Nondysplastic Barrett's Esophagus Research Articles

Spectral Endoscopy Enhances Contrast for Neoplasia in Surveillance of Barrett's Esophagus.

Early detection of esophageal neoplasia enables curative endoscopic therapy, but the current diagnostic standard of care has low sensitivity because early neoplasia is often inconspicuous with conventional white-light endoscopy. Here, we hypothesized that spectral endoscopy could enhance contrast for neoplasia in surveillance of patients with Barrett's esophagus. A custom spectral endoscope was deployed in a pilot clinical study of 20 patients to capture 715 in vivo tissue spectra matched with gold standard diagnosis from histopathology. Spectral endoscopy was sensitive to changes in neovascularization during the progression of disease; both non-dysplastic and neoplastic Barrett's esophagus showed higher blood volume relative to healthy squamous tissue (P = 0.001 and 0.02, respectively), and vessel radius appeared larger in neoplasia relative to non-dysplastic Barrett's esophagus (P = 0.06). We further developed a deep learning algorithm capable of classifying spectra of neoplasia versus non-dysplastic Barrett's esophagus with high accuracy (84.8% accuracy, 83.7% sensitivity, 85.5% specificity, 78.3% positive predictive value, and 89.4% negative predictive value). Exploiting the newly acquired library of labeled spectra to model custom color filter sets identified a potential 12-fold enhancement in contrast between neoplasia and non-dysplastic Barrett's esophagus using application-specific color filters compared with standard-of-care white-light imaging (perceptible color difference = 32.4 and 2.7, respectively). This work demonstrates the potential of endoscopic spectral imaging to extract vascular properties in Barrett's esophagus, to classify disease stages using deep learning, and to enable high-contrast endoscopy. SIGNIFICANCE: The results of this pilot first-in-human clinical trial demonstrate the potential of spectral endoscopy to reveal disease-associated vascular changes and to provide high-contrast delineation of neoplasia in the esophagus. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/12/3415/F1.large.jpg.

ID: 3521795 ENDOSCOPIC EXPERT REVISION OF PREVIOUS HISTOLOGICAL CONFIRMED FLAT LOW-GRADE DYSPLASIA IN BARRETT’S ESOPHAGUS

The strongest histologic predictor for progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in Barrett’s esophagus (BE) is expert confirmed diagnosis of low-grade dysplasia (LGD). However, previous studies showed that up to 85% of LGD diagnosis were downstaged to non-dysplastic BE during revision. Therefore, Dutch guidelines advise to only refer patients with confirmed LGD to a Barrett’s Expert Center (BEC). Aim was to assess if a finding of confirmed LGD in BE without visible lesions (VL), diagnosed in a community setting, is an indicator for higher grades of dysplasia and if referral to a BEC is indeed necessary.

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.

Multinational survey on the preferred approach to management of Barrett's esophagus in the Asia-Pacific region.

BACKGROUNDMajor societies provide differing guidance on management of Barrett’s esophagus (BE), making standardization challenging.AIMTo evaluate the preferred diagnosis and management practices of BE among Asian endoscopists.METHODSEndoscopists from across Asia were invited to participate in an online questionnaire comprising eleven questions regarding diagnosis, surveillance and management of BE.RESULTSFive hundred sixty-nine of 1016 (56.0%) respondents completed the survey, with most respondents from Japan (n = 310, 54.5%) and China (n = 129, 22.7%). Overall, the preferred endoscopic landmark of the esophagogastric junction was squamo-columnar junction (42.0%). Distal palisade vessels was preferred in Japan (59.0% vs 10.0%, P < 0.001) while outside Japan, squamo-columnar junction was preferred (59.5% vs 27.4%, P < 0.001). Only 16.3% of respondents used Prague C and M criteria all the time. It was never used by 46.1% of Japanese, whereas 84.2% outside Japan, endoscopists used it to varying extents (P < 0.001). Most Asian endoscopists (70.8%) would survey long-segment BE without dysplasia every two years. Adherence to Seattle protocol was poor with only 6.3% always performing it. 73.2% of Japanese never did it, compared to 19.3% outside Japan (P < 0.001). The most preferred (74.0%) treatment of non-dysplastic BE was proton pump inhibitor only when the patient was symptomatic or had esophagitis. For BE with low-grade dysplasia, 6-monthly surveillance was preferred in 61.9% within Japan vs 47.9% outside Japan (P < 0.001). CONCLUSIONDiagnosis and management of BE varied within Asia, with stark contrast between Japan and outside Japan. Most Asian endoscopists chose squamo-columnar junction to be the landmark for esophagogastric junction, which is incorrect. Most also did not consistently use Prague criteria, and Seattle protocol. Lack of standardization, education and research are possible reasons.

