Lower Esophageal Sphincter Function Research Articles

FRI0376 Beneficial effect of buspirone, an orally available 5-ht1a receptor agonist, on lower esophageal sphincter function in patients with systemic sclerosis

BackgroundDomperidone is widely used for the management of symptoms in patients with Systemic Sclerosis (SSc) and esophageal involvement, but its efficacy is under question. Recently, buspirone, an orally available 5-HT1A...

SAGES clinical spotlight review: endoluminal treatments for gastroesophageal reflux disease (GERD)

Auyang, Carter, Rauth, and Fanelli, along with the members of the SAGES Guidelines Committee, have produced a comprehensive, clear review of available medical literature on the topic of endoluminal treatments for gastroesophageal reflux disease (GERD). This represents an objective, fair, and credible assessment of a diverse body of literature covering a complex and thorny topic. The conclusions and recommendations are invaluable to the physician and surgeon caring for patients with GERD, helping guide not only their advice to patients, but also their own understanding of these offerings and where they fit in today’s treatment of the patient with GERD. I’d like to expand on two carefully chosen words out of the preceding paragraph, complex and thorny, and challenge us to consider better ways to assess new technology so as to achieve an earlier understanding of whether novel technology has a role in our care of patients. First, this clinical spotlight review (CSR) tackles a complex clinical condition and its treatment, GERD. Although GERD as a disease is complex, its basic definition is not: it is simply abnormal reflux of gastric content into the esophagus due to an ineffective lower esophageal sphincter (LES)—a fairly clear definition of a mechanical defect. Yet it has taken decades for us to develop and understand a series of diagnostics to accurately diagnose GERD. Even after decades of study, there remain challenging diagnostic situations, such as how to diagnose clinically significant laryngopharyngeal reflux or how to identify and quantitate clinically significant nonacid reflux. With this, innovation around diagnostics for GERD continues. Many recent introductions provide new insights and ultimately will result in better care for GERD patients (e.g., impedance pH and high-resolution manometry). In contrast, our therapeutic options have changed little in the past decades: acid suppression with proton pump inhibitors and H2 blockers, or a half-century-old operation to augment the ineffective LES, the esophagogastric fundoplication (Nissen or Toupet fundoplication). Although the basis for acid suppression with medication has been well understood and accepted, the mechanism of action of the fundoplication—and more importantly translating a mechanism of action into a standardized technique to achieve consistent and good results—has remained elusive. Hence, achieving a true augmentation of the ineffective LES remains complex. With this as a backdrop, the development and advancement of endoluminal therapies has introduced a whole new level of complexity and confusion to GERD management, largely based on new hypothetical mechanisms of action added to an already poorly understood mechanism for how fundoplication works. For example, when considering these endoluminal therapies, how exactly does delivering radiofrequency energy to the LES alter LES function to control GERD, or can any totally endoluminal technique dependent on tissue fixation really create a durable plication or effect a true fundoplication? Ideally, when assessing new technology, data associated with the development of these new devices will help answer some of these questions. This is where this topic gets thorny. As is true with many new surgical techniques introduced during the past 10–20 years, endoluminal treatments for GERD are oriented around new devices, and with this, these interventions are largely industry driven in their development and introduction into clinical practice. Industry’s interest and development of new devices are essential to our ability to develop and implement new C. D. Smith (&) Department of Surgery, Mayo Clinic Florida, 4500 San Pablo Road, Jacksonville, FL 32224, USA e-mail: smith.c.daniel@mayo.edu

Manometric study in patients with or without preserved lower esophageal sphincter 2 years or more after total gastrectomy reconstructed by Roux-en-Y for gastric cancer.

