Symptom-reflux Association Research Articles

Rumination Syndrome in Children Presenting With Refractory Gastroesophageal Reflux Symptoms.

Up to 40% of children presenting with reflux symptoms do not respond to standard medical interventions. In adults, 20% of patients presenting with Proton Pump Inhibitors refractory Gastro-Esophageal Reflux Disease (GERD) have rumination syndrome. The management of GERD and rumination differ significantly. Our study aimed to identify rumination syndrome amongst children presenting with persistent GERD symptoms based on a distinct pattern on impedance-pH monitoring. The parameters of impedance-pH monitoring were compared between children with rumination syndrome (n = 12), diagnosed on high-resolution manometry impedance (HRM/Z), children with GERD (n = 18), children with an alternative diagnosis (non-GERD, n = 12) and children negative for rumination based on HRM/Z (n = 14). The parameters that distinguish the rumination group were identified and incorporated into a scoring system, which was blindly applied on a separate group of children with refractory GERD (n = 18) to define its sensitivity and specificity. Rumination syndrome presents in 44% of children with refractory GERD. Children with rumination syndrome present with a large number of proximal reflux episodes (>57.5 episodes/24 hours); a high frequency of nonacid reflux events in the postprandial period (>2/hour); and a highly positive symptom-reflux association analysis (SAP ≥ 95%). A score of ≥2 out of the 3 points distinguishes children with rumination syndrome with 75% sensitivity and 80% specificity. Children with rumination syndrome have a distinct pattern of impedance-pH monitoring and can be distinguished amongst children presenting with refractory GERD. Applying a simple scoring system during impedance-pH analysis could lead to early diagnosis of children with rumination syndrome.

AGA Clinical Practice Update on Functional Heartburn: Expert Review

BEST PRACTICE ADVICE 1: A diagnosis of functional heartburn should be considered when retrosternal burning pain or discomfort persists despite maximal (double-dose) proton pump inhibitor (PPI) therapy taken appropriately before meals during a 3-month period. BEST PRACTICE ADVICE 2: A diagnosis of functional heartburn requires upper endoscopy with esophageal biopsies to rule out anatomic and mucosal abnormalities, esophageal high-resolution manometry to rule out major motor disorders, and pH monitoring off PPI therapy (or pH-impedance monitoring on therapy in patients with proven gastroesophageal reflux disease [GERD]), to document physiologic levels of esophageal acid exposure in the distal esophagus with absence of reflux-symptom association (ie, negative symptom index and symptom association probability). BEST PRACTICE ADVICE 3: Overlap of functional heartburn with proven GERD is diagnosed according to Rome IV criteria when heartburn persists despite maximal PPI therapy in patients with history of proven GERD (ie, positive pH study, erosive esophagitis, Barrett's esophagus, or esophageal ulcer), and pH impedance testing on PPI therapy demonstrates physiologic acid exposure without reflux-symptom association (ie, negative symptom index and symptom association probability). BEST PRACTICE ADVICE 4: PPIs have no therapeutic value in functional heartburn, the exception being proven GERD that overlaps with functional heartburn. BEST PRACTICE ADVICE 5: Neuromodulators, including tricyclic antidepressants, selective serotonin reuptake inhibitors, tegaserod, and histamine-2 receptor antagonists have benefit as either primary therapy in functional heartburn or as add-on therapy in functional heartburn that overlaps with proven GERD. BEST PRACTICE ADVICE 6: Based on available evidence, acupuncture and hypnotherapy may have benefit as monotherapy in functional heartburn, or as adjunctive therapy combined with other therapeutic modalities. BEST PRACTICE ADVICE 7: Based on available evidence, anti-reflux surgery and endoscopic GERD treatment modalities have no therapeutic benefit in functional heartburn and should not be recommended.

