle hyperplasia axis' may be the most important in the pathogenesis of Crohn's strictures.
Authors: Ilyssa O Gordon; Dominik Bettenworth; Arne Bokemeyer; Amitabh Srivastava; Christophe Rosty; Gert de Hertogh; Marie E Robert; Mark A Valasek; Ren Mao; Satya Kurada; Noam Harpaz; Paula Borralho; Reetesh K Pai; Rish K Pai; Robert Odze; Roger Feakins; Claire E Parker; Tran Nguyen; Vipul Jairath; Mark E Baker; David H Bruining; J G Fletcher; Brian G Feagan; Florian Rieder Journal: Gastroenterology Date: 2019-08-30 Impact factor: 22.682
Authors: Se Eun Ha; Lai Wei; Brian G Jorgensen; Moon Young Lee; Paul J Park; Sandra M Poudrier; Seungil Ro Journal: J Vis Exp Date: 2018-03-05 Impact factor: 1.355
Authors: Geert D'Haens; Florian Rieder; Brian G Feagan; Peter D R Higgins; Julian Panés; Christian Maaser; Gerhard Rogler; Mark Löwenberg; Robbert van der Voort; Massimo Pinzani; Laurent Peyrin-Biroulet; Silvio Danese Journal: Gastroenterology Date: 2019-06-27 Impact factor: 22.682
Authors: Joseph Sleiman; Sara El Ouali; Taha Qazi; Benjamin Cohen; Scott R Steele; Mark E Baker; Florian Rieder Journal: Expert Rev Gastroenterol Hepatol Date: 2020-12-28 Impact factor: 3.869