Barrett's esophagus is the known precursor to esophageal adenocarcinoma (EAC), a cancer with poor prognosis. While endoscopic surveillance detects early dysplasia and prevents progression, most Barrett's esophagus patients do not progress to EAC, leading to invasive and costly surveillance. This study aimed to identify cost-effective endoscopic surveillance strategies by risk stratifying patients based on Barrett's esophagus segment length and sex. A Markov cohort model was developed to simulate the natural history of Barrett's esophagus to EAC. The model assessed 85 surveillance strategies and varied endoscopy intervals from 2 to 10 years for nondysplastic Barrett's esophagus and 6-12 months for dysplasia. Risk stratification was based on segment length (≤ 2 and ≤ 3 cm) and sex. Costs, utilities and transition probabilities were derived from published literature and clinical databases. Deterministic and probabilistic sensitivity analyses were performed, and cost-effectiveness was evaluated from a third-party payer perspective using a threshold of AU$50 000/QALY (2023 US dollars 35 945/QALY). The most cost-effective strategy was biennial surveillance for long-segment BE (> 2 cm) and 12-month surveillance for LGD, excluding surveillance in low-risk patients (ICER US$23 737/QALY). Risk-based surveillance consistently outperformed nonstratified strategies. Sensitivity analyses confirmed the robustness of the model, with key drivers being transition rates and endoscopy costs. We identified cost-effective risk-stratified endoscopic surveillance strategies for Barrett's esophagus, particularly when excluding low-risk patients. Tailored risk-guided surveillance strategies could improve resource allocation and clinical outcomes in managing Barrett's esophagus. The conserved resources can then be utilized to identify high-risk individuals in the community.

BACKGROUNDDespite societal guidelines recommending targeted screening for Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) in individuals with gastroesophageal reflux symptoms (GERS), screening adherence is suboptimal. Current screening approaches fail to identify individuals not seeking medical consultation for GERS or whose GERS are managed with ‘over-the-counter’ (OTC) acid suppressant therapies.AIMTo assess patients’ self-management and help-seeking behavior for GERS.METHODSThis cross-sectional study collected data from the Dutch general population aged 18-75 years between January and April 2023 using a web-based survey. The survey included questions regarding self-management (e.g., use of acid suppressant therapy with or without prescription) and help-seeking behavior (e.g., consulting a primary care provider) for GERS. Simple random sampling was performed to select individuals within the target age group. In total, 18156 randomly selected individuals were invited to participate. The study protocol was registered in ClinicalTrials.gov (identifier: NCT05689918).RESULTSOf the 18156 invited individuals, 3214 participants (17.7%) completed the survey, of which 1572 participants (48.9%) reported GERS. Of these, 904 participants (57.5%) had never consulted a primary care provider for these symptoms, of which 331 participants (36.6%) reported taking OTC acid suppressant therapy in the past six months and 100 participants (11.1%) fulfilled the screening criteria for BE and EAC according to the European Society of Gastrointestinal Endoscopy Guideline.CONCLUSIONThe population fulfilling the screening criteria for BE and EAC is incompletely identified, suggesting potential underutilization of medical consultation. Raising public awareness of GERS as a risk factor for EAC is needed.

Barrett's esophagus is the only known precursor lesion to esophageal adenocarcinoma (EAC). Barrett's esophagus and EAC are less common in African Americans than in non-Hispanic Whites. Studies in European populations have identified Barrett's esophagus-associated risk loci; however, none have examined loci in African Americans cohorts. We conducted a case-control targeted replication study to investigate previously identified Barrett's esophagus risk loci in an African Americans cohort in the All of Us (AoU) Research Program. We abstracted phenomic and genomic data from 108 African Americans with Barrett's esophagus and 778 African Americans controls in the AoU database. We examined 16 single-nucleotide polymorphisms (SNPs) identified in individuals of European origin in the largest Barrett's esophagus genome-wide association study to date. We conducted a logistic regression, adjusting for age, sex, and global ancestry, to assess associations between SNPs and Barrett's esophagus/control status. Of 16 SNPs examined, logistic regression analysis showed three SNPs (rs42202, rs62217, and rs848092) were associated with Barrett's esophagus risk at Bonferroni-adjusted significance (P < 3.1e-3) and in the same direction as previously reported. One SNP, rs2701111, met significance but showed a discordant association with Barrett's esophagus in African Americans. The association with the remaining 12 SNPs was not replicated. Effect sizes were generally larger for each SNP in our African Americans cohort. This study evaluated 16 Barrett's esophagus-associated SNPs in African Americans and confirmed associations for only three Barrett's esophagus-associated variants shared across populations. The nonreplication of most loci and differences in association patterns suggest distinct genetic factors influence Barrett's esophagus in admixed populations. These findings underscore the need for discovery and replication in diverse populations.

