Prevalence and Predictors of Barrett's Esophagus After Negative Initial Endoscopy: Analysis From Two National Databases.

BACKGROUND & AIMS: Guidelines suggest a single screening esophagogastroduodenoscopy (EGD) in patients with multiple risk factors for Barrett's esophagus (BE). We aimed to determine BE prevalence and predictors on repeat EGD after a negative initial EGD, using 2 large national databases (GI Quality Improvement Consortium [GIQuIC] and TriNetX). METHODS: Patients who underwent at least 2 EGDs were included and those with BE or esophageal adenocarcinoma detected at initial EGD were excluded. Patient demographics and prevalence of BE on repeat EGD were collected. Multivariate logistic regression was performed to assess for independent risk factors for BE detected on the repeat EGD. RESULTS: In 214,318 and 153,445 patients undergoing at least 2 EGDs over a median follow-up of 28-35 months, the prevalence of BE on repeat EGD was 1.7% in GIQuIC and 3.4% in TriNetX, respectively (26%-45% of baseline BE prevalence). Most (89%) patients had nondysplastic BE. The prevalence of BE remained stable over time (from 1 to >5 years from negative initial EGD) but increased with increasing number of risk factors. BE prevalence in a high-risk population (gastroesophageal reflux disease plus ≥1 risk factor for BE) was 3%-4%. CONCLUSIONS: In this study of >350,000 patients, rates of BE on repeat EGD ranged from 1.7%-3.4%, and were higher in those with multiple risk factors. Most were likely missed at initial evaluation, underscoring the importance of a high-quality initial endoscopic examination. Although routine repeat endoscopic BE screening after a negative initial examination is not recommended, repeat screening may be considered in carefully selected patients with gastroesophageal reflux disease and ≥2 risk factors for BE, potentially using nonendoscopic tools.

Rates of Recurrent Intestinal Metaplasia and Dysplasia After Successful Endoscopic Therapy of Barrett's Neoplasia by Endoscopic Mucosal Resection vs Endoscopic Submucosal Dissection and Ablation: A Large North American Multicenter Cohort.

INTRODUCTION: Endoscopic eradication therapy (EET) combining endoscopic resection (ER) with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) followed by ablation is the standard of care for the treatment of dysplastic Barrett's esophagus (BE). We have previously shown comparable rates of complete remission of intestinal metaplasia (CRIM) with both approaches. However, data comparing recurrence after CRIM are lacking. We compared rates of recurrence after CRIM with both techniques in a multicenter cohort. METHODS: Patients undergoing EET achieving CRIM at 3 academic institutions were included. Demographic and clinical data were abstracted. Outcomes included rates and predictors of any BE and dysplastic BE recurrence in the 2 groups. Cox-proportional hazards models and inverse probability treatment weighting (IPTW) analysis were used for analysis. RESULTS: A total of 621 patients (514 EMR and 107 ESD) achieving CRIM were included in the recurrence analysis. The incidence of any BE (15.7, 5.7 per 100 patient-years) and dysplastic BE recurrence (7.3, 5.3 per 100 patient-years) were comparable in the EMR and ESD groups, respectively. On multivariable analyses, the chances of BE recurrence were not influenced by ER technique (hazard ratio 0.87; 95% confidence interval 0.51-1.49; P = 0.62), which was also confirmed by IPTW analysis (ESD vs EMR: hazard ratio 0.98; 95% confidence interval 0.56-1.73; P = 0.94). BE length, lesion size, and history of cigarette smoking were independent predictors of BE recurrence. DISCUSSION: Patients with BE dysplasia/neoplasia achieving CRIM, initially treated with EMR/ablation, had comparable recurrence rates to ESD/ablation. Randomized trials are needed to confirm these outcomes between the 2 ER techniques.

Clinical Outcomes After Endoscopic Management of Low-Risk and High-Risk T1a Esophageal Adenocarcinoma: A Multicenter Study.

