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Precise endoscopic assessment is necessary to detect neoplastic changes in an early stage. Electronic or virtual chromo-endoscopy (ECE) is an alternative to conventional dye-based chromo-endoscopy which markedly improves capillary pattern and hence can detect micro-vessel morphological changes of early neoplasia to target biopsies and aid in diagnosis. The clinical significance increased after the advent of endoscopic treatment modalities like ESD/EMR which requires precise delineation of extent and depth of lesion. Most of the studies have used narrow-band imaging (NBI) (Olympus Medical Systems Tokyo, Japan), although data from i-SCAN (PENTAX Endoscopy, Tokyo, Japan) and flexible spectral imaging color enhancement (FICE) (Fujinon, Fujifilm Medical Co, Saitama, Japan) are emerging. Electronic chromo-endoscopy is convenient compared to dye-based chromo-endoscopy in the sense that it is available at the push of a button in endoscope and reduces procedure time substantially with comparable efficacy. Scope of this review is to discuss available electronic chromo-endoscopy modalities and their role in the diagnosis, surveillance, and management of early GI neoplasia.

Background While opioid prescriptions have increased alarmingly in the United States (US), their use for unexplained chronic gastrointestinal (GI) pain (eg, irritable bowel syndrome) carries an especially high risk for adverse effects and questionable benefit. Aim To compare opioid use among US veterans with structural GI diagnoses (SGID) and those with unexplained GI symptoms or functional GI diagnoses (FGID), a group for whom opioids have no accepted role. Methods Veterans Health Administration (VHA) administrative data from fiscal year 2012 were used to identify veterans with diagnostic codes recorded for SGID and FGID. This cohort study examined VHA pharmacy data to compare groups receiving ≥ 1 opioid prescription during the year and number of prescriptions filled. Bivariate and multiple logistic regression analyses adjusted for potential confounding factors (demographics, medical diagnoses, social factors) and identified potential mediators (service use, psychiatric comorbidity) of opioid use in these groups. Results A greater proportion of veterans with FGID received an opioid prescription during fiscal year 2012 (36.0% of 272 431) compared to only 28.9% of 1 223 744 in the SGID group (Relative Risk [RR] = 1.25). In multivariate logistic regression, personality disorders and drug abuse (OR 1.23 for each group), recent homelessness (OR 1.22), psychotropic medication fills (OR 1.55) and emergency department encounters (OR 1.21) were independently associated with opioid prescription use. Conclusions Despite the potential for adverse consequences, opioids more often are prescribed for veterans with chronic, unexplained GI symptoms compared to those with structural diagnoses. Psychiatric comorbidities and frequent healthcare encounters mediate some of the opioid use risk.

Background and aims Coeliac disease (CD) is widely prevalent in North America, but case-finding techniques currently used may not be adequate for patient identification. We aimed to determine the adequacy of CD screening in an academic gastroenterology (GI) practice. Methods Consecutive initial visits to a tertiary academic GI practice were surveyed over a 3-month period as a fellow-initiated quality improvement project. All electronic records were reviewed to look for indications for CD screening according to published guidelines. The timing of screening was noted (before or after referral), as well as the screening method (serology or biopsy). Data were analysed to compare CD screening practices across subspecialty clinics. Results 616 consecutive patients (49±0.6 years, range 16–87 years, 58.5% females, 94% Caucasian) fulfilled inclusion criteria. CD testing was indicated in 336 (54.5%), but performed in only 145 (43.2%). The need for CD screening was highest in luminal GI and inflammatory bowel disease clinics, followed by biliary and hepatology clinics (p Conclusions More than 50% of patients in a tertiary GI clinic have indications for CD screening, but

