Citations

Gastric emptying, accommodation, and motility can be quantified with magnetic resonance imaging (MRI). The first step in image analysis entails segmenting the stomach from surrounding structures, usually by a time-consuming manual process. We have developed a semiautomated process to segment and measure gastric volumes with MRI. Gastric images were acquired with a three-dimensional gradient echo MRI sequence at 5, 10, 20, and 30 min after ingestion of a liquid nutrient (Ensure, 296 ml) labeled with gadolinium in 20 healthy volunteers and 29 patients with dyspeptic symptoms. The agreement between gastric volumes measured by manual segmentation and our new semiautomated algorithm was assessed with Lin's concordance correlation coefficient (CCC) and the Bland Altman test. At 5 min after a meal, food volumes measured by manual (352 ± 4 ml) and semiautomated (346 ± 4 ml) techniques were correlated {CCC[95% confidence interval (CI)] 0.70 (0.52, 0.81)}; air volumes measured by manual (88 ± 6 ml) and semiautomated (84 ± 6 ml) techniques were also correlated [CCC (95% CI) 0.89 (0.82, 0.94)]. Findings were similar at subsequent time points. The Bland Altman test was not significant. The time required for semiautomated segmentation ranged from an average of 204 s for the 5-min images to 233 s for the 20-min images. These times were appreciably smaller than the typical times of many tens of minutes, even hours, required for manual segmentation. To conclude, a semiautomated process can measure gastric food and air volume using MRI with comparable accuracy and far better efficiency than a manual process.

The pathobiology of irritable bowel syndrome (IBS) is multifaceted. We aimed to identify candidate genes predisposing to quantitative traits in IBS. In 30 healthy volunteers, 30 IBS-constipation, and 64 IBS-diarrhea patients, we measured bowel symptoms, bile acid (BA) synthesis (serum 7α-hydroxy-4-cholesten-3-one and FGF19), fecal BA and fat, colonic transit (CT by scintigraphy), and intestinal permeability (IP by 2-sugar excretion). We assessed associations of candidate genes controlling BA metabolism ( KLB rs17618244 and FGFR4 rs351855), BA receptor ( GPBAR1 rs11554825), serotonin (5-HT) reuptake ( SLC6A4 through rs4795541 which encodes for the 44-bp insert in 5HTTLPR), or immune activation ( TNFSF15 rs4263839) with three primary quantitative traits of interest: colonic transit, BA synthesis, and fecal BA excretion. There were significant associations between fecal BA and CT at 48 h ( r = 0.43; P < 0.001) and IP ( r = 0.23; P = 0.015). GPBAR1 genotype was associated with CT48 ( P = 0.003) and total fecal BA [ P = 0.030, false detection rate (FDR) P = 0.033]. Faster CT48 observed with both CC and TT GPBAR1 genotypes was due to significant interaction with G allele of KLB, which increases BA synthesis and excretion. Other univariate associations ( P < 0.05, without FDR correction) observed between GPBAR1 and symptom phenotype and gas sensation ratings support the role of GPBAR1 receptor. Associations between SLC6A4 and stool consistency, ease of passage, postprandial colonic tone, and total fecal BA excretion provide data in support of future hypothesis-testing studies. Genetic control of GPBAR1 receptor predisposing to pathobiological mechanisms in IBS provides evidence from humans in support of the importance of GPBAR1 to colonic motor and secretory functions demonstrated in animal studies.

SummaryBackgroundClostridium difficile infection (CDI) recurs in 20–30% of patients.AimTo describe the predictors of recurrence in out‐patients with CDI.MethodsOut‐patient cases of CDI in Olmsted County, MN residents diagnosed between 28 June 2007 and 25 June 2010 were identified. Recurrent CDI was defined as recurrence of diarrhoea with a positive C. difficile PCR test from 15 to 56 days after the initial diagnosis with interim resolution of symptoms. Patients who had two positive tests within 14 days were excluded. Cox proportional hazard models were used to assess the association of clinical variables with time to recurrence of CDI.ResultsThe cohort included 520 out‐patients; 104 had recurrent CDI (cumulative incidence of 17.5% by 30 days). Univariate analysis identified increasing age and antibiotic use to be associated with recurrent CDI. Severe CDI, peripheral leucocyte count and change in serum creatinine >1.5‐fold were not. In a multiple variable model, concomitant antibiotic use was associated with risk of recurrent CDI (HR = 5.4, 95% CI 1.6–17.5, P = 0.005), while age (HR per 10 year increase = 1.1, 95% CI 0.9–1.3, P = 0.22); peripheral leucocyte count >15 × 109/L (HR = 1.0, 95% CI 0.5–2.1, P = 0.92); and change in serum creatinine greater than 1.5‐fold (HR = 0.8, 95% CI 0.4–1.5, P = 0.44) were not.ConclusionsAntibiotic use was independently associated with a dramatic risk of recurrent Clostridium difficile infection in an out‐patient cohort. It is important to avoid unnecessary systemic antibiotics in patients with Clostridium difficile infection, and patients with ongoing antibiotic use should be monitored closely for recurrent infection.

