Elad Kaufman

Normative values and inter-observer agreement for liquid and solid bolus swallows in upright and supine positions as assessed by esophageal high-resolution manometry.

Background  High‐resolution manometry (HRM) with spatiotemporal representation of pressure data is a recent advance in esophageal measurement. At present, normal values are available for 5 mL water swallows in the supine position. This study provides reference values for liquid and solid bolus swallows in the upright seated and supine positions.

Failure to respond to physiologic challenge characterizes esophageal motility in erosive gastro-esophageal reflux disease

Background  Non‐specific esophageal dysmotility with impaired clearance is often present in patients with gastro‐esophageal reflux disease (GERD), especially those with erosive disease; however the physio‐mechanic basis of esophageal dysfunction is not well defined.

Gastroesophageal Junction: Structure and Function as Assessed by Using MR Imaging

PURPOSE To develop and validate magnetic resonance (MR) imaging protocols for quantitative assessment of the structural and functional properties of the gastroesophageal junction (GEJ) and to compare MR imaging detection of reflux events against concurrent manometry as a reference method. MATERIALS AND METHODS The local ethics committee approved this study, and written informed consent was obtained. Twelve healthy volunteers were examined. Three-dimensional models of the GEJ and proximal portion of the stomach were reconstructed from high-spatial-resolution anatomic MR images to assess the insertion angle of the esophagus into the stomach and proximal stomach distention before and after ingestion of a large test meal. A linear mixed-effects model was used to detect differences in the insertion angle and proximal stomach distention with respect to the respiratory cycle and gastric filling. Additionally, dynamic MR imaging at high temporal resolution was used to detect reflux events. RESULTS The esophageal insertion angle, given in units of plane angle (radians), was more acute in expiration than in inspiration (0.57 vs 0.73 radian, P = .004) but was not affected by feeding. Progressive distention of the proximal stomach was observed from baseline compared with the postprandial period (0.95 vs 0.65 radian(-1), P < .05). Eighteen reflux events detected by using MR imaging were also detected by using manometry. CONCLUSION MR imaging methods were developed and validated for the assessment of GEJ structure and function (a) to describe the effects of respiration and feeding on the reflux barrier and (b) to detect reflux events in real time. Anatomic and dynamic MR imaging may be useful techniques in the assessment of GEJ physiology and reflux.

Abnormal Structure and Function of the Esophagogastric Junction and Proximal Stomach in Gastroesophageal Reflux Disease

OBJECTIVES:This study applies concurrent magnetic resonance imaging (MRI) and high-resolution manometry (HRM) to test the hypothesis that structural factors involved in reflux protection, in particular, the acute insertion angle of the esophagus into the stomach, are impaired in gastroesophageal reflux disease (GERD) patients.METHODS:A total of 24 healthy volunteers and 24 patients with mild-moderate GERD ingested a test meal. Three-dimensional models of the esophagogastric junction (EGJ) were reconstructed from MRI images. Measurements of the esophagogastric insertion angle, gastric orientation, and volume change were obtained. Esophageal function was assessed by HRM. Number of reflux events and EGJ opening during reflux events were assessed by HRM and cine-MRI. Statistical analysis applied mixed-effects modeling.RESULTS:The esophagogastric insertion angle was wider in GERD patients than in healthy subjects (+7°±3°; P=0.03). EGJ opening during reflux events was greater in GERD patients than in healthy subjects (19.3 mm vs. 16.8 mm; P=0.04). The position of insertion and gastric orientation within the abdomen were also altered (both P<0.05). Median number of reflux events was 3 (95% CI: 2.5–4.6) in GERD and 2 (95% CI: 1.8–3.3) in healthy subjects (P=0.09). Lower esophageal sphincter (LES) pressure was lower (−11±2 mm Hg; P<0.0001) and intra-abdominal LES length was shorter (−1.0±0.3 cm, P<0.0006) in GERD patients.CONCLUSIONS:GERD patients have a wider esophagogastric insertion angle and have altered gastric morphology; structural changes that could compromise reflux protection by the “flap valve” mechanism. In addition, the EGJ opens wider during reflux in GERD patients than in healthy volunteers: an effect that facilitates volume reflux of gastric contents.

