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OBJECTIVE: To evaluate prospectively the complications that occurred during consecutive endoscopies of the upper gastrointestinal tract. PATIENTS AND METHODS: We evaluated all endoscopies of the upper gastrointestinal tract (except endoscopic retrograde cholangiopancreatography and endosonography) performed at the Ambulatory Surgical Center at the Mayo Clinic in Jacksonville, Fla, between January 1999 and June 2002. A staff gastroenterologist with or without a trainee performed these procedures. Therapeutic procedures included esophageal band ligation, injection sclerotherapy, botulinum toxin injection, extended upper endoscopy, pneumatic balloon dilation, endoscopic mucosal resection, and endoscopic ablation using thermal laser, argon beam coagulator, or photodynamic therapy. All complications were tabulated prospectively as per mandatory state licensure reporting. RESULTS: Complications after diagnostic endoscopy of the upper gastrointestinal tract were related to anesthesia in 2 of the 12,841 patients. Perforations in 5 patients were associated with esophageal dilation (2), resection of duodenal lesions (2), or passage of a side-viewing instrument into the duodenum (1). No deaths occurred. CONCLUSIONS: Diagnostic endoscopy of the upper gastrointestinal tract is safe, with a complication rate of less than 1 per 5000 cases. Therapeutic endoscopy increases the risk of complications. Compared with complication rates published previously, our results from a single center indicate a favorable reduction in complications related to endoscopy of the upper gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Background: Patients with erosive oesophagitis, and those with persistent symptomatic non-erosive gastro-oesophageal reflux disease, require long-term maintenance treatment with acid-suppressing agents., Aim: To evaluate the safety of vonoprazan, a potassium-competitive acid blocker, in an integrated analysis of data from clinical trials in adults., Methods: We included 14 clinical trials of vonoprazan conducted in multiple countries. Mean duration of exposure in person-years to vonoprazan (n = 5318) was 2068, to comparators lansoprazole (n = 1925) or esomeprazole (n = 86) was 751, and to placebo (n = 779) was 59. We report adverse events, serum gastrin, and liver enzyme levels as the main outcomes. Post-marketing safety data from December 26, 2014 (date of commercialisation in Japan) to December 25, 2023, are also provided., Results: Nasopharyngitis was the only adverse event reported by at least 5.0% of patients (6.94% vonoprazan, 5.07% proton pump inhibitor (PPI), 4.49% placebo). Incidence rates per 100 person-years for serious adverse events were 10.39 for vonoprazan, 10.65 for PPIs, and 1.69 for placebo. One patient each on vonoprazan and lansoprazole was diagnosed with gastric cancer. Mean serum gastrin levels were higher on vonoprazan than lansoprazole but normalised by 4 weeks after discontinuation. Elevated liver enzyme levels were infrequent and of low magnitude with no differences between vonoprazan and PPIs. There were four deaths; none was considered related to study drug., Conclusions: Vonoprazan was well tolerated. Its safety profile from both clinical trial and post-marketing data were consistent and comparable to that of its PPI comparators with respect to treatment-emergent adverse events., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Eosinophilic esophagitis (EoE) is an increasingly common cause of food impaction., Aims: This study aims to provide a nationwide analysis of food impaction in patients with or without EoE diagnosis, concentrating on patient demographics, interventions, outcomes, and development of predictive machine-learning models., Methods: A retrospective assessment was conducted using Nationwide Emergency Department Sample data from January 1, 2018, to December 31, 2019. We compared patients with food impaction with an associated EoE diagnosis to those without EoE and derived machine-learning models to predict EoE using International Classification of Diseases codes at discharge for identification., Results: Of 286,886,714 emergency department visits, 146,084 were for food impaction, with 7093 cases coinciding with an EoE diagnosis (4.9%). Patients with EoE were more commonly young men with fewer overall comorbidities but higher incidences of obesity, asthma, gastritis, and allergic rhinitis. A significantly larger proportion in the EoE group (89.6%) underwent esophagogastroduodenoscopy compared to the non-EoE group (51.1%; P < 0.001) and had a higher rate of biopsy during esophagogastroduodenoscopy in the emergency department (54.9% vs 13.4%; P < 0.001). Our machine-learning models, incorporating patient demographics, hospital attributes, and comorbidities, had a sensitivity of 86.1% and an area under the receiver operating characteristic curve of 0.828., Conclusions: This nationwide study demonstrates that EoE in food impaction is associated with specific patient demographics, comorbidities, and elevated interventions. Our machine-learning models hold promise as screening tools for EoE, aiding medical practitioners in determining the need for biopsy., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: Exempt for IRB review., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Approximately 30% of patients with typical gastroesophageal reflux disease (GERD) symptoms have endoscopic evidence of erosive esophagitis (EE). 1 The severity of EE is commonly graded using the Los Angeles (LA) classification system as grade A (minimal) to D (very severe), depending on the extent of endoscopically visible mucosal breaks (Supplementary Figure 1). 2 Accurate grading of EE severity is crucial in clinical trials of medical EE treatments, as EE severity strongly influences both initial rates of healing and the likelihood of recurrence during maintenance treatment. 3,4 Almost all EE treatment studies have relied exclusively on local investigators' grading of EE severity to determine study eligibility and response to treatment. Those few studies that included central adjudication did not assess the reliability of grading by local investigators. 5 Unlike typical studies of EE treatment, the phase III clinical trial of vonoprazan versus lansoprazole for the treatment of EE (NCT04124926) mandated central adjudication of endoscopic grading for study participation. 6 The aim of the present investigation was to evaluate the rate of agreement between local investigators and central adjudicators for EE grading during screening for entrance into that clinical trial., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: For many patients with lung disease the only proven intervention to improve survival and quality of life is lung transplantation (LTx). Esophageal dysmotility and gastroesophageal reflux (GER) are common in patients with respiratory disease, and often associate with worse prognosis following LTx. Which, if any patients, should be excluded from LTx based on esophageal concerns remains unclear. Our aim was to understand the effect of LTx on esophageal motility diagnosis and examine how this and the other physiological and mechanical factors relate to GER and clearance of boluses swallowed., Methods: We prospectively recruited 62 patients with restrictive (RLD) and obstructive (OLD) lung disease (aged 33-75 years; 42 men) who underwent high resolution impedance manometry and 24-h pH-impedance before and after LTx., Key Results: RLD patients with normal motility were more likely to remain normal (p = 0.02), or if having abnormal motility to change to normal (p = 0.07) post-LTx than OLD patients. Esophageal length (EL) was greater in OLD than RLD patients' pre-LTx (p < 0.001), reducing only in OLD patients' post-LTx (p = 0.02). Reduced EL post-LTx associated with greater contractile reserve (r = 0.735; p = 0.01) and increased likelihood of motility normalization (p = 0.10). Clearance of reflux improved (p = 0.01) and associated with increased mean nocturnal baseline impedance (p < 0.001) in RLD but not OLD. Peristaltic breaks and thoraco-abdominal pressure gradient impact both esophageal clearance of reflux and boluses swallowed (p < 0.05)., Conclusions and Inferences: RLD patients are more likely to show improvement in esophageal motility than OLD patients post-LTx. However, the effect on GER is more difficult to predict and requires other GI, anatomical and pulmonary factors to be taken into consideration., (© 2024 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Importance and Objective: Gastroesophageal reflux disease (GERD) is a chronic condition associated with several risk factors, but little is known about the association between hormone therapy (HT) and GERD in postmenopausal women., Evidence Review: We investigated the association between ever or current menopausal HT use and GERD using a systematic review and meta-analysis. Studies published between 2008 and August 31, 2022, were pooled using a DerSimonian and Laird random-effects model, and outcomes were reported as adjusted odds ratios (aOR) with a corresponding 95% CI., Findings: The pooled analysis of five studies found a significant direct association between estrogen use and GERD (aOR, 1.41; 95% CI, 1.16-1.66; I2 = 97.6%), and progestogen use and GERD (two studies: aOR, 1.39; 95% CI, 1.15-1.64; I2 = 0.0%). The use of combined HT was also associated with GERD (1.16; 95% CI, 1.00-1.33; I2 = 87.9%). Overall, HT use was associated with 29% higher odds for GERD (aOR, 1.29; 95% CI, 1.17-1.42; I2 = 94.8%). The large number of pooled participants, differences in study design, geography, patient characteristics, and outcome assessment resulted in significant high heterogeneity., Conclusions and Relevance: There is a significant association between ever or current HT use and GERD. However, the results should be interpreted with caution, given the small number of included studies and high heterogeneity. This warrants careful evaluation of GERD risk factors when prescribing HT to reduce the risk of potential GERD complications., Competing Interests: Financial disclosure/conflicts of interest: None reported., (Copyright © 2023 by The North American Menopause Society.)