INTRODUCTION: Endoscopic eradication therapy (EET) is standard of care for T1a esophageal adenocarcinoma (EAC). However, data on outcomes in high-risk T1a EAC are limited. We assessed and compared outcomes after EET of low-risk and high-risk T1a EAC, including intraluminal EAC recurrence, extraesophageal metastases, and overall survival. METHODS: Patients who underwent EET for T1a EAC at 3 referral Barrett's esophagus endotherapy units between 1996 and 2022 were included. Patients with submucosal invasion, positive deep margins, or metastases at initial diagnosis were excluded. High-risk T1a EAC was defined as T1a EAC with poor differentiation and/or lymphovascular invasion, with low-risk disease being defined without these features. All pathology was systematically assessed by expert gastrointestinal pathologists. Baseline and follow-up endoscopy and pathology data were abstracted. Time-to-event analyses were performed to compare outcomes between groups. RESULTS: One hundred eighty-eight patients with T1a EAC were included (high risk, n = 45; low risk, n = 143) with a median age of 70 years, and 84% were men. Groups were comparable for age, sex, Barrett's esophagus length, lesion size, and EET technique. Rates of delayed extraesophageal metastases (11.1% vs 1.4%) were significantly higher in the high-risk group ( P = 0.02). There was no significant difference in the rates of intraluminal EAC recurrence ( P = 0.79) and overall survival ( P = 0.73) between the 2 groups. DISCUSSION: Patients with high-risk T1a EAC undergoing successful EET had a substantially higher rate of extraesophageal metastases compared with those with low-risk T1a EAC on long-term follow-up. These data should be factored into discussions with patients while selecting treatment approaches. Additional prospective data in this area are critical.

Irregular Z-Line: To Biopsy or Not to Biopsy?

The z-line refers to the squamocolumnar junction which marks the transition between the normal stratified squamous epithelium of the distal esophagus and the columnar epithelium of the gastric cardia. An "irregular" z-line refers to an irregular appearing squamocolumnar junction characterized by the presence of columnar mucosa less than 1 cm in length that extends above the gastroesophageal junction. In contrast, Barrett's esophagus is diagnosed when columnar mucosa of at least 1 cm is seen in the distal esophagus extending above the gastroesophageal junction with biopsies demonstrating specialized intestinal metaplasia. Current guidelines recommend against taking routine biopsies from a normal or irregular z-line in the absence of visible abnormalities and advise against endoscopic surveillance in this patient population, in large part due to multiple studies demonstrating lack of progression to advanced neoplasia such as high-grade dysplasia or esophageal adenocarcinoma in patients with an irregular z-line. Despite these recommendations, a sizable number of patients without Barrett's esophagus undergo biopsies from the z-line and are subsequently recommended to have surveillance endoscopies. Furthermore, patients with an irregular z-line are often mislabelled as Barrett's esophagus resulting in significant downstream consequences including higher healthcare costs and reduced health-related quality of life. In this review, we highlight the importance of landmark identification of the distal esophagus and gastroesophageal junction at the time of endoscopy, share recommendations from current guidelines related to the z-line, examine rates of neoplastic progression in those with an irregular z-line, discuss consequences of routinely biopsying an irregular z-line, and highlight strategies on how to approach an irregular z-line if seen on endoscopy. A careful, high-quality endoscopic examination can help to identify visible abnormalities at the z-line, which, if present, should be targeted for biopsies to rule out dysplasia and neoplasia.

Bile Acid Sequestrants in Microscopic Colitis: Clinical Outcomes and Utility of Bile Acid Testing.

BACKGROUND & AIMS: Bile acid sequestrants (BAS) may be a treatment in microscopic colitis (MC), but efficacy data are limited. We evaluated the effectiveness of BAS in MC and assessed the utility of bile acid testing to predict response. METHODS: Adults with MC treated with BAS (2010-2020) at Mayo Clinic were identified. Bile acid malabsorption was defined by elevated serum 7⍺-hydroxy-4-cholesten-3-one or by fecal testing using previously validated cutoffs. Response was defined at 12 ± 4 weeks after BAS initiation as: complete (resolution of diarrhea), partial (≥50% improvement in diarrhea), nonresponse (<50% improvement), and intolerance (discontinuation due to side effects). Logistic regression was used to identify predictors of response to BAS. RESULTS: We identified 282 patients (median age, 59 years [range, 20-87 years]; 88.3% women) with median follow-up of 4.5 years (range, 0.4-9.1 years). Patients were treated with the following BAS: 64.9% cholestyramine, 21.6% colesevelam, and 13.5% colestipol. Clinical outcomes were: 49.3% complete response, 16.3% partial response, 24.8% nonresponse, and 9.6% intolerance. There were no differences in outcomes between those on BAS alone or BAS combined with other medications (P = .98). The dose of BAS was not associated with response (P = .51). Bile acid testing was done in 31.9% of patients, and 56.7% were positive. No predictors of response to BAS were identified. After BAS discontinuation, 41.6% had recurrence at a median of 21 weeks (range, 1-172 weeks). CONCLUSION: In one of the largest cohorts evaluating BAS treatment in MC, nearly two-thirds had a partial or complete response. Additional research is needed to determine the role of BAS and bile acid malabsorption in MC.

