Wout O. Rohof

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

BACKGROUND Many 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. METHODS We 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. RESULTS A 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). CONCLUSIONS After 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.).

Outcomes of Treatment for Achalasia Depend on Manometric Subtype

BACKGROUND & AIMS Patients with achalasia are treated with either pneumatic dilation (PD) or laparoscopic Heller myotomy (LHM), which have comparable rates of success. We evaluated whether manometric subtype was associated with response to treatment in a large population of patients treated with either PD or LHM (the European achalasia trial). METHODS Esophageal pretreatment manometry data were collected from 176 patients who participated in the European achalasia trial. Symptoms (weight loss, dysphagia, retrosternal pain, and regurgitation) were assessed using the Eckardt score; treatment was considered successful if the Eckardt score was 3 or less. Manometric tracings were classified according to the 3 Chicago subtypes. RESULTS Forty-four patients had achalasia type I (25%), 114 patients had achalasia type II (65%), and 18 patients had achalasia type III (10%). After a minimum follow-up period of 2 years, success rates were significantly higher among patients with type II achalasia (96%) than type I achalasia (81%; P < .01, log-rank test) or type III achalasia (66%; P < .001, log-rank test). The success rate of PD was significantly higher than that of LHM for patients with type II achalasia (100% vs 93%; P < .05), but LHM had a higher success rate than PD for patients with type III achalasia (86% vs 40%; P = .12, difference was not statistically significant because of the small number of patients). For type I achalasia, LHM and PD had similar rates of success (81% vs 85%; P = .84). CONCLUSIONS A higher percentage of patients with type II achalasia (based on manometric tracings) are treated successfully with PD or LHM than patients with types I and III achalasia. Success rates in type II are high for both treatment groups but significantly higher in the PD group. Patients with type III can probably best be treated by LHM. Trialregister.nl number NTR37; ISRCTN56304564.

Efficacy of treatment for patients with achalasia depends on the distensibility of the esophagogastric junction.

BACKGROUND & AIMS Many patients with persistent dysphagia and regurgitation after therapy have low or no lower esophageal sphincter (LES) pressure. Distensibility of the esophagogastric junction (EGJ) largely determines esophageal emptying. We investigated whether assessment of the distensibility of the EGJ is a better and more integrated parameter than LES pressure for determining efficacy of treatment for patients with achalasia. METHODS We measured distensibility of the EGJ using an endoscopic functional luminal imaging probe (EndoFLIP) in 15 healthy volunteers (controls; 8 male; age, 40 ± 4.1 years) and 30 patients with achalasia (16 male; age, 51 ± 3.1 years). Patients were also assessed by esophageal manometry and a timed barium esophagogram. Symptom scores were assessed using the Eckardt score, with a score <4 indicating treatment success. The effect of initial and additional treatment on distensibility and symptoms was evaluated in 7 and 5 patients, respectively. RESULTS EGJ distensibility was significantly reduced in untreated patients with achalasia compared with controls (0.7 ± 0.9 vs 6.3 ± 0.7 mm(2)/mm Hg; P < .001). In patients with achalasia, EGJ distensibility correlated with esophageal emptying (r = -0.72; P < .01) and symptoms (r = 0.61; P < .01) and was significantly increased with treatment. EGJ distensibility was significantly higher in patients successfully treated (Eckardt score <3) compared with those with an Eckardt score >3 (1.6 ± 0.3 vs 4.4 ± 0.5 mm(2)/mm Hg; P = .001). Even when LES pressure was low, EGJ distensibility could be reduced, which was associated with impaired emptying and recurrent symptoms. CONCLUSIONS EGJ distensibility is impaired in patients with achalasia and, in contrast to LES pressure, is associated with esophageal emptying and clinical response. Assessment of EGJ distensibility by EndoFLIP is a better parameter than LES pressure for evaluating efficacy of treatment for achalasia.

