Gastrointestinal stromal tumours (GIST) are the most common type of subepithelial lesions (SEL). Current guidelines recommend surgery as the standard treatment for potential resectable tumours. However, with the advancement of third‑space endoscopy, growing evidence supports endoscopic removal of gastric GIST as both effective and safe.

We report two cases of gastric GISTs removed endoscopically with a novel approach which integrates endoscopic submucosal dissection (ESD), full thickness resection (FTR), the clip-line technique and a new mucosal flap closure technique.

The first case involved a 62‑year‑old man with persistent abdominal pain. The second case concerned a 77‑year‑old woman transferred to our unit after multiple admissions in another hospital for recurrent upper gastrointestinal bleeding, requiring repeated transfusions. Both patients were diagnosed by gastroscopy and endoscopic ultrasound with fine‑needle biopsy. Computed tomography was performed to exclude metastasis. The therapeutic options were thoroughly discussed. Endoscopic removal was chosen in both cases—by patient preference in the first case and due to significant cardiopulmonary comorbidities and high surgical risk in the second one. In the first case, endoscopy revealed a 20 mm SEL on the lesser curvature, approximately 1 cm distal to the gastroesophageal junction. In the second case, an approximately 50 mm SEL with an eroded surface was observed at the corpus-fundus junction.

Both therapeutic procedures were performed under general anaesthesia with orotracheal intubation. In both cases, marking and incision were performed with an ESD hybrid knife, followed by application of the clip‑line technique to lift the submucosa. Layer‑by‑layer dissection was performed and coagulation with bipolar forceps due to marked vascularization had to be used. Because both lesions were adherent to the muscularis propria, FTR was carried out. Following these steps, complete en bloc removal of the lesions was achieved. A new mucosal flap closure technique – adjustment and repositioning of the mucosal flap and the subsequent placement of multiple clips - was then used to close the defects. Macroscopically, in sano resection was achieved in both cases. However, due to enucleation, R0 status could not be definitively assessed in the first case, whereas histology of the second confirmed tumour‑free circumferential margins. In both cases, second‑look gastroscopies confirmed intact resection sites with clips in situ. Prophylactic antibiotics were administered and the post‑interventional course was uneventful.

In conclusion, these two cases show that gastric GISTs, including larger lesions, can be safely and effectively treated using this novel endoscopic approach combining ESD, the clip-line technique with FTR and mucosal flap closure.