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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.

Background & Aims: Over the last decade, clinical experiences and research studies raised concerns regarding use of proton pump inhibitors (PPIs) as part of the diagnostic strategy for eosinophilic esophagitis (EoE). We aimed to clarify the use of PPIs in the evaluation and treatment of children and adults with suspected EoE to develop updated international consensus criteria for EoE diagnosis., Methods: A consensus conference was convened to address the issue of PPI use for esophageal eosinophilia using a process consistent with standards described in the Appraisal of Guidelines for Research and Evaluation II. Pediatric and adult physicians and researchers from gastroenterology, allergy, and pathology subspecialties representing 14 countries used online communications, teleconferences, and a face-to-face meeting to review the literature and clinical experiences., Results: Substantial evidence documented that PPIs reduce esophageal eosinophilia in children, adolescents, and adults, with several mechanisms potentially explaining the treatment effect. Based on these findings, an updated diagnostic algorithm for EoE was developed, with removal of the PPI trial requirement., Conclusions: EoE should be diagnosed when there are symptoms of esophageal dysfunction and at least 15 eosinophils per high-power field (or approximately 60 eosinophils per mm 2 ) on esophageal biopsy and after a comprehensive assessment of non-EoE disorders that could cause or potentially contribute to esophageal eosinophilia. The evidence suggests that PPIs are better classified as a treatment for esophageal eosinophilia that may be due to EoE than as a diagnostic criterion, and we have developed updated consensus criteria for EoE that reflect this change., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Clinical history, questionnaire data and response to antisecretory therapy are insufficient to make a conclusive diagnosis of GERD in isolation, but are of value in determining need for further investigation. Conclusive evidence for reflux on oesophageal testing include advanced grade erosive oesophagitis (LA grades C and D), long-segment Barrett's mucosa or peptic strictures on endoscopy or distal oesophageal acid exposure time (AET) >6% on ambulatory pH or pH-impedance monitoring. A normal endoscopy does not exclude GERD, but provides supportive evidence refuting GERD in conjunction with distal AET <4% and <40 reflux episodes on pH-impedance monitoring off proton pump inhibitors. Reflux-symptom association on ambulatory reflux monitoring provides supportive evidence for reflux triggered symptoms, and may predict a better treatment outcome when present. When endoscopy and pH or pH-impedance monitoring are inconclusive, adjunctive evidence from biopsy findings (histopathology scores, dilated intercellular spaces), motor evaluation (hypotensive lower oesophageal sphincter, hiatus hernia and oesophageal body hypomotility on high-resolution manometry) and novel impedance metrics (baseline impedance, postreflux swallow-induced peristaltic wave index) can add confidence for a GERD diagnosis; however, diagnosis cannot be based on these findings alone. An assessment of anatomy, motor function, reflux burden and symptomatic phenotype will therefore help direct management. Future GERD management strategies should focus on defining individual patient phenotypes based on the level of refluxate exposure, mechanism of reflux, efficacy of clearance, underlying anatomy of the oesophagogastric junction and psychometrics defining symptomatic presentations., Competing Interests: Competing interests: CPG: consulting: Ironwood, Torax, Quintiles; teaching and speaking: Medtronic, Diversatek, Reckitt-Benckiser. ES: consulting: AbbVie, Allergan, MSD, Takeda, Sofar, Janssen; teaching and speaking: Medtronic, Reckitt-Benckiser, Malesci, Zambon. FZ: research support: Medtronic, Sandhill Scientific; consulting: Allergan, Reckitt-Benckiser; speaking and teaching: Ipsen Pharma, Biocodex, Coloplast, Takeda, Vifor Pharma, Mayoly Spindler. PJK: consulting: Ironwood. FM: teaching and speaking: Laborie, Medtronic; consulting: Allergan, Endostim. AJPMS: none. MV: Vanderbilt University and Diversatek co-own patent on mucosal impedance technology. DS: research support: Diversatek, Reckitt-Benckiser; OMOM, Jinshan Science & Technology (Group) Co. Ltd., Chongqing, China. MRF: research support: Given Imaging/Covidien, Reckitt Benckiser, Mui Scientific. Educational events: Given Imaging/Covidien, MMS, Sandhill Scientific Instruments. Speaking and teaching: Given Imaging/Covidien, Reckitt Benckiser, Shire, Almirall. MV: consulting: Torax. RT: teaching: Laborie. JT: consulting: Ironwood. AJB: research support: Danone, Bayer; speaking and/or consulting: MMS, Astellas, AstraZeneca, Bayer, Almirall and Allergan. JP: research support: Impleo; speaking and/or consulting: Medtronic, Diversatek, Torax, Ironwood, Takeda, AstraZeneca; stock options: Crospon. SR: research support: Sandhill Scientific, Crospon; teaching: Medtronic; speaker: Mayoly Spindler., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Achalasia patients with longstanding disease are considered to be at risk for developing esophageal cancer. Endoscopic screening is not standardized and detection of dysplastic lesions is difficult, for which Lugol chromoendoscopy could be helpful. Aim was to evaluate the efficacy of screening for esophageal dysplasia and carcinoma in patients with longstanding achalasia using Lugol chromoendoscopy., Methods: In this cohort study achalasia patients underwent three-annual screening by Lugol chromoendoscopy between January 2000 and March 2016. Patients with low-grade dysplasia (LGD) underwent yearly screening, patients with high-grade dysplasia (HGD) or carcinoma were treated., Results: In total, 230 achalasia patients (144 male, median age 52 years (IQR 43-63) at first endoscopy) were included. Three patients (1.3%, 2 male, age 68 years (range 50-87)) developed esophageal squamous cell carcinoma (ESCC), without LGD at the preceding screening. Incidence rate for ESCC was 63 (95% CI 13-183) per 100 000 persons-years. LGD was observed in 4 patients (1.7%, 2 male, age 64 years (range 57-73)), without progression to HGD/ESCC during a follow-up of 9 (IQR 7-14) years. ESCC/LGD was diagnosed 30 (IQR 14-36) years after onset of symptoms and 22 (IQR 4-13) years after diagnosis. Lugol chromoendoscopy tripled the detection rate of suspected lesions (111 lesions white light versus 329 lesions Lugol), but only 8% was histopathological confirmed ESCC or LGD., Conclusion: Achalasia patients with longstanding disease (>20 years) have an increased risk to develop esophageal dysplasia and carcinoma. Endoscopic screening using white light and Lugol chromoendoscopy does not accurately identify precursor lesions for ESCC and therefore cannot be systematically recommended.

