Transient lower esophageal sphincter relaxation and the related esophageal motor activities

Transient lower esophageal sphincter (LES) relaxation (TLESR) is defined as LES relaxation without a swallow. TLESRs are observed in both of the normal individuals and the patients with gastroesophageal reflux disorder (GERD). However, TLESR is widely considered as the major mechanism of the GERD. The new equipments such as high resolution manometry and impedance pH study is helped to understand of TLESR and the related esophageal motor activities. The strong longitudinal muscle contraction was observed during development of TLESR. Most of TLESRs are terminated by TLESR related motor events such as primary peristalsis and secondary contractions. The majority of TLESRs are associated with gastroesophageal reflux. Upper esophageal sphincter (UES) contraction is mainly associated with liquid reflux during recumbent position and UES relaxation predominantly related with air reflux during upright position. The frequency of TLESR in GERD patients seems to be not different compared to normal individuals, but the refluxate of GERD patients tend to be more acidic during TLESR.     

The lower esophageal sphincter in gastroesophageal reflux in children.

Esophageal function was evaluated in 51 children less than 2 years of age with radiologic evidence of gastroesophageal reflux. Detection of an acid esophageal pH was a sensitive measure of gastroesophageal reflux. Lower esophageal sphincter pressures were greater in reflux patients with respiratory symptoms (18.0 +/- 1.4 mm Hg) than in reflux patients without respiratory symptoms (9.5 +/- 1.0 mm Hg). The intra-abdominal segment of the lower esophageal sphincter was shorter in patients with reflux than in controls (0.51 +/- 0.05 cm vs. 0.75 +/- 0.08 cm). It was also shorter in patients requiring surgical therapy (0.34 +/- 0.05 cm) than in those responding to medical therapy (0.63 +/- 0.07 cm).     

Lower esophageal sphincter pressure as an index of gastroesophageal acid reflux

The purpose of this study was to determine the relationship of lower esophageal sphincter (LES) pressure and the volume of acid placed into the stomach required to induce gastroesophageal reflux in man. LES pressure was recorded continuously and by station pull-through by three radially oriented catheters in both symptomatic and asymptomatic subjects during the graded infusions of 0.1 N HCl acid into the stomach. Sumptomatic subjects had a mean LES pressure of 7.5±0.7 mm Hg and refluxed at a volume of 140.0±21.0 ml. Fifty-five percent of asymptomatic subjects refluxed at a mean volume of 380.0±24.7 ml, and had a mean LES pressure of 13.8±0.4 mm Hg. Asymptomatic nonrefluxers at a volume of 500 ml of 0.1 HCL acid had a mean LES pressure of 18.9±1.1 mm Hg. The mean LES pressure and acid volumes showed statistical significance between the three groups (P<0.01). There was an excellent overall correlation between LES pressure and acid volume required to produce reflux in all subjects (r=0.91,P<0.001). Following reflux, asymptomatic but not symptomatic subjects showed a significant increase in LES pressure. These studies suggest that: (1) LES pressure does provide an accurate index of the gastroesophageal antireflux mechanism, provided that acid volume is considered; and (2) asymptomatic subjects showing acid reflux have higher LES pressures, reflux at higher volumes, and develop an LES contractile response after the reflux episode.This work was supported by a grant from the Smith Kline & French Laboratories, Philadelphia, Pennsylvania.     

Resting pressures in the lower esophageal sphincter

Interdeglutive pressures of the lower esophageal sphincter (LES) were studied by nonpullthrough techniques in 36 volunteers. Resting pressures did not remain at the high levels observed when the LES was entered. In 30 studies a gradual protracted decay ranging from 5 to 18 mm Hg was observed. These studies suggest that the LES may not pose a continuous barrier to reflux of gastric contents.     

Does lower esophageal sphincter incompetency contribute to esophageal bleeding?