The aim of this study was to perform a detailed clinical and pathologic analysis of biopsies from 180 BE patients with the goal of understanding the clinical significance and outcome of patients diagnosed with crypt dysplasia (CD). Biopsies from 58 progressors and 122 nonprogressors (372 biopsies) were graded by 3 gastrointestinal pathologists. A consensus biopsy diagnosis (agreement by ≥2 pathologists) was used for outcome analysis. The overall diagnostic agreement among all 3 observers was high (0.75) and was observed in 83.9% cases, with a moderate level of agreement (0.44) noted for CD. BE progressors had a significantly higher proportion of index biopsies with CD (17% vs. 2%) and LGD (9% vs. 0%; overall P<0.0001) compared with nonprogressors. Compared with an index consensus biopsy diagnosis of NDBE, a consensus biopsy diagnosis of IND, CD, and LGD had significantly increased odds of developing HGD/EAC by univariable (OR: 4.05; P<0.0001) as well as multivariable analysis (OR: 10.3; P=0.01). Furthermore, Kaplan-Meier analysis showed that patients diagnosed with CD or LGD on an index biopsy had a higher probability of developing HGD/EAC than those with NDBE (P<0.0001), and the timeline for progression among patients with CD was found to be intermediate between those diagnosed with NDBE and LGD. BE patients with an index biopsy diagnosis of CD are more likely to develop HGD/EAC compared with those without dysplasia, and these patients may benefit from surveillance and management strategies, similar to LGD.

Endoscopic prediction of depth of invasion in superficial Barrett's esophageal adenocarcinoma (s-BEA) is important for treatment selection. This study aimed to evaluate the endoscopic and histopathological characteristics in s-BEA demonstrating submucosal invasion. We retrospectively reviewed 105 tumors from 97 patients, diagnosed endoscopically and pathologically with s-BEA in short-segment Barrett's esophagus (60 lesions in 60 patients) and long-segment Barrett's esophagus (45 lesions in 37 patients); 105s-BEA lesions were classified into 60 intramucosal and 45 submucosal tumors. We compared the clinicopathological and endoscopic characteristics of these tumors. A multivariate analysis was conducted to predict submucosal invasion based on pretreatment endoscopic and histopathological findings. The presence of the poorly differentiated component (PDC) was then assessed histologically in both pretreatment biopsy specimens (biopsy-PDC) and resected specimens. Compared to intramucosal tumors, submucosal tumors demonstrated significantly higher frequency of the following features: biopsy-PDC (21/45, 46.7%; versus 1/60, 1.7%; odds ratio = 24.9), complex macroscopic type (33/45, 73.3%; versus 15/60, 25.0%; odds ratio = 6.26), and tumor diameter > 20mm (31/45, 68.9%; versus 13/60, 21.7%; odds ratio = 7.63). In 20 submucosal tumors with biopsy-PDC, the invasion at the biopsy site showed PDC extended to the submucosa in 95.0% (19/20) and was limited to the mucosa in 5.0% (1/20) cases. We showed biopsy-PDC, tumor diameter greater than 20mm, and complex macroscopic type independently predict submucosal invasion in Barrett's esophageal adenocarcinoma. Biopsy-PDC may predict submucosal cancer and submucosal invasion at the biopsy site more reliably, independent of endoscopic findings.