Effect of peroral endoscopic myotomy on esophagogastric junction physiology in patients with achalasia

BACKGROUND Pneumatic dilation and laparoscopic Heller myotomy improve parameters of esophageal function such as lower esophageal sphincter (LES) pressure, esophageal emptying, and esophagogastric junction (EGJ) distensibility. OBJECTIVE To evaluate the effect of peroral endoscopic myotomy (POEM) on esophagogastric function. DESIGN Prospective trial. SETTING Endoscopy department at a university hospital. PATIENTS All consecutive patients aged >17 years with achalasia and an Eckardt score of ≥3. INTERVENTION Before and 3 months after POEM, 10 consecutive patients underwent esophageal manometry, timed barium esophagograms, and EndoFLIP as well as an EGD. MAIN OUTCOME MEASUREMENTS Eckardt symptom score, LES resting pressure, centimeters of barium stasis, EGJ distensibility, and reflux esophagitis. RESULTS Compared with scores before POEM, patient symptom scores were significantly reduced (1, interquartile range [IQR 0-1] vs 8 [IQR 4-8]; P = .005). LES pressure decreased significantly (6.0 mm Hg [IQR 2.6-7.4] vs 19.0 mm Hg [IQR 13.0-28.0]; P = .008). Esophageal emptying increased significantly, and a 5-minute barium column measured 2.3 cm (IQR 0-3.2 cm) versus 10.1 cm (IQR 5.7-10.8 cm; P = .005). EGJ distensibility increased significantly (6.7 mm(2)/mm Hg [IQR 3.8-16.6] vs 1.0 mm(2)/mm Hg [IQR 0.4-2.3]; P = .02) at 50 mL. In 6 of 10 patients, reflux esophagitis was seen. Of these patients, 3 reported reflux symptoms. LIMITATIONS Small number of patients, short-term follow-up. CONCLUSION POEM improves esophagogastric function and suggests favorable long-term results based on Eckardt score, esophageal manometry, esophageal emptying, and EGJ distensibility. Long-term follow-up of larger series will determine whether the high rate of reflux esophagitis affects the clinical application of POEM.

An Alginate-Antacid Formulation Localizes to the Acid Pocket to Reduce Acid Reflux in Patients With Gastroesophageal Reflux Disease

BACKGROUND & AIMS Alginate rafts (polysaccharide polymers that precipitate into a low-density viscous gel when they contact gastric acid) have been reported to form at the acid pocket, an unbuffered pool of acid that floats on top of ingested food and causes postprandial acid reflux. We studied the location of an alginate formulation in relation to the acid pocket and the corresponding effects on reflux parameters and acid pocket positioning in patients with gastroesophageal reflux disease (GERD). METHODS We randomly assigned patients with symptomatic GERD and large hiatal hernias to groups who were given either (111)In-labeled alginate-antacid (n = 8, Gaviscon Double Action Liquid) or antacid (n = 8, Antagel) after a standard meal. The relative positions of labeled alginate and acid pocket were analyzed for 2 hours by using scintigraphy; reflux episodes were detected by using high-resolution manometry and pH-impedance monitoring. RESULTS The alginate-antacid label localized to the acid pocket. The number of acid reflux episodes was significantly reduced in patients receiving alginate-antacid (3.5; range, 0-6.5; P = .03) compared with those receiving antacid (15; range, 5-20), whereas time to acid reflux was significantly increased in patients receiving alginate-antacid (63 minutes; range, 23-92) vs those receiving antacid (14 minutes; range, 9-23; P = .01). The acid pocket was located below the diaphragm in 71% of patients given alginate-antacid vs 21% of those given antacid (P = .08). There was an inverse correlation between a subdiaphragm position of the acid pocket and acid reflux (r = -0.76, P < .001). CONCLUSIONS In a study of 16 patients with GERD, we observed that the alginate-antacid raft localizes to the postprandial acid pocket and displaces it below the diaphragm to reduce postprandial acid reflux. These findings indicate the importance of the acid pocket in GERD pathogenesis and establish alginate-antacid as an appropriate therapy for postprandial acid reflux.

Effect of azithromycin on acid reflux, hiatus hernia and proximal acid pocket in the postprandial period