The purpose of this study is to determine whether lower esophageal sphincter (LES) incompetency is a common occurrence in patients with liver cirrhosis and contributes to the development of variceal bleeding. Resting LES pressure (17.8 +/- 1.1 mm Hg) in 35 patients with cirrhosis was similar to that of our control population (17.3 +/- 2.0 mm Hg). No differences were found among patients with ascites, variceal hemorrhage, or with different degrees of hepatic decompensation. In both patients and control subjects the LES responded with a significant pressure increase to gastric alkalinization. Symptoms and radiological evidence of gastroesophageal reflux were extremely uncommon in patients with liver cirrhosis. Based on these data it is unlikely that acid-pepsin regurgitation is a significant factor in the development of variceal hemorrhage.     

Lower esophageal sphincter relaxation characteristics using a sleeve sensor in clinical manometry

Objective: We undertook this study to determine the characteristics of swallow-induced lower esophageal sphincter (LES) relaxation in the setting of clinical manometry using a standardized methodology.
Methods: We reviewed 170 manometric recordings performed using a perfused manometric assembly with a sleeve sensor and a computer polygraph. Patients were categorized as patient controls, gastroesophageal reflux disease (GERD), diffuse esophageal spasm (DES), or achalasia. Tracing were semiautomatically analyzed for basal LES pressure, LES pressure during deglutitive relaxation (relaxation LES pressure), duration of LES relaxation, timing of LES relaxation, and the success rate of primary peristalsis.
Results: Forty-six patient controls, 93 with GERD, five with DES, and 26 with achalasia were identified. GERD and achalasia patients had lower or higher basal LES pressures than patient controls, respectively. Compared with patient controls, achalasia patients had higher relaxation LES pressures, lower percent LES relaxation, and shorter durations of LES relaxation. The best single measure for distinguishing achalasia was the relaxation LES pressure; using the 95th percentile value of patient controls (12 mm Hg) as the upper limit of normal, its sensitivity and positive predictive value for the diagnosis of achalasia were 92% and 88%, respectively. Coupled with the finding of aperistalsis, a relaxation LES pressure ≥10 mm Hg achieved 100% sensitivity and positive predictive value among these patients.
Conclusion: Sleeve sensor recording is a practical method for clinical manometry that reliably records LES relaxation characteristics and is amenable to both a standardized manometry protocol and a semiautomated analysis routine. Relaxation LES pressure has a high diagnostic value for achalasia.     

Cholinergic stimulation of the lower esophageal sphincter in patients with vagotomy and antrectomy

Recently cholinergic stimulation of the lower esophageal sphincter (LES) with bethanechol has been shown to be effective in the treatment of chronic gastroesophageal reflux. Since chronic reflux and esophagitis also occur in patients with vagotomy and antrectomy, we studied the effect of bethanechol on sphincter pressure in 10 patients who had had vagotomy and antrectomy. Both subcutaneous (0.08 mg/kg) and oral (25 mg) administration of bethanechol caused significant increases in LES pressure in these patients. In addition, both subcutaneous and oral administration of bethanechol elevated hypotensive sphincter pressures to normal levels. Orally administered bethanechol produced a sustained increase in LES pressure throughout a 90-min study period. These studies suggest that cholinergic stimulation of the LES with bethanechol may be of therapeutic benefit in vagotomized and antrectomized patients with gastroesophageal reflux.     

Determinants of gastroesophageal junction incompetence: hiatal hernia, lower esophageal sphincter, or both?