Rare, Overlooked, or Underappreciated Causes of Recurrent Abdominal Pain: A Primer for Gastroenterologists.

Recurrent abdominal pain is a common reason for repeated visits to outpatient clinics and emergency departments, reflecting a substantial unmet need for timely and accurate diagnosis. A lack of awareness of some of the rarer causes of recurrent abdominal pain may impede diagnosis and delay effective management. This article identifies some of the key rare but diagnosable causes that are frequently missed by gastroenterologists and provides expert recommendations to support recognition, diagnosis, and management with the ultimate aim of improving patient outcomes.

Defining the Long-Term Clinical Course and Need for Repeat Dilation for Patients With Schatzki Rings.

Schatzki rings (SRs) are a well-known cause of intermittent solid-food dysphagia.1 Although some patients sustain improvement after 1 endoscopic dilation, others require repeated dilations for recurrent symptoms.2-4 SRs are believed to be distinct from strictures caused by gastroesophageal reflux disease. SRs are sharply localized lesions with clearly defined margins, whereas peptic strictures have a more gradual transition between normal and abnormal esophagus to produce a funnel-shaped narrowing.5,6 Consequently, it has been assumed that repeat dilation is less common in SRs dissimilar from medically untreated peptic strictures. The study aim was to identify clinical and radiologic predictors for repeated esophageal dilations in patients with SRs and to assess if peptic stricture-like characteristics of rings correspond to need for repeat dilation.

Association of Incidental Positron Emission Tomography Uptake in the Esophagus to Gastroesophageal Reflux Disease.

The Los Angeles (LA) classification is the most accurate means of assessing esophageal injury from caustic gastric acid with focused and greater concentrations in areas of erosive disease.1 However, data from animal models and patients have proposed that an initial diffuse inflammatory pathway contributes to injury in gastroesophageal reflux disease (GERD) mediated by interleukin (IL) 8, IL1ß,2,3 and hypoxia-inducible factors.4,5 These observations demonstrate a lymphocyte predominant inflammatory process over course of 1-2 weeks associated with basal zone hyperplasia and dilation of intercellular spaces.6 In cultured human esophageal epithelial cells and patients, it is further suggested that acid causes this chronic inflammatory reaction.

The Epidemiology of Microscopic Colitis in Olmsted County, Minnesota: Population-Based Study From 2011 to 2019.

BACKGROUND & AIMS: Epidemiologic studies from Europe and North America have reported an increasing incidence of microscopic colitis (MC) in the late 20th century, followed by a plateau. This population-based study assessed recent incidence trends and the overall prevalence of MC over the past decade. METHODS: Residents of Olmsted County, MN, diagnosed with collagenous colitis (CC) or lymphocytic colitis (LC) between January 1, 2011, and December 31, 2019 were identified using the Rochester Epidemiology Project. Clinical variables were abstracted by chart review. Incidence rates were age- and sex-adjusted to the 2010 US population. Associations between incidence and age, sex, and calendar periods were evaluated using Poisson regression analyses. RESULTS: A total of 268 incident cases of MC were identified with a median age at diagnosis of 64 years (range, 19-90 y); 207 (77%) were women. The age- and sex-adjusted incidence of MC was 25.8 (95% CI, 22.7-28.9) cases per 100,000 person-years. The incidence of LC was 15.8 (95% CI, 13.4-18.2) and CC was 9.9 (95% CI, 8.1-11.9) per 100,000 person-years. A higher MC incidence was associated with increasing age and female sex (P < .01). There was no significant trend in age- and sex-adjusted incidence rate over the study period (P = .92). On December 31, 2019, the prevalence of MC, LC, and CC (including cases diagnosed before 2011) was 246.2, 146.1, and 100.1 per 100,000 persons, respectively. CONCLUSIONS: The incidence of MC and its subtypes was stable between 2011 and 2019, but its prevalence was higher than in previous periods. The incidence of MC continues to be associated with increasing age and female sex.

