Matthias Sauter

Measuring the interaction of meal and gastric secretion: a combined quantitative magnetic resonance imaging and pharmacokinetic modeling approach

Background  The stimulation and intragastric accumulation of gastric secretion has been recognized as an important factor in gastroesophageal reflux disease. However, the interaction of gastric secretion and meal emptying has not been fully understood. Current methods to assess gastric secretion are either invasive or unable to provide information on its volume, distribution and dynamics. The aim of this study was to quantify the interaction between meal emptying and meal induced gastric secretion by using quantitative magnetic resonance imaging (MRI) and pharmacokinetic analysis.

Toward more accurate measurements of anorectal motor and sensory function in routine clinical practice: validation of high-resolution anorectal manometry and Rapid Barostat Bag measurements of rectal function.

Measurements of anorectal function using high‐resolution anorectal manometry (HR‐ARM) and rectal barostat technology provide more reliable results than standard ARM with an elastic balloon; however, HR‐ARM results have not been compared to ARM and standard barostat protocols are impractical in routine clinical practice. The aim of this study was to validate HR‐ARM against standard ARM and standard barostat against a novel Rapid Barostat Bag (RBB) measurement and elastic balloon measurements of rectal function.

The effect of standard compared to enhanced instruction and verbal feedback on anorectal manometry measurements

Background  Guidelines recommend instruction and motivation during anorectal manometry; however, its impact on findings has not been reported. This study assessed the effects of standard versus enhanced instruction and verbal feedback on the results of anorectal manometry.

Assessment of Obstructive Defecation by High-Resolution Anorectal Manometry Compared With Magnetic Resonance Defecography

BACKGROUND & AIMS Patients with obstructive defecation have abnormalities of anorectal function and/or structure. Conventional anorectal manometry (ARM) can identify abnormal function and behavior (dyssynergia); however, agreement between manometry and defecography is only fair. High-resolution (HR)-ARM may improve diagnostic agreement by differentiating pressure effects caused by dyssynergia and obstruction. We compared HR-ARM findings with magnetic resonance (MR) defecography in the clinical assessment of patients with symptoms of obstructive defecation defined by Rome III criteria. METHODS HR-ARM (Manoscan AR 360; Given Imaging, Yoqeam, Israel) assessed anal sphincter function and pressure during simulated defecation. Abnormal manometric findings were classified according to the Rao system and compared with MR defecography as the reference standard. RESULTS A total of 188 consecutive patients (155 women; age, 19-93 y) with obstructive defecation underwent a full investigation. Compared with patients with dyssynergia on MR imaging (n = 66), patients with structural pathology (n = 87) had lower resting (P < .003) and squeeze pressures (P < .011), but a higher rectoanal pressure gradient (P < .0001) on HR-ARM. High intrarectal pressure with a steep, positive pressure gradient consistent with outlet obstruction on HR-ARM was present in 24 patients with intra-anal intussusception on MR imaging. This pattern was not observed in other patients. Interobserver agreement was substantial for HR-ARM diagnoses (κ = 0.67; 95% confidence interval, 0.559-0.779). Diagnostic accuracy for dyssynergia was 82% compared with MR imaging (sensitivity, 77% [51 of 66]; specificity, 85% [104 of 122]). CONCLUSIONS The diagnostic agreement between anorectal HR-ARM and MR defecography is high and pressure measurements accurately identify recto-anal dyssynergia and intra-anal outlet obstruction by structural pathology as causes of obstructive defecation.

Validation of a golden angle radial sequence (GOLD) for abdominal T1 mapping during free breathing: Demonstrating clinical feasibility for quantifying gastric secretion and emptying

To validate a magnetic resonance imaging sequence suitable for quantitative assessment of acid suppression by a proton pump inhibitor (PPI) on gastric secretion and emptying in clinical practice.

Pharyngeal swallowing and oesophageal motility during a solid meal test: a prospective study in healthy volunteers and patients with major motility disorders