AbstractBackgroundThere is symptom overlap between gastro‐esophageal reflux disease (GERD) and functional dyspepsia (FD). We aimed to test the hypothesis that FD cases are now more likely mislabeled as GERD.MethodsIn subjects from Olmsted County, MN seen at Mayo Clinic: (i) Investigation of GERD and FD diagnosis rates between 1985 and 2009. (ii) Assessment of survey‐based upper gastrointestinal symptoms between 1988 and 2009. (iii) Analysis of patients reporting GERD and/or FD symptoms and subsequently receiving a consistent diagnosis of GERD and/or FD during a medical encounter. (iv) Assess the association between PPI use and GERD and/or FD symptoms and between actual diagnoses received.Key Results(i) Yearly GERD diagnosis rates rose between 1985 and 2009 (325–1866 per 100 000). FD diagnosis rates rose from 45 in 1985, to 964 in 1999 but decreased to 452 per 100 000 in 2009. (ii) Reported GERD symptoms did not significantly change between three survey waves in the years 1988–2009 (p = 0.052), whereas FD symptoms slightly increased (p = 0.01). (iii) 62.9% of subjects reporting GERD symptoms received a GERD diagnosis, however only 12.5% of subjects reporting FD symptoms received a FD diagnosis. (iv) PPI use was associated with documented GERD diagnosis (p < 0.001), however there was no significant association between GERD symptoms and PPI use (p = 0.078).Conclusions & InferencesWe have found evidence supporting a systematic bias away from diagnosing FD, favoring a GERD diagnosis.

Introduction BO is the strongest precursor of oesophageal adenocarcinoma. Participation patterns and effectiveness of BO community screening using unsedated transnasal endoscopy (uTNE) is unknown. Feasibility of mobile van screening closer to home is also unknown. We aimed to assess the effectiveness of this technique compared to sedated endoscopy (SE). Methods A population cohort ≥50 years of age, with no history of endoscopic evaluation, was identified from a group of subjects who previously completed a validated symptom questionnaire. Patients were randomised (stratified by age, sex and reflux symptoms) and invited to undergo either uTNE in a mobile research van (muTNE), uTNE in outpatient endoscopy suite (huTNE) or SE. uTNE was performed using a portable oesophagoscope with a disposable sheath. Procedure performance characteristics and validated tolerability scales (0 = none and 10 = severe) were recorded. Results 459 subjects were contacted and 209 (46%) agreed to undergo study procedures (muTNE n = 76, huTNE n = 72, SE n = 61). Baseline characteristics were comparable among the three groups. Participation rates were numerically higher in the unsedated arms (muTNE 47.5%, huTNE 45.7%) than in the SE arm (40.7%) (p = 0.27). Patients with acid reflux symptoms ≥1/week were more likely to participate (odds ratio 2.94, 95% confidence interval 1.47, 5.88). Complete evaluation of the oesophagus was comparable using muTNE (99%), huTNE (96%) and SE (100%) techniques. Successful biopsy acquisition was lower in the muTNE (79%) and huTNE (83%) groups compared to SE (100%) (p = 0.001). Mean duration (minutes) of examination was shorter in the SE arm (4.7) than in muTNE (8.0) and huTNE (8.5) groups (p < 0.001). However, recovery time was much longer for SE (67.3) compared to muTNE (15.5) and huTNE (18.5) techniques (p < 0.001). While overall tolerability for SE was better than muTNE and huTNE (mean score 0.4 vs. 1.9 and 2.2 respectively, p < 0.001), the majority of patients who underwent muTNE and huTNE were willing to undergo the same procedure again in future (79% and 83%, respectively). No serious adverse events were reported. 16 subjects (7.6%) were diagnosed with BO. Conclusion In this first large randomised trial evaluating novel approaches for community screening for BO, unsedated mobile van and clinic screening with TNE was feasible and effective. The patients’ visit was significantly shorter with adequate tolerability, acceptability and safety profiles. Mobile and outpatient techniques may provide a cost-effective alternative to SE for BO screening. Disclosure of Interest S. Sami: None Declared, K. Dunagan: None Declared, M. Johnson: None Declared, C. Schlek: None Declared, A. Zinsmeister: None Declared, L. M. Wong Kee Song: None Declared, K. Wang: None Declared, D. Katzka: None Declared, K. Ragunath Grant/research support from: Olympus (keymed, UK) and Intromed Ltd. (Seoul, South Korea), P. Iyer: None Declared.