The diagnosis of Barrett's esophagus (BE) requires identification of goblet cells in esophageal columnar-lined epithelium. Forceps biopsies (FB) may miss goblet cells due to sampling error. Additionally, pathologists may misidentify distended pseudo-goblet cells as true goblet cells. CDX2 and MUC2 are molecules involved in BE pathogenesis. To assess the utility of CDX2 and MUC2 immunohistochemistry in the diagnosis of BE. We performed a prospective, community-based registry study of GERD patients undergoing endoscopy for BE screening. All patients underwent both FB and WATS3D. CDX2 and MUC2 immunohistochemistry were performed on WATS3D samples. We assessed concordance between CDX2 and MUC2 staining and goblet cells, on both WATS3D and FB. Operating characteristics of FB for diagnosing BE were calculated using MUC2 positivity and goblet cells on WATS3D as the gold standard. Of 35,265 patients enrolled, 11,040 (31.3%) met endoscopic criteria for BE. Of these, 8,464 (76.7%) were CDX2+ and 3,563 (32.3%) were MUC2+. Whereas there was almost perfect concordance between MUC2 positivity and goblet cells on WATS3D, only 65.4% of patients with goblet cells on FB were MUC2+ on WATS3D. When using MUC2+ and goblet cells on WATS3D as the reference standard, FB diagnosed BE with sensitivity of 46.3%, specificity 88.3%, PPV 65.4%, and NPV 77.5%. MUC2 immunohistochemistry may be more sensitive and specific for diagnosing BE than goblet cells by FB. FB misses approximately half of BE when using MUC2/WATS3D as an alternative gold standard. The addition of MUC2 immunohistochemistry may aid in the recognition of BE.

Epidemiology of Barrett's Esophagus and Esophageal Adenocarcinoma.

Indefinite for dysplasia in Barrett's esophagus carries substantial risk for prevalent and incident neoplasia: updated outcomes and long-term follow-up.

Pathogenesis of Barrett's Esophagus: Evolving and Emerging Mechanisms.

The incidence of esophageal adenocarcinoma (EAC) arising in patients with long-segment Barrett's esophagus (LSBE) in Japan remains to be elucidated. This study aims to investigate the incidence of EAC in Japanese LSBE cases. This is a multicenter prospective cohort study involving 32 hospitals throughout Japan. Consecutive patients with Barrett's esophagus with a maximal length of ≥ 3 cm were prospectively enrolled. The study was initiated in June 2011, and the eligible cases were scheduled to undergo subsequent annual endoscopies for 10 years, concluding in December 2021. The cancer incidence was calculated with 95% confidence intervals and expressed as %/year of follow-up. The initial registry comprised 343 participants. After excluding 16 cases with prevalent EAC and 60 cases with < 1 year of follow-up, a total of 267 cases with LSBE were followed up for 1-10 years (58.0 ± 35.5 months), making the total patient-years 1290.4. During the observation period, 13 new EACs were identified, leading to an estimated EAC incidence of 1.01 (0.57-1.73)%/year. All the incident EAC cases were diagnosed as early cancers. Individuals who developed EAC demonstrated a higher prevalence of ever smoking (76.9% vs. 33.5%, p = 0.002) compared to those who did not. This prospective, 10-year follow-up study revealed a substantial EAC incidence in Japanese LSBE cases, 1.01 (0.57-1.73)%/year, similar to values reported in Western countries. This result is a significant indicator for developing effective endoscopy surveillance for Japanese LSBE. UMIN000016043.

ABSTRACT Russell body esophagitis (RBE) is a rare disease characterized by accumulation of Russell bodies (eosinophilic immunoglobulin inclusions) within plasma cells leading to esophageal inflammation. Fewer than 10 cases have been reported, and most are associated with chronic gastroesophageal reflux disease or Barrett's esophagus. We present a case of RBE in a 36-year-old woman with untreated human immunodeficiency virus at acquired immunodeficiency syndrome stage with esophageal candidiasis. To our knowledge, this represents the second RBE case report not associated with Barrett's esophagus. This report demonstrates the association of RBE with chronic inflammation and immunosuppression and contributes to the sparse literature on this rare condition.

Radiofrequency Ablation and Cryotherapy for Dysplastic Barrett's Esophagus.

