Introduction: Although L-menthol spray application on lesions has been shown to be effective for the endoscopic clarification of early gastric cancer (EGC), the currently available data are all based on subjective evaluations. Objectives: This study was aimed to objectively evaluate the effectiveness of L-menthol spray for the endoscopic classification of EGC. Methods: Patients with EGC treated by endoscopic submucosal dissection were included. Images taken by white light imaging (WLI) and narrow band imaging (NBI) before and after spraying L-menthol directly on a lesion were saved. The primary endpoint was a change in the color difference between the EGC lesion and surrounding mucosa (ΔExy) before and after L-menthol spray application. The secondary endpoints were patient factors related to the change in ΔExy after L-menthol spray application and the pathological findings. Results: Fifty cases of EGC were included in the analysis. The median ΔExy was significantly larger after L-menthol spray application than before, as assessed by either WLI (p <0.001) or NBI (p < 0.001). An increased ΔExy after L-menthol spray application was noted in 76 and 92% of patients by WLI and NBI, respectively. The percentage of patients with a ΔExy ≥5 (a level distinguishable by human eyes) was significantly larger after L-menthol spray application either by WLI (p <0.001) or NBI (p < 0.001). Pathologically, mucosal vasodilatation and stromal edema were noted after L-menthol spray application in the evaluated 2 cases. Conclusions: These results objectively demonstrate that L-menthol provides benefits in the endoscopic clarification of EGC.

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