Background: Eosinophilic esophagitis (EoE) is a chronic esophageal inflammation that may lead to stricture formation. This narrowing can cause major complications including food impactions. Despite increasing interest in EoE accurate data on its natural course is scarce. Therefore, we aimed to investigate the natural course of EoE and to evaluate the association between undiagnosed disease and the occurrence of complications over two decades in a large cohort., Methods: We retrospectively analyzed charts of patients diagnosed with EoE between 1996 and 2015, collected from 15 hospitals throughout the Netherlands. Histologic, clinical, and endoscopic characteristics were identified and stratified by age and diagnostic delay., Results: We included 721 patients (524 males, 117 children (≤18 years)). Dysphagia and food impactions were more common in adults whereas children more often presented with vomiting and abdominal pain (all p < 0.001). The prevalence of fibrotic endoscopic features was higher in adults (76%) than in children (39%) (p < 0.001). As time with undiagnosed disease progressed the percentage of patients with strictures and food impactions increased from 19% and 24% (diagnostic delay ≤ 2 years) to 52% and 57% (diagnostic delay ≥ 21 years) (p < 0.001), respectively. In a multivariate logistic regression model, diagnostic delay (odds ratio (OR) = 1.09; 95% confidence interval (CI) = 1.05-1.13) and male gender (OR = 2.69, 95% CI = 1.61-4.50) were the major risk factors for stricture presence., Conclusion: During the natural course of EoE, progression from an inflammatory to a fibrostenotic phenotype occurs. With each additional year of undiagnosed EoE the risk of stricture presence increases with 9%.

This corrects the article DOI: 10.1038/nrgastro.2017.130.

This corrects the article DOI: 10.1038/nrgastro.2017.132.

Background: The validity of the eosinophilic oesophagitis (EoE) histologic scoring system (EoEHSS) has been demonstrated, but only preliminary reliability data exist., Aim: Formally assess the reliability of the EoEHSS and additional histologic features., Methods: Four expert gastrointestinal pathologists independently reviewed slides from adult patients with EoE (N = 45) twice, in random order, using standardised training materials and scoring conventions for the EoEHSS and additional histologic features agreed upon during a modified Delphi process. Intra- and inter-rater reliability for scoring the EoEHSS, a visual analogue scale (VAS) of overall histopathologic disease severity, and additional histologic features were assessed using intra-class correlation coefficients (ICCs)., Results: Almost perfect intra-rater reliability was observed for the composite EoEHSS scores and the VAS. Inter-rater reliability was also almost perfect for the composite EoEHSS scores and substantial for the VAS. Of the EoEHSS items, eosinophilic inflammation was associated with the highest ICC estimates and consistent with almost perfect intra- and inter-rater reliability. With the exception of dyskeratotic epithelial cells and surface epithelial alteration, ICC estimates for the remaining EoEHSS items were above the benchmarks for substantial intra-rater, and moderate inter-rater reliability. Estimation of peak eosinophil count and number of lamina propria eosinophils were associated with the highest ICC estimates among the exploratory items., Conclusion: The composite EoEHSS and most component items are associated with substantial reliability when assessed by central pathologists. Future studies should assess responsiveness of the score to change after a therapeutic intervention to facilitate its use in clinical trials., (© 2018 John Wiley & Sons Ltd.)

Objective: Distal esophageal spasm (DES) is a rare motility disorder characterized by premature and rapidly propagated contractions of the distal esophagus. Treatment options are limited and often poorly effective. Peroral endoscopic myotomy (POEM) seems an effective and attractive new treatment option for DES. In this case report we describe some of the difficulties that could arise., Materials and Methods: A 84-year old man with therapy-refractory DES and complaints of severe dysphagia and chest pain underwent a POEM procedure under general anesthesia. A longer myotomy was performed to cleave the circular muscle layer from start till end of the spastic contractions., Results: The length of the myotomy was 16 cm. Hyperactive spastic contractions during the procedure complicated the creation of the submucosal tunnel, extended the duration (134 vs. 60-90 min for achalasia), increased postoperative pain and prolonged hospital admission. Intravenously nitroglycerin peroperative diminished spastic contractions. Postoperative a remnant of spastic contractions was present, proximal to the myotomy, causing persistent symptoms., Conclusion: Performing POEM for DES is challenging due to reactive hyperactive spastic contractions during the procedure causing technical difficulties and an extended procedure. A long myotomy, several centimeters above the proximal border of the spastic region, is essential to prevent remnants of spasticity.

Background: Recent reports show increasing incidence of achalasia in some populations. The aim of this study was to estimate incidence, prevalence, and healthcare costs of achalasia in a large cohort in The Netherlands., Methods: Data were obtained from the largest Dutch healthcare insurance company (±4.4 million insured). Adult achalasia patients were identified between 2006 and 2014 when having an achalasia diagnosis code registered. A total of 907 achalasia patients were identified and included in our database, along with 9068 control patients (non-achalasia patients), matched by age and gender., Key Results: The mean incidence over the 9-year period was 2.2 per 100 000 persons and the mean prevalence was 15.3 per 100 000 persons. Mean age of achalasia patients was 54 (range 18-98) years. Male to female ratio was 1:1. Socio-economic status distribution was similar in achalasia patients and controls. Prior to the diagnosis, 74% of achalasia patients received proton pump inhibitors and 26% received anti-emetic medication. The first year after diagnosis median total direct medical costs of achalasia patients were €2283 (IQR 969-3044) per year. Patients above the 90th percentile of €4717 were significantly older than other patients below the 90th percentile (mean age 63 vs 57); P = .005., Conclusion & Inferences: In this large study that used a database comprising about 25% of all inhabitants of The Netherlands, it is confirmed that achalasia affects individuals of both genders and all ages. The costs associated with diagnosis and treatment of new cases of achalasia increase with increasing age., (© 2017 John Wiley & Sons Ltd.)

Background: 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., Methods: 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., Key Results: 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 (<5 seconds) and ≤20% of swallows with incomplete LES relaxation (not reaching a value below 10 mm Hg). Dysphagia patients had significantly more often >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<.001) and a significantly higher intrabolus pressure (P<.001) than dysphagia patients who did not fulfill the criteria., Conclusions and Inferences: Subtle LES relaxation abnormalities, such as a delayed relaxation of the LES and/or incomplete LES relaxation, could be a cause of dysphagia in approximately one quarter of the patients with otherwise unexplained esophageal dysphagia., (© 2017 John Wiley & Sons Ltd.)