Pharyngeal acid load and different functional endoscopy findings

The findings of functional endoscopy (upper esophageal sphincter insufficiency, cardia insufficiency, esophagitis, gastric heterotopia, axial sliding hernia, and visible aerosols) can be traced back to pharyngeal acid exposure by oropharyngeal pH measurement. Significantly increased pharyngeal acid loads are seen in gastric heterotopy and axial sliding hernia. For all measured statistics, the pharyngeal acid load is in the pathological or even very pathological range. The value of functional endoscopy in the context of laryngopharyngeal reflux diagnosis is clearly documented. The findings "heterotopic gastric mucosa" and "axial sliding hernia" may cause marked airway symptoms and apathogenetic relationship with otorhinolaryngologic reflux-associated symptoms must be postulated for these entities.

Esophageal mucosal innervation in functional heartburn: Closer to healthy asymptomatic subjects than to non-erosive reflux disease patients.

Mucosal innervation in non-erosive reflux disease (NERD; pathological esophageal acid exposure, normal macroscopic mucosa) is clearly distinct from that of healthy volunteers (HV) and from patients with esophagitis or Barrett's esophagus: The nerves in NERD are situated much closer to the luminal surface of the mucosa. Patients with functional heartburn (FH) have a similar symptom profile to patients with NERD and indistinguishable macroscopic appearances. However, they have physiological acid exposure and no reflux-symptom association. The aim of our study was to delineate the position of esophageal mucosal nerve fibers in patients with FH and compare it with that in NERD and HV. Distal esophageal biopsies from patients with FH were immunohistochemically stained for CGRP. CGRP-positive nerve fibers were identified, and their position relative to the lumen was determined. These results were compared to our previously published cohort of HV and NERD. Eleven patients were included in the FH group with a mean age of 46years (range 33-69); 7F:4M. Nine patients had visible nerve fibers. The location of the afferent nerve fibers in the distal esophageal mucosa (median of 22, range 10.4-28) was similar to the HV group (median 25.5) and significantly deeper than the superficial nerves seen in NERD (median 9.5). The mucosal innervation pattern in FH is more alike that of healthy individuals than that of NERD, with afferent nerves lying deep in the mucosa, away from the luminal surface. This supports the theory that heartburn in FH has a distinct nociceptive pathophysiology.

Clinical Impact of Increasing the Threshold for Distal Esophageal Acid Exposure Time (AET)

Introduction: A wireless pH capsule study with a composite score is a reliable method to quantify acid exposure in the distal esophagus. The optimal cut-off value for pathological acid exposure time is not standardized and ranges from 4.4% - 5.8% in different studies. We evaluated the reflux burden and symptom association of patients when the threshold for acid exposure time (AET) is varied from 4% to 6%. Methods: All 96-hour wireless pH capsule studies in our urban, academic gastroenterology practice between January 2016 and December 2017 were analyzed using AET greater than 4%, 5%, and 6% as the threshold for abnormal acid reflux to evaluate the differential yield of pathologic acid exposure with these alternative thresholds. All antacids or acid suppression medications were held for at least 7 days prior to the examinations. Results: A total of 257 consecutive patients (94 male, mean age 52.6 years (19-84 years) were included for analysis. Using the 4%, 5%, and 6% threshold values for overall AET; 19.8% (51), 27.6% (71), and 33% (85) patients did not have evidence of abnormal acid reflux respectively, over a 96-hour period. The evaluation of the 34 patients who were “missed” by increasing the AET from 4% to 6% showed: Median symptom association probability (SAP) for heartburn and regurgitation was 98.6 (IQR 84.3) and 72.4 (IQR 97.3), respectively. The median symptom index (SI) for heartburn and regurgitation was 26.8 (IQR 37) and 12.3 (IQR 25.7) respectively and the mean DeMeester score was 19.5 (range: 12.9 - 27). At 5% threshold value (14 out of 34 missed patients), SAP was positive (>95%) in 8 and 4 patients for heartburn and regurgitation respectively. The SI was positive (>50%) in 1 patient for heartburn and none for regurgitation. At 4% threshold value for AET (20 out of 34 missed patients), SAP was positive in 12 and 5 patients for heartburn and regurgitation respectively. The SI was positive in 3 patients for heartburn and 3 patients regurgitation. Conclusion: Increasing the percent AET from 4% to 6% reduces the identification of pathologic acid reflux by 14%. Using 6% as the AET threshold primarily reduces the identification of positive SAP and SI for heartburn and regurgitation symptoms to acid reflux. Patients in this group may represent a subgroup of reflux patients that specific targeted therapies may improve therapeutic outcomes and warrants further study.

