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Introduction This study aimed to assess the diagnostic yield of routine esophageal biopsies in patients with refractory reflux symptoms. Methods We prospectively enrolled consecutive patients referred for upper endoscopy and collected histological, clinical, and endoscopic data. Results Of the 301 included patients, 14 (4.7%) patients met the clinicopathological diagnostic definition of eosinophilic esophagitis. Presence of dysphagia, food bolus impaction, atopic background, and typical endoscopic features were the factors with the strongest association and diagnostic accuracy for eosinophilic esophagitis. The diagnostic yield in patients lacking symptoms of dysphagia or endoscopic features was negligible (0% and 1.9%, respectively). Discussion Routine esophageal biopsy sampling in patients with refractory reflux symptoms has a low diagnostic yield. Esophageal biopsies should only be obtained in patients with refractory reflux symptoms who also present with dysphagia (see Visual abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B792).

Background In the past, ambulatory 24-h manometry has been shown useful for the evaluation of patients with non-cardiac chest pain (NCCP). With the diagnostic improvements brought by pH-impedance monitoring and high-resolution manometry (HRM), the contribution of ambulatory 24-h manometry to the diagnosis of esophageal hypertensive disorders has become uncertain. Our aim was to assess the additional diagnostic yield of ambulatory manometry to HRM and ambulatory pH-impedance monitoring in this patient population. Methods All patients underwent 24-h ambulatory pressure-pH-impedance monitoring and HRM. Patients had retrosternal pain as a predominant symptom and no explanation after cardiologic and digestive endoscopic evaluations. Diagnostic measurements were analyzed by two independent physicians. Key Results Fifty-nine patients met the inclusion criteria; 37.3% of the patients had their symptoms explained by abnormalities on pH-impedance monitoring and 6.8% by ambulatory manometry. Functional chest pain was diagnosed in 52.5% of the patients. High-resolution manometry, using the Chicago Classification v3.0 criteria alone, did not identify any of the four patients with esophageal spasm on ambulatory manometry. However, taking into account other abnormalities, such as simultaneous (rapid) or repetitive contractions, HRM had a sensitivity of 75% and a specificity of 98.2% for the diagnosis of esophageal spasm. Conclusions & Inferences In the work-up of NCCP, ambulatory 24-h manometry has a low additional diagnostic yield. However, it remains the best technique to identify esophageal spasm as the cause of symptoms. This is particularly useful when an unequivocal diagnosis is needed before treatment.

Reflux symptoms are common among athletes and can have a negative impact on athletic performance. At present, the mechanisms underlying excess reflux during exercise are still poorly understood. The aim of this study was to investigate the effect of exercise on reflux severity and examine the underlying reflux mechanisms. Healthy sporty volunteers were studied using both high-resolution manometry and pH-impedance monitoring. After a meal and a rest period, subjects ran on a treadmill for 30 min at 60% of maximum heart rate, followed by a short rest period and another 20-min period of running at 85% of maximum heart rate. Ten healthy volunteers were included. Exercise led to a significantly higher percentage of time with an esophageal pH

Background The prevalence of gastroesophageal reflux disease (GERD) has increased in the last decades and it is now one of the most common chronic diseases. Throughout time our insight in the pathophysiology of GERD has been characterized by remarkable back and forth swings, often prompted by new investigational techniques. Even today, the pathophysiology of GERD is not fully understood but it is now recognized to be a multifactorial disease. Among the factors that have been shown to be involved in the provocation or increase of reflux, are sliding hiatus hernia, low lower esophageal sphincter pressure, transient lower esophageal sphincter relaxation, the acid pocket, obesity, increased distensibility of the esophagogastric junction, prolonged esophageal clearance, and delayed gastric emptying. Moreover, multiple mechanisms influence the perception of GERD symptoms, such as the acidity of the refluxate, its proximal extent, the presence of gas in the refluxate, duodenogastroesophageal reflux, longitudinal muscle contraction, mucosal integrity, and peripheral and central sensitization. Understanding the pathophysiology of GERD is important for future targets for therapy as proton pump inhibitor-refractory GERD symptoms remain a common problem. Purpose In this review we provide an overview of the mechanisms leading to reflux and the factors influencing perception, in the light of historical developments. It is clear that further research remains necessary despite the recent advances in the understanding of the pathophysiology of GERD.

