Importance Achalasia significantly affects patients’ quality of life and can be difficult to diagnose and treat. Objective To review the diagnosis and management of achalasia, with a focus on phenotypic classification pertinent to therapeutic outcomes. Evidence Review Literature review and MEDLINE search of articles from January 2004 to February 2015. A total of 93 articles were included in the final literature review addressing facets of achalasia epidemiology, pathophysiology, diagnosis, treatment, and outcomes. Nine randomized controlled trials focusing on endoscopic or surgical therapy for achalasia were included (734 total patients). Findings A diagnosis of achalasia should be considered when patients present with dysphagia, chest pain, and refractory reflux symptoms after an endoscopy does not reveal a mechanical obstruction or an inflammatory cause of esophageal symptoms. Manometry should be performed if achalasia is suspected. Randomized controlled trials support treatments focused on disrupting the lower esophageal sphincter with pneumatic dilation (70%-90% effective) or laparoscopic myotomy (88%-95% effective). Patients with achalasia have a variable prognosis after endoscopic or surgical myotomy based on subtypes, with type II (absent peristalsis with abnormal pan-esophageal high-pressure patterns) having a very favorable outcome (96%) and type I (absent peristalsis without abnormal pressure) having an intermediate prognosis (81%) that is inversely associated with the degree of esophageal dilatation. In contrast, type III (absent peristalsis with distal esophageal spastic contractions) is a spastic variant with less favorable outcomes (66%) after treatment of the lower esophageal sphincter. Conclusions and Relevance Achalasia should be considered when dysphagia is present and not explained by an obstruction or inflammatory process. Responses to treatment vary based on which achalasia subtype is present.

https://jamanetwork.com/journals/jama/articlepdf/2290638/jrv150005.pdf

Achalasia: A Systematic Review

Background
An international group of experts evaluated and revised recommendations for ambulatory reflux monitoring for the diagnosis of gastro-esophageal reflux disease (GERD).

Methods
Literature search was focused on indications and technical recommendations for GERD testing and phenotypes definitions. Statements were proposed and discussed during several structured meetings.

Key Results
Reflux testing should be performed after cessation of acid suppressive medication in patients with a low likelihood of GERD. In this setting, testing can be either catheter-based or wireless pH-monitoring or pH-impedance monitoring. In patients with a high probability of GERD (esophagitis grade C and D, histology proven Barrett's mucosa >1 cm, peptic stricture, previous positive pH monitoring) and persistent symptoms, pH-impedance monitoring should be performed on treatment. Recommendations are provided for data acquisition and analysis. Esophageal acid exposure is considered as pathological if acid exposure time (AET) is greater than 6% on pH testing. Number of reflux episodes and baseline impedance are exploratory metrics that may complement AET. Positive symptom reflux association is defined as symptom index (SI) >50% or symptom association probability (SAP) >95%. A positive symptom-reflux association in the absence of pathological AET defines hypersensitivity to reflux.

Conclusions and Inferences
The consensus group determined that grade C or D esophagitis, peptic stricture, histology proven Barrett's mucosa >1 cm, and esophageal acid exposure greater >6% are sufficient to define pathological GERD. Further testing should be considered when none of these criteria are fulfilled.

Ambulatory reflux monitoring for diagnosis of gastro-esophageal reflux disease: Update of the Porto consensus and recommendations from an international consensus group.

Esophageal acid exposure decreases intraluminal baseline impedance levels.

This Review presents current knowledge on the complex popu-lation usually included under the umbrella term of nonerosive reflux disease. The authors outline the need to clearly separate the subsets of patients with real reflux disease from the sub-group with functional heartburn, which does not pertain to GERD.

NERD: an umbrella term including heterogeneous subpopulations

Background
The prevalence of gastroesophageal reflux disease (GERD) has increased in the last decades and it is now one of the most common chronic diseases. Throughout time our insight in the pathophysiology of GERD has been characterized by remarkable back and forth swings, often prompted by new investigational techniques. Even today, the pathophysiology of GERD is not fully understood but it is now recognized to be a multifactorial disease. Among the factors that have been shown to be involved in the provocation or increase of reflux, are sliding hiatus hernia, low lower esophageal sphincter pressure, transient lower esophageal sphincter relaxation, the acid pocket, obesity, increased distensibility of the esophagogastric junction, prolonged esophageal clearance, and delayed gastric emptying. Moreover, multiple mechanisms influence the perception of GERD symptoms, such as the acidity of the refluxate, its proximal extent, the presence of gas in the refluxate, duodenogastroesophageal reflux, longitudinal muscle contraction, mucosal integrity, and peripheral and central sensitization. Understanding the pathophysiology of GERD is important for future targets for therapy as proton pump inhibitor-refractory GERD symptoms remain a common problem.

