Alain Ropert

Esophageal pH-impedance monitoring and symptom analysis in GERD: a study in patients off and on therapy.

INTRODUCTION:Combined esophageal pH-impedance monitoring allows detection of nearly all gastroesophageal reflux episodes, acid as well as nonacid. However, the role of nonacid reflux in the pathogenesis of symptoms is poorly known. The aim of this study was to evaluate the diagnostic yield of this technique in patients with suspected reflux symptoms while on or off PPI therapy.PATIENTS AND METHODS:The recordings of 150 patients recruited at seven academic centers with symptoms possibly related to gastroesophageal reflux were analyzed. Reflux events were detected visually using impedance (Sandhill, CO) and then characterized by pHmetry as acid or nonacid reflux. The temporal relationship between symptoms and reflux episodes was analyzed: a symptom association probability (SAP) ≥95% was considered indicative of a positive association.RESULTS:One hundred fifty patients were included, 102 women (mean age 52 ± 14 yr, range 16–84). Among the 79 patients off PPI, five did not report any symptom during the recording period. A positive SAP was found in 41 of the 74 symptomatic patients (55.4%), including acid reflux in 23 (31.1%), nonacid reflux in three (4.1%), and acid and nonacid in 15 (20.3%). In the group of patients on PPI (N = 71, 46 women, mean age 51 ± 15 yr), 11 were asymptomatic during the study, SAP was positive in 22 of the 60 symptomatic patients (36.7%), including acid reflux in three (5.0%), nonacid reflux in 10 (16.7%), and acid and nonacid in nine (15.0%). The symptoms most frequently associated with nonacid reflux were regurgitation and cough.CONCLUSION:Adding impedance to pH monitoring improves the diagnostic yield and allows better symptom analysis than pHmetry alone, mainly in patients on PPI therapy. The impact of this improved diagnostic value on gastroesophageal reflux disease management remains to be investigated by outcome studies.

Erythromycin Enhances Fasting and Postprandial Proximal Gastric Tone in Humans

BACKGROUND & AIMS Low doses of erythromycin induce antral contractions and accelerate gastric emptying. However, the effect of erythromycin on the proximal stomach remains unknown. The aim of this study was to assess the effect and mechanism(s) of action of erythromycin on proximal gastric tone in humans. METHODS Gastric tone was measured using an electronic barostat in two groups of 6 subjects both in the fasting state and after a 200-kcal meal. On different occasions, subjects received saline, atropine alone (6 micrograms.kg-1.h-1 for 30 minutes), erythromycin alone (1.5 mg/kg in the fasting state and 1.5 and 3.0 mg/kg in the postprandial state), and erythromycin plus atropine. RESULTS Low-dose (1.5 mg/kg) erythromycin enhanced fasting gastric tone, but only the 3.0-mg/kg dose reduced the duration of meal-induced relaxation (37 +/- 14 vs. 105 +/- 20 minutes; P < 0.01). Atropine did not change the fasting or postprandial gastric tone as well as the erythromycin-induced responses. Plasma motilin levels were unaffected by erythromycin infusion. No correlation was observed between gastric tone and plasma motilin or erythromycin levels. CONCLUSIONS Erythromycin enhances fasting and postprandial proximal gastric tone in humans by a mechanism that does not seem to involve endogenous motilin release or a cholinergic pathway.

Achalasia: outcome of patients treated with intrasphincteric injection of botulinum toxin.

BACKGROUND: To evaluate the safety and clinical efficacy of botulinum toxin (BT) in patients with achalasia followed up for six months. METHODS: Fifty five symptomatic patients with manometrically proven achalasia were included in a multicentre prospective trial. Before and two weeks and two months after intrasphincteric injection of BT, symptoms of dysphagia, regurgitation, and chest pain were scored on a 0-3 scale, and lower oesophageal sphincter pressure (LOSP) was assessed. The symptom score was determined again at six months, clinical improvement being defined by < or = 3, relapse by > 3, and failure as a relapse after two injections or loss to follow up. RESULTS: Except for transient chest or epigastric pain (22%), no side effects were observed. There was a significant decrease in LOSP after treatment. Symptom scores were significantly improved at two weeks (2.0 (SD 1.6)), two months (1.7 (1.8)), and six months (1.9 (2.0)) compared with pretreatment values (5.1 (1.8), p < 0.001). At six months, 33 patients had clinical improvement (27 after one injection), 17 were considered failures, and five had just relapsed. Although there was a trend for age (older patients being more responsive), age, sex, prior duration of symptoms, initial symptom score, weight loss, LOSP, magnitude of oesophageal contractions, vigorous or non-vigorous achalasia, previous dilatations, and radiological features were not predictive of results. CONCLUSIONS: This multicentre series confirms that intrasphincteric injection of BT is a safe procedure, resulting in clinical improvement in 60% of patients with achalasia at six months. The therapeutic role of BT in achalasia needs further evaluation with regard to other alternatives.