Microscopic Colitis and Risk of Colon Adenomas: A Multicenter Retrospective Cohort Study.

Microscopic colitis (MC) is a common cause of chronic watery diarrhea, with the highest incidence in women over age 50.1 Cross-sectional studies have suggested that patients with MC have a lower incidence of adenomatous colon polyps compared with those without MC.2-4 The existing literature is limited by cross-sectional design, small sample sizes, lack of longitudinal follow-up, and the use of average-risk patients, rather than those with chronic diarrhea, as controls. We aimed to explore the association between MC and colon adenomas.

Clinical, Endoscopic, and Histopathology Features of Esophageal Graft-vs-Host Disease.

INTRODUCTION: To describe the clinical, endoscopic, and histopathology features of esophageal graft-vs-host disease (GVHD). METHODS: Patients with biopsy-proven esophageal GVHD diagnosed at Mayo Clinic between 2000 and 2021 were included. RESULTS: In 43 esophageal patients, other organ GVHD was present in 58% before and 86% at esophageal GVHD diagnosis. Esophageal specific symptoms were uncommon (dysphagia 26% and odynophagia/heartburn 5%). Esophagogastroduodenoscopy was abnormal in 72% patients demonstrating erosive esophagitis, ulceration, desquamation, or rings/furrows in a diffuse or focal pattern. DISCUSSION: There should be a low threshold for esophageal biopsies for GVHD because esophageal symptoms and endoscopic findings may be nonspecific or absent.

Budesonide Maintenance in Microscopic Colitis: Clinical Outcomes and Safety Profile From a Population-Based Study.

INTRODUCTION: Outcomes and safety of budesonide maintenance therapy in microscopic colitis (MC) are not well known. METHODS: Adult residents of Olmsted County, Minnesota, diagnosed with MC (2002-2019) and treated with budesonide were identified using the Rochester Epidemiology Project. Response was assessed at 12 ± 4 weeks after initiation of therapy and defined as complete (resolution of diarrhea), partial (≥50% improvement in the number of bowel movements), nonresponse (<50% improvement), and intolerance (discontinued because of side effects). For safety outcomes, cases (budesonide maintenance) and MC controls (no budesonide therapy) were matched by sex and age at diagnosis (±2 years). RESULTS: A total of 450 patients were identified, of whom 162 (36.0%) were treated with budesonide for induction of clinical remission (median age 67 [23-91] years and 126 women [77.8%] ). Clinical outcomes for induction were as follows: 130 (80.2%) complete response, 22 (13.6%) partial response, 8 (4.9%) no response, and 2 (1.2%) intolerance. After induction, 96 (63.2%) had recurrence after discontinuation, of whom 27 (28.1%) required further budesonide induction treatment without maintenance, 56 (58.3%) required long-term budesonide maintenance, and 13 (13.5%) were treated with other therapies. Of those receiving budesonide maintenance, all responded (55 [98.2%] complete and 1 [1.8%] partial). No patient stopped maintenance from adverse events. The median duration of follow-up was 5.6 years (0.3-18.9). There was no significant difference between cases and controls in the incidence of osteopenia/osteoporosis, diabetes mellitus, hypertension, glaucoma, or cataracts. DISCUSSION: The long-term use of budesonide in MC seems to be effective and generally well tolerated with limited adverse effects.

Clinical Characteristics and Treatment Response in Microscopic Colitis Based on Age at Diagnosis: A Multicenter Retrospective Study.

