Mechanisms of gastroesophageal reflux in children with sequelae of birth asphyxia

Patterns of childhood gastroesophageal reflux (GER) have been studied extensively; however, the mechanisms underlying its occurrence in neurologically impaired children (NIC) are poorly understood. Concurrent esophageal manometry and pH monitoring was conducted in 10 un-operated children (7 male; mean age: 59.5 months) with sequelae birth asphyxia and esophagitis. Reflux episodes were scored when esophageal pH decreased to <4 for at least 5s. When the rate of decrease of lower esophageal sphincter (LES) pressure was >1mmHg/s, the decrease of LES pressure was defined as LES relaxation. The time relationship of the pharyngeal manometric swallowing signal to LES relaxation onset was then evaluated in order to distinguish between LES relaxations associated with swallowing (type II or III, associated with one or more swallows, respectively) and those that occurred independently of swallowing (type I). Results: Esophageal manometry and pH monitoring were conducted for a mean duration of 91.5min. Basal LES pressure averaged (+/-SD) 9.2+/-4.8mmHg; in 4 of 10 patients (40%) the LES pressure was largely undetectable, varying between 0 and 2mmHg. Mean LES pressure was inversely correlated with age (r=0.7, P=0.02). The total number of reflux episodes/h averaged 32.1+/-12.1 LES pressure reached 0mmHg in 98% of reflux episodes. Type I LES relaxations were present in 3.15+/-1.1 reflux episodes/h, whereas type II LES relaxation occurred in 2.3+/-2.4 episodes/h. Acid reflux episodes appeared during absent basal LES tone periods, without phasic LES relaxations, in 74%. Conclusions: Absent basal LES tone is the main mechanism of GER in a subgroup of NIC, especially in older children. Transient LES relaxation, the most common known event associated with acid reflux in neurologically normal children, seems to precede a minority of reflux events in NIC.     

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.     

Gastroesophageal and laryngopharyngeal reflux profiles in patients with obstructive sleep apnea/hypopnea syndrome as determined by combined multichannel intraluminal impedance-pH monitoring

Background The profiles of gastroesophageal reflux (GER) and laryngopharyngeal reflux (LPR) in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) have never been explored. The aim of the study was to investigate the reflux profile in OSAHS patients. Methods Consecutive snoring out‐patients suspected with having OSAHS and 20 healthy volunteers were included. All subjects underwent simultaneous 24‐h combined multichannel intraluminal impedance–pH (MII–pH) monitoring and polysomnography. Obstructive sleep apnea/hypopnea syndrome was defined when the apnea/hypopnea index was over 5. Stepwise multiple logistic regression analysis was performed to determine the predictor for OSAHS. Key Results Fifty‐three patients were included, 37 with and 16 without OSAHS. The prevalence of reflux symptoms was similar between OSAHS (35.1%) and non‐OSHAS (37.5%) patients. More OSAHS patients, compared with non‐OSAHS patients and healthy volunteers, had pathologic acid GER, nocturnal acid GER, and prolonged acid clearance (P < 0.001). However, no difference in non‐acid reflux episodes was observed among the three groups. Laryngopharyngeal reflux was detected in 51.4%, 43.8%, and 35.0% of OSAHS, non‐OSAHS, and healthy volunteers, respectively (P = 0.034). In OSAHS patients, there was no difference in the sleep parameters between patients with and without LPR. Body mass index was the only predictor of OSAHS in the regression analysis. Conclusions & Inferences OSAHS patients have more pathologic acid GER and prolonged acid clearance than non‐OSAHS patients whereas non‐acid reflux was similar between the two groups. However, BMI, not GER, is the only independent predictor for OSAHS. Laryngopharyngeal reflux occurs in more than half of OSAHS patients despite no significant association with OSAHS.     

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.     

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.     

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.     

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.     

Overlap of dyspepsia and gastroesophageal reflux in the general population: one disease or distinct entities?

