Kyoto international consensus report on anatomy, pathophysiology and clinical significance of the gastro-oesophageal junction.

Objective: An international meeting was organised to develop consensus on (1) the landmarks to define the gastro-oesophageal junction (GOJ), (2) the occurrence and pathophysiological significance of the cardiac gland, (3) the definition of the gastro-oesophageal junctional zone (GOJZ) and (4) the causes of inflammation, metaplasia and neoplasia occurring in the GOJZ.

Design: Clinical questions relevant to the afore-mentioned major issues were drafted for which expert panels formulated relevant statements and textural explanations.A Delphi method using an anonymous system was employed to develop the consensus, the level of which was predefined as ≥80% of agreement.

What is causing the rising incidence of esophageal adenocarcinoma in the West and will it also happen in the East?

In the West, the incidence of esophageal adenocarcinoma, which is a long-term complication of damage by gastroesophageal reflux, has been rising over recent decades. Two main factors are likely to account for this increase. The first is the rising incidence of central obesity which promotes gastroesophageal reflux.

The Gastric Acid Pocket (or Coat) and Its Attenuation in Helicobacter pylori-infected Subjects.

In 2001, it was observed that the cardia region of the lumen of the stomach remained highly acidic after a meal and escaped the buffering effect of the food. This phenomenon was termed the acid pocket and is thought to explain why reflux symptoms occur after meals despite the buffering effect of food. This review describes the discovery of the acid pocket and our progress in understanding the intragastric physiology producing it, its exaggeration in hiatus hernia and role in reflux disease.

Abdominal Compression by Waist Belt Aggravates Gastroesophageal Reflux, Primarily by Impairing Esophageal Clearance.

Background & Aims: Central obesity promotes gastroesophageal reflux, which may be related to increased intra-abdominal pressure. We investigated the effect of increasing abdominal pressure by waist belt on reflux in patients with reflux disease.

Methods: We performed a prospective study of patients with esophagitis (n = 8) or Barrett's esophagus (n = 6); median age was 56 years and median body mass index was 26.

The gastric acid pocket is attenuated in infected subjects.

Objective: Gastric acid secretory capacity in different anatomical regions, including the postprandial acid pocket, was assessed in positive and negative volunteers in a Western population.

Design: We studied 31 positive and 28 negative volunteers, matched for age, gender and body mass index. Jumbo biopsies were taken at 11 predetermined locations from the gastro-oesophageal junction and stomach.

Short-segment and intrasphincteric gastroesophageal reflux.

Purpose Of Review: The traditional gold standard for measuring gastroesophageal acid reflux has been by placing a pH sensor 5 cm proximal to the lower esophageal sphincter. It is known that damage induced by reflux is maximal near to the gastroesophageal junction and this has stimulated interest in determining acid reflux at that site.

Recent Findings: The extent of esophageal exposure from refluxing gastric acid is inversely related to the distance proximal to the gastroesophageal junction.

Hiatus hernia in healthy volunteers is associated with intrasphincteric reflux and cardiac mucosal lengthening without traditional reflux.

Background And Aims: Hiatus hernia (HH) is a key mediator of gastro-oesophageal reflux disease but little is known about its significance in the general population. We studied the structure and function of the gastro-oesophageal junction in healthy volunteers with and without HH.

Methods: We compared 15 volunteers with HH, detected by endoscopy or MRI scan, but without gastro-oesophageal reflux disease with 15 controls matched for age, gender and body weight.

Worldwide Inverse Association between Gastric Cancer and Esophageal Adenocarcinoma Suggesting a Common Environmental Factor Exerting Opposing Effects.

Objectives: The incidence of esophageal adenocarcinoma (EAC) is increasing while adenocarcinoma of the stomach is decreasing. We have investigated whether the incidences of these two cancers and their time trends might be inversely related pointing to a common environmental factor exerting opposite effects on these cancers.

Methods: For cross-sectional analyses data were abstracted from "Cancer Incidence in Five Continents" (CI5) Volume X and GLOBOCAN 2012.

The Role of the Acid Pocket in Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease is one of the commonest chronic conditions in the western world and its prevalence is increasing worldwide. The discovery of the acid pocket explained the paradox of acid reflux occurring more frequently in the postprandial period despite intragastric acidity being low due to the buffering effect of the meal. The acid pocket was first described in 2001 when it was detected as an area of low pH immediately distal to the cardia using dual pH electrode pull-through studies 15 minutes after a meal.

In healthy volunteers, immunohistochemistry supports squamous to columnar metaplasia as mechanism of expansion of cardia, aggravated by central obesity.

Introduction: Recently, we showed that the length of cardiac mucosa in healthy volunteers correlated with age and obesity. We have now examined the immunohistological characteristics of this expanded cardia to determine whether it may be due to columnar metaplasia of the distal oesophagus.

