All M-NBI findings were reviewed retrospectively by two endoscopists board-certified by the Japan Gastroenterological Endoscopy Society (KY and HD, each with at least 10 years’ experience performing upper gastrointestinal magnifying endoscopy) who were blinded to the C-WLI and histological findings, and the absence or presence of biopsy. Five to ten clear M-NBI images obtained at maximal magnification were available per case.

We used the established vessel plus surface (VS) classification system for the M-NBI diagnosis of early gastric cancer 10 11 , which is the most commonly used system in clinical practice 12 13 .

We determined whether there was a demarcation line (DL) between the lesion and the background mucosa. The microvascular (MV) pattern and the microsurface (MS) pattern were categorized as regular/irregular/absent, as follows:

Regular MV pattern: The mucosal capillaries have a uniform shape, and their arrangement and distribution are regular and symmetrical.

Irregular MV pattern: The vessels differ in shape, and their arrangement and distribution are irregular and asymmetrical.

Absent MV pattern: The subepithelial MV pattern is obscured by the presence of a white opaque substance (WOS) 22 .

Regular MS pattern: The morphology of the marginal crypt epithelium (MCE) shows a uniform structure, symmetrical distribution, and regular arrangement. When WOS is present, regular WOS can be an additional marker of a regular microsurface pattern, defined as well-organized and symmetrical distribution of the WOS in a regular reticular/maze-like/speckled pattern.

Irregular MS pattern: The morphology of the MCE shows a heterogeneous morphology, asymmetrical distribution, and irregular arrangement. When WOS is present, irregular WOS is defined as disorganized, with an asymmetrical distribution of the WOS in an irregular reticular/speckled pattern.

Absent MS pattern: No epithelial structures are visible.

Lesions presenting with (1) an irregular MV pattern with a DL and/or (2) an irregular MV pattern with a DL were diagnosed as cancerous; i. e., high-grade adenoma or superficial adenocarcinoma. Lesions presenting with neither finding were diagnosed as non-malignant; i. e., low-grade adenoma.

When individual diagnoses differed among the raters, the final diagnosis of MV pattern and MS pattern was made by consensus.

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