PD06.10. Distinct GERD-Related Pathophysiological Differences Between Esophageal Adenocarcinoma and Esophageal Squamous Cell Carcinoma Involving the Esophagogastric Junction: A Prospective Study

Abstract

Benign Disease: Gastro-Esophageal Reflux and Hiatal Hernia Gastroesophageal reflux disease (GERD) is a well-established risk factor for esophageal adenocarcinoma (EAC), whereas its role in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aimed to evaluate GERD-related pathophysiological characteristics of EAC and ESCC involving the esophagogastric junction (EGJ) and to investigate their association with reflux parameters. Patients who underwent endoscopic submucosal dissection (ESD) for esophageal cancer involving the EGJ between July 2022 and August 2025 were prospectively enrolled. Preoperative high-resolution manometry (HRM) and multichannel intraluminal impedance–pH monitoring (MII-pH) were performed. Acid-suppressive agents, including proton pump inhibitors and vonoprazan, were discontinued for at least one week prior to testing. Esophageal cancer involving the EGJ was defined as tumors with their center located within 2 cm of the EGJ and extending into the esophagus. GERD symptoms were assessed using the Frequency Scale for the Symptoms of GERD (FSSG). Asymptomatic individuals who underwent the same functional assessments during the same period served as controls. Sixteen patients with esophageal cancer (10 EAC and 6 ESCC) and eight asymptomatic controls were analyzed. Body mass index (BMI) was significantly higher in the EAC group than in controls (p=0.0151). FSSG scores were higher in both cancer groups than in controls. Barrett’s esophagus was more prevalent in EAC (p=0.0010). Acid exposure time (AET) and DeMeester scores were significantly elevated in the EAC group compared with the other groups (p=0.0044 and p=0.0022, respectively), and these differences remained significant after adjustment for BMI. Proximal mean nocturnal baseline impedance (MNBI) was lower in ESCC, and distal MNBI was lower in EAC compared with controls; however, these differences were no longer significant after BMI adjustment. On HRM, integrated relaxation pressure (IRP) and resting lower esophageal sphincter (LES) pressure were lower in EAC than in controls, but these differences disappeared after BMI adjustment. Distal contractile integral (DCI) did not differ among groups. EAC was strongly associated with GERD-related parameters and Barrett’s esophagus, whereas ESCC was characterized by reflux symptoms and impaired proximal mucosal integrity without objective evidence of increased acid exposure. These findings suggest that if GERD contributes to the development of ESCC, mechanisms other than acid reflux may be involved.