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Background: Current investigations of gastric emptying rarely identify the cause of symptoms or provide a definitive diagnosis in patients with dyspepsia. This study assessed gastric function by magnetic resonance imaging (MRI) using the modular "Nottingham Test Meal" (NTM) in healthy volunteers (HVs).Methods: The NTM comprises (i) 400mL liquid nutrient (0.75kcal/mL) labelled with Gadolinium DOTA and (ii) an optional solid component (12 agar-beads (0kcal)). Filling sensations were documented. MRI measurements of gastric volume, emptying, contraction wave frequency and secretion were obtained using validated methods.Key Results: Gastric function was measured in a population of 73 HVs stratified for age and sex. NTM induced moderate satiety and fullness. Labelled fluid was observed in the small bowel in all subjects after meal ingestion ("early-phase" GE). Secretion was rapid such that postprandial gastric content volume was often greater than meal volume (GCV0 >400ml) and there was increasing dilution of the meal during the study (p less than 0.001). Gastric half‐time was median 66‐minutes (95% reference interval 35 to 161‐minutes [“late‐phase” GE]). The number of intact agar beads in the stomach was 7/12 (58%) at 60‐minutes and 1/12 (8%) at 120‐minutes. Age, bodyweight and sex had measurable effects on gastric function; however, these were small compared to inter‐individual variation for most metrics.Conclusions and Inferences: Reference intervals are presented for MRI measurements of gastric function assessed for the mixed liquid/solid NTM. Studies in patients will determine which metrics are of clinical value and also whether the reference intervals presented here offer optimal diagnostic sensitivity and specificity.

OBJECTIVES Gastrointestinal involvement and impaired nutritional status are frequent in patients with systemic sclerosis (SSc). Hereby, we hypothesised that micronutrients and/or prealbumin could be deficitary in SSc. METHODS Patients with SSc and very early SSc (veSSc) were prospectively included. Clinical assessment, data recording and quality controls followed EUSTAR standards. The UCLA SCTCGIT 2.0 questionnaire was applied and the serum levels of zinc, selenium, prealbumin, holotranscobalamin, folic acid were measured. RESULTS Half (52.4%) of the 176 patients with established SSc showed a deficiency in at least one of the measured nutrients. The most frequent deficit was seen in folic acid (17.9%), followed closely by selenium, prealbumin and zinc (around 15% each). Nearly a fifth (19%) of these patients had multiple deficiencies. Patients with more severe disease, including advanced skin fibrosis, positive ACR 1980 classification criteria, anemia and elevated serum inflammation markers were more likely to be nutrient deficient. Lower BMI

BACKGROUND: As treatments for constipation become increasingly available, it is important to know when to progress along the treatment algorithm if the patient is not better.AIM: To establish the definition of failure of a treatment to provide adequate relief (F-PAR) to support this management and referral process in patients with chronic constipation.METHODS: We conducted an international Delphi Survey among gastroenterologists and general practitioners with a special interest in chronic constipation. An initial questionnaire based on recognised rating scales was developed following a focus group. Data were collected from two subsequent rounds of questionnaires completed by all authors. Likert scales were used to establish a consensus on a shorter list of more severe symptoms.RESULTS: The initial focus group yielded a first round questionnaire with 84 statements. There was good consensus on symptom severity and a clear severity response curve, allowing 67 of the symptom-severity pairings to be eliminated. Subsequently, a clear consensus was established on further reduction to eight symptom statements in the final definition, condensed by the steering committee into five diagnostic statements (after replicate statements had been removed).CONCLUSIONS: We present an international consensus on chronic constipation, of five symptoms and their severities, any of which would be sufficient to provide clinical evidence of treatment failure. We also provide data representing an expert calibration of commonly used rating scales, thus allowing results of clinical trials expressed in terms of those scales to be converted into estimates of rates of provision of adequate relief.