BACKGROUND The factors that determine how people eat when they are healthy or have disease have not been defined. We used high resolution manometry (HRM) to assess pharyngeal swallowing and oesophageal motility during ingestion of a solid test meal (STM) in healthy volunteers and patients with motility disorders. METHODS This study was based at University Hospital Zurich (Zürich, Switzerland). Healthy volunteers who responded to an advertisement completed HRM with ten single water swallows (SWS) in recumbent and upright positions followed by a 200 g rice STM in the upright position. Healthy volunteers were stratified for age and sex to ensure a representative population. For comparison, consecutive patients with major motility disorders on SWS and patients with dysphagia but no major motility disorders on SWS (disease controls) were selected from a database that was assembled prospectively; the rice meal data were analysed retrospectively. During STM, pharyngeal swallows were timed and oesophageal contractions were classified as representing normal motility or different types of abnormal motility in accordance with established metrics. Factors that could potentially be associated with eating speed were investigated, including age, sex, body-mass index, and presence of motility disorder. We compared diagnoses based on SWS findings, assessed with the Chicago Classification v3.0, with those based on STM findings, assessed with the Chicago Classification adapted for solids. These studies are registered with ClinicalTrials.gov, numbers NCT02407938 and NCT02397616. FINDINGS Between April 2, 2014, and May 13, 2015, 72 healthy volunteers were recruited and underwent HRM. Additionally, we analysed data from 54 consecutive patients with major motility disorders and 53 with dysphagia but no major motility disorders recruited between April 2, 2013, and Dec 18, 2014. We found important variations in oesophageal motility and eating speed during meal ingestion in healthy volunteers and patients. Increased time between swallows was accompanied by more effective oesophageal contractions (in healthy volunteers, 20/389 [5%] effective swallows at <4 s between swallows vs 586/900 [65%] effective swallows at >11 s between swallows, p<0·0001). Obstructive, spastic, or hypercontractile swallows were rare in healthy volunteers (total <1%). Patients with motility disorders ate slower than healthy volunteers (14·95 g [IQR 11-25] per min vs 32·9 g [25-40] per min, p<0·0001) and pathological oesophageal motility were reproduced when patients consumed the STM. In healthy volunteers, eating speed was associated only with frequency of swallows (slope 2·5 g per min per pharyngeal swallow per min [95% CI 1·1-4·0], p=0·0009), whereas in patients with dysphagia, it was correlated with frequency of effective oesophageal contractions (6·4 g per min per effective contraction per min [4·3-8·5], p<0·0001). Diagnostic agreement was good between the HRM with SWS and rice STM (intra-class correlation coefficient r=0·81, 95% CI 0·74-0·87, p<0·0001). INTERPRETATION Our results show normative values for pharyngeal swallowing and oesophageal motility in healthy volunteers. Detailed analysis of HRM data acquired during an STM shows that the rate-limiting factor for intake of solids in health is the frequency of pharyngeal swallowing and not oesophageal contractility. The reverse is true in patients with oesophageal motility disorders, in whom the frequency of effective oesophageal contractions determines eating speed. FUNDING University Hospital Zurich.

The Cause of Dysphagia in Eosinophilic Esophagitis: Obstruction to Bolus Passage Not Oesophageal Dysmotility

Introduction Eosinophilic Oesophagitis (EO) presents with dysphagia and chest pain; however the cause of symptoms remains uncertain. Endoscopy reveals fibrotic and inflammatory mucosal disease but rarely tight stenosis. Conventional manometry with water swallows is usually normal; however this may not be clinically relevant as most patients report dysphagia on eating bread and meat but not on drinking liquids. This study applied HRM with water and solid bolus swallows to identify abnormal oesophageal function in EO patients and to associate abnormal pressure events with symptoms. Methods Retrospective case review of 14 consecutive patients (10 male; age 36 (26–65)) on two sites referred for HRM with EO on biopsy of proximal and distal oesophagus. HRM studies in the seated position included 10×5 ml water swallows and 5–10 solid (bread) swallows. 23 healthy volunteers (11 M:12 F, age 20–56) served as control. Association between abnormal pressure events and symptoms was assessed on a per patient and per swallow basis. Results HRM identified oesophageal dysfunction in 3/14 (21%) patients with water swallows and 11/14 (79%) patients with solids (p<0.008). All 11 had increased intrabolus pressure gradient (IBPG) ≥30 mm Hg with solids (maximum at lower oesophageal sphincter (LOS) (n=9), mid-oesophagus (n=1) and upper oesophageal sphincter (n=1)). Per patient: Typical symptoms were reported with IBPG >30 mm Hg by 1 (7%) patient with water and 7 (50%) patients with solids (p=0.039). Conversely, 7/11 (64%) patients with IBPG >30 mm Hg had symptoms (7/7 patients with IBPG >50 mm Hg). Per swallow: There was temporal association between raised IBPG and patient reports of symptoms (p<0.001). Pan-oesophageal pressurisation >30 mm Hg triggered dysphagia; compartmentalised IBP >50 mm Hg between peristalsis and LOS triggered either dysphagia or chest pain. No association was present for any other pressure event. Patients that had received steroids and/or dilation (n=7) had lower IBPG and reported less symptoms than untreated patients (n=7) (both p<0.001); however, if it occurred, the association between IBPG and symptoms remained. One healthy subject had increased frequency of low-amplitude oesophageal spasm; however none had raised OGPG >30 mm Hg with solids and none reported symptoms. Conclusion Patients with EO have normal motility but evidence of structural obstruction to solid bolus passage (usually across the LOS), presumably due to oesophageal stenosis or reduced LOS compliance due to fibrosis and inflammation. In all but one case this was evident only with solid bolus. Raised IBPG was closely associated with patient reports of symptoms and both improved on treatment.

