Analysis of Spontaneous Gastroesophageal Reflux and Esophageal Acid Clearance in Patients with Reflux Esophagitis

To characterize gastroesophageal reflux episodes and esophageal acid clearance in patients with reflux esophagitis, we obtained 12-hour overnight esophageal pH and manometry recordings in 20 patients with macroscopic reflux esophagitis and in 15 healthy volunteers. Compared to the control subjects, the patients had less pressure in the lower esophageal sphincter (LES) and higher rates of reflux, acid clearance time, and esophageal acid exposure. However, many patients had normal values for one or more of these variables. Transient LES relaxation accounted for 96% of reflux episodes in control subjects and 60% in patients. The remaining 40% of reflux episodes in patients occurred as stress or free reflux. In the control subjects, only one reflux episode occurred during estimated sleep. Of 22 reflux episodes during estimated sleep in patients, most were associated with low basal LES pressure. During esophageal acid clearance, the major esophageal motor event was swallow-induced peristalsis rather than secondary peristalsis. We conclude that esophagitis patients have lower LES pressures, more reflux episodes, impaired esophageal acid clearance, and more esophageal exposure to acid than control subjects. Individual patients, however, exhibit heterogeneous abnormalities with respect to these variables. Transient LES relaxation is the major mechanism of gastroesophageal reflux in both patients and healthy subjects.     

Analysis of Spontaneous Gastroesophageal Reflux and Esophageal Acid Clearance in Patients with Reflux Esophagitis

To characterize gastroesophageal reflux episodes and esophageal acid clearance in patients with reflux esophagitis, we obtained 12-hour overnight esophageal pH and manometry recordings in 20 patients with macroscopic reflux esophagitis and in 15 healthy volunteers. Compared to the control subjects, the patients had less pressure in the lower esophageal sphincter (LES) and higher rates of reflux, acid clearance time, and esophageal acid exposure. However, many patients had normal values for one or more of these variables. Transient LES relaxation accounted for 96% of reflux episodes in control subjects and 60% in patients. The remaining 40% of reflux episodes in patients occurred as stress or free reflux. In the control subjects, only one reflux episode occurred during estimated sleep. Of 22 reflux episodes during estimated sleep in patients, most were associated with low basal LES pressure. During esophageal acid clearance, the major esophageal motor event was swallow-induced peristalsis rather than secondary peristalsis. We conclude that esophagitis patients have lower LES pressures, more reflux episodes, impaired esophageal acid clearance, and more esophageal exposure to acid than control subjects. Individual patients, however, exhibit heterogeneous abnormalities with respect to these variables. Transient LES relaxation is the major mechanism of gastroesophageal reflux in both patients and healthy subjects.     

High‐resolution esophageal pressure topography is superior to conventional sleeve manometry for the detection of transient lower esophageal sphincter relaxations associated with a reflux event

Background Transient lower esophageal sphincter relaxations (TLESRs) are the main mechanism underlying gastro‐esophageal reflux and are detected during manometric studies using well defined criteria. Recently, high‐resolution esophageal pressure topography (HREPT) has been introduced and is now considered as the new standard to study esophageal and lower esophageal sphincter (LES) function. In this study we performed a head‐to‐head comparison between HREPT and conventional sleeve manometry for the detection of TLESRs. Methods A setup with two synchronized MMS‐solar systems was used. A solid state HREPT catheter, a water‐perfused sleeve catheter, and a multi intraluminal impedance pH (MII‐pH) catheter were introduced in 10 healthy volunteers (M6F4, age 19–56). Subjects were studied 0.5 h before and 3 h after ingestion of a standardized meal. Tracings were blinded and analyzed by the three authors according to the TLESR criteria. Key Results In the HREPT mode 156 TLESRs were scored, vs 143 during sleeve manometry (P = 0.10). Hundred and twenty‐three TLESRs were scored by both techniques. Of all TLESRs (177), 138 were associated with reflux (78%). High‐resolution esophageal pressure topography detected significantly more TLESRs associated with a reflux event (132 vs 119, P = 0.015) resulting in a sensitivity for detection of TLESRs with reflux of 96% compared to 86% respectively. Analysis of the discordant TLESRs associated with reflux showed that TLESRs were missed by sleeve manometry due to low basal LES pressure (N = 5), unstable pharyngeal signal (N = 4), and residual sleeve pressure >2 mmHg (N = 10). Conclusions & Inferences The HREPT is superior to sleeve manometry for the detection of TLESRs associated with reflux. However, rigid HREPT criteria are awaited.     