The role of esophageal pH-impedance testing in clinical practice.

Ambulatory reflux monitoring is typically performed when esophageal symptoms do not respond to usual antireflux medications, or prior to invasive antireflux therapy. Although pH-based metrics have been the standard in defining esophageal reflux burden, novel impedance parameters have been introduced in recent years that can either be extracted from pH-impedance monitoring or obtained directly from esophageal mucosa. This review evaluates the clinical role of esophageal pH-impedance monitoring in clinical practice in the present day. Elevated acid exposure time in the distal esophagus remains the primary metric that predicts symptom improvement from antireflux therapy. Although conventional impedance-based metrics (numbers of reflux episodes, reflux-symptom association) provide complementary evidence, novel impedance-based metrics show promise in documenting reflux-induced damage to esophageal mucosal integrity, and in potentially predicting treatment outcome. The postreflux swallow-induced peristaltic wave measures integrity of primary peristalsis triggered by a reflux episode. Baseline impedance values reflect histopathological damage to mucosal integrity, and improve following successful antireflux therapy. Mucosal impedance assessed at endoscopy is a new diagnostic tool that is currently being evaluated in multinational research studies. Esophageal pH-impedance monitoring has potential to augment confidence in a reflux diagnosis beyond that provided by pH-monitoring alone.

Nonerosive reflux disease: clinical concepts.

Esophageal symptoms can arise from gastroesophageal reflux disease (GERD) as well as other mucosal and motor processes, structural disease, and functional esophageal syndromes. GERD is the most common esophageal disorder, but diagnosis may not be straightforward when symptoms persist despite empiric acid suppressive therapy and when mucosal erosions are not seen on endoscopy (as for nonerosive reflux disease, NERD). Esophageal physiological tests (ambulatory pH or pH-impedance monitoring and manometry) can be of value in defining abnormal reflux burden and reflux-symptom association. NERD diagnosed on the basis of abnormal reflux burden on ambulatory reflux monitoring is associated with similar symptom response from antireflux therapy for erosive esophagitis. Acid suppression is the mainstay of therapy, and antireflux surgery has a definitive role in the management of persisting symptoms attributed to NERD, especially when the esophagogastric junction is compromised. Adjunctive approaches and complementary therapy may be of additional value in management. In this review, we describe the evaluation, diagnosis, differential diagnosis, and management of NERD.

Management options for patients with GERD and persistent symptoms on proton pump inhibitors: recommendations from an expert panel.

The aim of this study was to assess expert gastroenterologists' opinion on treatment for distinct gastroesophageal reflux disease (GERD) profiles characterized by proton pump inhibitor (PPI) unresponsive symptoms. Fourteen esophagologists applied the RAND/UCLA Appropriateness Method to hypothetical scenarios with previously demonstrated GERD (positive pH-metry or endoscopy) and persistent symptoms despite double-dose PPI therapy undergoing pH-impedance monitoring on therapy. A priori thresholds included: esophageal acid exposure (EAE) time >6.0%; symptom-reflux association: symptom index >50% and symptom association probability >95%; >80 reflux events; large hiatal hernia: >3 cm. Primary outcomes were appropriateness of four invasive procedures (laparoscopic fundoplication, magnetic sphincter augmentation, transoral incisionless fundoplication, radiofrequency energy delivery) and preference for pharmacologic/behavioral therapy. Laparoscopic fundoplication was deemed appropriate for elevated EAE, and moderately appropriate for positive symptom-reflux association for regurgitation and a large hiatal hernia with normal EAE. Magnetic sphincter augmentation was deemed moderately appropriate for elevated EAE without a large hiatal hernia. Transoral incisionless fundoplication and radiofrequency energy delivery were not judged appropriate in any scenario. Preference for non-invasive options was as follows: H2RA for elevated EAE, transient lower esophageal sphincter relaxation inhibitors for elevated reflux episodes, and neuromodulation/behavioral therapy for positive symptom-reflux association. For treatment of PPI unresponsive symptoms in proven GERD, expert esophagologists recommend invasive therapy only in the presence of abnormal reflux burden, with or without hiatal hernia, or regurgitation with positive symptom-reflux association and a large hiatus hernia. Non-invasive pharmacologic or behavioral therapies are preferred for all other scenarios.

