Neuronal Control of Esophageal Peristalsis and Its Role in Esophageal Disease.

PURPOSE OF REVIEW: Esophageal peristalsis is a highly sophisticated function that involves the coordinated contraction and relaxation of striated and smooth muscles in a cephalocaudal fashion, under the control of central and peripheral neuronal mechanisms and a number of neurotransmitters. Esophageal peristalsis is determined by the balance of the intrinsic excitatory cholinergic, inhibitory nitrergic and post-inhibitory rebound excitatory output to the esophageal musculature. RECENT FINDINGS: Dissociation of the longitudinal and circular muscle contractions characterizes different major esophageal disorders and leads to esophageal symptoms. Provocative testing during esophageal high-resolution manometry is commonly employed to assess esophageal body peristaltic reserve and underpin clinical diagnosis. Herein, we summarize the main factors that determine esophageal peristalsis and examine their role in major and minor esophageal motility disorders and eosinophilic esophagitis.

The 2018 ISDE achalasia guidelines.

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

The 2018 ISDE achalasia guidelines

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

Role of TRPV1 receptor in inflammation and impairment of esophageal mucosal integrity in a murine model of nonerosive reflux disease.

BACKGROUND: Microscopic inflammation and impairment of the esophageal epithelial barrier are considered relevant for perception of symptoms in patients with nonerosive reflux disease (NERD). In these patients, the receptor transient receptor potential vanilloid 1 (TRPV1) is overexpressed in the esophageal mucosa, but its role is not yet fully understood. We evaluated the role of TRPV1 in esophageal inflammation and mucosal barrier impairment in a murine model of NERD. METHODS: Nonerosive reflux disease was surgically induced in Swiss mice by pyloric substenosis and ligature of the gastric fundus, and the mice were killed 7 days post surgery. The experimental groups were: I, sham surgery (negative control); II, NERD untreated; III and IV, NERD + SB366791 or capsazepine (TRPV1 antagonists); and V, NERD + resiniferatoxin (for long-term desensitization of TRPV1). The esophagus was collected for western blotting and histopathology and for evaluation of wet weight, myeloperoxidase (MPO), keratinocyte-derived chemokine (KC), transepithelial electrical resistance (TEER), and basal permeability to fluorescein. KEY RESULTS: Compared to sham, NERD mice had increased esophageal wet weight and MPO and KC levels. The mucosa had no ulcers but exhibited inflammation. NERD mice showed mucosal TRPV1 overexpression, a more pronounced decrease in TEER at pH 0.5 (containing pepsin and taurodeoxycholic acid), and increased basal permeability. Pharmacological modulation of TRPV1 prevented esophageal inflammation development, TEER changes by acidic exposure, and increase in esophageal permeability. CONCLUSIONS & INFERENCES: The TRPV1 receptor has a critical role in esophageal inflammation and mucosal barrier impairment in NERD mice, suggesting that TRPV1 might be a pharmacological target in patients with NERD.

Treatment of supragastric belching with cognitive behavioral therapy improves quality of life and reduces acid gastroesophageal reflux.

OBJECTIVES: Excessive supragastric belching (SGB) manifests as troublesome belching, and can be associated with reflux and significant impact on quality of life (QOL). In some GERD patients, SGB-associated reflux contributes to up to 1/3 of the total esophageal acid exposure. We hypothesized that a cognitive-behavioral intervention (CBT) might reduce SGB, improve QOL, and reduce acid gastroesophageal reflux (GOR). We aimed to assess the effectiveness of CBT in patients with pathological SGB. METHODS: Patients with SGB were recruited at the Royal London Hospital. Patients attended CBT sessions focused on recognition of warning signals and preventative exercises. Objective outcomes were the number of SGBs, esophageal acid exposure time (AET), and proportion of AET related to SGBs. Subjective evaluation was by patient-reported questionnaires. RESULTS: Of 51 patients who started treatment, 39 completed the protocol, of whom 31 had a follow-up MII-pH study. The mean number of SGBs decreased significantly after CBT (before: 116 (47-323) vs. after 45 (22-139), P<0.0003). Sixteen of 31 patients were shown to have a reduction in SGB by >50%. In patients with increased AET at baseline, AET after CBT was decreased: 9.0-6.1% (P=0.005). Mean visual analog scale severity scores decreased after CBT (before: 260 (210-320) mm vs. after: 140 (80-210) mm, P<0.0001). CONCLUSIONS: Cognitive behavioral therapy reduced the number of SGB and improved social and daily activities. Careful analysis of MII-pH allows identification of a subgroup of GERD patients with acid reflux predominantly driven by SGB. In these patients, CBT can reduce esophageal acid exposure.