Prevalence and Predictors of Missed Dysplasia on Index Barrett’s Esophagus Diagnosing Endoscopy in a Veteran Population

Limitations of endoscopic sampling may result in missed dysplasia at the diagnosis of Barrett's esophagus (BE). However, the role of close follow-up endoscopy is unclear. The aim was to evaluate the proportion of patients diagnosed with "missed" dysplasia within 18 months of their index nondysplastic BE (NDBE) diagnosis. This was a retrospective analysis of a cohort of BE patients diagnosed during 1990-2019 at the Houston VA. Patients with BE on index esophagogastroduodenoscopy (EGD) were classified as NDBE, indefinite dysplasia, or dysplastic (low- or high-grade dysplasia) based on initial biopsies. We identified NDBE patients who had follow-up EGD within 3-18 months after index EGD. We used logistic regression models to estimate odds ratios and 95% confidence intervals for risk factors of dysplasia on follow-up EGD. We identified 614 patients who had BE on index EGD. Among those with NDBE and follow-up EGD within 3-18 months (n= 271), 4.1% had definite dysplasia on follow-up, and an additional 14.0% had indefinite dysplasia. Proportions of definite or indefinite dysplasia at follow-up within 3-18 months significantly decreased from 32.6% among patients with index EGD before 2009 to 11.7% among patients with index EGD after 2013 (P for trend= .068). Those with any indefinite or definite dysplastic BE at follow-up within 3-18 months after index EGD (n= 49) were more likely to have BE length ≥3 cm on index EGD (odds ratio, 3.39; 95% confidence interval, 1.63-7.08) than those with persistent NDBE or no BE on follow-up. The occurrence of missed dysplasia on an index EGD has decreased over time. However, those with long segment BE were more than 3 times as likely to have missed dysplasia, and this group could benefit from dysplasia surveillance within 18 months of BE diagnosis.

Taking the Next Steps in Endoscopic Visual Assessment of Barrett's Esophagus: A Pilot Study.

PurposePatients with Barrett’s esophagus (BE) undergo surveillance endoscopies to assess for pre-cancerous changes. We developed a simple endoscopic classification method for predicting non-dysplastic BE (NDBE), low-grade dysplasia (LGD)/indefinite for dysplasia (ID) and high-grade dysplasia (HGD)/early esophageal adenocarcinoma (EAC).Patients and MethodsTwenty-two patients with BE underwent endoscopy using the PENTAX Medical MagniView gastroscope and OPTIVISTA processor. Sixty-six video-still images were analyzed to characterize the microsurface, microvasculature and the presence of a demarcation line. Class A was characterized by regular microvascular and microsurface patterns and absence of a demarcation line, class B by changes in the microvascular and/or microsurface patterns compared to the background mucosa with presence of a demarcation line, and class C by irregular microvascular and/or irregular microsurface patterns with presence of a demarcation line.ResultsOf the class A images, 97.9% were NDBE. For class B, 69.2% were LGD/ID and 30.8% NDBE. One hundred percent of the class C samples were HGD/EAC. The sensitivity of our classification system was 93.8%, specificity 92%, positive predictive value 78.9%, negative predictive value 97.9% and an accuracy 92.4%.ConclusionIn this study, we developed a simple classification system for the prediction of NDBE, LGD/ID and HGD/EAC. Its real-time clinical applicability will be validated prospectively.

Racial Disparities in Adherence to Quality Indicators in Barrett's Esophagus: An Analysis Using the GIQuIC National Benchmarking Registry.