Physiological assessments in patients with or without preserved lower esophageal sphincter (LES) after total gastrectomy reconstructed by Roux-en-Y (TGRY) are still inconclusive. This study aims to clarify the significance of LES functions in patients, especially prevention of alkali reflux esophagitis (ARE) after TGRY for gastric cancer. Forty-eight patients after TGRY were divided into 2 groups. Group A: 20 patients without preserved LES and group B: 28 patients with preserved LES, and compared with 20 control subjects. The mean follow-up time from operation of TGRY was 27.1 months. Postoperative interview and endoscopic findings for ARE were conducted and esophageal manometry was performed on all patients in order to assess length of LES (LLES; cm) and maximum LES pressure (MLESP; mmHg). Both symptoms and endoscopic findings for ARE in group A were significantly higher than those in group B. The LLES in group A was significantly shorter than that in groups B and C. The MLESP in group A was significantly lower than in groups B and C. ARE after TGRY is due to an impairment of LES functions. Preservation of the LES may be necessary to prevent ARE after TGRY.

Multiple rapid swallow responses segregate achalasia subtypes on high-resolution manometry.

Multiple rapid swallows (MRS) inhibit esophageal peristalsis and lower esophageal sphincter (LES) tone; a rebound excitatory response then results in an exaggerated peristaltic sequence. Multiple rapid swallows responses are dependent on intact inhibitory and excitatory neural function and could vary by subtype in achalasia spectrum disorders. Consecutive subjects with incomplete LES relaxation on high-resolution manometry (HRM) (Sierra Scientific, Los Angeles, CA, USA) in the absence of mechanical obstruction were prospectively identified. Achalasia spectrum disorders were classified and HRM plots reviewed according to Chicago criteria. Esophageal peristaltic performance and LES function were assessed after 10 wet swallows and MRS (five 2 mL water swallows 2-3 s apart). Findings were compared with 18 healthy controls (28.5 ± 0.6 years, 44% women). A total of 46 subjects (57.1 ± 2.1 years, 52.2% women) met inclusion criteria. There was complete failure of peristalsis with MRS in all subjects with achalasia subtypes 1 and 2. In contrast, 80% of achalasia subtype 3 and incomplete LES relaxation (EGJ outflow obstruction) with preserved esophageal body peristalsis had a contractile response to MRS (P < 0.001 compared with subtypes 1 and 2); controls demonstrated 94.4% peristalsis. Percent decrease in LES residual pressure during MRS (compared to wet swallows) segregated achalasia subtypes; those with aperistalsis (subtypes 1 and 2) had a lesser decline (22.6%) compared to those with retained esophageal body peristalsis (40.5%) and controls (51.3%, P < 0.001 across groups). Multiple rapid swallow responses segregate achalasia spectrum disorders into two patterns differentiated by presence or absence of esophageal body contraction response to wet swallows. These findings support subtyping of achalasia, with pathophysiologic implications.

Ingestion of a carbonated beverage decreases lower esophageal sphincter pressure and increases frequency of transient lower esophageal sphincter relaxation in normal subjects

Transient lower esophageal sphincter relaxation (tLESR) and decreased basal lower esophageal sphincter (LES) pressure are postulated mechanisms of gastroesophageal reflux (GER). There is conflicting evidence on the effect of carbonated drinks on lower esophageal sphincter function. This study was conducted to assess the effect of a carbonated beverage on tLESR and LES pressure. High resolution manometry tracings (16 channel water-perfused, Trace 1.2, Hebbard, Australia) were obtained in 18 healthy volunteers (6 men) for 30 min each at baseline, and after 200 mL of chilled potable water and 200 mL of chilled carbonated cola drink (Pepsi [Pepsico India Ltd]). The sequence of administration of the drinks was determined by random number method generated by a computer. The analysis of tracings was done using TRACE 1.2 software by a physician who was unaware of the sequence of administration of fluids. The mean (SD) age of the participant was 37.3 (12.9) years. The median (range) frequency of tLESr was higher after the carbonated beverage (10.5 [0-26]) as compared to baseline (0 [0-3], p = 0.005) as well as after water (1 [0-14], p = 0.010). The LES pressure decreased after ingestion of the carbonated beverage (18.5 [11-37] mmHg) compared to baseline (40.5 [25-66] mmHg, p = 0.0001) and after water (34 [15-67] mmHg, p = 0.003). Gastric pressure was not different in the three groups. Ingestion of a carbonated beverage increases tLESr and lowers LES pressure in healthy subjects.

