Abstract
BACKGROUND: Endoscopic submucosal dissection is the standard treatment for superficial esophageal squamous cell carcinoma. However, esophageal preservation following this procedure increases the risk of metachronous multiple cancers. Lugol-voiding lesion grade and alcohol-related genetic polymorphisms have been identified as risk factors, but the role of nonspecific mediastinal lymphadenopathy remains unclear. METHODS: We retrospectively analyzed the data of 154 patients who underwent curative endoscopic submucosal dissection for esophageal squamous cell carcinoma at Hamamatsu University Hospital between 2015 and 2024. Pretreatment computed tomography was used to evaluate the Lugol-voiding lesion grade and nonspecific mediastinal lymphadenopathy. Associations with pathological findings and the development of metachronous multiple esophageal squamous cell carcinoma were assessed using Kaplan-Meier and Cox regression analyses. RESULTS: Nonspecific mediastinal lymphadenopathy was identified in 68 patients (59.6%). Pathological analysis including 154 patients revealed that nonspecific mediastinal lymphadenopathy was significantly associated with lymphovascular invasion (P = 0.026) but not with invasion depth or curative resection. During follow-up and metachronous analysis including 114 patients, 21 patients developed metachronous multiple esophageal squamous cell carcinoma. Both Lugol-voiding lesion grade and nonspecific mediastinal lymphadenopathy were independent predictors of recurrence. Subgroup analysis restricted to Lugol-voiding lesion grade B/C cases confirmed that nonspecific mediastinal lymphadenopathy remained predictive of recurrence-free survival (P = 0.007). CONCLUSIONS: Nonspecific mediastinal lymphadenopathy independently predicts the development of metachronous esophageal squamous cell carcinoma after endoscopic submucosal dissection. Evaluation of nonspecific mediastinal lymphadenopathy in combination with Lugol-voiding lesion grade may improve risk stratification and optimize surveillance strategies.