Background: The number of bottles of esophageal biopsies needed for the evaluation of eosinophilic esophagitis (EoE) is unclear, despite cost differences., Aims: Assess the clinical outcomes between patients with one and two bottles of esophageal biopsies for the assessment of EoE., Methods: Retrospective study of adults who underwent esophagogastroduodenoscopy (EGD) for esophageal symptoms between January 2015 and June 2021 and findings of ≥15 eosinophils per high power field (eos/hpf). Patients with one bottle (1 bottle-EoE) had biopsies from the entire or proximal esophagus. Patients with two bottles had biopsies separated from the distal and proximal esophagus and were separated into those with ≥ 15 eos/hpf in both bottles (2 bottle Dif-EoE), or the distal bottle alone (2 bottle Lim-EoE). The primary outcomes were endoscopic findings at follow-up EGD as assessed by the Eosinophilic Esophagitis Endoscopic Reference Score (EREFS) and the presence of ≥15 eos/hpf., Results: Of 85 patients with esophageal eosinophilia who met inclusion criteria, 49 had 2 bottle Dif-EoE, 18 had 2 bottle Lim-EoE, and 18 had 1 bottle-EoE. At median follow-up of 3.3-5.6 months, more patients with 1 bottle EoE had dysphagia (p = 0.029), however there were no differences in the EREFS (p = 0.14) or presence of ≥15 eos/hpf (p = 0.39). More patients with 2 bottle Dif-EoE were treated with topical steroids (16.3% vs. 0% vs. 0%, p = 0.039) and diet (20.4% vs. 0% vs. 5.6%, p = 0.05)., Conclusion: Endoscopic and histologic outcomes were similar in patients who had one and two bottles for esophageal biopsies in the evaluation of EoE., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Purpose: Gastro-oesophageal reflux disease (GORD) is commonly thought to play an important role in chronic cough and patients are often empirically treated with acid suppression therapy. We sought to investigate the response rate to acid suppression treatment in patients with and without heartburn attending two specialist cough clinics., Methods: A retrospective review of 558 consecutive patients referred to two specialist cough clinics was performed (UK and USA). Patients who were treated with acid suppression were included and their documented response to treatment was collected. Binary logistic regression was used to ascertain the value of reported heartburn in predicting the response of chronic cough to acid suppression therapy., Results: Of 558 consecutive referrals, 238 patients were excluded due to missing data or cough duration of < 8 weeks. The remaining 320 patients were predominantly female (76%), with mean age 61 yrs (± 13) and 96.8% non-smokers, with chronic cough for 36 (18-117) months. Of 72 patients with heartburn, 20 (28%) noted improvement in their cough with acid suppression, whereas of 248 without heartburn, only 35 (14%) responded. Patients reporting heartburn were 2.7 (95% C.I. 1.3-5.6) times more likely to respond to acid suppression therapy (p = 0.007)., Conclusion: In specialist cough clinics, few patients report a response of their chronic cough to acid suppression therapy. Nonetheless, heartburn is a useful predictor substantially increasing the likelihood of benefit., (© 2021. The Author(s).)

