Increase In Lower Esophageal Sphincter Pressure Research Articles

Oestrogen and Gastroesophageal Reflux Disease Dynamics in Premenopausal and Postmenopausal Women: A Cross-sectional Study

Introduction: Gastroesophageal Reflux Disease (GERD) is a common clinical disorder characterised by the reflux of stomach contents into the oesophagus, primarily due to the temporary relaxation of the Lower Oesophageal Sphincter (LES). The aetiology of GERD is multifactorial. The prevalence of GERD in females has been found to sharply increase throughout the postmenopausal period compared to the reproductive phase. Aim: To study the relationship between serum oestrogen levels in premenopausal and postmenopausal women with GERD. Materials and Methods: In this cross-sectional study, 60 patients with GERD were divided into 30 premenopausal and 30 postmenopausal groups. The study subjects underwent high-resolution oesophageal manometry. The Cobas e 411 immunoassay analyser was utilised to measure serum oestrogen levels through electrochemiluminescence. The independent, unpaired Student's t-test was employed to analyse the collected data. Results: The statistical analysis revealed that the mean reduced LES pressure of 9.76±3.80 mmHg and the mean reduced Oesophagogastric Junction Contractile Integral (EGJ-Cl) of 14.503±10.64 mmHg were lower in women with postmenopausal GERD who exhibited lower oestrogen levels compared to those with premenopausal GERD. An increase in LES pressure was also associated with an increase in EGJ-CI, demonstrating a statistically significant positive linear correlation between LES pressure and EGJ-CI. The p-value <0.05 was deemed highly statistically significant. Conclusion: Parameters such as basal LES pressure and EGJCl were observed to be reduced in postmenopausal women with GERD who had low oestrogen levels. This study suggests that oestrogen plays a crucial role in safeguarding the oesophageal epithelium against the reflux of gastric contents.

Manual Cervical Traction and Trunk Stabilization Cause Significant Changes in Upper and Lower Esophageal Sphincter: A Randomized Trial

ObjectivesDysfunctions in the lower esophageal sphincter (LES) and the upper esophageal sphincter (UES) levels can occur owing to poor muscle coordination, contraction, or relaxation. Such condition can possibly be addressed by functional rehabilitation. The aim of this study was to measure pressure changes in the UES and LES at rest and during routine rehabilitation techniques, that is, cervical manual traction and trunk stabilization maneuver. MethodsThis study was conducted in a University Hospital Gastrointestinal Endoscopy Center. Cervical manual traction and a trunk stabilization maneuver were performed in a convenient group of 54 adult patients with gastroesophageal reflux disease. High-resolution manometry was used to measure pressure changes in the LES and UES at rest and during manual cervical traction and trunk stabilization maneuver. ResultsAverage initial resting UES pressure was 90.91 mmHg. A significant decrease was identified during both cervical traction (average UES pressure = 42.13 mmHg, P < .001) and trunk stabilization maneuver (average UES pressure = 62.74 mmHg, P = .002). The average initial resting LES pressure was 14.31 mmHg. A significant increase in LES pressure was identified both during cervical traction (average LES pressure = 21.39 mmHg, P < .001) and during the trunk stabilization maneuver, (average pressure = 24.09 mmHg, P < .001). ConclusionCervical traction and trunk stabilization maneuvers can be used to decrease pressure in the UES and increase LES pressure in patients with gastroesophageal reflux disease.

Electrical stimulation therapy of the lower esophageal sphincter in GERD patients—a prospective single-center study

