Stanislas Bruley des Varannes

Pneumatic dilation versus laparoscopic Heller's myotomy for idiopathic achalasia.

BACKGROUNDnMany experts consider laparoscopic Hellers myotomy (LHM) to be superior to pneumatic dilation for the treatment of achalasia, and LHM is increasingly considered to be the treatment of choice for this disorder.nnnMETHODSnWe randomly assigned patients with newly diagnosed achalasia to pneumatic dilation or LHM with Dors fundoplication. Symptoms, including weight loss, dysphagia, retrosternal pain, and regurgitation, were assessed with the use of the Eckardt score (which ranges from 0 to 12, with higher scores indicating more pronounced symptoms). The primary outcome was therapeutic success (a drop in the Eckardt score to ≤3) at the yearly follow-up assessment. The secondary outcomes included the need for retreatment, pressure at the lower esophageal sphincter, esophageal emptying on a timed barium esophagogram, quality of life, and the rate of complications.nnnRESULTSnA total of 201 patients were randomly assigned to pneumatic dilation (95 patients) or LHM (106). The mean follow-up time was 43 months (95% confidence interval [CI], 40 to 47). In an intention-to-treat analysis, there was no significant difference between the two groups in the primary outcome; the rate of therapeutic success with pneumatic dilation was 90% after 1 year of follow-up and 86% after 2 years, as compared with a rate with LHM of 93% after 1 year and 90% after 2 years (P=0.46). After 2 years of follow-up, there was no significant between-group difference in the pressure at the lower esophageal sphincter (LHM, 10 mm Hg [95% CI, 8.7 to 12]; pneumatic dilation, 12 mm Hg [95% CI, 9.7 to 14]; P=0.27); esophageal emptying, as assessed by the height of barium-contrast column (LHM, 1.9 cm [95% CI, 0 to 6.8]; pneumatic dilation, 3.7 cm [95% CI, 0 to 8.8]; P=0.21); or quality of life. Similar results were obtained in the per-protocol analysis. Perforation of the esophagus occurred in 4% of the patients during pneumatic dilation, whereas mucosal tears occurred in 12% during LHM. Abnormal exposure to esophageal acid was observed in 15% and 23% of the patients in the pneumatic-dilation and LHM groups, respectively (P=0.28).nnnCONCLUSIONSnAfter 2 years of follow-up, LHM, as compared with pneumatic dilation, was not associated with superior rates of therapeutic success. (European Achalasia Trial Netherlands Trial Register number, NTR37, and Current Controlled Trials number, ISRCTN56304564.).

Endogenous cholecystokinin in postprandial lower esophageal sphincter function and fundic tone in humans

Transient lower esophageal sphincter (LES) relaxations (TLESRs) are the main underlying mechanism of gastroesophageal reflux. Although CCK acts through CCK-A receptors to increase the TLESRs induced by gastric distension, the respective roles of endogenous CCK and fundic tone in triggering postprandial TLESRs remain unknown. The aim of this study was to determine the effect of the CCK-A receptor antagonist, loxiglumide, on postprandial LES function and fundic tone in humans. LES motor events and fundic tone were simultaneously monitored in two groups of healthy volunteers. Recordings were performed during fasting and for 3 h after a liquid meal (200 ml/200 kcal) administered either orally or intraduodenally at a rate mimicking gastric emptying. Each subject received loxiglumide (10 mg. kg-1. h-1) or saline (control) in randomized order, which was started 40 min before the meal and maintained for 3 h thereafter. After the oral meal, loxiglumide significantly reduced TLESRs (P = 0.002) without significantly affecting LES pressure and fundic tone. After duodenal infusion of the meal, loxiglumide totally abolished the increase in TLESRs, reduced LES pressure fall (P < 0.02), and strongly inhibited fundic relaxation (P = 0.0001). We concluded that endogenous CCK is involved in the postprandial control of both LES function and fundic tone through activation of CCK-A receptors.Transient lower esophageal sphincter (LES) relaxations (TLESRs) are the main underlying mechanism of gastroesophageal reflux. Although CCK acts through CCK-A receptors to increase the TLESRs induced by gastric distension, the respective roles of endogenous CCK and fundic tone in triggering postprandial TLESRs remain unknown. The aim of this study was to determine the effect of the CCK-A receptor antagonist, loxiglumide, on postprandial LES function and fundic tone in humans. LES motor events and fundic tone were simultaneously monitored in two groups of healthy volunteers. Recordings were performed during fasting and for 3 h after a liquid meal (200 ml/200 kcal) administered either orally or intraduodenally at a rate mimicking gastric emptying. Each subject received loxiglumide (10 mg ⋅ kg-1 ⋅ h-1) or saline (control) in randomized order, which was started 40 min before the meal and maintained for 3 h thereafter. After the oral meal, loxiglumide significantly reduced TLESRs ( P = 0.002) without significantly affecting LES pressure and fundic tone. After duodenal infusion of the meal, loxiglumide totally abolished the increase in TLESRs, reduced LES pressure fall ( P < 0.02), and strongly inhibited fundic relaxation ( P = 0.0001). We concluded that endogenous CCK is involved in the postprandial control of both LES function and fundic tone through activation of CCK-A receptors.

