Psychological Processes, Not Physiological Parameters, Are Most Important Contributors to Symptom Severity in Patients With Refractory Heartburn/Regurgitation Symptoms.

BACKGROUND & AIMS: Physiological and psychological factors have been found to influence esophageal symptom reporting. We aimed to evaluate which of these factors are associated with 3 reflux symptom severity outcomes (ie, Total Reflux, Heartburn, and Sleep Disturbance) through a traditional statistical and a complementary machine-learning approach. METHODS: Consecutive adult patients with refractory heartburn/regurgitation symptoms underwent standard 24-hour pH-impedance monitoring and completed questionnaires assessing past and current gastrointestinal and psychological health. In the traditional statistical approach, hierarchical general linear models assessed relationships of psychological and physiological variables (eg, total number of reflux episodes) with reflux severity scores. Mediation analyses further assessed pathways between relevant variables. In the machine-learning approach, all psychological and physiological variables were entered into 11 different models and cross-validated model performance was compared among the different models to select the best model. RESULTS: Three hundred ninety-three participants (mean [SD] age, 48.5 [14.1] years; 60% were female) were included. General psychological functioning emerged as an important variable in the traditional statistical approach, as it was significantly associated with all 3 outcomes and mediated the relationship between childhood trauma and both Total Reflux and Heartburn Severity. In the machine-learning analyses, general psychological variables (eg, depressive symptoms) were most important for Total Reflux and Sleep Disturbance outcomes, and symptom-specific variables, like visceral anxiety, were more influential for Heartburn Severity. Physiological variables were not significant contributors to reflux symptom severity outcomes in our sample across reflux classifications and statistical methodology. CONCLUSIONS: Psychological processes, both general and symptom-specific, should be considered as another important factor within the multifactorial processes that impact reflux symptom severity reporting across the reflux spectrum.

Psychological symptoms do not discriminate between reflux phenotypes along the organic-functional refractory GERD spectrum.

OBJECTIVE: Historically, psychological processes are associated with disorders at the functional end of the gastro-oesophageal reflux disease (GERD) spectrum. However, recent research suggests that psychological symptoms are relevant across the entire GERD spectrum. We aim to investigate whether psychological symptoms are associated with reflux phenotype (True GERD, Borderline GERD, reflux hypersensitivity, functional heartburn) along the GERD spectrum in a cohort of refractory reflux patients. DESIGN: Consecutive adult patients with refractory reflux symptoms underwent standard 24-hour pH-impedance monitoring and completed questionnaires assessing demographic, clinical and psychological information. Bayesian one-way analysis of variance assessed whether psychological variables differed across reflux phenotypes. Next, we applied multinomial and ordinal logistic regressions with clinical, demographic and psychological variables set as independent variables and reflux phenotype as the outcome variable. The complementary machine-learning approach entered all demographic, clinical and psychological variables into models, with reflux phenotype set nominally and ordinally. Cross-validated model performance was used to select the best model. RESULTS: 393 participants (mean (SD) age=48.5 (14.1); 60% female) were included. The Bayesian analyses found no difference in psychological variables across reflux phenotypes. Similarly, age, gender and proton pump inhibitor use were the only significant variables in the multinomial logistic regression and body mass index was significant in both regressions. Machine-learning analyses revealed poorly performing models with high misclassification rates (67-68%) in both models. CONCLUSION: Psychological symptoms do not differ between nor predict reflux phenotype membership in refractory reflux patients. Findings suggest that psychological symptoms are relevant across the spectrum of GERD, rather than specific to functional oesophageal disorders.

Evaluating the impact of position, volume, and consistency on high-resolution esophageal manometry outcomes.