Background and Aims: Per-oral endoscopic myotomy (POEM) has been rapidly gaining ground as a treatment for achalasia. Although POEM is a safe and effective treatment, a subset of patients has persistent or recurrent symptoms after POEM. This study aimed to examine the efficacy of different retreatments after failed POEM., Methods: POEM was performed on 441 patients with achalasia at 3 tertiary-care hospitals between 2010 and 2015. A review of prospectively collected data was conducted. All patients with achalasia with significant persistent or recurrent symptoms within 3 years after POEM, defined as an Eckardt symptom score >3, were included., Results: Forty-three of 441 patients (9.8%) had persistent or recurrent symptoms after POEM, of which 34 (8%) received 1 or more retreatments. Retreatment with laparoscopic Heller myotomy and retreatment with POEM showed a modest efficacy of 45% and 63%, respectively, whereas pneumatic dilatation showed a poor efficacy of only 0% to 20%, depending on the size of the balloon. Male patients were more likely to have retreatment failure than female patients (P = .038)., Conclusions: In patients with achalasia with persistent or recurrent symptoms after failed POEM, retreatment with laparoscopic Heller myotomy or retreatment with POEM has a higher efficacy than retreatment with pneumatic dilatations. Failure of retreatment occurred more often in male patients., (Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Skin tests and measurement of serum levels of immunoglobulin E do not accurately identify foods for elimination from the diets of patients with eosinophilic esophagitis (EoE). We investigated whether an esophageal prick test, in which the esophageal mucosa is challenged by local injection of allergen extracts, could identify individuals with esophageal sensitization. During endoscopy, 6 allergens were injected in the esophagus of 8 patients with EoE and 3 patients without EoE (controls). A second endoscopy was performed after 24 hours to evaluate delayed responses. Five of the 8 patients with EoE had evidence for an acute response (luminal obstruction and mucosal blanching); 2 other patients had a delayed wheal or flare reaction. No responses were observed in controls. We conclude that esophageal mucosal food allergen injections induce acute and/or delayed responses in patients with EoE but not controls. The esophageal prick test deserves further exploration because it may guide elimination diets., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The incidence of eosinophilic esophagitis (EoE) has increased rapidly. Most epidemiologic data were gathered in single-center studies over a short timeframe, possibly explaining the heterogeneous incidences., Aim: The aim of this study was to retrospectively estimate the Dutch nationwide incidence of EoE over the last 20 years., Methods: The Dutch pathology registry (PALGA) was queried to identify pathology reports describing esophageal eosinophilia from 1996 to 2016. Cases were eligible if EoE was confirmed by the pathologist. Using the annual Dutch population data, the incidence of EoE was calculated., Key Results: The search yielded 11 288 reports of which 5080 described esophageal eosinophilia. Eosinophilic esophagitis was diagnosed in 2161 patients, 1574 (73%) males and 365 (17%) children. The incidence increased from 0.01 (95% CI 0-0.02) in 1996 to 2.07 (95% CI 2.05-2.23) per 100 000 inhabitants in 2015. The incidence was higher in males than in females, 3.02 (95% CI 2.66-3.41) vs 1.14 (95% CI 0.93-1.38), odds ratio (OR) 2.66 (95% CI 2.10-3.36) and higher in adults than in children, 2.23 (95% CI 1.99-2.49) vs 1.46 (95% CI 1.09-1.91), OR 1.78 (95% CI 1.32-2.40). Incidence of EoE increased more than 200-fold, whereas endoscopy rates only tripled, from 30 in 1996 to 105 per 100 000 inhabitants in 2015. We observed no seasonal variation., Conclusions and Inferences: In the last decades, the Dutch EoE incidence has increased tremendously and still continues to rise. This expansion is only partially driven by increased endoscopy rates., (© 2017 John Wiley & Sons Ltd.)

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., (© The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: High-resolution manometry (HRM) has resulted in new revelations regarding the pathophysiology of gastro-esophageal reflux disease (GERD). The impact of new HRM motor paradigms on reflux burden needs further definition, leading to a modern approach to motor testing in GERD., Methods: Focused literature searches were conducted, evaluating pathophysiology of GERD with emphasis on HRM. The results were discussed with an international group of experts to develop a consensus on the role of HRM in GERD. A proposed classification system for esophageal motor abnormalities associated with GERD was generated., Key Results: Physiologic gastro-esophageal reflux is inherent in all humans, resulting from transient lower esophageal sphincter (LES) relaxations that allow venting of gastric air in the form of a belch. In pathological gastro-esophageal reflux, transient LES relaxations are accompanied by reflux of gastric contents. Structural disruption of the esophagogastric junction (EGJ) barrier, and incomplete clearance of the refluxate can contribute to abnormally high esophageal reflux burden that defines GERD. Esophageal HRM localizes the LES for pH and pH-impedance probe placement, and assesses esophageal body peristaltic performance prior to invasive antireflux therapies and antireflux surgery. Furthermore, HRM can assess EGJ and esophageal body mechanisms contributing to reflux, and exclude conditions that mimic GERD., Conclusions & Inferences: Structural and motor EGJ and esophageal processes contribute to the pathophysiology of GERD. A classification scheme is proposed incorporating EGJ and esophageal motor findings, and contraction reserve on provocative tests during HRM., (© 2017 John Wiley & Sons Ltd.)

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., (© 2017 John Wiley & Sons Ltd.)

Objective: Gastro-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., Design: In 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., Results: The majority (72.4%) of the reflux episodes were acidic (pH<4). Compared with reflux episodes that were not followed by cough, reflux episodes that were followed by a cough burst were associated with a higher proximal extent (p=0.0001), a higher volume clearance time (p=0.002) and a higher acid burden in the preceding 15 min window (p=0.019) and higher reflux burden in the preceding 30 min window (p=0.044). No significant difference was found between the two groups when looking at the nadir pH, the pH drop, the acid clearance time or the percentage of reflux episodes which were acidic., Conclusions: The 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., Competing Interests: Competing interests: AJB received research funding from Endostim, Medical Measurement Systems, Danone and Given and received speaker and/or consulting fees from MMS, Astellas, AstraZeneca and Almirall; DS received a research grant from Sandhill Sc USA., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

GERD is a common condition worldwide. Key mechanisms of disease include abnormal oesophagogastric junction structure and function, and impaired oesophageal clearance. A therapeutic trial of acid-suppressive PPI therapy is often the initial management, with endoscopy performed in the setting of alarm symptoms and to exclude other conditions. If symptoms persist and endoscopy does not reveal evidence of GERD, oesophageal function tests are performed, including oesophageal manometry and ambulatory reflux monitoring. However, reflux episodes can be physiological, and some findings on endoscopy and manometry can be encountered in asymptomatic individuals without GERD symptoms. The diagnosis of GERD on the basis of functional oesophageal testing has been previously reported, but no updated expert recommendations on indications and the interpretation of oesophageal function testing in GERD has been made since the Porto consensus over a decade ago. In this Consensus Statement, we aim to describe modern oesophageal physiological tests and their analysis with an emphasis on establishing indications and consensus on interpretation parameters of oesophageal function testing for the evaluation of GERD in clinical practice. This document reflects the collective conclusions of the international GERD working group, incorporating existing data with expert consensus opinion.