The purpose of this study was to describe a newly developed speech therapy program as an innovating therapeutic approach and to assess the results of this intervention in patients with supragastric belching. This is a retrospective analysis of prospectively gathered data from 73 patients with supragastric belching who were treated with speech therapy between 2007 and 2017. Of these, 48 were included for evaluation of therapy. Thirty patients had supragastric belching proven by 24-h impedance measurements. Eighteen patients were diagnosed by an experienced speech language pathologist as having supragastric belching according to precise criteria. Speech therapy consists of explanation, creating awareness of esophageal air influx and exercises to discontinue the supragastric belching mechanism. Therapy effect was measured by comparing visual analogue scale (VAS) scores on belching and related symptoms. The median symptom duration at the start of therapy was 2 years. Supragastric belching symptoms decreased significantly with a total median VAS score of 406 (291–463) prior to treatment and a median VAS score of 125 (17–197) following treatment. Forty patients (83%) had a sufficient to major result with a median therapy duration of 3 months and ten sessions. Speech therapy was an effective treatment in the majority of patients with supragastric belching.

Gastroesophageal reflux is considered to be a significant contributing factor to chronic unexplained cough. Patients are often presumed to have reflux-induced cough and are exposed to high-dose and long-term empirical therapy with proton pump inhibitors (PPIs) despite the limited treatment efficacy in this population. We aimed to assess the diagnostic value of 24-hour ambulatory pH-impedance-pressure monitoring for the diagnosis of reflux-induced chronic cough. In this multicenter study, we evaluated 192 patients with chronic cough using 24-hour pH-impedance-pressure monitoring off PPIs. Manometry was used to detect all cough bursts while pH-impedance allowed for the evaluation of all reflux episodes, including weakly acidic reflux. The symptom association probability was used to determine a temporal relationship between reflux and cough. A diagnosis of reflux-induced cough was made in 25.5% of the patients. If only acid reflux episodes were used, 22.4% of those patients would not have been diagnosed. Significantly more patients with reflux-induced cough had typical reflux symptoms (P = 0.031) and a pathological distal acid exposure time (P = 0.025) in comparison to patients without the diagnosis. A diagnosis of cough-induced reflux was made in 24.0% of the patients. Only 59% of all cough bursts were registered by the patients. Overall, only approximately one quarter of patients with chronic unexplained cough have reflux-induced cough, explaining the observation that the vast majority of patients with chronic cough do not benefit from antireflux therapy. pH-impedance-pressure monitoring helps to identify patients who are likely to have reflux as a cause of their chronic cough.

Gastroesophageal reflux is considered to be the most common gastrointestinal cause of non-cardiac chest pain (NCCP). It remains unclear why some reflux episodes in the same patient cause chest pain while others do not. To understand more about the mechanisms by which reflux elicits chest pain, we aimed to identify factors which are important in triggering chest pain. In this multicenter study, 120 patients with NCCP were analyzed using 24-h pH-impedance monitoring. In the patients with a positive association between reflux and chest pain, the characteristics of the reflux episodes which were followed by a chest pain episode were compared with chest pain-free reflux episodes. Using 24-h pH-impedance monitoring, 40% of the NCCP patients were identified as having reflux as a possible cause of their chest pain. Reflux episodes that were associated with chest pain had a higher proximal extent (P=0.007), a higher volume clearance time (P=0.030), a higher 15-minute acid burden (P=0.041), were more often acidic (P=0.011), had a lower nadir pH (P=0.044), and had a longer acid duration time (P=0.027) than reflux episodes which were not followed by chest pain. Patients who experienced typical reflux symptoms were more likely to have reflux as the cause of their chest pain (52 vs. 31.4%, P=0.023). The presence of a larger volume of acid refluxate for a longer period of time appears to be an important determinant of perceiving a reflux episode as chest pain. 24-h pH-impedance monitoring is an important tool in identifying gastroesophageal reflux as a potential cause of symptoms in patients with NCCP

