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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 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.

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 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.

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.

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 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.

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).

The manometric common cavity phenomenon has been used as indicator of gastro-oesophageal reflux of liquid or gaseous substances. Using combined pH and impedance recording as reference standard the value of a common cavity as indicator of gastro-oesophageal reflux was tested. Ten healthy male subjects underwent combined stationary pressure, pH and impedance recording for 4.5 h. After 1.15 h of recording, a reflux-eliciting meal was consumed. The chi-squared and Kolmogorov–Smirnov tests were used for the statistical analysis. A common cavity was found in 95 (43%) of the 223 reflux events detected by impedance, while seven common cavities were unrelated to a reflux episode. In 54% of the reflux events detected by impedance without a common cavity, a possible common cavity was obscured by either contractile activity or artefacts of various origin. The types of reflux associated with a common cavity (liquid 60%, mixed 31%, gas 9%) and without a common cavity (liquid 59%, mixed 29%, gas 12%) did not differ, or did the acidity of the reflux episodes (with common cavity: acid 67%; without common cavity: acid 58%). The common cavity is a specific but not a sensitive marker of gastro-oesophageal reflux. Furthermore, common cavities are not specific for a particular type of reflux.

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

BACKGROUND Manometric criteria to diagnose achalasia are absent peristalsis and incomplete relaxation of the esophagogastric junction (EGJ), determined by an integrated relaxation pressure (IRP) >15 mm Hg. However, EGJ relaxation seems normal in a subgroup of patients with typical symptoms of achalasia, no endoscopic abnormalities, stasis on timed barium esophagogram (TBE), and absent peristalsis on high-resolution manometry (HRM). The aim of our study was to further characterize these patients by measuring EGJ distensibility and assessing the effect of achalasia treatment. METHODS Impedance planimetry (EndoFLIP) was used to measure EGJ distensibility and compared to previous established data of 15 healthy subjects. In case the EGJ distensibility was impaired, achalasia treatment followed. Eckardt score, HRM, TBE, and EGJ distensibility measurements were repeated >3 months after treatment. KEY RESULTS We included 13 patients (5 male; age 19-59 years) with typical symptoms of achalasia, Eckardt score of 7 (5-7). High-resolution manometry showed absent peristalsis with low basal EGJ pressure of 10 (5.8-12.9) mm Hg and IRP of 9.3 (6.1-12) mm Hg. Esophageal stasis was 4.6 (2.7-6.9) cm after 5 minutes. Esophagogastric junction distensibility was significantly reduced in patients compared to healthy subjects (0.8 [0.7-1.2] mm2 /mm Hg vs 6.3 [3.8-8.7] mm2 /mm Hg). Treatment significantly improved the Eckardt score (7 [5-7] to 2 [1-3.5]) and EGJ distensibility (0.8 [0.7-1.2] mm2 /mm Hg to 3.5 [1.5-6.1] mm2 /mm Hg). CONCLUSIONS & INFERENCES A subgroup of patients with clinical and radiological features of achalasia but manometrically normal EGJ relaxation has an impaired EGJ distensibility and responds favorably to achalasia treatment. Our data suggest that this condition can be considered as achalasia and treated as such.