AGA Clinical Practice Guideline on Endoscopic Eradication Therapy of Barrett's Esophagus and Related Neoplasia.

BACKGROUND & AIMS: Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Endoscopic eradication therapy (EET) can be effective in eradicating BE and related neoplasia and has greater risk of harms and resource use than surveillance endoscopy. This clinical practice guideline aims to inform clinicians and patients by providing evidence-based practice recommendations for the use of EET in BE and related neoplasia. METHODS: The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients, conducted an evidence review, and used the Evidence-to-Decision Framework to develop recommendations regarding the use of EET in patients with BE under the following scenarios: presence of (1) high-grade dysplasia, (2) low-grade dysplasia, (3) no dysplasia, and (4) choice of stepwise endoscopic mucosal resection (EMR) or focal EMR plus ablation, and (5) endoscopic submucosal dissection vs EMR. Clinical recommendations were based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 5 recommendations for the use of EET in BE and related neoplasia. Based on the available evidence, the panel made a strong recommendation in favor of EET in patients with BE high-grade dysplasia and conditional recommendation against EET in BE without dysplasia. The panel made a conditional recommendation in favor of EET in BE low-grade dysplasia; patients with BE low-grade dysplasia who place a higher value on the potential harms and lower value on the benefits (which are uncertain) regarding reduction of esophageal cancer mortality could reasonably select surveillance endoscopy. In patients with visible lesions, a conditional recommendation was made in favor of focal EMR plus ablation over stepwise EMR. In patients with visible neoplastic lesions undergoing resection, the use of either endoscopic mucosal resection or endoscopic submucosal dissection was suggested based on lesion characteristics. CONCLUSIONS: This document provides a comprehensive outline of the indications for EET in the management of BE and related neoplasia. Guidance is also provided regarding the considerations surrounding implementation of EET. Providers should engage in shared decision making based on patient preferences. Limitations and gaps in the evidence are highlighted to guide future research opportunities.

Predicting Incident Adenocarcinoma of the Esophagus or Gastric Cardia Using Machine Learning of Electronic Health Records.

BACKGROUND & AIMS: Tools that can automatically predict incident esophageal adenocarcinoma (EAC) and gastric cardia adenocarcinoma (GCA) using electronic health records to guide screening decisions are needed. METHODS: The Veterans Health Administration (VHA) Corporate Data Warehouse was accessed to identify Veterans with 1 or more encounters between 2005 and 2018. Patients diagnosed with EAC (n = 8430) or GCA (n = 2965) were identified in the VHA Central Cancer Registry and compared with 10,256,887 controls. Predictors included demographic characteristics, prescriptions, laboratory results, and diagnoses between 1 and 5 years before the index date. The Kettles Esophageal and Cardia Adenocarcinoma predictioN (K-ECAN) tool was developed and internally validated using simple random sampling imputation and extreme gradient boosting, a machine learning method. Training was performed in 50% of the data, preliminary validation in 25% of the data, and final testing in 25% of the data. RESULTS: K-ECAN was well-calibrated and had better discrimination (area under the receiver operating characteristic curve [AuROC], 0.77) than previously validated models, such as the Nord-Trøndelag Health Study (AuROC, 0.68) and Kunzmann model (AuROC, 0.64), or published guidelines. Using only data from between 3 and 5 years before index diminished its accuracy slightly (AuROC, 0.75). Undersampling men to simulate a non-VHA population, AUCs of the Nord-Trøndelag Health Study and Kunzmann model improved, but K-ECAN was still the most accurate (AuROC, 0.85). Although gastroesophageal reflux disease was strongly associated with EAC, it contributed only a small proportion of gain in information for prediction. CONCLUSIONS: K-ECAN is a novel, internally validated tool predicting incident EAC and GCA using electronic health records data. Further work is needed to validate K-ECAN outside VHA and to assess how best to implement it within electronic health records.

Endoscopic Surveillance of Intestinal Metaplasia of the Esophagogastric Junction: A Decision Modeling Analysis.