Background Tricyclic antidepressants (TCAs) have efficacy in treating irritable bowel syndrome (IBS). Some clinicians use TCAs to treat residual symptoms in inflammatory bowel disease (IBD) patients already on decisive IBD therapy or with quiescent inflammation, although this strategy has not been formally studied. Goals The aim of this study was to examine the efficacy of TCA therapy in IBD patients with residual symptoms, despite controlled inflammation, in a retrospective cohort study. Study Inclusion required initiation of TCA for persistent gastrointestinal symptoms. IBD patients had inactive or mildly active disease with persistent symptoms despite adequate IBD therapy as determined by their physician. Symptom response was compared with IBS patients. Established Likert scales were used to score baseline symptom severity (0=no symptoms, 3=severe symptoms) and TCA response (0=no improvement; 3=complete satisfaction). Results Eighty-one IBD [41.3±1.7 y, 56F; 58 Crohn's disease/23 ulcerative colitis (UC)] and 77 IBS (46.2±1.7 y, 60F) patients were initiated on a TCA therapy. Baseline symptom scores (IBD, 2.06±0.03; IBS, 2.12±0.04; P=0.15) and symptom response to TCA therapy (IBD, 1.46±0.09; IBS, 1.30±0.09; P=0.2) were similar in both the groups. At least moderate improvement (Likert score ≥2) on TCA was achieved by comparable proportions of patients (59.3% IBD vs. 46% IBS; P=0.09). Within IBD, response was better with UC than Crohn's disease (1.86±0.13 vs. 1.26±0.11, respectively, P=0.003). Conclusions In a clinical practice setting, TCA use led to moderate improvement of residual gastrointestinal symptoms in IBD patients for whom escalation of IBD therapy was not planned. UC patients demonstrated higher therapeutic success. IBD symptom responses were similar to IBS patients.

SummaryBackground High-resolution manometry has become the preferred choice of oesophagologists for oesophageal motor assessment, but the learning curve among trainees remains unclear. Aim To determine the learning curve of high-resolution manometry interpretation. Methods A prospective interventional cohort study was performed on 18 gastroenterology trainees, naive to high-resolution manometry (median age 32 ± 4.0 years, 44.4% female). An intake questionnaire and a 1-h standardised didactic session were performed at baseline. Multiple 1-h interpretation sessions were then conducted periodically over 15 months where 10 studies were discussed; 5 additional test studies were provided for interpretation, and results were compared to gold standard interpretation by the senior author. Hypothetical management decisions based on trainee interpretation were separately queried. Accuracy was compared across test interpretations and sessions to determine the learning curve, with a goal of 90% accuracy. Results Baseline accuracy was low for abnormal body motor patterns (53.3%), but higher for achalasia/outflow obstruction (65.9%). Recognition of achalasia reached 90% accuracy after six sessions (P = 0.01), while overall accurate management decisions reached this threshold by the 4th session (P < 0.001). Based on our data, the threshold of 90% accuracy for recognition of any abnormal from normal pattern was reached after 30 studies (3rd session) but fluctuated. Diagnosis of oesophageal body motor patterns remained suboptimal; accuracy of advisability of fundoplication improved, but did not reach 90%. Conclusions High-resolution manometry has a steep learning curve among trainees. Achalasia recognition is achieved early, but diagnosis of other abnormal motor patterns and management decisions require further supervised training.

Background Irritable bowel syndrome (IBS) is a common abdominal pain disorder without an organic explanation. Abuse histories (physical, sexual, emotional) are prevalent in IBS. While abuse relates to mood disorders (depression and anxiety) also common in IBS, the influence of abuse on gastrointestinal (GI) symptoms and health-related quality of life (HRQOL) and its independence from psychological symptom comorbidity has not been studied. Methods Consecutive GI outpatients completed the ROME III Research Diagnostic Questionnaire and questionnaires on trauma (Life-Stress Questionnaire), mood (Beck Depression/Anxiety Inventories), somatic symptoms (PHQ-12), and HRQOL (SF-36). Current GI symptom severity and bother were assessed using 10-cm Visual Analog Scales. Key Results 272 ROME-defined IBS (47.6 ± 0.9 years, 81% female) and 246 non-FGID (51.6 ± 1.0 years, 65% female) subjects participated. IBS patients reported greater rates of physical, sexual, and emotional abuse (p < 0.006 each), and higher depression, anxiety, and somatic symptoms (p < 0.001). Greater bowel symptom bother (7.4 ± 0.2 vs 6.7 ± 0.2, p = 0.040), severity (7.7 ± 0.2 vs 6.5 ± 0.2, p < 0.001), recent symptomatic days (9.8 ± 0.4 vs 8.5 ± 0.3, p = 0.02), and poorer HRQOL (40.9 ± 2.3 vs 55.5 ± 1.7, p < 0.001) were noted in IBS with abuse. Abuse effects were additive, with greater IBS symptom severity and poorer HRQOL noted in cases with multiple forms of abuse. Mediation analyses suggested that abuse effects on GI symptoms and HRQOL were partially mediated by mood. Conclusions & Inferences Abuse experiences common among IBS sufferers are associated with reports of greater GI symptoms and poorer HRQOL, particularly in those with multiple forms of abuse; this relationship may be partially mediated by concomitant mood disturbances.