Racial disparities in outcomes in esophageal adenocarcinoma are well established. Using a nationwide registry, we aimed to compare clinical and endoscopic characteristics of blacks and whites with Barrett's esophagus (BE) and adherence to defined quality indicators. We analyzed data from the Gastrointestinal Quality Improvement Consortium Registry between January 2012 and December 2019. Patients who underwent esophagogastroduodenoscopy with an indication of BE screening or surveillance, or an endoscopic finding of BE, were included. Adherence to recommended endoscopic surveillance intervals of 3-5 years for nondysplastic BE and adherence to Seattle biopsy protocol were assessed. Multivariate logistic regression was conducted to assess variables associated with adherence. A total of 100,848 esophagogastroduodenoscopies in 84,789 patients met inclusion criteria (blacks-3,957 and whites-96,891). Blacks were less likely to have histologically confirmed BE (34.3% vs 51.7%, P < 0.01), had shorter BE lengths (1.61 vs 2.35 cm, P < 0.01), and were less likely to have any dysplasia (4.3% vs 7.1%, P < 0.01). Although whites were predominantly male (62.2%), about half of blacks with BE were female (53.0%). Blacks with nondysplastic BE were less likely to be recommended appropriate surveillance intervals (OR 0.78; 95% CI 0.68-0.89). Adherence rates to the Seattle protocol were modestly higher among blacks overall (OR 1.12, 95% CI 1.04-1.20), although significantly lower among blacks with BE segments >6 cm. The use of sex as a risk factor for BE screening may be inappropriate among blacks. Fewer blacks were recommended appropriate surveillance intervals, and blacks with longer segment BE were less likely to undergo Seattle biopsy protocol.

Deep learning systems detect dysplasia with human-like accuracy using histopathology and probe-based confocal laser endomicroscopy

Probe-based confocal laser endomicroscopy (pCLE) allows for real-time diagnosis of dysplasia and cancer in Barrett’s esophagus (BE) but is limited by low sensitivity. Even the gold standard of histopathology is hindered by poor agreement between pathologists. We deployed deep-learning-based image and video analysis in order to improve diagnostic accuracy of pCLE videos and biopsy images. Blinded experts categorized biopsies and pCLE videos as squamous, non-dysplastic BE, or dysplasia/cancer, and deep learning models were trained to classify the data into these three categories. Biopsy classification was conducted using two distinct approaches—a patch-level model and a whole-slide-image-level model. Gradient-weighted class activation maps (Grad-CAMs) were extracted from pCLE and biopsy models in order to determine tissue structures deemed relevant by the models. 1970 pCLE videos, 897,931 biopsy patches, and 387 whole-slide images were used to train, test, and validate the models. In pCLE analysis, models achieved a high sensitivity for dysplasia (71%) and an overall accuracy of 90% for all classes. For biopsies at the patch level, the model achieved a sensitivity of 72% for dysplasia and an overall accuracy of 90%. The whole-slide-image-level model achieved a sensitivity of 90% for dysplasia and 94% overall accuracy. Grad-CAMs for all models showed activation in medically relevant tissue regions. Our deep learning models achieved high diagnostic accuracy for both pCLE-based and histopathologic diagnosis of esophageal dysplasia and its precursors, similar to human accuracy in prior studies. These machine learning approaches may improve accuracy and efficiency of current screening protocols.

TissueCypher Barrett's esophagus assay impacts clinical decisions in the management of patients with Barrett's esophagus.

Background and study aims The TissueCypher Barrett’s Esophagus Assay is a novel tissue biomarker test, and has been validated to predict progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett’s esophagus (BE). The aim of this study was to evaluate the impact of TissueCypher on clinical decision-making in the management of BE. Patients and methods TissueCypher was ordered for 60 patients with non-dysplastic (ND, n = 18) BE, indefinite for dysplasia (IND, n = 25), and low-grade dysplasia (LGD, n = 17). TissueCypher reports a risk class (low, intermediate or high) for progression to HGD or EAC within 5 years. The impact of the test results on BE management decisions was assessed. Results Fifty-two of 60 patients were male, mean age 65.2 ± 11.8, and 43 of 60 had long segment BE. TissueCypher results impacted 55.0 % of management decisions. In 21.7 % of patients, the test upstaged the management approach, resulting in endoscopic eradication therapy (EET) or shorter surveillance interval. The test downstaged the management approach in 33.4 % of patients, leading to surveillance rather than EET. In the subset of patients whose management plan was changed, upstaging was associated with a high-risk TissueCypher result, and downstaging was associated with a low-risk result ( P < 0.0001). Conclusions TissueCypher was used as an adjunct to support a surveillance-only approach in 33.4 % of patients. Upstaging occurred in 21.7 % of patients, leading to therapeutic intervention or increased surveillance. These results indicate that the TissueCypher test may enable physicians to target EET for TissueCypher high-risk BE patients, while reducing unnecessary procedures in TissueCypher low-risk patients.