A modified Nissen fundoplication: subjective and objective midterm results.

The failure rate of laparoscopic anti-reflux surgery is approximately 10-20%. The aim of our prospective study was to investigate whether a modified Nissen fundoplication (MNF) can improve reflux symptoms and prevent surgical treatment failure in the midterm. The MNF consisted of (1) suturing the esophagus to the diaphragmatic crura on each side using four non-absorbable stitches, (2) reinforcing clearly weak crura with a tailored Ultrapro mesh, and (3) fixing the upper stitch of the valve to the diaphragm. Forty-eight consecutive patients experiencing typical gastroesophageal reflux disease (GERD) symptoms at least three times per week for 6months or longer were assessed before and after surgery using validated symptom and quality of life (GERD-HRQL) questionnaires, high-resolution manometry, 24-h impedance-pH monitoring, endoscopy, and barium swallow. Mortality and perioperative complications were nil. At median follow-up of 46.7months, the patients experienced significant improvements in symptom and GERD-HRQL scores. One patient presented with severe dyspepsia and another complained of dysphagia requiring a repeat surgery 12months after the first operation. Esophageal acid exposure (8.8 vs 0.1; p < 0.0001), reflux number (62 vs 8.5; p < 0.0001), and symptom-reflux association (19 vs 0; p < 0.0001) significantly decreased postoperatively. The median esophagogastric junction contractile integral (EGJ-CI) from 31 cases (8.2 vs 21.2mmHgcm; p = 0.0003) and the abdominal length of the lower esophageal sphincter (LES) (0 vs 16mm; p = 0.01) increased postoperatively. Our data demonstrate that the MNF is a safe and effective procedure both in the short term and midterm.

Vegetal and Animal Food Proteins Have a Different Impact in the First Postprandial Hour of Impedance-pH Analysis in Patients with Heartburn.

Background and Aims By means of 24 h impedance-pH monitoring, we aimed to evaluate the effect of two different meals with a bromatological balanced composition: one with a prevailing component of animal proteins and the other with vegetable proteins. Patients and Methods We enrolled 165 patients with heartburn and negative endoscopy, who underwent impedance-pH monitoring off therapy. Patients were allocated to receive a Mediterranean diet with a total caloric intake of about 1694 kcal, divided into two meals: one with a prevailing component of animal proteins and the other with vegetable proteins. We evaluated the total reflux number, acid exposure time (AET), and symptom-reflux association with impedance-pH analysis. Moreover, during the first postprandial hour (at lunch and dinner), we evaluated the total reflux number, number of acid and weakly acidic refluxes, AET, and presence of symptoms. Results The male/female ratio was 80/85. Mean age was 51.9 ± 12.1 years. Impedance-pH analysis showed that 55/165 patients had pathological AET or a number of refluxes (nonerosive reflux disease (NERD)), 49/165 had normal AET and a number of refluxes but positive symptom-reflux association (hypersensitive esophagus (HE)), and 61/165 had normal AET and a number of refluxes with negative symptom-reflux association (functional heartburn (FH)). The overall first postprandial hour analysis showed a higher total reflux number, acid reflux number, and AET after the animal protein meal than after the vegetable protein meal. Moreover, more symptoms were reported after the animal protein meal. Similar results have been observed in the three different subcategories of patients (NERD, HE, and FH). Conclusions Vegetable proteins are associated with a lower number of refluxes, particularly acid refluxes, and with a reduced number of symptoms during the first postprandial hour. This is a pilot study and future investigations are warranted to confirm these results.

