K E L McColl

Studies of acid exposure immediately above the gastro-oesophageal squamocolumnar junction: evidence of short segment reflux

Background and aims: Oesophageal pH is conventionally recorded from a point 5 cm above the lower oesophageal sphincter. However, the mucosal changes of reflux oesophagitis and intestinal metaplasia tend to affect the segment of oesophagus distal to this and close to the squamocolumnar junction. This study set out to investigate oesophageal acid exposure of squamous mucosa close to the squamocolumnar junction. Methods: Dual channel 24 hour pH monitoring was carried out in 11 patients with endoscopy negative dyspepsia and no evidence of gastro-oesophageal reflux by conventional oesophageal pH metry. Oesophageal pH was recorded from electrodes positioned 5 mm and 55 mm proximal to the squamocolumnar junction. A novel technique was developed using metal clips to secure the pH catheter to the oesophageal mucosa and maintain these electrode positions. Oesophageal manometry indicated that the distal electrode was within the high pressure zone of the lower oesophageal sphincter. Results: We found that 24 hour oesophageal acid exposure (per cent time pH <4) was greater 5 mm above the squamocolumnar junction compared with the conventional position 5 cm more proximal (11.7% v 1.8%; p<0.001). The greater acid exposure at the distal versus the conventional site was apparent in both the upright (12.7% v 2.3%) and supine (10.5% v 1.3%) positions, as well as during preprandial (14.2% v 1.6%) and postprandial (21.8% v 2.8%) periods (p<0.001 for each). The number of reflux events recorded close to the squamocolumnar junction was also higher than at the conventional position (168 v 33; p<0.001). There was no correlation between acid exposure at the two sites. Conclusions: The squamous mucosa of the most distal oesophagus is exposed to substantial acidic reflux, even in patients without evidence of conventional reflux disease. This short segment reflux may explain the high incidence of metaplasia and neoplasia at the gastro-oesophageal junction.

Helicobacter pylori infection potentiates the inhibition of gastric acid secretion by omeprazole.

BACKGROUND Omeprazole has a greater intragastric pH elevating effect in Helicobacter pylori positive than negative subjects. Ammonia production byH pylori has been suggested as a probable mechanism. AIMS To assess the effect ofH pylori status on gastric acid secretion during omeprazole treatment, and to examine the possible role of ammonia neutralisation of intragastric acid in increased omeprazole efficacy in infected subjects. METHODS TwentyH pylori positive and 12H pylori negative healthy volunteers were examined before and six to eight weeks after commencing omeprazole 40 mg/day. On both occasions plasma gastrin and acid output were measured basally and in response to increasing doses of gastrin 17 (G-17). Gastric juice ammonium concentrations were also measured. RESULTS Prior to omeprazole, measurements were similar in the H pyloripositive and negative subjects. During omeprazole, median basal intragastric pH was higher in the H pyloripositive (7.95) versus negative (3.75) subjects (p<0.002). During omeprazole basal, submaximal (180 pmol/kg/h G-17), and maximal acid outputs (800 pmol/kg/h G-17) were lower in H pylori positive subjects (0.0, 3.6, 6.0 mmol/h respectively) versus negative subjects (0.3, 14.2, 18.6 mmol/h) (p<0.03 for each). This effect was not explained by neutralisation by ammonia. CONCLUSION The presence ofH pylori infection leads to a more profound suppression of acid secretion during omeprazole treatment. The effect cannot be explained by neutralisation of intragastric acid by bacterial ammonia production and its precise mechanism has to be explained.

The stomach in health and disease

The stomach is traditionally regarded as a hollow muscular sac that initiates the second phase of digestion. Yet this simple view ignores the fact that it is the most sophisticated endocrine organ with unique physiology, biochemistry, immunology and microbiology. All ingested materials, including our nutrition, have to negotiate this organ first, and as such, the stomach is arguably the most important segment within the GI tract. The unique biological function of gastric acid secretion not only initiates the digestive process but also acts as a first line of defence against food-borne microbes. Normal gastric physiology and morphology may be disrupted by Helicobacter pylori infection, the most common chronic bacterial infection in the world and the aetiological agent for most peptic ulcers and gastric cancer. In this state-of-the-art review, the most relevant new aspects of the stomach in health and disease are addressed. Topics include gastric physiology and the role of gastric dysmotility in dyspepsia and gastroparesis; the stomach in appetite control and obesity; there is an update on the immunology of the stomach and the emerging field of the gastric microbiome. H. pylori-induced gastritis and its associated diseases including peptic ulcers and gastric cancer are addressed together with advances in diagnosis. The conclusions provide a future approach to gastric diseases underpinned by the concept that a healthy stomach is the gateway to a healthy and balanced host. This philosophy should reinforce any public health efforts designed to eradicate major gastric diseases, including stomach cancer.