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

BACKGROUND & AIMSnCombined 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.nnnMETHODSnWe 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).nnnRESULTSnOff 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.nnnCONCLUSIONSnWe 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.

Gastroesophageal Acid Reflux Control 5 Years After Antireflux Surgery, Compared With Long-term Esomeprazole Therapy

BACKGROUND & AIMSnWe compared the ability of laparoscopic antireflux surgery (LARS) and esomeprazole to control esophageal acid exposure, over a 5-year period, in patients with chronic gastroesophageal reflux disease (GERD). We also studied whether intraesophageal and intragastric pH parameters off and on therapy were associated with long-term outcomes.nnnMETHODSnWe analyzed data from a prospective, randomized, open-label trial comparing the efficacy and safety of LARS vs esomeprazole (20 or 40 mg/d) over 5 years in patients with chronic GERD. Ambulatory intraesophageal and intragastric 24-hour pH monitoring data were compared between groups before LARS or the start of esomeprazole treatment, and 6 months and 5 years afterward. A secondary aim was to evaluate the association between baseline and 6-month pH parameters and esomeprazole dose escalation, reappearance of GERD symptoms, and treatment failure over 5 years in patients receiving LARS or esomeprazole.nnnRESULTSnIn the LARS group (n = 116), the median 24-hour esophageal acid exposure was 8.6% at baseline and 0.7% after 6 months and 5 years (P < .001 vs baseline). In the esomeprazole group (n = 151), the median 24-hour esophageal acid exposure was 8.8% at baseline, 2.1% after 6 months, and 1.9% after 5 years (P < .001, therapy vs baseline, and LARS vs esomeprazole). Gastric acidity was stable in both groups. Patients who required a dose increase to 40 mg/d had more severe supine reflux at baseline, and decreased esophageal acid exposure (P < .02) and gastric acidity after dose escalation. Esophageal and intragastric pH parameters, off and on therapy, did not predict long-term symptom breakthrough.nnnCONCLUSIONSnIn a prospective study of patients with chronic GERD, esophageal acid reflux was reduced greatly by LARS or esomeprazole therapy. However, patients receiving LARS had significantly greater reductions in 24-hour esophageal acid exposure after 6 months and 5 years. Esophageal and gastric pH, off and on therapy, did not predict long-term outcomes of patients. Abnormal supine acid exposure predicted esomeprazole dose escalation. ClinicalTrials.Gov identifier: NCT00251927 (available: http://clinicaltrials.gov/ct2/show/NCT00251927).

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.

Treatment of GORD: Three decades of progress and disappointments

The treatment of GORD has been revolutionized by the introduction, in the 1980s, of proton-pump inhibitors as the mainstay of medical therapy and by the development of laparoscopic antireflux surgery which has definitively replaced open surgery. However, despite these major advances, many unmet therapeutic needs still persist and justify novel therapeutic approaches. The aim of this historical review is to recall the main discoveries in the treatment of GORD that have occurred during the last three decades and to discuss why some initially promising drugs or techniques have not translated into clinical applications. A careful analysis of these previous disappointing experiences should help to identify high priorities and better research programmes on the management of GORD.

