André Smout

The acid pocket: a target for treatment in reflux disease?

The nadir esophageal pH of reflux observed during pH monitoring in the postprandial period is often more acidic than the concomitant intragastric pH. This paradox prompted the discovery of the “acid pocket”, an area of unbuffered gastric acid that accumulates in the proximal stomach after meals and serves as the reservoir for acid reflux in healthy individuals and gastroesophageal reflux disease (GERD) patients. However, there are differentiating features between these populations in the size and position of the acid pocket, with GERD patients predisposed to upward migration of the proximal margin onto the esophageal mucosa, particularly when supine. This upward migration of acid, sometimes referred to as an “acid film”, likely contributes to mucosal pathology in the region of the squamocolumnar junction. Furthermore, movement of the acid pocket itself to a supradiaphragmatic location with hiatus hernia increases the propensity for acid reflux by all conventional mechanisms. Consequently, the acid pocket is an attractive target for GERD therapy. It may be targeted in a global way with proton pump inhibitors that attenuate acid pocket development, or with alginate/antacid combinations that colocalize with the acid pocket and displace it distally, thereby demonstrating the potential for selective targeting of the acid pocket in GERD.

Long-term Outcomes of Patients Receiving a Magnetic Sphincter Augmentation Device for Gastroesophageal Reflux

BACKGROUND & AIMSnBased on results from year 2 of a 5-year trial, in 2012 the US Food and Drug Administration approved the use of a magnetic device to augment lower esophageal sphincter function in patients with gastroesophageal reflux disease (GERD). We report the final results of 5 years of follow-up evaluation of patients who received this device.nnnMETHODSnWe performed a prospective study of the safety and efficacy of a magnetic device in 100 adults with GERD for 6 months or more, who were partially responsive to daily proton pump inhibitors (PPIs) and had evidence of pathologic esophageal acid exposure, at 14 centers in the United States and The Netherlands. The magnetic device was placed using standard laparoscopic tools and techniques. Eighty-five subjects were followed up for 5 years to evaluate quality of life, reflux control, use of PPIs, and side effects. The GERD-health-related quality of life (GERD-HRQL) questionnaire was administered at baseline to patients on and off PPIs, and after placement of the device; patients served as their own controls. A partial response to PPIs was defined as a GERD-HRQL score of 10 or less on PPIs and a score of 15 or higher off PPIs, or a 6-point or more improvement when scores on vs off PPI were compared.nnnRESULTSnOver the follow-up period, no device erosions, migrations, or malfunctions occurred. At baseline, the median GERD-HRQL scores were 27 in patients not taking PPIs and 11 in patients on PPIs; 5 years after device placement this score decreased to 4. All patients used PPIs at baseline; this value decreased to 15.3% at 5 years. Moderate or severe regurgitation occurred in 57% of subjects at baseline, but only 1.2% at 5 years. All patients reported the ability to belch and vomit if needed. Bothersome dysphagia was present in 5% at baseline and in 6% at 5 years. Bothersome gas-bloat was present in 52% at baseline and decreased to 8.3% at 5 years.nnnCONCLUSIONSnAugmentation of the lower esophageal sphincter with a magnetic device provides significant and sustained control of reflux, with minimal side effects or complications. No new safety risks emerged over a 5-year follow-up period. These findings validate the long-term safety and efficacy of the magnetic sphincter augmentation device for patients with GERD. ClinicalTrials.gov no: NCT00776997.

Weight loss after laparoscopic adjustable gastric banding is not caused by altered gastric emptying.

BackgroundIn order to know the role of gastric emptying in the mechanism of weight loss and early satiety after a restrictive surgical procedure for treatment of morbid obesity, a consecutive series of patients were scintigraphically investigated before and after laparoscopic adjustable gastric banding.MethodsSixteen patients undergoing laparoscopic adjustable gastric banding underwent preoperatively, and at 6xa0months postoperatively, a gastric emptying study (solid meal and single isotope). Esophageal retention time, lag phase, peak activity time, gastric emptying rate, fundus emptying rate, and weight loss were recorded. Upper GI symptom assessment was carried out by using a standardized questionnaire. Gastric emptying parameters were correlated with the upper GI symptoms.ResultsGastric band placement showed no significant influence on postoperative gastric emptying rate [median % (interquartile range): 42 (23.3–59) preoperatively vs 38 (31–71) postoperatively and fundus emptying rate: 59(37–91) preoperatively vs 70 (53–89) postoperatively]; however, an increase in early satiety was found. Neither gastric emptying rate nor fundus emptying rate showed a relation with early satiety or weight loss. Furthermore, no correlation was found between early satiety and lag phase, esophageal retention time, start of activity, and peak activity time in proximal stomach.ConclusionLaparoscopic adjustable gastric banding seems not to affect gastric emptying. Neither a relation between postoperative gastric emptying rate and weight loss nor between early satiety and weight loss was found. Therefore, it is unlikely that gastric emptying plays a role in the mechanism of weight loss following laparoscopic adjustable gastric banding.

