The 100 most-cited articles in The American Journal of Gastroenterology, 2018

Crohn's disease is an idiopathic inflammatory disorder of unknown etiology with genetic, immunologic, and environmental influences. The incidence of Crohn's disease has steadily increased over the past several decades. The diagnosis and treatment of patients with Crohn's disease has evolved since the last practice guideline was published. These guidelines represent the official practice recommendations of the American College of Gastroenterology and were developed under the auspices of the Practice Parameters Committee for the management of adult patients with Crohn's disease. These guidelines are established for clinical practice with the intent of suggesting preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research, derived from extensive review of published literature. When exercising clinical judgment, health-care providers should incorporate this guideline along with patient's needs, desires, and their values in order to fully and appropriately care for patients with Crohn's disease. This guideline is…

Alcoholic liver disease (ALD) comprises a clinical-histologic spectrum including fatty liver, alcoholic hepatitis (AH), and cirrhosis with its complications. Most patients are diagnosed at advanced stages and data on the prevalence and profile of patients with early disease are limited. Diagnosis of ALD requires documentation of chronic heavy alcohol use and exclusion of other causes of liver disease. Prolonged abstinence is the most effective strategy to prevent disease progression. AH presents with rapid onset or worsening of jaundice, and in severe cases may transition to acute on chronic liver failure when the risk for mortality, depending on the number of extra-hepatic organ failures, may be as high as 20-50% at 1 month. Corticosteroids provide short-term survival benefit in about half of treated patients with severe AH and long-term mortality is related to severity of underlying liver disease and is dependent on abstinence from alcohol. General measures in patients hospitalized with ALD include inpatient management of liver disease complications, management of alcohol…

Pancreatic cysts are very common with the majority incidentally identified. There are several types of pancreatic cysts; some types can contain cancer or have malignant potential, whereas others are benign. However, even the types of cysts with malignant potential rarely progress to cancer. At the present time, the only viable treatment for pancreatic cysts is surgical excision, which is associated with a high morbidity and occasional mortality. The small risk of malignant transformation, the high risks of surgical treatment, and the lack of high-quality prospective studies have led to contradictory recommendations for their immediate management and for their surveillance. This guideline will provide a practical approach to pancreatic cyst management and recommendations for cyst surveillance for the general gastroenterologist.

OBJECTIVES: Chronic infection with hepatitis C virus (HCV) was previously the leading indication for liver transplant (LT) in the United States. However, since 2014 the use of direct-acting antivirals (DAAs) has decreased the chronic HCV burden, while the prevalence of nonalcoholic steatohepatitis (NASH) has risen substantially through the last decade. Both gender and ethnic disparities in indications for LT have been shown in the past but no data on this have been reported since the implementation of DAAs. METHODS: We assessed changes in etiologies for LT listing and in gender and ethnic differences in those listed for LT. Adult patients registered for LT in the United Network for Organ Sharing/Organ Procurement and Transplantation Network database between January 1, 2004 and December 31, 2016 were included. Multinomial logistic regression modeling was used to test for changes in waitlist or liver transplant rates. RESULTS: The study included 127,164 adult patients registered for LT. By 2016, alcoholic liver disease (ALD) was the leading etiology for waitlisting and LT; NASH was…

OBJECTIVES: Irritable bowel syndrome (IBS) is a chronic functional bowel disorder that is thought to be due to a disorder of brain-gut function. Drugs acting centrally, such as antidepressants, and psychological therapies may, therefore, be effective. METHODS: We updated a previous systematic review and meta-analysis of randomized controlled trials (RCTs). MEDLINE, EMBASE, PsychINFO, and the Cochrane Controlled Trials Register were searched (up to July 2017). Trials recruiting adults with IBS, which compared antidepressants versus placebo, or psychological therapies versus control therapy or "usual management" were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). RESULTS: The search strategy identified 5316 citations. Fifty-three RCTs, reported in 51 separate articles, were eligible for inclusion: 17 compared antidepressants with placebo, 35 compared psychological therapies with control therapy or "usual management", and one compared both psychological therapy and…

INTRODUCTION Irritable bowel syndrome (IBS) is the most prevalent of the functional gastrointestinal disorders (FGIDs). Current estimates are that IBS affects up to 10–12% of adults in North America [1, 2]. Although it can affect all individuals regardless of age, creed, or gender, IBS is more common among women and is most commonly diagnosed in younger individuals ( 0.10 for the ÷2 test, was arbitrarily chosen to represent low levels of heterogeneity [29]. Review Manager version 5.3.5 (RevMan for Windows 2014, The Nordic Cochrane Centre, Copenhagen, Denmark) was used to generate Forest plots of pooled RRs and SMDs for primary and secondary outcomes with 95% CIs, as well as funnel plots. The latter were assessed for evidence of asymmetry, and therefore possible publication bias or other small study effects, using the Egger test [30], if there were sufficient (10 or more) eligible studies included in the meta-analysis, in line with published recommendations [31]. GRADEpro version 3.6 (GRADE working group 2004–2007) was used to grade the quality of the evidence. Consensus was reached…

OBJECTIVE: Dietary triggers such as gluten and highly fermentable oligo-, di- and monosaccharides and polyols (FODMAP)-containing foods have been associated with worsening irritable bowel syndrome (IBS) symptoms. However, the true impact of dietary restriction on IBS symptoms has remained unclear. The aim of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) examining the efficacy of exclusion diets (we focused on low FODMAP and gluten-free diets (GFD)) in IBS. METHODS: We conducted a search of the literature using the electronic databases MEDLINE (1946 to November 2017), EMBASE (1974 to November 2017), Cochrane Central Register of Controlled Trials (November 2017), and Cochrane Database of Systematic Reviews (2005 to November, 2017) for RCTs of exclusion diets in IBS. Two independent reviewers screened citations and a third reviewer resolved disagreement. Two independent reviewers performed eligibility assessment and data abstraction. For inclusion, RCTs that evaluated an exclusion diet versus an alternative or usual diet and…

OBJECTIVES: The goal of the study was to determine whether endoscopic ultrasound (EUS)-guided biliary drainage (EUS-BD) is comparable to conventional transpapillary stenting with endoscopic retrograde cholangiopancreatography (ERCP) in palliation of malignant distal biliary obstruction. Although ERCP for the palliation of malignant biliary obstruction is the standard of care, post-procedure pancreatitis and stent dysfunctions are not uncommon. While EUS-BD has garnered interest as a viable alternative when ERCP is impossible, its role as a primary palliation of malignant distal biliary obstruction is yet to be proven. METHODS: We performed random allocation to EUS-BD or ERCP in 125 patients with unresectable malignant distal biliary obstruction at four tertiary academic referral centers in South Korea. RESULTS: Technical success rates were 93.8% (60/64) for EUS-BD and 90.2% (55/61) for ERCP (difference 3.6%, 95% 1-sided confidence interval lower limit -4.4%, P = 0.003 for noninferiority margin of 10%). Clinical success rates were 90.0% (54/60) in EUS-BD and 94.5% (52/55) in ERCP (P…

INTRODUCTION: Living in an urban environment may increase the risk of developing inflammatory bowel disease (IBD). It is unclear if this observation is seen globally. We conducted a population-based study to assess the relationship between urbanization and incidence of IBD in the Asia-Pacific region. METHODS: Newly diagnosed IBD cases between 2011 and 2013 from 13 countries or regions in Asia-Pacific were included. Incidence was calculated with 95% confidence interval (CI) and pooled using random-effects model. Meta-regression analysis was used to assess incidence rates and their association with population density, latitude, and longitude. RESULTS: We identified 1175 ulcerative colitis (UC), 656 Crohn's disease (CD), and 37 IBD undetermined (IBD-U). Mean annual IBD incidence per 100 000 was 1.50 (95% CI: 1.43-1.57). India (9.31; 95% CI: 8.38-10.31) and China (3.64; 95% CI, 2.97-4.42) had the highest IBD incidence in Asia. Incidence of overall IBD (incidence rate ratio [IRR]: 2.19; 95% CI: 1.01-4.76]) and CD (IRR: 3.28; 95% CI: 1.83-9.12) was higher across 19 areas of Asia with a…

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic esophageal inflammation that may lead to stricture formation. This narrowing can cause major complications including food impactions. Despite increasing interest in EoE accurate data on its natural course is scarce. Therefore, we aimed to investigate the natural course of EoE and to evaluate the association between undiagnosed disease and the occurrence of complications over two decades in a large cohort. METHODS: We retrospectively analyzed charts of patients diagnosed with EoE between 1996 and 2015, collected from 15 hospitals throughout the Netherlands. Histologic, clinical, and endoscopic characteristics were identified and stratified by age and diagnostic delay. RESULTS: We included 721 patients (524 males, 117 children (≤18 years)). Dysphagia and food impactions were more common in adults whereas children more often presented with vomiting and abdominal pain (all p < 0.001). The prevalence of fibrotic endoscopic features was higher in adults (76%) than in children (39%) (p < 0.001). As time with undiagnosed disease…

Primary biliary cholangitis (PBC) is a chronic, cholestatic, autoimmune disease with a variable progressive course. PBC can cause debilitating symptoms including fatigue and pruritus and, if left untreated, is associated with a high risk of cirrhosis and related complications, liver failure, and death. Recent changes to the PBC landscape include a name change, updated guidelines for diagnosis and treatment as well as new treatment options that have recently become available. Practicing clinicians face many unanswered questions when managing PBC. To assist these healthcare providers in managing patients with PBC, the American College of Gastroenterology (ACG) Institute for Clinical Research & Education, in collaboration with the Chronic Liver Disease Foundation (CLDF), organized a panel of experts to evaluate and summarize the most current and relevant peer-reviewed literature regarding PBC. This, combined with the extensive experience and clinical expertise of this expert panel, led to the formation of this clinical guidance on the diagnosis and management of PBC.

OBJECTIVES: Patients with irritable bowel syndrome (IBS) are more likely to be both absent from and impaired at work compared to non-IBS patients. We investigated the impact of IBS on work productivity and activity impairment and the relationship to disease specific and general health measures. METHOD: In total, 525 patients with IBS completed questionnaires assessing work productivity and activity impairment, IBS symptom severity, IBS-related quality of life and GI-specific anxiety. In addition, 155 of the patients completed questionnaires assessing severity of somatic symptoms, depression, anxiety and fatigue. Uni- and bivariate analyses were performed, as well as linear regression to determine factors independently associated with the work productivity and activity impairment measures. RESULTS: Of employed patients, 24.3% reported absenteeism and 86.8% reported presenteeism because of their IBS. With increasing severity of IBS symptoms and GI-specific anxiety, higher degrees of work impairment were seen. Work productivity impairment in IBS was also associated with low quality of…

OBJECTIVES: Inflammatory bowel diseases (IBD) need long-term treatment, which can influence pregnancies in young women. Uncontrolled IBD is associated with poor pregnancy outcomes. Despite the labeling of Anti-tumor necrosis factor (TNF) antibodies (anti-TNFα) which indicates that their use is not recommended during pregnancy, anti-TNFα are increasingly being used during pregnancy and may expose women and their fetuses to treatment-related complications. Existing recommendations on the timing of treatment during pregnancy are inconsistent. We aimed to assess the safety of anti-TNFα treatment in pregnant women with IBD, and up to the first year of life for their children. METHODS: An exposed/non exposed retrospective cohort was conducted on the French national health system database SNIIRAM (Système National d'Information Inter-Régimes de l'Assurance Maladie). All IBD women who became pregnant between 2011 and 2014 were included. Women with concomitant diseases potentially treated with anti-TNFα were excluded. Anti-TNFα exposure (infliximab, adalimumab, golimumab or certolizumab…