Objectives: There is no clear consensus regarding the most appropriate measure(s) of eosinophilic esophagitis (EoE) disease activity. We aimed to identify all scoring indices used for the measurement of disease activity in EoE, appraise their operating properties, and discuss their value as outcome measures., Methods: MEDLINE, EMBASE, and CENTRAL (The Cochrane library) were searched from inception to 11 May 2016. Randomized controlled trials (RCTs), cohort, case-control, and cross-sectional studies that reported outcomes to measure EoE disease activity or response to treatment were eligible. Operating properties of histologic, endoscopic, and patient reported/symptomatic and health-related quality of life measures were critically appraised according to guidelines proposed by the United States Food and Drug Administration., Results: Of 4,373 citations, 130 studies were eligible, of which 20 were RCTs. Although no index met all evaluative criteria, we found that: (1) the EoE histologic scoring system (EoEHSS) is the most valid histologic measure; (2) the Endoscopic Reference Score (EREFS) is the most reliable and responsive endoscopy measure; and (3) the Eosinophilic Esophagitis Activity Index (EEsAI) or the Dysphagia Symptoms Questionnaire (DSQ) had superior construct validity and responsiveness in adults. The Pediatric Quality of Life Inventory EoE was the most valid pediatric symptomatic measure., Conclusions: Current evidence supports the use of the EoEHSS and EREFS as measures of histologic and endoscopic EoE disease activity, respectively, and the EEsAI, DSQ, or Pediatric Quality of Life Inventory EoE as measures of adult and pediatric symptoms. Additional research is needed to optimize endpoint configuration to facilitate development of new therapies.

High-resolution manometry (HRM) and new analysis algorithms, summarized in the Chicago Classification, have led to a restructured classification of oesophageal motility disorders. This advance has led to increased detection of clinically relevant disorders, in particular achalasia. It has become apparent that the cardinal feature of achalasia - impaired lower oesophageal sphincter (LES) relaxation - can occur in several disease phenotypes: without peristalsis (type I), with pan-oesophageal pressurization (type II), with premature (spastic) distal oesophageal contractions (type III), or with preserved peristalsis (outlet obstruction). Furthermore, no manometric pattern is perfectly sensitive or specific for achalasia caused by a myenteric plexopathy, and there is no biomarker for this pathology. Consequently, physiological testing reveals other syndromes not meeting achalasia criteria that also benefit from therapies formerly reserved for achalasia. These findings have become particularly relevant with the development of a minimally invasive technique for performing a long oesophageal myotomy, the per-oral endoscopic myotomy (POEM). Optimal management is to render treatment in a phenotype-specific manner; that is, POEM calibrated to patient-specific physiology for spastic achalasia and the spastic disorders, and more conservative strategies such as pneumatic dilation for the disorders limited to the LES. This Consensus Statement examines the effect of HRM on our understanding of oesophageal motility disorders, with a focus on the diagnosis, epidemiology and management of achalasia and achalasia-like syndromes.

Objectives: 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., Methods: 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., Results: 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)., Conclusions: 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: An international group of experts evaluated and revised recommendations for ambulatory reflux monitoring for the diagnosis of gastro-esophageal reflux disease (GERD)., Methods: Literature search was focused on indications and technical recommendations for GERD testing and phenotypes definitions. Statements were proposed and discussed during several structured meetings., Key Results: Reflux testing should be performed after cessation of acid suppressive medication in patients with a low likelihood of GERD. In this setting, testing can be either catheter-based or wireless pH-monitoring or pH-impedance monitoring. In patients with a high probability of GERD (esophagitis grade C and D, histology proven Barrett's mucosa >1 cm, peptic stricture, previous positive pH monitoring) and persistent symptoms, pH-impedance monitoring should be performed on treatment. Recommendations are provided for data acquisition and analysis. Esophageal acid exposure is considered as pathological if acid exposure time (AET) is greater than 6% on pH testing. Number of reflux episodes and baseline impedance are exploratory metrics that may complement AET. Positive symptom reflux association is defined as symptom index (SI) >50% or symptom association probability (SAP) >95%. A positive symptom-reflux association in the absence of pathological AET defines hypersensitivity to reflux., Conclusions and Inferences: The consensus group determined that grade C or D esophagitis, peptic stricture, histology proven Barrett's mucosa >1 cm, and esophageal acid exposure greater >6% are sufficient to define pathological GERD. Further testing should be considered when none of these criteria are fulfilled., (© 2017 John Wiley & Sons Ltd.)

In eosinophilic esophagitis (EoE), the esophageal barrier integrity is impaired. Integrity can be assessed with different techniques. To assess the correlations between esophageal eosinophilia and various measures of mucosal integrity and to evaluate whether endoscopic impedance measurements can predict disease activity, endoscopies and mucosal integrity measurements were performed in adult EoE patients with active disease (≥15 eosinophils/high-power field) at baseline ( n = 32) and after fluticasone ( n = 15) and elemental dietary treatment ( n = 14) and in controls ( n = 19). Mucosal integrity was evaluated during endoscopy using electrical tissue spectroscopy (ETIS) measuring mucosal impedance and transepithelial electrical resistance (TER) and transepithelial molecule-flux through biopsy specimens in Ussing chambers. We included 61 measurements; 32 of patients at baseline and 29 after treatment, 3 patients dropped out. After treatment, 20 patients were in remission (≤15 eosinophils/high-power field) and these measurements were compared with 41 measurements of patients with active disease (at baseline or after failed treatment). All four mucosal integrity measures showed significant impairment in active EoE compared with remission. Eosinophilia was negatively correlated with ETIS and TER and positively with transepithelial molecule flux ( P ≤ 0.001). The optimal ETIS cutoff to predict disease activity was 6,000 Ω·m with a sensitivity of 79% [95% confidence interval (CI) 54-94%], specificity of 84% (95% CI 69-94%), positive predictive values of 89% (95% CI 77-95%) and negative predictive values of 71% (95% CI 54-84%). In EoE patients, markers of mucosal integrity correlate with esophageal eosinophilia. Additionally, endoscopic mucosal impedance measurements can predict disease activity. NEW & NOTEWORTHY In adult patients with eosinophilic esophagitis (EoE), the mucosal integrity, measured by making use of four different parameters, correlates strongly with esophageal eosinophilia. The accuracy of endoscopically measured mucosal impedance to distinguish active disease from remission was acceptable with moderate specificity and sensitivity. Mucosal impedance measurements can predict disease activity in adult EoE patients., (Copyright © 2017 the American Physiological Society.)