Ambulatory pH-impedance-pressure monitoring as a diagnostic tool for the reflux-cough syndrome.

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.

Classification of esophageal motor findings in gastro-esophageal reflux disease: Conclusions from an international consensus group.

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

Assessing the pre- and postpeak phases in a swallow using esophageal pressure topography.

BACKGROUND: The current paradigm of measuring esophageal contractile vigor assesses the entirety of a pressure wave using a single measurement, the distal contractile integral (DCI). We hypothesize that an assessment identifying separate phases of the contractile pressure wave before and after the pressure peak may help distinguish abnormalities in patients presenting with chest pain and dysphagia. The aim of the present study was to develop a technique to assess the individual phases and report on the values in healthy controls. METHODS: Seventy-one healthy controls were enrolled. High-resolution manometry studies of five intact liquid swallows in both supine and upright positions were analyzed using a customized MATLAB program to divide swallows into a prepeak phase and postpeak phase, and compute the contractile integral of both phases. The contractile integrals were also controlled by duration over each phase. KEY RESULTS: The composite DCI measurement in healthy controls appears to be weighted toward slightly higher contractile activity during postpeak phase based on postpeak to prepeak ratios in both the supine and upright position (1.50 and 1.49, respectively). The contribution of postpeak phase on the composite DCI was weakened when controlled by time (0.92 and 0.96 in both supine and upright position, respectively). CONCLUSIONS AND INFERENCES: We developed a novel measurement focused on separating the prepeak and postpeak components of the peristaltic contractile activity during swallowing. Using this technique, it appears that overall contractile activity is higher during postpeak phase and this is related to the longer time component during this phase.

Ambulatory reflux monitoring for diagnosis of gastro-esophageal reflux disease: Update of the Porto consensus and recommendations from an international consensus group.

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

Mechanisms underlying reflux symptoms and dysphagia in patients with joint hypermobility syndrome, with and without postural tachycardia syndrome.

BACKGROUND: The joint hypermobility syndrome (JHS) is a common non-inflammatory connective tissue disorder which frequently co-exists with postural tachycardia syndrome (PoTS), a form of orthostatic intolerance. Gastrointestinal symptoms and dysmotility have been reported in PoTS. Dysphagia and reflux are common symptoms in JHS, yet no studies have examined the physiological mechanism for these, subdivided by PoTS status. METHODS: Thirty patients (28 female, ages: 18-62) with JHS and symptoms of reflux (n=28) ± dysphagia (n=25), underwent high-resolution manometry and 24 hour pH-impedance monitoring after questionnaire-based symptom assessment. Esophageal physiology parameters were examined in JHS, subdivided by PoTS status. RESULTS: Fifty-three percent of JHS patients with reflux symptoms had pathological acid reflux, 21% had reflux hypersensitivity, and 25% had functional heartburn. Acid exposure was more likely to be increased in the recumbent than upright position (64% vs 43%). The prevalence of hypotensive lower esophageal sphincter (33%) and hiatus hernia (33%) was low. Forty percent of patients with dysphagia had minor disorders of motility, 60% had functional dysphagia. Eighteen (60%) patients had coexistent PoTS-they had significantly higher dysphagia (21 vs 11.5, P=.04) and reflux scores (24.5 vs 16.5, P=.05), and double the prevalence of pathological acid reflux (64% vs 36%, P=.1) and esophageal dysmotility (50% vs 25%, P=.2) though this was not significant. CONCLUSIONS AND INFERENCES: A large proportion of JHS patients with esophageal symptoms have true reflux-related symptoms or mild esophageal hypomotility, and this is more likely if they have PoTS.