INTRODUCTION: The incidence of esophagogastric junction adenocarcinoma (EGJAC) has been rising. Intestinal metaplasia of the esophagogastric junction (EGJIM) is a common finding in gastroesophageal reflux (irregular Z-line) and may represent an early step in the development of EGJAC in the West. Worldwide, EGJIM may represent progression along the Correa cascade triggered by Helicobacter pylori . We sought to evaluate the cost-effectiveness of endoscopic surveillance of EGJIM. METHODS: We developed a decision analytic model to compare endoscopic surveillance strategies for 50-year-old patients after diagnosis of non-dysplastic EGJIM: (i) no surveillance (standard of care), (ii) endoscopy every 3 years, (iii) endoscopy every 5 years, or (iv) 1-time endoscopy at 3 years. We modeled 4 progression scenarios to reflect uncertainty: A (0.01% annual cancer incidence), B (0.05%), C (0.12%), and D (0.22%). RESULTS: Cost-effectiveness of endoscopic surveillance depended on the progression rate of EGJIM to cancer. At the lowest progression rate (scenario A, 0.01%), no surveillance strategies were cost-effective. In moderate progression scenarios, 1-time surveillance at 3 years was cost-effective, at $30,989 and $16,526 per quality-adjusted life year for scenarios B (0.05%) and C (0.12%), respectively. For scenario D (0.22%), surveillance every 5 years was cost-effective at $77,695 per quality-adjusted life year. DISCUSSION: Endoscopic surveillance is costly and can cause harm; however, low-intensity longitudinal surveillance (every 5 years) is cost-effective in populations with higher EGJAC incidence. No surveillance or 1-time endoscopic surveillance of patients with EGJIM was cost-effective in low-incidence populations. Future studies to better understand the natural history of EGJIM, identify risk factors of progression, and inform appropriate surveillance strategies are required.

A Delphi Method for Development of a Barrett's Esophagus Question Prompt List as a Communication Tool for Optimal Patient-physician Communication.

BACKGROUND METHODS: The question prompt list content was derived through a modified Delphi process consisting of 3 rounds. In round 1, experts provided 5 answers to the prompts "What general questions should patients ask when given a new diagnosis of Barrett's esophagus" and "What questions do I not hear patients asking, but given my expertise, I believe they should be asking?" Questions were reviewed and categorized into themes. In round 2, experts rated questions on a 5-point Likert scale. In round 3, experts rerated questions modified or reduced after the previous rounds. Only questions rated as "essential" or "important" were included in Barrett's esophagus question prompt list (BE-QPL). To improve usability, questions were reduced to minimize redundancy and simplified to use language at an eighth-grade level (Fig. 1). RESULTS: Twenty-one esophageal medical and surgical experts participated in both rounds (91% males; median age 52 years). The expert panel comprised of 33% esophagologists, 24% foregut surgeons, and 24% advanced endoscopists, with a median of 15 years in clinical practice. Most (81%), worked in an academic tertiary referral hospital. In this 3-round Delphi technique, 220 questions were proposed in round 1, 122 (55.5%) were accepted into the BE-QPL and reduced down to 76 questions (round 2), and 67 questions (round 3). These 67 questions reached a Flesch Reading Ease of 68.8, interpreted as easily understood by 13 to 15 years olds. CONCLUSIONS: With multidisciplinary input, we have developed a physician-derived BE-QPL to optimize patient-physician communication. Future directions will seek patient feedback to distill the questions further to a smaller number and then assess their usability.

Endoscopic Screening Program for Control of Esophageal Adenocarcinoma in Varied Populations: A Comparative Cost-Effectiveness Analysis.