BACKGROUND: The Chicago classification primarily utilizes ten 5 mL liquid swallows in a supine position as the standard high-resolution esophageal manometry (HRM) protocol. HRM can be performed with varying volumes and consistencies and in an upright position. We aimed to determine the impact on HRM results by (1) position, (2) swallows of differing volume and consistency, and (3) perception of bolus passage. METHODS: HRM was performed in healthy volunteers (HV) with the following protocol of swallows: liquids 10 × 5 mL, 5 × 10 mL, and 3 × 10 mL multiple rapid swallows; applesauce 5 × 5 mL and 5 × 10 mL; and bread 5 × 2 × 2 cm and 5 × 4 × 4cm. HV rated difficulty of each swallow on a 5-point Likert scale. All HVs performed the protocol in supine position first and then in "semi-upright" (sitting 70 degrees in a bed) and "upright" (sitting in a chair) in a randomized order. KEY RESULTS: Thirty-seven HVs, median age 27 years, 64% female completed this study. Median distal contractile integral (DCI) and integrated relaxation pressure 4 s (IRP4) of 5 mL liquid swallows significantly differed (all p < 0.01) between position performed. Large volume swallows resulted in higher DCI and lower IRP4. IRP4 results were significantly increased for 2 × 2 cm pieces of bread compared to 5 mL water swallows. DCI results were higher for 2 × 2 cm pieces of bread compared to 5 mL water swallows. Distal latency was shorter in more upright positions. Among this cohort of HV, perceived difficulty of bolus passage was more likely to occur with solid boluses. CONCLUSIONS AND INFERENCES: The volume and consistency of a swallow and the position it is performed in, significantly alter HRM metrics. Interpretation of HRM studies should incorporate different normative values which are specific to the position and bolus type.

Clinical trial: a controlled trial of baclofen add-on therapy in PPI-refractory gastro-oesophageal reflux symptoms.

BACKGROUND: Proton pump inhibitors (PPI) have no effect on non-acid reflux events which can continue to provoke gastro-oesophageal reflux disease (GERD) symptoms. Baclofen, a γ-aminobutyric acid agonist, can decrease non-acid reflux but its symptomatic benefit in refractory GERD symptoms is understudied. AIMS: To assess the efficacy of baclofen 10 mg t.i.d. vs placebo as add-on therapy in PPI-refractory GERD symptoms, in a randomised, double-blind, placebo-controlled study. METHODS: Patients with persisting typical GERD symptoms on b.i.d. PPI therapy were randomised to 4 weeks of baclofen 10 mg or placebo t.i.d. Before and after treatment, patients underwent 24 h impedance-pH monitoring on-PPI. Throughout the study, patients filled out ReQuest diaries. Data were analysed using mixed models. RESULTS: About 60 patients were included (age 47.5 years [range 19-73], 41f/19 m), 31 patients were randomised to baclofen. One patient withdrew consent and five in the baclofen group stopped treatment due to side effects. There was a trend towards a better response for general wellbeing in the baclofen-treated group compared to placebo (p = 0.06). When subdividing patients according to symptom association probability (SAP), only the SAP+ (n = 25) group improved significantly with baclofen (pcorr  = 0.02), and worsened with placebo (pcorr  = 0.008). The total number of reflux events decreased over time (p = 0.01), mainly due to the baclofen condition (pcorr  = 0.1). The number of reflux events with a high proximal extent dropped significantly after baclofen (pcorr  = 0.009), but not placebo. CONCLUSION: Baclofen decreases several reflux parameters in PPI refractory GERD symptoms, but pH-impedance monitoring is necessary before treatment as only SAP+ patients experience clinical benefit after 4 weeks.

High-resolution colonic manometry interobserver analysis trial.