Background and aims: Vedolizumab inhibits leucocyte vascular adhesion and migration into the gastrointestinal tract through α4β7 integrin blockade. This agent became available in mid-2014 for the treatment of moderate to severe Crohn’s disease (CD) and UC (UC). The aim of this study was to assess the patterns of use, effectiveness and safety of vedolizumab in an inflammatory bowel disease (IBD) clinical practice. Methods: Patients beginning vedolizumab were enrolled with informed consent. A prospective cohort was followed with laboratory, disease activity and quality-of-life assessments made during infusion visits up to week 14. Duration of vedolizumab use, mucosal healing and safety were analysed retrospectively for all patients not captured in the prospective component of this study. Results: One hundred and two patients started vedolizumab, with 51 patients (30 CD, 21 UC) followed prospectively. The CD patients exhibited a significant decrease in Crohn’s Disease Activity Index ( p = 0.04) and Harvey–Bradshaw index ( p < 0.01) by week 14. The UC patients demonstrated improved partial Mayo scores at weeks 6 ( p < 0.01) and 14 ( p < 0.001). Ninety percent of all CD and UC patients remained on vedolizumab up to week 14. IBD-related quality of life was improved by week 6 in CD and UC cohorts ( p = 0.02 and p < 0.01 respectively). Colectomy for lack of response and systemic histoplamosis were notable reasons for early discontinuation of vedolizumab, which was otherwise well tolerated. Conclusions: Vedolizumab was efficacious and a high percentage of patients continued this therapy beyond induction dosing. Observed safety signals may be attributed to the refractory IBD disease state of this early-adopting clinical cohort.

Enhanced characterization of esophageal peristaltic and sphincter function provided by esophageal pressure topography (EPT) offers a potential diagnostic advantage over conventional line tracings (CLT). However, high-resolution manometry (HRM) and EPT require increased equipment costs over conventional systems and evidence demonstrating a significant diagnostic advantage of EPT over CLT is limited. Our aim was to investigate whether the inter-rater agreement and/or accuracy of esophageal motility diagnosis differed between EPT and CLT. Forty previously completed patient HRM studies were selected for analysis using a customized software program developed to perform blinded independent interpretation in either EPT or CLT (six pressure sensors) format. Six experienced gastroenterologists with a clinical focus in esophageal disease (attendings) and six gastroenterology trainees with minimal manometry experience (fellows) from three academic centers interpreted each of the 40 studies using both EPT and CLT formats. Rater diagnoses were assessed for inter-rater agreement and diagnostic accuracy, both for exact diagnosis and for correct identification of a major esophageal motility disorder. The total group agreement was moderate (κ=0.57; 95% CI: 0.56-0.59) for EPT and fair (κ=0.32; 0.30-0.33) for CLT. Inter-rater agreement between attendings was good (κ=0.68; 0.65-0.71) for EPT and moderate (κ=0.46; 0.43-0.50) for CLT. Inter-rater agreement between fellows was moderate (κ=0.48; 0.45-0.50) for EPT and poor to fair (κ=0.20; 0.17-0.24) for CLT. Among all raters, the odds of an incorrect exact esophageal motility diagnosis were 3.3 times higher with CLT assessment than with EPT (OR: 3.3; 95% CI: 2.4-4.5; P

Background Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Genetic polymorphisms can confer CD risk and influence disease phenotype. Indoleamine 2,3 dioxygenase-1 (IDO1) is one of the most over-expressed genes in CD and mediates potent anti-inflammatory effects via tryptophan metabolism along the kynurenine pathway. We aimed to determine whether non-synonymous polymorphisms in IDO1 or IDO2 (a gene paralog) are important either as CD risk alleles or as modifiers of CD phenotype. Methods Utilizing a prospectively collected database, clinically phenotyped CD patients (n = 734) and non-IBD controls (n = 354) were genotyped for established IDO1 and IDO2 non-synonymous single nucleotide polymorphisms (SNPs) and novel genetic variants elucidated in the literature. Allelic frequencies between CD and non-IBD controls were compared. Genotype-phenotype analysis was conducted. IDO1 enzyme activity was assessed by calculating the serum kynurenine to tryptophan ratio (K/T). Results IDO1 SNPs were rare (1.7% non-IBD vs 1.1% CD; p = NS) and not linked to Crohn's disease diagnosis in this population. IDO1 SNPs did however associate with a severe clinical course, presence of perianal disease, extraintestinal manifestations and a reduced serum K/T ratio during active disease suggesting lower IDO1 function. IDO2 minor allele variants were common and one of them, rs45003083, associated with reduced risk of Crohn's disease (p = 0.025). No IDO2 SNPs associated with a particular Crohn's disease clinical phenotype. Conclusions This work highlights the functional importance of IDO enzymes in human Crohn's disease and establishes relative rates of IDO genetic variants in a US population.

