Background: Differential diagnosis of superficial duodenal epithelial tumors (SDETs) and non-neoplastic lesions (NNLs) in duodenum by endoscopy is difficult. Here, we attempted to distinguish them by magnified endoscopic examination with image-enhanced endoscopy (IEE-ME). Methods: Various IEE-ME findings of 95 SDETs who underwent endoscopic resection and 58 NNLs who underwent biopsy were retrospectively reviewed. Results: When we compared the IEE-ME findings of SDETs and NNLs, the presence of demarcation line (DL) (97.9% vs. 79.3%, P = 0.0002), white opaque substance (WOS) (84.2% vs. 1.7%, P < 0.0001) and light blue crest (LBC) (93.7% vs. 32.8%, P < 0.0001) and the absence of enlarged marginal epithelium (EME) (98.9% vs. 62.1%, P < 0.0001) were significantly more frequent in SDETs than NNLs. When divided into each superficial structure, it was the most effective to evaluate the combination of WOS and LBC as SDET with open-loop structure (OLS), and the combination of DL and EME as SDET with closed-loop structure (CLS). However, LBC was excluded because of low inter- and intra-observer agreements. Finally, the sensitivity, specificity and accuracy for the diagnosis of SDETs were 88.4%, 98.3% and 92.2%, respectively, and we developed an algorithm for the differential diagnosis of duodenal lesions. Conclusion: We could distinguish SDET from NNL, diagnosed SDET as presence of WOS indicated OLS of superficial structure, and presence of DL and absence of EME indicated CLS of superficial structure.
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