Background: Irritable bowel syndrome (IBS) patients often experience meal-associated symptoms. However, the underlying mechanisms are unclear., Aim: To determine small intestinal mechanisms of lipid-induced symptoms and rectal hypersensitivity in IBS METHODS: We recruited 26 IBS patients (12 IBS-C, 14 IBS-D) and 15 healthy volunteers (HV). In vivo permeability was assessed using saccharide excretion assay. Rectal sensitivity was assessed using a barostat before and after small bowel lipid infusion; symptoms were assessed throughout. Next, an extended upper endoscopy with probe-based confocal laser endomicroscopy (pCLE) was performed with changes induced by lipids. Duodenal and jejunal mucosal biopsies were obtained for transcriptomics., Results: Following lipid infusion, a higher proportion of HV than IBS patients reported no pain, no nausea, no fullness and no urgency (P < 0.05 for all). In a model adjusted for sex and anxiety, IBS-C and IBS-D patients had lower thresholds for first rectal sensation (P = 0.0007) and pain (P = 0.004) than HV. In vivo small intestinal permeability and mean pCLE scores were similar between IBS patients and HV. Post-lipid, pCLE scores were higher than pre-lipid but were not different between groups. Baseline duodenal transient receptor potential vanilloid (TRPV) 1 and 3 expression was increased in IBS-D, and TRPV3 in IBS-C. Duodenal TRPV1 expression correlated with abdominal pain (r = 0.51, FDR = 0.01), and inversely with first rectal sensation (r = -0.48, FDR = 0.01) and pain (r = -0.41, FDR = 0.02) thresholds., Conclusion: Lipid infusion elicits a greater symptom response in IBS patients than HV, which is associated with small intestinal expression of TRPV channels. TRPV-mediated small intestinal chemosensitivity may mediate post-meal symptoms in IBS., (© 2021 John Wiley & Sons Ltd.)

Background: Lymphocytic esophagitis is a rare esophageal condition. Our knowledge of potential risk factors and treatment outcomes of lymphocytic esophagitis is limited., Aim: To investigate potential risk factors associated with the development of lymphocytic esophagitis and compare clinical characteristics and treatment outcomes of patients diagnosed with lymphocytic esophagitis to patients diagnosed with eosinophilic esophagitis., Methods: This is a multicenter retrospective study. Lymphocytic esophagitis patients were identified based on pathology results between 1997 and 2019. Control groups consisted of patients with normal esophageal biopsies and patients diagnosed with eosinophilic esophagitis. Thirteen potential risk factors for lymphocytic esophagitis were analyzed using univariate and multivariate models including IBD, achalasia, hyperlipidemia, hypothyroidism, celiac sprue, CVID, H. pylori, thymoma, aspirin, opioids, ACE-I, metformin, and statin use. Comparative statistics were performed., Results: Ninety-four adult patients with lymphocytic esophagitis, 344 with eosinophilic esophagitis, and 5202 control patients with normal esophageal biopsies were analyzed. Age older than 60 [adjusted odd ratio (AOR) 1.03, 95% CI 1.02-1.05, p = 0.001], aspirin use (2.7, 95% CI 1.4-4.9, p = 0.001), statin use (2.2, 95% CI 1.2-4.2, p = 0.01), or a diagnosis of achalasia (2.4, 95% 1.08-5.67, p = 0.03) were associated with lymphocytic esophagitis. Compared to eosinophilic esophagitis, lymphocytic esophagitis patients were more likely to respond to medical treatment (95% CI 2.54-12.8, p = 0.0001)., Conclusions: Our data suggests that lymphocytic esophagitis is more likely to be found in older female patients and is significantly associated with achalasia, statin, and aspirin use. Compared to eosinophilic esophagitis, lymphocytic esophagitis is more likely to respond to treatment with medical therapy., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Patients with Barrett's esophagus (BE) are more likely to have associated hiatal hernia (HH) compared to the general population. Studies show that HH are typically longer and wider in patients with BE., Aims: To determine whether patients with HH have associated increased odds of coexistence of BE by examining inpatient prevalence, as well as determining other inpatient outcomes., Methods: This was a case-control study using the NIS 2016, the largest public inpatient database in the USA. All patients with ICD10CM codes for BE were included. None were excluded. The primary outcome was determining the association between BE and HH in hospitalized patients, stratified by grade of dysplasia. Secondary outcomes included measuring use of endoscopic ablation in patients with BE and HH compared to patients with BE and no HH, determining the degree of association between HH and esophagitis in patients with or without BE, as well as the association between esophagitis and dysplasia in patients with BE and HH., Results: A total of 118,750 patients with BE were identified, of which 24,030 had associated HH. Adjusted odds of having associated BE in patients with HH was 10.9 (p < 0.01) compared to patients without HH. Patients with HH also displayed significantly higher odds of both low-grade dysplasia (aOR 34.5, p < 0.01) and high-grade dysplasia (aOR 14.7, p < 0.01). For secondary outcomes, the odds of undergoing ablation for BE was higher 4.77 (p < 0.01) in patients with HH., Conclusions: Patients with HH have significantly higher odds of having associated BE, regardless of the level of dysplasia. Furthermore, the odds of undergoing ablation are much higher, likely reflecting higher odds of dysplasia. This highlights the importance of BE in patients with HH, and potentially consider these patients as higher risk., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Gastroesophageal reflux plays a significant role in idiopathic pulmonary fibrosis (IPF). Given the morbidity and mortality associated with IPF, understanding the mechanisms responsible for reflux is essential if patients are to receive optimal treatment and management, especially given the lack of clear benefit of antireflux therapies. Our aim was to understand the inter-relationships between esophageal motility, lung mechanics and reflux (particularly proximal reflux-a prerequisite of aspiration), and pulmonary function in patients with IPF., Methods: We prospectively recruited 35 patients with IPF (aged 53-75 years; 27 men) who underwent high-resolution impedance manometry and 24-hour pH-impedance, together with pulmonary function assessment., Results: Twenty-two patients (63%) exhibited dysmotility, 16 (73%) exhibited ineffective esophageal motility (IEM), and 6 (27%) exhibited esophagogastric junction outflow obstruction. Patients with IEM had more severe pulmonary disease (% forced vital capacity: P = 0.032) and more proximal reflux (P = 0.074) than patients with normal motility. In patients with IEM, intrathoracic pressure inversely correlated with the number of proximal events (r = -0.429; P = 0.098). Surprisingly, inspiratory lower esophageal sphincter pressure (LESP) positively correlated with the percentage of reflux events reaching the proximal esophagus (r = 0.583; P = 0.018), whereas in patients with normal motility, it inversely correlated with the bolus exposure time (r = -0.478; P = 0.098) and number of proximal events (r = -0.542; P = 0.056). % forced vital capacity in patients with IEM inversely correlated with the percentage of reflux events reaching the proximal esophagus (r = -0.520; P = 0.039) and inspiratory LESP (r = -0.477; P = 0.062) and positively correlated with intrathoracic pressure (r = 0.633; P = 0.008)., Discussion: We have shown that pulmonary function is worse in patients with IEM which is associated with more proximal reflux events, the latter correlating with lower intrathoracic pressures and higher LESPs., (Copyright © 2021 by The American College of Gastroenterology.)