Over the past decades eosinophilic esophagitis (EoE) has been increasingly diagnosed, and significant progress has been made in our understanding of its pathophysiology. As EoE cannot be cured yet, treatment goals are suppression of disease activity and symptoms as well as the prevention of progression to a more severe disease phenotype. Disease-modifying treatment options can be divided into dietary therapy and immunosuppressive medications, of which topical steroids have been most investigated, yet are still prescribed off-label. In this review, we will summarize recent advances in our understanding of EoE and discuss the mechanisms of action of current treatment options, with emphasis on the role of the esophageal epithelial barrier and the effects of proton-pump inhibitors in the management of patients with EoE.

Purpose of Review: High-resolution manometry (HRM) is increasingly performed worldwide, to study esophageal motility. The Chicago classification is subsequently applied to interpret the manometric findings and facilitate a diagnosis of esophageal motility disorders. This review will discuss new insights regarding the diagnosis and management using the Chicago classification., Recent Findings: Recent studies have demonstrated that high-resolution manometry is superior to conventional manometry, and has a higher sensitivity to diagnose achalasia. Furthermore, the subclassification of achalasia as used in the Chicago classification has prognostic value and can be used to direct treatment. Diagnosis of esophageal spasm has been improved by using the distal latency as diagnostic criterion. Recently, criteria for minor disorders of peristalsis have been sharpened, leading to a lower rate of patients with abnormal results, thereby increasing the relevance of a diagnosis. High-resolution manometry is now considered the gold standard for diagnosis of esophageal motility disorders. The Chicago classification provides a standardized approach for analysis and categorization of abnormalities that has led to a significant increase in our knowledge regarding the diagnosis and management of motility disorders. Further refinement of the classification will be required.

Background: After achalasia treatment, a subset of patients has poor esophageal emptying without having symptoms. There is no consensus on whether to pre-emptively treat these patients. We hypothesized that, if left untreated, these patients will experience earlier symptom recurrence than patients without stasis., Methods: 99 treated achalasia patients who were in clinical remission (Eckardt ≤3) at 3 months after treatment were divided into two groups, based on presence or absence of esophageal stasis on a timed barium esophagogram performed after 3 months., Key Results: Two years after initial treatment, patients with stasis after treatment still had a wider esophagus (3 cm; IQR: 2.2-3.8) and more stasis (3.5 cm; IQR: 1.9-5.6) than patients without stasis (1.8 cm wide and 0 cm stasis; both P<.001). In patients with stasis, the esophageal diameter had increased from 2.5 to 3.0 cm within 2 years of follow-up. The symptoms, need for and time to retreatment were comparable between the two groups. Quality of life and reflux symptoms were also comparable between the two groups., Conclusions & Inferences: Although patients with stasis initially had a wider esophagus and 2 years after treatment also had a higher degree of stasis and a more dilated esophagus, compared to patients without stasis, they did not have a higher chance of requiring retreatment. We conclude that stasis in symptom-free achalasia patients after treatment does not predict treatment failure within 2 years and can therefore not serve as a sole reason for retreatment., (© 2017 John Wiley & Sons Ltd.)

Background: Patients with Barrett's esophagus (BE) usually have severe gastroesophageal reflux. However, they often have surprisingly few reflux symptoms. We hypothesized that BE patients are less sensitive to acid than gastroesophageal reflux disease (GERD) patients without Barrett and that this is due to an unusual preservation of mucosal integrity of the squamous epithelium prohibiting transepithelial acid diffusion., Methods: We prospectively analyzed esophageal sensitivity and esophageal mucosal integrity in GERD patients with and without BE and healthy subjects. An acid perfusion test was performed and mucosal integrity was assessed in vivo by electrical tissue impedance spectroscopy and ex vivo by Ussing chamber experiments with biopsy specimens., Key Results: Gastroesophageal reflux disease patients with BE were less sensitive to acid than GERD patients without BE, but more sensitive to acid than healthy controls (time to perception Barrett's 14.0 minutes, GERD 4.6 minutes, controls 17.5 minutes). However, extracellular impedance (6.2 and 5.7 vs 8.4×10 3  Ω/m) and transepithelial resistance (94.0 and 89 vs 118 Ω/cm 2 ) was similar in BE and GERD patients and significantly lower than in healthy subjects. Transepithelial fluorescein flux was equally increased in GERD patients with and without BE (1.6 and 1.7×10 3 vs 0.6×10 3  nmol/cm 2 /h)., Conclusions & Inferences: Esophageal hypersensitivity to acid is less pronounced in BE patients than in GERD patients without Barrett. However, mucosal integrity of the squamous epithelium is equally impaired in GERD patients with and without Barrett, indicating that factors other than esophageal mucosal barrier integrity explain the difference in acid sensitivity between those with BE and those without., (© 2017 John Wiley & Sons Ltd.)

Objectives: The esophageal mucosal integrity is impaired in eosinophilic esophagitis (EoE) and it has been suggested that the duodenal permeability is increased. The absence of food allergens may restore the integrity. The aims of this study were to assess duodenal permeability in EoE and to evaluate the effect of an elemental diet on the esophageal and duodenal integrity., Methods: In this prospective study 17 adult EoE patients and 8 healthy controls (HC) were included. Esophageal biopsy specimens were sampled before and after 4 weeks of elemental diet to measure eosinophil counts and gene expression of tight junction and barrier integrity proteins. Esophageal and duodenal impedance were measured by electrical tissue impedance spectroscopy and Ussing chambers were used to measure transepithelial resistance (TER) and transepithelial molecule flux. Small intestinal permeability was measured using a test, measuring lactulose/mannitol (L/M) ratios., Results: In EoE patients, the esophageal but not the duodenal integrity was impaired, compared with HC. We observed no significant difference between L/M ratios of HC and EoE patients. After diet, eosinophil counts decreased significantly, which was paralleled by normalization of esophageal impedance and transepithelial molecule flux. The esophageal TER improved significantly, but did not reach values seen in HC. Esophageal expression of genes encoding for barrier integrity proteins filaggrin and desmoglein-1 was impaired at baseline and restored after diet., Conclusions: An elemental diet restores esophageal integrity, suggesting that it is at least partly secondary to allergen exposure. Duodenal integrity seems not to be affected in EoE, and possibly plays a minor role in its pathophysiology.

