title: Smooth Muscle Hyperplasia/Hypertrophy is the Most Prominent Histological Change in Crohn's Fibrostenosing Bowel Strictures: A Semiquantitative Analysis by Using a Novel Histological Grading Scheme.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Wenqian
authors.initials: W
authors.lastname: Chen
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
authors.forename: Cathy
authors.initials: C
authors.lastname: Lu
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Christina
authors.initials: C
authors.lastname: Hirota
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Marietta
authors.initials: M
authors.lastname: Iacucci
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Subrata
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada xsean.gui@cls.ab.ca.|Calgary Laboratory Services, Calgary, AB, Canada.
authors.forename: Xianyong
authors.initials: X
authors.lastname: Gui
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003106:Colon / Q000473:pathology; D003251:Constriction, Pathologic; D003424:Crohn Disease / Q000150:complications / Q000473:pathology*; D005260:Female; D006801:Humans; D006965:Hyperplasia; D006984:Hypertrophy; D007082:Ileum / Q000473:pathology; D007415:Intestinal Obstruction / Q000209:etiology / Q000473:pathology; D007422:Intestines / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000473:pathology*; D012720:Severity of Illness Index; D055815:Young Adult
keywords: Crohn’s disease; fibrosis; fibrostenosis; muscular hypertrophy; smooth muscle hyperplasia; stricture