Summary Background Electrical stimulation therapy (EST) of the lower esophageal sphincter (LES) for gastro esophageal reflux disease (GERD) treatment increases LES pressure through chronic stimulation, with a low risk for gastrointestinal side effects and preservation of hiatal anatomy. The aim of this study was to evaluate the efficacy and safety of this novel technique in a high-output specialized reflux center. Methods This is a prospective single-center study including GERD patients indicated for anti-reflux therapy who consented to undergo LES-EST. Patients underwent prospective scheduled follow-up visits including interrogation of the stimulation device, clinical examination, and assessment of health-related quality of life (HRQL). Results Within a 4-year period, 37 LES-EST implantations were performed. The majority of patients were male (54.1%), mean BMI was 25.8 (SD 4.4), and mean age was 54.0 (SD 15.8). The median GERD HRQL composite score was 41 (IQR 21–49). Median total % of pH &lt;4 was 10.1 (IQR 4.4–17.3). Six (16.2%) individuals underwent explantation of the entire system (IPG and leads) due to technical defect (n = 4) or failure of therapy (n = 2). HRQL score improved from 41 (IQR 21–49) to 8.50 (IQR 4.25–20.5, p &lt; 0.001) and 9 (23.7%) patients were on at least occasional PPI treatment. Conclusion Due to the low rate of GI side effects and its minimal invasive character preserving the hiatal anatomy, this novel technique might find its place in anti-reflux surgery. However, the considerably high rate of device dysfunction needs further investigation.

Analysis of the efficacy of laparoscopic Toupet fundoplication treatment of hiatal hernia combined with gastroesophageal reflux disease

Objective To explore the efficacy of laparoscopic Toupet fundoplication treatment of hiatal hernia combined with gastroesophageal reflux disease. Methods Forty one patients' medical record information of hiatal hernia combined with gastroesophageal reflux disease that underwent laparoscopic Toupet fundoplication were collected in Xinjiang Uygur Autonomous Region People's Hospital from October 2012 to October 2015. Thirty six cases were adopted pure hiatal hernia suture, 2 cases were used biological patch repair, 1 case used Johnson PHY patch repair, 1 case used Bade patch repair, and 1 case used Tyco hiatal hernia dedicated anti-blocking patch repair. These patients were carried out 24 hours esophageal pH monitoring, esophageal manometry, gastroesophageal reflux disease questionnaire (GERDQ) score and postoperative complications before surgery and 6 months postoperative. The clinical efficacy of laparoscopic Floppy Nissen fundoplication treatment of hiatal hernia combined with gastroesophageal reflux disease was retrospectively analyzed. Results There was no perioperative deaths and serious complications during perioperation. The reflux symptoms were significantly improved postoperative. There was significantly lower in reflux time , the number of reflux (29.83±19.71), acid reflux time percentage , and DeMeester score (7.28±7.38) than the preoperative . GERD Q scale score (7.18±1.33) was significantly lower than preoperative (10.91±2.02) with statistically significant difference (P<0.05). lower esophagealsphincter (LES) pressure was significantly increased than preoperative . Residual pressure was significantly increased than preoperative . Relaxation rate was significantly reduced than preoperative . However, swallowing invalid was increased than preoperative , with statistically significant difference (P<0.05). The median follow-up was 10 months, and there was no recurrence during follow-up. Conclusions Laparoscopic Toupet fundoplication can effectively inhibit reflux symptoms, and increase LES pressure, which is worthy of promotion. However, there is slightly higher incidence of postoperative dysphagia. Key words: Laparoscopy; Fundoplication; Hernia, hiatal/CO/SU; Gastroesophageal reflux/CO/SU

Mechanism of bombesin-induced tonic contraction of the porcine lower esophageal sphincter.

Gastroesophageal reflux disease (GERD) is a disorder that is related to an incompetent lower esophageal sphincter (LES). Previous studies showed that bombesin could increase LES pressure in humans and opossums. The aim of the present study was to characterize the effects of bombesin on porcine LES contraction. We used the selective agonists, neuromedin B (NMB), gastrin-releasing peptide (GRP), and [D-Tyr6,Apa-4Cl11,Phe13,Nle14]bombesin-(6-14) (DTACPN-BN), as well as receptor antagonists of bombesin receptor subtype 2 (BB2), and 3 (BB3) for ex vivo contraction studies. Atropine, nifedipine, tetrodotoxin, and ω-conotoxin GVIA were used to explore the agonist-induced LES contraction mechanism. Reverse transcription polymerase chain reaction and immunohistochemistry were applied to detect bombesin receptor expression. Our results indicate that GRP and DTACPN-BN, but not NMB, induced tonic contractions of the porcine LES in a dose-dependent manner, and the contractions were inhibited with selective BB2 and BB3 antagonists. The GRP-induced contraction is mainly caused by L-type Ca2+ channel-mediated Ca2+ influx. However, DTACPN-BN-induced contractions are associated with neuronal conduction. RT-PCR and immunohistochemistry revealed that BB2 and BB3 were expressed in the porcine LES. Bombesin-induced tonic contraction of the LES is mediated through BB2 and BB3. Bombesin, BB2, and BB3 agonists might have the potential to treat GERD.