Mechanism of gastroesophageal reflux in patients with obstructive sleep apnea syndrome

Background It has been reported that the prevalence of gastroesophageal reflux (GER) disease is high in patients with obstructive sleep apnea (OSA). End‐inspiratory intra‐esophageal pressure decreases progressively during OSA, which has been thought to facilitate GER in OSA patients. The aim of our study was to clarify the mechanisms of GER during sleep (sleep‐GER) in OSA patients. Methods Eight OSA patients with reflux esophagitis (RE), nine OSA patients without RE, and eight healthy controls were studied. Polysomnography with concurrent esophageal manometry and pH recording were performed. Key Results Significantly more sleep‐GER occurred in OSA patients with RE than without RE or in controls (P < 0.05). The severity of OSA did not differ between OSA patients with RE and without RE. Sleep‐GER was mainly caused by transient lower esophageal sphincter relaxation (TLESR), but not by negative intra‐esophageal pressure during OSA. During OSA gastroesophageal junction pressure progressively increased synchronous to intra‐esophageal pressure decrease. OSA patients had significantly more TLESR events during sleep related to preceding arousals and shallow sleep, but the number of TLESR events was not related to RE. Conclusions & Inferences In OSA patients, sleep‐GER was mainly caused by TLESR, but not by negative intra‐esophageal pressure due to OSA.     

Validation of a Fully Automated Analysis of Esophageal Body Contractility and Lower Esophageal Sphincter Function: A Study on the Effect of the PGEI Analogue Rioprostil on Human Esophageal Motility

A new method for automatic analysis of resting lower esophageal sphincter pressure and postdeglutitive motor activity of esophageal body and lower esophageal sphincter (LES) is validated by comparing the results obtained with automatic and manual analysis of 11,700 esophageal body pressure peaks, 390 resting LES pressure measurements, and 3900 LES relaxations. The automatic analysis is based on the on-line transformation of pressure recordings into a mathematical formula using B-spline functions, which allows one to use the same parameters as those generally applied in manual analysis of esophageal manometric recordings. Statistical evaluation of the results indicates that this method provides a faithful analysis of the pressure tracings. The difference between manual and automatic analysis (mean ± SD) was only + 1.49 ± 4.26 mm Hg for wave amplitude, -0.15 ± 0.61 seconds for wave duration, +0.37 ± 1.05 cm/second for progression velocity, +0.95 ± 1.38 mm Hg for resting LES pressure, and -2.0 ± 1.67 mm Hg for residual LES pressure after deglutition. Wave form was correctly recognized in 95.3% of the waves. Pressure recordings were obtained from a study on the effect of the PGE₁ analogue rioprostil (600 and 300 μg), administered orally on esophageal motor function in 10 normal volunteers. The drug increased both the resting LES pressure and the amplitude of esophageal body contractions and decreased the completeness of LES relaxation after swallowing.     

Cardiovascular compression of the esophagus and spread of gastro‐esophageal reflux

Background Factors that determine the spread of gastro‐esophageal reflux (GER) along the length of the esophagus are not known. We investigated if cardiovascular (CV) compressions on the esophagus may determine the spread of refluxate into the proximal esophagus. Methods High‐resolution manometry (HRM) and multi‐channel intra‐luminal impedance recording (MIIR) were performed simultaneously in 10 normal subjects in the recumbent and upright positions. Pulsatile pressure increases on the esophagus (marker of CV compression) were identified on the HRM. Spread of refluxate into the esophagus was determined by the MIIR. Key Results Cardiovascular compression zones were observed in the esophagus in 9 out of 10 subjects in recumbent position. Forty percent of GER episodes were limited to the distal esophagus in the recumbent position and CV compression pressure was greater than distal esophageal pressure at the time of GER in all such cases. On the other hand, distal esophageal pressure was greater than CV compression pressure when the refluxate extended into the proximal esophagus. In the upright position, CV compression was less frequent than recumbent position and only 12% of GER episodes were limited to the distal esophagus. Conclusions & Inferences Cardiovascular compression of the esophagus is frequently observed in normal healthy subject and restricts the spread of refluxate into the proximal esophagus.     

