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Background:  This study evaluated the proportion of patients with residual neoplasia after endoscopic resection (ER) for Barrett's neoplasia with confirmed tumor-positive vertical resection margin (R1v)., Methods:  This retrospective cohort study included patients undergoing ER for Barrett's neoplasia with histologically documented R1v since 2008 in the Dutch Barrett Expert Centers. We defined R1v as cancer cells touching vertical resection margins and Rx as nonassessable margins. Reassessment of R1v specimens was performed by experienced pathologists until consensus was reached regarding vertical margins., Results:  101/110 included patients had macroscopically complete resections (17 T1a, 84 T1b), and 99/101 (98%) ER specimens were histologically reassessed, with R1v confirmed in 74 patients (75%), Rx in 16%, and R0 in 9%. Presence/absence of residual neoplasia could be assessed in 66/74 patients during endoscopic reassessment (52) and/or in the surgical resection specimen (14), and 33/66 (50%) had residual neoplasia. Residual neoplasia detected during endoscopy was always endoscopically visible and biopsies from a normal-appearing ER scar did not detect additional neoplasia. Of 25 patients who underwent endoscopic follow-up (median 37 months [interquartile range 12-50]), 4 developed local recurrence (16.0%), all detected as visible abnormalities., Conclusions:  After ER with R1v, 50% of patients had no residual neoplasia. Histological evaluation of ER margins appears challenging, as in this study 75% of documented R1v cases were confirmed during reassessment. Endoscopic reassessment 8-12 weeks after ER seems to accurately detect residual neoplasia and can help to determine the most appropriate strategy for patients with R1v., Competing Interests: B.L.A.M. Weusten has received financial research support from Pentax Medical and Aqua Medical, and has received lecture fees from and is a consultant for Pentax Medical. J.J.G.H.M. Bergman has received financial support for institutional review board-approved research from C2Therapeutics/Pentax Medical, Medtronic, and Aqua Medical. R.E Pouw is a consultant for Medtronic BV and MicroTech Europe, and has received speaker fees from Pentax. L. van Tilburg, E.P.D. Verheij, S.E.M. van de Ven, S.N. van Munster, L. Alvarez Herrero, W.B. Nagengast, E.J. Schoon, A. Alkhalaf, L. Oudijk, S.L. Meijer, M. Jansen, M. Doukas, and A.D. Koch declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

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)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Although endoscopic submucosal dissection (ESD) is established as first-choice treatment for early esophageal squamous cell carcinoma (ESCC) worldwide, most data are derived from Asian studies. We aimed to evaluate the long-term outcomes of ESD for patients with early ESCC in a Western cohort., Methods: In this retrospective cohort study, patients with early ESCC amenable to ESD were included from four tertiary referral hospitals in the Netherlands between 2012 and 2017. All ESD procedures were performed by experienced endoscopists, after which the decision for additional treatment was made on a per-patient basis. Outcomes were curative resection rate, ESCC-specific survival, and overall survival., Results: Of 68 included patients (mean age 69 years; 34 males), ESD was technically successful in 66 (97%; 95%CI 93%-100%), with curative resection achieved in 34/66 (52%; 95%CI 39%-64%). Among patients with noncurative resection, 15/32 (47%) underwent additional treatment, mainly esophagectomy (n = 10) or definitive chemoradiation therapy (n = 4). Endoscopic surveillance was preferred in 17/32 patients (53%), based on severe comorbidities or patient choice. Overall, 31/66 patients (47%) died during a median follow-up of 66 months; 8/31 (26%) were ESCC-related deaths. The 5-year overall and ESCC-specific survival probabilities were 62% (95%CI 52%-75%) and 86% (95%CI 77%-96%), respectively., Conclusion: In this Western cohort with long-term follow-up, the effectiveness and safety of ESD for early ESCC was confirmed, although the rate of noncurative resections was substantial. Irrespective of curative status, the long-term prognosis of these patients was limited mainly due to competing mortality., Competing Interests: C.N. Frederiks has received speaker fees from Pentax Medical. R.E. Pouw is a consultant for MicroTech, and has received speaker fees from Medtronic. J.J.G.H.M. Bergman is a consultant for Boston Scientific, Cook Medical, and Medtronic, and has received research funding from Aqua Medical, Fuji Film, Olympus Endoscopy, Pentax Medical, and Medtronic. B.L.A.M. Weusten is a consultant for Pentax Medical, has received speaker fees from Pentax Medical, and has received research funding from Aqua Medical and Pentax Medical. I.N. Beaufort, A. Overwater, L.A.A. Brosens, and A.D. Koch declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Background and Aims: Barrett's esophagus (BE) is accompanied by an increased risk of developing esophageal cancer. Accurate risk-stratification is warranted to improve endoscopic surveillance. Most data available on risk factors is derived from tertiary care centers or from cohorts with limited surveillance time or surveillance quality. The aim of this study was to assess endoscopic and clinical risk factors for progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in a large prospective cohort of BE patients from community hospitals supported by an overarching infrastructure to ensure optimal surveillance quality., Methods: A well-defined prospective multicenter cohort study was initiated in six community hospitals in the Amsterdam region in 2003. BE patients were identified by PALGA search and included in a prospective surveillance program with a single endoscopist performing all endoscopies at each hospital. Planning and data collection was performed by experienced research nurses who attended all endoscopies. Endpoint was progression to HGD/EAC., Results: Nine hundred eighty-five patients were included for analysis. During median follow-up of 7.9 years (IQR 4.1-12.5) 67 patients were diagnosed with HGD (n = 28) or EAC (n = 39), progression rate 0.78% per patient-year. As a clinical risk factor age at time of endoscopy was associated with neoplastic progression (HR 1.05; 95% CI 1.03-1.08). Maximum Barrett length and low-grade dysplasia (LGD) at baseline were endoscopic predictors of progression (HR 1.15; 95% CI 1.09-1.21 and HR 2.36; 95% CI 1.29-4.33)., Conclusion: Risk of progression to HGD/EAC in a large, prospective, community-based Barrett's cohort was low. Barrett's length, LGD and age were important risk factors for progression. (www.trialregister.nl NTR1789)., (© 2021 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

