Adjunctive Use of WATS-3D in Symptomatic GERD Patients Increases Detection of Barrett's Esophagus and Dysplasia.

BACKGROUND: Patients with gastroesophageal reflux (GERD) symptoms undergoing screening upper endoscopy for Barrett's esophagus (BE) frequently demonstrate columnar-lined epithelium (CLE), with forceps biopsies (FB) failing to yield intestinal metaplasia (IM). Repeat endoscopy is often necessary. AIM: Assess the yield of IM leading to a diagnosis of BE by the addition of Wide-Area Trans-epithelial Sampling (WATS-3D) to FB in the screening of GERD patients. METHODS: We performed a prospective registry study of GERD patients undergoing screening upper endoscopy. Patients had both WATS-3D and FB. Patients were classified by their Z line appearance: regular, irregular (<1 cm CLE), possible short-segment BE (1-<3cm), and possible long-segment BE (≥3cm). Demographics, IM yield, and dysplasia yield were calculated. Adjunctive yield was defined as cases identified by WATS-3D not detected by FB, divided by cases detected by FB. Clinicians were asked if WATS-3D results impacted patient management. RESULTS: Of 23,933 patients, 6,829(28.5%) met endoscopic criteria for BE. Of these, 2,878(42.1%) had IM identified by either FB or WATS-3D. Among patients fulfilling endoscopic criteria for BE, the adjunctive yield of WATS-3D was 76.5%, and absolute yield was 18.1%. 1,317 patients (19.3%) who fulfilled endoscopic BE criteria had IM detected solely by WATS-3D. Of 240 patients with dysplasia, 107(44.6%) were found solely by WATS-3D. Among patients with positive WATS-3D but negative FB, the care plan changed in 90.7%. CONCLUSION: The addition of WATS-3D to FB in GERD patients being screened for BE resulted in confirmation of BE in an additional 1/5 th of patients. Furthermore, dysplasia diagnoses approximately doubled.

Next-generation endoscopic probe for detection of esophageal dysplasia using combined OCT and angle-resolved low-coherence interferometry.

Angle-resolved low-coherence interferometry (a/LCI) is an optical technique that enables depth-specific measurements of nuclear morphology, with applications to detecting epithelial cancers in various organs. Previous a/LCI setups have been limited by costly fiber-optic components and large footprints. Here, we present a novel a/LCI instrument incorporating a channel for optical coherence tomography (OCT) to provide real-time image guidance. We showcase the system's capabilities by acquiring imaging data from in vivo Barrett's esophagus patients. The main innovation in this geometry lies in implementing a pathlength-matched single-mode fiber array, offering substantial cost savings while preserving signal fidelity. A further innovation is the introduction of a specialized side-viewing probe tailored for esophageal imaging, featuring miniature optics housed in a custom 3D-printed enclosure attached to the tip of the endoscope. The integration of OCT guidance enhances the precision of tissue targeting by providing real-time morphology imaging. This novel device represents a significant advancement in clinical translation of an enhanced screening approach for esophageal precancer, paving the way for more effective early-stage detection and intervention strategies.

Incidence and Prediction of Unrelated Mortality After Successful Endoscopic Eradication Therapy for Barrett's Neoplasia.

BACKGROUND & AIMS: Follow-up (FU) strategies after endoscopic eradication therapy (EET) for Barrett's neoplasia do not consider the risk of mortality from causes other than esophageal adenocarcinoma (EAC). We aimed to evaluate this risk during long-term FU, and to assess whether the Charlson Comorbidity Index (CCI) can predict mortality. METHODS: We included all patients with successful EET from the nationwide Barrett registry in the Netherlands. Data were merged with National Statistics for accurate mortality data. We evaluated annual mortality rates (AMRs, per 1000 person-years) and standardized mortality ratio for other-cause mortality. Performance of the CCI was evaluated by discrimination and calibration. RESULTS: We included 1154 patients with a mean age of 64 years (±9). During median 59 months (p25-p75 37-91; total 6375 person-years), 154 patients (13%) died from other causes than EAC (AMR, 24.1; 95% CI, 20.5-28.2), most commonly non-EAC cancers (n = 58), cardiovascular (n = 31), or pulmonary diseases (n = 26). Four patients died from recurrent EAC (AMR, 0.5; 95% CI, 0.1-1.4). Compared with the general Dutch population, mortality was significantly increased for patients in the lowest 3 age quartiles (ie, age <71 years). Validation of CCI in our population showed good discrimination (Concordance statistic, 0.78; 95% CI, 0.72-0.84) and fair calibration. CONCLUSION: The other-cause mortality risk after successful EET was more than 40 times higher (48; 95% CI, 15-99) than the risk of EAC-related mortality. Our findings reveal that younger post-EET patients exhibit a significantly reduced life expectancy when compared with the general population. Furthermore, they emphasize the strong predictive ability of CCI for long-term mortality after EET. This straightforward scoring system can inform decisions regarding personalized FU, including appropriate cessation timing. (NL7039).