BACKGROUND & AIMS: Guidelines suggest endoscopic screening for esophageal adenocarcinoma (EAC) among individuals with symptoms of gastroesophageal reflux disease (GERD) and additional risk factors. We aimed to determine at what age to perform screening and whether sex and race should influence the decision. METHODS: We conducted comparative cost-effectiveness analyses using 3 independent simulation models. For each combination of sex and race (White/Black, 100,000 individuals each), we considered 41 screening strategies, including one-time or repeated screening. The optimal strategy was that with the highest effectiveness and an incremental cost-effectiveness ratio <$100,000 per quality-adjusted life-year gained. RESULTS: Among White men, 536 EAC deaths were projected without screening, and screening individuals with GERD twice at ages 45 and 60 years was optimal. Screening the entire White male population once at age 55 years was optimal in 26% of probabilistic sensitivity analysis runs. Black men had fewer EAC deaths without screening (n = 84), and screening those with GERD once at age 55 years was optimal. Although White women had slightly more EAC deaths (n = 103) than Black men, the optimal strategy was no screening, although screening those with GERD once at age 55 years was optimal in 29% of probabilistic sensitivity analysis runs. Black women had a very low burden of EAC deaths (n = 29), and no screening was optimal, as benefits were very small and some strategies caused net harm. CONCLUSIONS: The optimal strategy for screening differs by race and sex. White men with GERD symptoms can potentially be screened more intensely than is recommended currently. Screening women is not cost-effective and may cause net harm for Black women.

Organizational Factors Driving Selection of Gastrointestinal Endoscopic Sedation in Veterans Health Administration and Community Settings.

INTRODUCTION: Previous studies suggest that unmeasured organizational factors drive variability in anesthesia-assisted sedation (AA) use. METHODS: A mixed-methods study of 11 Veterans Health Administration and community gastrointestinal endoscopy sites; qualitative interviews of key sedation decision-makers. RESULTS: Three key interview themes were identified: (i) Increased AA demand and changes in endoscopist sedation training in fellowship drove site-level AA capacity expansion; (ii) this expansion further influenced sedation decisions in favor of AA use; and (iii) additional organizational factors influencing AA use included site-level decision-making processes and differences between Veterans Health Administration and community practice economics/mission. DISCUSSION: Key organizational factors drive variability in AA use across settings.

Racial Disparity in Esophageal Squamous Cell Carcinoma Treatment and Survival in the United States.

INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) has a higher incidence and prevalence than esophageal adenocarcinoma among Black individuals in the United States. Black individuals have lower ESCC survival. These racial disparities have not been thoroughly investigated. We examined the disparity in treatment and survival stratified by ESCC stage at diagnosis. METHODS: The Surveillance, Epidemiology, and End Results database was queried to identify patients with ESCC between 2000 and 2019. The identified cohort was divided into subgroups by race. Patient and cancer characteristics, treatment received, and survival rates were compared across the racial subgroups. RESULTS: A total of 23,768 patients with ESCC were identified. Compared with White individuals, Black individuals were younger and had more distant disease during diagnosis (distant disease: 26.7% vs 23.8%, P < 0.001). Black individuals had lower age-standardized 5-year survival for localized (survival % [95% confidence interval]: 19.3% [16-22.8] vs 27.6% [25.1-30.2]), regional (14.3% [12-16.7] vs 21.1% [19.6-22.7]), and distant (2.9% [1.9-4.1] vs 6.5% [5.5-7.5]) disease. Black individuals were less likely to receive chemotherapy (54.7% vs 57.5%, P = 0.001), radiation (58.5% vs 60.4%, P = 0.03), and surgery (11.4% vs 16.3%, P < 0.0001). DISCUSSION: Black individuals with ESCC have a lower survival rate than White individuals. This could be related to presenting at a later stage but also disparities in which treatments they receive even among individuals with the same stage of disease. To what extent these disparities in receipt of treatment is due to structural racism, social determinants of health, implicit bias, or patient preferences deserves further study.

Yield of Repeat Endoscopy for Barrett's Esophagus After Normal Index Endoscopy.