Background The overlap of dyspepsia and gastroesophageal reflux (GER) is known to be frequent, but whether the overlap group is a distinct entity or not remains unclear. The aims of the study was to evaluate whether the overlap of dyspepsia and GER (dyspepsia‐GER overlap) occurs more than expected due to chance alone, and evaluate the risk factors for dyspepsia‐GER overlap. Methods In 2008 and 2009, a validated Bowel Disease Questionnaire was mailed to a total of 8006 community sample from Olmsted County, MN. Overall, 3831 of the 8006 subjects returned surveys (response rate 48%). Dyspepsia was defined by symptom criteria of Rome III; GER was defined by weekly or more frequent heartburn and/or acid regurgitation. Key Results Dyspepsia and GER occurred together more commonly than expected by chance. The somatic symptom checklist score was significantly associated with dyspepsia‐GER overlap vs GER alone or dyspepsia alone [OR = 1.9 (1.4, 2.5), and 1.6 (1.2, 2.1), respectively]. Insomnia was also significantly associated with dyspepsia‐GER overlap vs. GER alone or dyspepsia alone [OR = 1.4 (1.1, 1.7), OR = 1.3 (1.1, 1.6), respectively]. Moreover, proton pump inhibitor use was significantly associated with dyspepsia‐GER overlap vs dyspepsia alone [OR = 2.4 (1.5, 3.8)]. Conclusions & Inferences Dyspepsia‐GER overlap is common in the population and is greater than expected by chance.     

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.     

Serum lipid levels are positively associated with non‐erosive reflux disease,but not with functional heartburn

Background Metabolic syndrome and obesity are known risk factors for gastro‐esophageal reflux disease (GERD), especially for erosive esophagitis. Although non‐erosive reflux disease (NERD) is probably associated with obesity or other metabolic syndrome, there is little direct evidence to support this assertion. Methods Workers in Keio University who underwent a general health examination between September 2006 and August 2007 were enrolled. Reflux symptom questionnaires were administered and metabolic parameters were obtained. The severity of gastro‐esophageal reflux (GER) was scored using a validated scale of videoesophagography. Key Results Two hundred and eighty‐three subjects (243 men and 40 women; mean age 49.8 ± 6.9 years) with no radiographic evidence of erosive esophagitis were enrolled. The severity of GER was worse among men than among women, whereas the severity of reflux symptoms was worse among women. The severity of GER was associated with age and serum triglyceride levels in men, and with the serum low‐density lipoprotein cholesterol levels in women. The severity of reflux symptoms, however, was not associated with metabolic parameters. There were more women than men with reflux symptoms but without GER (‘presumed’ functional heartburn group), compared with subjects with neither GER nor reflux symptoms. In men, the presence of both reflux symptoms and GER (‘presumed’ NERD group) was associated with the serum triglyceride levels. Conclusions & Inferences While NERD is associated with serum lipid levels, functional heartburn is not. The prevalence of GER was greater among men; conversely, the prevalence of functional heartburn was greater among women.     

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.     

The frequency of apneas in very preterm infants is increased after non‐acid gastro‐esophageal reflux

Background To evaluate whether physical and/or chemical features of gastro‐esophageal reflux (GER) influence its relationship with apnea of prematurity (AOP). Methods Fifty‐eight preterm newborns (GA ≤33 weeks) with recurrent apneas were studied by simultaneous polysomnography and combined impedance and pH monitoring, to analyze whether the correlation between GER and AOP varies according to the acidity, duration and height of GERs. Key Results The frequency of apnea (number apnea/min) occurring after‐GER [median (range) 0.07 (0–0.25)] was higher than the one detected in GER‐free period [0.06 (0.04–0.13), P = 0.015], and also than the one detected before‐GER [0 (0–0.8), P = 0.000]. The frequency of apneas detected in the 30’’ after pH‐GER [median (range), 0 min^?1 (0–1.09)] was higher than the frequency detected in the 30’’ before [0 (0–0.91), P = 0.04]; even more, the frequency of apneas detected after non‐acid MII‐GER episodes [0 (0–2)] was significantly higher than the one detected before [0 (0–1), P = 0.000], whereas the frequency of apneas detected before acid MII‐GER episodes [0 (0–0.67)] did not differ from the one detected after [0 (0–2), P = 0.137]. The frequency of pathological apneas detected in the 30’’ after‐GER (0 min^?1, range 0–0.55) was higher than the frequency detected before (0, range 0–0.09; P = 0.001). No difference in mean height or in mean duration was found between GERs correlated and those non‐correlated to apnea. Conclusions & Inferences Non‐acid GER is responsible for a variable amount of AOP detected after‐GER: this novel finding must be taken into consideration when a therapeutic strategy for this common problem is planned.     