Background/Objectives: Barrett's esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC), and neoadjuvant chemoradiation therapy (NCRT) is commonly used in the treatment of EAC. However, the impact of NCRT on non-tumorous BE and dysplasia is poorly understood. Our study aims to evaluate the effects of NCRT on BE segment length and dysplasia in patients undergoing esophagectomy for EAC. Methods: This multicenter, retrospective cohort study includes EAC patients who underwent esophagectomy with or without NCRT between 2014 and 2020. Patients with histologically confirmed BE and dysplasia (low- or high-grade) were analyzed. Preoperative and postoperative pathology were compared to assess BE regression, dysplastic changes, and segment length. Statistical analyses included chi-square and t-tests, with p < 0.05 considered significant. Results: Of 101 patients who were diagnosed with EAC, 28 patients were found to have BE, with 18 receiving NCRT in addition to surgery and 10 undergoing surgery alone. The NCRT group showed significantly higher BE regression than the control group (77.8% versus 10%, p < 0.001). Regression of dysplasia occurred in 66.7% of the NCRT group versus 20% of the control group (p = 0.079) and residual dysplasia was lower in the NCRT group (33.3%) compared to the control group (80%) (p = 0.018). Conclusions: NCRT significantly reduces BE and dysplasia, suggesting it may improve surgical outcomes by minimizing residual disease. These findings support the potential of NCRT to enhance surgical precision in EAC treatment, though further research is needed to explore underlying mechanisms and refine treatment strategies.

Barrett's Esophagus in Patients with Gastroesophageal Reflux Disease: A Narrative Review of Current Evidence

Esophageal adenocarcinoma (EAC) has seen a dramatic rise in incidence in developed countries over the past three decades. Early detection of its precursors—gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and high-grade dysplasia (HGD) is critical for cancer prevention. This study presents the development and validation of a novel liquid biopsy assay based on circulating microbial DNA (cmDNA) for the early detection of EAC and HGD. Using metagenomic sequencing, we identified significant differences in microbial diversity and composition between EAC and HGD patients, as well as between BE and GERD patients. A total of 46 microbial candidates in tissue and 419 in serum were upregulated in EAC & HGD, with 11 consistently elevated in both sample types. Following qRT-PCR validation and LASSO regression, a 6-marker cmDNA panel was selected. This signature was incorporated into a diagnostic model trained with the XGBoost algorithm, achieving an AUC of 0.93 in the training cohort (52 HGD & EAC cases vs. 54 BE & GERD controls). Importantly, the model demonstrated robust performance in an independent testing cohort (23 HGD & EAC cases vs. 22 BE & GERD controls), yielding AUCs of 0.91 for EAC and 0.88 for HGD. These findings highlight the diagnostic potential of cmDNA-based profiling and support its utility as a minimally invasive, accurate, and generalizable tool for early detection of esophageal adenocarcinoma.

Accurate identification of dysplasia in Barrett's esophagus (BE) remains a challenge. Advanced optical imaging techniques may allow for better localization of dysplasia in BE. Here, we have assessed the potential clinical utility of a previously described multimodal imaging probe combining optical coherence tomography (OCT) with angle-resolved low coherence interferometry (a/LCI) to prospectively identify dysplasia in BE. Imaging was conducted on 37 patients undergoing endoscopic surveillance of BE, yielding co-registered biopsies of 50 esophageal sites. The a/LCI nuclear morphology data were compared to a previous decision line to prospectively predict dysplasia, demonstrating 100% sensitivity, 93% specificity, and 94% overall accuracy. The NPV was 100%, comparable to previous a/LCI studies. The addition of OCT imaging markedly improved PPV and specificity, compared to previous studies with a/LCI alone, illustrating the clinical utility of the combined platform. These findings suggest that combining OCT and a/LCI enables better detection of dysplasia by providing better guidance.

Esophageal cancer remains a global health burden with poor survival, largely due to late diagnosis. The two main subtypes-esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC)-differ in their epidemiology, risk factors, and geographic distribution, highlighting the importance of region-specific screening. In areas with a high incidence of ESCC, population-based endoscopic screening has improved early detection and outcomes. In contrast, in Western countries where EAC predominates, targeted screening for Barrett's esophagus (BE) offers the most practical approach. Advances in high-definition endoscopy, virtual chromoendoscopy, and minimally invasive resection have enhanced diagnostic precision and treatment efficacy. At the same time, novel nonendoscopic methods such as swallowable devices, biomarker assays, and artificial intelligence-assisted imaging are reshaping screening paradigms. This review outlines current and emerging strategies for early detection of ESCC and EAC, emphasizing technological innovation and its potential to improve global outcomes.