INTRODUCTION: Colonic high-resolution manometry (HRM) is a novel, not widely used diagnostic method used in the final workup of chronic constipation before surgery. Since its introduction, different motor patterns have been defined. However, it remains to be established whether these patterns are easily and reproducibly identified by different investigators. METHODS: The primary aim of this study was to determine agreement for motor pattern identification with HRM. To calculate the interobserver agreement (IOA), the Fleiss's kappa statistic for multiple observers was used. Seven participants analyzed 106 one-min time frames, derived from five measurements in healthy volunteers and five in patients with chronic constipation. The time frames were chosen to show a variety and combination of motor patterns consisting of short antegrade, short retrograde, cyclic anterograde, cyclic retrograde, long antegrade, long retrograde, slow retrograde motor pattern, high-amplitude propagating motor patterns, and pancolonic pressurizations. All of the measurements were performed with a solid-state colonic HRM catheter, comprising 40 pressure sensors spaced 2.5 cm apart. RESULTS: A median of 10.25 h (range 6-20) were required to analyze all time frames. High-amplitude propagating contractions achieved an almost perfect level of agreement (k = 0.91). Several motor patterns achieved substantial agreement; these included the short antegrade (k = 0.63), long antegrade (k = 0.68), cyclic retrograde (k = 0.70), slow retrograde motor pattern (k = 0.80), and abdominal pressure or movement artifacts (k = 0.67). Moderate agreement was found for short retrograde (k = 0.57), cyclic anterograde (k = 0.59), long retrograde motor patterns (k = 0.59) and simultaneous pressure waves (k = 0.59). CONCLUSION: For the majority of motor patterns, the overall IOA for colonic manometry was substantial or high. This high level of agreement supports the use of colonic manometry application in clinical and research settings. Harmonization has the potential to improve agreement for long anterograde motor patterns with high amplitudes and for mixed direction patterns.

High-Resolution Manometry Thresholds and Motor Patterns Among Asymptomatic Individuals.

OBJECTIVE: High-resolution manometry (HRM) is the current standard for characterization of esophageal body and esophagogastric junction (EGJ) function. We aimed to examine the prevalence of abnormal esophageal motor patterns in health, and to determine optimal thresholds for software metrics across HRM systems. DESIGN: Manometry studies from asymptomatic adults were solicited from motility centers worldwide, and were manually analyzed using integrated relaxation pressure (IRP), distal latency (DL), and distal contractile integral (DCI) in standardized fashion. Normative thresholds were assessed using fifth and/or 95th percentile values. Chicago Classification v3.0 criteria were applied to determine motor patterns across HRM systems, study positions (upright vs supine), ages, and genders. RESULTS: Of 469 unique HRM studies (median age 28.0, range 18-79 years). 74.6% had a normal HRM pattern; none had achalasia. Ineffective esophageal motility (IEM) was the most frequent motor pattern identified (15.1% overall), followed by EGJ outflow obstruction (5.3%). Proportions with IEM were lower using stringent criteria (10.0%), especially in supine studies (7.1%-8.5%). Other motor patterns were rare (0.2%-4.1% overall) and did not vary by age or gender. DL thresholds were close to current norms across HRM systems, while IRP thresholds varied by HRM system and study position. Both fifth and 95th percentile DCI values were lower than current thresholds, both in upright and supine positions. CONCLUSIONS: Motor abnormalities are infrequent in healthy individuals and consist mainly of IEM, proportions of which are lower when using stringent criteria in the supine position. Thresholds for HRM metrics vary by HRM system and study position.

Effect of slow, deep breathing on visceral pain perception and its underlying psychophysiological mechanisms.

BACKGROUND: Studies using somatic pain models have shown the hypoalgesic effects of slow, deep breathing. We evaluated the effect of slow, deep breathing on visceral pain and explored putative mediating mechanisms including autonomic and emotional responses. METHODS: Fifty-seven healthy volunteers (36 females, mean age = 22.0 years) performed controlled, deep breathing at a slow frequency (6 breaths per minute), controlled breathing at a normal frequency (14 breaths per minute; active control), and uncontrolled breathing (no-treatment control) in randomized order. Moderate painful stimuli were given during each condition by delivering electrical stimulation in the distal esophagus. Participants rated pain intensity after each stimulation. Heart rate variability and self-reported arousal were measured during each condition. KEY RESULTS: Compared to uncontrolled breathing, pain intensity was lower during slow, deep breathing (Cohen's d = 0.40) and normal controlled breathing (d = 0.47), but not different between slow, deep breathing and normal controlled breathing. Arousal was lower (d = 0.53, 0.55) and heart rate variability was higher (d = 0.70, 0.86) during slow, deep breathing compared to the two control conditions. The effect of slow, deep breathing on pain was not mediated by alterations in heart rate variability or arousal but was moderated by pain catastrophizing. CONCLUSIONS AND INFERENCES: Slow, deep breathing can reduce visceral pain intensity. However, the effect is not specific to the slow breathing frequency and is not mediated by autonomic or emotional responses, suggesting other underlying mechanisms (notably distraction). Whether a long-term practice of slow, deep breathing can influence (clinical) visceral pain warrants to be investigated.

