Exposed Endoscopic Full Thickness Resection (EFTR) Versus Submucosal Tunnelling Endoscopic Resection (STER) for Small Gastric Gastrointestinal Stromal Tumor (GIST) - an International Double Blinded Randomized Controlled Trial

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumors in the GI tract, often located in the stomach. Based on the latest World Health Organization (WHO) classification, all GISTs are now considered as malignant tumors. Large size overtly aggressive GISTs are relatively rare, occurring only in up to 8 per million population. However, smaller sizes GIST in the stomach are relatively common, and was found in up to 20% of patients based on autopsy series.

Conventionally, localized GISTs are treated by surgical resection. Several guidelines recommended resection of all histologically confirmed GIST, while some suggested surveillance if the lesion is small <2cm in size. The principle of surgery for GIST is for en-bloc margin negative complete resection, while lymph node dissection is not required. As such, laparoscopic resection of gastric GIST has been advocated when technically feasible, demonstrating short term benefits in recovery than open surgery, with similar oncological outcomes.

With the technological advances of endoscopic surgery including endoscopic submucosal dissection (ESD) for early epithelial cancers and per-oral endoscopic myotomy (POEM), there was a rapid expansion in the indication of endoscopic surgery, in particular resection of subepithelial tumors (SET) in the gastrointestinal tract, in which a significant proportion are GISTs. Systematic review revealed a shorter procedure time and improved short-term recovery by endoscopic resection versus laparoscopic resection, without significant difference in complication and survival. With the favourable outcomes consistently reported in the literature regarding endoscopic resection of upper gastrointestinal GISTs, several endoscopy and oncology society guidelines are now recommending endoscopic resection as an option for smaller size GISTs in institutions with expertise on therapeutic endoscopy.

Submucosal tunneling endoscopic resection (STER) was first reported by Xu, et al in 2012. The concept of the procedure is to create a submucosal tunnel away from the tumor that arose from the musclaris propria layer while protecting the mucosa directly overlying the lesion, so that only mucosal closure of the tunnel entrance would be required after resection. The technique was first used on esophageal SET, where majority of them are benign leiomyoma. STER was then subsequently applied to other upper gastrointestinal tract lesions including the stomach. The merit of the technique mainly lies in the simplicity of closure of the mucosal incision, which only requires simple through-the-scope (TTS) clips. A schematic diagram of the STER procedure is shown in Figure 1.

Development of various techniques that allowed secure endoscopic water-tight closure of full thickness wall defect has led to increasing application of endoscopic full thickness resection (EFTR). As opposed to the STER procedure, the tumor would be directly resected without creation of a submucosal tunnel. This would create a full thickness defect that required complete closure to avoid gastrointestinal leakage and peritonitis. Various methods have been reported for closure, ranging from simple TTS clip closure, over-the-scope clip closure, clip endo-loop purse string technique, re-openable clip over-the-line method (ROLM), endoscopic suturing etc. With appropriate selection of closure method based on the morphology of the defect, secure closure could be achieved with minimal post-procedural morbidity.