Jackhammer esophagus: Observations on a European cohort.

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

Validation of criteria for the definition of transient lower esophageal sphincter relaxations using high-resolution manometry.

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.

Anatomical and functional deficiencies of the crural diaphragm in patients with esophagitis.

BACKGROUND: Inspiratory esophagogastric junction (EGJ) pressure is lower in gastroesophageal reflux disease (GERD) and patients fail to increase EGJ pressure during the inspiratory effort. The aim of this study was to assess the EGJ activity during inspiratory maneuvers (high-resolution manometry, HRM) and the crural diaphragm (CD) thickness (endoscopic ultrasound, EUS) in GERD. METHODS: Twenty esophagitis patients (average age 45 years, 7 grade A, 13 grade B) had HRM and EUS. Forty-three controls were recruited; 30 had HRM (average age 33 years), and 13 had EUS (average age 40 years). The EGJ contractility index (EGJ-CI) (mm Hg×cm) was measured during normal respiration and two inspiratory maneuvers: without and with inspiratory loads of 12, 24, and 48 cmH2 O (TH-maneuvers). A composite metric for TH-maneuvers ("EGJ total activity") was defined as the product of the maximal EGJ pressure and the length of its aboral excursion during the maneuver (mm Hg×cm). The CD thickness (cm) was measured during expiration (12 MHz). KEY RESULTS: Expiratory lower esophageal sphincter pressure and integrated relaxation pressure were lower in GERD. The EGJ-CI and the "EGJ total activity" were lower in GERD during TH-maneuvers (48-cmH2 O load: 168.4 ± 13.8 vs 114.8 ± 9.6, P=.006). Patients failed to sustain the inspiratory CD activity across the 12 and 48-cmH2 O efforts. The CD was thinner in GERD patients (0.37 ± 0.03 vs 0.49 ± 0.04, P=.02). The CD thickness correlated with the increment in the "EGJ total activity" in GERD without a hiatal hernia (r=.702, P=.016, n=11). CONCLUSIONS & INFERENCES: There are anatomical changes and functional failure of the CD in esophagitis patients supporting the possibility of a skeletal muscle deficiency in GERD.

Topical protection of human esophageal mucosal integrity.

Patients with nonerosive reflux disease exhibit impaired esophageal mucosal integrity, which may underlie enhanced reflux perception. In vitro topical application of an alginate solution can protect mucosal biopsies against acid-induced changes in transepithelial electrical resistance (TER). We aimed to confirm this finding in a second model using 3D cell cultures and to assess prolonged protection in a biopsy model. We assessed the protective effect of a topically applied alginate solution 1 h after application. 3D cell cultures were grown by using an air-liquid interface and were studied in Ussing chambers. The apical surface was "protected" with 200 µl of either alginate or viscous control or was unprotected. The tissue was exposed to pH 3 + bile acid solution for 30 min and TER change was calculated. Distal esophageal mucosal biopsies were taken from 12 patients and studied in Ussing chambers. The biopsies were coated with either alginate or viscous control solution. The biopsies were then bathed in pH 7.4 solution for 1 h. The luminal chamber solution was replaced with pH 2 solution for 30 min. Percentage changes in TER were recorded. In five biopsies fluorescein-labeled alginate solution was used to allow immunohistological localization of the alginate after 1 h. In the cell culture model, alginate solution protected tissue against acid-induced change in TER. In biopsies, 60 min after protection with alginate solution, the acidic exposure caused a -8.3 ± 2.2% change in TER compared with -25.1 ± 4.5% change after protection with the viscous control (P < 0.05). Labeled alginate could be seen coating the luminal surface in all cases. In vitro, alginate solutions can adhere to the esophageal mucosa for up to 1 h and exert a topical protectant effect. Durable topical protectants can be further explored as first-line/add-on therapies for gastroesophageal reflux disease.

Normal esophageal pressure topography metrics for data derived from the Sandhill-Unisensor high-resolution manometry assembly in supine and sitting positions.