Acid and non-acid reflux patterns in patients with erosive esophagitis and non-erosive reflux disease (NERD): A study using intraluminal impedance monitoring

Background Non-erosive reflux disease (NERD) and erosive esophagitis (EE) are the most common phenotypic presentations of gastroesophageal reflux disease (GERD). Aim To assess acid and non-acid reflux patterns in patients with EE and NERD using combined esophageal pH-impedance monitoring. Methods A total of 26 GERD patients off acid-suppressive medication and ten healthy volunteers (HV) underwent upper endoscopy and 24-h pH-impedance monitoring. Analysis of the pH-impedance signals included total reflux time, number of reflux episodes according to gas–liquid composition, and pH (acid, non-acid). Results EE was identified in 13 patients and NERD in 13 patients. Pathologic acid reflux was found in 92.3 and 69.2% of patients with EE and NERD, respectively (Pxa0=xa00.15). When compared to HV, EE patients and NERD patients showed a higher incidence of acid (Pxa0=xa00.002 and Pxa0<xa00.001, EE vs. HV and NERD vs. HV, respectively) and non-acid reflux episodes (Pxa0=xa00.03 and Pxa0=xa00.001, EE vs. HV and NERD vs. HV, respectively). Mean reflux times, as assessed by both pH-metry and impedance monitoring, and incidence of acid and non-acid reflux episodes were similar in EE and NERD patients. In the supine position, however, EE patients showed a higher incidence of acid (Pxa0=xa00.048) and liquid reflux episodes (Pxa0=xa00.07). Conclusion Whereas EE patients have more acid reflux episodes in the supine position than NERD patients, patients with EE and NERD have similar non-acid reflux patterns. This observation lends support to the notion that non-acid reflux is less damaging to the esophageal mucosa than acid reflux.

Effect of laparoscopic gastric banding on esophageal motility

Background: Alterations in esophageal motility may occur after placement of an adjustable gastric band as treatment for morbid obesity, near the gastro-esophageal junction. It causes an outlet obstruction, especially during follow-up after the band is filled. Methods: 29 morbidly obese patients underwent conventional manometry preoperatively, 6 weeks postoperatively before and after filling the band and at 6 months postoperatively. A questionnaire was used to assess upper gastrointestinal symptoms during follow-up. Results: After band placement, there was a significant increase in lower esophageal sphincter (LES) end-expiratory pressure at 6 weeks with an empty band: 1.3 (0.9-1.9) kPa (median (interquartile range) (P=0.003), 6 weeks with a filled band: 2.1 (1.5-2.8) kPa (P=0.0001), and at 6 months: 1.5 (1.3-1.9) kPa (P=0.001), compared to the preoperative pressure: 0.8 (0.6-1.3) kPa. Also after band placement, the high pressure zone length increased (preop 5.0 (4.3-6.0) cm vs 6 weeks 6.0 (5.0-6.5) cm (P=0.003). The propagation of peristaltic contractions was not significantly altered after band placement. Heartburn decreased 6 weeks postoperatively (P=0.04) but increased at 6 months. Heartburn at 6 months was correlated with pouch formation (0.667; P<0.01). Conclusion: Adjustable gastric band placement causes an increase in LES pressure and length of the high pressure zone. It decreases reflux symptoms in the short-term, but this effect appears not to be related to an effect on LES pressure or length. Pouch formation increases reflux symptoms without having any relationship to LES pressure and length. Band placement in the short-term does not disturb propagation of esophageal contractions.

Review article: Clinical relevance of transient lower esophageal sphincter relaxations (TLESR) in gastroesophageal reflux disease.

Aliment Pharmacol Ther 2011; 33: 650–661

Systematic review: questionnaires for assessment of gastroesophageal reflux disease.

Numerous questionnaires with a wide variety of characteristics have been developed for the assessment of gastroesophageal reflux disease (GERD). Four well-defined dimensions are noticeable in these GERD questionnaires, which are symptoms, response to treatment, diagnosis, and burden on the quality of life of GERD patients. The aim of this review is to develop a complete overview of all available questionnaires, categorized per dimension of the assessment of GERD. A systematic search of the literature up to January 2013 using the Pubmed database and the Embase database, and search of references and conference abstract books were conducted. A total number of 65 questionnaires were extracted and evaluated. Thirty-nine questionnaires were found applicable for the assessment of GERD symptoms, three of which are generic gastrointestinal questionnaires. For the assessment of response to treatment, 14 questionnaires were considered applicable. Seven questionnaires with diagnostic purposes were found. In the assessment of quality of life in GERD patients, 18 questionnaires were found and evaluated. Twenty questionnaires were found to be used for more than one assessment dimension, and eight questionnaires were found for GERD assessment in infants and/or children. A wide variety of GERD questionnaires is available, of which the majority is used for assessment of GERD symptoms. Questionnaires differ in aspects such as design, validation and translations. Also, numerous multidimensional questionnaires are available, of which the Reflux Disease Questionnaire is widely applicable. We provided an overview of GERD questionnaires to aid investigators and clinicians in their search for the most appropriate questionnaire for their specific purposes.