An Urban Center Experience Exploring Barriers to Adherence to Endoscopic Surveillance for Non-Dysplastic Barrett's Esophagus.

BackgroundData regarding barriers to Barrett’s esophagus (BE) surveillance is limited. Studying an urban center population, we aimed to characterize non-dysplastic BE surveillance rates and identify health, racial, and socioeconomic disparities affecting surveillance.MethodsPatients with biopsy-confirmed BE were retrospectively identified between January 2002 and December 2012. Non-dysplastic BE patients were analyzed for adherence to established surveillance guidelines. Demographic, racial, comorbidities, and socioeconomic variables were extracted. Annual gross income (AGI) was utilized as a marker of socioeconomic status (SES). Univariate and multivariate analyses compared adherent vs. non-adherent patients to surveillance guidelines.ResultsA total of 217 patients with non-dysplastic BE were analyzed. The majority were male (67.3%) and Caucasian (75.6%), with only 47.5% adherent with the first surveillance endoscopy. Patients with a high average AGI were more likely to be adherent with the initial surveillance endoscopy than those with low AGI (p=0.032). Initial compliance with first surveillance was associated with better surveillance at regular intervals (p=0.001). No significant differences in age, primary language, insurance type, marital status, or Charlson Comorbidity Index (CCI) between adherent and non-adherent patients were found.ConclusionsAlthough overall adherence to guidelines was suboptimal, this study identifies important socioeconomic disparities in the endoscopic surveillance for non-dysplastic BE. Identifying and understanding the barriers to care among these lower socioeconomic groups may ultimately lead to improved screening compliance and early BE detection.

Massively Parallel Sequencing of Esophageal Brushings Enables an Aneuploidy-Based Classification of Patients With Barrett’s Esophagus

Aneuploidy has been proposed as a tool to assess progression in patients with Barrett's esophagus (BE), but has heretofore required multiple biopsies. We assessed whether a single esophageal brushing that widely sampled the esophagus could be combined with massively parallel sequencing to characterize aneuploidy and identify patients with disease progression to dysplasia or cancer. Esophageal brushings were obtained from patients without BE, with non-dysplastic BE (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (EAC). To assess aneuploidy, we used RealSeqS, a technique that uses a single primer pair to interrogate ∼350,000 genome-spanning regions and identify specific chromosome arm alterations. A classifier to distinguish NDBE from EAC was trained on results from 79 patients. An independent validation cohort of 268 subjects was used to test the classifier at distinguishing patients at successive phases of BE progression. Aneuploidy progression was associated with gains of 1q, 12p, and 20q and losses on 9p and 17p. The entire chromosome 8q was often gained in NDBE, whereas focal gain of 8q24 was identified only when there was dysplasia. Among validation subjects, a classifier incorporating these features with a global measure of aneuploidy scored positive in 96% of EAC, 68% of HGD, but only 7% of NDBE. RealSeqS analysis of esophageal brushings provides a practical and sensitive method to determine aneuploidy in BE patients. It identifies specific chromosome changes that occur early in NDBE and others that occur late and mark progression to dysplasia. The clinical implications of this approach can now be tested in prospective trials.

Factors influencing health-related quality of life in patients with Barrett's esophagus: a qualitative focus group study.