Systematic review: duodenogastroesophageal (biliary) reflux prevalence, symptoms, oesophageal lesions and treatment.

BACKGROUND: The prevalence of duodenogastroesophageal reflux (DGER) and its effect on symptoms and oesophageal lesions in gastroesophageal reflux disease (GERD) is unclear. AIMS: To conduct a systematic review to determine the prevalence of DGER among patients with GERD, the effect of DGER on symptoms and oesophageal lesions, and the treatment of DGER. METHODS: We searched Pubmed and MEDLINE for full text, English language articles until October 2020 that evaluated DGER prevalence among patients with GERD, the effect of DGER on symptoms and oesophageal lesions, and the treatment of DGER. RESULTS: We identified 3891 reports and included 35 which analysed DGER prevalence in GERD, 15 which evaluated its effect in non-erosive reflux disease (NERD), 17 on erosive oesophagitis, 23 in Barrett's, and 13 which evaluated the treatment of DGER. The prevalence of DGER, when evaluated by Bilitec, among all GERD patients ranged from 10% to 97%, in NERD 10%-63%, in erosive oesophagitis 22%-80% and in Barrett's 50%-100%. There were no differences in the presence or degree of DGER among patients who were asymptomatic or symptomatic on proton pump inhibitors (PPI). The most commonly evaluated treatments for DGER were PPIs and DGER reduced post-PPI therapy in all studies. CONCLUSIONS: The prevalence of DGER increased with more advanced oesophageal lesions and did not explain persisting symptoms among patients taking PPI therapy. PPIs appear to be effective in the treatment of DGER. DGER remains an important consideration in patients with GERD and future therapies deserve more study.

The bitter tastant denatonium benzoate has no influence on the number of transient lower esophageal sphincter relaxations in health.

BACKGROUND: Administration of a bitter compound can alter the intragastric pressure (IGP) after a meal. Additionally, a negative correlation between IGP and the number of transient lower esophageal sphincter relaxations (TLESRs) has been demonstrated. However, the effect of a bitter tastant on the number of TLESRs and subsequent reflux episodes has never been investigated and it is unclear whether bitter food items should be avoided in gastro-esophageal reflux disease. We hypothesize that bitter administration in healthy volunteers (HVs) will lead to an increase in the number of TLESRs. METHODS: After an overnight fast, 20 female HVs (36 years [21-63]) underwent a high-resolution impedance manometry (HRiM) measurement. After placement of the HRiM probe, 0.1 ml/kg of a 10 mM denatonium benzoate solution (bitter) or an identical volume of water (placebo) was administered directly into the stomach. The number of TLESRs and reflux episodes was quantified 30 min before and 2 h after consumption of a high caloric meal. KEY RESULTS: There was no significant difference in the number of TLESRs or reflux episodes between the bitter and placebo condition. Additionally, no differences were observed in the nature (gas or liquid) and extent of reflux events. Lower esophageal sphincter pressures dropped significantly in the first postprandial hour to start recovering slowly back to baseline values during the second postprandial hour (p < 0.0001), without any difference between both conditions. CONCLUSIONS & INTERFERENCES: Administration of the bitter tastant denatonium benzoate has no influence on the number of TLESRs or reflux episodes.

