Proton pump inhibitor responders who are not confirmed as GERD patients with impedance and pH monitoring: who are they? N. DE BORTOLI ,* I. MARTINUCCI ,* E. SAVARINO, † M. BELLINI ,* A. J. BREDENOORD, ‡ R. FRANCHI ,* L. BERTANI ,* M. FURNARI , § V. SAVARINO, § C. BLANDIZZI ¶ & S. MARCHI * *Division of Gastroenterology, University of Pisa, Pisa, Italy †Division of Gastroenterology, University of Padua, Padua, Italy ‡Department of Gastroenterology, Academic Medical Centre Amsterdam, University of Amsterdam, Amsterdam, The Netherlands §Division of Gastroenterology, Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy ¶Division of Pharmacology and Chemotherapy, Department of Internal Medicine, University of Pisa, Pisa, Italy Key Messages • Our study shows that in a substantial subgroup of PPI responders with typical reflux symptoms the diagnosis of GERD cannot be confirmed with MII-pH monitoring. Accordingly, antireflux surgery should always be preceded by reflux monitoring. • We aimed to evaluate patients with reflux symptoms and a negative endoscopy, who well respond to PPIs with MII-pH. • Patients with GERD symptoms and negative endoscopy undertook single standard dose PPI therapy for 8 weeks and then underwent MII-pH monitoring off-therapy. • Twenty eight out of 144 patients, who well respond to PPI therapy, showed negative AET, normal number of refluxes and lack of correlation between symptoms and reflux events. Abstract Background A short-course of proton pump inhibitors (PPIs) is often used to confirm gastroesophageal reflux disease (GERD). However, some patients with PPI responsive heartburn do not seem to have evidence of GERD on impedance-pH monitoring (MII-pH). The aim of the study was to evaluate patients with reflux symptoms and a negative endoscopy, who well respond to PPIs with MII-pH. Methods We enrolled 312 patients with GERD symptoms and negative endoscopy: 144 reported well-controlled symptoms after 8-week PPIs and 155 were non-responders. Symptom relief was evaluated with GERD Impact Scale and visual analog scale score. All patients underwent MII-pH off-therapy. Thirteen patients were excluded from analysis. Patients were grouped as follows: non-erosive reflux disease (NERD; increased acid exposure time, AET); hypersensitive esophagus (HE; normal AET, positive symptom association, SI/ SAP); MII-pH-/PPI+ (normal AET, negative SI/SAP) in the responder group; MII-pH-/PPI- in non-responders. Key Results MII-pH in PPI responders (symptom relief during PPI therapy > 75%) showed: 79/144 NERD (54.9%); 37/144 HE (25.7%); 28/144 MII-pH-/PPI+ (19.4%). MII-pH-/PPI+ patients reported the same symptom relief when compared with NERD and HE. In non-responder (symptom relief during PPI therapy < 50%) group, 27/155 patients were NERD (17.4%); 53/ 155 were HE (34.2%); 75/155 were MII-pH-/PPI- (48.4%). NERD diagnosis was significantly higher in responder group (p < 0.01). Conclusions & Inferences In a substantial subgroup of patients responding to PPI with typical reflux symptoms, the diagnosis of GERD Address for Correspondence Nicola de Bortoli, Gastroenterology Unit, University of Pisa, Cisanello Hospital, Via Paradisa 2, Pisa 56124, Italy. Tel: +39 050 997398; fax: +39 050 997398; e-mail: nick.debortoli@gmail.com Received: 24 April 2013 Accepted for publication: 31 July 2013 © 2013 John Wiley & Sons Ltd 28 Neurogastroenterol Motil (2014) 26, 28–35 doi: 10.1111/nmo.12221 Neurogastroenterology & Motility