Genetic risk factors for perception of symptoms in GERD: an observational cohort study.

Genetic polymorphisms in G-protein beta-3 subunit (GNβ3) and beta-2 adrenergic receptor (ADRB2) are associated with pain and gut hypersensitivity, which can overlap with gastroesophageal reflux disease (GERD). To evaluate relationships between single nucleotide polymorphisms (SNPs) within GNβ3 and ADRB2 systems, and reflux symptom burden, GERD phenotypes from ambulatory reflux monitoring, and quality of life. Symptomatic adults undergoing ambulatory reflux testing were recruited and phenotyped based on acid burden and symptom reflux association; major oesophageal motor disorders and prior foregut surgery were exclusions. A comparison asymptomatic control cohort was also identified. Subjects and controls completed questionnaires assessing symptom burden on visual analog scales, short-form health survey-36 (SF-36), and Beck Anxiety and Depression Inventories (BAI and BDI). Genotyping was performed from saliva samples; 6 SNPs selected from each of the two genes of interest were compared. Saliva from 151 study subjects (55.3 ± 1.2 years, 63.6% F) and 60 control subjects (50.9 ± 2.2 years, 66.7%) had sufficient genetic material for genotyping. Study subjects had higher symptom burden, worse total and physical health, and higher anxiety scores compared to controls (P ≤ .002). Tested SNPs within ADRB2 were similar between study subjects and controls (P > .09). Study subjects with recessive alleles in 3 GNβ3 SNPs (Rs2301339, Rs5443, and Rs5446) had worse symptom severity (P = .011), worse mental health (P = .03), and higher depression scores (P = .005) despite no associations with GERD phenotypes or reflux metrics. Genetic variation within GNβ3 predicts oesophageal symptom burden and affect, but not oesophageal acid burden or symptom association with reflux episodes.

Thickened infant formula: What to know.

This study aimed to provide an overview of the characteristics of thickened formulas to aid health care providers manage infants with regurgitations. The indications, properties, and efficacy of different thickening agents and thickened formulas on regurgitation and gastroesophageal reflux in infants were reviewed. PubMed and the Cochrane database were searched up to December 2016. Based on the literature review, thickened formulas reduce regurgitation, may improve reflux-associated symptoms, and increase weight gain. However, clinical efficacy is related to the characteristics of the formula and of the infant. Commercial thickened formulas are preferred over the supplementation of standard formulas with thickener because of the better viscosity, digestibility, and nutritional balance. Rice and corn starch, carob bean gum, and soy bean polysaccharides are available as thickening agents. Hydrolyzed formulas have recently shown promising additional benefit. Thickened formulas reduce the frequency and severity of regurgitation and are indicated in formula-fed infants with persisting symptoms despite reassurance and appropriate feeding volume intake.

Psychosocial Distress and Quality of Life Impairment Are Associated With Symptom Severity in PPI Non-Responders With Normal Impedance-pH Profiles.

Up to 50% of patients with reflux symptoms do not manifest a satisfactory symptom response to proton pump inhibitor (PPI) therapy. Our primary aim in this study was to identify factors associated with symptom perception among PPI non-responder phenotypes. This prospective observational cohort study was performed from September 2014 to January 2017 at a single academic medical center and included PPI non-responders who underwent 24-h impedance-pH monitoring and completed a questionnaire set measuring patient-reported symptom severity, quality of life (QOL), and psychosocial distress. Participants were separated into cohorts based on impedance-pH results: on PPI: -acid exposure time (AET)/-symptom-reflux association (SRA), +AET, and -AET/+SRA; off PPI: functional (-AET/-SRA), gastroesophageal reflux disease (GERD) (+AET), and reflux hypersensitivity (RHS) (-AET/+SRA). The primary outcome was abnormal GERD symptom severity defined by GerdQ≥8. One hundred and ninety-two participants were included. Impedance-pH on PPI was performed on 125: 72 (58%) -AET/-SRA, 42 (34%) +AET, and 11 (9%) -AET/+SRA. Among the -AET/-SRA group, younger age, higher dysphagia scores, QOL impairment, and higher brief symptom index were associated with GerdQ≥8. Among the +AET group, higher number of reflux-associated symptoms and lower distal contractile integral was associated with GerdQ≥8. Impedance-pH off PPI was performed on 67 participants: 39 (58%) functional, 16 (24%) GERD, and 12 (18%) RHS. Among the functional group, higher QOL impairment and dysphagia scores were seen with GerdQ≥8. Perceptions of reflux symptoms are associated with psychosocial distress, reduced QOL, and sensation of dysphagia among PPI non-responders with normal impedance-pH. Among PPI refractory GERD patients, patient-reported symptom severity is associated with physiological differences, as opposed to psychosocial factors.