OBJECTIVE: To examine the effects of hiatal hernia and lower esophageal sphincter (LES) pressure on the competence of the gastroesophageal junction under conditions of abrupt increases in intra-abdominal pressure. DESIGN: Acute experiments. SETTING: University-hospital-based gastroenterology practice. PARTICIPANTS: Sixteen asymptomatic volunteers and 34 patients with endoscopic findings suggestive of hiatal hernia. INTERVENTION: A series of eight provocative maneuvers entailing abrupt changes in intra-abdominal pressure. MEASUREMENTS: Five radiographic measurements relevant to the presence and extent of hiatal hernia were made from videotaped barium-swallow examinations. Lower esophageal sphincter pressure was measured immediately before each maneuver. The percentage of maneuvers that resulted in gastroesophageal reflux was calculated as the reflux score. A stepwise regression analysis was then used to model the relation between measured variables of the gastroesophageal junction (manometric and radiographic) with reflux score. RESULTS: Patients with hiatal hernia had substantially higher reflux scores and lower LES pressures than either patients without hernias or volunteers. In diminishing order of significance, the terms in the model of susceptibility to reflux were axial length of hernia measured between swallows; LES pressure; and an interaction term in which a progressive increase occurred in the risk for reflux associated with a hypotensive lower esophageal sphincter as hernia size increased. CONCLUSIONS: Gastroesophageal junction competence during abrupt increases in intra-abdominal pressure is compromised by both hiatal hernia and low LES pressure. These factors interact with each other to determine susceptibility to reflux.     

Relationship between straining, transient lower esophageal sphincter relaxation, and gastroesophageal reflux in children

OBJECTIVE: Physical straining such as deep inspiration or coughing may induce gastroesophageal reflux (GER) by overcoming feeble lower esophageal sphincter (LES) pressure. The role of straining as a provocant of GER has not been analyzed systematically in children. It was our aim to examine the contribution of straining to the occurrence of GER with particular attention to its relationship to transient LES relaxations, which are a major mechanism of the occurrence of GER in pediatric patients. METHODS: Concurrent esophageal manometry and pH monitoring was performed for 4 h postprandially in six children with esophagitis (age 9 months to 12 yr). Analysis was performed on isolated single strain episodes, defined as an increased intragastric pressure > 10 mm Hg. When a drop of esophageal pH < 4.0 was noted within 15 sec after any part of a strain, this strain was defined as related to the reflux episode. RESULTS: The median value of basal LES pressure was 10 mm Hg (range 1-18). In all, 134 analyzable strains and 87 analyzable reflux episodes were recorded. Isolated strains were associated with 20 reflux episodes (23%). Reflux was observed more frequently with strains that occurred during transient LES relaxations (12/40) than straining when the LES was contracted (8/94) (p < 0.01). Sustained strain (35%) and inspiratory strain (25%) were the major patterns of straining related to reflux. CONCLUSION: Straining provoked reflux infrequently and simultaneous occurrence of straining and transient LES relaxation was important in determining the occurrence of strain-related reflux in pediatric patients with reflux esophagitis.     

Upper esophageal sphincter function during belching

We studied the mechanism of belching with specific attention to the upper esophageal sphincter (UES) in 14 normal volunteers. Belching occurred by the following sequence of events: lower esophageal sphincter relaxation; gastroesophageal gas reflux, recorded manometrically as a gastroesophageal common cavity phenomenon; UES relaxation; esophagopharyngeal gas reflux; and restoration of intraesophageal pressure to baseline by a peristaltic contraction. Upper esophageal sphincter relaxations comparable to those associated with belches were induced by abrupt esophageal distention with air boluses. In contrast, fluid boluses injected into the midesophageal body either had no effect on UES pressure or increased UES pressure. Thus, the UES responded to esophageal body distention in two distinct ways: abrupt relaxation in response to air boluses and pressure augmentation in response to fluid boluses. Mucosal anesthesia did not alter the UES response to esophageal boluses of gas or liquid thereby making it unlikely that these substances are differentiated by a mucosal receptor. Rapid distention of the proximal esophagus with a cylindrical balloon (15 cm long) elicited UES relaxation. These findings suggest that the rapidity and spatial pattern of esophageal distention, rather than discrimination of the type of material causing the distention, determines whether or not UES relaxation occurs.     