Expression of dopamine receptors in human lower esophageal sphincter

Dopamine (DA) is considered to be an important modulator of enteric function. Recent experiments have suggested that DA receptors are widely expressed in animal gastrointestinal tract. The aim of this study was to explore the expression of DA receptors (D(1) R, D(2) R, D(3) R, D(4) R, D(5) R) in sling fibers and clasp fibers from the human lower esophageal sphincter (LES). Muscle strips of sling and clasp fibers from the LES were obtained from patients undergoing esophago-gastrectomy, and circular muscle strips from the esophagus and stomach were used as controls. Reverse transcription-polymerase chain reaction and western blotting were used to determine the expression of the five subtypes of DA receptors. Messenger RNA and protein for three of five DA receptors were identified in the sling and clasp fibers of the LES. Expression was highest for D(1) R, then D(5) R and D(2) R in decreasing levels. D(3) R and D(4) R mRNA and protein were not identified in the muscle strips. D(1) R, D(2) R, D(5) R can be detected in the human LES, and probably contribute to LES function. D(3) R and D(4) R are not expressed, and probably do not contribute to LES function in humans.

Sa1194 Repetitive Simultaneous Contraction (RSC) of the Upper Esophageal Sphincter and Striated Esophageal Muscle is Associated With Impairement of Bolus Transit in Patients Having Globus, Dysphagia, or Atypical Chest Pain

Introduction: Esophageal atresia is the most common congenital anomaly of the esophagus. It affects one in every 3000 live births and justifies a surgical intervention in the first days of life. Survival rate is over 90%. Adult patients present a high prevalence of gastro-esophageal reflux (GER) and dysphagia, but the physiopathological mechanism is unknown. Our hypothesis is that esophageal dysmotilities could explain the esophageal symptoms of adults operated on for esophageal atresia. The aim of this study is to describe the esophageal motility of adults operated on for esophageal atresia. Method : Prospective study was carried out between 2008 and 2011 in the motility laboratory of St-Luc Hospital. All patients operated on for esophageal atresia followed in the clinic were eligible. Patients included had a clinical examination, a standard symptom questionnaire and an esophageal manometry. Manometric parameters included the following: 1) for the upper esophageal sphincter (UES): relaxation and coordination during swallow, 2) for the esophageal body: presence, propagation, duration and amplitude of the contraction wave, 3) for the lower esophageal sphincter (LES): localisation, basal pressure and relaxation. Results: Over 41 patients followed at the clinic, 23 accepted manometry and were included (mean age: 26 ± 7 years, mean BMI : 24 ± 6, 61%male). In the esophageal body, aperistalsis was present in 78% (n=18). Hypomotility was detected in 100% of the patients and included: 1) an insufficient number of peristaltic waves in 96% (n=22), 2) nonpropagating peristalsis in 78% (n=18) and 3) low wave amplitude in 95% (n=21). High wave amplitude occurred in 14% (n=3). LES function was abnormal in 52% (n=12) and included hypotonia in 17% (n=4), hypertonia in 4% (n=1), or incomplete relaxation in 40% (n=8). The UES was always normal. Dysphagia occurred in 57% (n=13) and GER in 30% (n=9). Dysmotility was equally common in the dysphagia group (n=7) compared to the nondysphagic group (n=5) (54% vs 50%, NS), and in the GER group (n=6) compared to the group without GER (n=6), (67% vs 43%, NS). Conclusion: This study is the first demonstrating the high prevalence of esophageal dysmotilities in adults operated on for esophageal atresia: all patients had manometric anomalies. The main esophageal manometry findings included hypomotility of the esophagus body and abnormal LES relaxation. Theses anomalies could explain the esophageal symptoms in this population.