Background and Aims: The administration of intravenous conscious sedation to patients undergoing GI endoscopy carries a risk of cardiopulmonary adverse events. Our study aim was to create a score that stratifies the risk of occurrence of either high-dose conscious sedation requirements or a failed procedure., Methods: Patients receiving endoscopy via endoscopist-directed conscious sedation were included. The primary outcome was occurrence of sedation failure, which was defined as one of the following: (1) high-dose sedation, (2) the need for benzodiazepine/narcotic reversal agents, (3) nurse-documented poor patient tolerance to the procedure, or (4) aborted procedure. High-dose sedation was defined as >10 mg of midazolam and/or >200 μg of fentanyl or the meperidine equivalent. Patients with sedation failure (n = 488) were matched to controls (n = 976) without a sedation failure by endoscopist and endoscopy date., Results: Significant associations with sedation failure were identified for age, sex, nonclonazepam benzodiazepine use, opioid use, and procedure type (EGD, colonoscopy, or both). Based on these 5 variables, we created the high conscious sedation requirements (HCSR) score, which predicted the risk of sedation failure with an area under the curve of 0.70. Compared with the patients with a risk score of 0, risk of a sedation failure was highest for patients with a score ≥3.5 (odds ratio, 17.31; P = 2 × 10 -14 ). Estimated area under the curve of the HCSR score was 0.68 (95% confidence interval, 0.63-0.72) in a validation series of 250 cases and 250 controls., Conclusions: The HCSR risk score, based on 5 key patient and procedure characteristics, can function as a useful tool for physicians when discussing sedation options with patients before endoscopy., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Goals: To assess the effect of unilateral versus bilateral lung transplantation (LTx) on esophageal motility and gastroesophageal reflux, and the association with the development of obstructive chronic lung allograft dysfunction (o-CLAD)., Background: We have shown that esophagogastric junction outflow obstruction, incomplete bolus transit, and proximal reflux are all independent risk factors for the development of chronic allograft failure. However, it remains unclear whether these factors are influenced by the type of surgery and how this relates to allograft failure., Study: Patients post-LTx (n=48, 24 female; aged 20 to 73 y) completed high-resolution impedance manometry and 24-hour pH/impedance., Results: Patients who had undergone unilateral LTx were more likely to exhibit esophagogastric junction outflow obstruction (47% vs. 18%; P=0.046) and less likely to exhibit hypocontractility (0% vs. 21%; P=0.058) than those who had undergone bilateral LTx. Although the proportion of patients exhibiting gastroesophageal reflux was no different between groups (33% vs. 39%; P=0.505), those undergoing bilateral LTx were more likely to exhibit proximal reflux (8% vs. 37%; P=0.067). Univariate Cox proportion hazards regression analysis did not show a difference between unilateral versus bilateral LTx in the development of o-CLAD (hazard ratio=1.17; 95% confidence interval, 0.48-2.85; P=0.723)., Conclusion: The type of LTx performed seems to lead to different risk factors for the development of o-CLAD. Physicians should be aware of these differences, as they may need to be taken into account when managing patient's post-LTx.

Background: Proximal reflux and incomplete transit of boluses swallowed are risk factors for obstructive chronic lung allograft dysfunction (o-CLAD) post-lung transplantation (LTx). Likewise, so is esophagogastric junction outflow obstruction (EGJOO), but not hypo-contractility, when diagnosed using Chicago Classification (CC) v3.0. Given, peristaltic breaks as defined using CCv2.0 can prolong esophageal clearance, both swallowed and refluxed, but which are deemed within normality using CCv3.0, our aim was to determine whether hypo-contractility as diagnosed using CCv2.0, influences the association with reflux, along with its clearance, and that of boluses swallowed, and thus its association to allograft failure., Methods: Esophageal motility abnormalities were classified using CC v3.0 and v2.0 in 50 patients post-LTx (26 female, 55 years (20-73 years))., Results: Reclassification from CCv3.0 to v2.0 resulted in 7 patients with normal motility being reclassified to hypo-contractility (n = 6) or hyper-contractility (n = 1); 2 patients with hypo-contractility to normal motility; and 3 patients with EGJOO without hyper-contractility to EGJOO with hyper-contractility. The main consequence of reclassification was that the sub-group exhibiting hypo-contractility became more likely to have abnormal numbers of reflux events (P = .025) and incomplete bolus transit (P = .002) than those with normal motility using CCv2.0; associations not seen using CCv3.0. Irrespective of CC used only patients with EGJOO appeared more likely to develop o-CLAD than those with normal motility (P < .05)., Conclusions: Irrespective of CC used, o-CLAD appears linked to EGJOO. CCv2.0 however, accentuates the increased reflux and incomplete bolus transit associated with hypo-contractility post-LTx, suggesting that these motor abnormalities, though considered minor, may be of importance after lung transplant., (© 2018 John Wiley & Sons Ltd.)