Inter-observer reproducibility and analysis of gastric volume measurements and gastric emptying assessed with magnetic resonance imaging.

Background  Magnetic resonance (MR) imaging provides direct, non‐invasive measurements of gastric function and emptying. The inter‐observer variability (IOV) of MR volume measurements and the most appropriate analysis of MR data have not been established. To assess IOV of total gastric volume (TGV) and gastric content volume (GCV) measurements from MR images and the ability of standard power exponential (PowExp), and a novel linear exponential (LinExp) model to describe MR data.

Effects of clonidine and sumatriptan on postprandial gastric volume response, antral contraction waves and emptying: an MRI study.

Abstract  Gastric emptying (GE) may be driven by tonic contraction of the stomach (‘pressure pump’) or antral contraction waves (ACW) (‘peristaltic pump’). The mechanism underlying GE was studied by contrasting the effects of clonidine (α2‐adrenergic agonist) and sumatriptan (5‐HT1 agonist) on gastric function. Magnetic resonance imaging provided non‐invasive assessment of gastric volume responses, ACW and GE in nine healthy volunteers. Investigations were performed in the right decubitus position after ingestion of 500 mL of 10% glucose (200 kcal) under placebo [0.9% NaCl intravenous (IV) and subcutaneous (SC)], clonidine [0.01 mg min−1 IV, max 0.1 mg (placebo SC)] or sumatriptan [6 mg SC (placebo IV)]. Total gastric volume (TGV) and gastric content volume (GCV) were assessed every 5 min for 90 min, interspersed with dynamic scan sequences to measure ACW activity. During gastric filling, TGV increased with GCV indicating that meal volume dictates initial relaxation. Gastric contents volume continued to increase over the early postprandial period due to gastric secretion surpassing initial gastric emptying. Clonidine diminished this early increase in GCV, reduced gastric relaxation, decreased ACW frequency compared with placebo. Gastric emptying (GE) rate increased. Sumatriptan had no effect on initial GCV, but prolonged gastric relaxation and disrupted ACW activity. Gastric emptying was delayed. There was a negative correlation between gastric relaxation and GE rate (r2 = 49%, P < 0.001), whereas the association between ACW frequency and GE rate was inconsistent and weak (r2 = 15%, P = 0.05). These findings support the hypothesis that nutrient liquid emptying is primarily driven by the ‘pressure pump’ mechanism.

Effects of baclofen on the functional anatomy of the oesophago-gastric junction and proximal stomach in healthy volunteers and patients with GERD assessed by magnetic resonance imaging and high-resolution manometry: a randomised controlled double-blind study.

The mechanism of reflux protection may involve a ‘flap valve’ at the oesophago‐gastric junction (OGJ).

96 The Structure and Function of the Gastro-Esophageal Junction in Health and Reflux Disease Assessed By Magnetic Resonance Imaging and High Resolution Manometry

nitrate, and during acid reflux, generation of NO is shifted to the distal esophagus. We have demonstrated that high concentrations of luminal NO can impair the gastric mucosal barrier function by disrupting the tight junction (Gut 2008). We hypothesized that NO generated luminally during acid reflux could disrupt the esophageal barrier function and provoke DIS. Aim: To investigate the direct effects of luminal NO on the esophageal barrier function using an ex vivo chamber model. Design and Setting: A chamber model in which the rat esophageal mucosal membrane was mounted between the two halves of a chamber was designed to simulate the microenvironment of the lumen and the adjacent mucosa of the esophagus. On the mucosal side of the chamber, NO was generated by the acidification of physiologic concentrations of sodium nitrite. The epithelial barrier function was evaluated by electrophysiological transmembrane resistance (R) and membrane permeability with 3H-mannitol flux in four groups; Krebs buffer, acid alone (pH 1.5), acid + sodium nitrite 5.0 mM, and acid + sodium nitrite 1.0 mM. Intercellular space diameters were measured on transmission electron microscopy photomicrographs. Results: In all groups except for Krebs buffer, the R decreased rapidly within the initial 15 minutes, followed by gradual decrease thereafter. At 180 minutes, the R decreased by 34% in acid alone group, by 39% in acid + nitrite 1.0 mM group, by 45% in acid + nitrite 5.0 mM group by 55%. Consequently, the administration of acidified nitrite (1.0 mM or 5.0 mM) to the mucosal side significantly decreased the R compared with that of the acid alone (p<0.01). While epithelial permeability with 3Hmannitol slightly increased at 180 minutes in acid alone group, it remarkably increased in acid + nitrite 5.0 mM group. Thus, the administration of acidified nitrite to the mucosal side significantly increased epithelial permeability compared with the acid alone group (p<0.05). DIS was observed in the nitrite groups but not in the acid alone group. Conclusions: The NO generated luminally via acidification of nitrite disrupted the barrier function of the esophageal epithelium and provoked DIS, suggesting that NO generated luminally contributes to DIS observed in GERD patients and plays an important role in the pathophysiology of GERD.

