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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)

AimsThe histopathological diagnosis of low-grade dysplasia (LGD) in Barrett’s oesophagus (BO) is associated with poor interobserver agreement and guidelines dictate expert review. To facilitate nationwide expert review in the Netherlands, a web-based digital review panel has been set up, which currently consists of eight ‘core’ pathologists. The aim of this study was to evaluate if other pathologists from the Dutch BO expert centres qualify for the expert panel by assessing their performance in 80 consecutive LGD reviews submitted to the panel.MethodsPathologists independently assessed digital slides in two phases. Both phases consisted of 40 cases, with a group discussion after phase I. For all cases, a previous consensus diagnosis made by five core pathologists was available, which was used as reference. The following criteria were used: (1) percentage of ‘indefinite for dysplasia’ diagnoses, (2) percentage agreement with consensus diagnosis and (3) proportion of cases with a consensus diagnosis of dysplasia underdiagnosed as non-dysplastic. Benchmarks were based on scores of the core pathologists.ResultsAfter phase I, 1/7 pathologists met the benchmark score for all quality criteria, yet three pathologists only marginally failed the agreement with consensus diagnosis (score 68.3%, benchmark 69%). After a group discussion and phase II, 5/6 remaining aspirant panel members qualified with all scores within the benchmark range.ConclusionsThe Dutch BO review panel now consists of 14 pathologists, who—after structured assessments and group discussions—can be considered homogeneous in their review of biopsies with LGD.

Endoscopic resection (ER) is an important diagnostic step in management of patients with early Barrett’s esophagus (BE) neoplasia. Based on ER specimens, an accurate histological diagnosis can be made, which guides further treatment. Based on depth of tumor invasion, differentiation grade, lymphovascular invasion, and margin status, the risk of lymph node metastases and local recurrence is judged to be low enough to justify endoscopic management, or high enough to warrant invasive surgical esophagectomy. Adequate assessment of these histological risk factors is therefore of the utmost importance. Aim of this study was to assess pathologist concordance on these histological features on ER specimens and evaluate causes of discrepancy. Of 62 challenging ER cases, one representative H&E slide and matching desmin and endothelial marker were digitalized and independently assessed by 13 dedicated GI pathologists from 8 Dutch BE expert centers, using an online assessment module. For each histological feature, concordance and discordance were calculated. Clinically relevant discordances were observed for all criteria. Grouping depth of invasion categories according to expanded endoscopic treatment criteria (T1a and T1sm1 vs. T1sm2/3), ≥1 pathologist was discrepant in 21% of cases, increasing to 45% when grouping diagnoses according to the traditional T1a versus T1b classification. For differentiation grade, lymphovascular invasion, and margin status, discordances were substantial with 27%, 42%, and 32% of cases having ≥1 discrepant pathologist, respectively. In conclusion, histological assessment of ER specimens of early BE cancer by dedicated GI pathologists shows significant discordances for all relevant histological features. We present propositions to improve definitions of diagnostic criteria.

BACKGROUND AND AIMS: A prior randomized study (Surveillance versus Radiofrequency Ablation study [SURF study]) demonstrated that radiofrequency ablation (RFA) of Barrett's esophagus (BE) with confirmed low-grade dysplasia (LGD) significantly reduces the risk of esophageal adenocarcinoma. Our aim was to report the long-term outcomes of this study. METHODS: The SURF study randomized BE patients with confirmed LGD to RFA or surveillance. For this retrospective cohort study, all endoscopic and histologic data acquired at the end of the SURF study in May 2013 until December 2017 were collected. The primary outcome was rate of progression to high-grade dysplasia (HGD)/cancer. All 136 patients randomized to RFA (n = 68) or surveillance (n = 68) in the SURF study were included. After closure of the SURF study, 15 surveillance patients underwent RFA based on patient preference and study outcomes. RESULTS: With 40 additional months (interquartile range, 12-51), the total median follow-up from randomization to last endoscopy was 73 months (interquartile range, 46-85). HGD/cancer was diagnosed in 1 patient in the RFA group (1.5%) and in 23 in the surveillance group (33.8%) (P = .000), resulting in an absolute risk reduction of 32.4% (95% confidence interval [CI], 22.4%-44.2%) with a number needed to treat of 3.1 (95% CI, 2.3-4.5). Seventy-five of 83 patients (90%; 95% CI, 82.1%-95.0%) treated with RFA for BE reached complete clearance of BE and dysplasia. BE recurred in 7 of 75 patients (9%; 95% CI, 4.6%-18.0%), mostly minute islands or tongues, and LGD in 3 of 75 (4%; 95% CI, 1.4%-11.1%). CONCLUSIONS: RFA of BE with confirmed LGD significantly reduces the risk of malignant progression, with sustained clearance of BE in 91% and LGD in 96% of patients, after a median follow-up of 73 months. (Clinical trial registration number: NTR1198.). ispartof: GASTROINTESTINAL ENDOSCOPY vol:92 issue:3 pages:569-574 ispartof: location:United States status: published

Barrett′s esophagus (BE) is a premalignant condition defined by the replacement of squamous epithelium by columnar epithelium in the distal part of the esophagus. Patients with BE have an increased risk of progression to esophageal adenocarcinoma (EAC). Advanced EAC has a poor 5-year survival rate. However, if EAC is diagnosed at an early stage, endoscopic treatment has proven to be a safe and effective treatment, with excellent long-term survival rates. Currently it is not possible to accurately predict which patients with BE will develop EAC. Despite promising developments in genetic and molecular biomarker research, grade of dysplasia is still the best predictor for progression to EAC. Present guidelines advise surveillance endoscopies with biopsies for BE patients to detect early neoplasia at a treatable stage. Surveillance intervals are determined by length of the BE segment and on the histopathologic diagnosis of the biopsies. Accurate histopathologic assessment of biopsies to define surveillance intervals or to decide on a treatment strategy, is therefore of the utmost importance.

