Transient Lower Esophageal Sphincter Research Articles

1123 Gastroesophageal Pressure Signatures During Transient Lower Esophageal Sphincter Relaxations (TLESRs) Categorized by the Occurrence and Composition of Reflux

1123 Gastroesophageal Pressure Signatures During Transient Lower Esophageal Sphincter Relaxations (TLESRs) Categorized by the Occurrence and Composition of Reflux

Mo1062 Effect of Transoral Incisionless Fundoplication on the Occurrence of Transient Lower Esophageal Sphincter Relaxations (TLESRs) in GERD Patients

unanticipated adverse events, or untoward sensation due to LES-EST. There were no reports of treatment related dysphagia and the manometric evaluation of swallow was also normal. Conclusion: Long-term follow-up of 6 months showed LES-EST to be safe and effective for treating GERD patients with incomplete response to PPI therapy. Importantly, LES-EST can be optimized to individual patient needs to further improve patient outcomes. All patients had received significant clinical benefit from LES-EST and the trial has been extended with one-year follow-up results available after March 2012.

428 Characterization of Proximal Movement of Gastro-Oesophageal Junction During Transient Lower Oesophageal Sphincter Relaxations Using a Novel Hall Effect Probe

alcohol etiology were more likely to be male (65 vs. 36%, p<0.05), Black (18 vs. 4%, p= 0.04) and smokers (88 vs. 29%, p<0.01). Over a median follow up (which was similar across etiologies) of 9 years (IQR 6, 15), progression to CP occurred in 20 (18%) patients. The mean age at the time of CP diagnosis was 48 +/17 years and the median duration from the first episode of AP to the diagnosis of CP was 7 years (IQR 4, 13). The overall risk of progression to CP was significantly higher in patients with alcohol (vs. others) etiology (41 vs. 14%, p<0.05). On Cox-regression analysis, the risk of progression from AP to CP was 3 fold higher in patients with alcohol etiology (HR 3.1, 95% CI 1.2-7.7) (Figure 1). Conclusions: Progression from RAP to CP, although frequent in patients with alcohol etiology, also occurs in a subset of patients with other etiologies.

Esophageal high resolution manometry: a new gold standard for the detection of transient lower esophageal sphincter relaxations?

Esophageal high resolution manometry: a new gold standard for the detection of transient lower esophageal sphincter relaxations?

Effect of nitrite delivered in saliva on postprandial gastro-esophageal function

Objective.Acid reflux produces troublesome symptoms (heartburn) and complications including esophagitis, Barrett's esophagus, and adenocarcinoma. Reflux occurs due to excessive and inappropriate relaxation of the lower esophageal sphincter. An important mediator of this is nitric oxide, high concentrations of which are generated within the lumen when swallowed saliva meets gastric acid. Saliva contains nitrite, derived from the enterosalivary recirculation of dietary nitrate, which is reduced to nitric oxide by gastric acid. The aim of this study was to investigate whether salivary nitrite contributes to dysfunction of the lower esophageal sphincter. Materials and methods.In 20 volunteers, studies of gastro-esophageal function were performed on four separate days, following consumption of a standardized meal, with saliva nitrite concentrations modified differently each day by intra-oral nitrite infusion. Results.The infusions produced an appropriate range in saliva nitrite concentrations, from below to well above the physiological range. The standardized meal induced expected physiological changes in gastro-esophageal function confirming the recordings were sensitive and robust. Esophageal acid exposure (primary outcome) was similar on each study day. Secondary outcomes, including number and duration of reflux events, rate of transient lower esophageal sphincter relaxations, lower esophageal sphincter pressure and rate of gastric emptying were also unaffected by variations in saliva nitrite concentration. Conclusions.Nitrite in swallowed saliva does not modify gastro-esophageal junction function or predispose to gastro-esophageal reflux. The wide range in saliva nitrite concentrations, the sensitivity of the physiological recordings and the number of subjects studied make it very unlikely that an effect has been missed.

