Amine Hila

Arbaclofen placarbil decreases postprandial reflux in patients with gastroesophageal reflux disease.

OBJECTIVES:Arbaclofen placarbil (AP), previously designated as XP19986, is an investigational prodrug of the active R-isomer of baclofen, a γ-aminobutyric acid agonist reflux inhibitor. The aim of this study was to assess the efficacy and safety of AP for decreasing meal-induced reflux episodes in patients with gastroesophageal reflux disease (GERD).METHODS:We conducted a multicenter, randomized, double-blind, crossover study comparing single doses of AP with placebo. Different patients were enrolled at each of four escalating AP doses: 10, 20, 40, and 60 mg. Enrolled patients had GERD symptoms at least three times a week and 20 reflux episodes on impedance/pH monitoring over a period of 2 h. During study visits separated by periods of 3–7 days, patients received single doses of AP or placebo, followed by high-fat meals 2 and 6 h after treatment. The primary end point was the number of reflux episodes over 12 h after treatment.RESULTS:A total of 50 patients were treated; efficacy analysis included 44 patients who received both AP and placebo and had technically satisfactory impedance/pH data. For the combined data from all dose cohorts, there was a statistically significant (P=0.01) decrease in reflux episodes over 12 h after treatment with AP compared with placebo. The mean (s.d.) number of reflux episodes over 12 h after AP treatment was 50.5 (27.2), with a mean reduction of 10.4 (23.9) episodes (17%) compared with placebo, for which a mean (s.d.) number of 60.9 (35.3) episodes was observed. Heartburn events associated with reflux were reduced during treatment with AP compared with placebo. AP seemed to be the most efficacious in the 60-mg dose group, and was well tolerated at all dose levels.CONCLUSIONS:AP decreased reflux and associated symptoms with good tolerability in patients with GERD.

Pharyngeal and Upper Esophageal Sphincter Manometry in the Evaluation of Dysphagia

The use of esophageal manometry seems to be increasing, but the utility of pharyngeal and upper esophageal sphincter (UES) manometry is not widely recognized. This article is intended to clarify this subject. Initially, we review the anatomy and physiology of this area. Most studies indicate that the manometry of the UES and pharynx provides useful information primarily in patients that have symptoms of oropharyngeal dysfunction. Oropharyngeal dysphagia has high morbidity, mortality, and cost. It occurs in one third of all stroke patients and is common in the chronic care setting; up to 60% of nursing home occupants have feeding difficulties, of whom a substantial portion have dysphagia. For patients with oropharyngeal dysphagia, as for those with esophageal dysphagia, barium swallow study and manometry are complimentary. Their combined use permits us to enhance the understanding of the pathophysiologic process that causes the patient’s symptoms. Abnormalities have been noted in a variety of diseases, such as Parkinson’s disease, oculopharyngeal muscular dystrophy, achalasia, and scleroderma. Thus, it is possible to determine the primary pathology that is causing the patient’s dysphagia by analyzing the manometry results. Pharyngeal and UES manometry also has a value in evaluating patients who are candidates for myotomy or dilatation, as it can help identify patients with a prospective good outcome.

Clinical relevance of the nutcracker esophagus: suggested revision of criteria for diagnosis.

Background Nutcracker esophagus (NE) is a manometric finding defined by peristaltic contractions with a mean distal esophageal amplitude (DEA) >180 mm Hg. This threshold has been selected as it exceeds the average DEA in healthy volunteers by 2 SDs. Since its introduction the clinical significance of this finding has been challenged, as many patients with NE are asymptomatic. Aim To evaluate whether defining NE based on a different DEA threshold would be clinically more meaningful. Methods Retrospective review of prospectively collected manometry data between October 2001 and December 2003. Using previously published normal DEA values (mean and SD) patients with NE were stratified into 3 groups: group A (2 to 3 SD above mean): DEA 180 to 220 mm Hg; group B (3 to 4 SD above mean): DEA 220 to 260 mm Hg; and group C (>4 SD above mean): DEA >260 mm Hg. Symptoms, esophageal acid exposure, bolus transit data, and lower esophageal sphincter data were reviewed. Results The stratification of 56 NE patients into groups A, B, and C were 31, 16, and 9, respectively. The proportion of patients presenting with chest pain increased from 23% in group A to 69% in group B and 100% in group C. Patients in group C had significantly (P<0.05) higher mean lower esophageal sphincter pressure, shorter bolus transit time, and lower frequency of abnormal reflux. Conclusions A revised definition of NE to include patients with a DEA >260 mm Hg, and possibly those with >220 may have greater clinical relevance.