Background Postprandial accumulation of gastric secretions in the proximal stomach above the meal adjacent to the esophagogastric junction (EGJ), referred to as the ‘acid pocket’, has been proposed as a pathophysiological factor in gastro-esophageal reflux disease (GERD) and as a target for GERD treatment. This study assessed the effect of proton pump inhibitor (PPI) therapy on the volume, distribution and acidity of gastric secretions in GERD and healthy subjects (HS). Methods A randomized, double blind, cross-over study in 12 HS and 12 GERD patients pre-treated with 40 mg pantoprazole (PPI) or placebo b.i.d. was performed. Postprandial secretion volume (SV), formation of a secretion layer and contact between the layer and the EGJ were quantified by Magnetic Resonance Imaging (MRI). Multi-channel pH-monitoring assessed intragastric pH. Results A distinct layer of undiluted acid secretion was present on top of gastric contents in almost all participants on and off high-dose acid suppression. PPI reduced SV (193 ml to 100 ml, in HS, 227 ml to 94 ml in GERD; p, BMC Gastroenterology, 15, ISSN:1471-230X

High-resolution esophageal manometry (HRM) is a recent development used in the evaluation of esophageal function. Our aim was to assess the inter-observer agreement for diagnosis of esophageal motility disorders using this technology. Practitioners registered on the HRM Working Group website were invited to review and classify (i) 147 individual water swallows and (ii) 40 diagnostic studies comprising 10 swallows using a drop-down menu that followed the Chicago Classification system. Data were presented using a standardized format with pressure contours without a summary of HRM metrics. The sequence of swallows was fixed for each user but randomized between users to avoid sequence bias. Participants were blinded to other entries. (i) Individual swallows were assessed by 18 practitioners (13 institutions). Consensus agreement (≤2/18 dissenters) was present for most cases of normal peristalsis and achalasia but not for cases of peristaltic dysmotility. (ii) Diagnostic studies were assessed by 36 practitioners (28 institutions). Overall inter-observer agreement was 'moderate' (kappa 0.51) being 'substantial' (kappa > 0.7) for achalasia type I/II and no lower than 'fair-moderate' (kappa >0.34) for any diagnosis. Overall agreement was somewhat higher among those that had performed >400 studies (n = 9; kappa 0.55) and 'substantial' among experts involved in development of the Chicago Classification system (n = 4; kappa 0.66). This prospective, randomized, and blinded study reports an acceptable level of inter-observer agreement for HRM diagnoses across the full spectrum of esophageal motility disorders for a large group of clinicians working in a range of medical institutions. Suboptimal agreement for diagnosis of peristaltic motility disorders highlights contribution of objective HRM metrics.

Zusammenfassung. Die anorektale Funktionsdiagnostik ermöglicht die Messung des Analsphinkterdrucks, die Evaluierung der Rektumsensibilität sowie die Überprüfung der rektoanalen Reflexe, die wesentliche Elemente der Beurteilung der Darmentleerung darstellen. Sie wird mit einem Ballonexpulsionstest kombiniert, um sicherzustellen, dass die manometrischen Befunde mit der anorektalen Funktion übereinstimmen. Diese Tests finden in der diagnostischen Abklärung der chronischen Stuhlentleerungsstörung, der Obstipation und der fäkalen Inkontinenz ihre Anwendung, können aber auch im prä- und postoperativen Setting, bei funktionellen anorektalen Schmerzen und anderen Störungen der Beckenbodenfunktion Klärung bringen. Bei den meisten Patienten, die zur Untersuchung dieser Symptome überwiesen werden, ist eine umfassende Beurteilung der anorektalen Struktur und Funktion erforderlich. Aufgrund der hohen Variabilität der Normalwerte und Komplexität der anorektalen Funktion liefert keine einzelne Untersuchung alle Informationen, die für eine symptomerklärende, schlüssige Diagnose erforderlich sind und die Therapieentscheidung beeinflussen. Die anorektale Manometrie ist nützlich, um das Ausmass der Beeinträchtigung der anorektalen Funktion zu beurteilen und zwischen organischen und funktionellen Erkrankungen (inklusive Beckenbodendyssynergie) zu unterscheiden. Eine vorangehende ausführliche Anamnese sowie endoskopische (Prokto- / Rektoskopie) und bildgebende Verfahren (anorektale Endosonographie, dynamische MR-Defäkographie) vervollständigen die Diagnostik.

