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Introduction: Endoscopic pneumatic pyloric balloon dilation is a treatment option for early postoperative delayed gastric tube emptying following esophageal resection. This study aimed to determine the safety and effectiveness of endoscopic balloon dilation. Methods: Between 2015 and 2018, patients with delayed gastric emptying 8–10 days after esophageal resection with gastric tube reconstruction due to esophageal carcinoma were considered for inclusion. Inclusion criteria were ≥1 of the following: nasogastric tube production ≥500 mL/24 h, ≥300 mL gastric retention, ≥50% gastric tube dilatation on X-ray, or nasogastric tube replacement. Patients were excluded on evidence of anastomotic leakage or reintervention. Success was defined as the ability to expand intake without needing to replace the nasogastric tube. Dilation was performed using a 30-mm Rigiflex balloon. Results: Fifteen patients underwent pyloric dilation, 12 according to the study protocol. Treatment was performed at a median of 12 days (IQR 9–15) postoperatively. Success was achieved in 58%. At 3 months, 8 patients progressed to exclusively oral intake. The remaining 4 patients had supplementary nightly enteral tube feeding. There were no adverse events. Conclusion: Endoscopic balloon dilation of the pylorus is a safe, feasible therapy for early postoperative delayed gastric emptying. With a success rate of 58%, a clinical trial is a necessary next step.

IntroductionAchalasia is a primary motor disorder of the oesophagus characterised by absence of peristalsis and insufficient lower oesophageal sphincter relaxation. With new advances and developmen...

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.

BACKGROUND & AIMS: Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE. METHODS: We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity ≤2 on a scale of 0-10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count

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.

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.

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.

Objective MRI is increasingly used to evaluate small bowel contractility. The objective of this study was to validate a clinically practical stimulation test (300‐kcal meal) for small bowel motility. Methods Thirty‐one healthy subjects underwent dynamic MRI to capture global small bowel motility after ±10h fasting, of which 15 underwent bowel preparation consisting of 1 L 2.5% mannitol solution and 16 did not. Each subject underwent (1) a baseline motility scan (2) a food challenge (3) a post‐challenge scan, and (4) second post‐challenge scan (after ±20 minutes). This protocol was repeated within 2 weeks. Motility was quantified using a validated motility assessment technique. Key Results Motility in prepared subjects at baseline was significantly higher than motility in unprepared subjects (0.36 AU vs 0.18 AU, P, In this article, we present a practical MRI stimulation test and validate it in both mannitol prepared and unprepared healthy subjects to evaluate the stimulation test and provide guidance on MRI preparation for future MRI motility studies.

Background and Aims One of the most used treatments for achalasia is pneumatic dilation of the lower esophageal sphincter to improve esophageal emptying. Multiple treatment protocols have been described with a varying balloon size, number of dilations, inflation pressure, and duration. We aimed to identify the most efficient and safe treatment protocol. Methods We performed a systematic review and meta‐analysis of studies on pneumatic dilation in patients with primary achalasia. Clinical remission was defined as an Eckardt score ≤3 or adequate symptom reduction measured with a similar validated questionnaire. We compared the clinical remission rates and occurrence of complications between different treatment protocols. Results We included 10 studies with 643 patients. After 6 months, dilation with a 30‐mm or 35‐mm balloon gave comparable mean success rates (81% and 79%, respectively), whereas a series of dilations up to 40 mm had a higher success rate of 90%. Elective additional dilation in patients with insufficient symptom resolution was somewhat more effective than performing a predefined series of dilations: 86% versus 75% after 12 months. Perforations occurred most often during initial dilations, and significantly more often using a 35‐mm balloon than a 30‐mm balloon (3.2 vs 1.0%); P = 0.027. A subsequent 35‐mm dilation was safer than an initial dilation with 35 mm (0.97% vs 9.3% perforations), P = 0.0017. Conclusions The most efficient and safe method of dilating achalasia patients is a graded approach starting with a 30‐mm dilation, followed by an elective 35‐mm dilation and 40 mm when there is insufficient symptom relief., The optimal pneumatic dilation therapy for untreated achalasia patients is a 30‐mm dilation, followed by an elective dilation to 35 and 40 mm in patients with persisting or recurrent symptoms. Dilation to 35 and 40 mm is relatively safe when it is preceded by a 30‐mm dilation.