Purpose
In this review we provide an overview of the mechanisms leading to reflux and the factors influencing perception, in the light of historical developments. It is clear that further research remains necessary despite the recent advances in the understanding of the pathophysiology of GERD.

Pathophysiology of gastroesophageal reflux disease: new understanding in a new era.

P>The aim of the study is to compare the characteristics of reflux episodes in controls and in patients with various degrees of oesophagitis and Barrett's oesophagus. Ambulatory 24-h impedance-pH tracings were analysed from healthy volunteers, patients with non-erosive reflux disease (NERD), patients with grade A oesophagitis, grade B oesophagitis, grade C or D oesophagitis and patients with a short segment (<2 cm) of Barrett's metaplasia. The number of acid and weakly acidic reflux episodes increased from 25.9 +/- 3.9 to 17.9 +/- 1.5 in the controls, 39.9 +/- 6.3 to 33.4 +/- 5.7 in the patients with NERD, 46.6 +/- 6.2 to 40.4 +/- 9.2 in grade A, 68.2 +/- 9.2 to 49.2 +/- 12.3 in grade B, 79.8 +/- 15.6 to 47.4 +/- 4.6 in grade C/D and 75.1 +/- 7.9 to 37.3 +/- 8.5 in the patients with Barrett. The proportion of reflux episodes that is acidic or alkaline was similar all groups. Comparison with normal values revealed that none of the controls, 40% of the patients with NERD, 50% of the patients with grade A, 80% of the patients with grade B and all patients with grade C/D or Barrett's oesophagus had an abnormally high total number of reflux episodes. In the patients with severe oesophagitis a significantly higher percentage of reflux episodes reached the proximal oesophagus (43.8%) compared to the patients with Barrett's oesophagus (19.2%). With increasing degrees of oesophagitis, patients have more reflux episodes but a large overlap between the groups exists making comparison with normal values of limited relevance. In patients with Barrett's oesophagus fewer reflux episodes reach the proximal oesophagus which might explain their low sensitivity to reflux.

Relationship between gastro-oesophageal reflux pattern and severity of mucosal damage

In patients whose main symptom is excessive belching, supragastric belching appears to be the predominant mechanism. This belch pattern is characterized by a rapid influx of air into the oesophagus, immediately followed by rapid air expulsion. The rate at which supragastric belching occurs is influenced by attention and distraction, suggesting a behavioural disorder and speech therapy may be of benefit to these patients. In 17 consecutive patients with excessive belching, concurrent impedance monitoring and high-resolution manometry were performed to ascertain the mechanism of belching. Patients with supragastric belches were referred to a speech therapist, who was familiar with the concept of supragastric belching. Before and after treatment by the speech therapist, patients filled out a VAS scale regarding the severity of their symptoms. In all patients, supragastric belches were identified with impedance monitoring. Eleven patients were referred to a speech therapist, six patients were not able or willing to undergo repetitive treatments. Eleven patients completed treatment by the speech therapist consisting of 10 (8-10) sessions. Overall, the VAS scales showed a significant improvement of the severity of symptoms (P 30%) in their symptoms and four patients reported a modest decrease (<30%). In one patient, the VAS scores indicated an increase in symptoms. Speech therapy performed by a well-informed speech pathologist leads to a significant symptom reduction in patients with excessive supragastric belching. This is the first study indicating benefit of a treatment for excessive belching.

Speech therapy in patients with excessive supragastric belching – a pilot study

Background: With each swallow a certain amount of air is transported to the stomach. The stomach protects itself against excessive distention by swallowed air through belching (gas reflux). The mechanism of belching (transient lower oesophageal sphincter relaxation) is also one of the mechanisms underlying gastro-oesophageal reflux. Aim: To investigate whether swallowing of air leads to an increase in size of the intragastric air bubble and to gastro-oesophageal reflux. Methods: Multichannel intraluminal impedance measurement was used to quantify the incidence of swallowing of air in 20 healthy volunteers before and after a meal. Radiography was used to measure the size of the intragastric air bubble. Gastro-oesophageal reflux was assessed by concurrent impedance and pH measurement. Results: The rate of air swallowing was correlated to the size of the intragastric air bubble postprandially and to the rate of gaseous gastro-oesophageal reflux. The number of air swallows and the size of the intragastric air bubble did not correlate with the number of liquid acid and non-acid reflux episodes. Conclusions: in healthy subjects, air swallowing promotes belching but does not facilitate acid reflux.