Background: Pseudoachalasia is a condition in which clinical and manometric signs of achalasia are mimicked by another abnormality, most often a malignancy., Aim: To identify risk factors that suggest presence of malignancy-associated pseudoachalasia., Methods: In this retrospective cohort study, achalasia patients newly diagnosed by manometry were included. Patients with a normal initial endoscopy, clinical and manometric signs of achalasia who were afterwards found to have an underlying malignant cause were classified as pseudoachalasia. Clinical and diagnostic findings were compared between malignant pseudoachalasia and achalasia., Results: We included 333 achalasia patients [180 male, median age 50 (38-62)]. Malignant pseudoachalasia was diagnosed in 18 patients (5.4%). Patients with malignancy-associated pseudoachalasia were older at time of diagnosis [67 (54-71) vs. 49 (37-60) years], had a shorter duration of symptoms [6 (5-10) vs. 25 (11-60) months] and lost more weight [12 (9-17) vs. 5 (0-12) kg). In 61% of the pseudoachalasia patients, the oesophagogastric junction (OGJ) was difficult or impossible to pass during endoscopy, compared to 23% in achalasia. Age ≥55 years (OR 5.93), duration of symptoms ≤12 months (OR 14.5), weight loss ≥10 kg (OR 6.73) and difficulty passing the OGJ during endoscopy (OR 6.06) were associated with a higher risk of malignant pseudoachalasia., Conclusions: Advanced age, short duration of symptoms, considerable weight loss and difficulty in passing the OGJ during endoscopy, are risk factors that suggest potential malignancy-associated pseudoachalasia. To exclude pseudoachalasia, additional investigations are warranted when two or more risk factors are present., (© 2017 John Wiley & Sons Ltd.)

Background: Rumination syndrome is characterized by recurrent regurgitation of recently ingested food into the mouth. Differentiation with other diagnoses and gastroesophageal reflux disease (GERD) in particular, is difficult. Recently, objective pH-impedance (pH-MII) and manometry criteria were proposed for adults. The aim of this study was to determine diagnostic ambulatory pH-MII and manometry criteria for rumination syndrome in children., Methods: Clinical data and 24-hour pH-MII and manometry recordings of children with a clinical suspicion of rumination syndrome were reviewed. Recordings were analyzed for retrograde bolus flow extending into the proximal esophagus. Peak gastric and intraesophageal pressures closely related to these events were recorded and checked for a pattern compatible with rumination. Events were classified into primary, secondary, and supragastric belch-associated rumination., Key Results: Twenty-five consecutive patients (11 males, median age 13.3 years [IQR 5.9-15.8]) were included; recordings of 18 patients were suitable for analysis. Rumination events were identified in 16/18 patients, with 50% of events occurring <30 minutes postprandially. Fifteen of 16 patients showed ≥1 gastric pressure peak >30 mmHg, while only 50% of all events was characterized by peaks >30 mmHg and an additional 20% by peaks >25 mmHg. Four patients had evidence of acid GERD, all showing secondary rumination., Conclusions and Inferences: Combined 24-hour pH-MII and manometry can be used to diagnose rumination syndrome in children and to distinguish it from GERD. Rumination patterns in children are similar compared with adults, albeit with lower gastric pressure increase. We propose a diagnostic cutoff for gastric pressure increase >25 mmHg associated with retrograde bolus flow into the proximal esophagus., (© 2017 John Wiley & Sons Ltd.)

Introduction: Eosinophilic esophagitis (EoE) is one of the most prevalent esophageal diseases and the leading cause of dysphagia and food impaction in children and young adults. This underlines the importance of optimizing diagnosys and treatment of the condition, especially after the increasing amount of knowledge on EoE recently published. Therefore, the UEG, EAACI ESPGHAN, and EUREOS deemed it necessary to update the current guidelines regarding conceptual and epidemiological aspects, diagnosis, and treatment of EoE., Methods: General methodology according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used in order to comply with current standards of evidence assessment in formulation of recommendations. An extensive literature search was conducted up to August 2015 and periodically updated. The working group consisted of gastroenterologists, allergists, pediatricians, otolaryngologists, pathologists, and epidemiologists. Systematic evidence-based reviews were performed based upon relevant clinical questions with respect to patient-important outcomes., Results: The guidelines include updated concept of EoE, evaluated information on disease epidemiology, risk factors, associated conditions, and natural history of EoE in children and adults. Diagnostic conditions and criteria, the yield of diagnostic and disease monitoring procedures, and evidence-based statements and recommendation on the utility of the several treatment options for patients EoE are provided. Recommendations on how to choose and implement treatment and long-term management are provided based on expert opinion and best clinical practice., Conclusion: Evidence-based recommendations for EoE diagnosis, treatment modalities, and patients' follow up are proposed in the guideline.

Background: 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., Methods: 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., Key Results: 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., Conclusions & Inferences: 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., (© 2016 John Wiley & Sons Ltd.)

Background: Eosinophilic oesophagitis (EoE) is a chronic disease, driven by food allergens. Elemental diets are effective for the management of children with EoE, but studies on the effect of elemental diets in adults are scarce and poor palatability challenges dietary adherence., Aim: To assess the effects of an elemental diet (Neocate, Nutricia, Utrecht, the Netherlands) on the inflammation, symptoms and endoscopic signs in adult EoE patients., Methods: In this prospective study, 21 patients with active EoE, confirmed by biopsies showing ≥15 eosinophils per microscopic high power field (HPF) and symptoms of oesophageal dysfunction were included. Patients underwent endoscopy before and 4 weeks after diet. Histological disease activity (peak eosinophil count/HPF), and endoscopic signs were scored by physicians. Symptoms and adherence to the diet were evaluated by questionnaires. Serum total IgE levels and total eosinophil counts were determined and the expression of inflammatory cytokines was analysed by qPCR., Results: In total, 17 (81%) of the patients completed the diet, of whom 12 (71%) showed complete histological response (≤15 eosinophils/HPF) and 4 (24%) showed partial histological response (≥50% reduction of baseline eosinophil count). Peak eosinophil counts decreased significantly after the diet from 40 to 9 per HPF (P ≤ 0.001). A marked improvement in endoscopic signs was observed. Symptoms decreased significantly in all subjects, and 15 patients (88%) became completely asymptomatic (P ≤ 0.001). In 14 patients (82%), blood eosinophil count and serum IgE decreased (P ≤ 0.05)., Conclusion: Elemental diet reduces eosinophilic inflammation and induces clinical remission in adult patients with eosinophilic oesophagitis., (© 2017 The Authors. Alimentary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.)