BACKGROUND: Treatment options for achalasia include endoscopic and surgical techniques that carry the risk of esophageal bleeding and perforation. The rare coexistence of esophageal varices has only been anecdotally described and treatment is presumed to carry additional risk. METHODS: Experience from physicians/surgeons treating this rare combination of disorders was sought through the International Manometry Working Group. RESULTS: Fourteen patients with achalasia and varices from seven international centers were collected (mean age 61 ± 9 years). Five patients were treated with botulinum toxin injections (BTI), four had dilation, three received peroral endoscopic myotomy (POEM), one had POEM then dilation, and one patient underwent BTI followed by Heller's myotomy. Variceal eradication preceded achalasia treatment in three patients. All patients experienced a significant symptomatic improvement (median Eckardt score 7 vs 1; p

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

Background Using conventional manometry, gastro-esophageal reflux disease (GERD) was associated with a reduced lower esophageal sphincter (LES) pressure and impaired peristalsis. However, with a large overlap between GERD patients and controls, these findings are of limited clinical relevance. It is uncertain whether the more detailed information of high-resolution manometry (HRM) can discriminate GERD patients. Therefore, we aimed to determine to which extent HRM findings can predict GERD. Methods HRM measurements in 69 patients with GERD and 40 healthy subjects were compared and the predictive value of HRM for the diagnosis of GERD was explored. Key Results GERD patients had a significantly lower contraction amplitude (55 vs 64 mmHg; p = 0.045) and basal LES pressure (10 vs 13.2 mmHg; p = 0.034) than healthy controls. GERD patients more often had a hiatal hernia than healthy subjects (30% vs 7%; p = 0.005). Patients with reflux esophagitis had a lower DCI than patients without reflux esophagitis (558 vs 782 mmHg cm s; p = 0.045). No significant difference was seen in contractile front velocity, distal latency, number of peristaltic breaks, residual LES pressure and LES length. On multivariate logistic regression analysis, both esophagogastric junction type I (OR 4.971; 95% CI 1.33–18.59; p = 0.017) and mean wave amplitude (OR 0.95; 95% CI 0.90–0.98; p = 0.013) were found to be independent predictors of GERD. However, the sensitivity and specificity of these findings were low. Conclusions & Inferences Hiatal hernia, low contraction amplitude and LES pressure are associated with GERD, but do not predict the disease with sufficient accuracy. Routine esophageal HRM can therefore not be used to distinguish GERD patients from healthy subjects.

BACKGROUND Esophageal stasis is a hallmark of achalasia. Timed barium esophagogram (TBE) is used to measure stasis but exposes patients to ionizing radiation. It is suggested that esophageal stasis can be objectified on high-resolution manometry (HRM) as well using a rapid drinking challenge test (RDC). We aimed to assess esophageal stasis in achalasia by a RDC during HRM and compare this to TBE. METHODS Thirty healthy subjects (15 male, age 40 [IQR 34-49]) and 90 achalasia patients (53 male, age 47 [36-59], 30 untreated/30 treated symptomatic/30 treated asymptomatic) were prospectively included to undergo HRM with RDC and TBE. RDC was performed by drinking 200 mL of water. Response to RDC was measured by basal and relaxation pressure in the esophagogastric junction (EGJ) and esophageal pressurization during the last 5 seconds. KEY RESULTS EGJ basal and relaxation pressure during RDC were higher in achalasia compared to healthy subjects (overall P