Heterogeneity of Lower Esophageal Sphincter Function in Children With Achalasia

Achalasia is a rare esophageal motor disorder in children. The manometric hallmarks are esophageal body aperistalsis, lack of lower esophageal sphincter (LES) relaxation, and high LES pressure. However, LES relaxation and function may be heterogeneous, making the diagnosis difficult at times. The aim of the study was to describe LES function in children with achalasia. The present study is a retrospective review of manometric tracings of pediatric patients with achalasia and controls. LES response after each swallow was evaluated. LES parameters were defined as homogeneous (normal or abnormal) if the same response was observed in >75% of swallows. Otherwise, the LES parameters were considered heterogeneous. Twenty-nine patients with achalasia and 16 control patients were included. All of the controls had normal LES pressure and relaxation in all of the wet swallows. In the achalasia group, some LES relaxation was present in 74% of swallows and 25% of swallows had normal relaxation. Depending on the parameter, a heterogeneous LES (resting pressure, relaxation, residual pressure, and duration of relaxation) was observed in 27.6% to 34.5% of patients with achalasia versus 0% of the controls (P < 0.001). The rest of the patients with achalasia had homogeneous abnormal responses versus homogeneous normal responses in 100% of control patients (P < 0.001). The LES function in pediatric patients with achalasia is heterogeneous. The classic description of a nonrelaxing high-pressure LES in patients with achalasia is rarely found in children. Partial relaxations are common, and normal relaxations may be present.

Effect of buspirone, a 5-HT1A receptor agonist, on esophageal motility in healthy volunteers

There are limited data concerning the effects of 5-HT(1A) receptor activation on esophageal motility. Sumatriptan, a 5-HT(1A) receptor agonist, was recently reported to enhance esophageal peristalsis after intravenous administration. Buspirone, an orally available 5-HT(1A) receptor agonist, was shown to modulate gastroduodenal motor function. Our aim was to evaluate the effect of buspirone on esophageal motility of healthy volunteers. On two separate visits, 20 healthy volunteers aged 21-29 years (nine women) underwent esophageal manometry before and 10, 30, and 60 minutes after the administration of buspirone 20-mg or placebo capsule, according to a double-blind crossover design. At each time point, we compared buspirone and placebo effects on: resting pressure of the lower esophageal sphincter (LES); residual pressure and duration of LES relaxation; amplitude, duration, and onset velocity of esophageal body contractions, during 10 swallows of 5 mL of water. Significant analysis of variance differences (P < 0.05) are presented as mean ± standard deviation. Buspirone significantly increased mean distal esophageal wave amplitude (151 vs. 87 mmHg, P < 0.05) and duration (6.1 vs. 4.2 seconds, P < 0.05). Similarly, buspirone significantly increased mean LES resting pressure (26 vs. 21 mmHg, P < 0.05) and mean residual LES pressure (7.9 vs. 2 mmHg, P < 0.05), whereas reduced mean LES relaxation duration (7.2 vs. 8.0 seconds, P < 0.05) and mean distal onset velocity (7.6 vs. 14.7 cm/second, P < 0.05). Buspirone enhances esophageal peristalsis and LES function in healthy volunteers. Further study is warranted on the effects of buspirone on esophageal function and symptoms in patients with ineffective esophageal motility.