What to eat and drink in the festive season: A pan-European, observational, cross-sectional study

Background Digestive discomfort after meals is common in the community, especially during the festive season. It is uncertain whether this is related to intake of either high-calorie or high-fat foods or, alternatively, intake of specific foods. This prospective, cross-sectional study tested the hypothesis that the risk of reflux or dyspepsia is associated with the fat content of the meal independent of caloric load in a ‘real-life’ setting. Materials and methods Four festive meals were served to delegates attending a conference on four consecutive days. Test meals had the same volume, but varied in calorie and fat content. Study procedures and symptoms were monitored using a mobile application (SymTrack). The effect of alcoholic compared with nonalcoholic drinks was also assessed. Primary outcome was the occurrence of reflux or dyspeptic symptoms. Fullness was documented by a visual analogue scale. Results A total of 84/120 (70%) delegates aged 22–69 years consented to participate. At screening, 22 (31%) participants reported at least mild symptoms on the Leuven Dyspepsia Questionnaire. Specific ingredients did not appear to impact on postprandial symptoms. All high-calorie dinners [British, German, Italian (with alcohol)] induced more symptoms than the low-fat, low-calorie Czech dinner [odds ratio: 2.6, 95% confidence interval (CI): 0.97–6.9 (P=0.058), 1.5 (0.3–3.8), and 2.8 (0.7–10.5), respectively]. Self-reported fullness after the high-fat, high-calorie British dinner was higher by 23/100 (95% CI: 4–42, P=0.016) with respect to low-fat, low-calorie Czech and German dinners. Conclusion Study participants tolerated a range of food and drink well. Reflux or dyspeptic symptoms were least likely after the low-fat, low-calorie meal. Fullness was increased after the high-fat, high-calorie dinner, but not low-fat meals. These results will help the public to make evidence-based dietary choices during the carnival season!

The Vampire Study: Significant elevation of faecal calprotectin in healthy volunteers after 300 ml blood ingestion mimicking upper gastrointestinal bleeding:

Background Faecal calprotectin correlates with histological and clinical activity in inflammatory bowel disease. Gastrointestinal bleeding might also increase faecal calprotectin levels, erroneously implying intestinal inflammation; however, this possibility has not been systematically assessed. Methods Sixteen healthy volunteers without gastrointestinal disease and normal faecal calprotectin baseline values ingested their own blood twice, either by drinking or via nasogastric tube. Quantities of 100 ml and 300 ml blood were ingested in a randomised order, with a 28-day wash-out period. Faecal calprotectin, faecal occult blood test, and the occurrence of melaena were assessed. Faecal calprotectin ≥ 50 µg/g was considered elevated. Results Melaena was reported by all healthy volunteers after 300 ml and by 11/15 healthy volunteers (71%) after 100 ml blood ingestion. One day after ingestion of 300 ml blood, 8/16 faecal calprotectin tests were positive compared to 1/16 at baseline (p = 0.016). Faecal calprotectin levels above > 200 µg/g were rarely observed. There was a trend for faecal calprotectin test positivity also after ingestion of 100 ml. Conclusion Ingestion of blood resulted in an increase in faecal calprotectin-positive tests. Gastrointestinal bleeding should be considered as a potential cause of mild faecal calprotectin elevation > 50 µg/g; however, increased faecal calprotectin above > 250–300 µg/g, the established cut-off for relevant intestinal inflammation in patients with inflammatory bowel disease, is rare.

Abnormal esophageal motility during a solid test meal in systemic sclerosis-detection even in very early disease and association with disease progression

This study assessed whether high‐resolution manometry (HRM) with a test meal can detect clinically relevant, abnormal motility already in very early systemic sclerosis (SSc) and whether this finding is associated with subsequent disease progression.