A comparative study on the raft chemical properties of various alginate antacid raft-forming products.

OBJECTIVE: Research to measure the chemical characterization of alginate rafts for good raft performance and ascertain how formulation can affect chemical parameters. SIGNIFICANCE: A selection of alginate formulations was investigated all claiming to be proficient raft formers with significance between products established and ranked. METHODS: Procedures were selected which demonstrated the chemical characterization allowing rafts to effectively impede the reflux into the esophagus or in severe cases to be refluxed preferentially into the esophagus and exert a demulcent effect, with focus of current research on methods which complement previous studies centered on physical properties. The alginate content was analyzed by a newly developed HPLC method. Methods were used to determine the neutralization profile and the acid neutralization within the raft determined along with how raft structure affects neutralization. RESULTS: Alginate content of Gaviscon Double Action (GDA) within the raft was significantly superior (p < .0001) to all competitor products. The two products with the highest raft acid neutralization capacity were GDA and Rennie Duo, the latter product not being a raft former. Raft structure was key and GDA had the right level of porosity to allow for longer duration of neutralization. CONCLUSION: Alginate formulations require three chemical reactions to take place simultaneously: transformation to alginic acid, sodium carbonate reacting to form carbon dioxide, calcium releasing free calcium ions to bind with alginic acid providing strength to raft formation. GDA was significantly superior (p <.0001) to all other comparators.

Effect of baclofen on gastric acid pocket in subjects with gastroesophageal reflux disease symptoms.

Postprandial gastroesophageal reflux (PGER) in the distal esophagus (DE) is associated with a gastric juice 'acid pocket' (AP). Baclofen reduces AP extension into the DE in healthy volunteers, in part through increased lower esophageal sphincter (LES) pressure. We aimed to verify whether baclofen also affects postprandial AP location and extent in gastroesophageal reflux disease (GERD) patients. Thirteen treatment-naive heartburn-prevalent GERD patients underwent two AP studies, after pretreatment with baclofen 40 mg or placebo 30 minutes preprandially. We performed pH-probe stepwise pull-throughs (PT) (1 cm/min, LES -10 to +5 cm) before and every 30 minutes from 30 minutes before up to 150 minutes after a test meal. After the meal, both after placebo and baclofen, gastric pH significantly dropped at 30, 60, 90 minutes postprandially (P: nadir pHs of 3.9 ± 0.6, 2.3 ± 0.6, 2.1 ± 0.4; B: nadir pHs of 2.5 ± 0.4, 2.8 ± 0.4, 2.5 ± 0.3; all P < 0.05). After placebo, LES pressure decreased at 60, 90 and 120 minutes postprandially (32.7 ± 6.1 vs. 24.5 ± 3.1, 27.3 ± 5.9, 27.3 ± 6.0 mmHg; analysis of variance [ANOVA], P = 0.037), but this was prevented by baclofen (25.4 ± 3.4 vs. 29.4 ± 2, 32.2 ± 1.4, 35.5 ± 1.7 mmHg, ANOVA, P = not significant (NS)). Baclofen did not significantly decrease the postprandial AP extent above the LES but prevented the postprandial increase in transient lower esophageal sphincter relaxations (TLESRs) (preprandial vs. postprandial, placebo: 1.1 ± 0.3 vs. 3.7 ± 0.7, P < 0.05; baclofen: 1.4 ± 0.4 vs. 2 ± 0.5, P = NS). In GERD patients, baclofen significantly increases postprandial LES pressure, prevents the increase TLESRs but, unlike in healthy volunteers, does not affect AP extension into the DE.

Effect of baclofen on the acid pocket at the gastroesophageal junction.

Previous studies established that a pocket of highly acidic gastric juice is present postprandially at the gastroesophageal junction in man. The GABA-B agonist baclofen inhibits postprandial reflux events through its effects on the lower esophageal sphincter (LES). The aim of the current study was to investigate whether baclofen would affect the location and the extent of the postprandial acid pocket in healthy volunteers. Twelve healthy volunteers underwent acid pocket studies on two different occasions, at least 1 week apart. LES position was determined preprandially with pull-through manometry. Dual pH electrode and manometry probe stepwise pull-through (1 cm/minute, LES-10 to +5 cm) was performed at 30-minute intervals for 150 minutes, with administration of placebo or baclofen 40 mg after the first and ingestion of a liquid meal after the second pull-through. After placebo, a significant drop in intragastric gastric pH was present at the gastroesophageal junction after the meal, reflecting the acid pocket, and this was associated with a drop in LES pressure. Baclofen did not affect the presence of the acid pocket, but prevented the postprandial drop in LES pressure, and the extent of the acid pocket above the upper margin of the manometrically located LES was significantly decreased by baclofen (1.6 ± 0.7 vs. 0.3 ± 0.4 cm at 60 minutes, 2.2 ± 0.6 vs. 0.2 ± 0.6 at 90 minutes, and 1.5 ± 0.5 vs. 0.7 ± 0.7 cm at 120 minutes, all P < 0.05). Baclofen does not alter the intragastric acid pocket, but limits its extension into the distal esophagus, probably through an increase in postprandial LES pressure.