Background Gastro-esophageal reflux can be the cause of chronic cough. In the assessment of the temporal association between reflux and cough, previous studies have used a two-minute time window, based on studies in patients with heartburn. However, it remains unclear whether the optimal time window duration for the evaluation of reflux-induced cough is two minutes as well. Therefore, we aimed to determine whether a two-minute time window is optimal to diagnose reflux-induced cough. Methods In this multicenter study, 137 patients with chronic cough were evaluated using 24-h pH-impedance-pressure monitoring. Repetitive symptom association analysis was employed using an array of time windows of various duration. For each time window, the symptom association probability (SAP) and symptom index (SI) were calculated. Key Results A total of 4377 cough burst episodes and 5074 reflux episodes were detected. The number of patients with a positive SAP increased with increasing window duration until a plateau was reached around a time window duration of 1.5 min. Similarly, the SI increased steeply until a window duration of about 2 min, after which a linear increase was seen. Conclusions and Inferences A two-minute time window seems appropriate for evaluation of the relationship between reflux and chronic cough using 24-h pH-impedance-pressure monitoring. A time window duration of 30 s or 1 min is too short to diagnose patients with reflux-induced cough accurately.

Background Esophageal high-resolution manometry (HRM) has rapidly gained much popularity worldwide. The Chicago Classification for esophageal motility disorders is based on a set of normative values for key metrics that was obtained using one of the commercially available HRM systems. Thus, it is of great importance to evaluate whether these normative values can be used for other HRM systems as well. Purpose In this review, we describe the presently available HRM systems, the currently known normative thresholds and the factors that influence them, and assess the use of these thresholds. Numerous factors including the type of HRM system, demographic factors, catheter diameter, body position during testing, consistency of bolus swallows, and esophageal length have an influence on the normative data. It would thus be ideal to have different sets of normal values for each of these factors, yet at the moment the amount of normative data is limited. We suggest broadening the normal range for parameters, as this would allow abnormal values to be of more significance. In addition, we suggest conducting studies to assess the physiological relevance of abnormal values and stress that for each system different normative thresholds may apply.

ObjectiveGastro-oesophageal reflux is considered to be an important contributing factor in chronic unexplained cough. It remains unclear why some reflux episodes in the same patient causes cough while others do not. To understand more about the mechanism by which reflux induces cough, we aimed to identify factors which are important in triggering cough.DesignIn this multicentre study, 49 patients with reflux-associated chronic cough were analysed using 24-hour pH-impedance-pressure monitoring. The characteristics of reflux episodes that were followed by cough were compared with reflux episodes not associated with cough.ResultsThe majority (72.4%) of the reflux episodes were acidic (pHConclusionsThe presence of a larger volume of refluxate and oesophageal exposure to reflux for a longer period of time seems to play an important role in inducing cough, while the acidity of the refluxate seems to be less relevant. This helps explain the observation that most patients with chronic cough tend not to benefit from acid inhibitory treatment.

