Endoscopic submucosal dissection (ESD) is the standard treatment method for esophageal, gastric, and colorectal cancers. However, it has not been standardized for duodenal lesions because of its high complication rates. Recently, minimally invasive and simple methods such as cold snare polypectomy and underwater endoscopic mucosal resection have been utilized more for superficial nonampullary duodenal epithelial tumors (SNADETs). Although the rate of complications associated with duodenal ESD has been gradually decreasing because of technical advancements, performing ESD for all SNADETs is unnecessary. As such, the appropriate treatment plan for SNADETs should be chosen according to the lesion type, patient condition, and endoscopist’s skill.

Prediction of histology by endoscopic examination is important in the clinical management of non-ampullary duodenal epithelial tumors (NADETs), including adenoma and adenocarcinoma. The use of a simple scoring system based on the findings of white-light endoscopy or magnified endoscopy with narrow-band imaging is useful to differentiate between Vienna category 3 (C3) and C4/5 lesions. Less invasive endoscopic resection procedures, such as cold snare polypectomy, are quick to perform and convenient for small (<10 mm) C3 lesions. Neoplasms with higher grade histology, such as C4/5 lesions, should be treated by endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), or surgery. Although EMR often requires piecemeal resection, the complication rate is acceptable. Excellent complete resection rates could be achieved by ESD; however, it remains a challenging method considering the high risk of complications. Shielding or closure of the ulcer after ESD is effective at decreasing the risk of delayed bleeding and perforation. Laparoscopic endoscopic cooperative surgery is an ideal treatment with a high rate of en bloc resection and a low rate of complications, although it is limited to high-volume centers. Patients with NADETs could benefit from a multidisciplinary approach to stratify the optimal treatment based on endoscopic diagnoses.