Reply to “The importance of subgrouping refractory NERD patients according to esophageal pH-impedance testing”

Abstract

According to Rome III, evidence of a symptom relationship with reflux events either by subjective outcome from a proton pump inhibitor (PPI) trial or through direct reflux monitoring is sufficient to diagnose gastroesophageal reflux disease (GERD) [1]. Consequently, hypersensitive esophagus (HE) has been considered within the realm of GERD, whereas functional heartburn (FH) has been defined as absence of evidence that reflux is the cause of the symptom [1]. Unsatisfactory response to a PPI trial is then mandatory to define FH, whereas a positive symptom–reflux association at reflux monitoring defines HE, a condition in which a favorable response to PPI trial confirms the diagnosis of GERD [1]. Accordingly, by definition, patients with FH do not respond to PPI therapy and no benefit from antireflux surgery can be predicted in them, whereas many patients with HE respond to PPI therapy [1], to laparoscopic fundoplication [2], or to selective serotonin reuptake inhibitors [3]. The aim of our study [4] was to establish whether patients with refractory GERD (heartburn and/or regurgitation persisting despite high-dose PPI therapy) as diagnosed by on-PPI impedance-pH monitoring can achieve GERD cure by laparoscopic fundoplication, with GERD cure being defined as 3-year postoperative off-PPI normal impedance-pH findings associated with persistent total or subtotal heartburn and/or regurgitation remission. Therefore, patients with FH as defined by PPI refractoriness and negative on-PPI impedance-pH findings were excluded. The greatest merit of the classification of endoscopynegative heartburn patients proposed by Savarino et al. [5– 7] in their off-PPI impedance-pH studies is to highlight the limited sensitivity of pH-only criteria in diagnosing GERD. However, such a classification concerns heartburn only and has not yet been validated in the clinical setting of PPI refractoriness by outcome studies. It is well known that regurgitation is a major determinant of PPI refractoriness [8, 9]. Additionally, a recent study showed that off-PPI impedance-pH findings do not predict response to PPIs in patients with typical reflux symptoms [10]. According to Pandolfino and Vela [11] and also to recent ACG guidelines by Katz et al. [12], patients with PPI-refractory typical reflux syndrome (heartburn and/or regurgitation), given their high probability of having GERD, should be evaluated while they are receiving PPI therapy because this is the only way to establish whether persisting symptoms are due to reflux. Moreover, only on-PPI impedance-pH monitoring before surgery gives the opportunity to establish a cause-and-effect relationship between PPI-refractory symptoms and nonacid reflux. In fact, in our study [4], we showed for the first time that weakly acidic refluxes are the main determinants of PPI refractoriness. Preoperatively, positive symptom/reflux indexes and abnormal reflux parameters were mainly associated with weakly acidic refluxes; at 3-year postoperative follow-up, total or subtotal abolition of weakly acidic refluxes was associated with total or subtotal persistent remission of heartburn and/or regurgitation. Furthermore, at postoperative off-PPI assessment, the percentage of esophageal acid exposure time (%EAET) decreased significantly, despite restored gastric acidity. Thus, by comparing on-PPI preoperative M. Frazzoni (&) L. Frazzoni Fisiopatologia Digestiva, Nuovo Ospedale S. Agostino, Viale Giardini 1355, 41100 Modena, Italy e-mail: marziofrazzoni@gmail.com