Mechanisms of gastro-oesophageal reflux in the ferret

Transient lower oesophageal sphincter (LOS) relaxation is the major mechanism of gastro-oesophageal reflux in humans – an event unassociated with swallowing. Mechanisms involved in triggering transient LOS relaxation are poorly understood, and their further study requires a small animal model. In this study we aimed to establish methods for prolonged ambulant oesophageal manometry in ferrets, and to determine motor events associated with reflux episodes and their triggering by different gastric nutrient loads. Forty-two studies were performed on nine ferrets with chronic cervical oesophagostomies, through which a manometric assembly was introduced and secured to a collar, which incorporated a microphone for detection of swallows. The assembly included a gastric feeding channel, one gastric and four oesophageal manometric sideholes, a 2.5-cm-long LOS sleeve sensor, and an oesophageal pH electrode. Intragastric infusions were given over 2 min, the first after a 30-min control recording period, and in 29/42 studies, a second infusion was given 60 min later. Infusions were either 25 mL 10% dextrose solution, pH 3.5 (22 studies), 25 mL triglyceride emulsion (Intralipid) pH 3.5 (11 studies), or 25 mL air (nine studies). Episodes of oesophageal acidification were absent before gastric infusions. After infusion, 2.1 ± 0.2 episodes occurred over the first 30 min. After glucose infusion, 15/18 acidification episodes (83%) occurred during transient LOS relaxation, and 3/18 (17%) occurred after gradual (< 1 mmHg sec⁻¹) downward drifts in basal LOSP to < 2 mmHg. After lipid infusion two acidification episodes occurred, both during transient LOS relaxation. Mean duration of transient LOS relaxation was 8.0 ± 0.4 sec. All infusions increased occurrence of transient LOS relaxation to a similar extent, each of which ended with primary peristalsis. We conclude that gastric infusion of glucose, lipid and gas are all effective in provoking gastro-oesophageal reflux in ferrets. Reflux occurs through similar mechanisms to those seen in humans, i.e. increased triggering of transient LOS relaxation. The conscious ferret is therefore an appropriate model for future studies of manipulation of mechanisms giving rise to gastro-oesophageal reflux.     

Diagnosis of supra‐esophageal gastric reflux: correlation of oropharyngeal pH with esophageal impedance monitoring for gastro‐esophageal reflux

Background Oropharyngeal (OP) pH monitoring has been developed as a new way to diagnose supra‐esophageal gastric reflux (SEGR), but has not been well validated. Our aim was to determine the correlation between OP pH and gastro‐esophageal reflux (GER) events detected by multichannel intraluminal impedance‐pH (MII‐pH). Methods Fifteen patients (11 males, median age 10.8 years) with suspected GER were prospectively evaluated with ambulatory 24‐h OP pH monitoring (positioned at the level of the uvula) and concomitant esophageal MII‐pH monitoring. Potential OP events were identified by the conventional pH threshold of <4 and by the following alternative criteria: (i) relative pH drop >10% from 15‐min baseline and (ii) absolute pH drop below thresholds of <5.5, 5.0, and 4.5. The 2‐min window preceding each OP event was analyzed for correlation with an episode of GER detected by MII‐pH. Key Results A total of 926 GER events were detected by MII‐pH. Application of alternative pH criteria increased the identification of potential OP pH events; however, a higher proportion of OP events had no temporal correlation with GER (45–81%), compared with the conventional definition of pH < 4 (40%). A total of 306 full‐column acid reflux episodes were detected by MII‐pH, of which 10 (3.3%) were also identified by OP pH monitoring. Conclusions & Inferences Use of extended pH criteria increased the detection of potential SEGR events, but the majority of decreases in OP pH were not temporally correlated with GER. Oropharyngeal pH monitoring without concurrent esophageal measurements may overestimate the presence of SEGR in children.     

Gastroesophageal reflux in neurologically impaired children

We present here the indication, procedure and results of surgical treatment of gastroesophageal reflux (GER) for neurologically impaired children. We decide its indication based on clinical symptoms and findings of upper GI series, esophageal pH monitoring and GI fiberscopy, respecting the QOL of the patient and family. Laparoscopic fundoplication has become the first choice in surgical treatment of GER because of its good results. However, an anti-reflux procedure is not effective in patients with intractable aspiration. A laryngotracheal separation procedure should be applied for these cases.     