Simultaneous assessment of liquid emptying and proximal gastric tone in humans

BACKGROUND Barostat is the only technique that allows assessment of gastric tone in humans. Our aim was to simultaneously assess gastric emptying and relaxation in response to a liquid meal. METHODS Gastric tone was monitored using an electronic barostat in six healthy subjects after three liquid meals (200 mL, 400 mL, 600 mL, 1 kcal/mL). Scintigraphic imaging was obtained by using double isotopic labeling (technetium 99m for liquid of the 200 mL meal and xenon 133 for air into the barostat). RESULTS Profound gastric relaxation was detected in every subject. The duration of proximal gastric relaxation increased with meal size. The proximal stomach remained relaxed through the duration of gastric emptying. Gastric tone returned to the fasting values simultaneously with completion of liquid emptying. Repeated measures after the 200-mL meal showed that amplitude (i.e., maximal volume change) and duration of relaxations were reproducible. However, the presence of the bag slightly accelerated gastric emptying and modified the intragastric distribution of the meal. CONCLUSIONS The barostat is a sensitive and reproducible technique to measure gastric relaxation following liquid meals in humans. The results also suggest that the role of gastric tone as the driving force of gastric emptying of liquids has been overestimated.

Normal Values of Pharyngeal and Esophageal 24-Hour pH Impedance in Individuals on and off Therapy and Interobserver Reproducibility

BACKGROUND & AIMS Combined pH and impedance monitoring can detect all types of reflux episodes within the esophageal lumen and the pharynx. We performed a multicenter study to establish normal values of pharyngeal and esophageal pH-impedance monitoring in individuals on and off therapy and to determine the interobserver reproducibility of this technique. METHODS We collected ambulatory 24-hour pH-impedance recordings from 46 healthy subjects by using a bifurcated probe that allowed for detection of reflux events in the distal and proximal esophagus and pharynx. Data were collected when subjects had not received any medicine (off therapy) and after receiving 40 mg esomeprazole twice daily for 14 days (on therapy). The interobserver agreement for the detection of reflux events was determined in 20 subjects off and on therapy. Results were expressed as median (interquartile range). RESULTS Off therapy, subjects had a median of 32 reflux events (17-45) in the distal esophagus and 3 (1-6) in the proximal esophagus; they had none in the pharynx. On therapy, subjects had a median number of 21 reflux events (6-37) in the distal esophagus and 2 (0-5) in the proximal esophagus; again, there were none in the pharynx. Interobserver agreement was good for esophageal reflux events but poor for pharyngeal events. CONCLUSIONS We determined normal values of pharyngeal and gastroesophageal reflux events by 24-hour pH-impedance monitoring of subjects receiving or not receiving esomeprazole therapy. Analyses of esophageal events were reproducible, but analyses of pharyngeal events were not; this limitation should be taken into account in further studies.

Pharyngeal pH alone is not reliable for the detection of pharyngeal reflux events: A study with oesophageal and pharyngeal pH-impedance monitoring

Background Pharyngeal pH probes and pH-impedance catheters have been developed for the diagnosis of laryngo-pharyngeal reflux. Objective To determine the reliability of pharyngeal pH alone for the detection of pharyngeal reflux events. Methods 24-h pH-impedance recordings performed in 45 healthy subjects with a bifurcated probe for detection of pharyngeal and oesophageal reflux events were reviewed. Pharyngeal pH drops to below 4 and 5 were analysed for the simultaneous occurrence of pharyngeal reflux, gastro-oesophageal reflux, and swallows, according to impedance patterns. Results Only 7.0% of pharyngeal pH drops to below 5 identified with impedance corresponded to pharyngeal reflux, while 92.6% were related to swallows and 10.2 and 13.3% were associated with proximal and distal gastro-oesophageal reflux events, respectively. Of pharyngeal pH drops to below 4, 13.2% were related to pharyngeal reflux, 87.5% were related to swallows, and 18.1 and 21.5% were associated with proximal and distal gastro-oesophageal reflux events, respectively. Conclusions This study demonstrates that pharyngeal pH alone is not reliable for the detection of pharyngeal reflux and that adding distal oesophageal pH analysis is not helpful. The only reliable analysis should take into account impedance patterns demonstrating the presence of pharyngeal reflux event preceded by a distal and proximal reflux event within the oesophagus.