Visceral obesity is a recognized risk factor for Barrett's esophagus (BE). Circulating exosomal mirnas have been identified as potential biomarkers of BE. The aim of this study was to elucidate the characteristics of plasma exosomal miRNA expression in BE patients with or without visceral obesity and to explore its potential regulatory mechanisms in the pathogenesis of the disease. From June 1, 2017 to August 31, 2020, healthy people and BE patients were recruited at center and divided into four groups: Barrett's esophagus patients with visceral obesity (VOBE), Barrett's esophagus patients (BE), visceral obese controls (VOC), and healthy controls (HC).Serum samples were collected after approval by the Ethics Committee, exosomes were isolated by ultrafast centrifugation, and the expression of candidate mirnas was verified by qRT-PCR. Data showed that 19 of the common 27 differential miRNAs were up-regulated and two down-regulated among the three comparison groups of VOBE vs. VOC, VOBE vs. HC and VOBE vs. BE.By integrating TargetScan, miRDB and mirDIP databases, 594 target genes were predicted. The enrichment analysis of KEGG pathway suggested that these genes were significantly enriched in the cancer, PI3K-Akt and other pathway. There is an association between some circulating exosomal miRNAs and Barrett's esophagus in patients with visceral obesity.This provides some ideas for exploring the molecular mechanism of visceral obesity involved in the development of BE.

Intestinal metaplasia (IM) is a premalignant lesion within the columnar-lined esophagus (CLE). The detection of IM stratifies the risk of cancer progression. We aim to investigate the random biopsy yield of IM in Asian patients with CLE. A total of 117,526 consecutive esophagogastroduodenoscopies (EGDs) in the outpatient setting were retrospectively screened. The histopathological findings independently reviewed by two pathologists were correlated with the clinical and endoscopic features and the number of biopsies. Among 5963 EGDs, 3135 patients (5.1%) were diagnosed with CLE. A total of 4675 EGDs involving 8994 biopsies (median = 1, range 1-9) exhibited a 35.1% yield of IM per endoscopy. The yield of IM was higher in cases of long-segment CLE (74.8%) compared with short-segment (32.9%). IM detection was significantly associated with male gender (odds ratio, 95% confidence interval = 1.58, 1.37-1.83), chronological age (1.02, 1.02-1.03), longer segment CLE (1.75, 1.58-1.94), and number of biopsies per endoscopy (1.40, 1.32-1.49). One biopsy during each EGD resulted in a 26% IM yield, which was significantly lower than the yields after three biopsies (2.85, 2.25-3.62) and after following the Seattle protocol (2.86, 2.34-3.50). In 1772 patients without IM on index endoscopy, subsequent endoscopies increased the IM detection rate by 6%, with 4% attributed to the second endoscopy and 2% to the third through eighth endoscopy. This study provides insights into the number of biopsies needed to characterize IM in Barrett's esophagus. Further research is needed to optimize biopsy strategies, particularly in Asian countries.

Barrett's esophagus (BE) is a metaplastic, premalignant condition that can develop following sleeve gastrectomy (SG). While various treatment modalities exist for management of post-SG BE, conversion to Roux-en-Y gastric bypass (RYGB) can be an effective option which can also improve gastroesophageal reflux disease (GERD). However, the effectiveness of RYGB for resolving BE has not been rigorously studied. This systematic review evaluates the outcomes of BE in patients converted from SG to RYGB. A comprehensive literature search was conducted in Ovid MEDLINE, Ovid Embase, PubMed, and Cochrane Library. Studies reporting BE onset following SG and subsequent RYGB conversion were included. Data extracted included patient demographics, Prague classification, dysplasia status, time from SG to BE diagnosis and time to RYGB conversion, and resolution of BE post-RYGB. The validated MINORS tool was used to assess the quality and risk of bias of reviewed studies. A total of 4 studies were included, comprising 21 patients who underwent conversion from SG to RYGB with BE. The weighted mean age at RYGB was 46.7 ± 13.8years, with an initial BMI of 44.7 ± 2.7kg/m2 and post-SG BMI of 32.5 ± 6.9kg/m2. The time for conversion between SG and RYGB occurred at an average of 58 ± 19.31months. BE resolution was observed in 81% of patients, while dysplasia resolved in n = 1/1 patients. No significant perioperative complications were noted. Based on these results, SG to RYGB conversion appears to be an effective intervention for BE, with the majority of patients achieving histological regression and resolution of symptoms. While preliminary findings indicate favorable outcomes, further studies with bigger sample sizes, longer follow-ups and more diverse patient pools are needed.