OBJECTIVES: Digestive diseases account for >100 million ambulatory care visits annually in the U.S. Yet, comparatively less is known about the true burden of gastrointestinal (GI) symptoms in the general U.S. POPULATION: The aim of this study was to use data from the "National GI Survey"-a population-based audit of GI symptoms in >71,000 participants-to determine the prevalence and predictors of GI symptoms in community-dwelling Americans. METHODS: We conducted the National GI Survey using a mobile app called MyGiHealth, which employs a computer algorithm that systematically collects participants' GI symptoms. We recruited a nationally representative sample of Americans to complete the survey, which guided respondents through National Institutes of Health (NIH) GI Patient Reported Outcome Measurement Information System (PROMIS®) scales along with questions about relevant comorbidities and demographics. We measured the prevalence of GI symptoms in the past week and employed logistic regression to adjust for confounding. RESULTS: Overall, 71,812 individuals completed the survey, of…

OBJECTIVES: We aimed to quantify the safety and effectiveness of vedolizumab (VDZ) when used for UC, and to identify predictors of response to treatment. METHODS: Retrospective review (May 2014-December 2016) of VICTORY Consortium data. Adults with follow-up after starting VDZ for clinically active UC were included. Primary effectiveness outcomes were cumulative rates of clinical remission (resolution of all UC-related symptoms) and endoscopic remission (Mayo endoscopic sub-score 0). Key secondary effectiveness outcomes included cumulative rates of corticosteroid-free remission and deep remission (clinical remission and endoscopic remission). Cox proportional hazard analyses were used to identify independent predictors of treatment effectiveness. Non-response imputation (NRI) sensitivity analyses were performed for effectiveness outcomes. Key safety outcomes were rates of serious infection, serious adverse events, and colectomy. RESULTS: We included 321 UC patients (71% prior TNFα antagonist exposure, median follow-up 10 months). The 12-month cumulative rates of clinical remission…

OBJECTIVES: Ultra-processed foods (UPF) consumption has increased over the last decades and is raising concerns about potential adverse health effects. Our objective was to assess the association between UPF consumption and four functional gastrointestinal disorders (FGIDs): irritable bowel syndrome (IBS), functional constipation (FC), functional diarrhea (FDh), and functional dyspepsia (FDy), in a large sample of French adults. METHODS: We analyzed dietary data of 33,343 participants from the web-based NutriNet-Santé cohort, who completed at least three 24 h food records, prior to a Rome III self-administered questionnaire. Proportion (in weight) of UPF in the diet (UPFp) was computed for each subject. The association between UPFp quartiles and FGIDs was estimated by multivariable logistic regression. RESULTS: Participants included in the analysis were mainly women (76.4%), and the mean age was 50.4 (SD = 14.0) years. UPF accounted for 16.0% of food consumed in weight, corresponding to 33.0% of total energy intake. UPF consumption was associated with younger age, living alone,…

OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. RESULTS: The study population comprised 841 children, of whom 388 (46%) had been…

Technological advances in artificial intelligence (AI) represent an enticing opportunity to benefit gastroenterological practice. Moreover, AI, through machine or deep learning, permits the ability to develop predictive models from large datasets. Possibilities of predictive model development in machine learning are numerous dependent on the clinical question. For example, binary classifiers aim to stratify allocation to a categorical outcome, such as the presence or absence of a gastrointestinal disease. In addition, continuous variable fitting techniques can be used to predict quantity of a therapeutic response, thus offering a tool to predict which therapeutic intervention may be most beneficial to the given patient. Namely, this permits an important opportunity for personalization of medicine, including a movement from guideline-specific treatment algorithms to patient-specific ones, providing both clinician and patient the capacity for data-driven decision making. Furthermore, such analyses could predict the development of GI disease prior to the manifestation of symptoms,…

OBJECTIVES: Gastritis OLGA-staging ranks the risk for gastric cancer (GC) in progressive stages (0-IV). This long-term follow-up study quantifies the GC risk associated with each OLGA stage. METHODS: Consecutive patients (7436) underwent esophagogastroscopy (T-0), with mapped gastric biopsies, OLGA staging, andH. pyloristatus assessment. Patients with neoplastic lesion (invasive or noninvasive) at the index endoscopy (and/or within 12 months) were excluded. All patients were followed-up (T-1) by combining different sources of clinical/pathological information (Regional Registries of: (i) esophagogastroduodenoscopies; (ii) pathology reports; (iii) cancer, (iv) mortality). The endpoint was histologically documented development of gastric epithelial neoplasia. RESULTS: At T-0, the patients' distribution by OLGA stage was: Stage 0 = 80.8%; Stage I = 12.6%; Stage II = 4.3%; Stage III = 2.0%; Stage IV = 0.3%;H. pyloriinfection was detected in 25.9% of patients. At the end of the follow-up (mean/median = 6.3/6.6 years), 28 incident neoplasia were documented (overall prevalence = 0.60 per…

Antireflux surgery anatomically restores the antireflux barrier and is a therapeutic option for proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease or PPI intolerance. Laparoscopic fundoplication is the standard antireflux surgery, though its popularity has declined due to concerns regarding wrap durability and adverse events. As the esophagogastric junction is an anatomically complex and dynamic area subject to mechanical stress, wraps are susceptible to disruption, herniation or slippage. Additionally, recreating an antireflux barrier to balance bidirectional bolus flow is challenging, and wraps may be too tight or too loose. Given these complexities it is not surprising that post-fundoplication symptoms and complications are common. Perioperative mortality rates range from 0.1 to 0.2% and prolonged structural complications occur in up to 30% of cases. Upper gastrointestinal endoscopy with a comprehensive retroflexed examination of the fundoplication and barium esophagram are the primary tests to assess for structural complications. Management hinges on…

OBJECTIVES: Current guidelines for necrotizing pancreatitis (NP) recommend delay in drainage ± necrosectomy until 4 or more weeks after initial presentation to allow collections to wall off. However, evidence of infection with clinical deterioration despite maximum support may mandate earlier (<4 weeks) intervention. There are concerns, but scant data regarding risk of complications and outcomes with early endoscopic intervention. Our aim was to compare the results of an endoscopic centered step-up approach to NP when initiated before versus 4 or more weeks. METHODS: All patients undergoing intervention for NP were managed using an endoscopically centered step-up approach, with transluminal drainage whenever feasible, ±necrosectomy, and/or percutaneous catheter drainage as needed, with surgery only for failures. Interventions were categorized as early or standard based on timing of intervention (<4 weeks or ≥ 4 weeks from onset of pancreatitis). Demographic data, indications and timing for interventions, number and type of intervention, mortality and morbidity (length of stay in…

OBJECTIVES: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that compromise quality of life and may increase mortality. This study compared the mortality risk with prolonged corticosteroid use vs. antitumor necrosis factor-α (anti-TNF) drugs in IBD. METHODS: A retrospective cohort study was conducted among Medicaid and Medicare beneficiaries from 2001 to 2013 with IBD prescribed either >3,000 mg of prednisone or equivalent within a 12-month period or new initiation of anti-TNF therapy, each treated as time-updating exposures. The primary outcome was all-cause mortality. Secondary outcomes included common causes of death. Marginal structural models were used to determine odds ratios (ORs) and 95% confidence intervals (CIs) for anti-TNF use relative to corticosteroids. RESULTS: Among patients with CD, 7,694 entered the cohort as prolonged corticosteroid users and 1,879 as new anti-TNF users. Among patients with UC, 3,224 and 459 entered the cohort as prolonged CS users and new anti-TNF users, respectively. The risk of death was statistically…

BACKGROUND: Subtle histopathologic features such as eosinophilia and increased mast cells have been observed in functional gastrointestinal disorders (FGIDs), including functional dyspepsia (FD) and the irritable bowel syndrome (IBS). The mechanisms that drive recruitment of these cells to the gastrointestinal tract remain unexplained, largely due to the heterogeneity in phenotypes among patients diagnosed with such conditions. We aimed to systematically review the literature and collate the evidence for immune activation in FD and IBS, and where possible, detail the nature of activation. METHODS: Seven literature databases were searched using the keywords: 'functional gastrointestinal disorder', FGID, 'functional dyspepsia', 'non-ulcer dyspepsia', 'idiopathic dyspepsia', 'irritable bowel syndrome', IBS and 'immun*'. RESULTS: Fifty-one papers reporting discordant immune features met the selection criteria for this review. Changes in lymphocyte populations, including B and T lymphocyte numbers and activation status were reported in IBS and FD, in conjunction with duodenal…

OBJECTIVES: Two identical, phase 3, randomized, double-blind, placebo-controlled trials evaluated the efficacy and safety of plecanatide in patients with irritable bowel syndrome with constipation (IBS-C). METHODS: Adults meeting Rome III criteria for IBS-C were randomized (1:1:1) to placebo or plecanatide (3 or 6 mg) for 12 weeks. The primary efficacy end point was the percentage of overall responders (patients reporting ≥30% reduction from baseline in worst abdominal pain plus an increase of ≥1 complete spontaneous bowel movement (CSBM)/week from baseline in the same week for ≥6 of 12 treatment weeks). Safety was assessed by adverse events (AEs). RESULTS: Overall, 2189 individuals were randomized across the two studies and 1879 completed the studies. Demographic and baseline characteristics were similar across treatment groups and between studies. The percentage of overall responders in Study 1 was 30.2% and 29.5% for plecanatide 3 and 6 mg, respectively, vs. 17.8% placebo (P < 0.001 for each dose vs. placebo), and in Study 2 was 21.5% (P = 0.009) and 24.0% (P < 0.001) for…

OBJECTIVES: The role of smoking in the development of non-alcoholic fatty liver disease (NAFLD) remains controversial. We assessed the risk of incident NAFLD according to smoking status and urinary cotinine levels. METHODS: We performed a cohort study of 199,468 Korean adults without NAFLD at baseline who were followed annually or biennially for a median of 4.1 years. The presence of fatty liver was determined using ultrasound. NAFLD severity was assessed using NAFLD fibrosis score (NFS), a non-invasive fibrosis marker. RESULTS: During 1,070,991 person-years of follow-up, 45,409 participants developed NAFLD. Self-reported current smoking, pack-years, and urinary cotinine level were significantly associated with increased risk for NAFLD. For men, the multivariable-adjusted hazard ratios (aHR) (95% confidence intervals (CI)) for incident NAFLD comparing 10-19.9, and ≥20 pack-years to 0 pack-years were 1.25 (1.21- 1.29), and 1.36 (1.30-1.42), respectively; for women, aHR (95% CI) for NAFLD comparing 5-9.9, and ≥10 pack-years to 0 pack-years were 1.25 (1.04-1.50), and 1.46 (1.17-1.81),…

OBJECTIVES: Addressing procedure-related anxiety should improve adherence to colorectal cancer screening programs and diagnostic colonoscopy. We performed a systematic review to assess anxiety among individuals undergoing colonoscopy or flexible sigmoidoscopy (FS). METHODS: We searched multiple electronic databases for studies evaluating anxiety associated with colonoscopy or FS published from 2005 to 2017. Two reviewers independently identified studies, extracted data, and assessed study quality. The main outcomes were the magnitude of pre-procedure anxiety, types of concerns, predictors of anxiety, and effectiveness of anxiety-lowering interventions in individuals undergoing lower endoscopy. The protocol was prospectively registered in PROSPERO. RESULTS: Fifty-eight studies (24,490 patients) met the inclusion criteria. Patients undergoing colonoscopy had a higher mean level of anxiety than that previously reported in the general population, with some studies reporting more than 50% of patients having moderate-to-severe anxiety. Areas of anxiety-related concern included bowel…

