Controversies in GERD Diagnosis and Management

Daniel Sifrim, MD, PhD, from Barts and the London School of Medicine and Dentistry, and winner of this year’s research mentor award from the Esophageal, Gastric & Duodenal Disorders (EGD) section, clarified the rationale for when to do reflux testing. The purpose of catheter-based and wireless monitoring of esophageal acid exposure is to understand the relationship between reflux episodes and patient-reported symptoms. For patients who have unproven GERD, reflux testing should be performed off medication to establish reflux disease. For those with proven GERD, via previous endoscopy or reflux monitoring, subsequent monitoring should be done on medication (to understand why the patient is not responding to treatment). In addition, pH in the stomach and esophagus should be measured. Wireless pH monitoring is preferred for day-to-day monitoring of reflux that would be missed by 24-hour catheter-based monitoring. Wireless monitoring for 72 hours provided more information than at 48 hours and similar information as 96 hours. Dr. Sifrim recommended consulting the 2023 Lyon Consensus 2.0 framework for the diagnosis of reflux disease for more information.

Walter Wai-Yip Chan, from Brigham and Woman’s Hospital, discussed impedance testing for the evaluation of reflux and the esophageal mucosa. Impedance, the opposition or resistance to an electric current, can be used to measure bolus reflux of liquid or air between sensors along the esophagus. In multichannel intraluminal impedance monitoring, an intraluminal bolus movement of liquid has low impedance/high conductance, and movement of air has high impedance/low conductance. There is a subset of patients with regurgitation-predominant GERD where total reflux episodes can predict response to treatment. A pH-impedance catheter can reveal differences in reflux events along the esophagus; for example, in pharyngeal reflux, the reflux events are not acidic, and distal parameters are normal. Non-acidic reflux events correlate with lung transplant outcomes. Another measure, mean nocturnal baseline impedance (NMBI), differs across erosive reflux disease (ERD), non-erosive reflux disease (NERD), reflux hypersensitivity (RH), functional heartburn (FH), and healthy volunteers and can predict response to treatment. Impedance testing can also provide information about cell-to-cell adhesion within the esophageal mucosa. Impedence performed during endoscopy can provide real-time measures of mucosal integrity and differentiate between GERD and eosinophilic esophagitis (EoE). Visualization tools can also help diagnose extraesophageal reflux (EER). Wireless impedance monitoring is the more cost-effective choice in patients presenting with heartburn and chest pain, whereas catheter-based impedance monitoring is the better choice for regurgitation and behavioral syndromes, such as rumination.

C. Prakash Gyawali, MD, from Washington University School of Medicine, reviewed applications of high-resolution manometry and the functional lumen imaging probe (FLIP) to diagnose GERD and rule out achalasia, hypomotility disorders, and behavioral syndromes in patients with GERD symptoms who are not responding to proton-pump inhibitors (PPIs). Manometry is also useful for identifying morphological changes at the esophogastric junction (EGJ); the straight leg raise maneuver increases intra-abdominal pressure to test EGJ integrity and predict acid exposure to the esophagus. For hypomotility assessment, the contraction reserve is tested after a challenge of multiple rapid swallows. The Milan score is used to predict GERD and treatment response based on EGJ type, esophageal motility, the EGJ contractile integral, and response to the straight-leg maneuver with manometry. Post-prandial belching and rumination can also be seen on high-resolution manometry.

Livia Guadagnoli, PhD, from Northwestern University Feinberg School of Medicine, shifted the discussion to the evaluation and treatment of esophageal hypervigilance in reflux. Hypervigilance starts with the perception of a GI sensation that triggers a threat appraisal. This appraisal is determined by beliefs, expectations, prior experience, and stress. The lack of control can lead to fear and constant monitoring for additional threats, which in turn causes a more intense perception of the GI sensation. Hypervigilance is a normal protection response that has spiraled out of control. The EHAS and EHAS short form are quantitative assessments that can distinguish between hypervigilance and anxiety. Qualitative assessments start with an introduction of the concept of hypervigilance and normalization of the concept as a protective response that has become harmful. The work-up includes questions about frequency of scanning for symptoms, when scanning most often occurs, and whether the concept of hypervigilance is resonating with the patient. Treatment is multifactorial, but strategies should be matched to the patient-specific root causes of the problem; they include hypnotherapy, cognitive behavioral therapy, and repeat exposure with mindfulness to increase tolerance to symptoms and acknowledge them without reacting. Shared decision-making with the patient can help identify what skills would be most helpful to them. Dr. Guadagnoli referenced her review, “The psychobiological model of disorders of gut-brain interaction,” published in Lancet Gastroenterology and Hepatology in 2025, for more information.

In the final presentation, Jose Maria Remes-Troche, of the Instituto de Investigaciones Medico Biologicas, discussed the incorporation of potassium-competitive acid blockers (PCAB) in GERD treatment. Unlike PPIs that irreversibly bind proton pumps, PCABs are reversible competitors. Activity does not rely on food intake, and there is a faster onset than PPIs. Five PCABs are now available, each with a unique structure; only vonoprazan has been FDA-approved. PCABs are superior to PPI for grade C and D ERD, as well as for maintenance therapy for healed esophagitis. They are likely to be superior to PPI in NERD, most trials are placebo controlled. One challenge in NERD is the need for on-demand or intermittent therapy, which is a difficult indication to test in a clinical trial. One small RCT demonstrated equivalence of PCAB and double-dose PPI for refractory GERD, but more evidence is needed. PCAB and PPI appear to have similar efficacy for EER. Well-controlled trials are still needed for PCAB in RH and FH. PCABs are starting to be included as a first-line treatment in guidelines, but their availability is not equal worldwide. The P-CAB test is a one-week, high-dose treatment with tegoprazan, with a threshold of 75% reduction in symptoms for a diagnosis of GERD. Only one study in the UK with vonoprazan evaluated cost savings with PCABs for treatment of severe esophagitis; however, PPIs are lower cost with wider availability, which will likely make them the more cost-effective option for other indications.