Different healing process of esophageal large mucosal defects by endoscopic mucosal dissection between with and without steroid injection in an animal model

Abstract

BackgroundStricture formation is one of the major complications after endoscopic removal of large superficial squamous cell neoplasms of the esophagus, and local steroid injections have been adopted to prevent it. However, fundamental pathological alterations related to them have not been well analyzed so far. The aim of this study was to analyze the time course of the healing process of esophageal large mucosal defects resulting in stricture formation and its modification by local steroid injection, using an animal model.MethodsEsophageal circumferential mucosal defects were created by endoscopic mucosal dissection (ESD) for four pigs. One pig was sacrificed five minutes after the ESD, and other two pigs were followed-up on endoscopy and sacrificed at the time of one week and three weeks after the ESD, respectively. The remaining one pig was followed-up on endoscopy with five times of local steroid injection and sacrificed at the time of eight weeks after the ESD. The esophageal tissues of all pigs were subjected to pathological analyses.ResultsFor the pigs without steroid injection, the esophageal stricture was completed around three weeks after the ESD on both endoscopy and esophagography. Histopathological examination of the esophageal tissues revealed that spindle-shaped α-smooth muscle actin (SMA)-positive myofibroblasts arranged in a parallel fashion and extending horizontally were identified at the ulcer bed one week after the ESD, and increased contributing to formation of the stenotic luminal ridge covered with the regenerated epithelium three weeks after the ESD. The proper muscle layer of the stricture site was thinned with some myocytes which seemingly showed transition to the myofibroblast layer. By contrast, for the pig with steroid injection, esophageal stricture formation was not evident with limited appearance of the spindle-shaped myofibroblasts, instead, appearance of stellate or polygocal SMA-positive stromal cells arranged haphazardly in the persistent granulation tissue of the ulcer site.ConclusionsProliferation of spindle-shaped myofibroblasts arranged in a parallel fashion is likely to play an important role in stricture formation after circumferential mucosal defects by esophageal ESD, which may be related to the thinning of the proper muscle layer in the healing course of the defects. Local steroid injection seems to be effective to prevent the stricture through the modification of this process.

Systematic review: the prevention of oesophageal stricture after endoscopic resection

“…have administered triamcinolone not in the muscularis propria, but in the remaining submucosal tissue after partial EMR in dogs: the study was not designed to assess the stricture rate, but the authors showed that steroid injection deepened the oesophageal ulcers and delayed epithelialisation . This last finding was also supported by another recent animal study …”

“…Figure shows what remains of the oesophageal wall after EMR and the two main modes of wound healing. Most of our understanding of oesophageal healing and stricture formation derives from the application of general paradigms of scar tissue formation in the animal oesophagus, or in other human organs, such as the stomach or skin . The first step is an epithelial injury, leading to a loss of the barrier function of the epithelium, and the exposure of the submucosal space to several kinds of insults: mechanical through food boluses, chemical through acid or bile reflux and microbial due to the oesophageal bacterial and fungal flora.…”

The microscopic anatomy of the esophagus including the individual layers, specialized tissues, and unique components and their responses to injury

“…In the next 2 weeks, inflammation decreases and angiogenesis increases. By around 28 days after the procedure, in addition to dense fibrosis in the SM, the muscle layer also shows significant atrophy and fibrosis, which further reduces contractibility and flexibility of the esophageal wall …”

Efficacy and safety of steroid in the prevention of esophageal stricture after endoscopic submucosal dissection: A network meta‐analysis

“…Therefore, effective, simple, and safe preventions are urgently needed. The pathophysiology of stricture may involve inflammation, collagen synthesis, and the formation of fibrous in the process of postoperative mucosal healing and the scarring of the tissues …”