Summary Background The beta-2 adrenergic receptor (ADRB2) is an important target for epinephrine, a neurotransmitter in pain signalling. ADRB2 haplotypes affect receptor expression and ligand response, and have been linked to painful non-GI disorders. Aims To assess whether ADRB2 polymorphisms (rs1042713, rs1042714) are risk alleles for functional GI (FGID) and extraintestinal functional (EIFD) diagnoses, and whether ADRB2 predicts GI symptoms and health-related quality of life (HRQOL). Methods Of 398 subjects (49.6 ± 2.9 years, 68.0% female), 170 (42.5%) met Rome III criteria for ≥1 FGID [IBS (n = 139, 34.9%); functional dyspepsia (FD, n = 136, 34.1%), functional chest pain (FCP, n = 25, 6.2%)], while 228 were healthy controls. FGID subjects reported on bowel symptom severity and burden (10-cm VAS), frequency (days/last 2 weeks), EIFD, psychiatric diagnoses and HRQOL (SF 36). Multivariable models determined the contribution of ADRB2 polymorphisms to HRQOL, and mediational analyses assessed functional diagnoses as potential intermediates. Results rs1042714 minor G alleles were associated with FGID diagnoses (OR 1.8; 95% CI 1.2–2.7; P = 0.009), particularly FD (OR 2.1, 95% CI 1.3–3.3), with trends towards IBS (P = 0.19) and FCP (P = 0.06) diagnoses. Within IBS, G allele carriers had more severe bowel symptoms (P = 0.025), and symptomatic days (P = 0.009). G allele carriers had greater numbers of EIFD (1.0 ± 0.1 vs. 0.4 ± 0.07, P

Indoleamine 2,3 dioxygenase-1 (IDO1) is a tryptophan catabolizing enzyme with immunotolerance-promoting functions. We sought to determine if increased gut expression of IDO1 in Crohn's disease (CD) would result in detectable changes in serum levels of tryptophan and the initial IDO1 pathway catabolite, kynurenine.Individuals were prospectively enrolled through the Washington University Digestive Diseases Research Center. The Montreal Classification was used for disease phenotyping. Disease severity was categorized by the Physician's Global Assessment. Serum tryptophan and kynurenine were measured by high-pressure liquid chromatography. IDO1 immunohistochemical staining was performed on formalin-fixed tissue blocks.In all, 25 CD patients and 11 controls were enrolled. Eight CD patients had serum collected at two different timepoints and levels of disease activity compared. Strong IDO1 expression exists in both the lamina propria and epithelium during active CD compared to controls. Suppressed serum tryptophan levels and an elevated kynurenine/tryptophan (K/T) ratio were found in individuals with active CD as compared to those in remission or the control population. K/T ratios correlated positively with disease activity as well as with C-reactive protein and erythrocyte sedimentation rate. In the subgroup of CD patients with two serum measurements, tryptophan levels were elevated while kynurenine levels and the K/T ratio lowered as the disease activity lessened.IDO1 expression in CD is associated with lower serum tryptophan and an elevated K/T ratio. These levels may serve as a reasonable objective marker of gut mucosal immune activation and as a surrogate for CD activity.

Background: IBS is a common functional GI syndrome with a prominent pain component. History of physical, sexual, and/or emotional abuse is more prevalent among IBS sufferers. Previously we reported that abuse is linked to more severe and frequent IBS symptoms and poorer health related quality of life (HRQOL). If abuse experiences heighten brain neurocircuitry sensitivity to pain experiences as has been suggested (Ringel Y et al Gastroenterol 2008), this study then sought to examine the effects of an abuse history on rates of functional GI disorder (FGID) diagnoses, non-GI diagnoses, and recent pain symptoms among an IBS population; further, we aimed to determine whether experiences of multiple forms of abuse resulted in greater likelihood of developing functional GI and non-GI complaints. Methods: Consecutive GI outpatients were invited to complete ROME III Research Diagnostic Questionnaire to establish FGID criteria. Self-report questionnaires on abuse history (Life-Stress Questionnaire) were obtained, with a focus on physical, sexual, and emotional abuse. IBS patients with histories of any form of these abuse experiences were defined as IBS+/Abuse+. Recent non-GI somatic symptoms (PHQ-12), and historical somatic pain diagnoses (e.g., fibromyalgia, headache, chronic back pain) were recorded. 272 ROMEdefined IBS subjects (50.1±0.9 yrs, 81% female) were identified, and reported greater rates of abuse compared to a non-IBS comparator group (n=246): physical (18.1% vs 6.6%), sexual (15.5% vs 7.4%), and emotional (31.7% vs 16.9%) (p 1 form of abuse. Compared to IBS subjects without abuse histories (IBS+/Abuse-), IBS+/Abuse+ subjects had greater total numbers of ROME diagnoses (2.5±0.3 vs 2.1±0.3, p=0.10), non-GI pain diagnoses (1.9±0.2 vs. 0.9±0.08, p