Acetylcholine induces stem cell properties of gastric cancer cells of diffuse type

Gastric cancer is the third leading cause of cancer-related death worldwide, but the mechanisms of gastric carcinogenesis are not completely understood. Recently, the role of cholinergic neuronal pathways in promoting this process has been demonstrated. Our aim was to extend these studies and to evaluate, using an in vitro model of tumorspheres, the effect of acetylcholine on human gastric cancer cells, and the role of acetylcholine receptors and of the nitric oxide pathway, in this effect. The gastric cancer cell line MKN-45 of the diffuse type of gastric cancer was cultured in the presence of acetylcholine, or different agonists or inhibitors of muscarinic and nicotinic acetylcholine receptors, or nitric oxide donor or inhibitor of the nitric oxide pathway, and the number and size of tumorspheres were assessed. The expression of cancer stem cell markers (CD44 and aldehyde dehydrogenase) was also evaluated by immunofluorescence and quantitative reverse transcription polymerase chain reaction. We showed that acetylcholine increased both the number and size of tumorspheres and that this effect was reproduced with both muscarinic and nicotinic acetylcholine receptors agonists and was inhibited by both receptor antagonists. The nitric oxide donor stimulated the tumorsphere formation, while the nitric oxide synthesis inhibitor inhibited the stimulatory effect of acetylcholine. Moreover, acetylcholine increased the expression of stem cell markers on gastric cancer cells. These results indicate that acetylcholine induces the stem cell properties of gastric cancer cells and both muscarinic and nicotinic receptors and a nitrergic pathway might be involved in this effect.

Profil symptomatique et modalités de prise en charge des gastro-entérites aiguës de l'adulte en médecine générale

AIMnIn patients with acute gastroenteritis, general behaviour of patients as well as medical care remain poorly documented. The aim of this work was to determine clinical and demographic characteristics, reason for visiting a doctor, and medical care in adult patients with acute gastroenteritis.nnnMETHODSnDuring the winter epidemic peak of acute diarrhea, 2,217 general practitioners filled in standardized clinical observations of 17,273 patients (mean age 40 yrs) with acute gastroenteritis.nnnRESULTSnThere were abdominal pain, nausea, and vomiting in respectively 72%, 53% and 43% of patients. Thirty one percent of patients had fever. Nausea and vomiting were more frequently observed in younger patients (15-25 yrs) than in older ones. More severe diarrhea more frequent nausea, vomiting and abdominal pain (p<0.0001). Time for consulting was less than 24 and 48h in respectively 42% and 87% of patients, and was different according to professional classes. Predominant reason for consulting was the physical consequences of the disease (78%). Self medication was reported in 42% of patients and was different according to age and professional classes. Prescription of antidiarrheal drugs was reported by 91% of patients, sometimes in association with antiemetic (43%) and/or antispasmodic agents (35%). Additional explorations (mainly biological work-up) were rare but they were more frequently considered in older and female patients as well as in patients with severe and prolonged diarrhea. Stoppage of work was different among professional classes. It was reported in one third of patients, and was more frequent in patients with severe diarrhea.nnnCONCLUSIONSnThis study describes the behaviour of patients and doctors facing acute gastroenteritis and illustrates important fluctuations according age and professional classes. It shows high discomfort and repercussions of acute gastroenteritis especially regarding stoppage of work.

Profil symptomatique et modalités de prise en charge des gastro-entérites aiguës de l’adulte en médecine générale: Résultats d’une enquête transversale à grande échelle portant sur 17 273 patients

AIMnIn patients with acute gastroenteritis, general behaviour of patients as well as medical care remain poorly documented. The aim of this work was to determine clinical and demographic characteristics, reason for visiting a doctor, and medical care in adult patients with acute gastroenteritis.nnnMETHODSnDuring the winter epidemic peak of acute diarrhea, 2,217 general practitioners filled in standardized clinical observations of 17,273 patients (mean age 40 yrs) with acute gastroenteritis.nnnRESULTSnThere were abdominal pain, nausea, and vomiting in respectively 72%, 53% and 43% of patients. Thirty one percent of patients had fever. Nausea and vomiting were more frequently observed in younger patients (15-25 yrs) than in older ones. More severe diarrhea more frequent nausea, vomiting and abdominal pain (p<0.0001). Time for consulting was less than 24 and 48h in respectively 42% and 87% of patients, and was different according to professional classes. Predominant reason for consulting was the physical consequences of the disease (78%). Self medication was reported in 42% of patients and was different according to age and professional classes. Prescription of antidiarrheal drugs was reported by 91% of patients, sometimes in association with antiemetic (43%) and/or antispasmodic agents (35%). Additional explorations (mainly biological work-up) were rare but they were more frequently considered in older and female patients as well as in patients with severe and prolonged diarrhea. Stoppage of work was different among professional classes. It was reported in one third of patients, and was more frequent in patients with severe diarrhea.nnnCONCLUSIONSnThis study describes the behaviour of patients and doctors facing acute gastroenteritis and illustrates important fluctuations according age and professional classes. It shows high discomfort and repercussions of acute gastroenteritis especially regarding stoppage of work.