[Some issues of the diagnosis and treatment of gastroesophageal reflux disease]. / Nekotorye voprosy diagnostiki i lecheniia gastroézofageal'noi refliuksnoi bolezni.

The clinical inefficacy of proton pump inhibitors (PPIs) is very frequently encountered in nonerosive gastroesophageal reflux disease (NERD) in particular. Postprandial acid pocket, weak-acid or alkaline reflux, etc. are one of the causes of resistance to antisecretory drugs. Alginates serve as a good alternative to PPIs in treating NERD and gastroesophageal reflux in children and pregnant women. The alginate test may help diagnose NERD.

[Update on gastroesophageal reflux disease]. / Puesta al día en el reflujo gastroesofágico.

Gastroesophageal reflux disease is a highly frequent disorder classically characterized by the presence of heartburn and/or acid regurgitation that improves with drug therapy that reduces acid content in the stomach. However, especially in patients with non-erosive disease, response to proton pump inhibitors is unsatisfactory in approximately 1 out of 3 patients, and consequently, in these patients, it is important to establish a definitive diagnosis and an alternative therapeutic strategy. In the last few years, advances have been made in knowledge of the physiopathology of reflux, such as identification of the role of the acid pocket in producing reflux, technological advances that allow differentiation among acid reflux, non-acid reflux and slightly acid reflux, and advances in the treatment of reflux with drugs that attempt to act on the barrier function of the esophagogastric junction.

Postprandial proximal gastric acid pocket and its association with gastroesophageal acid reflux in patients with short-segment Barrett's esophagus.

OBJECTIVE: To determine the characteristics of postprandial proximal gastric acid pockets (PPGAPs) and their association with gastroesophageal acid reflux in patients with Barrett's esophagus (BE). METHODS: Fifteen patients with BE (defined by columnar lined esophagus of ≥1 cm) and 15 healthy individuals that were matched for age, gender, and body mass index, were recruited. The fasting intragastric pH and the appearance time, length, lowest pH, and mean pH of the PPGAP were determined using a single pH electrode pull-through experiment. For BE patients, a gastroesophageal reflux disease questionnaire (GerdQ) was completed and esophageal 24-h pH monitoring was carried out. RESULTS: The PPGAP was significantly longer (5 (3, 5) cm vs. 2 (1, 2) cm) and the lowest pH (1.1 (0.8, 1.5) vs. 1.6 (1.4, 1.9)) was significantly lower in patients with short-segment BE than in healthy individuals. The PPGAP started to appear proximally from the gastroesophageal pH step-up point to the esophageal lumen. The acidity of the PPGAP was higher in the distal segment than in the proximal segment. In short-segment BE patients, there were significant correlations between the acidity and the appearance time and length of the PPGAP. The length and acidity of the PPGAP were positively associated with gastroesophageal acid reflux episodes. The acidity of the PPGAP was associated with the DeMeester scores, the GerdQ scores, and the fasting intragastric pH. CONCLUSIONS: In patients with short-segment BE, a PPGAP is commonly seen. Its length and acidity of PPGAP are associated with gastroesophageal acid reflux, the DeMeester score, and the GerdQ score in patients with short-segment BE.

24-hour multi-pH recording of the postprandial acid pocket and the nocturnal acid distribution at the esophagogastric junction in healthy volunteers.

BACKGROUND: Postprandial stationary pH monitoring studies have identified the acid pocket. To what extent a similar pool of acid is present in the fasting state or at night remains however unclear. METHODS: The study was performed in 9 HV without a hiatal hernia. A pH-impedance-pressure catheter was positioned at the Z-line. First, the presence of the acid pocket was monitored under stationary conditions during 2 hours after ingestion of a standardized meal. Thereafter, the equipment was connected to an ambulatory monitoring device for 24-hour recording. RESULTS: Under stationary conditions, a postprandial acid pocket was present in 7 of the 9 HV, from 9 ± 7 minutes after meal onwards during 47 ± 8 minutes. During ambulatory 24-hour monitoring, postprandial acid pockets emerged significantly later, but no differences in duration or position were detected. During nighttime, an acid pool was detected with its proximal border at the level of the cardia, which at later, time points gradually moved to a more distal position. This led to a gradual decrease in nocturnal acid exposure from proximal to distal, a phenomenon that was preceded by a bust of gastric contractions. Nocturnal reflux originated from the cardiac region, and was more acidic in the early compared with late nocturnal period. CONCLUSION: The acid pocket is present in the postprandial period under both stationary and ambulatory conditions. Of interest, at night, a pool of acid can be demonstrated which is periodically shifted more distally. This pool of acid represents the reservoir from which nocturnal reflux originates.

Medical Therapy of Gastroesophageal Reflux Disease Beyond Proton Pump Inhibitors: Where Are We Heading?