Transient lower oesophageal sphincter relaxation reducers - have we hit a brick wall? authors’ reply

Transient lower oesophageal sphincter relaxation reducers - have we hit a brick wall? authors’ reply

Non-Erosive Reflux Disease and Neurogenic Inflammation: Association of Circulating Substance P and Nerve Growth Factor Levels With Heartburn Symptoms

AIM: During transient lower esophageal sphincter relaxations (TLESRs) the position of the gastric acid pocket mainly determines the acidity of the refluxate. However, to what extent the position or dynamics of the acid pocket determines acidity of the refluxate during other mechanisms of reflux (straining, low lower esophageal sphincter pressure (LESp) or during swallows) remains unclear. METHODS: Twenty patients with gastroesophageal reflux disease (GERD) were invited to undergo combined high resolution manometry (HRM) and pHimpedance recording after a standardized meal (550kcal) in the upright position. The acid pocket was visualized using scintigraphy after i.v. injection of 350MBq 99mTc-pertechnetate. The position of the pocket was classified as supradiaphramatic, extending into the hiatal opening (infradiaphragmatic) or subdiaphragmatic using radionuclide markers on the HRM catheter. The underlying reflux mechanism was determined using HRM, according to predefined criteria (v Herwaarden, Gastroenterology 2000, 1439-46). RESULTS: A total of 494 reflux episodes were detected, of which 244 (49%) were acidic. The underlying mechanism of reflux was a TLESR in 328 (66%), low LESp in 21 (4.3%), straining in 126 (26%), swallow-associated in 14 (2.9%) and unknown in 5 (1.0%) events respectively. Acidic reflux occurred with a supradiaphragmatic localisation of the acid pocket in 117 of 129 (91%) events, in 103 of 169 (62%) events with an infradiaphragmatic localisation and in 19 of 175 (11%) events with a subdiaphragmatic localisation. When straining was the underlying mechanism, the refluxate was more often acidic than during a TLESR (n=100 (80%) vs n= 130 (40%) respectively P<0.0001, Chi square). There was no difference in acidity between reflux events during low LESp or events associated to swallows compared to TLESRs. Scintigraphic imaging clearly illustrated that straining pushes the acid pocket upwards into the esophagus regardless of its initial position. CONCLUSION: Our data confirm that a supradiaphragmatic position of the acid pocket is an important factor determining the risk for acidic reflux, also during mechanisms of reflux different from TLESRs. Scinitgraphic imaging of the pocket demonstrates that the acid pocket is pushed into the esophagus during straining regardless of its position, further illustrating that the pocket is indeed the reservoir of acidic refluxate.

Reflex Increase in the Gastroesophageal Junction High Pressure Zone Pressure During Sedated Endoscopy With Gastric Distension in Normal Volunteers