INTRODUCTION: Telemedicine has shown promise in inflammatory bowel disease (IBD). The objective of this study was to compare disease activity and quality of life (QoL) in a 1-year randomized trial of IBD patients receiving telemedicine vs. standard care. METHODS: Patients with worsening symptoms in the prior 2 years were eligible for randomization to telemedicine (monitoring via texts EOW or weekly) or standard care. The primary outcomes were the differences in change in disease activity and QoL between the groups; change in healthcare utilization among groups was a secondary aim. RESULTS: 348 participants were enrolled (117 control group, 115 TELE-IBD EOW, and 116 TELE-IBD weekly). 259 (74.4%) completed the study. Age was 38.9 ± 12.3 years, 56.6% were women, 91.9% were Caucasian, 67.9% had Crohn's disease (CD) and 42.5% had active disease at baseline. In CD, all groups experienced a decrease in disease activity (control -5.2 ± 5.0 to 3.7 ± 3.6, TELE-IBD EOW 4.7 ± 4.1 to 4.2 ± 3.9, and TELE-IBD weekly 4.2 ± 4.2 to 3.2 ± 3.4, p < 0.0001 for each of the groups) In UC, only controls…

OBJECTIVES: Portal vein thrombosis (PVT) is a frequent complication of cirrhosis. Benefit, safety, and duration of anticoagulant treatment in this setting are controversial issues. The aim of this study was to analyze the course of PVT in a large cohort of cirrhotic patients undergoing or not anticoagulation therapy. METHODS: The data of 182 patients who presented between January 2008 and March 2016 with cirrhosis and PVT with at least 3 months of follow-up after the first PVT detection were analyzed. Eighty-one patients received anticoagulants and 101 were untreated per physician discretion. RESULTS: The extension of the thrombosis decreased by >50% in 46 (56.8%, with complete recanalization in 31/46) patients under anticoagulation and in 26 (25.7%) untreated patients. Of the 46 patients who underwent recanalization, 17 (36%) suffered recurrent thrombosis after stopping anticoagulation therapy. Kaplan-Meier analysis showed a higher survival rate in the treated group (p = 0.010). At multivariate analysis, anticoagulation was an independent factor associated with longer survival…

OBJECTIVES: The diagnostic criteria for irritable bowel syndrome (IBS) have recently been updated from Rome III to Rome IV. Whereas in Rome III a diagnosis of IBS entailed chronic abdominal pain or discomfort at least 3 days per month, in Rome IV the term discomfort has been removed and the frequency of abdominal pain increased to at least 1 day per week. We examined how this change in IBS criteria impacts on clinical characteristics and pathophysiological factors. METHODS: A total of 542 Swedish subjects with Rome III IBS completed a baseline questionnaire enquiring for the number of abdominal pain days in the last 10 days; this was subsequently used as a surrogate marker to identify Rome IV IBS, in that (a) those with 0 or 1 day of pain were classed as Rome IV-negative, and (b) those with ≥2 days of pain were classed as Rome IV-positive. Comparisons were made between Rome IV-positive and -negative IBS groups for demographics, IBS subtype, gastrointestinal and psychological symptoms, somatisation, fatigue, disease-specific quality of life, rectal sensitivity, and oro-anal transit…

BACKGROUND: Acute pancreatitis is linked to pancreatic cancer, but the direction of this association is not fully elaborated. METHODS: This was a population-based cohort study including all Swedish residents diagnosed with a first-time episode of acute pancreatitis between 1997 and 2013 and corresponding matched pancreatitis-free individuals from the general population. Hazard ratios for the association between acute pancreatitis and pancreatic cancer were estimated using multivariable Cox regression models. RESULTS: Overall, 49,749 individuals with acute pancreatitis and 138,750 matched individuals without acute pancreatitis were followed up for 1,192,134 person-years (median 5.3 years). A total of 769 individuals developed pancreatic cancer, of whom 536 (69.7%) had a history of acute pancreatitis. The risk of pancreatic cancer was substantially increased during the first few years after a diagnosis of acute pancreatitis but declined gradually over time, reaching a level comparable to the pancreatitis-free population after >10 years of follow-up. In those with non-gallstone-related…

Nausea is an uneasy feeling in the stomach while vomiting refers to the forceful expulsion of gastric contents. Chronic nausea and vomiting represent a diverse array of disorders defined by 4 weeks or more of symptoms. Chronic nausea and vomiting result from a variety of pathophysiological processes, involving gastrointestinal and non-gastrointestinal causes. The prevalence of chronic nausea and vomiting is unclear, although the epidemiology of specific conditions, such as gastroparesis and cyclic vomiting syndrome, is better understood. The economic impact of chronic nausea and vomiting and effects on quality of life are substantial. The initial diagnostic evaluation involves distinguishing gastrointestinal causes of chronic nausea and vomiting (e.g., gastroparesis, cyclic vomiting syndrome) from non-gastrointestinal causes (e.g., medications, vestibular, and neurologic disorders). After excluding anatomic, mechanical and biochemical causes of chronic nausea and vomiting, gastrointestinal causes can be grouped into two broad categories based on the finding of delayed, or normal,…

OBJECTIVES: Cirrhosis is associated with gut microbial dysbiosis, high readmissions and proton pump inhibitor (PPI) overuse, which could be inter-linked. Our aim was to determine the effect of PPI use, initiation and withdrawl on gut microbiota and readmissions in cirrhosis. METHODS: Four cohorts were enrolled. Readmissions study: Cirrhotic inpatients were followed throughout the hospitalization and 30/90-days post-discharge. PPI initiation, withdrawal/continuation patterns were analyzed between those with/without readmissions. Cross-sectional microbiota study: Cirrhotic outpatients and controls underwent stool microbiota analysis. Beneficial autochthonous and oral-origin taxa analysis vis-à-vis PPI use was performed. Longitudinal studies: Two cohorts of decompensated cirrhotic outpatients were enrolled. Patients on chronic unindicated PPI use were withdrawn for 14 days. Patients not on PPI were started on omeprazole for 14 days. Microbial analysis for oral-origin taxa was performed pre/post-intervention. RESULTS: Readmissions study: 343 inpatients (151 on admission PPI) were…

OBJECTIVES: Linaclotide and plecanatide are guanylate cyclase-C (GCC) agonists for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C). Our objective is to evaluate the efficacy and tolerability of GCC agonists based on data from multiple randomized controlled trials (RCTs). METHODS: We searched PubMED, EMBASE, Cochrane databases, clinicaltrials.gov, major conference abstracts, Food and Drug Administration (FDA) websites, and United States Securities and Exchange Commission filings of drug sponsors to identify RCTs of CIC or IBS-C patients. We assessed efficacy based on FDA-approved composite responder endpoints, diarrhea as an adverse event, and study withdrawal owing to diarrhea for each therapy. Trial results were pooled using DerSimonian and Laird random effects model of meta-analysis and exact logistic regression when appropriate with 95% confidence intervals. Meta-regression was performed to compare outcomes between therapies adjusting for placebo event rate. RESULTS: Eight linaclotide trials (five CIC; three IBS-C) and…

OBJECTIVES: Variants in patatin-like phospholipase domain-containing 3 (PNPLA3;rs738409), transmembrane 6 superfamily member 2 (TM6SF2;rs58542926), and membrane bound O-acyltransferase domain containing 7 (MBOAT7;rs641738) are risk factors for the development of alcohol-related cirrhosis. Within this population,PNPLA3rs738409 is also an established risk factor for the development of hepatocellular carcinoma (HCC). The aim of this study was to explore possible risk associations ofTM6SF2rs58542926 andMBOAT7rs641738 with HCC. METHODS: Risk variants inPNPLA3, TM6SF2, andMBOAT7were genotyped in 751 cases with alcohol-related cirrhosis and HCC and in 1165 controls with alcohol-related cirrhosis without HCC. Association with the risk of developing HCC was analyzed using multivariate logistic regression. RESULTS: The development of HCC was independently associated withPNPLA3rs738409 (ORadjusted 1.84 [95% CI 1.55-2.18],p= 1.85 × 10-12) andTM6SF2rs58542926 (ORadjusted 1.66 [1.30-2.13],p = 5.13 × 10-05), using an additive model, and controlling the sex, age, body mass index, and type 2…

Small intestinal histologic abnormalities in celiac disease include atrophy of the intestinal villi, hypertrophy of the crypts and lymphocytic infiltration of intraepithelial spaces and lamina propria. These findings are central to diagnosis and their severity and change over time are valuable to monitor disease course and response to therapy. Subjective methods to grade celiac disease histological severity include the Marsh-Oberhuber and Corazza-Villanacci systems. Quantitative histology uses villus height (Vh), crypt depth (Cd), and intra-epithelial lymphocyte count (per 100 enterocytes) to provide objective measures of histologic changes including Vh:Cd ratio. Here we examine the available literature regarding these methodologies and support the use of quantitative histology as the preferred method for accurately and reproducibly demonstrating change of relevant histologic end points over time. We also propose a Quantitative-Mucosal Algorithmic Rules for Scoring Histology (Q-MARSH) system to partially align quantitative histology results with the traditional Marsh,…

OBJECTIVES: Prokinetics are recommended for the treatment of functional dyspepsia (FD) but systematic reviews give conflicting results on the efficacy of these agents. We have therefore conducted an updated systematic review to support the 2017 joint ACG/CAG dyspepsia guidelines. METHODS: Electronic databases, including MEDLINE, EMBASE, and CENTRAL, were searched until September 2017 for randomized controlled trials (RCTs) comparing either prokinetics and placebo or two types of prokinetics to improve FD symptoms. The primary outcome was absence or improvement of dyspeptic symptoms at the end of treatment. Double-blind eligibility assessment and data extraction was performed. Pooled risk ratios of symptoms persisting or adverse events occurring, and standardized mean difference of quality-of-life (QoL) scores with 95% CI, using a random effects model, were calculated. Quality of evidence was assessed using GRADE. RESULTS: The search identified 1388 citations; 38 studies in 35 papers were included. Of these, 29 trials comparing prokinetics with placebo were found. There was a…

BACKGROUND: The aim of this study was to assess expert gastroenterologists' opinion on treatment for distinct gastroesophageal reflux disease (GERD) profiles characterized by proton pump inhibitor (PPI) unresponsive symptoms. METHODS: Fourteen esophagologists applied the RAND/UCLA Appropriateness Method to hypothetical scenarios with previously demonstrated GERD (positive pH-metry or endoscopy) and persistent symptoms despite double-dose PPI therapy undergoing pH-impedance monitoring on therapy. A priori thresholds included: esophageal acid exposure (EAE) time >6.0%; symptom-reflux association: symptom index >50% and symptom association probability >95%; >80 reflux events; large hiatal hernia: >3 cm. Primary outcomes were appropriateness of four invasive procedures (laparoscopic fundoplication, magnetic sphincter augmentation, transoral incisionless fundoplication, radiofrequency energy delivery) and preference for pharmacologic/behavioral therapy. RESULTS: Laparoscopic fundoplication was deemed appropriate for elevated EAE, and moderately appropriate for positive symptom-reflux…

OBJECTIVES: A systematic review and meta-analysis was performed to summarize the available evidence on risk scores for predicting advanced colorectal neoplasia (advanced adenomas and cancer) in average-risk and asymptomatic populations undergoing screening colonoscopy. METHODS: PubMed, EMBASE, and Web of Science databases were searched up to 28 March 2018. Studies that developed or validated a risk score to predict the risk of advanced colorectal neoplasia were included. Two reviewers independently extracted study characteristics including diagnostic performance indicators and assessed risk of bias and applicability in the included studies. Meta-analyses were conducted to determine the overall discrimination of risk scores evaluated by more than 1 study. RESULTS: A total of 22 studies including 17 original risk scores were identified. Risk scores included a median number of 5 risk factors. Factors most commonly included were age, sex, family history in first-degree relatives, body mass index and smoking. The area under the receiver operating characteristic curve of risk scores…

