The risk factors for lateral margin positivity (LM+) in patients undergoing endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) are not yet well established. The role of subepithelial (SE) spread of cancer in contributing to LM+ remains unclear. 

A study was conducted at a tertiary medical center in Daejeon, South Korea, targeting patients who underwent ESD for EGC between January 2014 and December 2024, those with recorded LM+. Patients who underwent ESD for EGC at the same institution in 2022 and achieved curative resection were selected as the control group.

During the study period, a total of 21 patients were diagnosed with LM+ and 227 patients were enrolled in the control group. In univariate analysis, differentiation, Lauren classification, lesion size, and discoloration changes were identified as risk factors for LM+ (chi-square test, p <0.05). In multivariate analysis, lesion size was the only significant risk factor (logistic regression, p < 0.05). The mean length of SE spread in the LM+ group was significantly longer than that in the control group. Furthermore, SE spread exceeding 5 mm was associated with an increased risk of LM+ (OR=15.077, p=0.019, logistic regression). 

Larger lesion size and longer SE spread were risk factors of LM+. Therefore, these factors should be carefully considered during ESD.