Background: Gastric distension is a strong trigger for transient lower esophageal sphincter relaxation. In addition, it has been shown in prior unsedated studies that as the stomach is distended the pressure and length within the Gastroesophageal Junction High pressure Zone (GEJHPZ) decreases (Ayazi, Shahin MD et al, Annals of Surgery: July 2010 Volume 252 Issue 1 pp 57-62) Purpose: To evaluate the GEJHPZ pressure during gastric distension. Methods: Five normal volunteers (56.2 Yrs, 4F and 1M) were evaluated during upper endoscopy. A custom made manometry catheter with pressure ports spaced 3mm apart was attached to an Olympus ultrathin endoscope (GIF-N 180). Simultaneous manometry and endoscopy was recorded on an MMS swallowing work station. The endoscopy was performed under conscious sedation with Midazolam and Fentanyl. The endoscope was retroflexed to visualize the manometry catheter placed across the entire GEJHPZ. Baseline sphincter and gastric pressures were measured. Air was then insufflated into the stomach through the air channel of the endoscope with the air flow settings set at low (20ml/sec). Gastric and GEJHPZ pressures were measured continuously during air insufflation until a peak pressure was attained or the sphincter relaxed. All the pressures reported were relative to the gastric baseline pressure. To analyze the data, the start time was selected based on the lowest pressure at or just before the start of air insufflation, and the end point was selected where the pressure reached the peak within the GEJHPZ or just before sphincter relaxation. The duration to reach the peak pressure varied widely from subject to subject so the total duration was converted into 100% and then divided into 5 equal zones and an average pressure was calculated for each zone in the subjects. The peak and baseline pressures within the stomach and GEJHPZ were compared to each other using a paired student T test. The slope of the pressure change was determined. Results: The intragastric pressure increased from a mean of 6.19 mmHg to 12.34 mmHg at a slope of 1.09 (p=0.123). The GEJHPZ pressure increased from a mean 12.16 mmHg to 63.68 mmHg at a slope of 9.47 (p≤0.001). Conclusions: During sedated endoscopy, contrary to prior unsedated studies, gastric distension elicits a marked and significant reflex increase in the pressure and tone within the GEJHPZ as measured by intersphincteric pressure measurements using ultra-high resolution manometry. We measured the absolute change and the slope of the change of the pressures in both the stomach and the GEJHPZ during distension of the stomach with air. We believe that this gastric/GEJHPZ reflex is an important mechanism that protects the esophagus from reflux of gastric contents during increases in intragastric pressure.

Increased Frequency of Transient Lower Esophageal Sphincter Relaxations: A Characteristic in GERD Patients

Increased Frequency of Transient Lower Esophageal Sphincter Relaxations: A Characteristic in GERD Patients

Scintigraphic Analysis of the Dynamics of the Acid Pocket During Different Mechanisms of Gastroesophageal Reflux

AIM: During transient lower esophageal sphincter relaxations (TLESRs) the position of the gastric acid pocket mainly determines the acidity of the refluxate. However, to what extent the position or dynamics of the acid pocket determines acidity of the refluxate during other mechanisms of reflux (straining, low lower esophageal sphincter pressure (LESp) or during swallows) remains unclear. METHODS: Twenty patients with gastroesophageal reflux disease (GERD) were invited to undergo combined high resolution manometry (HRM) and pHimpedance recording after a standardized meal (550kcal) in the upright position. The acid pocket was visualized using scintigraphy after i.v. injection of 350MBq 99mTc-pertechnetate. The position of the pocket was classified as supradiaphramatic, extending into the hiatal opening (infradiaphragmatic) or subdiaphragmatic using radionuclide markers on the HRM catheter. The underlying reflux mechanism was determined using HRM, according to predefined criteria (v Herwaarden, Gastroenterology 2000, 1439-46). RESULTS: A total of 494 reflux episodes were detected, of which 244 (49%) were acidic. The underlying mechanism of reflux was a TLESR in 328 (66%), low LESp in 21 (4.3%), straining in 126 (26%), swallow-associated in 14 (2.9%) and unknown in 5 (1.0%) events respectively. Acidic reflux occurred with a supradiaphragmatic localisation of the acid pocket in 117 of 129 (91%) events, in 103 of 169 (62%) events with an infradiaphragmatic localisation and in 19 of 175 (11%) events with a subdiaphragmatic localisation. When straining was the underlying mechanism, the refluxate was more often acidic than during a TLESR (n=100 (80%) vs n= 130 (40%) respectively P<0.0001, Chi square). There was no difference in acidity between reflux events during low LESp or events associated to swallows compared to TLESRs. Scintigraphic imaging clearly illustrated that straining pushes the acid pocket upwards into the esophagus regardless of its initial position. CONCLUSION: Our data confirm that a supradiaphragmatic position of the acid pocket is an important factor determining the risk for acidic reflux, also during mechanisms of reflux different from TLESRs. Scinitgraphic imaging of the pocket demonstrates that the acid pocket is pushed into the esophagus during straining regardless of its position, further illustrating that the pocket is indeed the reservoir of acidic refluxate.

What Is Nonacid Reflux Disease?