Methods: We used the squamocolumnar junction (SCJ), antral and body biopsies from the 52 Helicobacter pylori-negative healthy volunteers who had participated in our earlier physiological study and did not have hiatus hernia, transsphincteric acid reflux, Barrett's oesophagus or intestinal metaplasia (IM) at cardia.

Waist belt and central obesity cause partial hiatus hernia and short-segment acid reflux in asymptomatic volunteers.

Objective: There is a high incidence of inflammation and metaplasia at the gastro-oesophageal junction (GOJ) in asymptomatic volunteers. Additionally, the majority of patients with GOJ adenocarcinomas have no history of reflux symptoms. We report the effects of waist belt and increased waist circumference (WC) on the physiology of the GOJ in asymptomatic volunteers.

Pathophysiology of gastroesophageal reflux disease.

The gastroesophageal junction is structurally complex and functionally designed to ensure the acid secreted by the most proximal gastric mucosa flows towards the stomach and not up onto the oesophageal squamous mucosa. The pattern and mechanism of reflux vary with the severity of reflux disease and this probably represents different ends of a spectrum rather than distinct pathophysiological mechanisms. Nearly all patients with severe reflux disease have hiatus hernia, however, a substantial proportion of patients with mild reflux disease do not, and this may be a result of intermittent or partial hiatus hernia undetectable by current available tools.

Central obesity in asymptomatic volunteers is associated with increased intrasphincteric acid reflux and lengthening of the cardiac mucosa.

Background & Aims: In the West, a substantial proportion of subjects with adenocarcinoma of the gastric cardia and gastroesophageal junction have no history of reflux. We studied the gastroesophageal junction in asymptomatic volunteers with normal and large waist circumferences (WCs) to determine if central obesity is associated with abnormalities that might predispose individuals to adenocarcinoma.

Methods: We performed a study of 24 healthy, Helicobacter pylori-negative volunteers with a small WC and 27 with a large WC.

Towards minimally invasive monitoring for gastroenterology - An external Squamocolumnar Junction Locator.

Transient lower oesophageal sphincter relaxations (TLOSRs) occur frequently and are the main mechanism of acid reflux. The only means of currently detecting TLOSRs is intra-luminal manometry and the probes themselves may stimulate TLOSRs. The squamo-columnar junction moves 4-5 centimeters proximally during TLOSRs and this provides a means of detecting such episodes.

Measuring movement and location of the gastroesophageal junction: research and clinical implications.

Understanding the physiology of gastroesophageal junction (GEJ) is important as failure of its function is associated with reflux disease, hiatus hernia, and cancer. In recent years, there have been impressive developments in high resolution technologies allowing measurement of luminal pressure, pH, and impedance. One obvious deficiency is the lack of technique to monitor the movement and location of the GEJ over a prolonged period of time.

Pathophysiology of duodenal ulcer disease.

: Before the discovery of Helicobacter pylori infection some 12 years ago, three major disturbances in gastric physiology had been identified in patients with duodenal ulcer disease. These abnormalities were: impaired acid inhibition of gastrin release from the antral mucosa, increased basal and stimulated acid secretion by the body of the stomach and increased acid load in the duodenum. Some of these abnormalities in gastric function can now be explained by the effects of H.

Effect of nitrite delivered in saliva on postprandial gastro-esophageal function.

Objective: Acid reflux produces troublesome symptoms (heartburn) and complications including esophagitis, Barrett's esophagus, and adenocarcinoma. Reflux occurs due to excessive and inappropriate relaxation of the lower esophageal sphincter. An important mediator of this is nitric oxide, high concentrations of which are generated within the lumen when swallowed saliva meets gastric acid.

Mechanism of association between BMI and dysfunction of the gastro-oesophageal barrier in patients with normal endoscopy.

Introduction: The association between body mass index (BMI) and gastro-oesophageal pressure gradient (GOPG) is incompletely understood. We examined the association between BMI and gastro-oesophageal (GO) barrier function and the effect of mechanically increasing intra-abdominal pressure on GO physiology.

Methods: (A) 103 dyspeptic patients with normal endoscopy underwent 24 h pH-metry and upper gastrointestinal manometry.

BMI is superior to symptoms in predicting response to proton pump inhibitor: randomised trial in patients with upper gastrointestinal symptoms and normal endoscopy.

Objectives: In most patients undergoing endoscopy for upper gastrointestinal (GI) symptoms in the Western world, no macroscopic abnormality or evidence of Helicobacter pylori infection is identified. Following this negative investigation, proton pump inhibitor (PPI) therapy is usually prescribed. The aim of this study was to assess the value of such treatment compared with placebo and to identify predictors of response.