Objectives: Gastroesophageal reflux is common in patients post-lung transplantation (LTx) and thus considered a risk factor for aspiration and consequently allograft rejection and the development of chronic allograft failure. However, evidence supporting this remains unclear and often contradictory. Our aim was to examine the role played by esophageal motility on gastroesophageal reflux exposure, along with its clearance and that of boluses swallowed, and the relationship to development of obstructive chronic lung allograft dysfunction (o-CLAD)., Methods: Patients post-LTx (n=50, 26 female; mean age 55 years (range, 20-73 years)) completed high-resolution impedance manometry and 24-h pH/impedance. Esophageal motility abnormalities were classified based upon the Chicago Classification version 3.0., Results: Esophagogastric junction outflow obstruction alone (EGJOOa) (P=0.01), incomplete bolus transit (IBT) (P=0.006) and proximal reflux (P=0.042) increased the risk for o-CLAD. Patients with EGJOOa were most likely to present with o-CLAD (77%); despite being less likely to exhibit abnormal numbers of reflux events (10%) compared with those with normal motility (o-CLAD: 29%, P<0.05; abnormal reflux events: 64%, P<0.05). Patients with EGJOOa had lower total reflux bolus exposure time than those with normal motility (0.6 vs. 1.5%; P<0.05). In addition, poor esophageal clearance documented by abnormal post-reflux swallow-induced peristaltic wave index associated with o-CLAD; inversely correlating with the proportion of reflux events reaching the proximal esophagus (r=-0.251; P=0.052)., Conclusions: These observations support esophageal dysmotility, especially EGJOOa, and impaired clearance of swallowed bolus or refluxed contents, more so than just the presence of gastroesophageal reflux alone, as important risk factors in the development of o-CLAD.

Gastro-oesophageal reflux is associated with a wide range of respiratory disorders, including asthma, isolated chronic cough, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease and cystic fibrosis. Reflux can be substantial and reach the proximal margins of the oesophagus in some individuals with specific pulmonary diseases, suggesting that this association is more than a coincidence. Proximal oesophageal reflux in particular has led to concern that microaspiration might have an important, possibly even causal, role in respiratory disease. Interestingly, reflux is not always accompanied by typical reflux symptoms, such as heartburn and/or regurgitation, leading many clinicians to empirically treat for possible gastro-oesophageal reflux. Indeed, costs associated with use of acid suppressants in pulmonary disease far outweigh those in typical GERD, despite little evidence of therapeutic benefit in clinical trials. This Review comprehensively examines the possible mechanisms that might link pulmonary disease and oesophageal reflux, highlighting the gaps in current knowledge and limitations of previous research, and helping to shed light on the frequent failure of antireflux treatments in pulmonary disease.

Background & Aims: Based on results from year 2 of a 5-year trial, in 2012 the US Food and Drug Administration approved the use of a magnetic device to augment lower esophageal sphincter function in patients with gastroesophageal reflux disease (GERD). We report the final results of 5 years of follow-up evaluation of patients who received this device., Methods: We performed a prospective study of the safety and efficacy of a magnetic device in 100 adults with GERD for 6 months or more, who were partially responsive to daily proton pump inhibitors (PPIs) and had evidence of pathologic esophageal acid exposure, at 14 centers in the United States and The Netherlands. The magnetic device was placed using standard laparoscopic tools and techniques. Eighty-five subjects were followed up for 5 years to evaluate quality of life, reflux control, use of PPIs, and side effects. The GERD-health-related quality of life (GERD-HRQL) questionnaire was administered at baseline to patients on and off PPIs, and after placement of the device; patients served as their own controls. A partial response to PPIs was defined as a GERD-HRQL score of 10 or less on PPIs and a score of 15 or higher off PPIs, or a 6-point or more improvement when scores on vs off PPI were compared., Results: Over the follow-up period, no device erosions, migrations, or malfunctions occurred. At baseline, the median GERD-HRQL scores were 27 in patients not taking PPIs and 11 in patients on PPIs; 5 years after device placement this score decreased to 4. All patients used PPIs at baseline; this value decreased to 15.3% at 5 years. Moderate or severe regurgitation occurred in 57% of subjects at baseline, but only 1.2% at 5 years. All patients reported the ability to belch and vomit if needed. Bothersome dysphagia was present in 5% at baseline and in 6% at 5 years. Bothersome gas-bloat was present in 52% at baseline and decreased to 8.3% at 5 years., Conclusions: Augmentation of the lower esophageal sphincter with a magnetic device provides significant and sustained control of reflux, with minimal side effects or complications. No new safety risks emerged over a 5-year follow-up period. These findings validate the long-term safety and efficacy of the magnetic sphincter augmentation device for patients with GERD. ClinicalTrials.gov no: NCT00776997., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: High-resolution manometry of the esophagus has gained worldwide acceptance, using different solid-state catheters. Thus, normal values for lower esophageal sphincter (LES) resting pressure in suspected gastroesophageal reflux disease patients have been established using water-perfused manometry. These standard values are commonly applied using also solid-state techniques, although they have never been compared before. The aim of the study was to compare LES measurements obtained with water-perfused manometry with a solid-state technique., Methods: Thirty healthy subjects were studied twice on the same day: Technique 1: Station pull through using a water-perfused catheter with ports arranged at 0°, 90°, 180° and 270° which were averaged to give a mean LES pressure. Technique 2: Solid-state circumferential probe with a single station pull through. Data were collected using the same computer system and program. The LES pressures were randomly and blindly analyzed., Results: Twenty-seven subjects out of 30 were analyzed. Using the solid-state system, the mean LES pressure was higher (15.0 vs. 23.3 mmHg, p = 0.003) and 19 of 27 (70%) individual measurements were higher. Two subjects had a hypertensive LES by solid state (58.6 resp. 47.5 mmHg), while their pressures were normal with water-perfused manometry (21.0 resp. 23.4 mmHg). The distal esophageal pressures (mean of pressure at 3 and 8 cm above LES) were the same with the two techniques., Conclusion: In normal control subjects, LES measurement using circumferential solid-state transducers yields higher pressures than standard water-perfused manometry. Which system yields the "true" resting pressure of the physiologic LES remains to be determined.