Adherence to prescription proton pump inhibitor therapy amongst individuals diagnosed with Barrett's esophagus.

INTRODUCTION: In the United States, clinical guidelines recommend daily use of proton pump inhibitors (PPIs) amongst individuals diagnosed with Barrett's esophagus to decrease the risk of progression to dysplasia and neoplasia. Prior studies documenting adherence to PPIs in this population have not characterized heterogeneity in adherence patterns. Factors that may relate to adherence are incompletely described. METHODS: We used administrative claims data from the Merative MarketScan Commercial Claims and Encounters database to conduct a retrospective study of adherence to prescription PPIs. A cohort of individuals diagnosed with incident Barrett's esophagus between 2010 and 2019 was identified. Group-based trajectory models were generated to detect longitudinal adherence subgroups. RESULTS: 79 701 individuals with a new diagnosis of Barrett's esophagus were identified. The best fitting model detected five distinct adherence trajectory groups: consistently high (44% of the population), moderate decline (18%), slow decline (12%), rapid decline (10%), and decline-then-increase (16%). Compared to individuals starting PPIs, those already using PPIs were less likely to have a declining adherence pattern. Other factors associated with membership in a declining adherence group included (but were not limited to): female sex, having a past diagnosis of anxiety or depression, and having one or more emergency department visits in the past year. DISCUSSION: Using an exploratory method, we detected heterogeneity in adherence to prescription PPIs. Less than half of individuals were classified into the consistently high adherence group, suggesting that many individuals with Barrett's esophagus receive inadequate pharmacologic therapy.

LIQUID NITROGEN SPRAY CRYOTHERAPY FOR ERADICATION OF DYSPLASTIC BARRETT'S ESOPHAGUS: RESULTS FROM A MULTICENTER PROSPECTIVE REGISTRY.

BACKGROUND AND AIMS: Liquid nitrogen spray cryotherapy (SCT) is an alternative to radiofrequency ablation (RFA) for eradication of dysplastic Barrett's esophagus (BE). We aimed to assess the safety, efficacy, and durability of SCT in a multicenter U.S. registry. METHODS: This is a multicenter prospective registry of adults with BE treated with truFreeze Spray Cryotherapy (4 community and 11 academic sites, 2013-2022). Complete eradication of intestinal metaplasia (CEIM) and dysplasia (CED) were assessed in BE with dysplasia or intramucosal adenocarcinoma (IMC). Kaplan-Meier analysis of CEIM and CED was performed. Hazard ratios for CEIM stratified by baseline risk factors were calculated. RESULTS: Among 138 subjects, with LGD (24%), HGD (49%) and IMC (27%), 34% received prior RFA therapy. Subjects received a median of 2 SCT sessions. Adverse events were uncommon, with 5.5% reporting strictures and 0.7% a perforation. Rates of CEIM and CED, respectively, were 66% and 84% after two years, and 67% and 92% after three years. In RFA-naive patients, CEIM was 77% and CED was 96% at 3 years. Increasing BE length (adjusted hazard ratio [95% CI]:0.90 [0.83-0.96] per cm) and prior treatment with RFA (0.39 [0.22-0.69]) were associated with a lower rate of CEIM. Recurrence occurred in 8.8% (n=6) at a mean follow-up of 2.5 years after CEIM. CONCLUSION: In this largest reported prospective cohort, liquid nitrogen SCT was safe and effective for treatment of dysplastic and neoplastic BE. Response was lower in those with prior failed RFA; in that cohort approximately 50% attained CEIM at 3 years.

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.

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.

A Randomized Controlled Study on Clinical Adherence to Evidence-Based Guidelines in the Management of Simulated Patients With Barrett's Esophagus and the Clinical Utility of a Tissue Systems Pathology Test: Results From Q-TAB.