The hypertensive lower esophageal sphincter

Controversy exists as to whether the hypertensive lower esophageal sphincter (HLES) represents a clinical motility disorder of the esophagus or is merely the right-sided expression of a normal distribution curve. In the present study we describe 16 patients with HLES, defined as a lower esophageal sphincter (LES) pressure of 40 mm Hg (mean +3sd of controls) with normal peristalsis. All of the patients suffered from chest pain and nine from dysphagia. Delayed bolus transit at the gastroesophageal junction was demonstrated in four patients by radiography. Manometric studies showed that during swallowing the LES residual pressures were significantly greater (9.2±5.0 mm Hg) than observed in normal controls (1.8±2.2 mmHg) (mean±1sd). However, the percent LES relaxation in patients did not differ significantly from controls. Clinical improvement was associated with pharmacological or mechanical reduction of resting LES pressure with an accompanying fall in the nadir pressure. These observations suggest that HLES may have clinical and pathophysiological significance and that evidence for the entity should be sought during manometric studies in the clinical laboratory.     

A test of gastroesophageal sphincter competence

Gastroesophageal manometrics, using continuously perfused polyvinyl tubes, and acid reflux (pH test) were studied prospectively in 13 patients with, and 14, without symptoms and/or signs of gastroesophageal reflux. Pressures were recorded simultaneously from stomach, gastroesophageal sphincter and distal esophagus at rest and during gradual abdominal compression to 80 mm Hg. Neither the mean resting pressures nor the mean increase in gastric or sphincter pressures, during abdominal compression, were significantly different (P>0.10). Sphincteric yield pressures did not separate the 2 groups. However, the mean esophageal pressure rise was significantly greater (P<0.001) in the symptomatic patients (34±4.5 vs 9.9±3.2 mm Hg). The mean pressure in the stomach, sphincter and esophagus became almost identical in the symptomatic patients—a common cavity occurred between stomach and esophagus. Two symptomatic patients had negative pH but positive common cavity tests. No asymptomatic patient had evidence of either reflux or a positive common cavity test.Supported by the Denver Veterans Administration Hospital Training Grant in Gastroenterology, TR 110, and by the National Institute of Health Training Grant in Gastroenterology, AM 5122.     

下食管括约肌运动和功能与胃食管反流病

目的　观察胃食管反流病 (GERD)患者与对照组餐前、餐后食管pH情况 ,下食管括约肌(LES )运动模式的变化以及酸反流事件与一过性下食管括约肌松弛 (TLESR )、低LES压力 (LESP)的关系。方法　两组受试者均接受连续性 4h食管压力测定 (分别为空腹和餐后 1、2、3h)和食管pH监测 (GERD组检测 4h ,对照组检测 2 4h)。结果　GERD组酸反流事件明显高于对照组 (P <0 0 5 )。两组间TLESR发生率差异无显著性 (P >0 0 5 ) ,但与空腹比较 ,两组餐后 1h和 2hTLESR发生率明显增多 ;GERD组伴有酸反流的TLESR明显高于对照组 (P <0 0 0 1)。 4 3% (2 9/ 6 8)的酸反流事件发生在TLESR期间。 31% (2 1/ 6 8)的酸反流事件出现于低LESP状态中。结论　GERD是多因素参与的病理过程。LES运动形式变化和功能不全是GERD的重要背景因素。     

Antireflux surgery for symptomatic gastroesophageal reflux

To determine the effects of Nissen fundoplication upon the symptoms of reflux and the diagnostic tests employed to evaluate reflux and to examine the relationship between gastroesophageal reflux and lower esophageal sphincter pressure before and after fundoplication, 10 patients with symptomatic reflux were studied before and after operation. Clinical evaluation, barium esophagography, endoscopy with mucosal biopsy, esophageal manometry, acid-perfusion and acid-reflux testing, and gastroesophageal scintiscanning were performed on each patient before and after surgery. Following fundoplication, marked symptomatic, radiographic, endoscopic, and histologic improvement was observed. Serial acid-reflux tests at increasing gastroesophageal pressure gradients returned to normal after surgery. Lower-esophageal-sphincter (LES) pressure increased from 8.2±1.3 to 12.0±1.5 mm Hg (P<0.01). In addition, surgery resulted in a significant decrease in the gastroesophageal reflux index from 17.4±2.4 to 2.7±1.1% (P<0.001). Surprisingly, the pre- and postoperative resting LES pressures did not correlate significantly with corresponding gastroesophageal reflux indices for individual patients. We conclude that increased LES pressure alone does not explain adequately the functional and clinical improvement which follows fundoplication.     