Background: Gastroesophageal reflux plays an important role in chronic cough (CC). Whether disturbed esophageal motility contributes to increased esophageal reflux exposure or interferes with swallowed bolus clearance is unclear. This study used high resolution esophageal manometry and impedance (HRIM) together with Chicago Classification, and 24-h impedance pH (MII/pH) to address these questions in patients with CC compared with heartburn (HB)., Methods: A retrospective review of 32 patients with CC (mean age 57 [95% CI: 52-62] years) and 32 patients with symptoms of HB (55 [52-62] years) referred for HRIM and MII/pH between September 2012 and September 2013 was undertaken., Key Results: Weak peristalsis with large breaks (WPLBs) was observed in 34% of CC patients compared with only 12% of HB patients (p = 0.027). Pathological acid exposure time (AET) was identified in 81% of CC patients with WPLBs compared with 29% without (p = 0.011). Increased AET was associated with prolonged clearance time of refluxed events (p = 0.006) rather than increased number of events. AET correlated with the percentage of peristaltic events with large breaks in CC (ρ = 0.467, p = 0.007). Similar data were obtained for total bolus (acid and non-acid) exposure time. Only one of the CC patients with WPLBs exhibited complete bolus transit (CBT) on swallowing compared with 81% without WPLBs (p < 0.001). Moreover, the percentage of peristaltic events associated with CBT negatively correlated with the percentage of peristaltic events with large breaks (r = -0.653, p < 0.001) in CC., Conclusions & Inferences: One-third of CC patients exhibit WPLBs, which directly impacts on clearance of refluxed events and bolus's swallowed. These observations may have important implications for esophageal-bronchial interaction in CC., (© 2015 John Wiley & Sons Ltd.)

Nutcracker esophagus (NE) is a common esophageal motility disorder chacterized by high amplitude peristaltic contractions in the distal esophagus. While previous studies have examined selected aspects of this condition (e.g. pathogenesis and treatment), there is a paucity of data regarding demographic and clinical features in large cohorts of patients. The aim of this study was to describe demographics, clinical features, comorbidities, time to diagnosis, source of patient referral by specialty, and medication use in a large cohort of patients with NE. We retrospectively analyzed consecutive cases of NE diagnosed from 2008-2010. The electronic medical records of these patients were reviewed, and relevant information was extracted. We identified 115 patients with NE. The median age was 62 years (range 25-87 years), and 63% were female. The median time patients experienced symptoms prior to diagnosis was 24 months (0-480 months). Most patients presented to an internal medicine consultant (42%) or to a gastroenterologist (35%). Presenting symptoms were chest pain (31%) and dysphagia (21%). Gastroesophageal reflux disease (GERD) symptoms were common: heartburn occurred in 51% of patients, 77% had a prior history of GERD, and 78% were receiving acid suppressive medications. GERD was confirmed by testing in at least 35%. Psychiatric comorbidity occurred in 24% with half the patients receiving psychotropic medications. Irritable bowel syndrome (IBS) and fibromyalgia co-existed in 15% and 12% of patients, respectively. Surprisingly, opioids were prescribed to 26% of patients. No statistically significant correlation was found between esophageal motility parameters and symptoms. In this study, NE patients were more commonly middle-aged females experiencing a considerable amount of time between symptom onset and diagnosis. Many were initially evaluated by internists for dysphagia or chest pain and had a history of GERD. Medication prescribed prior to diagnoses frequently involved acid suppression, but narcotic and psychotropic prescriptions were also commonly used. Central sensitization syndromes (fibromyalgia and IBS), psychiatric comorbidity, and reflux commonly coexisted. Our study suggests that future investigations should address the role and interaction of GERD and psychiatric disorders in NE., (© 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Background: A new device for mechanical sphincter augmentation (MSA) of the lower esophageal sphincter was approved by the FDA on March 22, 2012. We report early experience with MSA, specifically addressing postoperative management., Study Design: Between October 1, 2011 and June 1, 2013, 150 patients were evaluated for MSA. Of these, 66 patients underwent device implantation; the first implant was April 10, 2012. All patients had objectively confirmed gastroesophageal reflux disease (GERD) with pH testing, acceptable esophageal motility, and no significant hiatal hernia (>3 cm). All patients experienced clinical improvement on antisecretory medication, but incomplete symptom control or medication intolerance., Results: All patients were successfully implanted without intra- or perioperative complications. Average length of hospital stay was 0.7 days. At an average follow-up of 5.8 months (range 1 to 18.6 months), 92% of patients are satisfied or neutral with their GERD condition, and 83% are proton pump inhibitor free. The GERD-Health-Related Quality of Life (HRQL) scores are similar to those of patients without GERD. There were no device ulcers or erosions and no devices explanted. Thirteen patients underwent additional testing for dysphagia or persistent symptoms. Calls with questions and nursing involvement in the first 6 months postoperatively were 3 times what is typical for fundoplication patients. Dysphagia and regurgitation were the most common concerns. All these symptoms were improving over time., Conclusions: Single-center early results are promising and parallel those from a multicenter trial. There is significant interest in MSA, with referrals and direct patient appointments specifically for MSA. Outcomes improve over time after implantation. The surgeon learning curve is different than with the Nissen, both in operative technique and postoperative management. This is a promising new offering for patients with GERD, and surgeons will need to learn how to integrate this into their practices., (Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Gastroesophageal reflux disease is a common disorder in all patients but a particular problem in the elderly, for whom the disease often presents with advanced mucosal damage and other complications. Symptoms are also not as reliable an indication of disease severity in older patients. Likewise, therapy is more difficult because of potential side effects and drug interactions., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Current diagnostic guidelines recommend that eosinophilic oesophagitis (EoE) should be diagnosed only after GERD is excluded by a lack of response to a trial of acid suppression. There is limited information available providing outcome data about the effectiveness of this approach., Aim: To examine the impact of double-dose proton pump inhibitor (PPI) therapy on symptoms, endoscopic and histological features in patients with documented oesophageal eosinophilia consistent with EoE (≥15 eosinophils/high-power field)., Methods: Sixty consecutive symptomatic patients with documented oesophageal eosinophilia received open-label omeprazole 20 mg orally twice daily before meals for 8 weeks. Clinical, endoscopic and histological (resolution: 0-5 eosinophils/HPF, partial improvement: 5-14 eosinophils/HPF), or no improvement: (≥15 eosinophils/HPF) evaluation was repeated at the end of this period. An expert GI pathologist, unaware of the study aims, reviewed all slides., Results: Clinical improvement occurred in 43 (71.6%), endoscopic signs were reduced in 34 (61.8%) and normalised in 12 (21.8%), and histologically, 34 (56.6%) improved, while 15 (25%) obtained complete resolution. Overall, 22 patients (36.7%) obtained both complete clinical and histological remission., Conclusions: More than 50% of patients with documented oesophageal eosinophilic infiltration in the EoE range improved when treated with a double-dose PPI trial for 8 weeks. These findings support the published guidelines recommending a PPI trial prior to diagnosing EoE, and confirm the existence of an eosinophilic oesophageal infiltrationPPI-responsive population., (© 2013 John Wiley & Sons Ltd.)