OBJECTIVES: Hereditary pancreatitis (HP), an autosomal dominant disease typically caused by mutations in PRSS1, has a broad range of clinical characteristics and high cumulative risk of pancreatic cancer. We describe survival and pancreatic cancer risk in the largest HP cohort in the US. METHODS: HP probands and family members prospectively recruited from 1995 to 2013 completed medical and family history questionnaires, and provided blood for DNA testing. Overall survival (until 12/31/2015) was determined from the Social Security Death Index (SSDI), National Death Index (NDI), and family members. Cause of death was obtained from the NDI. RESULTS: 217 PRSS1 carriers (181 symptomatic) formed the study cohort. The most frequently detected mutations were p.R122H (83.9%) and p.N29I (11.5%). Thirty-seven PRSS1 carriers (30 symptomatic, 7 asymptomatic) were deceased at conclusion of the study (5 from pancreatic cancer). Median overall survival was 79.3 years (IQR 72.2-85.2). Risk of pancreatic cancer was significantly greater than age- and sex- matched SEER data (SIR 59, 95% CI 19-138),…

OBJECTIVE: Obesity and diabetes are associated with an increased liver cancer risk. However, most studies have examined all primary liver cancers or hepatocellular carcinoma, with few studies evaluating intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. Thus, we examined the association between obesity and diabetes and ICC risk in a pooled analysis and conducted a systematic review/meta-analysis of the literature. DESIGN: For the pooled analysis, we utilized the Liver Cancer Pooling Project, a consortium of 13 US-based, prospective cohort studies with data from 1,541,143 individuals (ICC casesn= 414). In our systematic review, we identified 14 additional studies. We then conducted a meta-analysis, combining the results from LCPP with results from the 5 prospective studies identified through September 2017. RESULTS: In the LCPP, obesity and diabetes were associated with a 62% [Hazard Ratio (HR) = 1.62, 95% Confidence Interval (CI): 1.24-2.12] and an 81% (HR = 1.81, 95% CI: 1.33-2.46) increased ICC risk, respectively. In the meta-analysis of…

BACKGROUND: Traditionally uncomplicated acute diverticulitis was routinely treated with antibiotics, although evidence for this strategy was lacking. Recently, two randomized clinical trials (AVOD trial and DIABOLO trial) published short-term results of omitting antibiotics compared to routine antibiotic treatment. Both showed no significant differences regarding recovery from the initial episode, as well as rates of complicated or recurrent diverticulitis and sigmoid resection. However, both studies showed a trend of higher rates of sigmoid resection in the observational groups. Here, the long-term effects of omitting antibiotics in first episode uncomplicated acute diverticulitis were assessed. METHODS: A total of 528 patients with CT-proven, primary, left-sided, uncomplicated acute diverticulitis were randomized to either an observational or an antibiotic treatment strategy (DIABOLO trial). Outcome measures were complicated diverticulitis, recurrent diverticulitis and sigmoid resection at 24 months' follow up. Differences between the groups were explored and risk factors were…

INTRODUCTION: Diabetic individuals commonly report disordered bowel habits. This study aims to report the prevalence and associated factors of chronic diarrhea (CD) and chronic constipation (CC) in diabetics using a nationally representative sample of US adults. METHODS: Analyses were performed using data from subjects in the 2009-2010 National Health and Nutrition Examination Survey (NHANES) dataset who completed the Bowel Health Questionnaire. The NHANES dataset provides medical comorbidities, demographics, and dietary habits of a nationally representative group of adult survey participants in the United States. CC and CD were defined by Bristol Stool Form Scale (BSFS) Types 1 & 2 and BSFS Types 6 & 7 as the "usual or most common stool type," respectively, and frequent laxative users were also defined as having CC. Co-variables for all subjects included demographic and lifestyle factors, and co-variables evaluated only in diabetics included treatment and severity markers for diabetes. RESULTS: We identified 661 diabetic subjects and 4488 non-diabetic subjects. Diabetic subjects…

OBJECTIVES: Excessive supragastric belching (SGB) manifests as troublesome belching, and can be associated with reflux and significant impact on quality of life (QOL). In some GERD patients, SGB-associated reflux contributes to up to 1/3 of the total esophageal acid exposure. We hypothesized that a cognitive-behavioral intervention (CBT) might reduce SGB, improve QOL, and reduce acid gastroesophageal reflux (GOR). We aimed to assess the effectiveness of CBT in patients with pathological SGB. METHODS: Patients with SGB were recruited at the Royal London Hospital. Patients attended CBT sessions focused on recognition of warning signals and preventative exercises. Objective outcomes were the number of SGBs, esophageal acid exposure time (AET), and proportion of AET related to SGBs. Subjective evaluation was by patient-reported questionnaires. RESULTS: Of 51 patients who started treatment, 39 completed the protocol, of whom 31 had a follow-up MII-pH study. The mean number of SGBs decreased significantly after CBT (before: 116 (47-323) vs. after 45 (22-139), P<0.0003). Sixteen of 31…

OBJECTIVES: Few studies have examined the role of non-Clostridium difficile enteric infections in flares of inflammatory bowel disease (IBD). Our objective was to investigate enteric infection detected by multiplex PCR stool testing in patients with IBD. METHODS: We performed a cross-sectional analysis of 9403 patients who underwent 13,231 stool tests with a gastrointestinal pathogen PCR panel during a diarrheal illness from March 2015 to May 2017. Our primary outcome was the presence of an infection. Secondary outcomes included endoscopic and histologic predictors of infection, and IBD outcomes following testing. RESULTS: A total of 277 patients with Crohn's disease (CD), 300 patients with ulcerative colitis (UC), and 8826 patients without IBD underwent 454, 503, and 12,275 tests, respectively. Compared to patients without IBD, patients with IBD were less likely to test positive (CD 18.1%, UC 16.1%, no IBD 26.6%, p < 0.001). Compared to patients without IBD, CD had a higher prevalence of norovirus (p = 0.05) and Campylobacter (p = 0.043), whereas UC had a lower prevalence of…

OBJECTIVES: Patients with longstanding ulcerative colitis (UC) and colonic Crohn's disease (CD) have an increased risk of colorectal cancer (CRC). We assess the effectiveness of endoscopic surveillance in patients with inflammatory bowel disease (IBD) for diagnosing CRC and reducing CRC-related mortality. METHODS: MEDLINE, EMBASE, and CENTRAL were searched from inception to 19 September 2016. Randomized controlled trials (RCTs), observational cohorts, or case-control studies assessing any form of endoscopic surveillance for early CRC detection were eligible for inclusion; studies without a comparison non-surveillance group were excluded. The primary outcome was rate of CRC detection. Secondary outcomes were rate of early (Duke stage A and B) versus late (Duke stage C & D) CRC detection and rate of CRC-related death. Data were pooled using fixed or random effects models based on the degree of heterogeneity; pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method. RESULTS: Five observational studies evaluating 7199 IBD patients…

OBJECTIVES: No studies to date estimate the prevalence of chronic diarrhea in the United States using the Bristol stool form scale (BSFS). This study aims to report the prevalence and associated factors of chronic diarrhea using BSFS scores in a nationally representative sample of US adults. METHODS: We identified 5,246 adult participants (age ≥20 years) who completed the bowel health questionnaire in the National Health and Nutrition Examination Survey 2009-2010 data set. Chronic diarrhea was defined as type 6 or 7 rating on the BSFS (mushy or liquid consistency) as the "usual or the most common stool type." Co-variables included age, race, education, poverty income ratio, body mass index, number of medications, feeling depressed, physical activity, and dietary intake. Prevalence estimates and prevalence odds ratios (PORs) were analyzed in adjusted multivariable models using appropriate sampling weights. RESULTS: We found a prevalence of chronic diarrhea of 6.6% (95% confidence interval (CI) 5.8, 7.4) in the nationally representative data set. High daily carbohydrate intake (POR…

OBJECTIVES: In the United States, the Acute Liver Failure Study Group (ALFSG) registry lists approximately 11% of cases as of indeterminate etiology (IND-ALF) as determined by the respective local site principal investigator (PI). Traditionally, IND-ALF has prompted concern that other viruses or toxins might be implicated. We hypothesized that many IND- ALF cases would have an identifiable etiology upon further investigation. Improving the identification process should reduce the number of truly indeterminate cases. METHODS: Specific definitions for each etiology ("etiology-specific algorithms") were developed by a Causality Adjudication Committee that included six reviewers (each with 20 or more years of experience). Of 2718 patients with ALF, 303 initially deemed IND-ALF by site PIs underwent committee review guided by the algorithms. Acetaminophen (APAP) protein adducts were measured in sera when available, additional HEV testing was performed, and viral sequences sought by microarray analysis and metagenomic next-generation sequencing (mNGS). Study sites were asked to provide…

OBJECTIVES: The impact of irritable bowel syndrome (IBS)-type symptoms on the natural history of inflammatory bowel disease (IBD) is uncertain. We aimed to address this in a longitudinal study of secondary care patients. METHODS: Longitudinal disease activity was defined by disease flare, escalation of medical therapy, hospitalization, or intestinal resection. The number of investigations performed and clinics attended determined healthcare utilization. Psychological well-being and quality of life were assessed using validated questionnaires. These outcomes were compared over a minimum period of 2 years between patients reporting IBS-type symptoms and patients with quiescent disease, occult inflammation, and active disease at baseline. RESULTS: In 360 IBD patients, there were no differences in longitudinal disease activity between patients with IBS-type symptoms and patients with quiescent disease or occult inflammation. Disease flare and escalation of medical therapy was more common in patients with active disease than in patients with IBS-type symptoms (hazard ratio (HR) = 3.16;…

Over the course of the last 2 decades our knowledge of autoimmune pancreatitis has increased exponentially. In this review, we summarize the clinical presentation, diagnosis and treatment of AIP, to better allow general gastroenterologists and primary care providers to consider AIP as a as a rare but important cause of painless obstructive jaundice and recurrent acute pancreatitis. While steroids remain the mainstay of first line therapy, a number of patients with type 1 AIP require immunomodulators or rituximab to maintain remission; recommendations on the management of relapses continue to evolve.