INTRODUCTION: Guidelines suggest 1-time screening with esophagogastroduodenoscopy (EGD) for Barrett's esophagus (BE) in individuals at an increased risk of esophageal adenocarcinoma (EAC). We aimed to estimate the yield of repeat EGD performed at prolonged intervals after a normal index EGD. METHODS: We conducted a national retrospective analysis within the U S Veterans Health Administration, identifying patients with a normal index EGD between 2003 and 2009 who subsequently had a repeat EGD. We tabulated the proportion with a new diagnosis of BE, EAC, or esophagogastric junction adenocarcinoma (EGJAC) and conducted manual chart review of a sample. We fitted logistic regression models for the odds of a new diagnosis of BE/EAC/EGJAC. RESULTS: We identified 71,216 individuals who had a repeat EGD between 1 and 16 years after an index EGD without billing or cancer registry codes for BE/EAC/EGJAC. Of them, 4,088 had a new billing or cancer registry code for BE/EAC/EGJAC after the repeat EGD. On manual review of a stratified sample, most did not truly have new BE/EAC/EGJAC. A longer duration between EGD was associated with greater odds of a new diagnosis (adjusted odds ratio [aOR] for each 5 years 1.31; 95% confidence interval [CI] 1.19-1.44), particularly among those who were younger during the index EGD (ages 19-29 years: aOR 3.92; 95% CI 1.24-12.4; ages 60-69 years: aOR 1.19; 95% CI 1.01-1.40). DISCUSSION: The yield of repeat EGD for BE/EAC/EGJAC seems to increase with time after a normal index EGD, particularly for younger individuals. Prospective studies are warranted to confirm these findings.

Identifying individuals at risk of esophageal adenocarcinoma: challenges, existing tools and future steps.

PURPOSE OF REVIEW: This review aims to discuss some of the clinical and epidemiological challenges of risk prediction models; summarize the evidence supporting existing models; and highlight the translational requirements. RECENT FINDINGS: A variety of risk prediction models exist to identify prevalent Barrett's esophagus or predict future esophageal adenocarcinoma. External validation studies have investigated performance of these models in a variety of settings. These models appear to be more predictive than use of symptoms alone, but the added complexity means that implementation challenges may require investigation. SUMMARY: Risk prediction models could be useful for identifying individuals at an increased risk of esophageal adenocarcinoma, which could assist screening decisions. However, risk prediction models must be implemented with care. Implementation science to assist the translation of existing models into practice may be an important next step.

Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn.

BACKGROUND: Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine). METHODS: Patients who were referred to Veterans Affairs (VA) gastroenterology clinics for PPI-refractory heartburn received 20 mg of omeprazole twice daily for 2 weeks, and those with persistent heartburn underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance-pH monitoring. If patients were found to have reflux-related heartburn, we randomly assigned them to receive surgical treatment (laparoscopic Nissen fundoplication), active medical treatment (omeprazole plus baclofen, with desipramine added depending on symptoms), or control medical treatment (omeprazole plus placebo). The primary outcome was treatment success, defined as a decrease of 50% or more in the Gastroesophageal Reflux Disease (GERD)-Health Related Quality of Life score (range, 0 to 50, with higher scores indicating worse symptoms) at 1 year. RESULTS: A total of 366 patients (mean age, 48.5 years; 280 men) were enrolled. Prerandomization procedures excluded 288 patients: 42 had relief of their heartburn during the 2-week omeprazole trial, 70 did not complete trial procedures, 54 were excluded for other reasons, 23 had non-GERD esophageal disorders, and 99 had functional heartburn (not due to GERD or other histopathologic, motility, or structural abnormality). The remaining 78 patients underwent randomization. The incidence of treatment success with surgery (18 of 27 patients, 67%) was significantly superior to that with active medical treatment (7 of 25 patients, 28%; P = 0.007) or control medical treatment (3 of 26 patients, 12%; P<0.001). The difference in the incidence of treatment success between the active medical group and the control medical group was 16 percentage points (95% confidence interval, -5 to 38; P = 0.17). CONCLUSIONS: Among patients referred to VA gastroenterology clinics for PPI-refractory heartburn, systematic workup revealed truly PPI-refractory and reflux-related heartburn in a minority of patients. For that highly selected subgroup, surgery was superior to medical treatment. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT01265550.).