Gastroesophageal reflux disease (GERD) can be difficult to diagnose - symptoms alone are often not enough, and thus, objective testing is often required. GERD is a manifestation of pathologic levels of reflux into the esophagus of acidic, nonacidic, and/or bilious gastric content. However, in our current evidence-based knowledge approach, we only have reasonable outcome data in regards to acid reflux, as this particular type of refluxate predictably causes symptoms and mucosal damage, which improves with medical or surgical therapy. While there are data suggesting that nonacid reflux may be responsible for ongoing symptoms despite acid suppression in some patients, outcome data about this issue are limited. Therefore, this working group believes that it is essential to confirm the presence of acid reflux in patients with 'refractory' GERD symptoms or extraesophageal symptoms thought to be caused by gastroesophageal reflux before an escalation of antireflux therapy is considered. If patients do not have pathologic acid reflux off antisecretory therapy, they are unlikely to have clinically significant nonacid or bile reflux. Patients who do not have pathologic acid gastroesophageal reflux parameters on ambulatory pH monitoring then: (i) could attempt to discontinue antisecretory medications like proton pump inhibitors and H2-receptor antagonists (which are expensive and which carry risks - i.e. C. diff, etc.); (ii) may undergo further evaluation for other causes of their esophageal symptoms (e.g. functional heartburn or chest pain, eosinophilic esophagitis, gastroparesis, achalasia, other esophageal motor disorders); and (iii) can be referred to an ear, nose, and throat/pulmonary/allergy physician for assessment of non-GERD causes of their extraesophageal symptoms., (© 2012 Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Unlabelled: BACKGROUND& AIMS: Proton pump inhibitors and nonsteroidal anti-inflammatory drugs might prevent esophageal adenocarcinoma in patients with Barrett's esophagus (BE), but there are limited data from clinical trials to support this concept. We conducted a randomized, double-blind, placebo-controlled, phase 2 trial to assess the effects of the combination of aspirin (3 different doses) and esomeprazole on tissue concentrations of prostaglandin (PG) E(2) in patients with BE with no dysplasia or low-grade dysplasia., Methods: Participants were recruited through the multicenter Cancer Prevention Network and randomly assigned to groups that were given 40 mg esomeprazole twice daily in combination with an aspirin placebo once daily (arm A; n = 30), with 81 mg aspirin once daily (arm B; n = 47), or with 325 mg aspirin once daily (arm C; n = 45) for 28 days. We collected esophageal biopsy specimens before and after the intervention period to determine the absolute change in mean concentration of PGE(2) (the primary end point)., Results: Based on data from 114 patients, baseline characteristics were similar among groups. The absolute mean tissue concentration of PGE(2) was reduced by 67.6 ± 229.68 pg/mL in arm A, 123.9 ± 284.0 pg/mL in arm B (P = .10 vs arm A), and 174.9 ± 263.62 pg/mL in arm C (P = .02 vs arm A)., Conclusions: In combination with esomeprazole, short-term administration of higher doses of aspirin, but not lower doses or no aspirin, significantly reduced tissue concentrations of PGE(2) in patients with BE with either no dysplasia or low-grade dysplasia. These data support further evaluation of higher doses of aspirin and esomeprazole to prevent esophageal adenocarcinoma in these patients. Clinical trial registration number NCT00474903., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Diffuse esophageal spasm (DES) remains insufficiently understood. Here we aimed to summarize the demographic, clinical, radiographic, and manometric features in a large cohort of patients with DES. We identified all consecutive patients diagnosed with DES from 2000 to 2006 at Mayo Clinic Florida. The computerized records of these patients were reviewed to extract relevant information. We performed 2654 esophageal motilities during that period. There were 108 patients with esophageal spasm, and 55% were female. Median age was 71 years. The most common leading symptom was dysphagia in 55, followed by chest pain in 31. Weight loss occurred in 28 patients. The median of time from onset of symptoms to diagnosis was 48 months (range 0-480), with a median of time from the first medical consultation to diagnosis of 8 months (range 0-300). The most frequent comorbidities were hypertension and psychiatric problems. At presentation, 81 patients were taking acid-reducing medications, and 49 patients were taking psychotropic drugs. An abnormal esophagogram was noted in 46 of 76 patients with this test available, but most radiographic findings were nonspecific with the typical 'corkscrew' appearance seen in only three patients. Gastroesophageal reflux disease (GERD) was diagnosed by pH testing or endoscopy in 41 patients. We did not find any difference between the rate of simultaneous contractions or esophageal amplitude between patients with a leading symptom of dysphagia and those with chest pain. DES is an uncommon motility disorder that often goes unrecognized for years. Physicians should be aware of the clinical heterogeneity of DES and consider motility testing early in the course of unexplained esophageal symptoms. Given the high prevalence of GERD in DES, the role of GERD and the impact of acid-reducing therapy in DES deserve further study., (© 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.)