Relationships between air swallowing, intragastric air, belching and gastro-oesophageal reflux.

Background Esophageal high-resolution manometry (HRM) is a novel method for esophageal function testing that has prompted the development of new parameters for quantitative analysis of esophageal function. Until now, the reproducibility of these parameters has not been investigated.



Methods  Twenty healthy volunteers underwent HRM on two separate days. Standard HRM parameters were measured. In addition, in conventional (virtual) line tracings, lower esophageal sphincter (LES) resting pressure, relaxation pressure, and relative relaxation pressure were measured. Firstly, for each variable, the mean percentage of covariation (100 × SD/mean: %COV) was derived as a measure of inter- and intra-individual variation. Secondly, Kendall’s coefficients of concordance (W values) were calculated. Thirdly, Bland–Altman plots were used to express concordance graphically.



Key Results  Statistically significant concordance values were found for upper esophageal sphincter (UES) pressure (W = 0.90, P = 0.02), transition zone length (W = 0.92, P = 0.01), LES length (W = 0.81, P = 0.04), LES pressure (W = 0.75, P = 0.05), LES relaxation pressure (W = 0.75, P = 0.03), relative LES relaxation pressure (W = 0.78, P = 0.05), gastric pressure (W = 0.81, P = 0.04), and contraction amplitude 5 cm above the LES (W = 0.86, P = 0.03). In conventional setting, only LES resting pressure (W = 0.835, P = 0.03) proved significant. In HRM tracings, concordance values for contraction wave parameters, and in conventional line tracings, LES relaxation pressure and relative relaxation pressure did not reach levels of statistical significance.



Conclusions & Inferences  Esophageal HRM yields reproducible results. Parameters that represent anatomic structures show better reproducibility than contraction wave parameters. The reproducibility of LES resting and relaxation pressure assessed with HRM is better than with conventional manometry and further supports the clinical use of HRM.

Reproducibility of esophageal high-resolution manometry.

P>Gastro-oesophageal reflux disease (GORD) patients often report an increase in their reflux symptoms during stressful situations. The aim of this study was to assess the influence of acute psychological stress on oesophageal acid perception. In 15 healthy volunteers and 10 GORD patients with a positive symptom-reflux association an oesophageal acid perfusion test was performed, once with and once without the presence of an acute psychological stressor (IQ test). The order of the measurements was randomized. The time from onset of the acid infusion to first acid perception, discomfort and pain was noted. Blood pressure was measured to assess the effect of the stress task. In healthy volunteers, the time to first perception (control task: 617 +/- 174 s vs stress task: 561 +/- 162 s), discomfort (control task: 969 +/- 158 s vs stress task: 940 +/- 151 s) or pain (control task: 1393 +/- 122 s vs stress task: 1366 +/- 121 s) did not differ significantly between both measurements. In GORD patients, no significant differences between both measurements were found either in time to first perception (control task: 63 +/- 26 s vs stress task: 43 +/- 15 s), discomfort (control task: 153 +/- 44 s vs stress task: 249 +/- 62 s) or pain (control task: 558 +/- 139 s vs stress task: 633 +/- 118 s). Systolic blood pressure rose significantly during the stress task in both the healthy volunteers (6 +/- 1 mmHg) and the GORD patients (9 +/- 2 mmHg). Neither in the healthy volunteers nor in the GORD patients, the acute psychological stress induced by an IQ test increased oesophageal acid perception. The observed increase in systolic blood pressure shows that the experimental stressors were effective.

A. J. P. M. Smout

Papers

Relationship between gastro-oesophageal reflux pattern and severity of mucosal damage

Speech therapy in patients with excessive supragastric belching – a pilot study

Relationships between air swallowing, intragastric air, belching and gastro-oesophageal reflux.

Reproducibility of esophageal high-resolution manometry.

Does acute psychological stress increase perception of oesophageal acid