The effects of intraduodenal nutrient infusion on serum CCK,LES pressure,and gastroesophageal reflux

Background Fats cause reflux symptoms in many patients and cholecystokinin (CCK) may play a role. This study was designed to evaluate the effects of intraduodenal nutrient infusion on serum CCK levels, lower esophageal sphincter (LES) pressure, and gastroesophageal reflux (GER). Methods Twenty‐four asymptomatic volunteers were studied. A Dent sleeve catheter assessed LES function while an impedance‐pH catheter measured reflux events. Participants were randomized to fat (F), carbohydrate (C) or protein (P) infusion. Serum CCK and LES pressures were measured at baseline and after nutrient infusion. Key Results Baseline LES pressures and CCK levels were similar in all three groups. A significant linear decrease was found in LES pressure during F, but not C or P, infusion (P = 0.004). A significant interaction effect was noted between the infusion groups and CCK levels (P = 0.002). A significant linear increase was noted in CCK levels during F but not during C or P infusion (P = 0.02). A significant inverse correlation was found between CCK levels and LES pressure (ρ = ?0.43; P = 0.04). Esophageal acid exposure was significantly increased in the F infusion group (median; interquartile range: 1.10%; 0.25–4.7%) compared to both the C (0.03%; 0.00–0.39%) and P infusion (0.03%; 0.00–0.39%) groups (P = 0.04). Conclusions & Inferences Intraduodenal F infusion was associated with an increase in CCK levels, while P and C were not. LES pressure decreased significantly after fat infusion and reflux events were more frequent. Fat‐induced CCK release is another mechanism that contributes to GER.     

Increase of weakly acidic gas esophagopharyngeal reflux (EPR) and swallowing‐induced acidic/weakly acidic EPR in patients with chronic cough responding to proton pump inhibitors

Background Gastro‐esophageal reflux disease (GERD)‐related chronic cough (CC) may have multifactorial causes. To clarify the characteristics of esophagopharyngeal reflux (EPR) events in CC patients whose cough was apparently influenced by gastro‐esophageal reflux (GER), we studied patients with CC clearly responding to full‐dose proton pump inhibitor (PPI) therapy (CC patients). Methods Ten CC patients, 10 GERD patients, and 10 healthy controls underwent 24‐h ambulatory pharyngo‐esophageal impedance and pH monitoring. Weakly acidic reflux was defined as a decrease of pH by >1 unit with a nadir pH >4. In six CC patients, monitoring was repeated after 8 weeks of PPI therapy. The number of each EPR event and the symptom association probability (SAP) were calculated. Symptoms were evaluated by a validated GERD symptom questionnaire. Key Results Weakly acidic gas EPR and swallowing‐induced acidic/weakly acidic EPR only occurred in CC patients, and the numbers of such events was significantly higher in the CC group than in the other two groups (P < 0.05, respectively). Symptom association probability analysis revealed a positive association between GER and cough in three CC patients. Proton pump inhibitor therapy abolished swallowing‐induced acidic/weakly acidic EPR, reduced weakly acidic gas EPR, and improved symptoms (all P < 0.05). Conclusions & Inferences Most patients with CC responding to PPI therapy had weakly acidic gas EPR and swallowing‐induced acidic/weakly acidic EPR. A direct effect of acidic mist or liquid refluxing into the pharynx may contribute to chronic cough, while cough may also arise indirectly from reflux via a vago‐vagal reflex in some patients.     

Relationship between reflux diseases and obstructive sleep apnea together with continuous positive airway pressure treatment efficiency analysis

BackgroundObstructive sleep apnea (OSA) is known to be highly associated with reflux diseases. There is evidence that continuous positive airway pressure (CPAP) can decrease the clinical symptoms of gastroesophageal reflux (GER) in OSA patients, but whether CPAP can decrease nocturnal laryngopharyngeal reflux (LPR) episodes is still lack of strong evidence.ObjectiveTo investigate the efficiency of CPAP on LPR and the relationship between LPR, GER and OSA.Study designretrospective study.MethodsForty adult patients who had confirmed OSA by polysomnography and suspected LPR were enrolled. Their results of synchronous polysomnography and 24 h esophageal and oropharyngeal Dx-pH monitoring were analyzed. Twenty-seven OSA patients were treated with CPAP on the second night. The nocturnal reflux parameters with and without CPAP treatment were compared.Results15.0% and 42.5% of OSA patients were associated with LPR and GER through Dx-pH monitoring respectively. Nevertheless, more than one reflux attack falling below pH6.0 of oropharynx during sleep time was detected in 80.0% patients. There was a significant inverse correlation between the lowest/mean pH values of oropharynx and obstructive apnea index (OAI), so was the lowest pH values of esophagus. Significant positive correlation was calculated between the total number of reflux episodes below pH6.0 of oropharynx and apnea–hypopnea index (AHI)/OAI/hypopnea index (HI). A similar positive correlation was also significant between AHI/OAI and GER parameters. The assessment of the efficacy of CPAP treatment showed significant difference both in GER and LPR related parameter.ConclusionsOSA patients have a higher incidence of nocturnal LPR and GER. CPAP treatment can effectively reduce both GER and LPR attacks while disordered sleep events reduced in OSA patients.     