Background: Dysplasia in Barrett's esophagus (BE) biopsies is associated with low observer agreement among general pathologists. Therefore, expert review is advised. We are developing a web-based, national expert review panel for histological review of BE biopsies.Objective: The aim of this study was to create benchmark quality criteria for future members.Methods: Five expert BE pathologists, with 10-30 years of BE experience, weekly handling 5-10 cases (25% dysplastic), assessed a case set of 60 digitalized cases, enriched for dysplasia. Each case contained all slides from one endoscopy (non-dysplastic BE (NDBE), n = 21; low-grade dysplasia (LGD), n = 20; high-grade dysplasia (HGD), n = 19). All cases were randomized and assessed twice followed by group discussions to create a consensus diagnosis. Outcome measures: percentage of 'indefinite for dysplasia' (IND) diagnoses, intra-observer agreement, and agreement with the consensus 'gold standard' diagnosis.Results: Mean percentage of IND diagnoses was 8% (3-14%) and mean intra-observer agreement was 0.84 (0.66-1.02). Mean agreement with the consensus diagnosis was 90% (95% prediction interval (PI) 82-98%).Conclusion: Expert pathology review of BE requires the scoring of a limited number of IND cases, consistency of assessment and a high agreement with a consensus gold standard diagnosis. These benchmark quality criteria will be used to assess the performance of other pathologists joining our panel.

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.

SUMMARYPatient selection is suboptimal in most studies focused on identifying biological markers for neoplastic progression in Barrett's esophagus (BE). This study aims to describe a stringently selected community-based case-control cohort of non-dysplastic BE (NDBE) patients who progressed to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) and BE patients who never progressed to be used for future biomarker studies. We identified all patients referred for endoscopic work-up of BE neoplasia at three tertiary referral centers for treatment of BE neoplasia between 2000 and 2013. We performed a detailed registration of any endoscopic surveillance history before neoplastic progression. Controls were selected from a retrospective BE surveillance registration in 10 community hospitals. A total of 887 patients were referred for endoscopic work-up of BE neoplasia. Based on predefined selection criteria, we identified 165 progressor patients (82% men; mean age 55 years ± 10.4) with a baseline endoscopy demonstrating NDBE > 2 years before neoplastic progression. Using the same predefined selection criteria, 723 nonprogressor patients (67% men; mean age 57 years ± 11.3) with >2 years of endoscopic surveillance were identified. Median length of the BE segment was 5 cm (IQR 4–7) in progressors and 4 cm (IQR 2–6) in controls. Median duration of surveillance was 89 months (IQR 54–139) in progressors and 76 months (IQR 47–116) in nonprogressors. Paraffin embedded biopsies are available for biomarker research in all patients. Ethical approval was obtained and material transfer agreements were signed with all 58 contributing pathology labs. This is the largest community-based case-control cohort of BE patients with and without progression to early neoplasia. The stringent selection criteria and the availability of paraffin embedded biopsy specimens make this a unique cohort for biomarker studies.

In a prior study, baseline mutational load (ML) predicted progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE) with an area under the curve (AUC) of 0.95. We aimed to validate the test characteristics of this predictive biomarker panel using crude DNA lysates in a larger well-characterized cohort. We performed a nested case-control study of BE patients from three tertiary referral centers in the Netherlands. Cases had baseline nondysplastic BE (NDBE) and developed HGD/EAC ≥ 2 years later. Controls were matched 2:1, had baseline NDBE, and no progression. Polymerase chain reaction (PCR)-based mutational analysis was performed on crude lysates from formalin-fixed, paraffin-embedded tissue. ML was calculated from loss of heterozygosity (LOH) and microsatellite instability (MSI) at 10 genomic loci. Receiver operator characteristic (ROC) curves were created to assess the diagnostic utility of various cutoffs of ML for progression. Of 159 subjects, 58 were progressors and 101 were nonprogressors, there was no difference in mean ML in preprogression tissue in progressors and nonprogressors (ML = 0.73 ± 0.69 vs. ML = 0.74 ± 0.61, P = 0.93). ROC curves showed poor discrimination of ML in predicting progression with AUC of 0.50 at ML ≥ 1. AUC did not vary with different ML cut-points. The utility of the ML to stratify BE patients for risk of progression was not confirmed in this study. The etiology for discrepancies between this and prior studies showing high predictiveness is likely due to the use of crude lysates in this study, but requires further investigation.

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