Proton pump inhibitors (PPIs) are the gold standard treatment for gastroesophageal reflux disease. In clinical practice, failure of PPIs occurs frequently, and may affect up to 30% of patients in a typical gastroenterology practice. Multichannel impedance monitoring combined with pH monitoring helps to detect nonacid reflux, and if symptoms correlate with these nonacid reflux episodes, nonacid reflux disease can be diagnosed. In contrast to PPIs, reflux inhibitors target transient lower esophageal sphincter relaxations, which are involved in the pathophysiology of reflux disease and may be the appropriate future treatment for nonacid reflux disease. The present article discusses the current understanding of nonacid reflux disease, its diagnosis and treatment.

Herbs for Gastroesophageal Reflux Disease

Herbal medicines offer many potential ways to help people with gastroesophageal reflux disease (GERD), including by treating the underlying transient lower esophageal sphincter relaxations (TLESR), helping relieve symptoms, and reducing inflammation. Fumaria officinalis (fumitory-of-the-wall) and Chelidonium majus (celandine) are two among many cholagogues that empirically seem to be helpful. Another cholagogue, Artemisia asiatica (Asian wormwood), has been shown experimentally to reduce GERDrelated symptoms. Atropa belladonna (belladonna, deadly nightshade) and other anticholinergics may also correct TLESR. Demulcents, such as alginic acid, Ceratonia siliqua (carob), Ulmus rubra (slippery elm), Althaea officinalis (marshmallow), and Aloe vera (aloe) leaf gel can reduce acute symptoms and heal acid-damaged tissues. Inflammation modulators, such as deglycyrrhizinated licorice, Calendula off icinalis (calendula), Curcuma longa (turmeric), Zingiber off icinale (ginger), Rosmarinus off icinalis (rosemary), and Symphytum off icinale (comfrey) may also help with tissue repair and symptom control. Herbal medicine has much to offer patients with GERD but more clinical research is needed.

Evolving drugs in gastroesophageal reflux disease: pharmacologic treatment beyond proton pump inhibitors

Importance of the field: Despite the clinical success of proton pump inhibitors to treat gastroesophageal reflux disease (GERD), for the majority of patients in both gastroenterology and primary care clinics there is still a substantial group of patients (up to 40% in some studies) who do not completely respond symptomatically to a standard dose of proton pump inhibitors (PPIs). Specific explanations for these PPI noncomplete responders included transient lower esophageal sphincter relaxations (TLESRs), sensitivity to weakly acidic and/or alkaline reflux, large volume of reflux and esophageal hypersensitivity. There is a clear need for GERD therapies beyond the PPIs.Areas covered in this review: These drug classes include the GABAB receptor agonists (including lesogaberan and arbaclofen placarbil), mGluR5 receptor antagonists, P-CABs, cholecystokinin2 antagonists and add-on therapies to PPIs including mosapride and rikkunshito.What the reader will gain: Both physicians and patients are eagerly awaiting the development and FDA approval of a new class of anti-GERD medications targeting distinct mechanisms. This article provides information on pharmacologic strategies, clinical trials and side-effect profiles on several of the most promising and heavily researched compounds being developed today for the treatment of GERD symptoms and inflammation. Hopefully, this important research will help a large group of PPI noncomplete responding patients receive symptomatic relief and reduce esophageal inflammation through a unique pharmacologic mechanism in the near future.Take home message: The treatment of GERD has greatly improved with the PPI class of therapy. Despite excellent success, there is a sizeable population of patients who do not have adequate response to therapies directed only at acid suppression. Emerging new pharmacologic treatment options show promise in further advancing the treatment success of GERD.