INTRODUCTION: Barrett's esophagus (BE) is a precursor to esophageal adenocarcinoma. Physicians infrequently adhere to guidelines for managing BE, leading to either reduced detection of dysplasia or inappropriate re-evaluation. METHODS: We conducted a three-arm randomized controlled trial with 2 intervention arms to determine the impact of a tissue systems pathology (TSP-9) test on the adherence to evidence-based guidelines for simulated patients with BE. Intervention 1 received TSP-9 results, and intervention 2 had the option to order TSP-9 results. We collected data from 259 practicing gastroenterologists and gastrointestinal surgeons who evaluated and made management decisions for 3 types of simulated patients with BE: nondysplastic BE, indefinite for dysplasia, and low-grade dysplasia. RESULTS: Intervention 1 was significantly more likely to correctly assess risk of progression to high-grade dysplasia/esophageal adenocarcinoma and offer treatment in accordance with US society guidelines compared with the control group (+6.9%, 95% confidence interval +1.4% to +12.3%). There was no significant difference in ordering guideline-recommended endoscopic eradication therapy. However, for cases requiring annual endoscopic surveillance, we found significant improvement in adherence for intervention 1, with a difference-in-difference of +18.5% ( P = 0.019). Intervention 2 ordered the TSP-9 test in 21.9% of their cases. Those who ordered the test performed similarly to intervention 1; those who did not, performed similarly to the control group. DISCUSSION: The TSP-9 test optimized adherence to clinical guidelines for surveillance and treatment of both patients with BE at high and low risk of disease progression. Use of the TSP-9 test can enable physicians to make risk-aligned management decisions, leading to improved patient health outcomes.

Significant Reduction in the Diagnosis of Barrett's Esophagus and Related Dysplasia During the COVID-19 Pandemic.

INTRODUCTION: The coronavirus disease 19 (COVID-19) pandemic disrupted endoscopy practices, creating unprecedented decreases in cancer screening and surveillance services. We aimed to assess the impact of the pandemic on the proportion of patients diagnosed with Barrett's esophagus (BE) and BE-related dysplasia and adherence to established quality indicators. METHODS: Data from all esophagogastroduodenoscopies in the GI Quality Improvement Consortium, a national repository of matched endoscopy and pathology data, were analyzed from January 2018 to December 2022. Four cohorts were created based on procedure date and COVID-19 data: pre-pandemic (January 2018 to February 2020), pandemic-phase I (March 2020 to July 2020), pandemic-phase II (August 2020 to May 2021), and pandemic-phase III (June 2021 to December 2022). Observed and expected number of BE and BE-related dysplasia cases per month and adherence to the Seattle biopsy protocol and recommended surveillance intervals for nondysplastic BE (NDBE) were evaluated. RESULTS: Among 2,446,857 esophagogastroduodenoscopies performed during the study period, 104,124 (4.3%) had pathology-confirmed BE. The histologic distribution was 87.4% NDBE, 1.8% low-grade dysplasia, 2.4% indefinite for dysplasia, and 1.4% high-grade dysplasia. The number of monthly BE (-47.9% pandemic-phase I, -21.5% pandemic-phase II, and -19.0% pandemic-phase III) and BE-related dysplasia (high-grade dysplasia: 41.2%, -27.7%, and -19.0%; low-grade dysplasia: 49.1%, -35.3%, and -26.5%; any dysplasia: 46.7%, -32.3%, and -27.9%) diagnoses were significantly reduced during the pandemic phases compared with pre-pandemic data. Adherence rates to the Seattle protocol and recommended surveillance intervals for NDBE did not decline during the pandemic. DISCUSSION: There was a significant decline in the number of BE and BE-related dysplasia diagnoses during the COVID-19 pandemic, with an approximately 50% reduction in the number of cases of dysplasia diagnosed in the early pandemic. The absence of a compensatory increase in diagnoses in the pandemic-phase II and III periods may result in deleterious downstream effects on esophageal adenocarcinoma morbidity and mortality.

Gastrointestinal-isolated Distress is Common in Alpha-gal Allergic Patients on Mammalian Meat Challenge.

