The mechanism of esophageal stricture after endoscopic resection: Histological and biomechanical evaluation in a canine model

Abstract

Background and study aims: Benign esophageal stricture has major deleterious effects on a patient's quality of life and is often refractory. This study aims were to prepare the animal model and to investigate the mechanism of esophageal stricture in the view point of histological and biomechanical evaluation. Material and method: Nine beagle dogs were enrolled in this study. Under general anesthesia, circumferential endoscopic submucosal dissection was carried out 5 cm length in thoracic esophagus for preparing stricture models. The process of stricture formation was evaluated by the endoscopic observation and histological findings. Immunohistochemical staining was performed for collagen I or collagen III. In the biomechanical evaluation, rectangular-shaped specimens were obtained from the esophageal samples. The failure load and linear stiffness were measured using a tensile tester and compared healed tissue with normal. Results: The dogs developed severe stricture. The macroscopic appearance showed a deep ulcer formation and severe mucosal constriction. No esophageal glands or muscularis mucosae were evident, and instead, they were replaced with condensed granulation tissue that were composed type I and III collagen fibers. The inner circular muscular layer of the muscularis propria showed partial atrophy and fibrosis in the center of the lesion. The failure load and linear stiffness were significantly decreased in the healed tissue. Conclusion:The cause of benign esophageal stricture might have been the biomechanical deterioration that was caused the change of the collagen components in the submucosal layers or atrophic changes of inner circular muscles.

Pirfenidone prevents esophageal stricture by inhibiting nucleotide binding oligomerization domain like receptor protein 3 inflammasome activation

“…In esophageal stricture models of pigs and dogs, uniform ulcers are technically difficult to produce, and it is difficult to obtain sufficient accuracy for molecular studies in addition to various problems caused by the type of animal species. 9,10,34 The alkaline drinking model of rodents is suitable for studying the healing process at the molecular level 16,35 ; however, it is difficult to obtain strictures of the same size, and the influence of the alkali on other organs is a concern because of the characteristics of the procedure. Therefore, we improved the existing esophageal acetic acid-induced ulcer model and established a new rat model that can exhibit not only the healing process of the ulcer but also the condition of the esophageal stricture by adjusting the size of the ulcer.…”

“…Esophageal stricture formation after esophageal endoscopic treatment is a major clinical problem 4–8 ; however, there are a few good animal models to study this phenomenon. In esophageal stricture models of pigs and dogs, uniform ulcers are technically difficult to produce, and it is difficult to obtain sufficient accuracy for molecular studies in addition to various problems caused by the type of animal species 9,10,34 . The alkaline drinking model of rodents is suitable for studying the healing process at the molecular level 16,35 ; however, it is difficult to obtain strictures of the same size, and the influence of the alkali on other organs is a concern because of the characteristics of the procedure.…”

“…Furthermore, PFD has been shown to prevent gastrointestinal stricture formation in esophageal burn models and inflammatory bowel disease models by inhibiting the expression of fibrosis‐related molecules, including TGF‐β1 and collagen I 16,25,26 . The TGF‐β pathway is important in virtually all types of fibrosis, including esophagus fibrosis 9,12 . TGF‐β binds to its cognate cell surface receptors, initiating downstream signaling that ultimately leads to nuclear translocation of the transcriptional modulators Smad2/3 12 .…”

“…Esophageal stricture is caused by the formation of scars associated with esophageal injury and biomechanical deterioration due to excessive fibrosis in the submucosa. [9][10][11] Scar formation is an integral part of wound healing, which starts with inflammation and is followed by cell proliferation and fibrosis. 12 Although a variety of fibrosis-related molecules, including transforming growth factor (TGF)-β and collagens, are upregulated during esophageal ulcer healing, [13][14][15][16][17][18] the regulatory mechanisms and roles of these molecules remain unclear.…”

“…Esophageal stricture is caused by the formation of scars associated with esophageal injury and biomechanical deterioration due to excessive fibrosis in the submucosa 9–11 . Scar formation is an integral part of wound healing, which starts with inflammation and is followed by cell proliferation and fibrosis 12 .…”