Bowel stiffness associated with histopathologic scoring of stenosis in patients with Crohn's disease.

Intestinal stenosis is a common complication of Crohn's Disease (CD). Stenosis is associated with alteration of bowel mechanical properties. This study aims to quantitate the mechanical properties of the intestinal stenosis and to explore associations between histology and mechanical remodeling at stenotic intestinal sites in CD patients. Intestinal segments from stenotic sites were studied in vitro from 19 CD patients. A luminal catheter with a bag was used to stepwise pressurize the intestinal segments from 0-100 cmH2O with 10 cmH2O increments. B-mode ultrasound images were obtained at the narrowest part of the stenosis at each pressure level and morphometric parameters were obtained from ultrasound images. The mechanical behavior of the stenotic tissue were characterized by using an isotropic three dimensional strain energy function in Demiray model form, the mechanical constants were obtained by fitting the model to the recorded intraluminal pressure and the inner radius of the stenotic segment of the small bowel. Grading scores were used for histological analysis of inflammation, fibrosis, muscular hypertrophy and adipocyte proliferation in the intestinal layers. The collagen area fraction in intestinal layers was also calculated. Associations between histological and the mechanical constants (stiffness) were analyzed. Chronic inflammation was mainly located in mucosa whereas fibrosis was found in submucosa. The mechanical remodeling was performed with changed mechanical constants ranged between 0.35-13.68kPa. The mechanical properties changes were associated mainly with chronic inflammation, fibrosis and combination of inflammation and fibrosis (R>0.69, P<0.001). Furthermore, the mechanical properties correlated with the collagen fraction in submucosa and muscular layers (R>0.53, P<0.05). We quantitated the intestinal stenosis stiffness. Associations were found between bowel mechanical remodeling and histological changes at the stenotic site in CD patients. Although intestinal ultrasonography, CT and MRI can be used to diagnose Crohn's Disease (CD)-associated bowel strictures, these techniques may not have sufficient accuracy and resolution to differentiate predominantly inflammatory strictures from predominantly fibrotic strictures. The present study aims to quantitate the mechanical remodeling of intestinal stenosis and to explore the associations between histological parameters and mechanical properties at the intestinal stenotic sites in CD patients. For the first time, we quantitatively demonstrated that the mechanical properties of the intestinal wall in CD stenosis are associated with the chronic inflammation, fibrosis and collagen fraction in the intestinal layers. The results of this study may facilitate design and development of artificial biomaterials for gastrointestinal organs. The potential clinical implication of this study is that the histological characteristics in patients with CD can be predicted clinically by means of inflammation and fibrosis assessment in conjunction with tissue stiffness measurement.

Zhao J ，Liao D ，Wilkens R ，Krogh K ，Glerup H ，Gregersen H ... -  《-》

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.

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. 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. 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. 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.

Chen W ，Lu C ，Hirota C ，Iacucci M ，Ghosh S ，Gui X ... -  《-》

A novel collagen area fraction index to quantitatively assess bowel fibrosis in patients with Crohn's disease.

Li XH ，Fang ZN ，Guan TM ，Lin JJ ，Sun CH ，Huang SY ，Mao R ，Lu BL ，Cao QH ，Feng ST ，Li ZP ... -  《BMC GASTROENTEROLOGY》

Bowel Thickening in Crohn's Disease: Fibrosis or Inflammation? Diagnostic Ultrasound Imaging Tools.

Coelho R ，Ribeiro H ，Maconi G 《-》

Real-Time Shear Wave Ultrasound Elastography Differentiates Fibrotic from Inflammatory Strictures in Patients with Crohn's Disease.

Chen YJ ，Mao R ，Li XH ，Cao QH ，Chen ZH ，Liu BX ，Chen SL ，Chen BL ，He Y ，Zeng ZR ，Ben-Horin S ，Rimola J ，Rieder F ，Xie XY ，Chen MH ... -  《-》