BACKGROUND: Microscopic colitis (MC) primarily affects older adults; thus, data in younger patients are scarce. AIMS: To compare clinical characteristics and treatment response by age at diagnosis. METHODS: This retrospective cohort study was performed at Mayo Clinic and Massachusetts General Hospital. Patients were chosen consecutively using established databases. Patients were 'younger' if age at diagnosis was ≤ 50 years and 'older' if age > 50 years. Treatment outcomes were captured for induction (12 ± 4 weeks), based on the total number of daily stools, and defined as remission (complete resolution), response (≥ 50% improvement), non-response (< 50% improvement), and intolerance. Patients were considered 'responders' if they had remission or response and 'non-responders' if they had non-response or intolerance. RESULTS: We included 295 patients (52 younger, 243 older). There were no differences in sex, race, MC subtype, and diarrhea severity between groups (all P > 0.05). Younger patients were more likely to have celiac disease (17.3% vs. 5.8%, P = 0.01), while older patients had higher BMI (mean 25.0 vs. 23.8 kg/m2, P = 0.04) were more likely smokers (53.9% vs. 34.6%, P = 0.01) and use NSAIDs (48.6% vs. 15.4%, P < 0.01) and statins (22.6% vs. 3.8%, P < 0.01). Overall treatment response was highest for budesonide (88.3%) and did not differ when comparing older to younger patients (90.6% vs. 77.8%, P = 0.12) or by MC subtype (LC, 81.5% vs. CC, 92.9%, P = 0.07). CONCLUSIONS: There are no significant differences in MC treatment response based on age or disease subtype. These findings support treating patients with MC based on symptom severity rather than age.

Changes in National Google Trends and Local Healthcare Utilization After High-Impact Gastroenterology Publications.

INTRODUCTION: We examined national Google Trends and local healthcare utilization after 3 high-impact gastroenterology publications. METHODS: Changes in US Google Trends and Olmsted County health utilization were studied. RESULTS: Publication views within 30 days were 51,458 (Imperiale), 49,759 (Pimentel), and 18,750 (Gomm). Colonoscopy searches (P = 0.04) and Cologuard tests performed (P < 0.01) increased while colonoscopies decreased (P < 0.01). Searches for rifaximin (P = 0.05), irritable bowel syndrome (P < 0.01), diarrhea (P < 0.01), and rifaximin prescriptions (P = 0.02) increased. Increase in hydrogen-2 blocker searches (P = 0.02) and prescriptions (P < 0.01) and gastroesophageal reflux disease (P < 0.01) and dementia office visits (P < 0.01) occurred. DISCUSSION: High-impact gastroenterology publications influence Google searches and local population-based healthcare utilization.

Esophageal Epidermoid Metaplasia: Clinical Characteristics and Risk of Esophageal Squamous Neoplasia.

INTRODUCTION: Esophageal epidermoid metaplasia (EEM) is a rare disease. METHODS: Patients with EEM diagnosed between 2014 and 2020 were reviewed. RESULTS: Forty EEM cases were identified. EEM occurred in 9 (23%) patients before, concordant, or after esophageal squamous cell carcinoma (ESCC). EEM was associated with previous esophageal lichen planus in 5 patients, Barrett's esophagus 7, and esophageal adenocarcinoma 1. EEM was focal in 28 (70%) or diffuse in 12 (30%) and not detected in 45% on recent previous endoscopy. DISCUSSION: EEM is a premalignant underrecognized condition associated with multiple conditions. Close follow-up or endoscopic treatment may be warranted because of its ESCC association.

Risk Factors, Endoscopic Features, and Clinical Outcomes of Cytomegalovirus Esophagitis Based on a 10-year Analysis at a Single Center.

Cytomegalovirus (CMV) can infect multiple areas of the gastrointestinal tract, most commonly the esophagus and colon.1 CMV esophagitis is the third leading cause of infectious esophagitis, after Candida and herpes simplex virus.2 It occurs predominantly in immunocompromised hosts such as patients with human immunodeficiency virus (HIV) and is considered an acquired immunodeficiency syndrome (AIDS) defining illness.1 However, more recent case reports suggest that this disease may also affect the non-HIV immunosuppressed patient population.3 The aim of this study was to reevaluate predictors for development of CMV esophagitis in the post highly active antiretroviral therapy era and describe clinical and endoscopic features of CMV esophagitis as well as patient outcomes from a large tertiary care center.

Phases of Metabolic and Soft Tissue Changes in Months Preceding a Diagnosis of Pancreatic Ductal Adenocarcinoma.

