John P. Seenan

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. Abdominal fat was quantified by magnetic resonance imaging. Jumbo biopsy specimens were taken across the squamocolumnar junction (SCJ). High-resolution pH-metry (12 sensors) and manometry (36 sensors) were performed in upright and supine subjects before and after a meal; the SCJ was visualized fluoroscopically. RESULTS The cardiac mucosa was significantly longer in the large WC group (2.5 vs 1.75 mm; P = .008); its length correlated with intra-abdominal (R = 0.35; P = .045) and total abdominal (R = 0.37; P = .034) fat. The SCJ was closer to the upper border of the lower esophageal sphincter (LES) in subjects with a large WC (2.77 vs 3.54 cm; P = .02). There was no evidence of excessive reflux 5 cm above the LES in either group. Gastric acidity extended more proximally within the LES in the large WC group, compared with the upper border (2.65 vs 4.1 cm; P = .027) and peak LES pressure (0.1 cm proximal vs 2.1 cm distal; P = .007). The large WC group had shortening of the LES, attributable to loss of the distal component (total LES length, 3 vs 4.5 cm; P = .043). CONCLUSIONS Central obesity is associated with intrasphincteric extension of gastric acid and cardiac mucosal lengthening. The latter might arise through metaplasia of the most distal esophageal squamous epithelium and this process might predispose individuals to adenocarcinoma.

Paradox of gastric cardia: it becomes more acidic following meals while the rest of stomach becomes less acidic

Introduction: The proximal cardia region of the stomach has a high incidence of inflammation, metaplasia and neoplasia. It demonstrates less acid buffering following meals than the more distal stomach. Novel high definition pHmetry was employed to investigate acidity at the cardia under fasting conditions and in response to a meal. Methods: 15 healthy subjects were studied. A custom-made 12-electrode pH catheter was clipped at the squamocolumnar junction with four electrodes recording proximal to and eight distal to the squamocolumnar junction. The most distal pH electrode was located at the catheter tip, and nine electrodes in the region of the squamocolumnar junction were 11 mm apart. Results: The electrode situated in the cardia 5.5 mm distal to the squamocolumnar junction differed from all other intragastric electrodes during fasting in recording minimal acidity (pH <4 = 2.2%) while all other intragastric electrodes recorded high intragastric acidity (pH <4 = >39%) (p<0.05). The cardia also differed from the rest of the stomach, showing a marked increase in acidity in response to the meal (from 2.2% fasting to 58.4% at 60–70 min after the meal; p<0.05) while the electrodes distal to the cardia all showed a marked decrease in acidity (p<0.05). These changes in acidity at the cardia following the meal caused the gastric acidity to extend 10 mm closer to the squamocolumnar junction. Conclusion: Whereas the rest of the stomach shows a marked fall in acidity on ingesting a meal, the cardia paradoxically increases in acidity to become the most acidic region throughout the postprandial period.

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.

Acid pocket, hiatus hernia and acid reflux

Acid reflux and its associated symptoms occur most frequently following the ingestion of a meal. This observation presented a dilemma as intragastric pH is at its least acidic following eating due to the buffering effect of the food. However, the observation by Fletcher et al that the proximal cardia region of the stomach escapes the buffering effect of the meal provided a rational explanation for the acidic nature of the postprandial refluxate.1 The zone of high acidity detected in the proximal stomach after a meal has been termed the acid pocket. The presence of the acid pocket has been confirmed by a substantial number of investigators and by a variety of different investigative techniques. The latter have included pH pull-through,2–4 multiple static pH electrodes3 and single photon emission CT (SPECT) of the stomach following intravenous injection of [99MTc]pertechnetate which is secreted by the acid-secreting cells of the gastric mucosa.5 It had been suggested that the acid pocket might represent only a film of acid lining the proximal stomach without any significant volume.6 In the current issue of Gut ( see page 441 ) Beaumont et al placed a catheter at the anatomical site of the acid pocket and aspirated 50–70 ml of gastric juice pH 1.7–2.5 during the postprandial period.7 They were also able to show that the SPECT imaging of …

Development and validation of a probe allowing accurate and continuous monitoring of location of squamo-columnar junction