The gastro-sphincteric pressure gradient: A new parameter to diagnose a rumination episode.

BACKGROUND: Rumination is defined as the repetitive, effortless regurgitation of recently ingested food into the mouth. These episodes are preceded by a rise in intragastric pressure (IGP) and mainly occur postprandially. IGP peaks >30 mmHg have been proposed as a cutoff to differentiate rumination from reflux events. In clinical practice, we observed that this cutoff, which does not consider esophagogastric junction (EGJ) resistance, is not always reached. METHODS: We studied 27 patients with rumination syndrome [age: 43.6, 59% female] and 28 gastro-esophageal reflux disease patients [age: 45.9, 54% female]. For each rumination episode, reflux event, transient lower esophageal sphincter relaxation (TLESR), or straining without regurgitation, the following parameters were registered: maximal IGP, IGP, and EGJ pressure preceding the respective episodes. We also quantified the gastro-sphincteric pressure gradient (GSPG) prior to the respective episodes. KEY RESULTS: Five reflux episodes were characterized by a maximal IGP >30 mmHg. In 28% of the rumination episodes, the IGP peak did not exceed 30 mmHg. Median GSPG was positive for rumination episodes and significantly higher compared with TLESRs, reflux episodes, and straining without regurgitation (7 [3-13] vs. 0 [-1-0] vs. 0 [-1-0] vs. -9 [-13--2]; p < 0.0001). CONCLUSIONS & INTERFERENCES: Applying the proposed cutoff of 30 mmHg, 28% of the rumination episodes were missed. We found that the GSPG differentiates between rumination (positive GSPG), TLESRs and reflux events (GSPG around 0), and straining without regurgitation (negative GSPG). We propose a GSPG value ≥2 mmHg to distinguish rumination from reflux episodes, TLESRs, and straining without regurgitation.

European Society for Neurogastroenterology and Motility (ESNM) recommendations for the use of high-resolution manometry of the esophagus.

BACKGROUND: Several patients in gastroenterology practice present with esophageal symptoms, and in case of normal endoscopy with biopsies, high-resolution manometry (HRM) is often the next step. Our aim was to develop a European consensus on the clinical application of esophageal HRM, to offer the clinician guidance in selecting patients for HRM and using its results to optimize clinical outcome. METHODS: A Delphi consensus was initiated with 38 multidisciplinary experts from 16 European countries who conducted a literature summary and voting process on 71 statements. Quality of evidence was evaluated using grading of recommendations assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 33 statements. RESULTS: The process generated guidance on when to consider esophageal HRM, how to perform it, and how to generate the report. The Delphi process also identified several areas of uncertainty, such as the choice of catheters, the duration of fasting and the position in which HRM is performed, but recommended to perform at least 10 5-ml swallows in supine position for each study. Postprandial combined HRM impedance is considered useful for diagnosing rumination. There is a large lack of consensus on treatment implications of HRM findings, which is probably the single area requiring future targeted research. CONCLUSIONS AND INFERENCES: A multinational and multidisciplinary group of European experts summarized the current state of consensus on technical aspects, indications, performance, analysis, diagnosis, and therapeutic implications of esophageal HRM.

The role of serotonin in the control of esophageal sensitivity assessed by multimodal stimulation in health.