The evaluation of esophageal motility in patients with persistent dysphagia after fundoplication

Persistent postoperative dysphagia (PPD) is a relatively rare but troublesome complication of laparoscopic fundoplication in patients with gastroesophageal reflux disease. Although it is mainly attributed to impaired distal esophageal body (EB) function, it may develop in patients with preserved motility as well. Since little is known about the pre- and postoperative motility patterns of such patients we aimed to compare the esophageal motor function in patients with PPD and a matched control group of patients without swallowing problems after fundoplication. Patients, Methods: Eleven patients (M/F 3/8, mean age: 52.6 ys., BMI: 24.2) with PPD after laparoscopic fundoplication were evaluated. Standard water perfusion esophageal manometry was performed before and 3 months after fundoplication in all subjects and results were compared to an age, sex, BMI and preoperative dysphagia score matched group of 11 control patients without PPD. Results: Preoperative esophageal manometry showed similar lower esophageal sphincter (LES) length, pressure, relaxation time, and EB peristaltic wave duration in both groups. The amplitude of contractions in the distal EB were also similar, while patients with PPD had significantly lower amplitudes in the proximal esophagus than controls after dry (25.5 vs. 61.8mmHg, p=0.01) and wet (45.1 vs. 76.7mmHg, p=0.05) swallows. Propagation velocity of the contractions were slower in patients with PPD after wet swallows (2.56 vs. 3.27cm/s, p=0.05). The number of simultaneous contractions tended to be higher in PPD. Postoperatively both groups had similarly improved LES function. In the EB, distal contraction amplitudes were decreased in patients with PPD (95.6 vs. 75.5mmHg, p=0.05) but not in controls, compared to the preoperative values. After fundoplication the number of simultaneous contractions were significantly higher in patients with PPD than in controls. Conclusions: In patients with preserved distal EB contraction amplitudes, decreased peristaltic wave propagation velocity, and proximal amplitudes may be predictive for PPD after fundoplication. Patients with PPD have decreased distal EB contraction amplitudes after fundoplication compared to their preoperative results. TÁMOP421/B09/1, ETT340/09

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

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

Decreased Motility of the Lower Esophageal Sphincter in a Rat Model of Gastroesophageal Reflux Disease May Be Mediated by Reductions of Serotonin and Acetylcholine Signaling

To elucidate the altered function of the lower esophageal sphincter (LES) in gastroesophageal reflux disease (GERD), we evaluated the motility proximal to LES using force transducers, contraction and relaxation responses to neurotransmitters in LES strips, and gene expression of neurotransmitter receptors in GERD rats. Force transducers were applied to the proximal LES, and contraction of the LES was monitored during free moving. In addition, LES was isolated from sham-operated and GERD rats to investigate the LES function in an organ bath, and to determine gene expression. The in vivo motility proximal to LES (% motility index) in conscious rats was decreased by atropine treatment and increased by cisapride (5-HT(4) receptor agonist) treatment. Acetylcholine- and serotonin (5-HT)-induced LES contraction and sodium nitroprusside-induced relaxation in LES strips of GERD rats markedly decreased compared to sham-operated rats. The mRNA expressions of 5-HT(4) and muscarinic acetylcholine 3 receptors were significantly reduced in esophageal LES strips of GERD rats compared with sham-operated rats. Intraperitoneal administration of cisapride improves the erosive damage in the esophagus in GERD rats. It is suggested that the reduction of 5-HT-induced contraction in LES strips in GERD rats may be partly due to the decrease in 5-HT(4)-receptor activation. The reduction of LES function may be due to the decrease in neurotransmitters signal transduction, leading to the deterioration of histopathological damage in GERD.

The effects of itopride on oesophageal motility and lower oesophageal sphincter function in man

The effects of itopride on oesophageal motility and lower oesophageal sphincter function in man

The effects of itopride on oesophageal motility and lower oesophageal sphincter function in man