Murine genetic deficiency of neuronal nitric oxide synthase (nNOS‐/‐) and interstitial cells of Cajal (W/Wv): Implications for achalasia?

Nitric oxide (NO) is an important inhibitory mediator of esophageal function, and its lack leads to typical features of achalasia. In contrast, the role of intramuscular interstitial cells of Cajal (ICC-IM) and vasoactive intestinal peptide (VIP) in lower esophageal sphincter (LES) function is still controversial. Therefore, we examined the function and morphology of the LES in vivo in NO-deficient (nNOS(-/-) ), ICC-IM-deficient (W/W(v) )-, and wild-type (WT) mice. Esophageal manometry was performed with a micro-sized transducer catheter to quantify LES pressure, swallow evoked LES relaxation, and esophageal body motility. The LES morphology was examined by semiquantitative analysis of the immunoreactivity (reduction grade I-IV) of neuronal NOS (nNOS), ICC-IM, and VIP and their correlation with esophageal function. nNOS(-/-) in comparison to WT mice showed a significantly higher LES mean resting pressure with an impaired swallow induced relaxation, whereas W/W(v) mice had a hypotensive LES with decreased relaxation. W/W(v) and nNOS(-/-) mice demonstrated differing degrees of tubular esophageal dysfunction. The reduced immunoreactivity of nNOS correlated with an increased LES pressure and decreased LES relaxation, respectively. Cajal-cell reduction correlated with impaired LES relaxation, whereas VIP reduction revealed no correlation with esophageal function. The reduction of ICC-IM and nNOS can cause dysfunction of the LES and esophageal peristalsis, whereas VIP reduction seems to have no effect. ICC-IM and nNOS deficiency might be independent relevant causes of esophageal dysfunction similar to that seen in human achalasia.

Lower esophageal sphincter augmentation by endoscopic injection of dextranomer hyaluronic acid copolymer in a porcine gastroesophageal reflux disease model

BackgroundWe previously demonstrated feasibility, safety, and a reproducible histologic bulking effect after injection of dextranomer hyaluronic acid copolymer (DxHA) into the gastroesophageal junction of rabbits. In the current study, we investigated the potential for DxHA to augment the lower esophageal sphincter (LES) in a porcine model of gastroesophageal reflux disease (GERD). MethodsTwelve Yucatan miniature pigs underwent LES manometry and 24-hour ambulatory pH monitoring at baseline, after cardiomyectomy, and 6weeks after randomization to endoscopic injection of either DxHA or saline at the LES. After necropsy, the foregut, including injection sites, was histologically examined. ResultsPigs in both groups had similar weight progression. Cardiomyectomy induced GERD in all animals, as measured by a rise in the median % of time pH <5 from 0.6 to 11.6 (p=0.02). Endoscopic injection of DxHA resulted in a higher median difference in LES length (1.8cm vs. 0.4cm, p=0.03). In comparison with saline injection, DxHA resulted in 120% increase in LES pressure, and 76% decrease in the mean duration of reflux episodes, but these results were not statistically significant. Injection of DxHA induced a foreign body reaction with fibroblasts and giant cells. ConclusionsPorcine cardiomyectomy is a reproducible animal GERD model. Injection of DxHA may augment the LES, offering a potential therapeutic effect in GERD.