In achalasia and spastic esophageal motility disorders, botulinum toxin (botox) injection is considered an effective and low-risk procedure for short-term symptom relief. It is mainly offered to medically high-risk patients. However, no analysis of risks of botox injections has been performed. To determine the incidence and risk factors of procedure-related complications after esophageal botox injections, we analyzed the records of all patients undergoing botox injection therapy for esophageal motility disorders at four university hospitals in Europe and North America between 2008 and 2014. Complications were assigned grades according to the Clavien-Dindo classification. In 386 patients, 661 botox treatments were performed. Main indications were achalasia (51%) and distal esophageal spasm (DES) (30%). In total, 52 (7.9%) mild complications (Clavien-Dindo grade I) were reported by 48 patients, the majority consisting of chest pain or heartburn (29 procedures) or epigastric pain (5 procedures). No ulceration, perforation, pneumothorax, or abscess were reported. One patient died after developing acute mediastinitis (Clavien-Dindo grade V) following injections in the body of the esophagus. In univariate logistic regression, younger age was associated with an increased risk of complications (OR 1.43, 95%CI 1.03-1.96). Treatment for DES, injections into the esophageal body, more injections per procedure, more previous treatments and larger amount of injected botulinum toxin were no risk factors for complications. Esophageal botox injection seems particularly appropriate for high-risk patients due to low complication rate. However, it should not be considered completely safe, as it is associated with rare side effects that cannot be predicted., (© 2016 International Society for Diseases of the Esophagus.)

Background: Criteria for transient lower esophageal sphincter relaxations (TLESRs) are well-defined for Dentsleeve manometry. As high-resolution manometry (HRM) is now the gold standard to assess esophageal motility, our aim was to propose a consensus definition of TLESRs using HRM., Methods: Postprandial esophageal HRM combined with impedance was performed in 10 patients with gastroesophageal reflux disease. Transient lower esophageal sphincter relaxations identification was performed by 17 experts using a Delphi process. Four investigators then characterized TLESR candidates that achieved 100% agreement (TLESR events) and those that achieved less than 25% agreement (non-events) after the third round. Logistic regression and decision tree analysis were used to define optimal diagnostic criteria., Key Results: All diagnostic criteria were more frequently encountered in the 57 TLESR events than in the 52 non-events. Crural diaphragm (CD) inhibition and LES relaxation duration >10 seconds had the highest predictive value to identify TLESR. Based on decision tree analysis, reflux on impedance, esophageal shortening, common cavity, upper esophageal sphincter relaxation without swallow and secondary peristalsis were alternate diagnostic criteria., Conclusion & Inferences: Using HRM, TLESR might be defined as LES relaxation occurring in absence of swallowing, lasting more than 10 seconds and associated with CD inhibition., (© 2016 John Wiley & Sons Ltd.)

Background: Manometric criteria to diagnose achalasia are absent peristalsis and incomplete relaxation of the esophagogastric junction (EGJ), determined by an integrated relaxation pressure (IRP) >15 mm Hg. However, EGJ relaxation seems normal in a subgroup of patients with typical symptoms of achalasia, no endoscopic abnormalities, stasis on timed barium esophagogram (TBE), and absent peristalsis on high-resolution manometry (HRM). The aim of our study was to further characterize these patients by measuring EGJ distensibility and assessing the effect of achalasia treatment., Methods: Impedance planimetry (EndoFLIP) was used to measure EGJ distensibility and compared to previous established data of 15 healthy subjects. In case the EGJ distensibility was impaired, achalasia treatment followed. Eckardt score, HRM, TBE, and EGJ distensibility measurements were repeated >3 months after treatment., Key Results: We included 13 patients (5 male; age 19-59 years) with typical symptoms of achalasia, Eckardt score of 7 (5-7). High-resolution manometry showed absent peristalsis with low basal EGJ pressure of 10 (5.8-12.9) mm Hg and IRP of 9.3 (6.1-12) mm Hg. Esophageal stasis was 4.6 (2.7-6.9) cm after 5 minutes. Esophagogastric junction distensibility was significantly reduced in patients compared to healthy subjects (0.8 [0.7-1.2] mm 2 /mm Hg vs 6.3 [3.8-8.7] mm 2 /mm Hg). Treatment significantly improved the Eckardt score (7 [5-7] to 2 [1-3.5]) and EGJ distensibility (0.8 [0.7-1.2] mm 2 /mm Hg to 3.5 [1.5-6.1] mm 2 /mm Hg)., Conclusions & Inferences: A subgroup of patients with clinical and radiological features of achalasia but manometrically normal EGJ relaxation has an impaired EGJ distensibility and responds favorably to achalasia treatment. Our data suggest that this condition can be considered as achalasia and treated as such., (© 2016 John Wiley & Sons Ltd.)

Background: The relationship between the severity of endoscopic signs scored according to the Endoscopic Reference Score (EREFS) and histopathologic signs of eosinophilic esophagitis (EoE) has not been sufficiently explored. We aimed to determine if the EREFS system predicts histopathologic activity in EoE patients., Methods: We included 69 patients with EoE (age 35 [IQR 29-48] years; 80% male) who, between 2006 and 2014, underwent esophagogastroduodenoscopy (EGD) during which high-quality endoscopic images were taken and esophageal biopsy specimens were obtained. Per EGD, three or more depersonalized images were scored by an expert endoscopist, and histopathologic signs were scored by a pathologist with gastrointestinal expertise; both in a blinded fashion. The predictive values of endoscopic signs for disease activity (peak eosinophil count) were calculated. In addition, we measured the utility of the EREFS in the follow-up of 35 EoE patients., Key Results: Individual endoscopic signs did not correspond to the peak eosinophil count or other histopathologic signs. Although the composite fibrotic signs score, inflammatory signs score, and total EREFS correlated weakly to moderately with the peak eosinophil count, none of these scores had both high positive and negative predictive values for histopathologic disease activity. In the follow-up of 35 patients, lower peak eosinophil counts were not associated with a decrease in endoscopic abnormalities., Conclusions & Inferences: In adult patients with EoE, the EREFS system correlates with peak eosinophil counts, but their predictive value for disease activity is insufficient for clinical use. Therefore, biopsies remain indispensable for the assessment of disease activity., (© 2016 John Wiley & Sons Ltd.)