SummaryBackgroundThe population ≥65 years is rapidly increasing, but remarkably little is known about the natural history of abdominal pain with ageing.AimTo prospectively evaluate the natural history of abdominal pain (severity and frequency) in a US population, and evaluate potential risk factors (including somatisation) for the onset and disappearance of abdominal pain with increasing age.MethodsBetween 1988 and 2004, valid self‐report questionnaires that recorded gastrointestinal symptoms including severity and frequency of abdominal pain were mailed to randomly selected cohorts of community residents followed over time. This study identified all respondents who answered abdominal pain questions at an initial and follow‐up survey.ResultsOne thousand nine hundred and thirteen subjects were included (mean age in years at first survey: 48 ± 12 (SD), mean age at second survey: 59 ± 13 (SD); 53% female). The onset and disappearance rate of abdominal pain over the follow‐up were 18% (95% CI, 16, 20) and 47% (43, 50) respectively. The rates of increasing vs. decreasing abdominal pain score were 18% (16, 20) vs. 21% (20, 23) respectively. While younger age at initial survey was associated with the onset of abdominal pain {vs. subjects without abdominal pain, [OR 0.9 (0.7, 1.0)]}, older age at initial survey and times between surveys were associated with the disappearance of abdominal pain {vs. subjects with abdominal pain, [OR 1.2 (1.0, 1.5)]}. Female gender (OR 1.4 [1.0, 2.1]), higher somatisation scores (OR 5.3 [3.2, 8.7]) and larger changes in somatisation score (OR 2.1 [1.4, 3.2]) were positively associated with the onset of abdominal pain.ConclusionIncreasing age is associated with the disappearance of abdominal pain in the community.

The study objectives were: to mine the complete exome to identify putative rare single nucleotide variants (SNVs) associated with irritable bowel syndrome (IBS)-diarrhea (IBS-D) phenotype, to assess genes that regulate bile acids in IBS-D, and to explore univariate associations of SNVs with symptom phenotype and quantitative traits in an independent IBS cohort. Using principal components analysis, we identified two groups of IBS-D ( n = 16) with increased fecal bile acids: rapid colonic transit or high bile acids synthesis. DNA was sequenced in depth, analyzing SNVs in bile acid genes ( ASBT, FXR, OSTα/β, FGF19, FGFR4, KLB, SHP, CYP7A1, LRH-1, and FABP6). Exome findings were compared with those of 50 similar ethnicity controls. We assessed univariate associations of each SNV with quantitative traits and a principal components analysis and associations between SNVs in KLB and FGFR4 and symptom phenotype in 405 IBS, 228 controls and colonic transit in 70 IBS-D, 71 IBS-constipation. Mining the complete exome did not reveal significant associations with IBS-D over controls. There were 54 SNVs in 10 of 11 bile acid-regulating genes, with no SNVs in FGF19; 15 nonsynonymous SNVs were identified in similar proportions of IBS-D and controls. Variations in KLB (rs1015450, downstream) and FGFR4 [rs434434 (intronic), rs1966265, and rs351855 (nonsynonymous)] were associated with colonic transit (rs1966265; P = 0.043), fecal bile acids (rs1015450; P = 0.064), and principal components analysis groups (all 3 FGFR4 SNVs; P < 0.05). In the 633-person cohort, FGFR4 rs434434 was associated with symptom phenotype ( P = 0.027) and rs1966265 with 24-h colonic transit ( P = 0.066). Thus exome sequencing identified additional variants in KLB and FGFR4 associated with bile acids or colonic transit in IBS-D.