Impedance-pH Monitoring for Diagnosis of Reflux Disease: New Perspectives.

Heartburn is the most specific symptom of gastroesophageal reflux disease (GERD). In clinical practice, heartburn relief by a proton pump inhibitor (PPI) trial does suffice to confirm GERD. However, an objective diagnosis of GERD is required before anti-reflux endoscopic or surgical interventions, independently from PPI response. Thus, since normal findings at upper endoscopy are detected in the majority of patients with heartburn, reflux monitoring is often required. When traditional catheter-based or wireless pH tests are used, reflux episodes are conventionally identified by pH drops below 4.0 units. Combined impedance-pH monitoring has the advantage to provide a comprehensive assessment of both physical and chemical properties of refluxate and the distinction between acid and weakly acidic refluxes, both proven to cause heartburn. Unfortunately, the conventional impedance-pH parameters, namely acid exposure time and number of reflux events, are characterized by suboptimal diagnostic sensitivity, and the reliability of symptom-reflux association indexes remains questionable. Therefore, novel impedance parameters, namely the post-reflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI), have recently been proposed in order to achieve a better diagnostic yield. In fact, they proved to be highly accurate in distinguishing reflux-related from reflux-unrelated heartburn, off- as well as on-PPI therapy. Currently, manual review of impedance-pH tracings is needed because of the modest accuracy of available software tools for automated analysis. PSPW index and MNBI are highly applicable and reproducible, and their calculation requires a few additional minutes during the manual review of impedance-pH tracings. So far, we believe that PSPW index and MNBI are ready for prime time and should become part of the standard analysis of impedance-pH tracings for GERD diagnosis in patients with endoscopy-negative heartburn.

The Additional Role of Symptom-Reflux Association Analysis of Diagnosis of Gastroesophageal Reflux Disease Using Bravo Capsule pH Test

Since the development of ambulatory esophageal pH monitoring test to diagnose gastroesophageal reflux disease (GERD), several parameters have been introduced. The aim of this study was to assess whether using the symptom index (SI), symptom sensitivity index (SSI), and symptom association probability (SAP), in addition to the DeMeester score (DS), would be useful for interpreting the Bravo pH monitoring test. A retrospective study, which included 68 patients with reflux symptoms refractory to proton pump inhibitor (PPI) therapy who underwent a Bravo capsule pH test between October 2006 and May 2015, was carried out. Acid reflux parameters and symptom reflux association parameters were analyzed. The median percent time of total pH<4 and DS were 2.90% (interquartile range [IQR] 1.13-6.03%) and 11.10 (IQR 4.90-22.80), respectively. According to the analysis of the day-to-day variation in percent time of total pH<4 (r=0.724) and DS (r=0.537), there was a significant correlation between Day 1 and Day 2. The positive rate of Bravo test according to DS was 27 (39.7%). Although thirty patients experienced symptoms during the test, there were no significant differences of reflux parameters compared with other patients. In the symptom group, 7 patients (23.3%) were identified as having negative DS and an abnormal symptom-related index. There were no significant test-related complications. In addition to the analysis of traditional acid parameters of the Bravo capsule pH test, diagnosis of GERD, including reflux hypersensitivity, can be improved by performing an analysis of the symptom-reflux association and of the day-to-day variation.