High-resolution manometric evaluation of the effects of cisapride and metoclopramide hydrochloride administered orally on lower esophageal sphincter pressure in awake dogs

To evaluate the effects of cisapride and metoclopramide hydrochloride administered orally on the lower esophageal sphincter (LES) resting pressure in awake healthy dogs. 6 adult Beagles. Each dog was evaluated after administration of a single dose of cisapride (0.5 mg/kg), metoclopramide (0.5 mg/kg), or placebo (empty gelatin-free capsule) in 3 experiments performed at 3-week intervals. To measure LES pressure, a high-resolution manometry catheter equipped with 40 pressure sensors spaced 10 mm apart was used. For each experiment, LES pressure was recorded during a 20-minute period with a virtual electronic sleeve emulation before treatment (baseline) and at 1, 4, and 7 hours after drug or placebo administration. A linear mixed-effects model was used to test whether the 3 treatments affected LES pressure differently. In the cisapride, metoclopramide, and placebo experiments, median baseline LES pressures were 29.1, 30.5, and 29.0 mm Hg, respectively. For the cisapride, metoclopramide, and placebo treatments, median LES pressures at 1 hour after administration were 44.4, 37.8, and 36.6 mm Hg, respectively; median LES pressures at 4 hours after administration were 50.7, 30.6, and 31.1 mm Hg, respectively; and median LES pressures at 7 hours after administration were 44.3, 28.5, and 33.3 mm Hg, respectively. The LES pressures differed significantly only between the placebo and cisapride treatments. Results suggested that orally administered cisapride may be of benefit in canine patients for which an increase in LES pressure is desirable, whereas orally administered metoclopramide did not affect LES resting pressures in dogs.

Effect of electrical stimulation of the lower esophageal sphincter using endoscopically implanted temporary stimulation leads in patients with reflux disease

Electrical stimulation therapy (EST) has been shown to increase lower esophageal sphincter (LES) pressure in animals; however, data on the effect of EST on LES pressure in patients with gastroesophageal reflux disease (GERD) are lacking. The aim of our study was to investigate the effect of EST on LES pressure and esophageal function in patients with GERD. Patients with a diagnosis of GERD responsive to proton pump inhibitors (PPIs), increased esophageal acid on 24-h pH monitoring off GERD medications, basal LES pressure >5 mmHg, hernia <2 cm and esophagitis <LA grade B were included. A temporary pacemaker lead was placed endoscopically in the LES by creating a 3 cm submucosal tunnel, secured to the esophagus using endoscopic clips along the body of the lead and exteriorized nasally. EST was delivered 6-12 h post-implant per protocol using (i) short-pulse 200 μs, 20 Hz, and (ii) intermediate-pulse 3 ms, 20 Hz, each for 20 min at varying amplitudes. High-resolution manometry was performed pre-, during and post-EST. Symptoms of heartburn, chest or abdominal pain and dysphagia pre-, during and post-stimulation and 7 days post-procedure were recorded. Continuous cardiac monitoring was performed during and after the EST to evaluate any effect of EST on cardiac rhythm. Six male patients (mean age 34.6 years) underwent successful endoscopic lead implantation; the first patient had premature lead dislodgement and did not undergo EST. The remaining five patients underwent successful EST. All patients had a significant increase in LES pressure with all sessions of EST. There was no effect on swallow-induced LES relaxation, And there were no EST-related adverse symptoms or any cardiac rhythm abnormalities. In patients with GERD, short-term EST delivered using electrodes endoscopically implanted in the LES results in a significant increase in LES pressure without affecting patients' swallow function or causing any adverse symptoms or cardiac rhythm disturbances. EST may offer a novel therapy to patients with GERD.

Long-term results of electrical stimulation of the lower esophageal sphincter for the treatment of gastroesophageal reflux disease