Fundoplication eliminates chronic cough due to non-acid reflux identified by impedance pH monitoring

The symptoms of extra-oesophageal gastro-oesophageal reflux disease (GORD) (such as chronic cough and hoarseness) are traditionally more difficult to treat than typical GORD symptoms (heartburn and regurgitation). Patients with extra-oesophageal manifestations may require longer and higher doses of acid suppressive therapy. In patients not responding to acid suppressive therapy the physician faces a dilemma as to whether the symptoms are due to ongoing acid reflux, non-acid reflux, or not associated with reflux. We report the case of a 45 year old woman with a history of a chronic cough referred for fundoplication after documenting her symptoms were associated with non-acid reflux using multichannel intraluminal impedance and pH (MII-pH).

Nighttime reflux is primarily an early event.

Goals: Our clinical impression gleaned from reading large numbers of ambulatory pH studies is that recumbent reflux episodes mostly occur in the early part of the nighttime period. In this study, we propose to test this hypothesis. Study: A total of 201 consecutive pH studies performed in our laboratory between November 2001 and October 2002 were analyzed. Population characteristics: 75 males and 126 females; mean age, 50.4 yrs (range, 16-88 years). Reflux was defined by a drop in pH to less than 4. Abnormal total recumbent reflux was defined as >1.2% time pH < 4. For patients with abnormal recumbent reflux, the recumbent period was divided into two halves and the reflux time in each period was calculated. In all patients, ingestion of a meal within 2 hours of retiring was also identified. Results: A total of 59 patients had abnormal recumbent reflux: 24 males and 35 females; mean age, 48.9 years. In patients with abnormal recumbent reflux, acid reflux was significantly more frequent in the first half of the recumbent period compared with the second half (median, 6.3%; vs. 0.3%, respectively; P < 0.001; Wilcoxon signed rank test, two-tailed analysis). Those patients (N = 118) having had a meal within 2 hours of retiring were 2.46 times more likely to develop recumbent reflux than those whose last meal was more than 2 hours earlier (N = 83). Conclusion: These results support our hypothesis that nighttime reflux occurs primarily during the first half of the recumbent period. In addition, they reinforce the concept of maintaining control of early nighttime reflux and the importance of counseling patients with nocturnal symptoms against late meals and snacks.

Bethanechol improves smooth muscle function in patients with severe ineffective esophageal motility