INTRODUCTION Most pathology of the upper gastrointestinal tract now occurs close to the gastro-oesophageal squamo-columnar junction (SCJ). Studying the pathophysiology of this region even using high resolution pH, impedance and manometry is unreliable due to constant movement with respiration, swallowing and transient lower oesophageal sphincter relaxations. AIMS AND METHODS A technique is reported allowing continuous real-time monitoring of the position of the SCJ. It involves endoscopically clipping a magnet (2 mm × 1 mm) to the SCJ and monitoring its position relative to a probe in the oesophago-gastric lumen. The latter has 26 Hall-Effect sensors mounted at 5mm spacing on a circuit board within a silicone tube. RESULTS Bench studies: The recorded position of the magnet along the length of the probe was compared with its actual position. Accuracy was related to the distance between magnet and probe, orientation of the magnet relative to the probe and whether the magnet was anterior, posterior or lateral to the probe. Including all possible orientations of the magnet at or nearer than 10mm from the probe, the median accuracy along the length of probe was 2.4 mm (IQR 2.1 mm). The proportion of all possible orientations within 10mm of the probe giving an accuracy of ±10 mm was 88.9%. In vivo studies: With simultaneous fluoroscopy, eight healthy subjects were asked to perform normal breathing, deep breathing, water swallows and finally advancement and retraction of probe over a 12 cm segment. The position recorded by fluoroscopy and probe at each second interval were compared. The correlation co-efficient for all 224 position readings was 0.96 (95% CI: 0.89-0.96). No significant interference was observed when the probe was tested alongside high resolution pH and manometry. CONCLUSION Used in conjunction with high resolution pH, impedance and manometry, this technique will allow for the first time detailed studies at the squamo-columnar junction.

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

Abstract Objective. Acid reflux produces troublesome symptoms (heartburn) and complications including esophagitis, Barretts 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. Saliva contains nitrite, derived from the enterosalivary recirculation of dietary nitrate, which is reduced to nitric oxide by gastric acid. The aim of this study was to investigate whether salivary nitrite contributes to dysfunction of the lower esophageal sphincter. Materials and methods. In 20 volunteers, studies of gastro-esophageal function were performed on four separate days, following consumption of a standardized meal, with saliva nitrite concentrations modified differently each day by intra-oral nitrite infusion. Results. The infusions produced an appropriate range in saliva nitrite concentrations, from below to well above the physiological range. The standardized meal induced expected physiological changes in gastro-esophageal function confirming the recordings were sensitive and robust. Esophageal acid exposure (primary outcome) was similar on each study day. Secondary outcomes, including number and duration of reflux events, rate of transient lower esophageal sphincter relaxations, lower esophageal sphincter pressure and rate of gastric emptying were also unaffected by variations in saliva nitrite concentration. Conclusions. Nitrite in swallowed saliva does not modify gastro-esophageal junction function or predispose to gastro-esophageal reflux. The wide range in saliva nitrite concentrations, the sensitivity of the physiological recordings and the number of subjects studied make it very unlikely that an effect has been missed.