Background and Study Aims: Colonoscopy is widely used to detect and remove precancerous polyps, but fails to detect some polyps. Recent studies evaluating different image-enhanced methods have revealed conflicting results. The efficacy of colonoscopy imaging with simultaneous use of commercially available improvements, including high definition narrow band imaging (HD-NBI), and monochromatic charge-coupled device (CCD) video, was compared with a widely used standard definition white light (SDWL) colonoscopy system for detecting colorectal polyps. The primary aim was to determine whether the combination of image-enhanced colonoscopy systems resulted in fewer missed polyps compared with conventional colonoscopy., Patients and Methods: In a randomized controlled trial (Clinicaltrials.gov. study number NCT00825292) patients having routine screening and surveillance underwent tandem colonoscopies with SDWL and image-enhanced (HD-NBI) colonoscopy. The main outcome measurement was the per-polyp false-negative ("miss") rate. Secondary outcomes were adenoma miss rate, and per-patient polyp and adenoma miss rates., Results: 100 patients were randomized and 96 were included in the analysis. In total, 177 polyps were detected; of these, 72 (41 %) were adenomatous. Polyp and adenoma miss rates for SDWL colonoscopy were 57 % (60/105) and 49 % (19/39); those for image-enhanced colonoscopy were 31 % (22/72) and 27 % (9/33) (P = 0.005 and P = 0.036 for polyps and adenomas, respectively). Image-enhanced and SDWL approaches had similar per-patient miss rates for polyps (6/35 vs. 9/32, P = 0.27) and adenomas (4/22 vs. 8/20, P = 0.11)., Conclusions: Utilization of multiple recent improvements in image-enhanced colonoscopy was associated with a reduced miss rate for all polyps and for adenomatous polyps. It is not known which individual feature or combination of image-enhancement features led to the improvement., (© Georg Thieme Verlag KG Stuttgart · New York.)

The following on proton pump inhibitors (PPIs) and chemoprevention in relation to Barrett's esophagus includes commentaries on 48-h pH monitoring, pH-impedence, bile acid testing, dyspepsia, long/short segment Barrett's esophagus, nonerosive reflux disease (NERD), functional heartburn, dual-release delivery PPIs, immediate-release PPIs, long-term PPI use, prokinetic agents, obesity, baclofen, nocturnal acid breakthrough, nonsteroidal anti-inflammatory drugs (NSAIDs), and new PPIs., (© 2011 New York Academy of Sciences.)

This collection of summaries on endoscopic diagnosis of Barrett's esophagus (BE) includes the best endoscopic markers of the extent of BE; the interpretation of the diagnosis of ultra-short BE; the criteria for endoscopic grading; the sensitivity and specificity of endoscopic diagnosis; capsule and magnifying endoscopy; narrow band imaging; balloon cytology; the distinction between focal and diffuse dysplasia; the techniques for endoscopic detection of dysplasia and the grading systems; and the difficulty of interpretation of inflammatory or regenerative changes., (© 2011 New York Academy of Sciences.)

Background: Eosinophilic oesophagitis clinically presents with recurrent episodes of dysphagia and food impaction. Recently, we observed patients with noncardiac chest pain and eosinophilic oesophagitis., Aims: To estimate the prevalence of abnormal eosinophilic infiltration in noncardiac chest pain patients and examine diagnostic utility of demographic, clinical and endoscopic variables to predict eosinophilic oesophagitis., Methods: Retrospective study of 171 consecutive patients referred for EGD evaluation of noncardiac chest pain. Endoscopic signs consistent with eosinophilic oesophagitis were recorded. The histological findings were grouped as normal: 0-5 eosinophils/high power field (e/hpf), indeterminate: 6-20 e/hpf, and eosinophilic oesophagitis: ≥21 e/hpf. Abnormal eosinophilic infiltration was defined as ≥6 e/hpf., Results: Abnormal eosinophilic infiltrate was noted in 24 patients (14%). Thirteen (8%) had indeterminate counts, while 11 (6%) had eosinophilic oesophagitis. Compared with normal, those with abnormal oesophageal eosinophilic infiltration were more likely to be male (71% vs. 34%, P=0.001), have allergies (29% vs. 12%, P=0.050), have current GER symptoms (42% vs. 18%, P=0.013), rings (54% vs. 22%, P=0.002), furrows (21% vs. 1%, P<0.001) and abnormal eosinophilic oesophagitis findings on endoscopy (67% vs. 32%, P=0.001). Of the 24 abnormal patients, 23 (96%) were either male or had rings, furrows, or white specks. Conversely, 68 of 69 patients (99%) who were female did not have rings, furrows, or white specks, and endoscopy was normal. Eight patients (33%) with abnormal eosinophilic infiltration had a normal endoscopy., Conclusions: Eosinophilic oesophagitis should be considered in the evaluation of noncardiac chest pain. Our findings suggest that oesophageal biopsies should be obtained particularly in males with recurrent unexplained chest pain, whether endoscopy is normal or abnormal., (© 2011 Blackwell Publishing Ltd.)

A patient with a spontaneous esophageal perforation was unsuccessfully managed elsewhere by repeated stent placement. Because of inability to remove the stents and persistent empyema, staged procedures of esophagectomy and later restoration of gastrointestinal continuity were necessary., (Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)