Decreased sympathetic inhibition in gastroesophageal reflux disease

This study was undertaken to evaluate autonomic nervous system function in patients with gastroesophageal reflux disease. Based on clinical criteria, 28 consecutive patients with no history of heart, metabolic, or neurologic disease (mean age 41 y, range 20–62 y) reporting with upper gastrointestinal symptoms typical of gastroesophageal reflux underwent esophageal manometry, ambulatory 24-hour pH study with electrocardiographic monitoring, power spectral analysis of heart rate variability, and cardiovascular tests. Twelve healthy subjects served as controls. A positive result of prolonged esophageal pH study (pH in the distal esophagus less than 4, lasting more than 4.2% of recording time) was observed in 21 patients (reflux group); seven patients were categorized in the nonreflux group. No patient showed arrhythmias or any correlation between heart rate variability changes during electrocardiographic monitoring and episodes of reflux (pH less than 4, lasting more than 5 minutes). A decrease of sympathetic function occurred only in the reflux group (p<0.05) supported by the lower increase of systolic/diastolic blood pressure at sustained handgrip. No other cardiovascular tests showed statistically significant differences in the control or nonreflux groups. Total time reflux showed an inverse correlation with sympathetic function in the reflux group (r=-0.415, p<0.028). We concluded that there is some evidence for a slightly decreased sympathetic function in patients with gastroesophaged reflux disease that is inversely correlated with total time reflux. In these patients, decreased sympathetic function may cause dysfunction of intrinsic inhibitory control with increased transient spontaneous lower-esophageal sphincter relaxations, thus resulting in gastroesophageal reflux disease.     

Motor events underlying gastro-oesophageal reflux in ambulant patients with reflux oesophagitis

Abstract Information on the mechanism of gastro-oesophageal reflux in patients with reflux disease is limited largely to studies in resting recumbent subjects. Evidence exists that both posture and physical activity may influence reflux. The aim of this study was to investigate reflux mechanisms in ambulant patients with reflux oesophagitis. Concurrent ambulatory oesophageal manometry and pH monitoring were performed in 11 ambulant patients with erosive oesophagitis. Lower oesophageal sphincter (LOS) pressure was monitored with a perfused sleeve sensor. Recordings were made for 90 min before and 180 min after a meal. At set times patients sat in a chair or walked. LOS pressure was ≤2 mmHg at the time of reflux for 98% of reflux episodes. Transient LOS relaxation was the most common pattern overall and the predominant pattern in seven patients, whilst persistently absent basal LOS pressure was the most common pattern in four patients. The pattern of LOS pressure was not altered by the presence of hiatus hernia or by walking. Straining occurred at the onset of 31% of acid reflux episodes but often followed the development of an oesophageal common cavity. The occurrence of straining was not influenced by walking. In ambulant patients with reflux oesophagitis: (1) LOS pressure is almost always absent at the time of reflux, usually because of transient LOS relaxation, (2) persistently absent basal LOS pressure is an important mechanism of reflux in a few patients, (3) straining may help to induce acid reflux in a variable proportion of occasions and may in some instances be a response to gas reflux, and (4) walking does not influence the occurrence of reflux or its mechanisms.     

