Safety and Efficacy of Underwater Endoscopic Mucosal Resection for Type I Gastric Neuroendocrine Tumors Measuring 5-9 mm

Study design This is a prospective, single-centre, single-arm cohort study evaluating UEMR for type I gastric NETs. Outcomes will be assessed at the lesion level, with statistical methods accounting for clustering of multiple lesions within individual patients.

Study population Inclusion criteria Patient-level

1. Age ≥18 years 2. Fit for endoscopic therapy and sedation 3. Written informed consent Lesion-level

3.Endoscopically visible gastric neuroendocrine tumor 4.Size 5-9 mm (endoscopic estimation) 5.Clinical and/or histologic features consistent with type I gastric NET 6.No endoscopic features suggestive of deep invasion 7.Technically amenable to snare resection Exclusion criteria

Lesion-level

1. Lesions \<5 mm (managed with surveillance in routine practice) 2. Lesions ≥10 mm 3. Type II or type III gastric NET 4. Evidence of muscularis propria invasion on EUS 5. Distant metastasis or nodal disease on DOTANOC PET-CT 6. Prior attempted resection at the same site with significant fibrosis 7. Non-lifting lesion due to scarring

Patient-level

1. Uncorrectable coagulopathy 2. Inability to manage antithrombotic therapy as per guidelines 3. Pregnancy 4. Inability to provide informed consent

Pre-procedure evaluation

1. Detailed clinical assessment and laboratory work-up as per institutional protocol 2. Endoscopic documentation of: 3. Lesion size, location, morphology 4. Number of lesions 5. Background mucosal atrophy 6. EUS performed for lesions ≥8 mm, atypical morphology, or suspected deeper invasion 7. DOTANOC PET-CT performed where clinically indicated to exclude metastatic disease

Intervention: Underwater EMR technique

1. Standard diagnostic gastroscope 2. Minimal insufflation followed by complete deflation of the gastric lumen 3. Lumen filled with normal saline to achieve complete submersion of the lesion 4. Optional marking for flat or ill-defined lesions 5. Snare capture with a 1-2 mm margin under water 6. Resection using standardized electrosurgical settings 7. Defect management (clips or coagulation) at endoscopist discretion 8. Retrieval of intact specimen 9. Specimen orientation and pinning on cork for histopathologic assessment

Histopathologic assessment:

All specimens will be evaluated by experienced gastrointestinal pathologists.

Reported parameters:

1. Tumor size 2. Tumor grade and Ki-67 index 3. Depth of invasion 4. Lateral and vertical margins 5. Lymphovascular invasion 6. Resection status classified as: 7. R0: negative lateral and vertical margins 8. R1: microscopic margin positivity 9. Rx: indeterminate margins

Outcome measures Primary outcome

1. R0 resection rate per lesion Secondary outcomes 2. En bloc resection rate 3. Immediate bleeding (requiring endoscopic hemostasis) 4. Delayed bleeding (within 14 days requiring medical attention) 5. Perforation 6. Procedure time (scope insertion to removal) 7. Residual disease at scar on surveillance endoscopy (3-6 months) 8. Metachronous lesions during follow-up

Follow-up protocol

1. Clinical follow-up at 24-72 hours and at 14 days 2. Surveillance endoscopy at 3-6 months post-resection 3. Further surveillance as per institutional protocol for type I gastric NETs

• Immediate and delayed adverse events [Time frame: 24 hours]
• Procedure time [Time frame: 30 minutes]
• Histologic quality of resection (deep and lateral margins) [Time frame: 5 days]