OBJECTIVES: Prisons are major reservoirs of hepatitis C virus (HCV) in which a therapeutic approach has been particularly difficult so far. Our aim was to create a permanent program of HCV elimination in a prison based on a "test and treat" strategy. METHODS: This open-label clinical trial was conducted in the Spanish prison "El Dueso" between May 2016 and July 2017. Viremic patients were treated with a ledipasvir-sofosbuvir regimen (8-12 weeks) according to the 2015 Spanish Guidelines. A teleconsultation program was established to follow-up patients from the hospital. Non-responders were submitted for a phylogenetic analysis and offered retreatment. An evaluation of new cases of HCV infection was performed every 6 months and upon release in all inmates. RESULTS: 847 (99.5%) inmates accepted to participate. HCV antibodies were present in 110 (13.0%) and 86 (10.2%) had detectable viremia. Most of them were genotype 1 or 3 (82.6%) and had

INTRODUCTION: It is unclear whether low levels of alcohol are harmful in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to determine whether quantity, binge pattern consumption, or type of alcohol was associated with liver fibrosis in patients with NAFLD. METHODS: Previous and current alcohol consumption was assessed in NAFLD patients undergoing liver biopsy. All subjects currently consumed <210 g per week (male) or <140 g per week (female). Binge consumption was defined as ≥4 standard drinks (female) or ≥5 standard drinks (male) in one sitting. Liver biopsies were scored according to the NASH CRN system with F3/4 fibrosis defined as advanced. RESULTS: Among 187 patients (24% with advanced fibrosis), the median weekly alcohol consumption was 20 (2.3-60) g over an average of 18 years. Modest consumption (1-70 g per week) was associated with lower mean fibrosis stage compared to lifetime abstainers (p < 0.05) and a decreased risk of advanced fibrosis (OR 0.33, 95% CI 0.14-0.78, p = 0.01). The association with reduced fibrosis was not seen in subjects drinking in a…

OBJECTIVES: The Pancreatitis Activity Scoring System (PASS) has been derived by an international group of experts via a modified Delphi process. Our aim was to perform an external validation study to assess for concordance of the PASS score with high face validity clinical outcomes and determine specific meaningful thresholds to assist in application of this scoring system in a large prospectively ascertained cohort. METHODS: We analyzed data from a prospective cohort study of consecutive patients admitted to the Los Angeles County Hospital between March 2015 and March 2017. Patients were identified using an emergency department paging system and electronic alert system. Comprehensive characterization included substance use history, pancreatitis etiology, biochemical profile, and detailed clinical course. We calculated the PASS score at admission, discharge, and at 12 h increments during the hospitalization. We performed several analyses to assess the relationship between the PASS score and outcomes at various points during hospitalization as well as following discharge. Using…

Eosinophilic esophagitis (EoE), a disorder identified by its esophageal mucosal features, often is associated with esophageal motility abnormalities, which are manifestations of esophageal muscle dysfunction. Those motility abnormalities sometimes normalize with treatments that reduce esophageal eosinophilia, suggesting that eosinophils can cause reversible esophageal motility disturbances, perhaps by releasing myoactive and neuroactive eosinophil products. Although achalasia uncommonly is associated with EoE as currently defined, most achalasia patients have evidence of an abnormal accumulation of eosinophils and/or their degranulation products in the esophageal muscularis propria, a location inaccessible to routine endoscopic evaluation. Achalasia is an idiopathic condition resulting from destruction of neurons in the myenteric plexus of the esophagus, and degranulating eosinophils release toxic proteins capable of destroying those neurons, thereby causing the irreversible motility abnormalities of achalasia. This report reviews data on the association of esophageal eosinophilia…

OBJECTIVES: Epidemiological studies ofHelicobacter pyloriinfection and risk of Barrett's esophagus (BE) have reported conflicting results. We examined the association betweenH. pyloriinfection and BE and sought to determine whether the association is mediated by gastroesophageal reflux disease (GERD) and to identify potential effect modifiers. METHODS: We used individual level data from 1308 patients with BE (cases), 1388 population-based controls, and 1775 GERD controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). We estimated study-specific odds ratios (ORs) and 95% CIs using multivariable logistic regression models and obtained summary risk estimates using a random-effects meta-analytic approach. We examined potential effect modification by waist-to-hip ratio (WHR), body mass index (BMI), and smoking status by conducting stratified analyses. RESULTS: For comparisons with population-based controls,H. pyloriinfection was inversely associated with the risk of BE (adjusted OR = 0.44, 95% CI = 0.36-0.55), with no evidence of between-study heterogeneity (I2 =…

Ascites, a common complication of liver cirrhosis, eventually becomes refractory to diuretic therapy and sodium restriction in ∼10% of patients. Multiple pathogenetic factors are involved in the development of refractory ascites, which ultimately lead to renal hypoperfusion and avid sodium retention. Therefore, renal dysfunction commonly accompanies refractory ascites. Management includes continuation of sodium restriction, which needs frequent reviews for adherence; and regular large volume paracentesis of 5 L or more with albumin infusions to prevent the development of paracentesis-induced circulatory dysfunction. In the appropriate patients with reasonable liver reserve, the insertion of a transjugular intrahepatic portosystemic stent shunt (TIPS) can be considered, especially if the patient is relatively young and has no previous hepatic encephalopathy or anatomical contraindications, and no past history of renal or cardiopulmonary disease. Response to TIPS with ascites clearance can lead to nutritional improvement. Devices such as an automated low-flow ascites pump may be…

OBJECTIVES: Wheat avoidance in the absence of celiac disease (CD) is common but occurrence of concurrent functional gastrointestinal disorders (FGIDs) in this group is uncertain. The aims of this study were to determine the prevalence of self-reported wheat or gluten sensitivity and doctor diagnosed CD in an Australian population, define the associated gastrointestinal (GI) symptoms and FGIDs, and determine the relationship between self-reported wheat sensitivity, demographic and medical factors. METHODS: A total of 3542 people randomly selected from the Australian population returned a mail survey which contained questions on wheat avoidance, GI symptoms, demographic, medical, and lifestyle factors. We defined self-reported wheat sensitivity as people who reported gastrointestinal symptoms on ingestion of wheat based foods, but did not suffer from celiac disease, inflammatory bowel disease or colorectal cancer. Functional dyspepsia (FD) and irritable bowel syndrome (IBS) were diagnosed by Rome III criteria. CD status was self-reported. RESULTS: The prevalence of self-reported wheat…

OBJECTIVES: Adalimumab is usually self-injected at home, making prospective serial-sampling studies challenging and scarce. This has led to a gap in knowledge about evolution of anti-adalimumab antibodies (AAAs) over time and its correlation with clinical and inflammatory outcomes. METHODS: A program for home visits by physicians at induction, every 3 months and at event of relapse, was established prospectively for Crohn's disease (CD) patients. At each visit, patients' clinical scores were determined and sera were obtained for C-reactive protein, drug, and AAA levels. This cohort was compared to a parallel prospective cohort of infliximab-treated CD patients. In a subgroup of 29 patients, trough and in-between-trough levels were compared, to elucidate the importance of timing of sampling during the injection cycle. RESULTS: Ninety-eight CD patients starting adalimumab were prospectively followed (median follow-up 44 weeks) and 621 serum samples were analyzed. Thirty-three patients (32%) developed AAA; 18/33 (55%) of them as early as week 2, and 26/33 (79%) by week 14. Induction…

OBJECTIVE: Heartburn is the most specific symptom of reflux disease and is highly responsive to proton pump inhibitor (PPI) therapy. Some patients do not respond to PPIs, but mechanisms of refractoriness have not yet been fully elucidated. Impedance-pH monitoring, allowing comprehensive on-therapy assessment of reflux, represents a valuable test to investigate PPI refractoriness. METHODS: Prospective multicenter study comparing endoscopy-negative patients with PPI-refractory and PPI-responsive heartburn. Reflux disease was demonstrated by off-PPI impedance-pH monitoring and mechanisms of refractoriness were studied with on-PPI impedance-pH monitoring. Assessment of impedance-pH tracings comprised conventional parameters, post-reflux swallow-induced peristaltic wave (PSPW) index, and mean nocturnal baseline impedance (MNBI). RESULTS: Sixty-four patients entered the study, 32 with PPI-refractory and 32 with PPI-responsive heartburn. On PPI, median percentage gastric and esophageal acid exposure time and number of acid refluxes did not differ between the two groups; conversely, number…

BACKGROUND: Baveno-VI guidelines recommend that patients with compensated cirrhosis with liver stiffness by transient elastography (LSM-TE) <20 kPa and platelets >150,000/mm(3) do not need an esophagogastroduodenoscopy (EGD) to screen for varices, since the risk of having varices needing treatment (VNT) is <5%. It remains uncertain if this tool can be used in patients with cholestatic liver diseases (ChLDs): primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). These patients may have a pre-sinusoidal component of portal hypertension that could affect the performance of this rule. In this study we evaluated the performance of Baveno-VI, expanded Baveno-VI (LSM-TE <25 kPa and platelets >110,000/mm(3)), and other criteria in predicting the absence of VNT. METHODS: This was a multicenter cross-sectional study in four referral hospitals. We retrospectively analyzed data from 227 patients with compensated advanced chronic liver disease (cACLD) due to PBC (n = 147) and PSC (n = 80) that had paired EGD and LSM-TE. We calculated false negative rate (FNR) and number of…

OBJECTIVES: Optimal adherence to nucleoside analogue treatment is necessary to achieve undetectable levels of hepatitis B virus (HBV) DNA in patients with chronic hepatitis B (CHB), and to prevent cirrhotic complications. However, any large long-term follow-up study has not been investigated the effect of adherence to entecavir (ETV) treatment on specific liver-related events (LREs), namely, hepatocellular carcinoma (HCC), cirrhotic complications, and mortality. METHODS: This was a 10-year longitudinal observational study of treatment-naïve patients with CHB who received ETV treatment. The primary outcome was the cumulative probability of LREs. The cumulative level of adherence to medication was categorized as good (≥90%) or poor (<90%). RESULTS: Data from 894 treatment-naïve CHB patients who received ETV were analyzed. Overall mean adherence rates were 89.1%. Patients with poor adherence had a higher risk of virologic breakthrough (VBT) (HR, 22.42; 95% CI, 19.57-52.52; P < 0.001) than those with good adherence. Multivariate analyses showed a higher risk of liver-related (HR, 14.29;…

OBJECTIVES: Rising trends in eosinophilic esophagitis (EoE) have been repeatedly linked to declining Helicobacter pylori (H. pylori) infection, mostly in retrospective studies. We aimed to prospectively evaluate this inverse association. METHODS: Prospective case-control study conducted in 23 centers. Children and adults naïve to eradication therapy for H. pylori were included. Cases were EoE patients, whereas controls were defined by esophageal symptoms and <5 eos/HPF on esophageal biopsies. H. pylori status was diagnosed by non-invasive (excluding serology) or invasive testing off proton pump inhibitor (PPI) therapy for 2 weeks. Atopy was defined by the presence of IgE-mediated conditions diagnosed by an allergist. RESULTS: 808 individuals, including 404 cases and 404 controls (170 children) were enrolled. Overall H. pylori prevalence was 38% (45% children vs. 37% adults, p 0.009) and was not different between cases and controls (37% vs. 40%, p 0.3; odds ratio (OR) 0.97; 95% confidence interval (CI) 0.73-1.30), neither in children (42% vs. 46%, p 0.1) nor in adults (36% vs. 38%, p…

BACKGROUND: Minimally invasive methods have been described to detect Barrett's esophagus (BE), but are limited by subjectivity and suboptimal accuracy. We identified methylated DNA markers (MDMs) for BE in tissue and assessed their accuracy on whole esophagus brushings and capsule sponge samples. METHODS: Step 1: Unbiased whole methylome sequencing was performed on DNA from BE and normal squamous esophagus (SE) tissue. Discriminant MDM candidates were validated on an independent patient cohort (62 BE cases, 30 controls) by quantitative methylation specific PCR (qMSP). Step 2: Selected MDMs were further evaluated on whole esophageal brushings (49 BE cases, 36 controls). 35 previously sequenced esophageal adenocarcinoma (EAC) MDMs were also evaluated. Step 3: 20 BE cases and 20 controls were randomized to swallow capsules sponges (25 mm, 10 pores or 20 pores per inch (ppi)) followed endoscopy. DNA yield, tolerability, and mucosal injury were compared. Best MDM assays were performed on this cohort. RESULTS: Step 1: 19 MDMs with areas under the ROC curve (AUCs) >0.85 were carried…

OBJECTIVES: Real-world, prospective, long-term studies in Crohn's disease (CD) characterizing adalimumab safety data and lymphoma risk were lacking. We present the final results from the PYRAMID registry, which was designed to rule out a doubling of lymphoma risk in adalimumab-treated patients with CD. METHODS: Patients with moderately to severely active CD newly prescribed or currently receiving adalimumab according to local product labels were followed for up to 6 years and analyzed for adverse events (AEs). The registry exposure-adjusted observed rate of lymphoma was compared with the estimated background lymphoma rate from a sex-matched general population in the Surveillance, Epidemiology, and End Results 17 Registry database adjusted for anticipated prior or concurrent thiopurine use in a CD population. RESULTS: A total of 5025 patients were evaluated (16680.4 PY of adalimumab registry exposure, ≈3 years/patient mean follow-up). Registry treatment-emergent AEs included 4129 serious AEs (n = 1853 [36.9%]; 24.8 E/100 PY), 792 serious infections (n = 556 [11.1%]; 4.7 E/100 PY),…