Background The diagnosis of a sliding hiatal hernia is classically made with endoscopy or barium esophagogram. Spatial separation of the lower esophageal sphincter (LES) and diaphragm, the hallmark of hiatal hernia, can also be observed on high-resolution manometry (HRM), but the diagnostic accuracy of this finding has not yet been investigated. To determine the diagnostic value of HRM in the detection of hiatal hernia. Methods HRM recordings, endoscopy reports, and barium esophagograms of 90 patients were analyzed for the presence and size of a hiatal hernia. The diagnostic value of a hernia specific HRM pressure pattern was calculated, and the agreement of HRM with endoscopy and barium esophagogram for the assessment of hernia size. Key Results HRM was found to be highly sensitive and specific for hiatal hernia detection, with a sensitivity of 92% and specificity of 95%, exceeding the sensitivity of endoscopy or radiography alone (both 73%). Patients with a hiatal hernia on HRM were manometrically characterized by an esophagogastric junction (EGJ) with partial or complete separation of the LES and crural diaphragm (CD), the latter being associated with significantly lower EGJ pressure. A cutoff value of spatial LES-CD separation on HRM of 1.85 cm yielded the optimal performance in identifying hiatal hernia. Agreement between HRM, endoscopy, and radiography for size of hiatal hernias was good (ICC [95% CI] 0.74 [0.65–0.82]). Conclusions & Inferences With HRM, the presence or absence and size of a hiatal hernia can be assessed with greater sensitivity than with endoscopy or radiography alone.

Item does not contain fulltext BACKGROUND: The clinical management of patients with non-obstructive dysphagia is notoriously difficult. Esophageal impedance measurement can be used to measure esophageal bolus transit without the use of radiation exposure to patients. However, validation of measurement of bolus transit with impedance monitoring has only been performed in healthy subjects with normal motility and not in patients with dysphagia and esophageal motility disorders. The aim was, therefore, to investigate the relationship between transit of swallowed liquid boluses in healthy controls and in patients with dysphagia. METHODS: Twenty healthy volunteers and 20 patients with dysphagia underwent concurrent impedance measurement and videofluoroscopy. Each subject swallowed five liquid barium boluses. The ability of detecting complete or incomplete bolus transit by means of impedance measurement was assessed, using radiographic bolus transit as the gold standard. KEY RESULTS: Impedance monitoring recognized stasis and transit in 80.5% of the events correctly, with 83.9% of bolus transit being recognized and 77.2% of stasis being recognized correctly. In controls 79.8% of all swallows were scored correctly, whereas in patients 81.3% of all swallows were scored correctly. Depending on the contractility pattern, between 77.0% and 94.3% of the swallows were scored correctly. CONCLUSIONS & INFERENCES: Impedance measurement can be used to assess bolus clearance patterns in healthy subjects, but can also be used to reliably assess bolus transit in patients with dysphagia and motility disorders.

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.

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

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

Background For over 50 years, barium studies have been used to diagnose gastro-esophageal reflux disease (GERD), but the value of this test is controversial. Our study aimed to determine if barium esophagograms can be used to diagnose GERD. Methods Barium esophagograms and pH-impedance measurement were performed in 20 subjects with reflux symptoms. pH-impedance measurements were used as gold standard for the diagnosis of GERD. Gastro-esophageal reflux measured with the barium study was defined as a positive outcome. Key Results 50% of patients presented gastro-esophageal reflux on the barium esophagogram. No significant differences were observed in acid exposure time between subjects with (median: 7.4%; interquartile range, IQR: 8.4%) or without reflux at barium esophagography (median: 5.95%; IQR: 13.05%; p > 0.05). Nor did we find differences in median proximal extent of reflux measured with impedance monitoring between patients with a positive (median: 6.7%; IQR: 1.95%) and negative barium study (median: 7.1%; IQR: 0.68%; p > 0.05). Patients with reflux on barium esophagogram did not have a positive symptom association probability more often than those who did not have reflux at barium esophagography. Lastly, there were no differences in numbers of acid, weakly acidic or total reflux episodes between those with positive or negative barium esophagogram (p > 0.05). No correlations were found between the maximum proximal extent of gastro-esophageal reflux during esophagography and pH-impedance parameters. Conclusions & Inferences Presence or absence of gastro-esophageal reflux during barium esophagography does not correlate with incidence or extent of reflux observed during 24-h pH-impedance monitoring and is not of value for the diagnosis of GERD.