BACKGROUND AND AIMS: Alpha-gal allergy causes a delayed reaction to mammalian meats and has been reported worldwide. Patients with the allergy may present with isolated gastrointestinal (GI) symptoms, but this phenotype is poorly understood. METHODS: We pooled and analyzed symptoms and demographics of patients from two prospective cohorts of patients with a diagnosis of alpha-gal allergy who reacted after eating mammalian meat under observation. We compared the characteristics of patients who demonstrated GI-isolated symptoms on a challenge with those who exhibited symptoms outside the GI tract (skin, respiratory, and circulatory). RESULTS: Among the 91 children and adult alpha-gal allergic patients who exhibited symptoms after oral challenge with mammalian meat, 72.5% experienced GI distress with one or more GI symptoms, which was the most frequent class of symptoms, compared with skin changes in 57.1% and respiratory distress in 5.5%. The most common GI symptoms were abdominal pain (71%) and vomiting (22.0%). GI-isolated symptoms occurred in 37 patients (40.7%) who reacted, and those patients reacted more quickly than patients who exhibited systemic symptoms (median onset of symptoms in GI-isolated group 90 min vs 120 min) and were more likely to be children than adults (relative risk=1.94, 95% CI: 1.04-3.63). CONCLUSIONS: Isolated-GI distress occurred in 4 in every 10 alpha-gal allergic individuals who developed symptoms on oral food challenge with mammalian meat. Alpha-gal allergic patients, particularly children, may exhibit GI distress alone, and adult and pediatric gastroenterologists should be aware of the diagnosis and management of the allergy.

Patients With Esophageal Adenocarcinoma With Prior Gastroesophageal Reflux Disease Symptoms Are Similar to Those Without Gastroesophageal Reflux Disease: A Cross-Sectional Study.

INTRODUCTION: A substantial proportion of patients with esophageal adenocarcinoma (EAC) do not report gastroesophageal reflux disease (GERD) symptoms. This study aimed to compare the risk factor profiles and cancer stage at presentation of patients with EAC with and without prior GERD. METHODS: In this retrospective cross-sectional study, patients with EAC were divided into 2 cohorts: (i) EAC with prior GERD: patients who reported typical GERD symptoms (heartburn or regurgitation) ≥1 year before cancer diagnosis and (ii) EAC without prior GERD: patients who did not report prior GERD symptoms or reported symptoms within 1 year of their cancer diagnosis. Baseline demographics, risk factors, and cancer stage at presentation were compared between the 2 cohorts. In addition, the distribution of patients based on numbers of BE/EAC-associated risk factors (1, 2, 3, 4, and 5 or more) was examined in the symptomatic and asymptomatic cohorts. RESULTS: Over 13 years, 388 patients with EAC with prior GERD and 245 patients with EAC without prior GERD were recruited. Both groups had similar baseline demographics and risk factors, but patients with EAC with prior GERD were more likely to have a history of BE. Asymptomatic patients had more advanced disease. Patients with 3 or more BE/EAC-related risk factors formed the largest proportion of patients in both the symptomatic and asymptomatic cohorts. DISCUSSION: Patients with EAC with and without prior GERD symptoms are phenotypically similar, suggesting that BE screening efforts to prevent or detect early EAC should not be restricted to just those with GERD.

Magnitude and Time-Trends of Post-Endoscopy Esophageal Adenocarcinoma and Post-Endoscopy Esophageal Neoplasia in a Population-Based Cohort Study: The Nordic Barrett's Esophagus Study.

BACKGROUND & AIMS: Post-endoscopy esophageal adenocarcinoma (PEEC) and post-endoscopy esophageal neoplasia (PEEN) undermine early cancer detection in Barrett's esophagus (BE). We aimed to assess the magnitude and conduct time-trend analysis of PEEC and PEEN among patients with newly diagnosed BE. METHODS: This population-based cohort study was conducted in Denmark, Finland, and Sweden between 2006 and 2020 and included 20,588 patients with newly diagnosed BE. PEEC and PEEN were defined as esophageal adenocarcinoma (EAC) or high-grade dysplasia (HGD)/EAC, respectively, diagnosed 30-365 days from BE diagnosis (index endoscopy). HGD/EAC diagnosed from 0-29 days and HGD/EAC diagnosed >365 days from BE diagnosis (incident HGD/EAC) were assessed. Patients were followed up until HGD/EAC, death, or end of study period. Incidence rates (IR) per 100,000 person-years with 95% confidence interval (95% CI) were calculated using Poisson regression. RESULTS: Among 293 patients diagnosed with EAC, 69 (23.5%) were categorized as PEEC, 43 (14.7%) as index EAC, and 181 (61.8%) as incident EAC. The IRs/100,000 person-years for PEEC and incident EAC were 392 (95% CI, 309-496), and 208 (95% CI, 180-241), respectively. Among 279 patients diagnosed with HGD/EAC (Sweden only), 17.2% were categorized as PEEN, 14.6% as index HGD/EAC, and 68.1% as incident HGD/EAC. IRs/100,000 person-years for PEEN, and incident HGD/EAC were 421 (95% CI, 317-558), and 285 (95% CI, 247-328), respectively. Sensitivity analyses that varied time interval for occurrence of PEEC/PEEN demonstrated similar results. A time-trend analysis for IRs demonstrated rising incidence rates of PEEC/PEEN. CONCLUSIONS: Almost a quarter of all EACs are detected within a year after an ostensibly negative upper endoscopy in patients with newly diagnosed BE. Interventions to improve detection may reduce PEEC/PEEN rates.