BACKGROUND: Normal values of the esophageal motor function parameters for high-resolution manometry (HRM-EPT) adopted by the Chicago classification were established using the proprietary system of Given Imaging. It is conceivable that normal values of a system do not apply to data from others. Most studies using HRM were based on supine swallows, whereas deglutition occurs mostly in the upright position. We wished to establish normal values for HRM-EPT parameters obtained with the Sandhill's HRM-EPT system and compare the results in supine and sitting positions. METHODS: Sixty-nine healthy volunteers, 38 females, median age 27 years, were included in this study. All underwent supine HRM, and 34 of them underwent sitting HRM, with at least 10 single 5-mL swallows for analysis obtained in each position. KEY RESULTS: The normal range (5-95th percentiles) for the following parameters was calculated: distal contractile integral (DCI), 606-4998 mmHg·s·cm; contractile front velocity (CFV), 2.0-6.5 cm/s; distal latency (DL), 5.1-8.8 s; intrabolus pressure (IBP), 1.9-17.6 mmHg; upper esophageal sphincter (UES) pressure, 45.2-186.9 mmHg; esophagogastric junction (EGJ) length, 1.8-4 cm; EGJ resting pressure, 8.1-61.6 mmHg, and integrated relaxation pressure (IRP) 2.5-23.5 mmHg. Normal values of EGJ resting pressure, IRP, DCI, and IBP but not CFV, DL, and UES resting pressure were significantly lower in the sitting posture. CONCLUSIONS & INFERENCES: Studies performed with Sandhill's HRM-EPT system should use its own specific normal data. Normal values should be established for different study.

Regionally dependent neuromuscular functions of motilin and 5-HT4 receptors in human isolated esophageal body and gastric fundus.

BACKGROUND: Motilin agonists promote human gastric motility and cholinergic activity, but excitatory and inhibitory actions are reported in the esophagus. The effect of 5-HT4 agonists in esophagus is also unclear. Perhaps the use of drugs with additional actions explains the variation. The aim, therefore, was to examine how motilin and prucalopride, selective motilin and 5-HT4 receptor agonists, modulate neuromuscular functions in human esophagus and gastric fundus. METHODS: Electrical field stimulation (EFS) evoked nerve-mediated contractions of circular and longitudinal muscle from human esophageal body and circular muscle from gastric fundus. KEY RESULTS: In esophageal circular muscle EFS evoked brief contraction, followed by another contraction on termination of EFS, each prevented by atropine. Nitric oxide synthase inhibition facilitated contraction during EFS and the overall contraction became monophasic. In esophagus longitudinal muscle and gastric fundus, EFS evoked cholinergically mediated, monophasic contractions, attenuated by simultaneous nitrergic activation. Motilin (100-300 nM) reduced esophagus circular muscle contractions during EFS, unaffected by L-NAME or apamin. Motilin 300 nM also reduced EFS-evoked contractions of longitudinal muscle. Similar concentrations of motilin facilitated cholinergic activity in the fundus and increased baseline muscle tension. Prucalopride facilitated EFS-evoked contractions in esophagus (tested at 30 µM) and fundus (0.1-30 µM). CONCLUSIONS & INFERENCES: Selective motilin and 5-HT4 agonists have different, region-dependent abilities to modulate human esophageal and stomach neuromuscular activity, exemplified by weak inhibition (motilin) or excitation (5-HT4) in esophageal body and excitation for both in stomach. In different patients with motility dysfunctions, motilin and 5-HT4 agonists may reduce gastro-esophageal reflux in different ways.

Sensiprobe--a miniature thermal device incorporating Peltier technology as a diagnostic tool for studying human oesophageal sensitivity.

