Esophagogastric junction distensibility identifies achalasia subgroup with manometrically normal esophagogastric junction relaxation.

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.

A pregnant patient with excessive belching.

We present a patient that developed severe belching during pregnancy. Esophageal pH-impedance monitoring revealed frequent supragastric belching, but not gastroesophageal reflux disease (GERD). Thus, severe belching during pregnancy can be due to a behavioral disorder in the absence of GERD. Belching complaints during pregnancy should therefore not always be treated as GERD.

Normal values of esophageal motility after antireflux surgery; a study using high-resolution manometry.

BACKGROUND: Fundoplication is an effective therapy for gastroesophageal reflux disease (GERD), but can be complicated by postoperative dysphagia. High-resolution manometry (HRM) can assess esophageal function, but normal values after fundoplication are lacking. Our aim was to obtain normal values for HRM after successful Toupet and Nissen fundoplication. METHODS: Esophageal HRM was performed 3 months after Toupet or Nissen fundoplication in 40 GERD patients without postoperative dysphagia and with a normal barium esophagogram. Normal values for all measures of the Chicago classification were calculated as 5th and 95th percentile ranges. KEY RESULTS: The normal values (5th-95th percentiles) for integrated relaxation pressure (IRP) were higher after Nissen (5.1-24.4 mmHg) than after Toupet fundoplication (3.1-15.0 mmHg), and upper limit of normal was significantly higher after Nissen fundoplication than observed in the asymptomatic subjects that were described in the Chicago Classification. Distal contractile integral was significantly higher after Nissen (357-4947 mmHg*s*cm) than after Toupet (68-2177 mmHg*s*cm), and transition zone length was significantly shorter after Nissen (0-4.8 cm) than after Toupet fundoplication (0-12.8 cm). CONCLUSIONS & INFERENCES: HRM metrics for subjects after a Toupet fundoplication are similar to the normal values derived from healthy subjects used for the Chicago classification. However, after Nissen fundoplication a higher esophagogastric junction resting pressure and higher IRP are observed in asymptomatic subjects and this can be considered normal in the postoperative state. In addition, more vigorous contractions and less and smaller peristaltic breaks are normal after Nissen fundoplication.

Systematic review: questionnaires for assessment of gastroesophageal reflux disease.

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.

Prucalopride decreases esophageal acid exposure and accelerates gastric emptying in healthy subjects.

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 < 0.05). The total number of reflux events was unaffected by prucalopride, however, the number of reflux events extending to the proximal esophagus was reduced by prucalopride (15.5 [9.8-25.5] vs 10.5 [5.3-17.5], p < 0.05). Furthermore, prucalopride improved acid clearance time (77.5 [47.8-108.8] vs 44.0 [30.0-67.8] s, p < 0.05). Prucalopride did not affect the number of transient lower esophageal sphincter (LES) relaxations or their association with reflux events. Esophageal motility and basal pressure of the LES were not affected by prucalopride. Prucalopride increased gastric emptying (T1/2 ; 32.7 [27.9-44.6] vs 49.8 [37.7-55.0] min, p < 0.05) and decreased residue after 120 min (8.8 [4.4-14.8] vs 2.7 [1.3-5.4] %, p < 0.05). CONCLUSIONS & INFERENCES: Prucalopride reduces esophageal acid exposure and accelerates gastric emptying in healthy male volunteers. These findings suggest that the drug could be effective for treatment of patients with reflux disease and functional dyspepsia.

Impact of spatial resolution on results of esophageal high-resolution manometry.

BACKGROUND: The Chicago classification for esophageal motility disorders was designed for a 36-channel manometry system with sensors spaced at 1 cm. However, many motility laboratories outside the USA use catheters with a lower resolution in the segments outside the esophagogastric junction. Our aim was to investigate the effect of spatial resolution on the Chicago metrics and diagnosis. METHODS: In 20 healthy volunteers and 47 patients with upper gastrointestinal symptoms, high-resolution manometric studies of the esophagus were retrospectively reanalyzed using the original 1-cm spacing in the segments outside the 7-cm esophagogastric junction segment, and again after manually increasing the spacing between sensors to 2, 3, and 4 cm (above the lower esophageal sphincter region). Measurements were analyzed in random order and the investigator was blinded to the outcome of the analyses performed in another resolution of the same patient. Intra-class correlation coefficients (ICC) and Kappa values were determined. KEY RESULTS: There was a very strong correlation between the 1-cm and 2-cm analysis for all Chicago metrics studied in healthy volunteers (ICCs: distal contractile integral 0.998; contractile front velocity (CFV) 0.964; distal latency 0.919; peristaltic break size 0.941). The 2-cm spacing analysis also correlated very well with the 1-cm analysis for the different Chicago diagnoses obtained in the patients (Kappa values ranging from 0.665 to 1.000). When the sensor spacing was increased to 3 and 4 cm, the correlation was reduced to moderate for the Chicago metrics, especially for break size and CFV of peristalsis. CONCLUSIONS & INFERENCES: The Chicago classification for esophageal motility disorders is still valid and the same normal values can be used when catheters with a slightly lower resolution are used (i.e., 2-cm vs 1-cm spacing). For larger sensor intervals, the classification and the normal values will need to be adjusted.