NON-ENDOSCOPIC ESOPHAGEAL SAMPLING DEVICE AND BIOMARKER PANEL FOR DETECTION OF BARRETT'S ESOPHAGUS (BE) AND ESOPHAGEAL ADENOCARCINOMA (EAC).

BACKGROUND: We previously reported an encapsulated balloon (EsoCheck TM , EC), which selectively samples the distal esophagus, that coupled with a two methylated DNA biomarker panel (EsoGuard TM , EG), detected Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), with a sensitivity and specificity of 90.3% and 91.7%, respectively. This previous study utilized frozen EC samples. AIM: To assess a next generation EC sampling device and EG assay that utilizes a room temperature sample preservative to enable office-based testing. METHODS: Cases with nondysplastic (ND) and dysplastic (indefinite=IND, low grade dysplasia = LGD, high grade dysplasia = HGD) BE, EAC, junctional adenocarcinoma (JAC) and controls with no intestinal metaplasia (IM) were included. Nurses or physician assistants at six institutions, who were trained in EC administration, delivered the encapsulated balloon per orally and inflated it in the stomach. The inflated balloon was pulled back to sample 5 cm of the distal esophagus, then deflated and retracted into the EC capsule to prevent sample contamination from proximal esophagus. Nextgen EG sequencing assays performed on bisulfite-treated DNA extracted from EC samples determined levels of methylated Vimentin (mVIM) and methylated Cyclin A1 (mCCNA1) in a CLIA-certified laboratory, blinded to patients' phenotypes. RESULTS: A total of 243 evaluable patients - 88 cases (median age 68 years, 78% men, 92% white) and 155 controls (median age 57 years, 41% men, 88% white) - underwent adequate EC sampling. Mean time for EC sampling was just over 3 minutes. The cases included 31 NDBE, 16 IND/LGD, 23 HGD, and 18 EAC/JAC. Thirty-seven (53%) of the non-dysplastic and dysplastic BE cases were short-segment BE (SSBE; < 3 cm). Overall sensitivity for detecting all cases was 85% (95% CI= 0.78-0.93) and specificity was 85% (95% CI=0.79-0.90). Sensitivity for NDBE was 84% (n=37). The EC/EG test detected 100% of cancers. CONCLUSION: The next-generation EC/EG technology has been both successfully updated to incorporate a room temperature sample collection preservative and successfully implemented in a CLIA certified laboratory. When performed by trained personnel, EC/EG detects non-dysplastic BE, dysplastic BE, and cancer with high sensitivity and specificity, replicating the operating characteristics of the initial pilot study of this technology. Future applications utilizing EC/EG to screen broader populations at risk for developing cancer are proposed. SIGNIFICANCE: This multi-center study demonstrates the successful performance of a commercially available clinically implementable non-endoscopic screening test for BE in the U.S., as recommended in the most recent ACG Guideline and AGA Clinical Update. It transitions and validates a prior academic laboratory-based study of frozen research samples over to a CLIA laboratory, one that also integrates a clinically practical room temperature method for sample acquisition and storage, enabling office-based screening.

Alpha-Gal Sensitization in a US Screening Population Is Not Associated With a Decreased Meat Intake or Gastrointestinal Symptoms.