Heightened perception of gastrointestinal sensation is termed visceral hypersensitivity (VH) and is commonly observed in patients with gastrointestinal disorders. VH is thought to be a major contributory factor in oesophageal disease, particularly gastro-oesophageal reflux disease that does not respond to standard (proton pump inhibitor) treatment, and in functional heartburn. Clinical tools that can help phenotype according to the mechanism of chronic pain and thus allow targeted drug treatment (e.g. with pain modulator therapy) would be very desirable. A technique that produces repeatable and controllable thermal stimuli within the oesophagus could meet this need. The aims of this study were to develop a method for linear control of the heat stimulation in the oesophagus, to assess the reproducibility of this method, and obtain normal thermal sensitivity values in the distal and proximal oesophagus. The 7 mm diameter Peltier-based thermal device was investigated on 27 healthy subjects using a heating ramp of 0.2 °C s(-1). The pain detection threshold (PDT) temperature was recorded. To assess the reproducibility of the device, each subject underwent the procedure twice, with a minimum of two weeks between each procedure. The mean PDT temperature measured in the distal oesophagus, was 53.8 ± 2.9 °C and 53.6 ± 2.6 °C, for visits 1 and 2 respectively. The mean PDT temperature measured in the proximal oesophagus was 54.1 ± 2.4 °C and 54.0 ± 2.8 °C, for visits 1 and 2 respectively. The reproducibility of the PDT temperature in the distal and proximal oesophagus, was good (intra-class correlation >0.6). Future studies should be aimed to determine whether oesophageal thermal sensitivity can act as a biomarker of transient receptor potential vallanoid 1 upregulation.

Postprandial cardiac vagal tone and transient lower esophageal sphincter relaxation (TLESR).

BACKGROUND: Transient lower esophageal sphincter relaxation (TLESR) is a vagally mediated reflex that occurs most frequently after a meal. Cardiac vagal tone (CVT) decreases after a meal, and correlates with changes in gastric electrical activity. Furthermore, decreased CVT has been reported in patients with gastro-esophageal reflux disease. We therefore aimed to characterize the association between postprandial changes in CVT and the occurrence of TLESR and reflux. METHODS: Ten healthy volunteers underwent simultaneous autonomic nervous system, gastric myoelectric activity, lower esophageal-sphincter pressure, and reflux monitoring for 30 min in the fasting state, followed by a standard meal, and a further 4 h postprandially. Results are in mean ± SEM. KEY RESULTS: The number of TLESRs (P < 0.0001) and reflux episodes (P < 0.0001) increased after the meal, while CVT decreased (P < 0.01). Cardiac sensitivity to baroreceptor reflex (CSB) showed similar time course changes to CVT (P = 0.06). During the first postprandial hour there was a strong correlation between the number of TLESRs and reflux episodes with CVT (R(2)  = 0.51 and R(2)  = 0.50, respectively; P < 0.05). There was also an increase in the dominant power and power ratio on electrogastrography (P < 0.05) after the meal. CONCLUSIONS & INFERENCES: In healthy volunteers, the increase in the number of TLESRs and reflux episodes after a meal occurred mostly at a time of reduced CVT. Further studies should explore whether modulation of CVT can modify frequency of TLESRs and also this relationship should be further explored in patients with reflux disease.

Evaluation of esophageal contractile propagation using esophageal pressure topography.

BACKGROUND: High-resolution manometry and esophageal pressure topography have enhanced our ability to analyze esophageal motor disturbances by improving the detail and accuracy of measurements of peristaltic activity.This has been extremely helpful in the evaluation of disorders of rapid propagation as the technique is able to define important time points and physiologic landmarks that are crucial in defining peristaltic velocity and latency intervals. PURPOSE: The goal of the current review will be to assess how esophageal pressure topography has impacted our ability to define important phenotypes of rapid propagation. Additionally, this review will also be utilized to complement the description of the Chicago Classification of Esophageal Motor Disorders, which is presented in this supplement issue.

Anatomy and physiology of the esophageal body.

The primary role of the esophagus is to propel swallowed food or fluid into the stomach and to prevent or clear gastroesophageal reflux. This function is achieved by an organized pattern that involves a sensory pathway, neural reflexes, and a motor response that includes esophageal tone, peristalsis, and shortening. The motor function of the esophagus is controlled by highly complex voluntary and involuntary mechanisms. There are three different functional areas in the esophagus: the upper esophageal sphincter, the esophageal body, and the LES. This article focused on anatomy and physiology of the esophageal body.