High-resolution esophageal manometry (HRM) is a recent development used in the evaluation of esophageal function. Our aim was to assess the inter-observer agreement for diagnosis of esophageal motility disorders using this technology. Practitioners registered on the HRM Working Group website were invited to review and classify (i) 147 individual water swallows and (ii) 40 diagnostic studies comprising 10 swallows using a drop-down menu that followed the Chicago Classification system. Data were presented using a standardized format with pressure contours without a summary of HRM metrics. The sequence of swallows was fixed for each user but randomized between users to avoid sequence bias. Participants were blinded to other entries. (i) Individual swallows were assessed by 18 practitioners (13 institutions). Consensus agreement (≤ 2/18 dissenters) was present for most cases of normal peristalsis and achalasia but not for cases of peristaltic dysmotility. (ii) Diagnostic studies were assessed by 36 practitioners (28 institutions). Overall inter-observer agreement was 'moderate' (kappa 0.51) being 'substantial' (kappa > 0.7) for achalasia type I/II and no lower than 'fair-moderate' (kappa >0.34) for any diagnosis. Overall agreement was somewhat higher among those that had performed >400 studies (n = 9; kappa 0.55) and 'substantial' among experts involved in development of the Chicago Classification system (n = 4; kappa 0.66). This prospective, randomized, and blinded study reports an acceptable level of inter-observer agreement for HRM diagnoses across the full spectrum of esophageal motility disorders for a large group of clinicians working in a range of medical institutions. Suboptimal agreement for diagnosis of peristaltic motility disorders highlights contribution of objective HRM metrics.

Background It is common belief that symptoms of patients with non-obstructive dysphagia are the result of impaired bolus clearance in the esophagus, usually caused by esophageal motility disorders. We therefore investigated the relationship between transit of swallowed boluses and the symptom dysphagia. Methods Twenty healthy volunteers and 20 patients with dysphagia underwent videofluoroscopy. Success of bolus transport was graded on a 7-point scale. Each subject swallowed five liquid and five solid barium boluses. Key Results For liquids, patients reported dysphagia during 1 [0–3] of the five swallows, while controls reported no dysphagia (median 0 [0–0]; p = 0.003). For solids, patients reported dysphagia during 3 [2–4] of five swallows, while controls reported dysphagia in 0.5 [0–2] of five swallows (p = 0.001). When correlating dysphagia to ineffective clearance (score ≥3), in 3 [2–4] of five liquids, the subjects perception of clearance was related to the clearance result on fluoroscopy in patients and also 3 [1–5] were correctly perceived in controls (p = 0.6). For solids, in 4 [3–5] of five swallows, the subjects perception of clearance was related to the clearance result on fluoroscopy in patients, but only 2 [1–3] of five swallows were correctly perceived by controls, the difference being statistically significant. Conclusions & Inferences Patients very frequently report dysphagia when bolus clearance is successful. Therefore, the major underlying problem in patients with non-obstructive dysphagia is disordered perception and increased sensitivity to physiological bolus stasis. Treatment should therefore be directed at reducing increased sensitivity rather than at improving motility.

Background The 5-HT4 receptor agonist prucalopride is a prokinetic drug which improves colonic motility. Animal data and in vitro studies suggest that prucalopride also affects gastric and esophageal motor function. We aimed to assess the effect of prucalopride on gastric emptying, esophageal motility, and gastro-esophageal reflux in man. Methods In this double-blind, placebo-controlled, randomized, crossover study, we included 21 healthy volunteers who received 4 mg prucalopride or placebo per day for 6 days. We performed high-resolution manometry (HRM) followed by 120-min HRM-pH-impedance monitoring after a standardized meal, ambulatory 24-h pH-impedance monitoring, and gastric emptying for solids. Key Results Prucalopride decreased (median [IQR]) total acid exposure time (3.4 [2.5–5.6] vs 1.7 [0.8–3.5] %, p

