TY - JOUR
T1 - Constrictive and Hypertrophic Strictures in Ileal Crohn's Disease
AU - Liu, Qingqing
AU - Zhang, Xiaofei
AU - Ko, Huaibin Mabel
AU - Stocker, Daniel
AU - Ellman, Jordan
AU - Chen, Joyce
AU - Hao, Yansheng
AU - Bhardwaj, Swati
AU - Liang, Yuanxin
AU - Cho, Judy
AU - Colombel, Jean Frederic
AU - Taouli, Bachir
AU - Harpaz, Noam
N1 - Funding Information:
The authors thank Dr Florian Rieder, Professor of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, Ohio, for reviewing an early draft of this manuscript and providing helpful comments. Qingqing Liu, MD PhD (Conceptualization: Equal; Data curation: Lead; Formal analysis: Lead; Methodology: Equal; Validation: Lead; Writing – original draft: Equal), Xiaofei Zhang, MD,PhD (Data curation: Lead; Formal analysis: Lead; Methodology: Equal; Validation: Lead), Huaibin Mabel Ko, MD (Data curation: Equal; Formal analysis: Equal; Validation: Equal), Daniel Stocker, MD (Data curation: Supporting), Jordan Ellman, MD (Data curation: Supporting), Joyce Muhan Chen, MD PhD (Conceptualization: Supporting), Yansheng Hao, MD PhD (Conceptualization: Supporting), Yuanxin Liang, MD PhD (Visualization: Supporting), Judy Cho, MD (Writing – review & editing: Supporting), Jean Frederic Colombel, MD (Writing – review & editing: Supporting), Bachir Taouli, MD (Writing – review & editing: Supporting), Noam Harpaz, MD PhD (Conceptualization: Lead; Formal analysis: Lead; Funding acquisition: Lead; Investigation: Lead; Methodology: Lead; Supervision: Lead; Validation: Equal; Writing – original draft: Lead) Conflicts of interest These authors disclose the following: Jean Frederic Colombel reports research grants from AbbVie, Janssen Pharmaceuticals, and Takeda; payment for lectures from AbbVie, Amgen, Allergan, Bristol-Myers Squibb Company, Ferring Pharmaceuticals, Shire, and Takeda; consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb Company, Celgene Corporation, Celltrion, Eli Lilly, Enterome, Ferring Pharmaceuticals, Genentech, Gilead, Iterative Scopes, Ipsen, Immunic, lmtbio, Inotrem, Janssen Pharmaceuticals, Landos, LimmaTech Biologics AG, Medimmune, Merck, Novartis, O Mass, Otsuka, Pfizer, Shire, Takeda, Tigenix, and Viela bio; and stock options in Intestinal Biotech Development. Bachir Taouli reports research grants from Bayer, Regeneron, and Takeda. Noam Harpaz reports consultant for and service contracts with Celgene, Abbvie, Bristol Myers Squibb, and Lilly USA. Funding This work was supported by the Dr Sanford J. Grossman Trust for Integrative Studies in IBD and by a grant from the International Organization for the Study of IBD.
Funding Information:
Funding This work was supported by the Dr Sanford J. Grossman Trust for Integrative Studies in IBD and by a grant from the International Organization for the Study of IBD.
Publisher Copyright:
© 2022 AGA Institute
PY - 2022/6
Y1 - 2022/6
N2 - Background & Aims: Strictures in Crohn's disease (CD) are classically attributed to fibromuscular hypertrophy of the intestinal wall. We have identified and characterized CD-related ileal strictures that result instead from mural constriction (ie, reduced external circumference). Methods: Twenty-four strictures and internal controls from 17 adults with obstructive CD were analyzed by cross-sectional morphometry. Results: The stricture-to-control circumference ratios (CRs) ranged from 0.53 to 1.7. Six strictures with CR ≥1.0, designated hypertrophic, had concentrically thickened walls, mean 3-fold increases in cross-sectional area and stainable fibromucular tissue, and high transmural inflammation scores. In contrast, 18 strictures with CR <1.0, designated constrictive, had thin, pliant walls, cross-sectional areas and stainable fibromuscular tissue comparable with control values, and low transmural inflammation scores. Eight mildly constrictive strictures also showed mild fibromuscular mural expansion that fell short of statistical significance. Twelve of 18 constrictive strictures (67%) occurred multiply (2–4 strictures per specimen) in contrast with hypertrophic strictures, all of which occurred singly (P = .01). Constriction correlated quantitatively with circumferential serosal fat wrapping (P = .003) and was associated with myenteric lymphocytic plexitis (P = .02). Disease duration was shortest among subjects with constrictive strictures and correlated with increasing circumference (CR ≤0.8, 6.3 ± 6.2 years; CR >0.8, 8.7 ± 6.4 years; and CR ≥1.00, 13.7 ± 5.0 years, respectively; P = .03). Conclusions: Constrictive ileal strictures in CD differ pathologically and clinically from hypertrophic strictures, featuring little or no fibromuscular mural expansion, frequent multiplicity, and earlier onset. Mesenteric fat wrapping and myenteric plexitis may contribute to their pathogenesis. Pathologic manifestations of constriction and hypertrophy can coexist, suggesting that stricture heterogeneity may be shaped in part by the dynamics of constrictive and hypertrophic processes.
AB - Background & Aims: Strictures in Crohn's disease (CD) are classically attributed to fibromuscular hypertrophy of the intestinal wall. We have identified and characterized CD-related ileal strictures that result instead from mural constriction (ie, reduced external circumference). Methods: Twenty-four strictures and internal controls from 17 adults with obstructive CD were analyzed by cross-sectional morphometry. Results: The stricture-to-control circumference ratios (CRs) ranged from 0.53 to 1.7. Six strictures with CR ≥1.0, designated hypertrophic, had concentrically thickened walls, mean 3-fold increases in cross-sectional area and stainable fibromucular tissue, and high transmural inflammation scores. In contrast, 18 strictures with CR <1.0, designated constrictive, had thin, pliant walls, cross-sectional areas and stainable fibromuscular tissue comparable with control values, and low transmural inflammation scores. Eight mildly constrictive strictures also showed mild fibromuscular mural expansion that fell short of statistical significance. Twelve of 18 constrictive strictures (67%) occurred multiply (2–4 strictures per specimen) in contrast with hypertrophic strictures, all of which occurred singly (P = .01). Constriction correlated quantitatively with circumferential serosal fat wrapping (P = .003) and was associated with myenteric lymphocytic plexitis (P = .02). Disease duration was shortest among subjects with constrictive strictures and correlated with increasing circumference (CR ≤0.8, 6.3 ± 6.2 years; CR >0.8, 8.7 ± 6.4 years; and CR ≥1.00, 13.7 ± 5.0 years, respectively; P = .03). Conclusions: Constrictive ileal strictures in CD differ pathologically and clinically from hypertrophic strictures, featuring little or no fibromuscular mural expansion, frequent multiplicity, and earlier onset. Mesenteric fat wrapping and myenteric plexitis may contribute to their pathogenesis. Pathologic manifestations of constriction and hypertrophy can coexist, suggesting that stricture heterogeneity may be shaped in part by the dynamics of constrictive and hypertrophic processes.
KW - Contrictive
KW - Crohn's Disease
KW - Strictures
UR - http://www.scopus.com/inward/record.url?scp=85119053935&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2021.08.012
DO - 10.1016/j.cgh.2021.08.012
M3 - Article
C2 - 34400338
AN - SCOPUS:85119053935
SN - 1542-3565
VL - 20
SP - e1292-e1304
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 6
ER -