Conclusion
Most patients with refractory reflux symptoms do not have abnormal oesophageal acid exposure. Multiple pathophysiological mechanisms have been proposed to account for the persistent symptoms. To better understand these mechanisms, research comparing data from PPI responders versus PPI non-responders is mandatory ( Box 5 ).
The diagnostic evaluation consists of excluding alternative diagnoses and demonstrates a positive reflux–symptom association during reflux monitoring studies. The current algorithms for reflux–symptom analysis have important shortcomings and there is an urgent need for outcome studies that will help to identify the pretreatment statistical algorithm that best predicts the outcome.
Several new classes of medications are under investigation. They focus on the following targets: further improving suppression of gastric acid secretion, decreasing TLOSR rate, improving oesophago-gastric motility (prokinetics), improving oesophageal mucosal resistance and developing oesophagus-specific pain modulators. Endoscopic treatments can affect distal oesophageal innervations reducing sensitivity (Stretta) and/or reducing reflux volume and proximal extent, both factors being considered critical for persistent reflux perception. Finally, the role of antireflux surgery for patients with incomplete response to PPIs remains controversial. A controlled, randomised study including a significant number of well-selected patients (excluding functional heartburn) with prolonged follow-up to account for placebo effects is mandatory to establish the real efficacy of surgery in these patients.