AbstractBackgroundNausea and vomiting are thought to result from upper gastrointestinal dysfunctions. Our clinical observations led to the hypothesis that colonic motor dysfunction is associated with nausea and vomiting.MethodsWe reviewed electronic medical records (EMR) of 149 patients presenting with complaints of nausea and/or vomiting in a tertiary gastroenterology practice to investigate the association with disorders of colonic motor or evacuation disorders. We extracted demographics, gastric emptying (GEin 149) and colonic transit (CTin 138) of solids, ascending colon emptying half‐time (ACt1/2), rectal evacuation by anorectal manometry (ARM) in 91 and balloon expulsion test (BE) in 55 patients. We estimated the proportions with delayedGEorCT, based on the 5th percentile ofGE(in 319) andCTin 220 healthy volunteers using same method.Key ResultsAmong 11 patients with nausea and/or vomiting with onlyGEmeasured, five had delayed and six normalGE. Among the 149 patients, 77 (52%) patients had evacuation disorders, confirmed by objective tests in 68 patients, and clinical examination in nine patients. In the 138 patients with bothGEandCTmeasured, 106 (76%) had both normalGEandCT, 11 (8%) only delayedGE, 16 (11%) normalGEwith delayedCT, and five (3%) delayedGEandCT. Among 21 patients (15%) with delayedCT, nine had slowACt1/2and 12 evacuation disorder.Conclusions & InferencesIn patients with chronic nausea and/or vomiting in gastroenterology practice, evaluation of colonic motility and rectal evacuation should be considered, since about half the patients have abnormal functions that conceivably contribute to the presenting nausea and/or vomiting.

The contribution of elevated glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism after Roux-en-Y gastric bypass (RYGB) has been the subject of uncertainty. We used exendin-9,39, a competitive antagonist of GLP-1, to examine glucose metabolism, islet hormone secretion, and gastrointestinal transit in subjects after RYGB and in matched control subjects. Subjects were studied in the presence or absence of exendin-9,39 infused at 300 pmol/kg/min. Exendin-9,39 resulted in an increase in integrated postprandial glucose concentrations post-RYGB (3.6 ± 0.5 vs. 2.0 ± 0.4 mol/6 h, P = 0.001). Exendin-9,39 decreased insulin concentrations (12.3 ± 2.2 vs. 18.1 ± 3.1 nmol/6 h, P = 0.002) and the β-cell response to glucose (ϕTotal, 13 ± 1 vs. 11 ± 1 × 10−9 min−1, P = 0.01) but did not alter the disposition index (DI). In control subjects, exendin-9,39 also increased glucose (2.2 ± 0.4 vs. 1.7 ± 0.3 mol/6 h, P = 0.03) without accompanying changes in insulin concentrations, resulting in an impaired DI. Post-RYGB, acceleration of stomach emptying during the first 30 min by exendin-9,39 did not alter meal appearance, and similarly, suppression of glucose production and stimulation of glucose disappearance were unaltered in RYGB subjects. These data indicate that endogenous GLP-1 has effects on glucose metabolism and on gastrointestinal motility years after RYGB. However, it remains uncertain whether this explains all of the changes after RYGB.

AbstractBackgroundLow basal lower esophageal sphincter (LES) pressure and transient LES relaxations are major causes of gastroesophageal reflux disease (GERD). Pumosetrag, a novel selective partial 5HT3 receptor agonist, showed a promising effect on reducing reflux events in health. We aimed to evaluate the effect of pumosetrag on changes in reflux episodes, lower esophageal sphincter pressure (LESP), and specific symptoms in patients with GERD receiving a refluxogenic meal.MethodsPatients with GERD, who developed heartburn and/or regurgitation after ingestion of a refluxogenic meal, were randomized to 1 of 3 dose levels of pumosetrag (0.2, 0.5, or 0.8 mg) or placebo. Before and after 7 days of treatment, patients underwent manometry, intraesophageal multichannel, intraluminal impedance and pH after a standard refluxogenic meal.Key ResultsA total of 223 patients with GERD [125 (56%) women, mean (SD) age = 36 (12) years] were enrolled. No overall treatment effects were detected for the total number of reflux episodes (acidic and weakly acidic) (p > 0.5); however, significant treatment effects (p < 0.05) on the number of acid reflux episodes were observed with lower values on pumosetrag 0.2 mg (10.8 ± 1.1), 0.5 mg (9.5 ± 1.1), and 0.8 mg (9.9 ± 1.1) compared with placebo (13.3 ± 1.1). Significant treatment effects (p < 0.05) were also observed for the percentage of time pH was <4, with less time for pumosetrag at 0.5 mg (10%) and 0.8 mg (10%) compared with placebo (16%).Conclusions & InferencesIn GERD, the partial 5HT3 agonist pumosetrag significantly reduced the rate of acid reflux events but did not result in a significant change in LESP or symptomatic improvement over a 1‐week treatment period.