In patients with gastroesophageal reflux disease (GERD), temporary electrical stimulation of the lower esophageal sphincter (LES) increases LES pressure without interference with LES relaxation. The aim of the current study was to investigate the safety and efficacy of long term LES electrical stimulation therapy (LES-EST), using a permanently implanted stimulator for the treatment of GERD. Patients with GERD who were at least partially responsive to proton pump inhibitors (PPIs) and who had hiatal hernia of ≤ 3 cm and esophagitis of Los Angeles Grade A, B, or C were included in the study. Stimulation electrodes were placed in the LES and a pulse generator (EndoStim LES Stimulation System; EndoStim BV, The Hague, The Netherlands) was implanted laparoscopically. LES stimulation was delivered at 20 Hz, 215 μs, 3 - 8 mA in multiple 30-minute sessions. Patients were evaluated at follow-up using the GERD Health-Related Quality of Life (HRQL) questionnaire, daily symptom and medication diaries, the SF-12 Health Survey, esophageal pH testing, and high resolution manometry. A total of 24 patients (mean age 53 ± 12 years; 14 men) were implanted and 23 completed the 12-month evaluation. No serious implantation or stimulation-related adverse affects or sensations were reported. Median composite GERD-HRQL score at 12 months was 2.0 (interquartile range [IQR] 0 - 3.0), which was significantly better than baseline scores both on PPI therapy (median 9.0, IQR 6.0 - 10.0; P = 0.002) and off PPIs (median 23.5, IQR 21 - 25.75; P < 0.001). The median percentage of the 24-hour period with esophageal pH < 4.0 at baseline was 10.1 % (IQR 7.7 - 15.5), which was reduced to 3.3 % (1.8 - 6.9) at 12 months (P < 0.001), with 69 % of patients showing either normalization or > 50 % improvement in their distal esophageal pH. At 12 months, 96 % of patients (22/23) were completely off PPI medication. During the long term follow-up of 12 months, LES - EST was safe and effective for the treatment of GERD. There was a significant and sustained improvement in GERD symptoms, reduction in esophageal acid exposure with elimination of daily PPI usage, and no stimulation-related adverse effects.

Helicobacter pylori Infection Has No Impact on Manometric And pH-Metric Findings in Adolescents and Young Adults with Gastroesophageal Reflux and Antral Gastritis: Eradication Results to no Significant Clinical Improvement

The relationship between Helicobacter pylori (Hp) gastritis and gastroesophageal reflux disease (GERD) remains controversial. The aim was to investigate the association between Hp infection and gastroesophageal reflux (GER) and the impact of Hp eradication on esophageal acid exposure and motility in adolescents and young adults with Hp gastritis and GERD. Sixty-four patients with symptoms suggestive for GERD, of which 40 Hp-positive (group A) and 24 Hp-negative (group B), underwent endoscopy-biopsy, esophageal manometry and 24-hour pH-metry. All group A patients received eradication treatment and were re-evaluated six months later again with 24-hour pH-metry, esophageal manometry, endoscopy-biopsy and clinical assessment.At inclusion, there were no significant differences between the two groups regarding sex, age, grade of endoscopic esophagitis, manometric and pH-metry findings. All Hp-positive patients had an antral predominant gastritis. Eradication of Hp was successful in all patients, and gastritis and esophagitis were healed in all patients. The mean lower esophageal sphincter pressure (LESP) increased significantly from 11.25 mmHg before to 11.71 mmHg after eradication (P<0.05). A significant decrease in reflux index was observed (mean RI 6.02% before versus 4.96% after eradication (P<0.05). However clinical symptoms of GER improved not significantly after 6 months follow up. Conclusively, in children and young adults with GER symptoms and GERD, the presence or absence of Hp has no impact on manometric and pH-metric findings. Eradication of Hp infection results in increase in LESP with a consequent decrease in esophageal acid exposure but not significant clinical improvement.

Helicobacter pylori infection has no impact on manometric and pH-metric findings in adolescents and young adults with gastroesophageal reflux and antral gastritis: eradication results to no significant clinical improvement

The relationship between Helicobacter pylori (Hp) gastritis and gastroesophageal reflux disease (GERD) remains controversial. The aim was to investigate the association between Hp infection and gastroesophageal reflux (GER) and the impact of Hp eradication on esophageal acid exposure and motility in adolescents and young adults with Hp gastritis and GERD. Sixty-four patients with symptoms suggestive for GERD, of which 40 Hp-positive (group A) and 24 Hp-negative (group B), underwent endoscopy-biopsy, esophageal manometry and 24-hour pH-metry. All group A patients received eradication treatment and were re-evaluated six months later again with 24-hour pH-metry, esophageal manometry, endoscopy-biopsy and clinical assessment. At inclusion, there were no significant differences between the two groups regarding sex, age, grade of endoscopic esophagitis, manometric and pH-metry findings. All Hp-positive patients had an antral predominant gastritis. Eradication of Hp was successful in all patients, and gastritis and esophagitis were healed in all patients. The mean lower esophageal sphincter pressure (LESP) increased significantly from 11.25 mmHg before to 11.71 mmHg after eradication (P&lt;0.05). A significant decrease in reflux index was observed (mean RI 6.02% before versus 4.96% after eradication (P&lt;0.05). However clinical symptoms of GER improved not significantly after 6 months follow up. Conclusively, in children and young adults with GER symptoms and GERD, the presence or absence of Hp has no impact on manometric and pH-metric findings. Eradication of Hp infection results in increase in LESP with a consequent decrease in esophageal acid exposure but not significant clinical improvement.