INTRODUCTION: Patients with alpha-gal syndrome, a delayed reaction to mammalian meat, can present with isolated gastrointestinal (GI) symptoms. We aimed to estimate the frequency of alpha-gal sensitization in a Southeastern US population and determine the association between sensitization and mammalian product dietary intake or GI symptoms. METHODS: We performed a cross-sectional study of participants who underwent a screening colonoscopy at our center between 2013 and 2015. We quantified serum alpha-gal immunoglobulin E antibodies in participants who were prospectively enrolled at screening colonoscopy and compared diet intake and lower GI symptoms reported in standardized questionnaires among those with elevated versus no alpha-gal IgE antibodies. RESULTS: Alpha-gal IgE antibodies were common-31.4% of screening colonoscopy participants (127 of 404) had elevated serum alpha-gal IgE >0.1 kU/L. Alpha-gal-sensitized participants endorsed similar rates of abdominal pain compared with those without alpha-gal antibodies (33% vs 38%, adjusted odds ratio 0.9, 95% confidence interval 0.7-1.3). Mammalian meat consumption did not differ based on alpha-gal sensitization status (average 1.43 servings/d in sensitized subjects vs 1.50 in alpha-gal IgE-negative subjects, P = 0.9). Alpha-gal-sensitized participants with levels ≥10 (n = 21) were overrepresented in the lowest quartiles of mammalian meat consumption, but not among those with GI symptoms in general. Participants with high alpha-gal antibody levels >2 kU/L (n = 45) or ≥10 U/L (n = 21) did not have a reduced mean daily mammalian meat intake compared with seronegative people. DISCUSSION: Elevated alpha-gal IgE antibodies were common and not associated with a reduced mammalian meat intake, abdominal pain, or diarrhea. Seropositivity did not predict symptomatic alpha-gal sensitization in this general screening population. Other host factors likely contribute to the phenotypic expression of alpha-gal syndrome.

Trimodality Therapy vs Definitive Chemoradiation in Older Adults With Locally Advanced Esophageal Cancer.

BACKGROUND: The comparative effectiveness of trimodality therapy vs definitive chemoradiation for treating locally advanced esophageal cancer in older adults is uncertain. Existing trials lack generalizability to older adults, a population with heightened frailty. We sought to emulate a hypothetical trial comparing these treatments using real-world data. METHODS: A cohort of adults aged 66-79 years diagnosed with locally advanced esophageal cancer between 2004 and 2017 was identified in the Surveillance Epidemiology and End Results-Medicare database. The clone-censor-weight method was leveraged to eliminate time-related biases when comparing outcomes between treatments. Outcomes included overall mortality, esophageal cancer-specific mortality, functional adverse events, and healthy days at home. RESULTS: A total of 1240 individuals with adenocarcinomas and 661 with squamous cell carcinomas were identified. For adenocarcinomas, the standardized 5-year risk of mortality was 73.4% for trimodality therapy and 83.8% for definitive chemoradiation (relative risk [RR] = 0.88, 95% confidence interval [CI] = 0.82 to 0.95). Trimodality therapy was associated with mortality risk reduction for squamous cell carcinomas (RR = 0.87, 95% CI = 0.70 to 1.01). The 1-year incidence of functional adverse events was higher in the trimodality group (adenocarcinomas RR = 1.40, 95% CI = 1.22 to 1.65; squamous cell carcinomas RR = 1.21, 95% CI = 1.00 to 1.49). Over 5 years, trimodality therapy was associated with 160 (95% CI = 67 to 229) and 177 (95% CI = 51 to 313) additional home days in individuals with adenocarcinomas and squamous cell carcinomas, respectively. CONCLUSIONS: Compared with definitive chemoradiation, trimodality therapy was associated with reduced mortality but increased risk of function-related adverse events. Discussing these tradeoffs may help optimize care plans.

Management of Dysplastic Barrett's Esophagus and Early Esophageal Adenocarcinoma.

While patients with Barrett's esophagus without dysplasia may benefit from endoscopic surveillance, those with low-grade dysplasia may be managed with either endoscopic surveillance or endoscopic eradication. Patients with Barrett's esophagus with high-grade dysplasia and/or intramucosal adenocarcinoma will generally require endoscopic eradication therapy. The management of Barrett's esophagus with dysplasia and early esophageal adenocarcinoma is predominantly endoscopic, with multiple effective methods available for the resection of raised neoplasia and ablation of flat neoplasia. High-dose proton-pump inhibitor therapy is advised during the treatment of Barrett's esophagus with dysplasia and early esophageal adenocarcinoma. After the endoscopic eradication of Barrett's esophagus and associated neoplasia, surveillance is required for the diagnosis and retreatment of recurrence or progression.