BACKGROUND: Esophageal hypersensitivity is considered an important pathophysiological mechanism in refractory gastroesophageal reflux disease (GERD) patients. Serotonin (5-HT) plays an important role in the regulation of GI (gastrointestinal) secretion, motility and sensitivity. Previous studies found that altered 5-HT availability has no clear effects on esophageal/GI sensations. Our aim was therefore to investigate the role of 5-HT in esophageal sensitivity in healthy volunteers (HV). METHODS: Esophageal sensitivity to thermal, mechanical, electrical, and chemical stimuli was assessed in 3 different placebo-controlled studies. In the first study, the effect of citalopram (40 mg; 5-HT reuptake inhibitor; intravenous) was investigated (n = 14). In the second study, the effect of buspirone (20 mg; 5HT1A agonist; oral) was investigated (n = 10). In the third study, acute tryptophan depletion (ATD) was used to decrease 5-HT levels to investigate the effect of reduced 5-HT availability on esophageal sensitivity (n = 15). KEY RESULTS: No difference was observed in esophageal sensitivity after the administration of citalopram or buspirone (all p > 0.06). In contrast, pain perception threshold to chemical stimulation was increased after ATD (p = 0.017, Cohen's d+ = 0.67). No effect was found on the first perception or pain tolerance threshold. ATD had no influence on esophageal sensitivity to thermal, mechanical, and electrical stimulation compared with placebo. CONCLUSIONS AND INFERENCES: ATD, which induces 5-HT depletion, significantly decreased pain perception threshold during chemical stimulation, without affecting sensitivity to mechanical, thermal, or electrical stimulation. These findings confirm the involvement of 5-HT in the control of esophageal acid sensitivity, but identifying the receptors involved requires more ligands and studies.

Codeine induces increased resistance at the esophagogastric junction but has no effect on motility and bolus flow in the pharynx and upper esophageal sphincter in healthy volunteers: A randomized, double-blind, placebo-controlled, cross-over trial.

BACKGROUND: Chronic opioid use can induce esophageal dysfunction with symptoms resembling achalasia and a manometric pattern of esophagogastric junction-outflow obstruction (EGJ-OO). However, the effect of opioids in acute setting on pharyngeal function and esophageal body contractility has not been investigated. METHODS: After positioning the high-resolution impedance manometry (HRiM) catheter, codeine (60 mg) or placebo (glucose syrup) was infused intragastrically. Forty-five minutes post-infusion, participants received liquid, semi-solid, and solid boluses to assess esophageal and pharyngeal function. HRiM analysis was performed adhering to the Chicago classification v3.0. (CC v3.0). Pressure flow analysis (PFA) for the esophageal body and the pharynx was performed using the SwallowGateway™ online platform. KEY RESULTS: Nineteen healthy volunteers (HV) [5 male; age 38.3] were included. After codeine administration, higher integrated relaxation pressure 4 s values resulted in significantly reduced deglutitive EGJ relaxation and distal latency was significantly shorter. Distal contractility was similar in both conditions. Bolus flow resistance at the EGJ and distention pressures increased significantly after codeine infusion. Based on CC v3.0, acute infusion of codeine induced EGJ-OO in six HV (p = 0.0003 vs. placebo). Codeine administration induced no significant alterations in any of the pharyngeal PFA metrics. CONCLUSIONS & INFERENCES: In HV, acute administration of codeine increased bolus resistance at the EGJ secondary to induced incomplete EGJ relaxation leading to major motility disorders in a subset of subjects including EGJ-OO. However, an acute single dose of codeine did not affect motility or bolus flow in pharynx and UES. ClinicalTrials.gov number, NCT03784105.

Esophagogastric junction morphology and contractile integral on high-resolution manometry in asymptomatic healthy volunteers: An international multicenter study.