Respiratory physiotherapy can increase lower esophageal sphincter pressure in GERD patients

Inspiratory muscle training (IMT) has been shown to increase diaphragm thickness. We evaluated the effect of IMT on mid-respiratory pressure (MRP) in patients with gastroesophageal reflux disease (GERD) and hypotensive lower esophageal sphincter (LES), and compared the results with a sham group. Twenty consecutive patients (progressive loading group) and 9 controls (sham group) were included. All patients had end expiratory pressure (EEP) between 5 and 10mmHg, underwent esophageal manometry and pulmonary function tests before and after 8weeks of training, and used a threshold IMT twice daily. The threshold IMT was set at 30% of the maximal inspiratory pressure for the progressive loading group; while, the threshold for sham-treated patients was set at 7cmH(2)O for the whole period. There was an increase in MRP in 15 (75%) patients in the progressive loading group, with an average gain of 46.6% (p<0.01), and in six (66%) patients in the sham group with a mean increase of 26.2% (p<0.01). However, there was no significant difference between the groups (p=0.507). The EEP also increased compared with measurements before training (p<0.01), but it did not differ between groups (p=0.727). IMT increased LES pressure in patients with GERD, in both the treatment and sham groups, after an eight-week program. Although there was no statistically significant difference between groups, suggesting the pressure increase in LES occurs regardless of the resistance load of the threshold IMT. These findings need to be confirmed in further studies with a larger sample. 0922/09.

Inspiratory Muscle Training Can Increase Lower Esophageal Sphincter Pressure in GERD Patients – A Sham Controlled Trial

Inspiratory Muscle Training Can Increase Lower Esophageal Sphincter Pressure in GERD Patients – A Sham Controlled Trial

Effects of propofol on oesophageal sphincters: a study on young and elderly volunteers using high-resolution solid-state manometry

The oesophageal sphincters play an important role in protecting the airway. During manometric studies, administration of an anxiolytic agent is often required to make insertion of the catheter acceptable for the patient. The anxiolytic should not affect the results of the measurements. This study evaluates the effects of two different doses of propofol on the pressures in the oesophageal sphincters. The effect of increased abdominal pressure was also studied. Twenty healthy volunteers, 10 young (mean age 25 years) and 10 elderly (mean age 71 years), were recruited. The effects of a low dose of propofol [0.3 mg kg(-1) intravenously (i.v.)] and a high dose of propofol (young group 0.9 mg kg(-1) i.v. and elderly group 0.6 mg kg(-1) i.v.) were studied with and without external abdominal pressure. There were no statistically significant changes in lower oesophageal sphincter (LOS) pressure after the low dose of propofol. After the high dose, there was an increase in LOS pressure, which was statistically significant in the young group (P < 0.05). The upper oesophageal sphincter (UOS) pressure decreased after both doses of propofol (P < 0.01 for the higher dose and P < 0.05 for the lower dose). A low dose of propofol (0.3 mg kg(-1) i.v.) leaves the LOS unaffected in young and elderly volunteers and can be used safely as an anxiolytic agent during studies of the LOS without influencing the results. However, the UOS is more sensitive to the effects of propofol and we do not recommend the use of propofol as an anxiolytic agent during manometric studies of the UOS.