Numerous questionnaires with a wide variety of characteristics have been developed for the assessment of gastroesophageal reflux disease (GERD). Four well-defined dimensions are noticeable in these GERD questionnaires, which are symptoms, response to treatment, diagnosis, and burden on the quality of life of GERD patients. The aim of this review is to develop a complete overview of all available questionnaires, categorized per dimension of the assessment of GERD. A systematic search of the literature up to January 2013 using the Pubmed database and the Embase database, and search of references and conference abstract books were conducted. A total number of 65 questionnaires were extracted and evaluated. Thirty-nine questionnaires were found applicable for the assessment of GERD symptoms, three of which are generic gastrointestinal questionnaires. For the assessment of response to treatment, 14 questionnaires were considered applicable. Seven questionnaires with diagnostic purposes were found. In the assessment of quality of life in GERD patients, 18 questionnaires were found and evaluated. Twenty questionnaires were found to be used for more than one assessment dimension, and eight questionnaires were found for GERD assessment in infants and/or children. A wide variety of GERD questionnaires is available, of which the majority is used for assessment of GERD symptoms. Questionnaires differ in aspects such as design, validation and translations. Also, numerous multidimensional questionnaires are available, of which the Reflux Disease Questionnaire is widely applicable. We provided an overview of GERD questionnaires to aid investigators and clinicians in their search for the most appropriate questionnaire for their specific purposes.

SummaryBackground 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.

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 8.4×103 Ω/m) and transepithelial resistance (94.0 and 89 vs 118 Ω/cm2) 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 1.7×103 vs 0.6×103 nmol/cm2/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.

Esophageal motor function is highly coordinated between central and enteric nervous systems and the esophageal musculature, which consists of proximal skeletal and distal smooth muscle in three functional regions, the upper and lower esophageal sphincters, and the esophageal body. While upper endoscopy is useful in evaluating for structural disorders of the esophagus, barium esophagography, radionuclide transit studies, and esophageal intraluminal impedance evaluate esophageal transit and partially assess motor function. However, esophageal manometry is the test of choice for the evaluation of esophageal motor function. In recent years, high-resolution manometry (HRM) has streamlined the process of acquisition and display of esophageal pressure data, while uncovering hitherto unrecognized esophageal physiologic mechanisms and pathophysiologic patterns. New algorithms have been devised for analysis and reporting of esophageal pressure topography from HRM. The clinical value of HRM extends to the pediatric population, and complements preoperative evaluation prior to foregut surgery. Provocative maneuvers during HRM may add to the assessment of esophageal motor function. The addition of impedance to HRM provides bolus transit data, but impact on clinical management remains unclear. Emerging techniques such as 3-D HRM and impedance planimetry show promise in the assessment of esophageal sphincter function and esophageal biomechanics.

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.

Background Esophageal impedance monitoring has made it possible to distinguish two types of belches, designated gastric and supragastric. We aimed to compare the esophageal pressure characteristics during supragastric belches and gastric belches using combined high-resolution manometry and impedance monitoring. Methods We included 10 patients with severe and frequent belching. Combined high-resolution manometry and impedance monitoring was performed. Key Results Whereas gastric belching was relatively rare in all patients (median incidence 2 per 90-min period), nine of the 10 patients exhibited excessive supragastric belching (36 in 90 min). Supragastric belches were characterized by: (i) movement of the diaphragm in aboral direction and increased esophagogastric junction (EGJ) pressure, (ii) decrease in esophageal pressure, (iii) upper esophageal sphincter (UES) relaxation, (iv) antegrade airflow into the esophagus, and (v) increase in esophageal and gastric pressure leading to expulsion of air out of the esophagus in retrograde direction. In contrast, gastric belches were characterized by: (i) decreased or unchanged EGJ pressure, which was significantly lower than during supragastric belches, (ii) absence of decreased esophageal pressure preceding entrance of air into the esophagus (iii) retrograde airflow into the esophagus, (iv) common cavity phenomenon, and (v) upper esophageal sphincter relaxation after the onset of the retrograde airflow. Conclusions & Inferences In gastric belching UES relaxation is a late event, allowing efflux of air that entered the esophagus from the stomach. In most patients with supragastric belching air is brought into the esophagus by movement of the diaphragm in aboral direction, creation of negative esophageal pressure, and UES relaxation.