BACKGROUND: Esophagogastric junction contractile integral (EGJ-CI) and EGJ morphology are high-resolution manometry (HRM) metrics that assess EGJ barrier function. Normative data standardized across world regions and HRM manufacturers are limited. METHODS: Our aim was to determine normative EGJ metrics in a large international cohort of healthy volunteers undergoing HRM (Medtronic, Laborie, and Diversatek software) acquired from 16 countries in four world regions. EGJ-CI was calculated by the same two investigators using a distal contractile integral-like measurement across the EGJ for three respiratory cycles and corrected for respiration (mm Hg cm), using manufacturer-specific software tools. EGJ morphology was designated according to Chicago Classification v3.0. Median EGJ-CI values were calculated across age, genders, HRM systems, and regions. RESULTS: Of 484 studies (28.0 years, 56.2% F, 60.7% Medtronic studies, 26.0% Laborie, and 13.2% Diversatek), EGJ morphology was type 1 in 97.1%. Median EGJ-CI was similar between Medtronic (37.0 mm Hg cm, IQR 23.6-53.7 mm Hg cm) and Diversatek (34.9 mm Hg cm, IQR 22.1-56.1 mm Hg cm, P = 0.87), but was significantly higher using Laborie equipment (56.5 mm Hg cm, IQR 35.0-75.3 mm Hg cm, P < 0.001). 5th percentile EGJ-CI values ranged from 6.9 to 12.1 mm Hg cm. EGJ-CI values were consistent across world regions, but different between manufacturers even within the same world region (P ≤ 0.001). Within Medtronic studies, EGJ-CI and basal LESP were similar in younger and older individuals (P ≥ 0.3) but higher in women (P < 0.001). CONCLUSIONS: EGJ morphology is predominantly type 1 in healthy adults. EGJ-CI varies widely in health, with significant gender influence, but is consistent within each HRM system. Manufacturer-specific normative values should be utilized for clinical HRM interpretation.

Normal values and regional differences in oesophageal impedance-pH metrics: a consensus analysis of impedance-pH studies from around the world.

OBJECTIVE: Limitations of existing impedance-pH thresholds include small sample size of normative studies, inclusion of artefactual pH drops and incorrect identification of impedance reflux events. We aimed to obtain new impedance-pH thresholds from expert consensus analysis of tracings from a large number of healthy subjects. DESIGN: Of 541 studies performed worldwide using two different systems (Diversatek, USA, and Laborie, Netherlands), 150 tracings with oesophageal diagnoses, behavioural disorders and study-related artefacts were excluded. The remainder studies were subject to two reviewer consensus analysis, in-person or through video conference, consisting of editing meals and pH drops, identification of impedance reflux and postreflux swallow-induced peristaltic wave (PSPW) using strict pre-established criteria and measurement of distal mean nocturnal baseline impedance (MNBI). RESULTS: Consensus analysis was performed in 391 tracings (age 32.7 years, range 18-71, 54.2% female). Normative thresholds were significantly different between Diversatek and Laborie (total acid exposure time: 2.8% and 5%; reflux episodes: 55 and 78; MNBI at 3 cm: 1400 and 1500 ohms, at 5 cm: 1400 and 1800 ohms). Males had higher acid exposure, more reflux episodes and lower MNBI. Significant regional differences were identified, including higher PSPW scores in Western countries, and higher MNBI in Asia using Diversatek, and higher acid exposure in the Netherlands, higher MNBI in Asia and South Africa, and lower MNBI in Turkey using Laborie. CONCLUSION: Normal impedance-pH monitoring thresholds have regional and system-related differences. Clinical interpretation needs to use normal thresholds valid for the system used and world region, following careful editing of the tracings.

Gastroesophageal Reflux Disease-Functional Dyspepsia Overlap: Do Birds of a Feather Flock Together?

INTRODUCTION: Gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) are 2 of the most prevalent upper gastrointestinal (GI) disorders in the Western world. Previous Rome definitions excluded patients with predominant heartburn from the definition of FD because they were considered to have GERD. However, more recent studies showed that heartburn and acid regurgitation are also common symptoms in patients with FD. The aim of this study is to provide an overview of the prevalence of overlap between GERD and FD, the underlying pathophysiology and implications for treatment. METHODS: A review of the literature was performed using the PubMed database, and a meta-analysis with random effects model was completed. RESULTS: This review showed considerable overlap between GERD and FD. A meta-analysis on the data included in this review showed 7.41% (confidence interval [CI]: 4.55%-11.84%) GERD/FD overlap in the general population, 41.15% (CI: 29.46%-53.93%) GERD with FD symptoms, and 31.32% (CI: 19.43%-46.29%) FD with GERD symptoms. Although numerous committees and consensus groups attempted to develop uniform definitions for the diagnosis of GERD and FD, various diagnostic criteria are used across studies and clinical trials (frequency, severity, and location of symptoms). Several studies showed that the overlap between GERD and FD can be explained by a shared pathophysiology, including delayed gastric emptying and disturbed gastric accommodation. DISCUSSION: For diagnoses of GERD and FD, uniform definitions that are easy to implement in population studies, easy to interpret for physicians, and that need to be well explained to patients to avoid overestimation or underestimation of true prevalence are needed. Both GERD and FD coexist more frequently than expected, based on coincidence, suggesting a potential pathophysiological link. More research is needed to explore the common GERD/FD overlap population to identify the underlying pathophysiological mechanisms, which may lead to a more effective therapeutic approach.