Heartburn, gastro-oesophageal reflux disease and non-erosive reflux disease

Reflux is a normal process that occurs in healthy infants, children and adults. Most episodes are short-lived and do not cause bothersome symptoms of complications. Gastro-oesophageal reflux disease (GORD) develops when the reflux of stomach acid causes troublesome reflux-associated symptoms and/or complications. The most common symptom of GORD is heartburn. Depending on how severe the symptoms of GORD are, treatment may involve one or more of the following: lifestyle changes, medications, or surgery. Acid suppressive medications include, in increasing order of potency, over-the-counter antacids, alginates and H2 antagonists at non-prescription strength, prescription strength H2 antagonists and proton pump inhibitors. In patients with mild to moderate GORD, symptom severity and previous treatments can guide the selection of an initial acid suppressive regimen. The most common and effective treatment of oesophagitis and GORD is to reduce gastric acid secretion with a proton pump inhibitor.

Effect of Severity of Esophageal Acidification on Sleep vs Wake Periods in Infants Presenting with Brief Resolved Unexplained Events

To describe the pattern of gastroesophageal reflux (GER) events in wake and sleep states with increasing acid reflux index (ARI) in neonates and to test the hypothesis that GER-related symptoms are frequent in ARI >7% in wake state. Infants underwent 24-hour pH-impedance studies with 6-hour concurrent video-polysomnography studies. Data were stratified based on the 24-hour ARI (% duration that esophageal pH is <4) into ARI < 3% (normal), ARI 3 ≥ to ≤7% (intermediate), and ARI >7% (abnormal). GER frequency, clearance mechanisms, and symptoms were distinguished during wake state and sleep state. Total wake and sleep duration was similar (P ≥ .2) in all ARI groups. Acidic events were frequent with increasing ARI in wake state vs sleep state (P ≤ .03). The symptom index increased with increasing ARI (P ≤ .02) in both wake state and sleep state. Acid clearance time increased with increasing ARI in wake state (P ≤ .02). In ARI > 7% vs ARI ≤ 7%, frequency of acidic GER events was higher (P ≤ .02) in wake state and sleep state; proximal migration of acid (P = .03) and acid clearance time were higher in wake state (P = .0005) only. Symptom index was higher in ARI >7% vs ARI ≤ 7% in wake state (P < .0001), comparable in normal vs intermediate (P = .4), and higher in abnormal vs intermediate (P = .0004) groups. Severe esophageal acid exposure (ARI >7%) is associated with increased reflux-associated symptoms in wake state. Sleep state appears to be protective regardless of ARI, likely because of greater chemosensory thresholds. Attention to posture and movements during wake state can be helpful. Scrutiny for non-GER etiologies should occur for infants presenting with life-threatening symptoms.

Between GERD and NERD: the relevance of weakly acidic reflux.

Nonerosive reflux disease (NERD) is a common condition and the most frequent phenotype of gastroesophageal reflux disease (GERD). NERD is extremely heterogeneous and includes patients with negative endoscopy but abnormal esophageal acid exposure and/or positive reflux-symptom association analysis (hypersensitive esophagus). This segregation is only possible owing to the use of impedance-pH monitoring. Indeed, weakly acidic reflux represents one of the most common causes of refractory symptoms in patients evaluated off antisecretory therapy and, more importantly, during antisecretory drug treatment. Patients with heartburn who do not have any type of reflux underlying their symptoms (functional heartburn) must be excluded from the category of GERD. The drawbacks of impedance-pH are mainly due to the day-to-day variability of the test and the fact that the accuracy of the symptom-reflux correlation scores is often far from perfect. Some histopathological characteristics, such as dilated intercellular spaces, can be helpful in distinguishing patients with NERD through esophageal biopsies. Patients with NERD in whom acid is the main pathogenetic factor respond successfully to proton pump inhibitor therapy, while those with hypersensitive esophagus to weakly acidic reflux could be treated with reflux inhibitors or surgery, although further controlled studies are required.