Proton pump inhibitors (PPI) have greatly improved the treatment of gastroesophageal reflux disease. However, recent investigations have revealed that reflux symptoms persist in a substantial number of patients. Therefore, treatment strategies beyond PPI are urgently required. One such strategy may involve more reliable acid suppression, e.g., with new acid inhibitory drugs. Furthermore, the rapid appearance of an acidic compartment in the proximal stomach after a meal, which is largely responsible for postprandial heartburn, requires a specific kind of therapy in addition to PPI which still needs to be established. Pharmacological augmentation of the lower esophageal sphincter may represent another approach to diminish reflux, but the clinical efficacy of compounds tested so far is limited. Altered e-sophageal perception represents a major component involved in the generation of reflux symptoms, particularly in non-erosive reflux disease, but effective pharmacological intervention is largely lacking. Presumed reflux-induced respiratory symptoms (cough, laryngitis, etc.) in the absence of typical esophageal symptoms (e.g., heartburn) remain a hot topic, but recent research points towards a hypersensitivity syndrome and only a minor role of gastroesophageal reflux. Treatment options for this condition are still pending.

Mechanisms of Barrett's oesophagus (clinical): LOS dysfunction, hiatal hernia, peristaltic defects.

Barrett's oesophagus, with the potential to develop into oesophageal adenocarcinoma (OAC), is a major complication of gastrooesophageal reflux disease (GORD). However, about 50% of patients developing OAC had no known GORD beforehand. Hence, while GORD symptoms, oesophagitis, and Barrett's have a number of common determinants (oesophagogastric junction (OGJ) incompetence, impaired oesophageal clearance mechanisms, hiatus hernia) they also have some independent determinants. Further, although excess oesophageal acid exposure plays a major role in the genesis of long-segment Barrett's oesophagus there is minimal evidence supporting this for short-segment Barrett's. Hence, these may have unique pathophysiological features as well. Long-segment Barrett's seems to share most, if not all, of the risk factors for oesophagitis, particularly high-grade oesophagitis. However, it is uncertain if OGJ function and acid clearance are more severely impaired in patients with long-segment Barrett's compared to patients with high-grade oesophagitis. With respect to short-segment Barrett's, the acid pocket may play an important pathogenic role. Conceptually, extension of the acid pocket into the distal oesophagus, also known as intra-sphincteric reflux, provides a mechanism or acid exposure of the distal osophageal mucosa without the occurrence of discrete reflux events, which are more likely to prompt reflux symptoms and lead to the development of oesophagitis. Hence, intra-sphincteric reflux related to extension of the acid/no acid interface at the proximal margin of the acid pocket may be key in the development of short segment Barrett's. However, currently this is still somewhat speculative and further studies are required to confirm this.

Pathophysiology of gastroesophageal reflux disease.

The gastroesophageal junction is structurally complex and functionally designed to ensure the acid secreted by the most proximal gastric mucosa flows towards the stomach and not up onto the oesophageal squamous mucosa. The pattern and mechanism of reflux vary with the severity of reflux disease and this probably represents different ends of a spectrum rather than distinct pathophysiological mechanisms. Nearly all patients with severe reflux disease have hiatus hernia, however, a substantial proportion of patients with mild reflux disease do not, and this may be a result of intermittent or partial hiatus hernia undetectable by current available tools. The acid pocket is an area of post-prandial unbuffered gastric acidity immediately distal to the gastroesophageal junction and which is enlarged in patients with hiatus hernia. The acid pocket provides a reservoir of acid available to reflux when the intrinsic sphincter fails. Central obesity is an important factor in the aetiology of reflux and does this by the increased abdomino-thoracic pressure gradient inducing hiatus hernia and increasing the rate of flow of reflux when sphincter opens. Central obesity also induces short segment intrasphincteric reflux and thereby columnar metaplasia of the most distal oesophagus.

Varying marginal ulcer rates in patients undergoing laparoscopic Roux-en-Y gastric bypass for morbid obesity versus gastroesophageal reflux disease: is the acid pocket to blame?

BACKGROUND: Nissen fundoplication failure rates are increased in obese patients; however, conversion to laparoscopic Roux-en-Y gastric bypass (LRYGB) can resolve or improve gastroesophageal reflux disease (GERD) symptoms. Acid pockets near the gastroesophageal junction may influence these surgical outcomes. Our objective was to compare the outcomes for patients who underwent LRYGB for morbid obesity (MO) versus GERD. METHODS: A retrospective review of our institution's bariatric database was completed. Statistical analysis included t test and χ(2) test. RESULTS: LRYGBs were performed from 2001-2011 for MO and 2009-2010 for GERD. Eighty-three percent of patients in the GERD group had undergone previous antireflux surgery. The median time from initial presentation to LRYGB was significantly shorter in the GERD versus the MO group (105 days versus 241 days; P = .009). There was an increased rate of marginal ulcers in the GERD group compared with the MO group, at 50% versus 4.5%, respectively (P = .001). Stomal stenosis was also increased in the GERD group compared with the MO group, at 8.3% and .7%, respectively (P = .091). There were no in-hospital or 30-day mortalities. CONCLUSION: Patients undergoing LRYGB for GERD had a shorter interval to surgery and an increased rate of marginal ulcers compared with those undergoing LRYGB for MO. Operative time was longest among patients in the GERD group. The acid pocket may explain the increased ulcer rate in the GERD population. Use of a smaller sized pouch may improve this outcome.