Modern diagnosis of GERD: the Lyon Consensus

Clinical history, questionnaire data and response to antisecretory therapy are insufficient to make a conclusive diagnosis of GERD in isolation, but are of value in determining need for further investigation. Conclusive evidence for reflux on oesophageal testing include advanced grade erosive oesophagitis (LA grades C and D), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal oesophageal acid exposure time (AET) >6% on ambulatory pH or pH-impedance monitoring. A normal endoscopy does not exclude GERD, but provides supportive evidence refuting GERD in conjunction with distal AET <4%u2009and <40u2009reflux episodes on pH-impedance monitoring off proton pump inhibitors. Reflux-symptom association on ambulatory reflux monitoring provides supportive evidence for reflux triggered symptoms, and may predict a better treatment outcome when present. When endoscopy and pH or pH-impedance monitoring are inconclusive, adjunctive evidence from biopsy findings (histopathology scores, dilated intercellular spaces), motor evaluation (hypotensive lower oesophageal sphincter, hiatus hernia and oesophageal body hypomotility on high-resolution manometry) and novel impedance metrics (baseline impedance, postreflux swallow-induced peristaltic wave index) can add confidence for a GERD diagnosis; however, diagnosis cannot be based on these findings alone. An assessment of anatomy, motor function, reflux burden and symptomatic phenotype will therefore help direct management. Future GERD management strategies should focus on defining individual patient phenotypes based on the level of refluxate exposure, mechanism of reflux, efficacy of clearance, underlying anatomy of the oesophagogastric junction and psychometrics defining symptomatic presentations.

Expert consensus document: Advances in the management of oesophageal motility disorders in the era of high-resolution manometry: a focus on achalasia syndromes

High-resolution manometry (HRM) and new analysis algorithms, summarized in the Chicago Classification, have led to a restructured classification of oesophageal motility disorders. This advance has led to increased detection of clinically relevant disorders, in particular achalasia. It has become apparent that the cardinal feature of achalasia — impaired lower oesophageal sphincter (LES) relaxation — can occur in several disease phenotypes: without peristalsis (type I), with pan-oesophageal pressurization (type II), with premature (spastic) distal oesophageal contractions (type III), or with preserved peristalsis (outlet obstruction). Furthermore, no manometric pattern is perfectly sensitive or specific for achalasia caused by a myenteric plexopathy, and there is no biomarker for this pathology. Consequently, physiological testing reveals other syndromes not meeting achalasia criteria that also benefit from therapies formerly reserved for achalasia. These findings have become particularly relevant with the development of a minimally invasive technique for performing a long oesophageal myotomy, the per-oral endoscopic myotomy (POEM). Optimal management is to render treatment in a phenotype-specific manner; that is, POEM calibrated to patient-specific physiology for spastic achalasia and the spastic disorders, and more conservative strategies such as pneumatic dilation for the disorders limited to the LES. This Consensus Statement examines the effect of HRM on our understanding of oesophageal motility disorders, with a focus on the diagnosis, epidemiology and management of achalasia and achalasia-like syndromes.

Esophageal dilation after laparoscopic adjustable gastric banding: a more systematic approach is needed

BackgroundThe occurrence of esophageal dilation after laparoscopic adjustable silicone gastric banding (LASGB) had not been yet investigated systematically.MethodsIn this study, standardized barium swallow studies were used to assess 45 LASGB patients for the development of esophageal dilation after the operation and after a mean follow-up period of 39.3xa0months. The diameter of the esophagus postoperatively and during the follow-up period was calculated in millimeters using the known diameter of the gastric band. An increase in diameter exceeding 130% compared with the postoperative diameter was considered as dilation. Symptoms were assessed by a questionnaire. For 11 patients with dilation, the band was emptied and a barium swallow performed to assess whether the dilation was reversible.ResultsA significant increase in the esophageal diameter (median and interquartile range [IQR]) was found by comparing the early postoperative and follow-up data: median, 16.3xa0mm (IQR, 14–18.7xa0mm) versus median, 20.7xa0mm (IQR, 18.1–26.8xa0mm; pxa0<xa00.01). For 25 (55.6%) of the 45 patients, the dilation percentage exceeded 130%. For 7 of the 11 patients, the dilation after emptying of the band still exceeded 130%. The increase in esophageal diameter was significantly correlated with the duration of follow-up evaluation, regurgitation, heartburn at night, and slow esophageal clearance.ConclusionLaparoscopic adjustable gastric banding causes esophageal dilation in about half of patients. This dilation is correlated with symptoms and is partly reversible after emptying of the band. The clinical relevance of the dilation is unclear.