Background Non-obstructive dysphagia patients prove to be a difficult category for clinical management. Esophageal high-resolution manometry (HRM) is a novel method, used to analyze dysphagia. However, it is not yet clear how findings on HRM relate to bolus transport through the esophagus. Methods Twenty healthy volunteers and 20 patients with dysphagia underwent HRM and videofluoroscopy in a supine position. Each subject swallowed five liquid and five solid barium boluses. Esophageal contraction parameters and bolus transport were evaluated with HRM and concurrent videofluoroscopy. Key Results Stasis of liquid and solid barium boluses occurred in patients and in healthy volunteers in 64% and 41% and in 84% and 82% of the swallows, respectively. Overall, 70% of the liquid and 72% of the solid bolus swallows were followed by a peristaltic contraction, the difference not being statistically significant. Statistically significant associations were found for transition zone length of liquid and solid boluses, and for DCI and distal contraction amplitudes for liquid stasis. No correlation was found between the degree of stasis and other manometric parameters. Conclusions & Inferences Stasis of both liquid and solid boluses occurs frequently in patients and in controls and can be regarded as physiological. Motility patterns can predict the effectiveness of bolus transit and level of stasis to some degree but the relationship between esophageal motility and transit is complex and far from perfect. Esophageal manometry is therefore currently deemed unfit to be used for the prediction of bolus transit, and should rather be used for the identification of treatable esophageal motility disorders.

Background According to the Chicago classification of esophageal motility disorders, distal esophageal spasm (DES) is defined as premature esophageal contractions (distal latency [DL]

SUMMARY Background Frequent belching is a common symptom in patients with functional dyspepsia with a reported incidence up to 80%. We hypothesized that patients with functional dyspepsia possibly have a higher frequency of belching than healthy subjects secondary to frequent air swallowing. Aim To assess air swallowing, belching, acid and non-acid reflux patterns of patients with functional dyspepsia. Methods Combined 24-h oesophageal impedance and pH monitoring was performed in 10 functional dyspepsia patients and 10 controls. Analysis of the impedance-pH signals included incidence of air swallows, belching, acid and non-acid reflux. Results The incidence of air swallows in functional dyspepsia patients were significantly higher compared with controls (153 15 vs. 79 10, P < 0.001), while the incidence of liquid-only swallows were not significantly increased. The proportions of gas-containing reflux episodes (belches) and non-acid reflux episodes in functional dyspepsia patients were significantly higher when compared with controls (66.4 vs. 44.4%, P = 0.04 and 70.1 vs. 45.9%, P = 0.009, respectively).

Enhanced characterization of esophageal peristaltic and sphincter function provided by esophageal pressure topography (EPT) offers a potential diagnostic advantage over conventional line tracings (CLT). However, high-resolution manometry (HRM) and EPT require increased equipment costs over conventional systems and evidence demonstrating a significant diagnostic advantage of EPT over CLT is limited. Our aim was to investigate whether the inter-rater agreement and/or accuracy of esophageal motility diagnosis differed between EPT and CLT. Forty previously completed patient HRM studies were selected for analysis using a customized software program developed to perform blinded independent interpretation in either EPT or CLT (six pressure sensors) format. Six experienced gastroenterologists with a clinical focus in esophageal disease (attendings) and six gastroenterology trainees with minimal manometry experience (fellows) from three academic centers interpreted each of the 40 studies using both EPT and CLT formats. Rater diagnoses were assessed for inter-rater agreement and diagnostic accuracy, both for exact diagnosis and for correct identification of a major esophageal motility disorder. The total group agreement was moderate (κ=0.57; 95% CI: 0.56-0.59) for EPT and fair (κ=0.32; 0.30-0.33) for CLT. Inter-rater agreement between attendings was good (κ=0.68; 0.65-0.71) for EPT and moderate (κ=0.46; 0.43-0.50) for CLT. Inter-rater agreement between fellows was moderate (κ=0.48; 0.45-0.50) for EPT and poor to fair (κ=0.20; 0.17-0.24) for CLT. Among all raters, the odds of an incorrect exact esophageal motility diagnosis were 3.3 times higher with CLT assessment than with EPT (OR: 3.3; 95% CI: 2.4-4.5; P

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