New methodsExperimental endoscopyBio-sheet graft therapy for artificial gastric ulcer after endoscopic submucosal dissection: an animal feasibility study

BackgroundVarious bio-sheet grafts have been attempted either to accelerate healing of artificial ulcers or to prevent adverse events after endoscopic submucosal dissection (ESD), but neither prospective nor mechanistic studies were available.ObjectiveTo evaluate the substantial effect of a bio-sheet graft on artificial ulcer healing and its feasibility as an endoscopic treatment modality.DesignPreclinical, in vivo animal experiment and proof-of-concept study.SettingAnimal laboratory.SubjectsThree mini-pigs, Sus scrofa, mean age 14 months.InterventionMultiple ulcers sized 2.5 cm in diameter were generated by ESD in 3 mini-pigs and were assigned randomly into the following 3 groups; control group, bio-sheet group, or combination (bio-sheet plus drug) group. Bio-sheet grafts or bio-sheet plus drug combinations were applied on the artificial ulcers immediately after the ESD.Main Outcome MeasurementsFeasibility and efficacy of endoscopic bio-sheet graft therapy for the management of artificial ulcers and the evaluation of healing conditions based on histology changes in the remaining gastric bed tissues harvested from the stomachs.ResultsThirty-three ESD specimens were obtained. On an image analysis of the ratio of healed area in the remaining gastric bed tissue compared with the matched dissected gastric mucosa, the control group showed the most significant improvement in healing activity among the 3 groups (P < .05), whereas the severity of inflammation in the remaining ulcer tissue was significantly attenuated in bio-sheet and combination groups (P < .05).LimitationsAnimal model.ConclusionAlthough the bio-sheet grafts provided physical protection from gastric acid attack as reflected in the attenuated inflammation on the ulcer beds, unexpected delayed ulcer healing was noted in the bio-sheet graft group because of its physical hindrance of the healing process.