Itopride is a new prokinetic agent that combines antidopaminergic and cholinesterase inhibitory actions. Previous studies suggested that itopride improves heartburn in functional dyspepsia, and decreases oesophageal acid exposure in gastro-oesophageal reflux disease. It remains unclear whether this effect is due to effects of itopride on the lower oesophageal sphincter (LES). To study the effects of itopride on fasting and postprandial LES function in healthy subjects. Twelve healthy volunteers (five men; 32.6 ± 2.0 years) underwent three oesophageal sleeve manometry studies after 3 days premedication with itopride 50 mg, itopride 100 mg or placebo t.d.s. Drug was administered after 30 min and a standardized meal was administered after 90 min, with measurements continuing to 120 min postprandially. Throughout the study, 10 wet swallows were administered at 30-min intervals, and gastrointestinal symptoms were scored on 100 mm visual analogue scales at 15-min intervals. Lower oesophageal sphincter resting pressures, swallow-induced relaxations and the amplitude or duration of peristaltic contractions were not altered by both doses of itopride, at all time points. Itopride pre-treatment inhibited the meal-induced rise of transient LES relaxations (TLESRs). Itopride inhibits TLESRs without significantly affecting oesophageal peristaltic function or LES pressure. These observations support further studies with itopride in gastro-oesophageal reflux disease.

Mechanisms of nocturnal gastroesophageal reflux events in obstructive sleep apnea

Obstructive sleep apnea (OSA) is associated with increased nocturnal gastroesophageal reflux (nocturnal GER) events and symptoms. Treatment of OSA with continuous positive airway pressure (CPAP) reduces nocturnal GER in patients with OSA. This study sought to determine the: (1) relationship of nocturnal GER events with apnea/hypopnea and arousal, (2) effect of upper airway obstruction on the barrier function of the lower esophageal sphincter (LES), (3) mechanism of LES failure for each nocturnal GER event and (4) effect of CPAP on LES function during sleep. Eight patients with OSA and nocturnal GER underwent polysomnography with esophageal manometry and pH monitoring. The first half of the night was spent without CPAP and the second half with 10 cmH(2)O CPAP. Baseline LES barrier pressure (P (b)) was low in these patients. When patients were off CPAP, there were 2.7 ± 1.8 nocturnal GER events per hour and 70 ± 39 obstructive respiratory events per hour. There was no direct relationship between the occurrence of GER and obstructive events. While upper airway obstruction did not alter P (b), CPAP tended to increase the nadir P (b) during LES relaxation (LESR) and decreased the duration of LESR. Upper airway obstructive and nocturnal GER events are not directly related. The relatively low P (b) in these OSA patients raises the possibility of weakening of the gastroesophageal junction from repetitive strain associated with obstructed breathing events. The favourable effect of CPAP on nocturnal GER is possibly due to an increase in nadir P (b) and decrease in the duration for which the LES relaxes during swallow-induced and transient LESR.

Continuing Medical Education Exam 1: Effects of Lesogaberan on Reflux and Lower Esophageal Sphincter Function in Patients With Gastroesophageal Reflux Disease

Continuing Medical Education Exam 1: Effects of Lesogaberan on Reflux and Lower Esophageal Sphincter Function in Patients With Gastroesophageal Reflux Disease

Evidence-based appraisal in laparoscopic Nissen and Toupet fundoplications for gastroesophageal reflux disease

To demonstrate the optimal surgical procedure for gastroesophageal reflux disease. The electronic databases of Medline, Elsevier, Springerlink and Embase over the last 16 years were searched. All clinical trials involved in the outcomes of laparoscopic Nissen fundoplication (LNF) and laparoscopic Toupet fundoplication (LTF) were identified. The data of assessment in benefits and adverse results of LNF and LTF were extracted and compared using meta-analysis. We ultimately identified a total of 32 references reporting nine randomized controlled trials, eight prospective cohort trials and 15 retrospective trials. These studies reported a total of 6236 patients, of whom 4252 (68.18%) underwent LNF and 1984 (31.82%) underwent LTF. There were no differences between LNF and LTF in patients' satisfaction, perioperative complications, postoperative heartburn, reflux recurrence and re-operation. Both LNF and LTF enhanced the function of lower esophageal sphincter and improved esophagitis. The postoperative dysphagia, gas-bloating syndrome, inability to belch and the need for dilatation after LNF were more common than after LTF. Subgroup analyses showed that dysphagia after LNF and LTF was similar in patients with normal esophageal peristalsis (EP), but occurred more frequently in patients with weak EP after LNF than after LTF. Furthermore, patients with normal EP after LNF still had a higher risk of developing dysphagia than did patients with abnormal EP after LTF. Compared with LNF, LTF offers equivalent symptom relief and reduces adverse results.

