Symptomatic reflux disease: the present, the past and the future.

The worldwide incidence of GORD and its complications is increasing along with the exponentially increasing problem of obesity. Of particular concern is the relationship between central adiposity and GORD complications, including oesophageal adenocarcinoma. Driven by progressive insight into the epidemiology and pathophysiology of GORD, the earlier belief that increased gastroesophageal reflux mainly results from one dominant mechanism has been replaced by acceptance that GORD is multifactorial. Instigating factors, such as obesity, age, genetics, pregnancy and trauma may all contribute to mechanical impairment of the oesophagogastric junction resulting in pathological reflux and accompanying syndromes. Progression of the disease by exacerbating and perpetuating factors such as obesity, neuromuscular dysfunction and oesophageal fibrosis ultimately lead to development of an overt hiatal hernia. The latter is now accepted as a central player, impacting on most mechanisms underlying gastroesophageal reflux (low sphincter pressure, transient lower oesophageal sphincter relaxation, oesophageal clearance and acid pocket position), explaining its association with more severe disease and mucosal damage. Since the introduction of proton pump inhibitors (PPI), clinical management of GORD has markedly changed, shifting the therapeutic challenge from mucosal healing to reduction of PPI-resistant symptoms. In parallel, it became clear that reflux symptoms may result from weakly acidic or non-acid reflux, insight that has triggered the search for new compounds or minimally invasive procedures to reduce all types of reflux. In summary, our view on GORD has evolved enormously compared to that of the past, and without doubt will impact on how to deal with GORD in the future.