High Resolution Oesophageal Manometry: Addressing Thermal Drift

Introduction High resolution manometry (HRM) is a sophisticated and widely used technology allowing detailed examination of oesophageal function. A described limitation of the HRM system is its propensity to ‘thermal drift’. Thermal drift is a false change in the measured pressure attributed to the change from ambient to body temperature. In prolonged studies this effect can be marked. We sought to investigate the nature and magnitude of this phenomenon and to validate the currently employed corrections. Methods Six experiments were performed with the HRM catheter placed in a water bath at a constant depth and temperature of 37°C. Recordings were carried out for 2 h. Pressure readings for the thirty-six sensors were plotted against time. Results The mean pressure change for six experiments and thirty six sensors was 13.1 mmHg (range 1.9–44.7 mmHg). The rate of drift varied between sensors and for an individual sensor between experiments. For an individual sensor within an experiment the pressure increase was linear (R2 > 0.9 in 211 of 216 graphs). In the standard correction for thermal drift, the pressure increase in each sensor at the end of the study is subtracted from the data set to reset the baseline. This was replicated in the recorded pressures and the residual error calculated. The mean error increased with study duration and for a given study was maximal for the early data. For data captured at the start of a 15-min study the mean error with 95% confidence intervals was 1.4 +/− 0.12 mmHg. Corresponding values for a 30-min study were 2.8 +/− 0.24 mmHg and for a 60-min study 6.1 +/− 0.52 mmHg. The distal border of the lower oesophageal sphincter, used to calculate sphincter length, is defined by an increase in pressure of 2 mmHg from intragastric pressure. Errors of this magnitude therefore have the potential to affect measured physiological parameters. A linear correction was then applied to the data, using the best fit line for each sensor within each experiment. For this tailored correction the mean error with 95% confidence intervals was 0.4 +/− 0.017 mmHg and was independent of study duration. Conclusion Thermal drift is better considered as ‘Baseline drift’ a continuous upward drift of the baseline pressure with time rather than a ‘once and for all’ baseline change. A correction process which takes into account the ongoing and linear nature of the drift reduces the error associated with this phenomenon. Incorporating this correction into existing software would improve the accuracy of the system without impact on ease of use.

The development of squamo-columnar junction locator probe and its performance on bench studies

Introduction The position of the squamo-columnar (SC) junction is constantly changing and this precludes accurate monitoring of acid exposure of the most distal oesophagus. The authors have developed a novel probe to allow continuous monitoring of the SC junction location. The method involves endoscopically clipping a small magnet (2 mm diameter and 1 mm thick) to the SC junction and monitoring its position relative to the probe comprising 26 Hall Effect sensors mounted at 5 mm spacing on a circuit board contained within a silastic tube (diameter 3.2 mm). The aim of the current study was to assess the accuracy of the system on the bench. Methods The accuracy was determined by comparing the recorded position of the magnet along the length of the probe with its actual position along the probe. This was assessed with the magnet in various rotations and orientations both anterior and posterior to the probe and various distances away from the probe. As the conductive property of Hall Effect sensors is dependent on temperature, bench studies were performed to assess effects of rising temperature on the systems accuracy. The potential electro-magnetic interference of the locator probe with multi-channels pH probe (Synectics, UK) and solid state high resolution manometer (Synmed, UK) was also investigated. Results The accuracy was related to the distance between magnet and probe, orientation of the field of the magnet relative to the probe and whether the magnet was positioned anterior, posterior or lateral to the probe. Greatest accuracy was with the magnet anterior to the probe and its magnetic field perpendicular to the length of probe with position errors of ±2.3, ±2.9, ±2.7 mm at 5, 10 and 15 mm distance from the probe respectively. The poorest accuracy was with the magnet lateral to the probe and its magnetic field horizontal to the line of the probe, with position errors of ±2.3, ±7.1, ±7.9 mm at 5, 10 and 15 mm distance from the probe respectively. Over 95% of all studied orientations, an accuracy of less than ±10 mm was achieved up to a distance of 15 mm between the magnet and the probe. Increase in temperature from 20°C to 37°C did not affect accuracy of the system even though it reduces the magnetic field strength. The manometer had a minor impact on the systems accuracy due to metallic properties of its sensors but no interference was seen with the pH probe. Conclusion This technique should allow monitoring of the location of the SC junction to an accuracy greater than that of currently available high resolution manometry or multiple pH sensor devices.