M1877 Two Functional Categories of Reflux-Inhibiting GABA B Receptor Agonists Defined By Their Affinity for the GABA Transporter

Background: Proton pump inhibitors (PPI) are the drug of first choice for treating patients with gastroesophageal reflux disease (GERD). However, about 50% of non-erosive reflux disease (NERD) patients have a poor response to PPI treatment. It is reported that esophageal motility disorder involving a decline in esophageal clearance contributes to the poor PPI response. Accordingly, a drug capable of enhancing esophageal motility would be beneficial in the treatment of NERD patients. Rikkunshito, a gastrointestinal prokinetic agent, is known to improve esophageal clearance in GERD patients and gastric emptying in functional dyspepsia patients and to increase secretion of ghrelin in rats. Aim: To clarify the efficacy of rikkunshito in NERD patients, we evaluated the effects of rikkunshito on esophageal and lower esophageal sphincter (LES) motility and symptoms. Methods: Fifteen patients were enrolled in the study. They were diagnosed as having NERD according to endoscopic testing and the score (6 points or more) obtained on the questionnaire for the diagnosis of reflux disease (QUEST). All patients stopped taking all gastrointestinal-related drugs for over 1 week prior to rikkunshito treatment, and were administered rikkunshito (7.5 g per day, orally) for 8 weeks. Esophageal and LES functions during liquid or semisolid swallow were evaluated using MII-EM following gold standard methods before and after rikkunshitotreatment. Symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS) before, 4 weeks after, and 8 weeks after treatment. Results: Rikkunshito-treatment significantly improved the mean of complete bolus transit (CBT) during liquid or semisolid swallow from 60.7±7.7% to 90.0±5.8% (p 79%, semisolid: >69%) for CBT decreased from 53.3% to 16.7% and from 60.0% to 33.3% after treatment, respectively. In manometry evaluation, rikkunshito significantly improved the mean of LES residual pressure during liquid swallow from 6.0±1.3 mmHg to 3.8±1.4 mmHg (p<0.05). In addition, rikkunshito significantly ameliorated total GI symptom scores in GSRS (from 2.1±0.2 to 1.6±0.1: (p<0.05)) and showed a tendency toward improvement of subscales for reflux symptoms, abdominal pain and dyspeptic symptoms. Conclusion: We found that rikkunshito improved the esophageal clearance and symptoms in NERD patients through the amelioration of esophageal and LES motility disorder. Thus, rikkunshito may become a useful drug for treating NERD patients.

M1876 Rikkunshito Improves Esophageal Motility Disorder and Symptoms in Patients with NERD - a Study Using Combined Multichannel Intraluminal Impedance and Manometry (MII-EM) -