Background There is no therapeutic intervention that reliably restores smooth muscle contractility for patients with ineffective esophageal motility (IEM). Bethanechol, a direct-acting muscarinic receptor agonist, has been shown in healthy volunteers to produce a significant increase in peristaltic amplitude in the distal esophagus. Aim To identify whether bethanechol improves smooth muscle contractility and bolus transit in patients with IEM. Methods Seven patients diagnosed with severe IEM documented by combined multichannel intraluminal impedance and esophageal manometry were asked to participate. IEM was defined by using the new proposed criteria of greater than or equal to 50% saline swallows with contraction amplitude <30 mm Hg either 5 and/or 10 cm above the lower esophageal sphincter (LES). In the supine position, the patients were given 10 swallows of 5 mL of normal saline then 10 swallows of viscous solution, each 20 to 30 seconds apart. Patients were then given 50 mg oral bethanechol. After 20 and 40 minutes, 5 swallows of saline and viscous solution were repeated. Studies were then analyzed by an investigator blinded to the relationship of bethanechol administration to the swallows. The analysis included measurement of distal esophageal amplitude (DEA) or the mean amplitude at 5 and 10 cm above the LES. Results The use of bethanechol significantly increased (P<0.05) the esophageal contraction pressures at 5 and 10 cm above the LES. The DEA increased (P<0.05) for liquid and viscous, 20 minutes after its administration. Forty minutes after bethanechol administration, DEA and also individual pressures at 5 and 10 cm above the LES were still increased (P<0.05) for liquid, but only the DEA increased (P<0.05) with viscous solution. There was also a significant increase in complete bolus transit for saline swallows, both 20 and 40 minutes (P=0.03 and 0.01, respectively) after bethanechol. Conclusions Oral bethanechol significantly improves contraction pressures and bolus transit in the smooth muscle portion of the esophagus in patients with severe IEM.

Revised criterion for diagnosis of ineffective esophageal motility is associated with more frequent dysphagia and greater bolus transit abnormalities

BACKGROUND:Ineffective esophageal motility (IEM) has been defined by the presence of ≥30% liquid swallows with contraction amplitude <30 mmHg (ineffective swallows) in the distal esophagus (“old” IEM). A recent study with combined multichannel intraluminal impedance and manometry (MII-EM) raised the question whether the manometric diagnosis of IEM should be based on a new definition: ≥50% ineffective liquid swallows (“new” IEM). The aim of this study was to evaluate the association between the number of ineffective liquid swallows and symptoms and bolus transit in patients with “new” or “old” IEM who underwent MII-EM studies using 10 liquid and 10 viscous swallows.MATERIALS AND METHODS:There were 150 patients with “old” IEM included in the study. The patients diagnosed with “old” IEM (N = 150) (group A) were compared with those who retained a manometric diagnosis of IEM by the new definition (N = 101) (group B). The patients who did not retain their manometric diagnosis of IEM by the new definition (N = 49) (group C) were compared with group B. IEM was characterized as mild (normal bolus transit for both liquid and viscous swallows), moderate (abnormal bolus transit either for liquid or viscous swallows), or severe (abnormal bolus transit for both liquid and viscous swallows).RESULTS:There was no statistical difference in frequency of mild, moderate, or severe IEM and frequency of symptoms between group A and B. Group C had a significantly higher frequency of mild IEM and significantly lower frequency of severe IEM than group B. Heartburn (25.7% vs 10.2%, P = 0.03) and dysphagia (24.8% vs 12.3%, P = 0.08) showed a trend towards a greater frequency in group B than in group C.CONCLUSION:Our study indicates that IEM with ≥50% ineffective liquid swallows is frequently associated with bolus transit abnormalities and esophageal symptoms. Our results underscore the rationale for using the new definition of IEM.

Postprandial stomach contents have multiple acid layers.

Goals The purpose of this study was to evaluate patterns in gastric pH both fasting and postprandially in different body positions. Study Ten healthy volunteers were studied. A pH probe was positioned with an electrode 15 cm below the lower esophageal sphincter proximal border then withdrawn 1 cm every 30 seconds to 5 cm above the lower esophageal sphincter. Volunteers were tested on 2 occasions. Initially, they were studied in a semirecumbent position (45 degrees), with the first pull-through after 6 hour fasting. After a meal, a pull-through was repeated 4 consecutive times (approximately 15, 30, 45, and 60 min). On a subsequent day, the positions were changed with each pull-through: upright, supine, right decubitus, and left decubitus. The order of these positions was randomly selected. Results The pH step-up is defined as a change in pH from a gastric to an esophageal pH (<4→>4). No significant difference was found between location of the pH step-up in the fasting and postprandial pull-throughs. An area of lower pH was consistently found within 2 cm distal to the step-up area. Distal to the area of higher gastric pH (median pH at 5), a second acid layer was found. This pattern persisted through the 4 postprandial pull-throughs, irrespective of body position. Conclusions The pH step-up was persistent in the fasting period and for 1 hour postprandially, but did not migrate proximally. Gastric buffering from a meal creates a nonuniform environment with at least 2 acid layers. This pattern is present irrespective of body position. The lack of homogeneity of stomach content postprandially helps to explain the observation of occasional persistent acid gastroesophageal reflux after a meal.

