# Risk Factors for Lateral Margin Positivity Following Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer

## TL;DR

This study finds that extensive subepithelial spread of cancer cells increases the risk of incomplete removal during endoscopic treatment for early gastric cancer.

## Contribution

The study identifies subepithelial spread of 5 mm or more as a strong predictor of lateral margin positivity in early gastric cancer endoscopic resection.

## Key findings

- Lesion size ≥ 2 cm was the only independent predictor of lateral margin positivity.
- Subepithelial spread ≥ 5 mm significantly increased the risk of lateral margin positivity (OR 15.077).
- Wider resection margins may be needed for lesions with extensive subepithelial spread.

## Abstract

Endoscopic submucosal dissection is a standard treatment for early gastric cancer, but lateral margin positivity remains a clinically important issue because it may lead to residual disease and additional treatment. One proposed mechanism is subepithelial spread of cancer cells beneath normal-appearing mucosa, which can obscure the true tumor boundary during endoscopic resection. In this study, we evaluated clinicopathologic and endoscopic factors associated with lateral margin positivity and focused on the extent of subepithelial spread. Although the mere presence of subepithelial spread was not significantly associated with lateral margin positivity, a greater extent of spread was strongly correlated with positive lateral margins. In particular, subepithelial spread measuring five millimeters or more was associated with a markedly increased likelihood of lateral margin positivity. These findings suggest that lateral margin positivity cannot be explained solely by technical or operator-related factors and that intrinsic tumor growth patterns play an important role. Awareness of extensive subepithelial spread may help endoscopists consider wider resection margins in selected lesions and potentially reduce incomplete lateral resection during endoscopic treatment of early gastric cancer.

Background: Lateral margin positivity (LM+) after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) may lead to residual disease and additional treatment. Subepithelial (SE) spread beneath normal mucosa has been suggested as a mechanism, but its association with LM+ is unclear. Methods: We retrospectively reviewed patients who underwent ESD for EGC from 2011 to 2021. Twenty-one LM+ cases were identified, and 227 LM– controls treated in 2019 were selected. Clinicopathologic and endoscopic factors were compared, and multivariate logistic regression was used to identify predictors. SE spread extent was evaluated pathologically. Results: Differentiation, Lauren classification, lesion size, and endoscopic color change were associated with LM+ in univariate analysis. Lesion size ≥ 2 cm was the only independent predictor. SE spread length was greater in LM+ cases than controls (5.80 ± 1.30 mm vs. 2.60 ± 2.36 mm, p = 0.004). SE spread ≥ 5 mm significantly increased the risk of LM+ (OR 15.077, 95% CI 1.550–146.670). Conclusions: SE spread—particularly when ≥5 mm—may contribute to LM+ by obscuring the true tumor boundary. Wider marking and resection margins may be considered in lesions with features suggesting SE spread.