OBJECTIVE: Despite availability of highly effective direct acting antivirals (DAA), barriers in access to these therapies limit our ability to achieve HCV eradication. We aim to evaluate overall rates and predictors of HCV treatment across four community-based health-care systems focusing on race/ethnicity and insurance-specific disparities. METHODS: We retrospectively evaluated all adults with chronic HCV at four health care systems from 1 January 2011 to 28 February 2017, which included a large proportion of ethnic minorities, two safety-net systems, and a broad payer mix across four states. Overall and stratified HCV treatment rates were calculated using Kaplan-Meier methods. Multivariate logistic regression models evaluated for predictors of receiving treatment. RESULTS: Among 29,544 chronic HCV patients (60.5% male, 38.4% black, 8.8% Hispanic, 18.7% Medicaid, 25.9% Medicare, 22.5% private/commercial), overall annual treatment rates were stable from 2011 (0.5%) to 2013 (2.0%), but increased from 2014 (4.8%) to 2017 (16.9%) after availability of DAAs. While similar treatment…

The Montreal definition of gastroesophageal reflux disease (GERD) provided a rationale for acid suppression medication without investigation, thus enhancing the management of the substantial symptom burden in these patients. Increased proton-pump inhibitor use has also highlighted their limitations, with one third of "typical" symptoms known to be refractory. Most refractory symptoms are ascribed to reflux hypersensitivity (RH) and functional heartburn (FH). RH may be caused by impaired esophageal mucosal barrier function and sensitization of peripheral esophageal receptors. Central sensitization may also contribute to the perception of non-pathologic reflux in RH, and the perception of physiological stimuli in FH. Importantly, mechanisms underlying GERD, RH, and FH are (in theory) not mutually exclusive, further complicating patient management. Methods used to distinguish GERD from RH and FH are impractical for use in epidemiological studies and pragmatic care and may have limited diagnostic accuracy. This is impeding accurate prevalence estimates and risk factor determination and…

BACKGROUND: Malignancy may occur as long-term complication of inflammatory bowel disease (IBD) due to different risk factors. We assessed prevalence and incidence of malignancy, and predictive factors in the Swiss IBD Cohort Study (SIBDCS). METHODS: All IBD patients in the SIBDCS were analyzed from a cross-sectional and longitudinal perspective. Patients with malignancies were compared to controls. Standardized incidence ratios (SIR) were calculated based on age-specific and sex-specific background rates. RESULTS: Malignancies were identified in 122 of 3119 patients (3.9%). In a logistic regression model, age (OR 1.04 per year), intestinal surgery (OR 3.34), and treatment with steroids (OR 2.10) were the main predictors for the presence of malignancy, while treatment with 5-ASA (OR 0.57) and biologics (OR 0.38) were protective. From a longitudinal perspective, 67 out of 2580 patients (2.6%) were newly diagnosed with malignancy during a follow-up of 12,420.8 years (median 4.9 years). While there was no increased risk for malignancy overall (SIR 0.93, 95% CI 0.72-1.18) and colorectal…

OBJECTIVES: In order to screen for gastric cancer effectively, its interval should be set according to the risk. This study aimed to determine whether risk stratification is possible using the data obtained from medical examination or endoscopic findings. METHODS: First, subjects who underwent both cancer screening and medical examination from 2009 to 2015 and underwent cancer screening once more by 2016 were studied. Data such as the lipid profile and history of smoking obtained during the medical examination, and the grade of atrophy and presence of peptic ulcers were studied using multivariate analysis. Next, subjects who underwent cancer screening twice or more between 2009 and 2015 with or without medical examinations were studied to analyze any correlation between the grade of atrophy and cancer occurrence using univariate analysis. In both studies, the status of Helicobacter pylori (HP) infection was determined. RESULTS: In the multivariate analysis, 9378 subjects were included. Aging, advanced atrophy, presence of ulcers, and uric acid levels were identified as risk factors.…

OBJECTIVE: Endoscopic balloon dilation (EBD) is a standard treatment for anastomotic strictures after esophagectomy, and requires multiple dilations. We conducted a randomized controlled trial to assess the efficacy of adding a steroid injection to EBD to reduce restricture. METHODS: Patients were randomized to receive EBD combined with either triamcinolone or placebo injection. The primary endpoint was the number of dilations required to resolve the stricture. The secondary endpoints were restricture-free survival and adverse events. Patients with a dysphagia symptom score of ≥2 after esophagectomy with an endoscopy-confirmed anastomotic stricture were included. A total of 50 mg of triamcinolone acetonide (50 mg/5 mL) or an identical volume of normal saline solution as a placebo was injected per site using a 25-gauge needle immediately after EBD. Both the patient and treating physician were blinded to the treatment given. RESULTS: During the 4-year study period, 65 patients were randomized to either the steroid group (n = 33) or placebo group (n = 32). The median number of EBDs…

OBJECTIVES: We described pregnancy outcomes in Crohn's disease (CD) patients enrolled in the TREAT Registry who received infliximab before, or during pregnancy and those not treated with infliximab or any biologic agent. METHODS: In the TREAT Registry (1999-2012), pregnancy outcomes were analyzed from maternal and paternal patients exposed to infliximab ≤365 days (gestational exposure), >365 days (pre-gestational exposure) of pregnancy outcome or without infliximab exposure (non-biologic exposed). "Healthy infants" were defined as those with no congenital abnormalities, neonatal complications (e.g., jaundice, prematurity, heart murmur, cortical vision/fine motor delay, cardiac failure, hemophilia, or torticollis), prolonged hospitalization, or those who received no special treatment. Disease activity and concomitant medications were also evaluated. RESULTS: Overall, 92.3% (324/351) of pregnancies had known outcomes. The majority of both maternal pregnancies (92.6, 91.2, and 87.8%) and partner outcomes (92.7, 93.8, and 91.7%) resulted in live births of healthy infants across…

OBJECTIVES: The impact of recurrent acute pancreatitis (RAP) on quality of life (QOL) is unknown. We hypothesized that RAP would reduce QOL even in the absence of chronic pancreatitis (CP). METHODS: Data were pooled from three prospective, cross-sectional studies conducted across 27 U.S. centers (the North American Pancreatitis Studies); these included subjects with chronic pancreatitis (n = 1086), RAP alone (n = 508), and non-disease controls (n = 1025). QOL was measured using the Short Form 12 (SF-12), generating a Physical Component Summary (PCS) and the Mental Component Summary score (MCS). Multivariable regression models were developed to measure the effect of RAP on QOL, the predictors of lower QOL in those with RAP, and the differential effect QOL predictors between CP and RAP. RESULTS: Compared to controls (51.0 ± 9.4), subjects with RAP (41.1 ± 11.4) and CP (37.2 ± 11.8) had lower PCS (p < 0.01). Subjects with CP had lower PCS compared to those with RAP (p < 0.01). Similarly, MCS was lower among RAP (44.6 ± 11.5) and CP (42.8 ± 12.2) subjects compared to controls (51.7 ±…

OBJECTIVES: Non-celiac gluten sensitivity (NCGS) is characterized by intestinal and extra-intestinal symptoms that are related to the ingestion of gluten in subjects who are not affected by either celiac disease (CD) or wheat allergy (WA). In this multicenter study, we aim for the first time to evaluate the prevalence of NCGS in pediatric subjects with chronic functional gastrointestinal symptoms associated with gluten ingestion using a double-blind placebo-controlled (DBPC) gluten challenge with crossover. METHODS: Among 1,114 children with chronic gastrointestinal symptoms (negative CD and WA), those exhibiting a positive correlation between symptoms and gluten ingestion were eligible for a diagnostic challenge including the following phases: run-in, open gluten-free diet (GFD) and DBPC crossover gluten challenge. Patients were randomized to gluten (10 g/daily) and placebo (rice starch) for 2 weeks each, separated by a washout week. The gluten challenge was considered positive in the presence of a minimum 30% decrease of global visual analogue scale between gluten and placebo.…

OBJECTIVES: 5-aminosalicylates (5-ASA) are frequently continued in patients with moderate-severe ulcerative colitis (UC), even after escalation to biologic agents, without evaluation of the benefit of this approach. We conducted an individual participant data (IPD) pooled analysis of trials of infliximab and golimumab in UC, to evaluate whether concomitant use of 5-ASA modifies clinical outcomes among anti-tumor necrosis factor (TNF)-α-treated patients. METHODS: We included IPD from five trials of infliximab and golimumab in patients with moderate-severe UC (ACT-1 and -2, PURSUIT-SC, PURSUIT-M, NCT00336492). Patients treated with infliximab or golimumab were categorized as receiving concomitant 5-ASA or not at time of trial entry. Primary outcome was clinical remission (Mayo Clinic Score < 3) at last follow-up for each trial; secondary outcomes were clinical response and mucosal healing. Using multivariable logistic regression analysis, we evaluated association between concomitant 5-ASA and clinical remission, after adjusting for sex, smoking, baseline disease activity, disease…

OBJECTIVES: Colorectal cancer (CRC) screening uptake is suboptimal, despite national efforts to increase screening rates. Behavioral economic approaches such as changing defaults may increase participation. We compare response rates to opt-in or opt-out messaging in mailed fecal immunochemical test (FIT) outreach. METHODS: This is a two-arm randomized controlled trial among 314 patients aged 50-74 years who had at least two primary care visits in the 2-year pre-enrollment period and were screening-eligible but not up-to-date. Eligible patients received invitation by electronic health record (EHR) portal or mail with randomization to receive mailed FIT: (1) only if they actively opted-in to do so (opt-in) or (2) unless they opted-out of screening (opt-out). The primary outcome was FIT completion rate within 3 months of initial outreach. RESULTS: Patients randomized to opt-in agreed to participate 23.1% of the time, and only 2.5% of those in opt-out chose not to participate. FIT kits were mailed to 22.4% and 93% of patients in opt-in and opt-out arms, respectively. In…

OBJECTIVES: Hyponatremia is associated with poor outcomes in cirrhosis independent of MELD. While intravenous albumin has been used in small series, its role in hyponatremia is unclear. The aim of this study is to determine the effect of albumin therapy on hyponatremia. METHODS: Hospitalized cirrhotic patients included in the NACSELD (North American Consortium for End-Stage Liver Disease) cohort with hyponatremia (Na <130mmol/L) were divided into those receiving intravenous albumin or not. Determinants of hyponatremia resolution (Na ≥135 meq/L) and 30-day survival were analyzed using regression and ANCOVA models. RESULTS: Overall, 2435 patients, of whom 1126 had admission hyponatremia, were included. Of these, 777 received 225 (IQR 100,400) g of albumin, while 349 did not. Patients given albumin had a higher admission MELD score, and serum creatinine and lower admission Na and mean arterial pressure (MAP). However they experienced a higher maximum Na and hyponatremia resolution (69% vs 61%, p = 0.008) compared to those who did not. On regression, delta Na was independently…

BACKGROUND: Hyperbaric oxygen therapy (HBOT) markedly increases tissue oxygen delivery. Case series suggest it may have a potential therapeutic benefit in ulcerative colitis (UC). We investigated the therapeutic potential of HBOT as an adjunct to steroids for UC flares requiring hospitalization. METHODS: The study was terminated early due to poor recruitment with 18 of the planned 70 patients enrolled. UC patients hospitalized for moderate-severe flares (Mayo score ≥6, endoscopic sub-score ≥2) were block randomized to steroids + daily HBOT (n = 10) or steroids + daily sham hyperbaric air (n = 8). Patients were blinded to study assignment, and assessments were performed by a blinded gastroenterologist. Primary outcome was the clinical remission rate at study day 5 (partial Mayo score ≤2 with no sub-score >1). Key secondary outcomes were: clinical response (reduction in partial Mayo score ≥2, rectal bleeding sub-score of 0-1) and progression to second-line therapy (colectomy or biologic therapy) during the hospitalization. RESULTS: A significantly higher proportion of HBOT-treated…