Effect of proximal gastric volume on hiatal hernia

Background Spatial separation of the diaphragm and the lower esophageal sphincter (LES) occurs frequently and intermittently in patients with a sliding hiatus hernia and favors gastro‐esophageal reflux. This can be studied with high‐resolution manometry. Although fundic accommodation is associated with a lower basal LES pressure, its effect on esophagogastric junction configuration and hiatal hernia is unknown. Therefore, the aim of this study was to investigate the relationship between proximal gastric volume, the presence of a hiatal hernia profile and acid reflux. Methods Twenty gastro‐esophageal reflux disease (GERD) patients were studied and compared to 20 healthy controls. High‐resolution manometry and pH recording were performed for 1 h before and 2 h following meal ingestion (500 mL per 300 kcal). Volume of the proximal stomach was assessed with three‐dimensional ultrasonography before and every 15 min after meal ingestion. Key Results During fasting, the hernia profile [2 separate high‐pressure zones (HPZs) at manometry] was present for 31.9 ± 4.9 min h^?1 (53.2%) in GERD patients, and 8.7 ± 3.3 min h^?1 (14.5%) in controls (P < 0.001). In GERD patients, the presence of hernia profile decreased during the first postprandial hour to 15.9 ± 4.2 min h^?1, 26.5%, P < 0.01 whilst this phenomenon was not observed in controls. The rate of transition between the two profiles was 5.7 ± 1.1 per hour in GERD patients and 2.5 ± 1.0 per hour in controls (P < 0.001). The pre and postprandial acid reflux rate in GERD patients during the hernia profile (6.4 ± 1.1 per hour and 18.4 ± 4.3 per hour respectively) was significantly higher than during reduced hernia (2.1 ± 0.6 per hour; P < 0.05 and 3.8 ± 0.9 per hour; P < 0.05). A similar difference was found in controls. Furthermore, an inverse correlation was found between fundic volume and the time the hernia profile was present (r = ?0.45; P < 0.05) in GERD patients, but not in controls. Conclusions & Inferences (i) In GERD patients a postprandial increase in proximal gastric volume is accompanied by a decrease in hernia prevalence, which can be explained by a reduction of the intra‐thoracic part of the stomach. (ii) A temporal hernia profile also occurs in healthy subjects. (iii) During the hernia profile, acid reflux is more prevalent, especially after meal ingestion.     

Modulation of upper and lower esophageal sphincter tone during sleep

BACKGROUND AND PURPOSE: The pressures generated within the upper esophageal sphincter (P(UES)) and lower esophageal sphincter (P(LES)) reflect the integrity of these barriers to gastroesophageal and pharyngoesophageal reflux, respectively. This study sought to describe the effects of sleep, respiration and posture on the function of the UES and the LES and the pressure differentials developed across them. METHODS: Ten healthy volunteers (7M, 3F: 38+/-10 yr) without a history of sleep-disordered breathing or reflux underwent overnight polysomnography with simultaneous measurement of P(LES) and P(UES) using a purpose-built sleeve device (Dentsleeve). Posture was recorded but not controlled. RESULTS: Subjects slept for 4.3+/-1.6h. Compared to waking values, both end-inspiratory and end-expiratory Pues were significantly less during slow wave sleep (SWS) (p<0.05). However, P(LES) was unaffected by sleep stage. During wakefulness and all stages of sleep, both P(UES) and P(LES) were greater at end-inspiration than end-expiration (p<0.05). Similar relationships were observed whether subjects were supine or in the lateral decubitus position. CONCLUSION: Sleep decreases the effectiveness of the UES to act as a barrier to pharyngoesophageal reflux, particularly during slow wave sleep (SWS). UES pressure varies with respiration, with minimal values observed during expiration. Hence, barrier function of the UES appears most impaired during SWS, in the expiratory phase of the respiratory cycle. The LES pressure and its barrier pressure also vary with respiration, being least during expiration. However, unlike the UES, the function of the LES was unaffected by sleep.     

The effect of baclofen on nocturnal gastroesophageal reflux and measures of sleep quality: a randomized, cross-over trial

Background Baclofen, a GABA_b agonist, has been shown to reduce episodes of gastroesophageal reflux (GER). To determine if baclofen would significantly reduce reflux during sleep, and also improve objective and subjective measures of sleep. Methods Twenty‐one individuals with complaints of nighttime heartburn at least twice a week and a Carlsson GERD score of at least 5 were studied. Patients underwent polysomnography (PSG) and simultaneous esophageal pH monitoring on two occasions separated by approximately 1 week in a cross‐over design. The night of each polysomnographic study, patients consumed a refluxogenic meal. Baclofen (40 mg) or placebo was given in random order 90 min prior to the start of the PSG. Key Results Baclofen significantly reduced the number of reflux events compared with placebo. Upright and recumbent acid contact times were both reduced by baclofen vs placebo, but the differences were not significant. Regarding sleep outcomes, several variables were significantly improved by baclofen. Total sleep time and sleep efficiency increased, and wake after sleep onset decreased in the baclofen condition compared with placebo. Proportion of Stage 1 sleep was also significantly decreased on baclofen. Conclusions & Inferences In addition to reducing the number of reflux events during sleep, baclofen significantly improved several measures of sleep in patients with documented GER and sleep disturbances. Baclofen could therefore be considered as a useful adjunct therapy to proton pump inhibitors (PPIs) in patients with nighttime heartburn and sleep disturbance who continue to have heartburn and/or sleep complaints despite PPI therapy.     