Squamo-columnar junction locator probe: an in vivo validation study

Introduction The gastro-oesophageal junction is very mobile and constantly changing position with breathing, swallowing and transient lower oesophageal sphincter relaxation (TLESR). The only method currently available for studying its location is fluoroscopic screening and this is limited by radiation exposure. We have developed a method allowing continuous real-time monitoring of the squamo-columnar (SC) junction without radiation exposure. It involves clipping a small magnet endoscopically to the SC junction and monitoring its location by a series of 26 Hall Effect sensors placed at 5 mm interval within a probe placed in oesophageal lumen. The aim of the study was to validate the new technique against fluoroscopy. Methods In eight subjects, the magnet was attached and locator probe inserted. During simultaneous fluoroscopy, subjects were asked to perform normal breathing, deep breathing, water swallows and finally advancement and retraction of locator probe over 12 cm segment. The fluoroscopy recorded images at a rate of 5 frames per seconds and the locator at 8 Hz. The position recorded by fluoroscopy and locator at each second interval were compared as well as amplitude of each complete manoeuvre. Results The correlation co-efficient for all 224 position readings was 0.96 (95% CI 0.89 to 0.96) and adjusted residual squared (R2) of 0.91. The amplitude for the different manoeuvres was similar by the two techniques (see table 1). Table 1 PWE-123 Comparison and correlation of data from locator probe and fluoroscopy screening Manoeuvre (N; n) Correlation co-efficient (95% CI) Adjusted R2 Median fluoroscopy amplitude (mm) Median locator amplitude (mm) Normal breathing (N=6, n=24) 0.94 (0.93 to 1.28) 0.88 5.50 5.17 Deep breathing (N=10,n=66) 0.95 (0.91 to 1.07) 0.90 12.25 12.01 Water Swallow (N=7,n=55) 0.92 (0.58 to 0.94) 0.84 25.00 26.23 Insertion and Withdrawal (N=6,n=80) 0.95 (0.82 to 0.96) 0.90 92.80 85.59 N; number of events, n; number of 1 s interval data points from events, R2; residual squared, mm; millimetres Conclusion The locator allows continuous monitoring of the location of the SC junction with an accuracy equivalent to fluoroscopic screening and without any radiation exposure.

PTH-040 The effect of salivary nitrite on gastric emptying

Introduction Human saliva has a high nitrite concentration from the entero-salivary recirculation of dietary nitrate. Swallowed nitrite reacts with acidic gastric juice forming nitric oxide (NO). Increasing NO bioactivity, by inhibiting phosphodiesterase, enhances gastric accommodation and delays gastric emptying. Aims To determine (1) whether nitrite in saliva affects gastric emptying and (2) whether nitrite in saliva alters postprandial intragastric pressure (IGP). Methods 20 healthy subjects (11 males) were studied. On four separate days high-resolution manometry was performed during 15 min fasting and for 90 min following a standardised meal. Post-prandially, solutions of 0, 0.286, 2 and 14 mmol/l potassium nitrite were infused into the oral cavity. Solutions were randomised and double-blinded. Saliva was collected at baseline, 30, 60 and 90 min after the meal. Salivary nitrite concentrations were quantified by Griess reaction. Gastric emptying was assessed by means of a specially designed breath test. 14C labelled sodium acetate was incorporated, during baking, into a rolled oats flapjack which constituted part of our standardised meal. Following consumption of the flapjack, breath samples were taken at regular intervals. The quantity of 14C appearing in breath per unit time (μmol/minute) was calculated. A generalised linear regression method was used to estimate gastric half-emptying times (T½). Mean IGP was defined relative to atmospheric pressure as the lowest mean pressure recorded in the six most distal manometry sensors. Results are medians and ranges. Results Salivary nitrite concentrations at 60 min were 24.35 μmol/l (3.86–65.46), 80.42 μmol/l (20.88–158.79), 358.4 μmol/l (118.2–726.6) and 2694 μmol/l (600–8087) for the solutions containing 0, 0.286, 2 and 14 mmol/l nitrite, respectively. There was no significant difference in the rate of gastric emptying (T½) between the control solution (103.5 min, 56.2–239.1) and those containing 0.286 mmol/l (113.4 mins, 68.7–254.8, p=0.56), 2 mmol/l (121.7 min, 39.8–270.0, p=0.93) and 14 mmol/l (114.4 mins, 79.1–390.1, p=0.75). There was no difference in the increase in IGP recorded between the control solution (4.06 mm Hg, −2.64–7.31) and those containing 0.286 mmol/l (4.42 mm Hg, −4.55–8.45, p=0.61), 2 mmol/l (4.66 mm Hg, −0.94-9.16, p=0.27) and 14 mmol/l (4.24 mm Hg, −2.12–8.17, p=0.81) potassium nitrite. Conclusion Despite an excellent range of salivary nitrite concentrations, extending over and beyond the normal physiological range, no difference in the rate of gastric emptying or postprandial rise in IGP was seen. This suggests salivary nitrite does not affect gastric emptying.