Reflux monitoring in children

Recently, multichannel intraluminal impedance (MII) monitoring was added to the repertoire of tests to evaluate the (patho)physiology of gastroesophageal reflux (GER) in children. Its advantage above the sole monitoring of the esophageal pH lies in the ability of the detection of both acid and nonacid GER and to discern between liquid and gas GER. Currently, combined 24 h pH‐MII monitoring is recommended for evaluation of gastro‐esophageal reflux disease (GERD) and its relation to symptoms in infants and children, despite the lack of reference values in these age groups. There is new evidence in the current issue of this Journal supporting the role of pH‐MII monitoring for the evaluation of children presenting with gastrointestinal symptoms suggestive of GERD and the prediction of the presence of reflux esophagitis. However, several issues should be taken into account when performing pH‐MII clinically.     

The lower esophageal sphincter

The lower esophageal sphincters (LES) together with the crural diaphragm are the major antireflux barriers protecting the esophagus from reflux of gastric content. However, reflux of gastric contents into the esophagus is a normal phenomenon in healthy individuals occurring primarily during episodes of transient lower esophageal sphincter relaxation (TLESR), defined as LES relaxation in the absence of a swallow. Transient lower esophageal sphincter relaxation is also the dominant mechanism of pathologic reflux in gastroesophageal reflux disorder (GERD) patients. Frequency of TLESR does not differ significantly between healthy individuals and those with GERD, but TLESRs are more likely to be associated with acid reflux in GERD patients. Understanding the mechanisms responsible for elicitation of a TLESR, using recently introduced novel technology is an area of intense interest. Pharmacologic and non‐pharmacologic manipulation of receptors involved in the control of TLESR has recently emerged as a potential target for GERD therapy.     

Upper sphincter function during transient lower oesophageal sphincter relaxation (tLOSR); it is mainly about microburps

Transient lower oesophageal sphincter relaxations (tLOSRs) are both a dominant mechanism of reflux and an element of the belch reflex. This study aimed to analyse the interplay between reflux and upper oesophageal sphincter (UOS) activity during meal-induced tLOSRs. Fifteen normal subjects were studied with a solid-state high-resolution manometry assembly positioned to record from the hypopharynx to the stomach and a catheter pH electrode 5 cm above the LOS. Subjects ate a 1000-calorie high-fat meal and were monitored for 120 min in a sitting posture. The relationship among tLOSRs, common cavities, pressure changes within the oesophagus and UOS contractile activity were analysed. A total of 218 tLOSRs occurred among the 15 subjects. The majority (79%) were coupled with UOS relaxation and 84% (145/173) of these occurred in association with a common cavity. Upper oesophageal sphincter relaxation was usually preceded by a pressure change in the oesophagus; however, some relaxations (16%) occurred without a discernable increase in pressure or before the pressure increase began. Acid reflux did not appear to play a role in determining UOS response to tLOSRs. The majority of post-prandial tLOSRs were associated with brief periods of UOS relaxation, likely permissive of gas venting (microburps). Intraoesophageal pressure changes likely modulate this UOS response; however, an anticipatory characteristic was evident in some subjects. Whether or not GORD patients with extra-oesophageal symptoms exhibit an exaggeration of the UOS relaxation response during reflux is yet to be determined.     

Reproducibility of meal-induced transient lower oesophageal sphincter relaxations in patients with gastro-oesophageal reflux disease

AIM: To calculate the number of subjects required in trials investigating drugs reducing the number of transient lower oesophageal sphincter relaxations (TLOSRs), the inter- and intra-individual variability of TLOSRs were determined, using meal ingestion as a trigger of TLOSRs and reflux. METHODS: A total of 23 gastro-oesophageal reflux disease (GORD) patients with no to grade B oesophagitis and a hiatal hernia < or =3 cm underwent oesophageal manometry and pHmetry 1 h before and 3 h after ingestion of a solid meal on two separate days approximately 4 weeks apart. Reflux episodes and the underlying mechanisms and the number of TLOSRs were evaluated. RESULTS: The number of TLOSRs, reflux episodes and % time with pH < 4 after meal ingestion did not differ significantly between the two sessions. The intra-individual variation of TLOSRs in the 3 h postprandial period (24.4) was smaller compared with the inter-individual variation (47.5). Transient lower oesophageal sphincter relaxations were the predominant cause of reflux accounting for 61 +/- 7 and 70 +/- 5% of the reflux episodes in visits 1 and 2, respectively. CONCLUSIONS: These data for the first time provide information on the variability of TLOSRs and reflux evoked by meal ingestion, which is of crucial importance for the design and power calculations of future clinical studies evaluating the efficacy of new drugs targeting TLOSRs.     