The Optimal Age to Stop Endoscopic Surveillance of Patients With Barrett's Esophagus Based on Sex and Comorbidity: A Comparative Cost-Effectiveness Analysis.

BACKGROUND AND AIMS: Current guidelines recommend surveillance for patients with nondysplastic Barrett's esophagus (NDBE) but do not include a recommended age for discontinuing surveillance. This study aimed to determine the optimal age for last surveillance of NDBE patients stratified by sex and level of comorbidity. METHODS: We used 3 independently developed models to simulate patients diagnosed with NDBE, varying in age, sex, and comorbidity level (no, mild, moderate, and severe). All patients had received regular surveillance until their current age. We calculated incremental costs and quality-adjusted life-years (QALYs) gained from 1 additional endoscopic surveillance at the current age versus not performing surveillance at that age. We determined the optimal age to end surveillance as the age at which incremental cost-effectiveness ratio of 1 more surveillance was just less than the willingness-to-pay threshold of $100,000/QALY. RESULTS: The benefit of having 1 more surveillance endoscopy strongly depended on age, sex, and comorbidity. For men with NDBE and severe comorbidity, 1 additional surveillance at age 80 years provided 4 more QALYs per 1000 patients with BE at an additional cost of $1.2 million, whereas for women with severe comorbidity the benefit at that age was 7 QALYs at a cost of $1.3 million. For men with no, mild, moderate, and severe comorbidity, the optimal ages of last surveillance were 81, 80, 77, and 73 years, respectively. For women, these ages were younger: 75, 73, 73, and 69 years, respectively. CONCLUSIONS: Our comparative modeling analysis illustrates the importance of considering comorbidity status and sex when deciding on the age to discontinue surveillance in patients with NDBE.

Gastroesophageal Reflux Disease Is Not a Great Screening Criterion: Time to Move on to Other Strategies for Controlling the Burden of Esophageal Adenocarcinoma.

ABSTRACT: Gastroesophageal reflux disease (GERD) is key in the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma (EAC). Endoscopic screening of select individuals with GERD symptoms for Barrett's esophagus and EAC has been recommended, but the great majority of patients with EAC had never undergone prior screening, despite over a million esophagogastroduodenoscopies (EGDs) performed annually in the United States among individuals with GERD symptoms. This is likely due to a conflation among providers regarding diagnostic EGD in those with refractory symptoms and screening EGD. An alternative approach is needed that de-emphasizes GERD to avoid confusion and increase uptake of appropriate screening.

Proanthocyanidins mitigate bile acid-induced changes in GSTT2 levels in a panel of racially diverse patient-derived primary esophageal cell cultures.

Persistent and symptomatic reflux of gastric and duodenal contents, known as gastroesophageal reflux disease (GERD), is the strongest risk factor for esophageal adenocarcinoma (EAC). Despite similar rates of GERD and other risk factors across racial groups, EAC progression disproportionately impacts Caucasians. We recently reported that elevated tissue levels of the detoxification enzyme GSTT2 in the esophagi of Blacks compared to Caucasians may contribute protection. Herein, we extend our research to investigate whether cranberry proanthocyanidins (C-PAC) mitigate bile acid-induced damage and GSTT2 levels utilizing a racially diverse panel of patient-derived primary esophageal cultures. We have shown that C-PACs mitigate reflux-induced DNA damage through GSTT2 upregulation in a rat esophageal reflux model, but whether effects are recapitulated in humans or differentially based on race remains unknown. We isolated normal primary esophageal cells from Black and Caucasian patients and assessed GSTT2 protein levels and cellular viability following exposure to a bile acid cocktail with and without C-PAC treatment. Constitutive GSTT2 levels were significantly elevated in Black (2.9-fold) compared to Caucasian patients, as were GSTT2 levels in Black patients with GERD. C-PAC treatment induced GSTT2 levels 1.6-fold in primary normal esophageal cells. GSTT2 induction by C-PAC was greatest in cells with constitutively low GSTT2 expression. Overall, C-PAC mitigated bile-induced reductions of GSTT2 and subsequent loss of cell viability regardless of basal GSTT2 expression or race. These data support that C-PAC may be a safe efficacious agent to promote epithelial fitness through GSTT2 induction and in turn protect against bile acid-induced esophageal injury.