T1893 Effects of Red Chili, a Natural Capsaicin Receptor Agonist, on Gastroesophageal Reflux (GER) Symptoms and Transient Lower Esophageal Sphincter Relaxations (TLESRs) in Healthy Humans

Capsaicin or TRPV1 receptors have been reported to be increased in the esophagus of patients with non-erosive reflux disease. The effects of red chili, a natural capsaicin agonist, on TLESRs have not been reported. Aim: To investigate the effects of red chili on gastroesophageal reflux symptoms and TLESRs in healthy humans. Methods: After an overnight fast, 8 healthy volunteers (5 males, mean age 31±3 years) underwent high resolution esophageal manometry with ingestion of 2 gm red chili (capsaicin = 1.46 mg) or placebo in capsules, in a randomized double blind cross-over fashion with a one-week washout period. Lower esophageal sphincter pressure monitoring began at 15 minutes before chili or placebo ingestion. All subjects ingested standard liquid meals (250 ml of Ensure®) at 15 minutes after the ingestion of chili or placebo capsules. Lower esophageal sphincter monitoring was continued for 2 hours after the meal ingestion. The TLESRs were defined as the relaxations which fulfilled the 4 following criteria: 1) absent of swallowing between 4 seconds before and 2 seconds after the onset of LES relaxations, 2) relaxation rate of >1 mmHg/second, 3) time from onset to complete relaxation of 10 seconds and fulfilled the last 3 criteria. The number of TLESRs and other esophageal manometry parameters were compared between after placebo and chili ingestion. GER and dyspeptic symptoms were evaluated using 10 cm long visual analog scales. Results: (data were expressed as mean±SEM or median and interquartile range) All subjects completed the studies. After ingestion of red chili, heartburn, acid regurgitation, food regurgitation and abdominal burning symptom scores were significantly increased compared to placebo (2.5±0.9, 1.6±0.4, 2.1±0.4, and 5.9±0.7 vs 0.3±0.3, 0.9±0.2, 0.9±0.2, and 0.5±0.2, respectively, p 0.05). The resting LES pressure (19.8±0.9 vs 19.8±0.7 mmHg) was not significantly different between after chili and placebo ingestions (p>0.05). There was no significant correlation between the number of TLESRs and heartburn, acid regurgitation, or food regurgitation scores (p>0.05). Conclusions: Ingestion of red chili increases GER symptoms and epigastrium burning symptoms in healthy volunteers. However, red chili has no significant effect on TLESRs. This suggests that, in healthy volunteers, red chili modulates GER symptoms by its effect on esophageal sensation rather than on the TLESRs.

551 Effect of Gastric Emptying on Pressure-Flow Dynamics of Oesophago-Gastric Junction

Introduction Oesophago-gastric junction (OGJ) incompetence is a primary determinant of gastrooesophageal reflux disease (GORD) severity. Especially, the pressure-flow gradients across the OGJ during lower oesophageal sphincter (LOS) relaxation have important implications in GORD pathogenesis and subsequent planning of its treatment. Our aim was to evaluate the pressure-flow dynamic changes occurring at GOJ barrier during transient lower oesophageal sphincter relaxation (TLOSRs) and study the impact of gastric emptying after a meal on those events using combined high-resolution manometery and high-resolution impedance monitoring (HRMZ, ManoScan Z™). Methods HRMZ was performed in eight healthy subjects (6M and 2F, 27±7 years) for 4 h after a refluxogenic meal (1000 kcal). Pressure–flow dynamics of OGJ during TLOSR events including their frequency, duration, gastro-oesophageal pressure gradient (GO pressure gradient) and proximal extent of migration of the reflux episodes were computed. Gastric emptying of the meal was assessed by 13C-labelled octanoic acid breath test and gastric emptying lag time, half emptying time and gastric retention time were calculated. Results All subjects completed the study. During TLOSR events there was reciprocal relationship between GE pressure grad. and retrograde flow of gastric contents, the gradient was greatest at the onset of retrograde flow, decreasing progressively as the flow continued and became lowest by the end of flow across the OGJ (GO pressure gradient start of flow=9.5±2.6, peak flow=6.05±2.5 (p= Conclusion Our results suggest HRMZ is effective in elucidating the pressure-flow dynamics of OGJ. The proximal extent of the reflux episode correlates with gastric retention time of the meal; however other gastric emptying parameters did not show significant correlation despite promising trends. Further studies involving GORD patients might give us important insights into the role of OGJ pressure flow dynamics in the pathophysiology of GORD.