Experimental gastroesophageal reflux in the Australian brush-tailed possum.

It has been suggested that the lower esophageal sphincter (LES) plays an important role in preventing gastroesophageal reflux. This study was designed to determine if abolition of the LES alone is sufficient to induce gastroesophageal reflux and esophagitis. Studies were performed in the Australian brush-tailed possum (Trichosurus vulpecula) which has a lower esophagus resembling that of man. Esophageal manometry, esophagoscopy, and contrast radiography of the lower esophagus and stomach were performed before and after surgery in a group of animals undergoing cardioplasty and in a group of sham operated control animals. In the animals undergoing cardioplasty, LES pressure fell from a preoperative level of 12.6 +/- 1.3 mm Hg to 0 mm Hg. This was followed by the development of gastroesophageal reflux and esophagitis. Sham operation did not alter LES pressure or result in either gastroesophageal reflux or esophagitis. In 4 of 5 animals undergoing cardioplasty, LES activity returned after 10 weeks, and this time gastroesophageal reflux ceased and esophagitis healed. It is concluded that abolition of the LES alone can induce gastroesophageal reflux and esophagitis.     

Manometric characteristics of the upper esophageal sphincter recorded with a microsleeve

OBJECTIVES: We compared manometric recordings of the upper esophageal sphincter (UES) recorded with a miniature sleeve to those obtained using standard manometry. METHODS: The UES pressure of eight volunteer subjects was measured by station pull-through (SPT), by rapid pull-through (RPT), and with a microsleeve sensor for 30 min, followed by 15 min of esophageal acid infusion. Deglutitive UES relaxation recorded with a microsleeve and solid state sensor were compared. RESULTS: The UES pressure recorded with the microsleeve (25+/-9 mm Hg) was significantly less than that by SPT (114+/-18 mm Hg) or RPT (152+/-19 mm Hg), and was unaffected by acid infusion. Periods of low UES pressure were observed during long interswallow intervals (11+/-4, range 6-18 mm Hg). Deglutitive relaxation duration and intrabolus pressure measured with the microsleeve were less than those recorded by the solid state transducer. CONCLUSIONS: "Normal" UES pressure is heavily dependent on measurement technique; pressures obtained with a miniature sleeve are a fraction of those obtained by SPT or RPT. During periods of relative comfort with minimal swallowing, UES tone is approximately 10 mm Hg, similar to that during sleep. Volume modulation of deglutitive UES relaxation is demonstrable with a microsleeve, albeit with less precision than with a solid-state transducer.     

Clinical and manometric findings in benign peptic strictures of the esophagus

To determine the possible factors that may contribute to the development of peptic stricture of the esophagus, clinical and manometric features were compared in patients with symptomatic gastroesophageal reflux and those with peptic strictures of the esophagus. Patients with stricture were older and had a longer duration of heartburn than patients without a stricture. Most importantly, patients with stricture had a more marked decrease in lower esophageal sphincter (LES) pressure, 4.9±0.5 mm Hg, than patients without a stricture, 7.5±0.6 mm Hg, P<0.01. The LES pressure in all patients with stricture was below 8 mm Hg, and did not overlap with normal values. Patients with stricture had either a nonspecific motor abnormality or aperistalsis (64%), compared to patients with symptomatic reflux (32%), P<0.05. Thus, peptic stricture of the esophagus is commonly associated with a long duration of reflux symptoms in patients with a very low LES pressure and esophageal motor disorder.     