Detection of Barrett's neoplasia with a near-infrared fluorescent heterodimeric peptide.

BACKGROUND: Esophageal adenocarcinoma (EAC) is a molecularly heterogeneous disease with poor prognosis that is rising rapidly in incidence. We aimed to demonstrate specific binding by a peptide heterodimer to Barrett's neoplasia in human subjects. METHODS: Peptide monomers specific for EGFR and ErbB2 were arranged in a heterodimer configuration and labeled with IRDye800. This near-infrared (NIR) contrast agent was topically administered to patients with Barrett's esophagus (BE) undergoing either endoscopic therapy or surveillance. Fluorescence images were collected using a flexible fiber accessory passed through the instrument channel of an upper gastrointestinal endoscope. Fluorescence images were collected from 31 BE patients. A deep learning model was used to segment the target (T) and background (B) regions. RESULTS: The mean target-to-background (T/B) ratio was significantly greater for high grade dysplasia (HGD) and EAC versus BE, low grade dysplasia (LGD), and squamous epithelium. At a T/B ratio of 1.5, sensitivity and specificity of 94.1 % and 92.6 %, respectively, were achieved for the detection of Barrett's neoplasia with an area under the curve of 0.95. No adverse events attributed to the heterodimer were found. EGFR and ErbB2 expression were validated in the resected specimens. CONCLUSIONS: This "first-in-human" clinical study demonstrates the feasibility of detection of early Barrett's neoplasia using a NIR-labeled peptide heterodimer.

What patients with eosinophilic esophagitis may not share with their providers: a qualitative assessment of online health communities.

BACKGROUND: Little is known about how patients with eosinophilic esophagitis (EoE) experience their symptoms, receive care, and cope with their disease. Patients commonly seek peer support from online communities, which provide insights on unmet needs and barriers to care. We performed a qualitative analysis of electronic health forums to characterize patient-to-patient conversations about EoE symptoms and the experience of disease. METHODS: We identified three publicly accessible electronic health forums hosting EoE communities. Conversation threads posted between July 2018 and June 2020 were coded using emergent and a priori codes based on the THRIVE conceptual framework of coping with chronic illness. RESULTS: Of 659 threads (4,933 posts) collected over two years, a random sample of 240 threads (30 per 3-month quarter) were selected for analysis. Thematic saturation was reached after 172 threads. Patient experience of EoE was driven by their perspectives in four key domains: (i) perception of EoE as episodic rather than chronic, (ii) treatment choices, (iii) personal definitions of success in the disease, and (iv) views of providers. CONCLUSION: Online health communities are a valuable and unfiltered source of patient perspectives that can be used to understand patient needs and goals. EoE patients interpret their disease as sporadic events and lack reliable sources of knowledge, which may influence how patients prioritize treatment. If providers are to succeed in providing high-quality EoE care, they need to equip themselves with evidence-based knowledge, engage in shared decision making, and look outside of clinical settings to recognize barriers to disease management.

Incomplete Response of Gastroesophageal Reflux Symptoms Poorly Predicts Erosive Esophagitis or Barrett's Esophagus.