Ingestion of acidic foods mimics gastroesophageal reflux during pH monitoring

Ingestion of acidic foods may produce artifactual drops in pH to < 4 that may be difficult to differentiate from a true acid reflux event. We aimed to evaluate intraesophageal pH changes during the ingestion of acidic food and describe the frequency and implications of acidic food ingestion on ambulatory pH monitoring. Ten normal volunteers (six females; mean age, 34) underwent combined impedance–pH testing with a pH electrode placed 5 cm above the lower esophageal sphincter. Each volunteer received 50 ml each of acidic foods in random order. Nadir and mean pH for 30 sec after ingestion of each substance were recorded. Subsequently 100 randomly selected reflux monitor diaries were reviewed, searching for ingestion of acidic foods, and 100 pH tracings were reviewed to evaluate the impact of including/excluding meal periods on percentage time pH < 4 and DeMeester scores. All foods produced abrupt drops to pH < 4, in 80% of cases exceeding 30 sec. During ambulatory pH monitoring 78% of patients recorded ingestion of at least 1 of the 10 tested substances during meals, the majority admitting ingesting carbonated beverages. Not excluding meal periods would have led to the misinterpretation of 6–16% of tracings, depending on the criteria used to identify abnormal acid exposure. We conclude that ingestion of acidic foods is frequent and carries the risk of overdiagnosing GERD. Current findings support the recommendations to carefully instruct patients to record all oral intake and to exclude meal periods from the analysis.

Manometry and impedance characteristics of achalasia. Facts and myths.

Background Achalasia is defined manometrically by an aperistaltic esophagus. Variations in the manometric findings occur in achalasia suggesting that all manometric features should not be required to diagnose achalasia. Combined multichannel intraluminal impedance and esophageal manometry (MII-EM) allows both a functional and a manometric evaluation of esophageal motility and identifies chronic fluid retention. Aim To compare manometric and MII characteristics in patients with achalasia. Methods Retrospective review of 73 MII-EM tracings from patients with achalasia done in our laboratory between October 2001 and December 2004 (38 females; mean age=53.5 y). Patients with previous esophageal interventions were excluded. Manometric and MII characteristics were identified and compared during 10 liquid and 10 viscous swallows. Patients were also divided into 2 groups: vigorous achalasia (VA) and achalasia. Results Twenty-two of the seventy-one (31%) achalasia patients had a hypertensive lower esophageal sphincter (LES). The mean lower esophageal sphincter pressure (LESP) for the 71 patients with achalasia was 37.9±21.2 mm Hg compared with 27.3±9.3 mm Hg (P<0.05) in the 73 patients with normal motility. The mean LESP in patients with achalasia was 36±20.3 mm Hg compared with 47±23.2 mm Hg (P<0.05) in patients with VA. Elevated intraesophageal pressure (IEP) was noted in 45/73 (61.6%). The mean LESP in this group was 41.1±22.9 mm Hg compared with 32.5±17 mm Hg (P<0.05) with normal IEP. The mean baseline impedance for achalasia was 801±732 compared with 1265.2±829.5 Ω (P<0.05) for the VA patients. Conclusions Most patients with achalasia have elevated IEP, elevated LES residual pressure, normal LES pressure, and low baseline impedance. All manometric features should not be required to diagnose achalasia. Patients with an elevated IEP are likely to have an elevated LES pressure and LES residual pressure. Low MII values identify chronic fluid retention and helps confirm the diagnosis.