OBJECTIVES: Our aim was to characterize upper gastrointestinal (UGI) symptoms and associations in individuals with diabetes mellitus (DM) who had undergone evaluation of gastric emptying (GE) and accommodation (GA) at a referral center. METHODS: From the Mayo Clinic Rochester electronic medical records of adults with diabetes types 1 and 2 (DM1 and DM2) evaluated between January 1997 and December 2015, we extracted demographics, UGI symptoms, current medications, treatments for diabetes, GE solids by scintigraphy, GA by single photon emission computed tomography (SPECT), and diabetes complications. We compared subgroups with delayed (GE at 2 h <25% or GE at 4 h <75%), rapid (GE at 1 h > 35%), and normal GE, as well as reduced (<428 mL) and normal GA. RESULTS: We reviewed 108 patients (60.2% females, median age 49.0 years). Overall, 71.3% had DM2; one-third of these were insulin dependent and had fairly well-controlled diabetes (median HbA1c 6.7% (IQR 6.2; 7.9)). Manifestations of diabetic triopathy (peripheral neuropathy, nephropathy, and retinopathy) were uncommon at presentation…

OBJECTIVES: To assess whether obesity may affect response to infliximab, we conducted an individual participant data pooled analysis using data from clinical trials of infliximab in inflammatory bowel diseases (IBD), using the Yale Open Data Access (YODA) Project. METHODS: ) vs. non-obese, and by quartiles based on BMI or weight at time of trial entry. Primary outcome was clinical remission (Crohn's disease activity index [CDAI] < 150 or pediatric CDAI <10, Mayo Clinic Score <3); secondary outcomes were clinical response and mucosal healing. Multivariable logistic regression analysis was performed, after adjusting for sex, smoking, disease activity, and concomitant prednisone and/or immunomodulators. RESULTS: We included 1205 infliximab-treated patients (mean age 37 years, 51.6% males, 14% obese). Obesity was not associated with odds of achieving clinical remission (obese vs. non-obese: adjusted OR, 0.93 [95% CI, 0.47-1.46]; Q4 vs. Q1: aOR, 0.94 [0.61-1.47], p-value for trend = 0.97), clinical response (Q4 vs. Q1: aOR, 0.84 [0.52-1.35], p = 0.45) or mucosal healing (Q4 vs. Q1: aOR,…

BACKGROUND: Distinguishing perihilar cholangiocarcinoma (PHC) from benign forms of sclerosing cholangitis affecting the hilar bile ducts is challenging, since histological confirmation of PHC is difficult to obtain and accurate non-invasive diagnostic tests are not available. IgG4-associated cholangitis (IAC), an imitator of PHC, may present with clinical and radiographical signs of PHC. IAC can be accurately diagnosed with a novel qPCR test. The aim of this study was to investigate the incidence and long-term activity of IAC in patients resected for PHC in a single tertiary center over a period of 30 years. METHODS: All patients with benign disease who underwent surgery for presumed PHC in our institute between 1984 and 2015 were identified. Benign liver and bile duct specimens were re-evaluated by a pathologist and scored according to international consensus pathology criteria for IgG4-related disease (IgG4-RD). Patients with benign disease still alive were followed-up and a clinical diagnosis of IAC was made using a combination of the HISORt group C (response to steroids)…

OBJECTIVES: Colorectal cancer (CRC) screening using fecal immunochemical tests (FIT) may reduce CRC-related mortality but its effectiveness is influenced by the limited accuracy of FIT. Identifying individuals at increased risk of a false FIT result could improve screening, but the available evidence is conflicting. We performed a systematic review and meta-analysis on risk factors for false-positive and false-negative FIT results in CRC screening. METHODS: A systematic search in MEDLINE, EMBASE, and Cochrane Library identified publications (before 29 January 2017) on risk factors (known at time of FIT invitation) associated with false FIT results (presence/absence of advanced neoplasia) in a CRC screening setting. Risk of bias was assessed using QUIPS. In meta-analysis, summary relative risk ratios and corresponding 95% confidence intervals were calculated for each risk factor. RESULTS: Of 518 records identified, 14 studies with 54,499 participants in total were included for analysis. In meta-analysis, male sex was associated with a significantly lower risk of false-positivity (RR…

Hepatic encephalopathy is a state of brain dysfunction resulting from decompensation of cirrhosis. The mortality and morbidity associated with the overt form of hepatic encephalopathy are high, and even the covert form associates with poor outcomes and poor quality of life. We know that the dysfunction is not just an acute insult to the brain but rather results in long-standing cognitive issues that get worse with each episode of HE. Hence, there is an urgency to accurately diagnose these conditions, start appropriate therapy, and to maintain remission. Currently, we have two mainstay pharmacological treatment options (lactulose and rifaximin), but the narrative is evolving with new therapies under trial. Microbiome manipulation resulting in a favorable change to the gut microbiota seems to be a promising new area of therapy.

OBJECTIVES: Minimal hepatic encephalopathy (HE) is common, characterized by deficits in reaction time and executive function, and strongly associated with disability and mortality. Point-of-care diagnostics performed without specialized skills or equipment are now available, albeit with limited data regarding their generalizability. METHODS: We systematically reviewed MEDLINE, EMBASE, Cochrane Library, and Scopus for diagnostic studies of MHE using broad search terms including HE and minimal, covert, or the names of published diagnostic modalities. We included tests that provide results during clinical visits without requiring neuropsychologists to administer and/or special equipment. These include the Inhibitory Control Test (ICT, n=16), EncephalApp Stroop (n=3), an algorithm based on the Sickness Impact Profile (n=2), and the Animal Naming Test (ANT, n=1). RESULTS: The populations enrolled in the included study were highly selected, excluding patients with recent (6-months) alcohol or psychoactive medications use. Cutoffs for MHE for each test varied widely. For the ICT, the…

BACKGROUND: There is a need for safe and effective IBS treatments that provide immediate and sustained improvement of IBS symptoms, particularly among more severe patients. The aim was to assess long-term clinical response of cognitive behavioral therapy (CBT) with reference to IBS education. METHODS: A total of 436 Rome III-diagnosed IBS patients (80% F, M age = 41 years) were randomized to: 4 session home-based CBT (minimal contact (MC-CBT)), 10 session clinic-based CBT (standard (S-CBT)), or 4 session IBS education (EDU). Follow-up occurred at 2 weeks and 3, 6, 9, and 12 months following treatment completion. Treatment response was based a priori on the Clinical Global Improvement Scale (global IBS symptom improvement) and IBS Symptom Severity Scale (IBS-SSS). RESULTS: Post-treatment CGI gains were generally maintained by MC-CBT patients at quarterly intervals through 12-month follow-up with negligible decay. For MC-CBT and S-CBT, 39 and 33% of respondents maintained treatment response at every follow-up assessment. The corresponding percent for EDU was 19%, which was…

1CURE Hemostasis Research Group, CURE Digestive Diseases Research Center, Division of Digestive Diseases, Ronald Reagan Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. 2VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA. Correspondence: D.M.J. (email: [email protected]) Published online 11 May 2018

Postural tachycardia syndrome (POTS) is one of the most common causes of orthostatic intolerance and is being increasingly recognized in clinical practice. Gastrointestinal (GI) symptoms are reported commonly in patients with POTS and pose a considerable management challenge, making it imperative that gastroenterologists be aware of this condition and its GI comorbidities. Although the evidence presented herein does not prove causation, it does support an association between GI symptoms, GI dysmotility, and POTS. At present, the evaluation and treatment of GI symptoms in patients with POTS remains largely empirical. General measures to treat POTS may lead to improvement in both GI and non-GI symptoms. GI symptoms refractory to these measures should prompt further diagnostic evaluation of gastrointestinal dysmotility and appropriate dietary and pharmacologic management. This review focuses its attention on the involvement of the GI tract in POTS including a discussion of GI symptoms and conditions associated with POTS, followed by an analysis of abnormalities in gut physiology…

OBJECTIVES: Non alcoholic fatty liver disease (NAFLD) is a leading cause of liver damage in childhood, its occurrence is influenced by genetic and environmental factors. Recently, the rs626283 polymorphism in the MBOAT7 gene has been found to be associated with alcoholic liver disease and NAFLD in adults. METHODS: In a multiethnic cohort of obese children and adolescents we genotyped the rs626283 polymorphism in the MBOAT7 gene, evaluated insulin sensitivity by an oral glucose tolerance test, and measured the intra-hepatic fat content (HFF%) by magnetic resonance imaging. RESULTS: In Caucasian youth, the minor allele (C) was associated with HFF% in (P=0.003), fasting insulin (P=0.03), area under the curve of glucose (P=0.03), and lower degree of whole-body insulin sensitivity (P=0.01) independent of age, gender, and body mass index z-score. A partial correlation showed that the association between the rs626283 variant and insulin resistance was driven by the presence of hepatic steatosis (P=0.009). However, there was no association between the rs626283 and hepatic steatosis among…

BACKGROUND: Functional gastrointestinal disturbance occurs after abdominal surgeries and could last for an extended period of time in some cases. This study was designed (1) to evaluate the effects of needleless transcutaneous electrical acustimulation (TEA) on postoperative recovery, and (2) to investigate the mechanisms involving autonomic function in postoperative patients after removal of gastrointestinal cancers. METHODS: Forty-two patients (33 male, age: 69.5 ± 1.5 years) scheduled for abdominal surgical removal of gastrointestinal cancers were randomized to TEA (n = 21) and sham-TEA (n = 21). TEA was performed via acupoints ST36 and PC6 1 h twice daily from the postoperative day (POD) 1 to day 3. Sham-TEA was performed at non-acupoints. RESULTS: (1) TEA improved major postoperative symptoms by about 30%, including a reduction in time to defecation by 31.7% (P < 0.01 vs. sham-TEA), time to first flatus by 35.9% (P < 0.001), time to ambulation by 42.8% (P < 0.01), time to resuming diet by 26.5% (P < 0.01) and hospital stay by 30% (P < 0.05) as well as pain score by 50% (P <…

OBJECTIVES: Existing algorithms predicting the risk of colorectal cancer (CRC) assign a fixed score for family history of CRC. Whether the increased CRC risk attributed to family history of CRC was higher in younger patients remains inconclusive. We examined the risk of CRC associated with family history of CRC in first-degree relative (FDR) according to the age of index subjects (<40 vs. ≥40; <50 vs. ≥50; and <60 vs. ≥60 years). METHODS: Ovid Medline, EMBASE, and gray literature from the reference lists of all identified studies were searched from their inception to March 2017. We included case-control/cohort studies that investigated the relationship between family history of CRC in FDR and prevalence of CRC. Two reviewers independently selected articles according to the PRISMA guideline. A random effects meta-analysis pooled relative risks (RR). RESULTS: We analyzed 9.28 million subjects from 63 studies. A family history of CRC in FDR confers a higher risk of CRC (RR = 1.76, 95% CI = 1.57-1.97, p < 0.001). This increased risk was higher in younger individuals (RR = 3.29, 95% CI =…