T1883 Upper Esophageal Sphincter Relaxation as a Determinant of Reflux and Symptoms During Transient Lower Esophageal Sphincter Relaxation (TLESR)?

T1883 Upper Esophageal Sphincter Relaxation as a Determinant of Reflux and Symptoms During Transient Lower Esophageal Sphincter Relaxation (TLESR)?

T1687 The Effect of Salivary Nitrite on Gastro-Esophageal Reflux

Introduction Human saliva has a high nitrite concentration from the entero-salivary recirculation of dietary nitrate. Swallowed nitrite reacts with gastric acid to form nitric oxide (NO) at the gastro-oesophageal junction. This may contribute to the pathogenesis of reflux disease. NO has been shown to reduce lower oesophageal sphincter (LOS) pressure, impair oesophageal clearance and may be the final mediator in the production of transient lower oesophageal sphincter relaxations (TLOSRs). Aims To determine (1) whether nitrite in saliva increases oesophageal acid exposure and (2) whether nitrite in swallowed saliva modifies the manometric characteristics of the LOS and distal oesophagus. Methods 20 asymptomatic subjects (11 males) were studied. Each underwent endoscopy to document normal anatomy. On four separate days, high-resolution manometry and pH were performed during 15 min fasting and for 90 min following a standardised meal. Postprandially, solutions containing 0, 0.286, 2 and 14 mmol/l potassium nitrite were infused into the oral cavity. Solutions were randomised and double-blinded. Saliva was collected at baseline, 30, 60 and 90 min following the meal. Nitrite concentrations were quantified by Griess reaction. Acid exposure was calculated as per cent time pH Results Salivary nitrite concentrations at 60 min were 24.35 μmol/l (3.86–65.46), 80.42 μmol/l (20.88–158.79), 358.4 μmol/l (118.2–726.6) and 2694 μmol/l (600–8087) for the solutions containing 0, 0.286, 2 and 14 mmol/l nitrite, respectively. There was no difference in acid exposure between the control and the nitrite-containing solutions (p>0.04). There was no difference in the number (p>0.05), duration (p>0.4) or nadir pH (p>0.2) of reflux events. The mean number of TLOSRs and the reduction in postprandial LOS pressure were similar (p>0.04 and p>0.07). There was no difference in peristaltic wave velocity or amplitude (p>0.1 and p>0.6). Conclusion Despite an excellent range of salivary nitrite concentrations, over and beyond the normal physiological range, no difference in oesophageal acid exposure or oesophageal motility was seen between the control solution and those containing nitrite. These findings suggest that salivary nitrite does not potentiate oesophageal reflux.

Beyond Acid Suppression: New Pharmacologic Approaches for Treatment of GERD

Proton pump inhibitors are highly successful in treating gastroesophageal reflux disease, but a significant proportion of patients have persistent symptoms from weakly or nonacidic reflux. Transient lower esophageal sphincter relaxation (TLESR) represents the dominant mechanism of gastroesophageal reflux and has therefore become the most intensely investigated therapeutic target. The triggering of TLESR involve the vagal pathways and the gamma-aminobutyric type B (GABA(B)) and metabotropic glutamate type 5 (mGluR5) receptors. Baclofen is a GABA(B) receptor agonist that is effective in inhibiting TLESR and reducing the number of reflux episodes, but is associated with significant central nervous system (CNS) side effects. The newer GABA(B) agonists, such as AZD9343 and AZD3355, and mGluR5 antagonists, such as 2-methyl-6-(phenylethynyl)-pyridine (MPEP), have been shown in small, randomized, controlled trials to have comparable efficacy to baclofen, but possibly a more favorable CNS side effect profile. Cannibinoid agonists, such as Delta(9)-THC, have also been demonstrated to reduce TLESRs and reflux events respectively. Macrolide antibiotics (eg, erythromycin) show early promise in a select group of patients with possible reflux associated post-lung transplant problems.