International audience; NeuroGUT is a EU-funded initial training network (ITN) of 14 research projects in neurogastroenterology that have employed an equal number of early-stage researchers. Neurogut trainees haveamong other activitiesattended an international conference on irritable bowel syndrome (IBS) in Bologna in 2016 and were asked to critically review and evaluate the current knowledge on IBS for their respective research activities, and to state what they were missing. Most appreciated were the topics brain imaging of gut activity, the role of the gut microbiota, the pharmacology of gut functions, the IBS-IBD interrelation, the new Rome IV criteria, the role of gas, and the placebo response in functional disorders. Missed were more detailed coverage of high-resolution manometry, functional brain imaging, advanced systems medicine approaches and bioinformatics technology, better sub-classification of IBS patients, and the development of disease biomarkers, extended at the molecular (genetic/epigenetic, proteonomic) level. They summarize that despite excellent specialized research, there is a gap open that should be filled with systems medicine. For this, it would be necessary that medical research learns even more from the data sciences and other basic disciplines, for example, information technology and system biology, and also welcomes a change in paradigm that enhances open sharing of data, information, and resources.

Background In patients with typical reflux symptoms that persist despite proton pump inhibitors (PPIs) it is sometimes overlooked that treatment fails due to the presence of other disorders than gastroesophageal reflux disease (GERD). The aim of this study was to determine the underlying cause of reflux symptoms not responding to PPI therapy in tertiary referral patients. Methods Patients with reflux symptoms refractory to PPI therapy who underwent 24-h pH-impedance monitoring were analyzed. Patients in whom a diagnosis was already established before referral, who had previous esophageal or gastric surgery, or who had abnormalities on gastroscopy other than hiatus hernia, were excluded. Key Results In total, 106 patients were included. Esophageal manometry showed achalasia in two patients and distal esophageal spasm in another two. Twenty-four-hour pH-impedance monitoring revealed a total acid exposure time

Esophageal dysphagia is a relatively common symptom. We aimed to evaluate whether subtle, presently not acknowledged forms of dysfunction of the lower esophageal sphincter (LES) could explain dysphagia in a subset of patients with normal findings at high-resolution manometry (HRM) according to the Chicago classification v3.0. We used HRM to compare LES relaxation characteristics in 97 patients with unexplained dysphagia with those in 44 healthy subjects. In addition, normative values for time to LES relaxation and completeness of LES relaxation were calculated. Patients with delayed or incomplete LES relaxation were compared with patients with normal relaxation. Dysphagia patients had a higher nadir LES pressure (P=.001) and a longer time to LES relaxation (P=.012) than healthy subjects. Based on the findings in healthy subjects, normal values of LES relaxation were defined as: ≥50% of swallows with normal LES relaxation time ( 50% swallows with delayed and/or incomplete LES relaxation than healthy controls (25% vs 4.5%; P=.004). Dysphagia patients with >50% delayed and/or incomplete LES relaxation had a significantly higher LES resting pressure (P

With the advent of high-resolution manometry (HRM), a new diagnosis, jackhammer esophagus, was introduced. Little is known about this rare condition, and the relationship between symptoms and hypercontractility is not always straightforward. The aim of our study was to describe a large cohort of patients with jackhammer esophagus and to investigate whether manometric findings are associated with the presence of symptoms. All patients from 06, 2014 until 12, 2015 seen at two tertiary centers with at least one hypercontractile swallow (distal contractile integral [DCI] >8000 mm Hg/s/cm) on HRM were analyzed. Patients with ≥20% premature swallows, or patients with another diagnosis explaining their symptoms were excluded. Of the 34 patients identified with jackhammer esophagus, most suffered from dysphagia (67.6%) and/or chest pain (47.1%). The symptom chest pain was not associated with any of the manometric findings, whereas dysphagia was associated with the DCI of the hypercontractile swallows and with intrabolus pressure. In addition, all patients who had an isolated DCI of the lower esophageal sphincter (LES) zone >2000 mm Hg/s/cm had dysphagia. The differences in HRM and clinical characteristics between subgroups based on the contraction type (single- or multi-peaked) or based on meeting criteria of the Chicago Classification v3.0 and v2.0 were limited. The symptom dysphagia is accompanied with strong contractions of the LES, signs of a possible outflow obstruction, and a very high DCI. The presence of a multipeaked contraction seems to be of limited relevance, and caution is warranted in labeling patients with one hypercontractile swallow as normal