OBJECTIVES: Anastomotic reconstruction following intestinal resection in Crohn's disease (CD) may employ side-to-side anastomosis (STSA; anti-peristaltic orientation) or end-to-end anastomosis (ETEA). Our aim was to determine the impact of these two anastomotic techniques on long-term clinical status in postoperative CD patients. METHODS: We performed a comparative effectiveness study of prospectively collected observational data from consented CD patients undergoing their first or second ileocolonic bowel resection and re-anastomosis between 2008 and 2012, in order to assess the association between anastomosis type and 2-year postoperative quality of life (QoL), healthcare utilization, disease clinical or endoscopic recurrence, use of medications, and need for repeat resection. RESULTS: One hundred and twenty eight postoperative CD patients (60 STSA and 68 ETEA) were evaluated. At 2 years postoperatively, STSA patients had higher rates of emergency department visits (33.3% vs. 14.7%; P=0.01), hospitalizations (30% vs. 11.8%; P=0.01), and abdominal computed tomography scans (50% vs.…

OBJECTIVES: For technical reasons, the histologic characterization of eosinophilic esophagitis (EoE)-specific alterations is almost exclusively based on those found in the esophageal epithelium, whereas little is known about subepithelial abnormalities. In this study, we aimed to systematically assess the nature of subepithelial histologic alterations, and analyze their relationship with epithelial histologic findings, endoscopic features, and symptoms. METHODS: Adult patients with established EoE diagnosis were prospectively included during a yearly follow-up visit. Patients underwent assessment of clinical, endoscopic, and histologic disease activity using EoE-specific scores. RESULTS: We included 200 EoE patients (mean age 43.5±15.7 years, 74% males) with a median peak count of 36 intraepithelial eosinophils/hpf (IQR 14-84). The following histologic features were identified in the subepithelial layer: eosinophilic infiltration (median peak count of 20 eosinophils/hpf (IQR 10-51)), eosinophil degranulation (43%), fibrosis (82%), and lymphoid follicles (56%). Peak intraepithelial…

OBJECTIVES: In a population-based study, we examined time trends in chronic liver disease (CLD)-related hospitalizations in a large and diverse metroplex. METHODS: We examined all CLD-related inpatient encounters (2000-2015) in Dallas-Fort Worth (DFW) using data from the DFW council collaborative that captures claims data from 97% of all hospitalizations in DFW (10.7 million regional patients). RESULTS: There were 83,539 CLD-related hospitalizations in 48,580 unique patients across 84 hospitals. The age and gender standardized annual rate of CLD-related hospitalization increased from 48.9 per 100,000 in 2000 to 125.7 per 100,000 in 2014. Mean age at hospitalization increased from 54.0 (14.1) to 58.5 (13.5) years; the proportion of CLD patients above 65 years increased from 24.2% to 33.1%. HCV-related hospitalizations plateaued, whereas an increase was seen in hospitalizations related to alcohol (9.1 to 22.7 per 100,000) or fatty liver (1.4 per 100,000 to 19.5 per 100,000). The prevalence of medical comorbidities increased for CLD patients: coronary artery disease (4.8% to 14.3%),…

Proton pump inhibitors (PPIs) are among the most widely used class of drugs prescribed over the long term in all of clinical medicine with 8-10% of ambulatory adults have been prescribed a PPI in the past 30 days. However, numerous studies have raised doubts about the long term safety of PPI use. The purpose of this review is threefold: (i) To provide an overview of the current evidence demonstrating associations between PPI use and adverse health outcomes and the likelihood of the associations being causal (Why?); (ii) To be able to identify long-term PPI users in whom the intensity of PPI therapy could be reduced or in whom PPIs could be eliminated outright (Who?); and (iii) To provide strategies on how to reduce or stop chronic PPI therapy while maintaining symptom control and reducing the risk for symptom or upper GI disease recurrence (How?).

INTRODUCTION: Surveillance programs on high-risk individuals (HRIs) can detect pre-malignant lesions or early pancreatic cancer (PC). We report the results of the first screening round of the Italian multicenter program supported by the Italian Association for the study of the Pancreas (AISP). METHODS: The multicenter surveillance program included asymptomatic HRIs with familial (FPC) or genetic frailty (GS: BRCA1/2, p16/CDKN2A, STK11/LKB1or PRSS1, mutated genes) predisposition to PC. The surveillance program included at least an annual magnetic resonance cholangio pancreatography (MRCP). Endoscopic ultrasound (EUS) was proposed to patients who refused or could not be submitted to MRCP. RESULTS: One-hundreds eighty-seven HRIs underwent a first-round screening examination with MRCP (174; 93.1%) or EUS (13; 6.9%) from September 2015 to March 2018.The mean age was 51 years (range 21-80).One-hundreds sixty-five (88.2%) FPC and 22 (11.8%) GF HRIs were included. MRCP detected 28 (14.9%) presumed branch-duct intraductal papillary mucinous neoplasms (IPMN), 1 invasive carcinoma/IPMN and one…

OBJECTIVES: Rates of pregnancy in women with cirrhosis are increasing. Risk of hepatic decompensation during pregnancy, therefore, merits tailored obstetric and hepatology care. Prognostic markers that determine pregnancy outcomes are lacking. METHODS: Medical records of women who attended hepatology clinic at King's College Hospital with chronic liver disease (CLD) who became pregnant from 1983 to 2017 were reviewed. Information on demographics, clinical history, serology, and outcome of pregnancy was collected. RESULTS: In all, 165 pregnancies occurred in 100 women with CLD including 80 pregnancies in 48 women with cirrhosis. Median age of conception in cirrhotic and non-cirrhotic women were 26 years (16-44) and 28 years (16-51) respectively (p = 0.015). Whilst women with cirrhosis had similar live birth rate to non-cirrhotic women (75 vs. 85% p = 0.119), they were significantly less likely to proceed beyond 37 weeks gestation (45 vs. 58% p = 0.033). Women who received preconception counseling were more likely to have stable liver disease at conception (100 vs 86% p = 0.02).…

BACKGROUND: The increasing incidence of inflammatory bowel disease (IBD) in western countries has led to the hypothesis that obesity-related inflammation could play a role in the etiology of IBD. However, this hypothesis lacks confirmation in studies of individuals prior to the typical onset of IBD in young adulthood. METHODS: In a cohort of 316,799 individuals from the Copenhagen School Health Records Register (CSHRR), we examined whether BMI at ages 7 through 13 years was associated with later IBD. Linking the CSHRR to the Danish National Patient Register, we identified cases of Crohn's disease (CD) and ulcerative colitis (UC) diagnosed during follow-up. Cox regression was used to estimate the hazard ratios (HR) with 95% confidence intervals. RESULTS: During 10 million person-years of follow-up, 1500 individuals were diagnosed with CD and 2732 with UC. At all examined ages, a 1 unit increase in BMI z-score was associated with a significantly decreased risk of UC (HRs = 0.9) and with a significantly increased risk of CD when diagnosed before age 30 (HRs = 1.2). We observed no…

BACKGROUND AND AIMS: Serrated polyps (SPs) and conventional high-risk adenomas (HRAs) derive from two distinct biological pathways but can also occur synchronously. Adults with synchronous SPs and adenomas have been shown to be a high-risk group and may have a unique risk factor profile that differs from adults with conventional HRAs alone. We used the population-based New Hampshire Colonoscopy Registry (NHCR) to examine the risk profile of individuals with synchronous conventional HRAs and SPs. METHODS: Our study population included 20,281 first time screening colonoscopies from asymptomatic NHCR participants 40 years or older between 2004-15. Exams were categorized by findings: (1) normal, (2) HRA only (adenomas ≥ 1 cm, villous, high grade dysplasia, multiple adenomas ( > 2) and adenocarcinoma), (3) clinically significant SP (CSSP) only (any hyperplastic polyp ≥ 1 cm, sessile serrated adenomas/polyps or traditional serrated adenomas), and (4) synchronous HRA + CSSP. Risk factors examined included exposure of interest, smoking (never, past, and current/pack years), as well as age,…

Chronic diarrhea is a common clinical problem, affecting roughly 5% of the population in any given year. Evaluation and management of these patients can be difficult due to the extensive differential diagnosis of this symptom. Many patients with chronic diarrhea have structural problems, such as inflammatory bowel disease or celiac disease, that can be readily identified. Others do not, and often are given a diagnosis of irritable bowel syndrome with diarrhea (IBS-D). When based on generally accepted clinical criteria, a diagnosis of IBS-D identifies a group of patients who are unlikely to have disorders producing anatomical changes in the gut. It is less clear that a diagnosis of IBS-D identifies a specific pathophysiology or leads to better management of symptoms. Disorders such as small intestinal bacterial overgrowth, bile acid malabsorption, food intolerance, and motility disorders may account for symptoms in patients with IBS-D. More effective tests are being developed to identify the clinical problems underlying IBS-D and may lead to more specific diagnoses that may improve…

Division of Gastroenterology and Hepatology, Medical College of Georgia, Augusta University, Augusta, GA, USA. Correspondence: S.S.R. (email: [email protected]) Received 28 september 2017; revised 21 November 2017; accepted 11 December 2017; published online 16 February 2018

OBJECTIVES: Balloon expulsion testing (BET) is recommended to evaluate for dyssynergic defecation in patients with chronic constipation (CC). However, it remains poorly standardized and is limited to specialized centers. Our goal was to assess the clinical utility of balloon expulsion as an initial test for dyssynergic defecation and to determine appropriate testing parameters. METHODS: We performed a literature search to identify cohort studies of unselected subjects with CC and case-control studies of subjects with/without dyssynergic defecation. We defined dyssynergic defecation by constipation symptoms and a positive reference test (anorectal manometry [ARM], defecography, or electromyography [EMG]). We performed a meta-analysis using a bivariate mixed-effects regression model to assess summary sensitivity, specificity, and area under the curve (AUC) with 95% confidence intervals (CI). We conducted a meta-regression to investigate individual test parameters and demographic variables. RESULTS: We identified 15 eligible studies comprising 2090 individual assessments of BET. Among…

Probiotic usage has become popular with both medical practitioners and the community in general; patients commonly seek advice regarding what, if any, such preparation would be useful for their own diseases. Since such advice should be evidence-based, identified randomized clinical trials (RCTs) for a number of gastrointestinal conditions were reviewed; the data were organized by individual probiotic genera/species. Only trials in adults were considered. Most of the identified RCTs were small and low-quality, so any conclusions to be drawn will be limited at least by methodologic problems. Using the GRADE system to consider the reliability of the evidence generated from these RCTs, it did appear that the use of fecal microbial transplantation to treat recurrent Clostridium difficile infection is well justified. Given the methodologic issues, there was moderately good evidence for preventing antibiotic-associated diarrhea with Lactobacillus, Bifidobacterium, Streptococcus, or Saccharomyces boulardii and for using Lactobacillus, Bifidobacterium, or Saccharomyces as adjunct therapy in…

INTRODUCTION: Hepatic encephalopathy (HE) is the most common potentially modifiable reason for admission in patients with cirrhosis. Cognitive and physical components of frailty have pathophysiologic rationale as risk factors for HE. We aimed to assess the utility of a composite score (MoCA-CFS) developed using the Montreal Cognitive Assessment (MoCA) and the Clinical Frailty Scale (CFS) for predicting HE admissions within 6 months. METHODS: Consecutive adult patients with cirrhosis were followed for 6 months or until death/transplant. Patients with overt HE and dementia were excluded. Primary outcome was the prediction of HE-related admissions at 6 months. RESULTS: A total of 355 patients were included; mean age 55.9 ± 9.6; 62.5% male; Hepatitis C and alcohol etiology in 64%. Thirty-six percent of patients had cognitive impairment according to the MoCA (≤24) and 14% were frail on the CFS (>4). The MoCA-CFS independently predicted HE hospitalization within 6 months, a MoCA-CFS score of 1 and 2 respectively increasing the odds of hospitalization by 3.3 (95% CI:1.5-7.7) and 5.7 (95%…