Recent developments in the pathophysiology and therapy of gastroesophageal reflux disease and nonerosive reflux...

Gastroesophageal reflux disease is a very common disorder. Proton pump inhibitors are the highly successful mainstay of medical gastroesophageal reflux disease treatment. However, some limitations of proton pump inhibitor therapy continue to drive studies that aim at better understanding and managing manifestations of gastroesophageal reflux disease. This review summarizes recent progress in our understanding of the pathophysiology and treatment of gastroesophageal reflux disease.

Recent studies have demonstrated a potential role of increased gastric acid secretion in gastroesophageal reflux disease, a factor largely neglected during the last decade. Failure to respond adequately to proton pump inhibitor therapy has been attributed to diagnostic inaccuracy, to nocturnal acid breakthrough, to ongoing non-acid reflux and to esophageal hypersensitivity. The relevance of nocturnal acid breakthrough has been recently challenged. Transient lower esophageal sphincter relaxations are a major mechanism of gastroesophageal reflux disease; inhibition of transient lower esophageal sphincter relaxations is a potentially important therapeutic target. Recent studies have focused on GABA receptor stimulation using baclofen or sodium valproate. The role of esophageal body peristalsis in the clearance of reflux events has been questioned. Endoscopic antireflux therapies aim at perendoscopic reinforcement of the antireflux barrier as a novel therapeutic approach to gastroesophageal reflux disease. At present, long-term and controlled data are scarce. Recent observations have challenged the long-term efficacy of surgical antireflux therapy.

Increased understanding of the pathophysiology of gastroesophageal reflux disease may lead to new or improved treatments. Major advances have been made in the role of gastric acid secretion, the control of transient lower esophageal sphincter relaxations and mechanisms underlying esophageal hypersensitivity. Recent studies have highlighted some shortcomings of proton pump inhibitor therapy and of antireflux surgery. Novel approaches are treatments aimed at decreasing transient lower esophageal sphincter relaxations and endoscopic antireflux procedures. Large-scale controlled studies are lacking for both treatments.