The role of excessive esophageal acid exposure in patients with gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD), especially reflux esophagitis (RE), is characterized by excessive esophageal acid exposure. Transient lower esophageal sphincter (LES) relaxation is the major mechanism of acid reflux episodes in both healthy subjects (HS) and patients with GERD. In the sitting position, where acid reflux episodes often occur, there is no difference in the frequency of transient LES relaxations between these two groups; however, in patients with GERD, at 5cm above the LES, the proportion of acid reflux episodes during transient LES relaxations is significantly greater than in the HS group. This difference is considered to be one of the causes of excessive esophageal acid exposure in patients with GERD, but its cause is still unclear. A recent study, which investigated the proportion of acid reflux episodes during transient LES relaxations at 2 and 7cm above the LES, showed that there was no difference at 2cm above the LES between HS and patients with RE, but at 7cm they were significantly greater in patients with RE than in HS. Evaluation of acid reflux at 2cm above the LES is difficult to measure, but the proximal extent of refluxate could be one of the important factors of excessive acid esophageal exposure in patients with RE. Ineffective esophageal motility, found in patients with moderate to severe RE, impairs esophageal bolus clearance of acid, therefore both the proximal extent of refluxate and the delay of esophageal bolus clearance of acid could be major causes of excessive esophageal acid exposure. Hiatus hernia also causes acid reflux, due to its association with hypotensive LES, and also impairs esophageal bolus clearance of acid.

M1882 Response to Air Insufflation in Patients with Non-Erosive Gastroesophageal Reflux Disease (NERD) - Including Assessment Under a Rabeprazole Load

Gastro-esophageal reflux disease (GERD) is a multifactorial condition whose main pathogenetic factor is represented by Transient Lower Esophageal Sphincter Relaxations (TLESRs). Many hypotheses have been proposed to identify the mechanisms underlying the onset of TLESRs. One evidence suggested that colonic fermentation of indigestible carbohydrates (fructooligosaccharides, FOS) increases the rate of TLESRs and the number of acid reflux episodes. Alpha-galactosidase is an enzyme allowing better digestion of food rich in FOS that is commonly used to control symptoms of patients affected by Irritable Bowel Sindrome. Aim of our study was therefore to test the possible effect of the assumption of alphagalactosidase on esophageal pH profile in GERD patients. Patients and methods: 9 patients with low-grade esophagitis and typical GI symptoms underwent a basal 24-hour esophageal pH-metric recording. Once confirmed the GERD diagnosis, patients were instructed to assume 1 tablet of alpha-galactosidase 300 GalU (n=5) or placebo (n=4) before meals for the following four weeks. At the end of treatment a second 24-h esophageal pH-metry was performed. Heartburn and regurgitation were also scored (score: intensity x duration) at baseline and after 4 weeks. Results: Patients receiving alpha-galactosidase showed a reduced number of acid reflux episodes/24 hours as compared to baseline (60±25 vs 118±40, p<0.01); percentage of time with pH<4 was also reduced in such patients as compared to baseline values (4.2±1.7 vs 6.7±2.7, p<0.05); no difference was detected in the group receiving placebo. Heartburn was reduced in patients assuming alpha-galactosidase as compared to baseline (1.2±0.4 vs 2±0.6, p<0.05) with no differences in the placebo group. Regurgitation showed a trend toward a decrease after alpha-galactosidase which did not reach statistical significance (1.2±0.4 vs 1.5±0.3, n.s.). Summary and Conclusions: chronic assumption of alpha-galactosidase is associated to a decreased amount of gastro-esophageal reflux episodes in GERD patients. Such patients also experienced an initial improvement in clinical features of the disease. It seems likely that this change in esophageal pH pattern could depend on the modulation of TLESRs due to the reduced fermentation of FOS in the colon.