High incidence of adenocarcinoma arising from the right side of the gastric cardia in NW Iran

Background: In the West, the subsite incidence of gastric cancer has changed in recent decades, with cancer of the cardia increasing in incidence and that of the more distal stomach decreasing. NW Iran has a very high incidence of upper gastrointestinal cancer and we have examined the anatomical site specific incidence in this geographical region. Method and materials: Of 33 718 patients who visited our clinic from March 2000 to Jan 2003, 3119 (9.3%) with persistent upper gastrointestinal symptoms underwent upper gastrointestinal fibreoptic endoscopy. Exact tumour site, subsite, and axial view were determined. Demographic data including age, sex, and place of residence were assessed. Using matched data from the cancer registry and endoscopic survey, age standardised rates (ASR) for all subsites were calculated. Results: Upper gastrointestinal cancer was diagnosed histologically in 499 patients (16.0%). The most frequent site was the gastric cardia (126 (25.3%)) followed by the oesophageal body (90 (18.0%)), antrum (82 (16.4%)), corpus (74 (14.8%)), distal oesophagus (57 (11.4%)), gastro-oesophageal junction (47 (9.4%)), and proximal oesophagus (22 (4.4%)). From axial views of the cardia, 51.4% and 6.8% of tumours were found to originate from the lesser and greater curve, respectively. ASR for gastric cancer were 51.2 in males and 15.4 in females. Cardia cancer with ASR of 26.4 in males and 8.6 in females was the major component of gastric cancer. Conclusion: NW Iran is a geographical region with a very high incidence of cardia cancer and with the great majority originating from the right side of the cardia. This suggests a locally acting luminal carcinogen. Studying the aetiology of this cancer in NW Iran is likely to increase our understanding of the rising incidence of this cancer throughout the Western world.

Gastric histology, serological markers and age as predictors of gastric acid secretion in patients infected with Helicobacter pylori.

Background: Acid secretion is intimately associated with most upper gastrointestinal diseases. Helicobacter pylori infection is a major environmental factor modifying acid secretion. Aim: To study the association between the pattern of H pylori gastritis and gastric secretory function in a large number of subjects without specific upper gastrointestinal disease. Methods and materials: Maximal acid output (MAO) was measured in 255 patients with dyspepsia showing normal endoscopy. Activity and severity of gastritis, atrophy and H pylori infection were assessed in body and antral biopsies. The correlations of histological parameters as well as age, sex, height, weight, smoking, serum gastrin, pepsinogen I and II, and their ratio with MAO were determined. Multiple linear regression was used to show the best possible predictors of MAO. Results: Negative relationships: Body atrophy and body-combined (active and chronic) inflammatory scores showed a potent inverse correlation with MAO (correlation coefficients (CC) 0.59 and 0.50, respectively). Body:antral chronic gastritis ratio and body:antral combined inflammation ratio (both with CC = 0.49) and age (CC = 0.44) were also inversely correlated with MAO. Intestinal metaplasia at both antral and body sites had negative relationships with acid output with CC = 0.23 and 0.20, respectively. Positive relationships: Serum pepsinogen I, body H pylori density:combined inflammation ratio and pepsinogen I:II ratio with CC of 0.38, 0.38 and 0.30, respectively, correlated with MAO. The H pylori density: combined inflammation of both antrum and body positively correlated with MAO (CC = 0.29 and 0.38, respectively). Male sex and patient height also positively correlated with acid output. Modelling showed that body combined inflammatory score, body atrophy, age and serum pepsinogen I are independent predictors of acid output (R2 = 0.62). Conclusion: Combination of body gastritis, body atrophy, age and serum pepsinogen I can be used as predictors of acid-secretory state in populations infected with H pylori.

High-resolution esophageal manometry: addressing thermal drift of the manoscan system.

Background  The high resolution esophageal manometry system manufactured by Sierra Scientific Instruments is widely used. The technology is liable to ‘thermal drift’, a change in measured pressure due to change in temperature. This study aims to characterize ‘thermal drift’ and minimize its impact.

Kinetics of transient hiatus hernia during transient lower esophageal sphincter relaxations and swallows in healthy subjects

Background  Proximal displacement of the gastro‐esophageal junction (GEJ) is present in hiatus hernia but also occurs transiently during transient lower esophageal sphincter relaxations (TLESRs) and swallows. Using a novel magnetic‐based technique we have performed detailed examination of the GEJ movement during TLESRs and swallows in healthy subjects.