Background Standard high-resolution manometry (HRM) protocols are based on 10 single water swallows acquired in the supine position. Aims To assess the impact of position, rapid drink challenge and solid test meal on the diagnosis of oesophageal motility disorders. Methods Seventy-two healthy volunteers (20-76 years) and 366 consecutive patients (18-90 years) completed HRM with 10 single water swallows in the supine and upright positions. Rapid drink challenge was performed twice, before and after the solid test meal. Diagnosis based on single water swallows in the supine position (Chicago Classification v3.0) was compared with results in the upright position and with provocative tests. Results Overall, diagnostic agreement in the supine and upright positions was present in 296/438 (67.6%) subjects. This increased to 90.0% when ineffective oesophageal motility was considered with normal motility. Integrated relaxation pressure was 4 mm Hg higher in the supine position. There was a higher prevalence of inconsistent, likely false positive, diagnoses of outlet obstruction in the supine compared to the upright position (16/20 vs 1/4 patients, P = 0.0007). Similarly, the difference in concordance for the diagnosis of oesophago-gastric junction obstruction or achalasia between single water swallows in the supine and upright positions with solid test meal was significant (12/29 (41.4%) vs 12/14 (85.7%), P = 0.0087). Conclusion Diagnostic agreement for oesophageal motility disorders based on single water swallows in the upright and supine positions was moderate, with frequent discordant findings for ineffective motility and outlet obstruction. HRM studies can be performed in either position, using appropriate reference values. Rapid drink challenge or solid test meal can resolve diagnostic discrepancies.

Symptoms related to abnormal gastrointestinal motility and function are common. Oropharyngeal and oesophageal dysphagia, heartburn, bloating, abdominal pain and alterations in bowel habits are among the most frequent reasons for seeking medical attention from internists or general practitioners and are also common reasons for referral to gastroenterologists and colorectal surgeons. However, the nonspecific nature of gastrointestinal symptoms, the absence of a definitive diagnosis on routine investigations (such as endoscopy, radiology or blood tests) and the lack of specific treatments make disease management challenging. Advances in technology have driven progress in the understanding of many of these conditions. This Review serves as an introduction to a series of Consensus Statements on the clinical measurements of gastrointestinal motility, function and sensitivity. A structured, evidence-based approach to the initial assessment and empirical treatment of patients presenting with gastrointestinal symptoms is discussed, followed by an outline of the contribution of modern physiological measurement on the management of patients in whom the cause of symptoms has not been identified with other tests. Discussions include the indications for and utility of high-resolution manometry, ambulatory pH-impedance monitoring, gastric emptying studies, breath tests and investigations of anorectal structure and function in day-to-day practice and clinical management.

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.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.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 at4 s between swallows vs 586/900 [65%] effective swallows at11 s between swallows, p0·0001). Obstructive, spastic, or hypercontractile swallows were rare in healthy volunteers (total1%). 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, p0·0001) 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], p0·0001). 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, p0·0001).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.University Hospital Zurich.

Dark chocolate is claimed to have effects on gastrointestinal function and to improve well-being. This randomised controlled study tested the hypothesis that cocoa slows gastric emptying and intestinal transit. Functional brain imaging identified central effects of cocoa on cortical activity. Healthy volunteers (HV) ingested 100 g dark (72 % cocoa) or white (0 % cocoa) chocolate for 5 d, in randomised order. Participants recorded abdominal symptoms and stool consistency by the Bristol Stool Score (BSS). Gastric emptying (GE) and intestinal and colonic transit time were assessed by scintigraphy and marker studies, respectively. Combined positron emission tomography–computed tomography (PET–CT) imaging assessed regional brain activity. A total of sixteen HV (seven females and nine males) completed the studies (mean age 34 (21–58) years, BMI 22·8 (18·5–26·0) kg/m2). Dark chocolate had no effect on upper gastrointestinal function (GE half-time 82 (75–120) v. 83 (60–120) min; P=0·937); however, stool consistency was increased (BSS 3 (3–5) v. 4 (4–6); P=0·011) and there was a trend to slower colonic transit (17 (13–26) v. 21 (15–47) h; P=0·075). PET–CT imaging showed increased [18F]fluorodeoxyglucose (FDG) in the visual cortex, with increased FDG uptake also in somatosensory, motor and pre-frontal cortices (P