BACKGROUND & AIMS: Many patients with symptoms of gastroesophageal reflux disease (GERD) not responding to a proton pump inhibitor (PPI) undergo an upper endoscopy. We hypothesized that an incomplete response to a PPI is not associated with findings of esophageal pathology on endoscopy, and that psychological distress is associated inversely with pathology. METHODS: We enrolled consecutive individuals aged 40 to 79 years with prior heartburn or regurgitation. Logistic regression was used to estimate the effects of incomplete response of GERD symptoms and psychological distress on the odds of finding erosive esophagitis or Barrett's esophagus. RESULTS: A total of 625 patients completed the study. A total of 254 (66.8% of those taking PPI) had GERD symptoms incompletely responsive to a PPI and 352 (56.3%) had severe somatization. An incomplete response to a PPI was associated with psychological distress (P < .001). Erosive esophagitis was found in 148 subjects (23.7%) and Barrett's esophagus in 58 (9.3%). Overall, an incomplete response to a PPI was not found to be associated with these pathologies (odds ratio, 1.17; 95% CI, 0.720-1.91). In contrast, greater psychological distress was associated inversely with erosive esophagitis or Barrett's esophagus (in particular, highest vs lowest tertile somatization: odds ratio, 0.590; 95% CI, 0.365-0.952). CONCLUSIONS: Patients undergoing upper endoscopy frequently have GERD symptoms incompletely responding to a PPI and a high burden of somatization. However, an incomplete response of GERD symptoms is a poor predictor for endoscopic pathology, and should not be relied upon for selecting patients for screening for Barrett's esophagus. Patients with high psychological distress are less likely to have esophageal pathology.

Validation and Comparison of Tools for Selecting Individuals to Screen for Barrett's Esophagus and Early Neoplasia.

BACKGROUND & AIMS: Guidelines suggest endoscopic screening of individuals who are at increased risk for Barrett's esophagus (BE) and esophageal adenocarcinoma. Tools based on clinical factors are available for identifying patients at risk, but only some have been validated. We aimed to compare and validate available tools. METHODS: We performed a prospective study of 1241 patients, ages 40 to 79 years, presenting either for their first esophagogastroduodenoscopy (EGD) or their first endoscopic therapy of early neoplastic BE, from April 2015 through June 2018. We calculated risk scores for 6 previously published tools (the Gerson, Locke, Thrift, Michigan BE pREdiction Tool [M-BERET], Nord-Trøndelag Health Study [HUNT], and Kunzmann tools). We also investigated the accuracy of frequency and duration of gastroesophageal reflux disease (GERD), using data from a randomly selected 50% of patients undergoing their first EGD. We compared the ability of all these tools to discriminate patients with BE and early neoplasia from patients without BE, using findings from endoscopy as the reference standard. RESULTS: BE was detected in 81 of 1152 patients during their first EGD (7.0%). GERD symptoms alone identified patients with BE with an area under the receiver operating characteristic curve (AuROC) of 0.579. All of the tools were more accurate in identifying patients with BE than the frequency and duration of GERD (AuROC for GERD, 0.579 vs range for other tools, 0.660-0.695), and predicted risk correlated well with observed risk (calibration). The AUROCs of the HUNT tool (0.796), the M-BERET (0.773), and the Kunzmann tool (0.763) were comparable in discriminating between patients with early neoplasia (n = 94) vs no BE. Each tool was more accurate in discriminating BE with early neoplasia than GERD frequency and duration alone (AuROC, 0.667; P < .01). CONCLUSIONS: The HUNT, M-BERET, and Kunzmann tools identify patients with BE with AuROC values ranging from 0.665 to 0.695, and discriminate patients with early neoplasia from patients without BE with AuROC values ranging from 0.763 to 0.796. These tools are more accurate than frequency and duration of GERD in identifying individuals at risk for neoplastic BE.

Variability in Practices of Compounding Budesonide for Eosinophilic Esophagitis.

INTRODUCTION: Little is known about the use of compounded steroids for eosinophilic esophagitis (EoE). METHODS: We conducted a telephone survey of all compounding pharmacies in Michigan and queried about practices and costs of compounded budesonide for EoE. RESULTS: Of 68 Michigan pharmacies, 93% responded, and 20 (29%) offer compounded budesonide suspension for EoE. Formulations, dose, and instructions for use varied across pharmacies. The mean cost for a 30-day supply was $74.50. DISCUSSION: Although few compounding pharmacies offer budesonide suspension and there are substantial variations in formulations, this may be a significantly more affordable treatment option for many.