Esophagogastric junction opening during relaxation distinguishes nonhernia reflux patients, hernia patients, and normal subjects

BACKGROUND AND AIMS: Flow across the esophagogastric junction (EGJ) is strongly related to opening dimensions. This study aimed to determine whether opening of the relaxed EGJ was altered in patients with gastroesophageal reflux disease (GERD). METHODS: Seven normal subjects (NL), 9 GERD patients without hiatus hernia (NHH), and 7 with hiatus hernia (HH) were studied. Cross-sectional area (CSA) of the relaxed EGJ was measured during low-pressure distention using a modified barostat technique that resulted in filling a compliant bag straddling the EGJ with renograffin to the set pressure. Swallows were imaged fluoroscopically at distensive pressures of 2-12 mm Hg. The diameter of the narrowest point of the EGJ in PA and lateral projections was measured from digitized images. CSA was determined as a function of intrabag pressure. RESULTS: The minimal EGJ opening aperture occurred at the diaphragmatic hiatus in all subjects. At pressures 0 mm Hg, there were significant increases in EGJ CSA both for HH and NHH compared with NL (P < 0.001) and for HH compared with NHH (P < 0.005). This difference may explain the diminished air/water discrimination seen during transient lower esophageal sphincter (LES) relaxation-associated reflux in GERD patients. CONCLUSIONS: Anatomic degradation of the EGJ distinguishes GERD patients from normal subjects, and these changes may impact on both the observed mechanisms of reflux and the constituents of reflux during transient LES relaxation. Therapy focused on EGJ compliance may benefit GERD patients.     

Is abdominal compression a useful stimulation test for analysis of lower esophageal sphincter function?

The change in pressure of competent and incompetent lower esophageal sphincter (LES) due to abdominal compression is still a controversial subject. Therefore, we studied the effect of sustained (SAC) and intermittent (IAC) abdominal compression on lower esophageal sphincter pressure (LESP) in normals (N), patients with hiatus hernia (HH), and patients with scleroderma (S). When resting lower esophageal sphincter pressure exceeded 15 mm Hg, response to SAC and IAC was similar in patients with HH and in normals. On the other hand when basal LESP was below 15 mm Hg, stimulated sphincter pressure during IAC was significantly lower than during SAC. Values recorded during SAC were also falsely high in patients with scleroderma. Values obtained during either SAC or IAC did not depend on presence or absence of reflux symptoms in any group. LES stimulation with IAC gives valid results which correlate closely with LESP. Stress tests with IAC therefore seem to be a useful stimulation test for the analysis of LES function.     

Lower esophageal sphincter pressure in normal individuals and patients with gastroesophageal reflux. A comparison between end-hole and side-hole recording techniques

The advantage of a single-lumen end-hole catheter compared with the usual composite side-hole catheter for lower esophageal sphincter (LES) manometry has been studied in vitro and in vivo. In the present study LES pull-through manometry was performed with a special catheter, enabling simultaneous end-hole and side-hole recording of LES pressure. Eighteen normal individuals with normal 24-h pH-monitoring (control group) and 42 reflux patients with pathologic 24-h pH-monitoring (reflux group) were studied. End-hole recorded resting sphincter pressure (RSP) in the control group was 15.4 +/- 5.0 cm H2O and in the reflux group 6.4 +/- 6.4 (p less than 0.0005). Side-hole recorded RSP (mean S1-S3) was 20.8 +/- 11.6 and 11.9 +/- 6.8, respectively (p less than 0.005). End-hole recorded total sphincter length (SL) in the control group was 34 +/- 9 mm and in the reflux group 27 +/- 12 (p less than 0.025) and abdominal sphincter length (ASL) 23 +/- 7 and 16 +/- 9, respectively (p less than 0.005). Side-hole recorded SL was 30 +/- 7 and 30 +/- 12, respectively (NS) and ASL 22 +/- 6 and 18 +/- 9 respectively (NS). After intake of 500 ml of water both LES pressure and length decreased in both groups but the separation between the groups was neither improved nor impaired. The results support the view that LES insufficiency is an important cause of gastroesophageal reflux. That LES had a lower pressure and was shorter in patients with reflux was best demonstrated by end-hole recorded pressure.