title: The two sides of the coin: Similarities and differences in the pathomechanisms of fistulas and stricture formations in irritable bowel disease.
abstract: Fistulas and fibrosis or strictures represent frequent complications in irritable bowel disease (IBD) patients. To date, treatment options for fistulas are limited and surgery is often required. Similarly, no preventive treatment for fibrosis and stricture formation has been established. Frequently, stricture formation and fibrosis precede fistula formation, indicating that both processes may be connected or interrelated. Knowledge about the pathology of both processes is limited. A crucial role for the epithelial-to-mesenchymal transition (EMT) in fistula development has been demonstrated. Of note, EMT also plays a major role in the pathogenesis of fibrosis in many organs, and most likely also plays that role in the intestine. In addition, aberrant matrix remodeling, as well as soluble factors such as tumor necrosis factor (TNF), interleukin 13 (IL-13) and tumor growth factor beta (TGFβ) were involved, both in the onset of the fistula and fibrosis formation. Both fistulas and fibrosis may occur due to deregulated wound healing mechanisms from chronic and severe intestinal inflammation; however, further research is required to obtain a better understanding of the complex pathophysiology of fistula and intestinal fibrosis formation, to allow the development of new and more effective preventive treatment options for those important disease complications.
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Scharl
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Ramona S
authors.initials: RS
authors.lastname: Bruckner
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
keywords: Epithelial-mesenchymal transition; fibrosis; fistula; interleukin 13; irritable bowel disease; metalloproteinase; tumor growth factor beta; wound healing