Validation of Tools for Predicting Incident Adenocarcinoma of the Esophagus or Esophagogastric Junction.

INTRODUCTION: Guidelines suggest screening of individuals who are at increased risk of esophageal adenocarcinoma (EAC). Tools for identifying patients at risk of Barrett's esophagus have been validated. Here, we aimed to compare and validate the tools for the primary outcomes of interest: EAC and esophagogastric junction adenocarcinoma (EGJAC). METHODS: Retrospective longitudinal analysis of the Kaiser Permanente Northern California Multiphasic Health Checkup Cohort, a community-based cohort including 206,974 patients enrolled between 1964 and 1973 followed through 2016. Baseline questionnaires and anthropometrics classified predictor variables for each tool and were linked to cancer registry outcomes. Analyses used logistic regression, Cox proportional hazards regression, and Kaplan-Meier survival curves. RESULTS: We identified 168 incident EAC cases and 151 EGJAC cases at a mean of 32 years after enrollment (mean follow-up among controls 26 years). Gastroesophageal reflux disease (GERD) symptoms predicted incident EAC (hazard ratio 2.66; 95% confidence interval 1.01, 7.00), but not EGJAC. The Nord-Trøndelag Health Study tool, Kunzmann tool, and Michigan Barrett's Esophagus pREdiction Tool were more accurate than GERD for predicting EAC, with individuals in the fourth quartile of Kunzmann having 17-fold the risk of those in the 1st quartile (hazard ratio = 16.7, 95% confidence interval = 4.72, 58.8). Each tool also predicted incident EGJAC with smaller magnitudes of effect. DISCUSSION: The study independently validated 4 tools for predicting incident EAC and EGJAC in a large community-based population. The Kunzmann tool appears best calibrated; all appear preferable to using GERD alone for risk stratification. Future studies should determine how best to implement such tools into clinical practice.

Comparative Cost Effectiveness of Reflux-Based and Reflux-Independent Strategies for Barrett's Esophagus Screening.

INTRODUCTION: Minimally invasive tests for Barrett's esophagus (BE) detection have raised the prospect of broader nonreflux-based testing. Cost-effectiveness studies have largely studied men aged 50 years with chronic gastroesophageal reflux disease (GERD) symptoms. We evaluated the comparative cost effectiveness of BE screening tests in GERD-based and GERD-independent testing scenarios. METHODS: Markov modeling was performed in 3 scenarios in 50 years old individuals: (i) White men with chronic GERD (GERD-based); (ii) GERD-independent (all races, men and women), BE prevalence 1.6%; and (iii) GERD-independent, BE prevalence 5%. The simulation compared multiple screening strategies with no screening: sedated endoscopy (sEGD), transnasal endoscopy, swallowable esophageal cell collection devices with biomarkers, and exhaled volatile organic compounds. A hypothetical cohort of 500,000 individuals followed for 40 years using a willingness to pay threshold of $100,000 per quality-adjusted life year (QALY) was simulated. Incremental cost-effectiveness ratios (ICERs) comparing each strategy with no screening and comparing screening strategies with each other were calculated. RESULTS: In both GERD-independent scenarios, most non-sEGD BE screening tests were cost effective. Swallowable esophageal cell collection devices with biomarkers were cost effective (<$35,000/QALY) and were the optimal screening tests in all scenarios. Exhaled volatile organic compounds had the highest ICERs in all scenarios. ICERs were low (<$25,000/QALY) for all tests in the GERD-based scenario, and all non-sEGD tests dominated no screening. ICERs were sensitive to BE prevalence and test costs. DISCUSSION: Minimally invasive nonendoscopic tests may make GERD-independent BE screening cost effective. Participation rates for these strategies need to be studied.