Introduction: After endoscopic resection (ER) of neoplasia in Barrett's esophagus (BE), it is recommended to ablate the remaining BE to minimize the risk for metachronous disease. However, we report long-term outcomes for a nationwide cohort of all patients who did not undergo ablation of the remaining BE after ER for early BE neoplasia, due to clinical reasons or performance status., Methods: Endoscopic therapy for BE neoplasia in the Netherlands is centralized in 8 expert centers with specifically trained endoscopists and pathologists. Uniformity is ensured by a joint protocol and regular group meetings. We report all patients who underwent ER for a neoplastic lesion between 2008 and 2018, without further ablation therapy. Outcomes include progression during endoscopic FU and all-cause mortality., Results: Ninety-four patients were included with mean age 74 (± 10) years. ER was performed for low-grade dysplasia (LGD) (10%), high-grade dysplasia (HGD) (25%), or low-risk esophageal adenocarcinoma (EAC) (65%). No additional ablation was performed for several reasons; in 73 patients (78%), the main argument was expected limited life expectancy. Median C2M5 BE persisted after ER, and during median 21 months (IQR 11-51) with 4 endoscopies per patient, no patient progressed to advanced cancer. Seventeen patients (18%) developed HGD/EAC: all were curatively treated endoscopically. In total, 29/73 patients (40%) with expected limited life expectancy died due to unrelated causes during FU, none of EAC., Conclusion: In selected patients, ER monotherapy with endoscopic surveillance of the residual BE is a valid alternative to eradication therapy with ablation.

Introduction: An automated risk prediction assay has previously been shown to objectively identify patients with nondysplastic Barrett's esophagus (NDBE) who are at increased risk of malignant progression. To evaluate the predictive performance of the assay in 76 patients with NDBE of which 38 progressed to high-grade dysplasia/esophageal adenocarcinoma (progressors) and 38 did not (nonprogressors) and to determine whether assessment of additional (spatial) levels per endoscopy and/or multiple (temporal) time points improves assay performance., Methods: In a blinded, nested case-control cohort, progressors and nonprogressors were matched (age, sex, and Barrett's esophagus length). All random biopsy levels from the baseline endoscopy (spatial samples) and all available previous endoscopies back to 10 years before progression (temporal samples) were assayed. Because the 1:1 ratio of progressors to nonprogressors does not reflect the real-world Barrett's population, negative and positive predictive values were adjusted for prevalence., Results: Seventy-six patients (58 men), mean age of 63 ± 9 years, were studied. A high-risk score was associated with a prevalence-adjusted annual progression rate of 6.9%. The assay identified 31% of progressors when assessing a single biopsy level from the baseline endoscopy. Sensitivity increased to 50% and 69% in spatial and temporal analyses, respectively, while specificity remained at 95%., Discussion: The assay identified a significant subset of NDBE patients who progress at a rate comparable with published estimates for expert-confirmed low-grade dysplasia. Assessing additional spatial and temporal biopsies increased the predictive accuracy, allowing for identification of most future progressors. Additional studies will evaluate the predictive performance of the assay in low-prevalence settings.