Post-prandial reflux suppression by a raft-forming alginate (Gaviscon Advance) compared to a simple antacid documented by magnetic resonance imaging and pH-impedance monitoring: mechanistic assessment in healthy volunteers and randomised, controlled, doub

Alginates form a raft above the gastric contents, which may suppress gastro‐oesophageal reflux; however, inconsistent effects have been reported in mechanistic and clinical studies.

OC-068 Structure and function of the gastro-oesophageal junction in patients after laparoscopic fundoplication: concurrent magnetic resonance imaging and high-resolution manometry studies

Introduction Laparoscopic fundoplication provides effective reflux control in patients with gastro-oesophageal reflux disease (GERD); however a proportion of patients that undergo surgery experience troublesome symptoms. Improved results may be possible if more was known about the structural factors that effect treatment outcome. This study applied concurrent MRI and HRM technology to compare the structure and function of the GEJ in GERD patients after fundoplication to control groups of GERD patients and healthy participants (HPs). Methods Eight GERD patients were studied at least 3 months after laparoscopic fundoplication with subjectively good treatment outcome (7M, age 18–67 years). Results of pH-impedance monitoring off acid suppression before and after fundoplication were available. 12 patients with GERD on medical therapy (7M, age 20–55 years) and 12 HPs (7M, age 26–36 years) with no history of gastro-intestinal disease or surgery. Validated MRI measurements of the oesophago-gastric insertion angle (Radiology in press) and gastric volumes were performed at baseline and after ingestion of high calorie meal (McDonalds Cheeseburger, Chips, Milkshake, 735 kcal). Visual Analogue Scales (100 mm VAS) documented dyspeptic symptoms. Results GEJ pressure increased from before to after fundoplication (8.3±1.2 vs 14.2±1.7 mm Hg, p=0.03) whereas acid exposure (10.3±2.2 vs 5.4±2.1, p=0.001) and reflux episodes reduced (39±3 vs 24±2, p=0.019). The insertion angle after the meal was more obtuse after surgery than in the disease and healthy controls (61° vs 48° vs 41°, p<0.008). Moreover normal variation of insertion angle with respiration was lost. Postprandial gastric air content was higher after fundoplication compared to the disease and healthy controls in absolute terms (523 vs 146 vs 178 ml, p<0.001) and as a proportion of total gastric content (78% vs 12% vs 16%, p<0.005). There was a positive correlation between insertion angle and gastric air content (r2=0.95, p=0.050). Postprandial abdominal bloating was higher for the fundoplication group compared to the GERD and healthy groups. (VAS 55±21 vs 13±23 vs 20±10 mm, p=0.049) and there was also an association between gastric air content and the this symptom (r2=0.82, p=0.07). Conclusion Novel, quantitative MRI measurements demonstrate alterations to GEJ structure after fundoplication, specifically to the oesophago-gastric insertion angle, that are linked to gastric retention of air and the sensation of bloating, even in patients with a good subjective outcome. Modification of surgical technique to restore more normal GEJ morphology may be equally effective for reflux protection but cause less troublesome bloating.