Disruption of the gastroesophageal junction by central obesity and waist belt: role of raised intra-abdominal pressure

Obesity is a major reason for the recent increase in incidence of reflux disease and cancers at the distal esophagus and gastroesophageal junction (GOJ) and is mediated through a rise in the intra-abdominal pressure (IAP) but the exact mechanisms are unclear. Raised IAP from obesity and with application of waist belt produces mechanical distortion of the GOJ through formation of partial hiatus hernia. Even though there is no trans-sphincteric acid reflux, there is increased ingress of acid into the lower sphincter (intra-sphincteric reflux) as a consequence of raised IAP. In addition, short segment acid reflux is more evident in obese subjects with a belt on. Acid pocket is also enlarged in hiatus hernia, and acts as a reservoir of acid available to reflux whenever the sphincter fails. Above mechanisms may explain the common occurrence of cardiac lengthening and inflammation found in asymptomatic obese subjects. The inflamed cardia is also immunohistochemically similar to non-intestinal Barretts mucosa, which is of etiological importance for cancers at the GOJ. Interventions that can reduce the mechanical distortion and acid exposure at the GOJ, including diet, exercise, drugs, sphincter augmentation therapy, and surgery, are clinically relevant in the treatment of gastroesophageal reflux disease but more data are needed whether if these strategies are also effective in preventing cancer. As a conclusion, raised IAP produces silent mechanical disruption of the GOJ, which may explain the high occurrence of cancers in this region and it is potentially reversible with early interventions.

PTU-138 Central Obesity and Waist Belt Cause Partial Hiatus Hernia and Short Segment Acid Reflux in Healthy Volunteers

Introduction Epidemiology demonstrates an association between obesity, hiatus hernia and acid reflux but mechanism is unclear. We have examined the structure and function of the gastro-oesophageal (GO) junction in healthy subjects with and without obesity and the effects of elevating intra-abdominal pressure with belt. Methods We recruited 8 subjects with normal ( < 94 cm males < 80 cm females) and 8 with increased ( > 102 cm males > 88 cm females) waist circumference, matched for age and gender. To allow accurate monitoring of location of the GO junction and its proximal movement during TLOSRs, a magnet (2x1 mm) was endoscopically clipped to the SCJ. Combined assembly of locator probe, high-resolution pH catheter and slimline manometer was passed nasally. After a standard meal, recording seated upright was continued for an hour. A waist belt was applied on a separate day throughout the entire recording. The effect of obesity was assessed by comparing obese vs. non-obese, both without belt. The effect of belt was assessed by comparing entire group with and without belt. The effect of belt in obesity was assessed by comparing belt-on vs. off in obese subjects. All results were in mean (SEM). Results Location of the SCJ (P = 0.006) and pH step-down (P = 0.01) were displaced proximally in obese vs. non-obese but the diaphragm was not displaced as reflected by peak LOS pressure (pLOS) and pressure inversion point (PIP) (Figure). With belt-on vs. off, there was similarly proximal displacement of SCJ and pH step-down and also of the diaphragm (P = 0.003) and LOS (upper and lower border, P = 0.01 and 0.03 respectively). In obese subjects with belt-on vs. off, there was proximal displacement of SCJ, pH step-down and diaphragm. There was marked proximal migration of SCJ during TLOSRs with its magnitude being less in obese vs. non-obese (4.2 vs. 6.8 cm, P = 0.04) and belt-on vs. off (3.9 vs. 5.5 cm, P = 0.01), consistent with its resting position being already proximally displaced. At traditional site (5 cm above LOS), the mean % time pH < 4 was minimal (0 – 0.5%) in all studied groups, however, acid exposure above the SCJ but below upper border LOS was increased in belt-on vs. off (6.2% vs. 1.6%, P = 0.01) and in obesity with belt-on vs. off (9.7% vs. 3.0%, P = 0.04) but not obese vs. non-obese (P = 0.2). Abstract PTU-138 Figure Conclusion Our findings indicate that in asymptomatic volunteers, central obesity and waist belt cause partial hiatus herniation and that waist belt also causes short segment reflux. Disclosure of Interest None Declared

Mechanisms involved in the development of hypochlorhydria and pangastritis in Helicobacter pylori infection

Helicobacter pylori infection exerts diverse effects on gastric physiology. It may increase gastric acid secretion, reduce it or result in no overall change in acid output1. The disturbance in acid secretion is related to the pattern of gastritis induced by the infection (Figure 1). In subjects with an antral-predominant non-atrophic H. pylori gastritis, acid secretion is normal or increased. This is the pattern of gastritis seen in patients who develop duodenal ulceration. In other subjects it produces an atrophic pangastritis or body-predominant gastritis. This results in markedly reduced acid secretion or achlorhydria and is seen in patients who develop non-cardia gastric cancer.