Electrical Stimulation Therapy (EST) Significantly and Consistently Increases Lower Esophageal Sphincter (LES) Pressure in GERD Patients

Purpose: EST can increase LES pressures (LESP) in animals. To study the safety and effect of EST on LESP and esophageal function in GERD patients. Methods: Thirteen patients with GERD responsive to PPI, increased esophageal acid exposure off medications, basal LESP >5 mmHg, hiatal hernia <2 cm and esophagitis < LA Grade C were included in the study. Endoscopic (Endo) group (n=6; all men)-Temporary pacer lead (Medtronic 6416, 200 cm) were placed in the LES. The lead was secured to the esophagus with endoclips and exteriorized nasally. Laparoscopic (Lap) group (n=7; 1M, 6F) - Bipolar stitch lead (CCC, Uruguay) were placed in the LES during an elective lap cholecystectomy, and exteriorized through the abdominal wall. EST delivered various stimulation algorithms (Pulse width =250 μsec, 3 msec and 300 msec; pulse amplitude=5 to 15mAmp and pulse frequency=5 cps and 20 Hz) per protocol. EST was delivered in 20 minute sessions followed by a 20 minute washout or till LESP returned to baseline, whichever was longer. Manometery was performed pre-, end- and post-EST. Symptoms of heartburn, chest pain, abdominal pain and dysphagia pre-, during and post-EST and 7-days post-EST were recorded. Continuous cardiac monitoring was performed during and post-EST. LESP data pre-, end- and post-EST were compared using a t-test (paired, 2-tailed). Results: Endo Group -5 patients completed the EST study 6-12 h post-implant (the first patient had a premature lead dislodgement). EST, using various algorithms, resulted in a significant and sustained increase in LESP in all patients (5/5), from 11.4+/-4.9 mm Hg at baseline to 37.1+/-17.2 mm Hg at end EST (p<0.05) and 20.1+/-11.6 mm Hg during post-EST period (p<0.01). Lap Group -All (7/7) patients received per-protocol EST 24h post lead implant and had a significant and sustained increase in LESP. Optimal EST parameters resulted in an increase in mean LESP from 10.7+/-2.1 mm Hg pre-EST to 18.4+/-2.2 mm Hg at end-EST (p<0.01) and 24.0+/-2.6 mm Hg during post-EST period (p<0.001). Swallow induced LES relaxation was not affected, esophageal body pressures were improved, and post-swallow LES pressure was enhanced with EST in all patients and in both groups. In the Lap group, 2 patients had an abnormal sensation with EST at amplitudes of 13-15 mAmp which resolved at amplitudes < 13mAmp. There were no adverse events or any cardiac rhythm abnormalities with EST in either group. Conclusion: In GERD patients, EST results in a significant, consistent and sustained increase in LES pressure without effecting patients' swallow function or causing any adverse symptoms or cardiac rhythm disturbances. EST may offer a novel therapy to patients with GERD. Disclosure: Dr Virender K Sharma - Consultant, Equity Interest - EndoStim Inc. Dr Edy Soffer - Consultant, Equity Interest - EndoStim Inc. This research was supported by an industry grant from EndoStim, Inc.

Effects of Lesogaberan on Reflux and Lower Esophageal Sphincter Function in Patients With Gastroesophageal Reflux Disease

Transient lower esophageal sphincter relaxations (TLESRs) are a major mechanism behind reflux. This study assessed the effects of lesogaberan (AZD3355), a novel gamma-aminobutyric acid type B receptor agonist, on reflux and lower esophageal sphincter (LES) function when used as add-on treatment in patients with reflux symptoms despite proton pump inhibitor (PPI) treatment. In this randomized, double-blind, placebo-controlled, crossover study, patients received lesogaberan (65 mg) or placebo twice on day 1 (morning/evening) and once on day 2 (morning), in addition to existing PPI treatment. Patients consumed a standardized meal 45-60 minutes after morning doses. Ambulatory impedance-pH monitoring was conducted for 24 hours after the first dose on day 1. Stationary manometry and impedance-pH monitoring was conducted for 4 hours after the third dose on day 2. Of 27 randomized patients, 21 were included in the per-protocol efficacy analysis. During the 24 hours after treatment start, lesogaberan reduced the mean number of reflux events by approximately 35% compared with placebo. During the 3 postprandial hours on day 2, lesogaberan reduced the geometric mean number of TLESRs by 25% and increased geometric mean LES pressure by 28% compared with placebo. The most common adverse events were headache (placebo: 11/27 patients; lesogaberan: 8/25 patients) and paresthesia (transient; placebo: 3/27 patients; lesogaberan: 5/25 patients). In patients with reflux symptoms despite PPI treatment, lesogaberan decreased the number of TLESRs and reflux episodes, and increased LES pressure compared with placebo. These findings support further evaluation of lesogaberan as an add-on treatment in patients partially responding to PPIs.