Background: Heller myotomy is an effective treatment for the majority of achalasia patients. However, a small proportion of patients suffer from persistent or recurrent symptoms after surgery and they are usually subsequently treated with pneumodilation (PD). Data on the efficacy of PD as secondary treatment for achalasia are scarce. Therefore, this study aimed to investigate the efficacy of PD as treatment for achalasia patients suffering from persistent or recurrent symptoms after Heller myotomy., Methods: Patients with recurrent or persistent symptoms (Eckardt score >3) after Heller myotomy were selected. Patients were treated with PD, using a graded distension protocol with balloon sizes ranging from 30 to 40 mm. After each dilation symptoms were assessed to evaluate whether a subsequent dilation with a larger balloon size was required. Patients with recurrent or persistent symptoms (Eckardt score >3) after treatment with a 40-mm balloon were identified as failures., Key Results: Twenty-four patients were included in total; 15 patients with achalasia type I, seven with achalasia type II and two with achalasia type III. Median relapse time was 2.5 years after Heller myotomy (IQR: 9 years and 3 months). Three patients were not suitable for PD; one patient was morbidly obese and not fit for any form of sedation and two had a siphon-shaped esophagus leaving 21 patients to treat. Eight patients were successfully treated with a single 30-mm balloon dilation (median follow-up time: 6.5 years; IQR: 7.5 years). Four patients required dilations with 30- and 35-mm balloons (median follow-up time: 11 years; IQR: 3 years). Nine patients failed on the 35-mm balloon dilation and underwent a subsequent dilation with a 40-mm balloon, and all failed on this balloon as well. Thus, PD was successful in 12 of the 21 treatable patients, resulting in a success rate of 57% for treatable patients or 50% for all patients. Baseline Eckardt scores were also higher in those that failed (median: 8; IQR: 2) than those that were treated successfully (median: 5.5; IQR: 2) treated (p = 0.009). Furthermore, baseline barium column height at 5 min was higher in patients with failed (median: 6 cm; IQR: 6 cm) treatment than in patients with successful (median: 2.6 cm; IQR: 4.7 cm) treatment (p = 0.016). Baseline lower esophageal sphincter pressure was not different between patients who were treated successfully (median: 11 mmHg; IQR: 5 mmHg) and those that failed on PD (median: 17.5 mmHg; IQR: 10.8 mmHg) treatment (p > 0.05). Baseline symptom pattern was also not a predictor of successful treatment. No adverse events were recorded during or after PD., Conclusions & Inferences: Pneumodilation for recurrent symptoms after previous Heller myotomy is safe and has a modest success rate of 57%, using 30- and 35-mm balloons. Patients with recurrent symptoms after PD with 35-mm balloon are likely to also fail after subsequent dilation with a 40-mm balloon., (© 2016 John Wiley & Sons Ltd.)

Background: Patients with functional heartburn (FH) experience troublesome heartburn that is not related to gastroesophageal reflux. The etiology of the heartburn sensation in FH patients is unknown. In patients with reflux disease, esophageal hypersensitivity seems associated with impaired mucosal integrity. We aimed to determine esophageal sensitivity and mucosal integrity in FH and non-erosive reflux disease (NERD) patients., Methods: In this prospective experimental study, we performed an acid perfusion test and upper endoscopy with biopsies in 12 patients with NERD and nine patients with FH. Mucosal integrity was measured during endoscopy using electrical tissue impedance spectroscopy and biopsy specimens were analyzed in Ussing chambers for transepithelial electrical resistance and transepithelial permeability., Key Results: Lag time to heartburn perception was significantly longer in FH patients (median 12 min) than in NERD patients (median 3 min). Once perceived, intensity of heartburn was scored equal with median visual analog scale 6.5 and 7.1 respectively. Esophageal mucosal integrity was also comparable between FH and NERD patients, both in vivo extracellular impedance and ex vivo transepithelial resistance and permeability were similar., Conclusions & Inferences: Patients with FH did not show acid hypersensitivity as seen in patients with NERD. However, once perceived, intensity of heartburn is similar. Esophageal mucosal integrity is similar between NERD and FH patients, and is therefore unlikely to be the underlying cause of the observed difference in esophageal acid perception., (© 2016 John Wiley & Sons Ltd.)

Background and aims: After Peroral Endoscopic Myotomy (POEM), the mucosal incision is closed with endoscopically applied clips. After each clip placement, a subsequent clipping device has to be introduced through the working channel. With the Clipmaster3, three consecutive clips can be placed without reloading which could reduce closure time. We performed a prospective study evaluating efficacy, safety, and ease of use. Closure using Clipmaster3 was compared to closure with standard clips. Methods: Patients undergoing closure with the Clipmaster3 were compared to patients who underwent POEM with standard clip closure. Results: In total, 12 consecutive POEM closures with Clipmaster3 were compared to 24 standard POEM procedures. The Clipmaster3 and the standard group did not differ in sex distribution, age (42 years [29 - 49] vs 41 years [34 - 54] P  = 0.379), achalasia subtype, disease duration, length of the mucosal incision (25.0 mm [20 - 30] vs 20.0 mm [20 - 30], P  = 1.0), and closure time (622 seconds [438 - 909] vs 599 seconds [488 - 664] P  = 0.72). Endoscopically successful closure could be performed in all patients. The proportion of all clips used that were either displaced or discarded was larger for Clipmaster3 (8.8 %) compared to standard closure (2.0 %, P  = 0.00782). Ease of handling VAS (visual analogue scale) score for Clipmaster3 did not differ between endoscopist and endoscopy nurse (7 out of 10). Conclusions: Clipmaster3 is feasible and safe for closure of mucosal incisions after POEM. Clipmaster3 was not associated with reduced closure time. Compared to standard closure, more Clipmaster3 clips were displaced or discarded to achieve successful closure. A training effect cannot be excluded as a cause of these results., Study Registration: NCT01405417.

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., (© 2016 John Wiley & Sons Ltd.)