Background: IBS is a common functional GI syndrome with a prominent pain component. History of physical, sexual, and/or emotional abuse is more prevalent among IBS sufferers. Previously we reported that abuse is linked to more severe and frequent IBS symptoms and poorer health related quality of life (HRQOL). If abuse experiences heighten brain neurocircuitry sensitivity to pain experiences as has been suggested (Ringel Y et al Gastroenterol 2008), this study then sought to examine the effects of an abuse history on rates of functional GI disorder (FGID) diagnoses, non-GI diagnoses, and recent pain symptoms among an IBS population; further, we aimed to determine whether experiences of multiple forms of abuse resulted in greater likelihood of developing functional GI and non-GI complaints. Methods: Consecutive GI outpatients were invited to complete ROME III Research Diagnostic Questionnaire to establish FGID criteria. Self-report questionnaires on abuse history (Life-Stress Questionnaire) were obtained, with a focus on physical, sexual, and emotional abuse. IBS patients with histories of any form of these abuse experiences were defined as IBS+/Abuse+. Recent non-GI somatic symptoms (PHQ-12), and historical somatic pain diagnoses (e.g., fibromyalgia, headache, chronic back pain) were recorded. 272 ROMEdefined IBS subjects (50.1±0.9 yrs, 81% female) were identified, and reported greater rates of abuse compared to a non-IBS comparator group (n=246): physical (18.1% vs 6.6%), sexual (15.5% vs 7.4%), and emotional (31.7% vs 16.9%) (p 1 form of abuse. Compared to IBS subjects without abuse histories (IBS+/Abuse-), IBS+/Abuse+ subjects had greater total numbers of ROME diagnoses (2.5±0.3 vs 2.1±0.3, p=0.10), non-GI pain diagnoses (1.9±0.2 vs. 0.9±0.08, p

demands from health authorities and the public regarding physician training in general. There are however very little actual quantitative data regarding the contribution of simulator training to the early learning curve of novice endoscopists. Objective The aim of this study therefore was to assess the performance of novice endoscopists during patient-based colonoscopy after intensive and prolonged training on a virtual reality endoscopy simulator.DesignTrainees without any endoscopic experience were included in the study. They were divided into two groups. The simulator-training program consisted of either 50 or 100 virtual-reality colonoscopies on the GI Mentor II simulator (Simbionix, Israel). After 10, 30 and 50 virtual colonoscopies in the first group and after 20, 60 and 100 virtual colonoscopies in the second group, trainees were assessed both simulator-based (SBA) and patient-based (PBA). At each PBA 2 single-handed colonoscopies were performed with a 20-minute time limit. Objective assessment consisted of the time to reach the cecum, or the maximum distance from the anal verge after fully straightening the colonoscope. Subjective assessment was done by two independent expert endoscopists using tri-split video assessment including camera view, endoscope view, and ScopeGuide magnetic imaging view. Results Eighteen novices participated in the study. All participants completed virtual training and assessments. The mean cecal intubation time on the SBA improved from baseline 7.08 to 2.08 minutes at completion of the training (P 0.007). Colonic insertion depth during PBA improved from 37 to 60 cm (P 0.002). The learning effect of simulator training slowed down after 60 simulator colonoscopies. The cecum was intubated 4 times by 3 novices, during 2nd PBA (n 1), and during the final PBA (n 3) (P 0.11). Subjective PBA demonstrated a general increase in the efficiency of movements, instrument handling and planned endoscopy. Measured on a 5 point scale, performance significantly improved from 1.67 to 2.20 (P 0.02) Conclusion Virtual reality training on the GI Mentor II simulator leads to a significant improvement of performance on the simulator itself and -more importantlyto significantly improved performances during patient-based colonoscopy. This study is the first to demonstrate the rationale for intensive simulator training in the early learning curve of novices performing colonoscopy.