Acid reflux episodes, volume, and acid clearance are important factors in the pathogenesis of reflux-induced lesions. Nonacid reflux contributes less to esophageal mucosa damage, but is involved in the development of reflux symptoms in both NERD and EE patients.

Introduction: The introduction of proton pump inhibitors (PPIs) into clinical practice has greatly improved our therapeutic approach to acid-related diseases for their efficacy and safety. Areas Covered:The following evidence-based indications for PPI use are acknowledged by many scientific societies : treatment of the various forms and A c c e p t e d M a n u s c r i p t 2 complications of gastroesophageal reflux disease, eradication of H. pylori infection in combination with two or more antibiotics, short-and long-term therapy of H. pylori-negative peptic ulcers, healing and prevention of NSAID/COXIB-associated gastric ulcers, co-therapy with endoscopic procedures to control upper digestive bleeding and medical treatment of Zollinger Ellison syndrome. Expert Commentary:Despite the above well defined indications, however, the use of PPIs continues to grow every year in both western and eastern countries and the endless expansion of PPI market has created important problems for many regulatory authorities for two relevant features : the progressive increase of the costs of therapy and the greater potential harms for the patients. The major reasons for the misuse of PPIs are the prevention of gastro-duodenal ulcers in patients without risk factors and the stress ulcer prophylaxis in nonintensive care units, steroid therapy alone, anti-platelet or anti-coagulant treatment in patients without risk of gastric injury and the overtreatment of functional dyspepsia.

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A defective EGJ-CI at HRM is clearly associated with evidence of GERD at impedance-pH monitoring. Evaluating EGJ-CI may be useful to predict an abnormal impedance-pH testing.

The administration of ADA after intestinal resective surgery was greatly effective in preventing endoscopic and clinical recurrence of CD. Further larger studies are necessary to confirm the therapeutic advantage and to show the economic implications of biologic therapy in this field.