Background: Proton pump inhibitors (PPI) are the drug of first choice for treating patients with gastroesophageal reflux disease (GERD). However, about 50% of non-erosive reflux disease (NERD) patients have a poor response to PPI treatment. It is reported that esophageal motility disorder involving a decline in esophageal clearance contributes to the poor PPI response. Accordingly, a drug capable of enhancing esophageal motility would be beneficial in the treatment of NERD patients. Rikkunshito, a gastrointestinal prokinetic agent, is known to improve esophageal clearance in GERD patients and gastric emptying in functional dyspepsia patients and to increase secretion of ghrelin in rats. Aim: To clarify the efficacy of rikkunshito in NERD patients, we evaluated the effects of rikkunshito on esophageal and lower esophageal sphincter (LES) motility and symptoms. Methods: Fifteen patients were enrolled in the study. They were diagnosed as having NERD according to endoscopic testing and the score (6 points or more) obtained on the questionnaire for the diagnosis of reflux disease (QUEST). All patients stopped taking all gastrointestinal-related drugs for over 1 week prior to rikkunshito treatment, and were administered rikkunshito (7.5 g per day, orally) for 8 weeks. Esophageal and LES functions during liquid or semisolid swallow were evaluated using MII-EM following gold standard methods before and after rikkunshitotreatment. Symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS) before, 4 weeks after, and 8 weeks after treatment. Results: Rikkunshito-treatment significantly improved the mean of complete bolus transit (CBT) during liquid or semisolid swallow from 60.7±7.7% to 90.0±5.8% (p 79%, semisolid: >69%) for CBT decreased from 53.3% to 16.7% and from 60.0% to 33.3% after treatment, respectively. In manometry evaluation, rikkunshito significantly improved the mean of LES residual pressure during liquid swallow from 6.0±1.3 mmHg to 3.8±1.4 mmHg (p<0.05). In addition, rikkunshito significantly ameliorated total GI symptom scores in GSRS (from 2.1±0.2 to 1.6±0.1: (p<0.05)) and showed a tendency toward improvement of subscales for reflux symptoms, abdominal pain and dyspeptic symptoms. Conclusion: We found that rikkunshito improved the esophageal clearance and symptoms in NERD patients through the amelioration of esophageal and LES motility disorder. Thus, rikkunshito may become a useful drug for treating NERD patients.

M1878 The Novel 5-HT4 Receptor Partial Agonist RQ-00000010 Enhances a Rate of Gastric Emptying in Dog Without QT Interval Prolongation

Background: Proton pump inhibitors (PPI) are the drug of first choice for treating patients with gastroesophageal reflux disease (GERD). However, about 50% of non-erosive reflux disease (NERD) patients have a poor response to PPI treatment. It is reported that esophageal motility disorder involving a decline in esophageal clearance contributes to the poor PPI response. Accordingly, a drug capable of enhancing esophageal motility would be beneficial in the treatment of NERD patients. Rikkunshito, a gastrointestinal prokinetic agent, is known to improve esophageal clearance in GERD patients and gastric emptying in functional dyspepsia patients and to increase secretion of ghrelin in rats. Aim: To clarify the efficacy of rikkunshito in NERD patients, we evaluated the effects of rikkunshito on esophageal and lower esophageal sphincter (LES) motility and symptoms. Methods: Fifteen patients were enrolled in the study. They were diagnosed as having NERD according to endoscopic testing and the score (6 points or more) obtained on the questionnaire for the diagnosis of reflux disease (QUEST). All patients stopped taking all gastrointestinal-related drugs for over 1 week prior to rikkunshito treatment, and were administered rikkunshito (7.5 g per day, orally) for 8 weeks. Esophageal and LES functions during liquid or semisolid swallow were evaluated using MII-EM following gold standard methods before and after rikkunshitotreatment. Symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS) before, 4 weeks after, and 8 weeks after treatment. Results: Rikkunshito-treatment significantly improved the mean of complete bolus transit (CBT) during liquid or semisolid swallow from 60.7±7.7% to 90.0±5.8% (p 79%, semisolid: >69%) for CBT decreased from 53.3% to 16.7% and from 60.0% to 33.3% after treatment, respectively. In manometry evaluation, rikkunshito significantly improved the mean of LES residual pressure during liquid swallow from 6.0±1.3 mmHg to 3.8±1.4 mmHg (p<0.05). In addition, rikkunshito significantly ameliorated total GI symptom scores in GSRS (from 2.1±0.2 to 1.6±0.1: (p<0.05)) and showed a tendency toward improvement of subscales for reflux symptoms, abdominal pain and dyspeptic symptoms. Conclusion: We found that rikkunshito improved the esophageal clearance and symptoms in NERD patients through the amelioration of esophageal and LES motility disorder. Thus, rikkunshito may become a useful drug for treating NERD patients.