Reproducibility of esophageal high‐resolution manometry

Background Esophageal high‐resolution manometry (HRM) is a novel method for esophageal function testing that has prompted the development of new parameters for quantitative analysis of esophageal function. Until now, the reproducibility of these parameters has not been investigated. Methods Twenty healthy volunteers underwent HRM on two separate days. Standard HRM parameters were measured. In addition, in conventional (virtual) line tracings, lower esophageal sphincter (LES) resting pressure, relaxation pressure, and relative relaxation pressure were measured. Firstly, for each variable, the mean percentage of covariation (100 × SD/mean: %COV) was derived as a measure of inter‐ and intra‐individual variation. Secondly, Kendall’s coefficients of concordance (W values) were calculated. Thirdly, Bland–Altman plots were used to express concordance graphically. Key Results Statistically significant concordance values were found for upper esophageal sphincter (UES) pressure (W = 0.90, P = 0.02), transition zone length (W = 0.92, P = 0.01), LES length (W = 0.81, P = 0.04), LES pressure (W = 0.75, P = 0.05), LES relaxation pressure (W = 0.75, P = 0.03), relative LES relaxation pressure (W = 0.78, P = 0.05), gastric pressure (W = 0.81, P = 0.04), and contraction amplitude 5 cm above the LES (W = 0.86, P = 0.03). In conventional setting, only LES resting pressure (W = 0.835, P = 0.03) proved significant. In HRM tracings, concordance values for contraction wave parameters, and in conventional line tracings, LES relaxation pressure and relative relaxation pressure did not reach levels of statistical significance. Conclusions & Inferences Esophageal HRM yields reproducible results. Parameters that represent anatomic structures show better reproducibility than contraction wave parameters. The reproducibility of LES resting and relaxation pressure assessed with HRM is better than with conventional manometry and further supports the clinical use of HRM.     

Short-term electrical stimulation of the lower esophageal sphincter increases sphincter pressure in patients with gastroesophageal reflux disease

Background Electrical stimulation (ES) of the lower esophageal sphincter (LES) increases resting LES pressure (LESP) in animal models. Our aims were to evaluate the safety of such stimulation in humans, and test the hypothesis that ES increases resting LESP in patients with gastroesophageal reflux disease (GERD). Methods A total of 10 subjects (nine female patients, mean age 52.6 years), with symptoms of GERD responsive to PPIs, low resting LES pressure, and abnormal 24‐h intraesophageal pH test were enrolled. Those with hiatal hernia >2 cm and/or esophagitis >Los Angeles Grade B were excluded. Bipolar stitch electrodes were placed longitudinally in the LES during an elective laparoscopic cholecystectomy, secured by a clip and exteriorized through the abdominal wall. Following recovery, an external pulse generator delivered two types of stimulation for periods of 30 min: (i) low energy stimulation; pulse width of 200 μs, frequency of 20 Hz and current of 5–15 mA (current was increased up to 15 mA if LESP was less than 15 mmHg), and (ii) high energy stimulation; pulse width of 375 ms, frequency of 6 cpm, and current 5 mA. Resting LESP, amplitude of esophageal contractions and residual LESP in response to swallows were assessed before and after stimulation. Symptoms of chest pain, abdominal pain, and dysphagia were recorded before, during, and after stimulation and 7‐days after stimulation. Continuous cardiac monitoring was performed during and after stimulation. Key Results All patients were successfully implanted nine subjects received high frequency, low energy, and four subjects received low frequency, high energy stimulation. Both types of stimulation significantly increased resting LESP: from 8.6 mmHg (95% CI 4.1–13.1) to 16.6 mmHg (95% CI 10.8–19.2), P < 0.001 with low energy stimulation and from 9.2 mmHg (95% CI 2.0–16.3) to 16.5 mmHg (95% CI 2.7–30.1), P = 0.03 with high energy stimulation. Neither type of stimulation affected the amplitude of esophageal peristalsis or residual LESP. No subject complained of dysphagia. One subject had retrosternal discomfort with stimulation at15 mA that was not experienced with stimulation at 13 mA. There were no adverse events or any cardiac rhythm abnormalities with either type of stimulation. Conclusions & Inferences Short‐term stimulation of the LES in patients with GERD significantly increases resting LESP without affecting esophageal peristalsis or LES relaxation. Electrical stimulation of the LES may offer a novel therapy for patients with GERD.