W1076 Inspiratory Muscle Training Can Increase Lower Esophageal Sphincter Pressure – A Prospective Study

W1076 Inspiratory Muscle Training Can Increase Lower Esophageal Sphincter Pressure – A Prospective Study

Long-term outcome of Nissen fundoplication in non-erosive and erosive gastro-oesophageal reflux disease

Non-erosive (NERD) and erosive (ERD) gastro-oesophageal reflux disease (GORD) show similar severity of symptoms and impact on quality of life (QoL). Prospective data on long-term outcomes of antireflux surgery in NERD are lacking. Subjective and objective 5-year outcomes of Nissen fundoplication were compared in 96 patients with NERD and 117 with ERD, operated on for proton-pump inhibitor (PPI)-refractory GORD. Preoperative and postoperative QoL, PPI use, acid exposure time, symptom-reflux correlation, lower oesophageal sphincter (LOS) pressure and reoperation rates were similar in the two groups. At 5 years, relief of reflux symptoms was similar (NERD 89 per cent versus ERD 96 per cent), PPI use showed a similar reduction (82 to 21 per cent versus 81 to 15 per cent respectively; both P < 0.001) and QoL score improved equally (50.3 to 65.2 (P < 0.001) versus 52.0 to 60.7 (P = 0.016)). Five patients with NERD developed erosions after surgery; oesophagitis healed in 87 per cent of patients with ERD. Reduction in total acid exposure time (NERD 12.7 to 2.0 per cent versus ERD 13.8 to 2.9 per cent; both P < 0.001) and increase in LOS pressure (1.3 to 1.8 kPa versus 1.2 to 1.8 kPa; both P < 0.001) were similar. The reintervention rate was comparable (NERD 15 per cent versus ERD 12.8 per cent). Patients with PPI-refractory NERD and ERD benefit equally from Nissen fundoplication. The absence of mucosal lesions on endoscopy in patients with proven PPI-refractory reflux disease is not a reason to refrain from antireflux surgery.

Effect of Atilmotin, a Motilin Receptor Agonist, on Esophageal, Lower Esophageal Sphincter, and Gastric Pressures

Motilin, an endogenous gastrointestinal (GI) hormone, increases upper gastrointestinal tract motility and is associated with phase III of the gastric migrating motor complex. The motilin receptor agonist, atilmotin, at doses of 6, 30 or 60 microg intravenously (IV), increases the early phase of gastric emptying. Prior studies at higher doses of 100-450 microg IV demonstrated that some subjects developed noncardiac chest pain. The aim of this study is to determine the effects of atilmotin on esophageal, lower esophageal sphincter (LES), and gastric contractility and the development of esophageal-related symptoms. Ten healthy volunteers underwent esophageal manometry to study the effects of atilmotin on upper GI motility. Five subjects were studied on three separate days following administration of saline placebo and subsequent IV bolus dose of atilmotin (6, 30 or 150 microg). Another five subjects were studied at the highest dose (150 microg). Atilmotin at 150 microg increased proximal gastric pressure by 6.5 mmHg (P = 0.001 compared with placebo). Atilmotin increased LES pressure at all studied doses; LES pressure increased from 24 +/- 2 mmHg following placebo injection to 34 +/- 4 mmHg following a 30 microg dose of atilmotin (P = 0.007). In the esophagus, atilmotin increased the percentage of failed swallows at the highest dose studied. Failed swallows increased from 17 +/- 7% following placebo injection to 36 +/- 7% following a 150 microg dose of atilmotin (P = 0.016). Atilmotin decreased distal esophageal contractile amplitude only at the highest dose studied, from 69 +/- 8 mmHg (placebo) to 50 +/- 5 mmHg following 150 microg atilmotin (P = 0.018). There were no serious adverse effects or episodes of chest pain with atilmotin. Atilmotin affects esophageal, LES, and gastric motility. LES and gastric pressures were increased, whereas there was disruption of esophageal peristalsis characterized by lower amplitude and failed contractions.