Normal values for solid-state esophageal high-resolution manometry in a European population; an overview of all current metrics.

BACKGROUND: Esophageal high-resolution manometry (HRM) allows accurate evaluation of esophageal motility. Normal values for HRM were established in the United States and several new parameters were introduced since. We aimed to provide a complete set of normal values for HRM obtained in a European population, including all current metrics used to describe the function of the upper esophageal sphincter (UES), the esophageal body, and the esophagogastric junction (EGJ). METHODS: Fifty healthy volunteers underwent esophageal HRM. Subjects swallowed 10 liquid boluses in supine position, after which UES, EGJ, and contraction wave parameters were evaluated. Mean and median values with 5-95th percentile ranges were calculated. KEY RESULTS: The normative thresholds (5-95th percentile) for the various parameters were; UES resting pressure 34.6-137.7 mmHg, UES residual pressure 0.0-8.5 mmHg, UES 0.2-s integrated relaxation pressure (IRP) 0.0-14.5 mmHg, EGJ length 3.1-6.3 cm, EGJ resting pressure 3.0-31.2 mmHg, EGJ 4-s IRP 2.0-15.5 mmHg, intrabolus pressure (IBP) 6.6-19.5 mmHg, distal contractile integral 178-2828 mmHg*s*cm, contractile front velocity (CFV) 2.9-5.9 cm s(-1) , distal latency 5.4-8.5 s, and transition zone length 0.0-8.2 cm. CONCLUSIONS & INFERENCES: Most HRM parameters assessed in this study resemble the previously described values on which the current criteria are based, supporting the widespread use of these criteria for clinical purposes. However, vigor of the esophageal contraction was lower and transition zone length larger than in previous reports. Peristaltic breaks occur frequently in healthy subjects.

Mechanisms of gastric and supragastric belching: a study using concurrent high-resolution manometry and impedance monitoring.

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.

Supragastric belches are the main determinants of troublesome belching symptoms in patients with gastro-oesophageal reflux disease.

BACKGROUND: Patients with gastro-oesophageal reflux disease (GERD) frequently report excessive belching but it is not known what determines the severity of these complaints. AIM: To determine what causes troublesome belching symptoms in GERD patients. METHODS: We included 90 consecutive patients who were referred for ambulatory 24-h pH-impedance measurement as part of the analysis of reflux symptoms. Overall severity of belching was reported by the patients using a 3-point scale. Furthermore, each belch perceived during the ambulatory measurement was reported by the patients using a symptom diary. RESULTS: No significant differences in frequency of gastric belches or combined liquid reflux and gastric belches were observed. However, the number of supragastric belches was significantly higher in patients with severe belching complaints compared to patients with moderate and none to mild complaints. Moreover, the number of supragastric belches which coincided with a liquid reflux episode was significantly higher in patients with severe complaints than in those with moderate and none to mild complaints. Per-patient analysis showed that belches coinciding with a liquid reflux event were more often symptomatic than isolated belches. CONCLUSIONS: The type of belch determines the burden of belching complaints in patients with GERD. Supragastric belches, not gastric belches determine the severity of belching complaints.

Review article: the clinical relevance of transient lower oesophageal sphincter relaxations in gastro-oesophageal reflux disease.

BACKGROUND: Transient lower oesophageal sphincter relaxations (TLOSR) are considered the physiological mechanism that enables venting of gas from the stomach and appear as sphincter relaxations that are not induced by swallowing. It has become increasingly clear that most reflux episodes occur during TLOSRs and therefore play a key role in gastro-oesophageal reflux disease (GERD). AIM: To describe the current knowledge about TLOSRs and its clinical implications. METHODS: Search of the literature published in English using the PubMed database and relevant abstracts presented at international conventions. RESULTS: Several factors influence the rate of TLOSRs including anti-reflux surgery, meal, body position, nutrition, lifestyle and a wide array of neurotransmitters. Ongoing insights in the neurotransmitters responsible for the modulation of TLOSRs, as well as the neural pathways involved in TLOSR induction, have lead to novel therapeutic targets. These therapeutic targets can serve as an add-on therapy in patients with an unsatisfactory response to proton pump inhibitor by inhibiting TLOSRs and its associated reflux events. However, the TLOSR-inhibiting drugs that are currently available still have significant side effects. CONCLUSION: It is likely that in the future, selected GERD patients may benefit from transient lower oesophageal sphincter relaxation inhibition when compounds are found without significant side effects.