Lactose is the main source of calories in milk, an essential nutriedigestion, patients with visceral hypersensitivity nt in infancy and a key part of the diet in populations that maintain the ability to digest this disaccharide in adulthood. Lactase deficiency (LD) is the failure to express the enzyme that hydrolyses lactose into galactose and glucose in the small intestine. The genetic mechanism of lactase persistence in adult Caucasians is mediated by a single C→T nucleotide polymorphism at the LCTbo -13'910 locus on chromosome-2. Lactose malabsorption (LM) refers to any cause of failure to digest and/or absorb lactose in the small intestine. This includes primary genetic and also secondary LD due to infection or other conditions that affect the mucosal integrity of the small bowel. Lactose intolerance (LI) is defined as the onset of abdominal symptoms such as abdominal pain, bloating and diarrhoea after lactose ingestion by an individual with LM. The likelihood of LI depends on the lactose dose, lactase expression and the intestinal microbiome. Independent of lactose digestion, patients with visceral hypersensitivity associated with anxiety or the Irritable Bowel Syndrome (IBS) are at increased risk of the condition. Diagnostic investigations available to diagnose LM and LI include genetic, endoscopic and physiological tests. The association between self-reported LI, objective findings and clinical outcome of dietary intervention is variable. Treatment of LI can include low-lactose diet, lactase supplementation and, potentially, colonic adaptation by prebiotics. The clinical outcome of these treatments is modest, because lactose is just one of a number of poorly absorbed carbohydrates which can cause symptoms by similar mechanisms. ispartof: GUT vol:68 issue:11 pages:2080-2091 ispartof: location:England status: published

Lactose intolerance related to primary or secondary lactase deficiency is characterized by abdominal pain and distension, borborygmi, flatus, and diarrhea induced by lactose in dairy products. The biological mechanism and lactose malabsorption is established and several investigations are available, including genetic, endoscopic and physiological tests. Lactose intolerance depends not only on the expression of lactase but also on the dose of lactose, intestinal flora, gastrointestinal motility, small intestinal bacterial overgrowth and sensitivity of the gastrointestinal tract to the generation of gas and other fermentation products of lactose digestion. Treatment of lactose intolerance can include lactose-reduced diet and enzyme replacement. This is effective if symptoms are only related to dairy products; however, lactose intolerance can be part of a wider intolerance to variably absorbed, fermentable oligo-, di-, monosaccharides and polyols (FODMAPs). This is present in at least half of patients with irritable bowel syndrome (IBS) and this group requires not only restriction of lactose intake but also a low FODMAP diet to improve gastrointestinal complaints. The long-term effects of a dairy-free, low FODMAPs diet on nutritional health and the fecal microbiome are not well defined. This review summarizes recent advances in our understanding of the genetic basis, biological mechanism, diagnosis and dietary management of lactose intolerance.

SummaryBackground The mechanism of reflux protection may involve a ‘flap valve’ at the oesophago-gastric junction (OGJ). Aim To assess the effects of baclofen, a gamma-aminobutyric acid receptor type-B (GABA-B) agonist known to suppress reflux events, on the ‘functional anatomy’ of the OGJ and proximal stomach after a large test meal. Methods Twelve healthy volunteers (HVs) and 12 patients with gastro-oesophageal reflux disease (GERD); with erosive oesophagitis or pathological oesophageal acid exposure completed a randomised, double-blind, cross-over study. On 2 test days participants received 40-mg baclofen or placebo before ingestion of a large test meal. OGJ structure and function were assessed by high-resolution manometry (HRM) and magnetic resonance imaging (MRI) using validated methods. Measurements of the oesophago-gastric angle were derived from three-dimensional models reconstructed from anatomic MRI images. Cine-MRI and HRM identified postprandial reflux events. Mixed model analysis and Wilcoxon rank signed tests assessed differences between participant groups and treatment conditions. Results In both HVs and GERD patients, baclofen reduced the frequency of postprandial reflux events. The oesophago-gastric insertion angle in GERD patients was reduced (−4.1 ± 1.8, P = 0.025), but was unchanged in healthy controls. In both study groups, baclofen augmented lower oesophageal sphincter (LES) pressure (HVs: +7.3 ± 1.8 mmHg, P

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.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.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 P0.05). 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; P0.0001) and intra-abdominal LES length was shorter (-1.0 ± 0.3 cm, P0.0006) in GERD patients.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.