Pathophysiology of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is one of the most common digestive diseases in the Western world, with typical symptoms, such as heartburn, regurgitation, or retrosternal pain, reported by 15% to 20% of the general population. The pathophysiology of GERD is multifactorial. Our understanding of these factors has significantly improved in recent years, with increased understanding of the acid pocket and hiatal hernia and how these factors interact. Although our insight has significantly increased over the past years, more studies are required to better understand symptom generation in GERD, especially in patients with therapy-resistant symptom

Proton pump inhibitors reduce the size and acidity of the acid pocket in the stomach

The gastric acid pocket is believed to be the reservoir from which acid reflux events originate. Little is known about how changes in position, size, and acidity of the acid pocket contribute to the therapeutic effect of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD). Thirty-six patients with GERD (18 not taking PPIs, 18 taking PPIs; 19 men; age, 55 ± 2.1 y) were analyzed by concurrent high-resolution manometry and pH-impedance monitoring after a standardized meal. The acid pocket was visualized using scintigraphy after intravenous administration of (99m)technetium-pertechnetate. The size of the acid pocket was measured and its position was determined, relative to the diaphragm, using radionuclide markers on a high-resolution manometry catheter. At the end of the study, the acid pocket was aspirated, and its pH level was measured. The number of reflux episodes was comparable between patients on and off PPIs, but the number of acid reflux episodes was reduced significantly in patients on PPIs. In patients on PPIs, the acid pocket was smaller and more frequently located below the diaphragm. The mean pH of the acid pocket was significantly lower in patients not taking PPIs (n = 6) than in those who were (n = 16) (0.9; range, 0.7-1.2 vs 4.0; range, 1.6-5.9; P <.001). The pH of acid pockets correlated significantly with the lowest pH values measured for refluxate (r = 0.72; P <.01). Based on analyses of acid pockets in patients with GERD, the acid pocket appears to be a reservoir from which reflux occurs when patients are receiving PPIs. PPIs might affect the size, acidity, or position of the acid pocket, which contributes to the efficacy in patients with GER

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 3 (1.6 +/- 0.3 vs 4.4 +/- 0.5mm(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 achalasi

Increased proximal reflux in a hypersensitive esophagus might explain symptoms resistant to proton pump inhibitors in patients with gastroesophageal reflux disease

Approximately 30% of patients with gastroesophageal reflux disease have symptoms resistant to treatment with proton pump inhibitors (PPIs). Several mechanisms such as esophageal hypersensitivity, increased mucosal permeability, and possibly the position of the gastric acid pocket might underlie a partial response to PPIs. To what extent these mechanisms interact and contribute to PPI-resistant symptoms, however, has not been investigated previously. In 18 gastroesophageal reflux disease patients (9 PPI responders and 9 PPI partial responders), esophageal sensitivity, mucosal permeability, and postprandial reflux parameters were determined during PPI use. Esophageal sensitivity for distension was measured by gradual balloon inflation at 5 and 15 cm above the lower esophageal sphincter. The mucosal permeability of 4 esophageal biopsy specimens per patient was determined in Ussing chambers by measuring the transepithelial electrical resistance and transmucosal flux of fluorescein. Postprandial reflux parameters were determined using concurrent high-resolution manometry/pH impedance after a standardized meal. In addition, the acid pocket was visualized using scintigraphy. No difference in the rate of postprandial acid reflux, in the pH of the acid pocket (PPI responders 3.7 ± 0.7 vs PPI partial responders 4.2 ± 0.4; P = .54), or in the position of the acid pocket was observed in PPI partial responders compared with PPI responders. In addition, the permeability of the esophageal mucosa was similar in both groups, as shown by a similar transepithelial electrical resistance and flux of fluorescein. PPI partial responders had more reflux episodes with a higher mean proximal extent, compared with PPI responders, and were more sensitive to balloon distension, both in the upper and lower esophagus. PPI-resistant symptoms most likely are explained by increased proximal reflux in a hypersensitive esophagus and less likely by increased mucosal permeability or the position of the acid pocke

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

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. To evaluate the effect of peroral endoscopic myotomy (POEM) on esophagogastric function. Prospective trial. Endoscopy department at a university hospital. All consecutive patients aged >17 years with achalasia and an Eckardt score of ≥3. Before and 3 months after POEM, 10 consecutive patients underwent esophageal manometry, timed barium esophagograms, and EndoFLIP as well as an EGD. Eckardt symptom score, LES resting pressure, centimeters of barium stasis, EGJ distensibility, and reflux esophagitis. 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. Small number of patients, short-term follow-up. 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 POE