Barrett's esophagus is a premalignant condition in the lower part of the esophagus, caused by gastroesophageal reflux disease. Previous studies found that having a Barrett's esophagus is associated with a significant decrease of health-related quality of life (HRQOL). Over the past decade, a considerable amount of literature has been published on the development of endoscopic treatment for (early) neoplasia in Barrett's esophagus. Though, currently very little is known about the impact of those endoscopic treatments on HRQOL from the perspective of patients. In this study, we aim to assess the factors influencing HRQOL according to Barrett's esophagus patients. By using a qualitative focus group design, patients with nondysplastic Barrett's esophagus and patients with a history of endoscopic treatment for Barrett's dysplasia were included. Data were analysed following the conventional content analyses approach. A total of 34 patients participated in the four focus group sessions. Experiencing symptoms was valued as the most important factor in both groups. Other factors identified as important HRQOL influencers were: use of medication, fear of cancer and trust in physicians and endoscopic procedures. In general, Barrett's esophagus patients experienced a good HRQOL, with a minimal emotional burden from the diagnosis of Barrett's esophagus. Most influencing factor on HRQOL was: experiencing reflux and dyspepsia symptoms. This study underlines the importance of adequate gastroesophageal reflux treatment and providing information to Barrett's esophagus patients, tailored to their personal needs.

LGR5 in Barrett's Esophagus and its Utility in Predicting Patients at Increased Risk of Advanced Neoplasia

INTRODUCTION:The expression of LGR5, a known stem cell marker, is poorly understood in Barrett's esophagus (BE) and related neoplasia. The aim of this study was to evaluate LGR5 in BE and related neoplasia and to evaluate its utility as a potential biomarker of progression to advanced neoplasia.METHODS:We evaluated total 137 patients, including 119 with BE and 18 with normal gastroesophageal mucosa for expression of LGR5 using RNA in situ hybridization; this also included 28 progressors and 30 nonprogressors. The LGR5 stain was evaluated using 1 qualitative and 2 quantitative parameters, using manual and automated platforms.RESULTS:Surface LGR5 expression was mainly seen in high-grade dysplasia (12/18) compared with low-grade dysplasia (1/8) and nondysplastic BE (0/17) (P < 0.0001). In contrast to nondysplastic BE, low- and high-grade dysplasia showed a higher percentage of mean number of LGR5-positive crypts per patient (P < 0.0001) and an increase in the mean number of LGR5 transcripts per cell (P < 0.0001). The mean percentage of LGR5-positive crypts per patient and the mean number of LGR5 transcripts per cell were also significantly higher in nondysplastic BE from progressor compared with nonprogressor (P < 0.0001, P = 0.014). The sensitivity and specificity of LGR5 for distinguishing progressor from nonprogressor were 50% and 87%, respectively.DISCUSSION:BE-related advanced neoplasia shows an expansion of the LGR5-positive cellular compartment, supporting its role as a stem cell marker in this disease. Quantitative LGR5 expression and surface epithelial reactivity are novel biomarkers of increased risk of progression to advanced neoplasia in BE.

Benefit of radiofrequency ablation after widespread endoscopic resection of neoplastic Barrett's esophagus in daily practice.

BackgroundHigh-grade dysplasia (HGD) and intramucosal carcinoma (IMC) in Barrett’s esophagus (BE) are now well-established indications for endoscopic resection (ER). Radiofrequency ablation (RFA) can be combined with ER in case of flat or long-segment BE ablation. We report here our experience of complementary RFA after widespread ER of neoplastic BE in daily practice.MethodWe retrospectively reviewed data of 89 patients, treated between 2006 and 2013 by ER alone (group 1) or by ER combined with RFA (group 2).ResultsFifty-five patients in group 1 (7F/48M, mean age 68 years) underwent widespread ER with eradication of residual non-dysplastic BE. Complete eradication of HGD/IMC and intestinal metaplasia (IM) was achieved in 32/32 (100%) and 48/55 (87.3%) patients, respectively. Thirty-four patients in group 2 (3F/31M, mean age 67 years) had a multimodal treatment strategy, with widespread ER followed by RFA. Mean Prague classification of BE in this group was significantly longer (C4.4M6.6 vs. C2.7M4.5, P<0.001). Complete eradication of HGD/IMC and non-dysplastic BE was confirmed in 26/27 (96.3%) and 20/34 (58.8%) patients, respectively. There was no significant difference between groups concerning adverse events (16.4% vs. 23.5%, P=0.58) or recurrence rate of HGD/IMC (9.1% vs. 14.7%, P=0.42). The mismatch rate between preoperative and final histological diagnosis was high in both groups, at 45.5% and 26.5%.ConclusionsA combination of ER and RFA can treat significantly longer neoplastic BE than ER alone, with the same efficiency and safety. Widespread ER, in contrast, is the only method of obtaining a reliable histological diagnosis.