Effect of Esophageal Acid Exposure on Upper Esophageal Sphincter Pressure

To investigate the relationship between gastroesophageal reflux and upper esophageal sphincter (UES) pressure, total esophageal acid exposure times on 23-hour ambulatory pH monitoring were compared with UES manometric results in 98 subjects, 85 with laryngopharyngeal symptoms and 13 asymptomatic controls. There was no correlation of acid exposure time with tonic UES pressure nor with any UES wet swallow parameter. The response of the UES to acute upper esophageal acid infusion was assessed in another 13 patients by a sleeve catheter. There was no significant increase of tonic sleeve UES pressure during acid infusion. In contrast to most previous reports, our results indicate that esophageal acid exposure, whether acute or chronic, has little influence on the UES.     

Effect of lateral positioning on gastroesophageal reflux (GER) and underlying mechanisms in GER disease (GERD) patients and healthy controls

Background Posture has been shown to influence the number of transient lower esophageal sphincter relaxation (TLESRs) and gastroesophageal reflux (GER), however, the physiology explaining the influence of right lateral position (RLP), and left lateral position (LLP) is not clear. The aim of this study was to determine the influence of RLP and LLP on TLESRs and GERD after a meal in GER disease (GERD) patients and healthy controls (HC) while monitoring gastric distension and emptying. Methods Ten GERD patients and 10 HC were studied for 90 min (30 min test meal infusion, 30 min postprandial in either RLP or LLP (randomly assigned) and 30 min in alternate position). The study was repeated on a separate day in reverse position order. TLESRs, GER, and gastric emptying rate were recorded using manometry, multichannel intraluminal impedance, and ¹³C‐octanoate breath tests. Gastric distension was visualized by five serial gastric volume scintigraphy scans during the first 30 min. Key Results Gastroesophageal reflux, (GER) disease patients had increased numbers of TLESRs in RLP compared to LLP in the first postprandial hour [5 (4–14) and 4.5 (2–6), respectively, P = 0.046] whereas the number of TLESRs was not different in RLP and LLP [4 (2–4) and 4 (3–6), respectively, P = 0.7] in HC. Numbers of GER increased similar to TLESRs in GERD patients. In GERD patients, gastric emptying reached peak ¹³CO₂ excretion faster and proximal gastric distension was more pronounced. Conclusions & Inferences In GERD patients, TLESRs, GER, distension of proximal stomach, and gastric emptying are increased in RLP compared to LLP. This effect is not seen in HC.     

Mechanisms of gastro-oesophageal reflux in the lateral decubitus positions

Gastro-oesophageal reflux is more common in the right than in the left lateral position but the reasons why are not well understood. We have therefore studied the mechanisms underlying reflux in the lateral decubitus positions in patients with reflux disease. Fifteen patients with symptomatic reflux and excessive oesophageal acid exposure were studied (nine male, age 25-63 years). Each was intubated with a perfused manometric assembly, incorporating a Dent sleeve, and a pH probe. Following a 30-min basal period, a 400-kCal meal was infused into the stomach and patients were studied for 60 min in each lateral position. Following infusion of the meal, lower oesophageal sphincter (LOS) pressure fell and transient LOS relaxation (TLOSR) frequency increased. Acid reflux episodes were more common in the postprandial period (fasting 0 (0-6) h, first postprandial hour 1 (0-9) h, P = 0.0002, second postprandial hour 1 (0-22) h, P = 0.02) and occurred more than twice as often in the right lateral position (right 3 (0-22) h, left 0 (0-10) h, P = 0.01). However, TLOSRs, swallow-related relaxations and low basal LOS pressures were equally common in both lateral positions. In patients with reflux disease, postprandial reflux is twice as common in the right lateral position. This does not relate to differences in gastro-oesophageal junctional pressure, suggesting that other aspects of barrier function or differences in the intragastric distribution of chyme may be important.     

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.