Background: Dysplasia assessment of Barrett's esophagus biopsies is associated with low observer agreement; guidelines advise expert review. We have developed a web-based review panel for dysplastic Barrett's esophagus biopsies., Objective: The purpose of this study was to test if 10 gastrointestinal pathologists working at Dutch Barrett's esophagus expert centres met pre-set benchmark scores for quality criteria., Methods: Ten gastrointestinal pathologists twice assessed 60 digitalized Barrett's esophagus cases, enriched for dysplasia; then randomised (7520 assessments). We tested predefined benchmark quality criteria: (a) percentage of 'indefinite for dysplasia' diagnoses, benchmark score ≤14% for all cases, ≤16% for dysplastic subset, (b) intra-observer agreement; benchmark score ≥0.66/≥0.39, (c) percentage agreement with 'gold standard diagnosis'; benchmark score ≥82%/≥73%, (d) proportion of cases with high-grade dysplasia underdiagnosed as non-dysplastic Barrett's esophagus; benchmark score ≤1/78 (≤1.28%) assessments for dysplastic subset., Results: Gastrointestinal pathologists had seven years' Barrett's esophagus-experience, handling seven Barrett's esophagus-cases weekly. Three met stringent benchmark scores; all cases and dysplastic subset, three met extended benchmark scores. Four pathologists lacked one quality criterion to meet benchmark scores., Conclusion: Predefined benchmark scores for expert assessment of Barrett's esophagus dysplasia biopsies are stringent and met by some gastrointestinal pathologists. The majority of assessors however, only showed limited deviation from benchmark scores. We expect further training with group discussions will lead to adherence of all participating gastrointestinal pathologists to quality criteria, and therefore eligible to join the review panel.

Progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is uncommon but the consequences are serious. Predictors of progression are essential to optimize resource utilization. This study assessed the utility of a promising panel of biomarkers applicable to routine paraffin embedded biopsies (FFPE) to predict progression of BE to EAC in a large population-based, nested case-control study.We utilized the Amsterdam-based ReBus nested case-control cohort. BE patients who progressed to high-grade dysplasia (HGD)/EAC (n = 130) and BE patients who never progressed (n = 130) were matched on age, sex, length of the BE segment, and duration of endoscopic surveillance. All progressors had minimum 2 years of endoscopic surveillance without HGD/EAC to exclude prevalent neoplasia. We assessed abnormal DNA content, p53, Cyclin A, and Aspergillus oryzae lectin (AOL) in FFPE sections. We performed conditional logistic regression analysis to estimate odds ratio (OR) of progression based on biomarker status.Expert LGD (OR, 8.3; 95% CI, 1.7-41.0), AOL (3 vs. 0 epithelial compartments abnormal; OR, 3.6; 95% CI, 1.2-10.6) and p53 (OR, 2.3; 95% CI, 1.2-4.6) were independently associated with neoplastic progression. Cyclin A did not predict progression and DNA ploidy analysis by image cytometry was unsuccessful in the majority of cases, both were excluded from the multivariate analysis. The multivariable biomarker model had an area under the receiver operating characteristic curve of 0.73.Expert LGD, AOL, and p53 independently predict neoplastic progression in BE patients and are applicable to routine practice. These biomarkers can aid in selecting patients for endoscopic ablation or more intensive surveillance.

Background & Aims: Radiofrequency ablation (RFA), with or without endoscopic resection effectively eradicates Barrett's esophagus (BE) containing high-grade intraepithelial neoplasia and/or early-stage cancer. We followed patients who received RFA for BE containing high-grade intraepithelial neoplasia and/or early-stage cancer for 5 years to determine the durability of treatment response., Methods: We followed 54 patients with BE (2-12 cm), previously enrolled in 4 consecutive cohort studies in which they underwent focal endoscopic resection in case of visible lesions (n = 40 [72%]), followed by serial RFA every 3 months. Patients underwent high-resolution endoscopy with narrow-band imaging at 6 and 12 months after treatment and then annually for 5 years (median, 61 months; interquartile range, 53-65 months); random biopsy samples were collected from neosquamous epithelium and gastric cardia. After 5 years, endoscopic ultrasound and endoscopic resection of neosquamous epithelium were performed. Outcomes included sustained complete remission of neoplasia or intestinal metaplasia (IM), IM in gastric cardia, or buried glands in neosquamous epithelium., Results: After 5 years, Kaplan-Meier analysis showed sustained complete remission of neoplasia and intestinal metaplasia in 90% of patients; neoplasia recurred in 3 patients and was managed endoscopically. Focal IM in the cardia was found in 19 of 54 patients (35%), in 53 of 1143 gastric cardia biopsies (4.6%). The incidence of IM of the cardia did not increase over time; and IM was diagnosed based on only a single biopsy in 89% of patients. Buried glands were detected in 3 of 3543 neosquamous epithelium biopsies (0.08%, from 3 patients). No endoscopic resection samples had buried glands., Conclusions: Among patients who have undergone RFA with or without endoscopic resection for neoplastic BE, 90% remain in remission at 5-year follow-up, with all recurrences managed endoscopically. This treatment approach is therefore an effective and durable alternative to esophagectomy; www.trialregister.nl number, NTR2938., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)