BACKGROUND & AIMS: Identifying metabolic abnormalities that occur before pancreatic ductal adenocarcinoma (PDAC) diagnosis could increase chances for early detection. We collected data on changes in metabolic parameters (glucose, serum lipids, triglycerides; total, low-density, and high-density cholesterol; and total body weight) and soft tissues (abdominal subcutaneous fat [SAT], adipose tissue, visceral adipose tissue [VAT], and muscle) from patients 5 years before the received a diagnosis of PDAC. METHODS: We collected data from 219 patients with a diagnosis of PDAC (patients) and 657 healthy individuals (controls) from the Rochester Epidemiology Project, from 2000 through 2015. We compared metabolic profiles of patients with those of age- and sex-matched controls, constructing temporal profiles of fasting blood glucose, serum lipids including triglycerides, cholesterol profiles, and body weight and temperature for 60 months before the diagnosis of PDAC (index date). To construct the temporal profile of soft tissue changes, we collected computed tomography scans from 68 patients, comparing baseline (>18 months before diagnosis) areas of SAT, VAT, and muscle at L2/L3 vertebra with those of later scans until time of diagnosis. SAT and VAT, isolated from healthy individuals, were exposed to exosomes isolated from PDAC cell lines and analyzed by RNA sequencing. SAT was collected from KRAS+/LSLG12D P53flox/flox mice with PDACs, C57/BL6 (control) mice, and 5 patients and analyzed by histology and immunohistochemistry. RESULTS: There were no significant differences in metabolic or soft tissue features of patients vs controls until 30 months before PDAC diagnosis. In the 30 to 18 months before PDAC diagnosis (phase 1, hyperglycemia), a significant proportion of patients developed hyperglycemia, compared with controls, without soft tissue changes. In the 18 to 6 months before PDAC diagnosis (phase 2, pre-cachexia), patients had significant increases in hyperglycemia and decreases in serum lipids, body weight, and SAT, with preserved VAT and muscle. In the 6 to 0 months before PDAC diagnosis (phase 3, cachexia), a significant proportion of patients had hyperglycemia compared with controls, and patients had significant reductions in all serum lipids, SAT, VAT, and muscle. We believe the patients had browning of SAT, based on increases in body temperature, starting 18 months before PDAC diagnosis. We observed expression of uncoupling protein 1 (UCP1) in SAT exposed to PDAC exosomes, SAT from mice with PDACs, and SAT from all 5 patients but only 1 of 4 controls. CONCLUSIONS: We identified 3 phases of metabolic and soft tissue changes that precede a diagnosis of PDAC. Loss of SAT starts 18 months before PDAC identification, and is likely due to browning. Overexpression of UCP1 in SAT might be a biomarker of early-stage PDAC, but further studies are needed.

Nonfatal Pediatric Injuries Associated With Consumer Products and Sports and Recreational Activities in the United States.

OBJECTIVE: The aim of this study was to investigate the epidemiology of nonfatal consumer product- and sports and recreational activity-related injuries among US children. METHODS: National Electronic Injury Surveillance System data regarding children younger than 18 years who were treated in US emergency departments (EDs) for nonfatal consumer product- or sports and recreational activity-related injuries were analyzed. RESULTS: From 1990 through 2012, an estimated 121,489,024 (95% confidence interval, 104,226,323-138,751,726) children younger than 18 years were treated in US EDs for nonfatal injuries meeting study criteria, yielding an average of 5,282,131 children annually, or 74.12 injuries per 1000 children. During 1990 to 2005, the overall annual injury rate decreased by 14.0% (P < 0.001), followed by an increase of 7.3% (P = 0.157) during 2005 to 2012. The concussion/closed head injury rate increased by 199.3% (P < 0.001) from 1996 to 2012. Injury rates were highest among children 0 to 4 years old and lowest among children 5 to 9 years old. Sports and recreational activities accounted for 46.5% of all injuries. Falls (40.2%) and "struck-by" (22.6%) were the leading mechanisms of injury, and 62.3% of all injuries were among boys. Injuries often occurred to the head/neck (37.8%) or upper extremities (31.9%), were frequently diagnosed as lacerations (29.0%) or soft tissue injuries (21.0%), and 2.7% were admitted to the hospital. CONCLUSIONS: On average, a child was treated in a US ED for a nonfatal consumer product- or sports and recreational activity-related injury every 6 seconds. Although injury rates decreased early in the study period, there was a nonsignificant increasing trend from 2005 to 2012. Multilevel injury prevention efforts are recommended.