Background The risk for acidic reflux is mainly determined by the position of the gastric acid pocket. It was hypothesised that compounds affecting proximal stomach tone might reduce gastro-oesophageal reflux by changing the acid pocket position. Objective To study the effect of azithromycin (Azi) on acid pocket position and acid exposure in patients with gastro-oesophageal reflux disease (GORD). Methods Nineteen patients with GORD were included, of whom seven had a large hiatal hernia (≥3 cm) (L-HH) and 12 had a small or no hiatal hernia (S-HH). Patients were randomised to Azi 250 mg/day or placebo during 3 days in a crossover manner. On each study day, reflux episodes were detected using concurrent high-resolution manometry and pH-impedance monitoring after a standardised meal. The acid pocket was visualised using scintigraphy, and its position was determined relative to the diaphragm. Results Azi reduced the number of acid reflux events (placebo 8.0±2.2 vs Azi 5.6±1.8, p<0.01) and postprandial acid exposure (placebo 10.5±3.8% vs Azi 5.9±2.5%, p<0.05) in all patients without affecting the total number of reflux episodes. Acid reflux occurred mainly when the acid pocket was located above, or at the level of, the diaphragm, rather than below the diaphragm. Treatment with Azi reduced hiatal hernia size and resulted in a more distal position of the acid pocket compared with placebo (below the diaphragm 39% vs 29%, p=0.03). Azi reduced the rate of acid reflux episodes in patients with S-HH (38% to 17%) to a greater extent than in patients with L-HH (69% to 62%, p=0.04). Conclusion Azi reduces acid reflux episodes and oesophageal acid exposure. This effect was associated with a smaller hiatal hernia size and a more distal position of the acid pocket, further indicating the importance of the acid pocket in the pathogenesis of GORD. clinical trial registration http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1970 NTR1970.

Esophageal Stasis on a Timed Barium Esophagogram Predicts Recurrent Symptoms in Patients With Long-Standing Achalasia

OBJECTIVES:In achalasia, early recognition of the need for retreatment is of crucial importance to reduce morbidity and long-term complications such as esophageal decompensation. In clinical practice, symptoms and parameters of esophageal function including lower esophageal sphincter (LES) pressure and esophageal emptying are used to decide whether additional treatment is required. However, which of these tests performs best remains unclear.METHODS:A cohort of 41 patients with long-standing achalasia (median 17 years), underwent esophageal manometry, timed barium esophagogram and symptom evaluation. Patients were followed up for 10 years, and were regarded as a therapeutic failure if Eckardt score was >3 or when retreatment was needed. Predictors of therapeutic failure were evaluated.RESULTS:Of the 41 included patients, 7 patients had an elevated LES pressure (>10 mm Hg) and 26 had esophageal stasis >5 cm on timed barium esophagogram. During follow-up, 25 patients had recurrence of symptoms and were considered therapeutic failures. Of the 25 patients, 5 had an elevated LES pressure, whereas 22 had esophageal stasis on barium esophagogram. Hence, the sensitivity to predict the need of retreatment is higher for esophageal stasis (88%) compared with LES pressure (20%). A total of 16 patients (39%) were in long-term remission, of which 12 patients (75%) did not have stasis at their initial visit.CONCLUSIONS:In contrast to LES pressure, esophageal stasis is a good predictor of treatment failure in patients with long-standing achalasia. Based on these findings, we propose to use timed barium esophagogram rather than esophageal manometry as test to decide on retreatment.

The effects of a novel metabotropic glutamate receptor 5 antagonist (AZD2066) on transient lower oesophageal sphincter relaxations and reflux episodes in healthy volunteers

Selective metabotropic glutamate receptor 5 (mGluR5) antagonists inhibit transient lower oesophageal sphincter relaxations (TLESRs) in animals and acid reflux in humans.

Electrical tissue impedance spectroscopy: a novel device to measure esophageal mucosal integrity changes during endoscopy

Patients with gastroesophageal reflux disease (GERD) have impaired esophageal mucosal integrity. Measurement of the mucosal integrity is complex and time‐consuming. Electrical tissue impedance spectroscopy (ETIS) is a device that measures impedance of tissue in vivo during endoscopy. In this study, we aimed to validate ETIS as a measure of esophageal mucosal integrity.

High-resolution esophageal pressure topography is superior to conventional sleeve manometry for the detection of transient lower esophageal sphincter relaxations associated with a reflux event

Background  Transient lower esophageal sphincter relaxations (TLESRs) are the main mechanism underlying gastro‐esophageal reflux and are detected during manometric studies using well defined criteria. Recently, high‐resolution esophageal pressure topography (HREPT) has been introduced and is now considered as the new standard to study esophageal and lower esophageal sphincter (LES) function. In this study we performed a head‐to‐head comparison between HREPT and conventional sleeve manometry for the detection of TLESRs.