Acute administration of fructans increases the number of transient lower esophageal sphincter relaxations in healthy volunteers.

INTRODUCTION: Dietary measures are often advised to patients with gastro-esophageal reflux disease (GERD). Fermentable Oligo-, Di-, Mono-saccharides and Polyols (FODMAPs) induce lower gastrointestinal (GI) symptoms. However, their effects on esophageal motility, including transient lower esophageal sphincter relaxations (TLESRs), reflux events and GERD symptoms are unknown. We investigated the effect of acute administration of two FODMAPs, fructose, and fructans, on the number of TLESRs, reflux episodes and symptom perception in healthy volunteers (HVs). MATERIALS: After an overnight fast, 20 HVs (10 males; 32.6 ± 2.8 years) underwent a high-resolution impedance manometry. The number of TLESRs and reflux episodes was quantified during five hours after consumption of a high-caloric meal (740 kcal) enriched with 40 g of either fructose, fructans or glucose (as placebo). Results were analyzed using mixed models. RESULTS: There was a trend for a change in the number of TLESRs between the three conditions (P = .06). Post hoc analysis revealed a trend toward a higher number of TLESRs in the fructan condition compared with placebo (Pcorr  = .06). Acute administration of fructose did not influence the number of TLESRs. The total number of reflux events was not affected by either FODMAP condition. Lower esophageal sphincter (LES) pressures dropped significantly in the first postprandial hour to recover slowly back to baseline values (P < .0001), without any difference in LES pressure between the three conditions. CONCLUSION: Ingestion of fructans increased the number of TLESRs slightly compared with placebo. The effect of FODMAPs such as fructans or a low FODMAP diet on reflux parameters in GERD patients remains to be investigated.

How to select patients for antireflux surgery? The ICARUS guidelines (international consensus regarding preoperative examinations and clinical characteristics assessment to select adult patients for antireflux surgery).

OBJECTIVE: Antireflux surgery can be proposed in patients with GORD, especially when proton pump inhibitor (PPI) use leads to incomplete symptom improvement. However, to date, international consensus guidelines on the clinical criteria and additional technical examinations used in patient selection for antireflux surgery are lacking. We aimed at generating key recommendations in the selection of patients for antireflux surgery. DESIGN: We included 35 international experts (gastroenterologists, surgeons and physiologists) in a Delphi process and developed 37 statements that were revised by the Consensus Group, to start the Delphi process. Three voting rounds followed where each statement was presented with the evidence summary. The panel indicated the degree of agreement for the statement. When 80% of the Consensus Group agreed (A+/A) with a statement, this was defined as consensus. All votes were mutually anonymous. RESULTS: Patients with heartburn with a satisfactory response to PPIs, patients with a hiatal hernia (HH), patients with oesophagitis Los Angeles (LA) grade B or higher and patients with Barrett's oesophagus are good candidates for antireflux surgery. An endoscopy prior to antireflux surgery is mandatory and a barium swallow should be performed in patients with suspicion of a HH or short oesophagus. Oesophageal manometry is mandatory to rule out major motility disorders. Finally, oesophageal pH (±impedance) monitoring of PPI is mandatory to select patients for antireflux surgery, if endoscopy is negative for unequivocal reflux oesophagitis. CONCLUSION: With the ICARUS guidelines, we generated key recommendations for selection of patients for antireflux surgery.