PWE-073 Comparison of Cost-Effectiveness Between 96 Hour Wireless Bravo Reflux Monitoring and 24 Hour PH-Impedance in The Diagnosis of Gastroesophageal Reflux Disease: Abstract PWE-073 Table 1

Introduction 24 hour pH-impedance reflux monitoring is considered the gold standard in diagnosing pathological gastroesophageal reflux (GOR). Alternative method is catheter-free Bravo capsules (96 hours). To date, their cost-effectiveness has yet to be compared. At Guy’s Hospital, London, UK, the cost of Bravo is estimated to be £1,200 (including endoscopy) and pH-impedance to be £800 (including high resolution manometry). It is generally assumed that the higher cost of Bravo monitoring is justifiable as it is thought to have a higher diagnostic yield due to better patient compliance and a longer monitoring time. Methods Patients who had a Bravo or pH-impedance study during May-November 2015 were selected. The more cost-effective method was defined as the technique with lower cost (including cost of non-diagnostic results) per diagnostic procedure. To identify non-diagnostic results, the patients with pathological GOR, patients with positive symptom-reflux associations, patients with supragastric belching and patients who were adequately symptomatic (therefore having negative symptom-reflux association) were removed. Positive symptom-reflux association was considered as symptom association probability (SAP) ≥95% and/or symptom index (SI) ≥50%. Results 81 Bravo patients and 145 pH-impedance patients were analysed. 50 (61.7%) Bravo patients and 69 (47.5%) pH-impedance patients were diagnosed with pathological GOR, 14 (17.3%) Bravo and 44 (30.3%) pH-impedance patients had hypersensitive oesophagus, 3 (2.1%) pH-impedance were patients diagnosed with supragastric belching causing symptoms, and 10 (12.3%) Bravo and 14 (9.7%) pH-impedance patients experienced symptoms unexplained by reflux events (negative symptom-reflux association). The remaining 7 (8.6%) Bravo and 15 (10.3%) pH-impedance entries therefore represent the proportion of non-diagnostic investigations. Cost calculations revealed that each Bravo with diagnostic yield costs £1313.5 whilst each pH-impedance with diagnostic yield costs £892.3 (Table 1). This means that for each diagnosis made by Bravo there is an additional cost of £421.2. Conclusion The cost-effectiveness of pH-impedance reflux monitoring seems to be superior to Bravo system to make a reflux-related diagnosis. However, this study does not take into account other advantages of each method in clinical use. Disclosure of Interest None Declared

Effect of Vagus Nerve Integrity on Short and Long-Term Efficacy of Antireflux Surgery.

Vagus nerve injury is a feared complication of antireflux surgery (ARS) that may negatively affect reflux control. The aim of the present prospective study was to evaluate short-term and long-term impact of vagus nerve injury, evaluated by pancreatic polypeptide response to insulin-induced hypoglycemia (PP-IH), on the outcome of ARS. In the period from 1990 until 2000, 125 patients with gastroesophageal reflux disease (GERD) underwent ARS at a single center. Before and 6 months after surgery, vagus nerve integrity testing (PP-IH), 24-h pH-monitoring, gastric emptying, and reflux-associated symptoms were evaluated. In 2014, 14-25 years after surgery, 110 patients were contacted again for evaluation of long-term symptomatic outcome using two validated questionnaires (Gastrointestinal Symptom Rating Scale (GSRS) and GERD-Health Related Quality of Life (HRQL)). Short-term follow-up: vagus nerve injury (PP peak ≤47 pmol/l) was observed in 23 patients (18%) 6 months after fundoplication. In both groups, a comparable decrease in reflux parameters and symptoms was observed at 6-month follow-up. Postoperative gastric emptying was significantly delayed in the vagus nerve injury group compared with the vagus nerve intact group. Long-term follow-up: patients with vagus nerve injury showed significantly less effective reflux control and a higher re-operation rate. Vagus nerve injury occurs in up to 20% of patients after ARS. Reflux control 6 months after surgery was not affected by vagus nerve injury. However, long-term follow-up showed a negative effect on reflux symptom control and re-operation rate in patients with vagus nerve injury.