The Utility of P53 Immunohistochemistry in the Diagnosis of Barrett's Esophagus with Indefinite for Dysplasia

Background: Barrett's esophagus with indefinite for dysplasia (BE-IND) is a subjective diagnosis with a low interobserver agreement (IOA) among pathologists and uncertain clinical implications. This study aimed to assess the utility of p53 immunohistochemistry (p53-IHC) in assessing BE-IND specimens. Methods: Archive endoscopic biopsies with a BE-IND diagnosis from two academic centers were analyzed. Firstly, hematoxylin and eosin-stained slides (H&E) were reviewed by four expert GI pathologists allocated into two groups (A and B). After a wash-out period of at least eight weeks, H&E slides were re-assessed side-to-side with p53-IHC available. We compared the rate of changed diagnosis and the IOA for all BE grades before and after p53-IHC. Findings: We included 216 BE-IND specimens from 185 patients, of which 44.0% and 32.9% were confirmed after H&E slide revision by Groups A and B, respectively. Over half of the cases were downgraded to a non-dysplastic BE (NDBE), while 5.6% of cases in Group A and 7.4% in Group B were upgraded to dysplasia. The IOA for NDBE, BE-IND, low-grade dysplasia (LGD), and high-grade dysplasia (HGD)/intramucosal cancer (IMC) was 0.31, 0.21, -0.03, and -0.02, respectively. Use of p53-IHC led to a >40% reduction in BE-IND diagnoses (P<.001), and increased IOA for all BE grades (κ=0.46 [NDBE], 0.26 [BE-IND], 0.49 [LGD], 0.35 [HGD/IMC]). An aberrant p53-IHC pattern significantly increased the likelihood of reclassifying BE-IND to definite dysplasia (odds ratio 44.3, 95%CI:18.8-113.0). Interpretation: P53-IHC reduces the rate of BE-IND diagnoses and improves the IOA among pathologists when reporting BE with equivocal epithelial changes. Funding: This study received infrastructure support from the NIHR Cambridge Biomedical Research Centre. Declaration of Interest: None to declare. Ethical Approval: An ethics committee approval for this study was granted at both institutions (Cambridge University: 7 LREC01/149; Mayo Clinic: 9-000514).

Neutrophil to lymphocyte ratio and risk of neoplastic progression in patients with Barrett's esophagus.

Patient's with Barrett's esophagus (BE) are at risk of progression to esophageal adenocarcinoma (EAC). Neutrophil to lymphocyte ratio (NLR) was found to be a predictor of poor prognosis in patients with EAC; however, its performance in premalignant esophageal lesions is vague. We aimed to evaluate the utility of NLR as a predictor of histologic progression in patients with BE. METHODS : A prospective cohort of patients with proven BE in a tertiary referral center was retrospectively analyzed. All biopsies were reviewed by an expert gastrointestinal pathologist. The discriminatory capacity of NLR was evaluated by area under the receiver operating characteristic (AUC) curve analysis and Cox regression analysis. 324 patients (mean age 62.3 years, 241 [74.4 %] males) were included in the final analysis. Overall, 13 patients demonstrated histologic progression to neoplasia over a mean follow-up of 3.7 years (progression risk 1.0 % per year). The AUC of NLR for progression to high grade dysplasia (HGD) or EAC was 0.88 (95 % confidence interval [CI] 0.83 - 0.96), and baseline NLR was associated with a 3-fold increase of progression to HGD and EAC during follow-up (hazard ratio [HR] 3.2, 95 %CI 1.5 - 5.8; P < 0.001). Notably, in a subgroup analysis of patients with nondysplastic BE (NDBE) at presentation, NLR was also a risk factor for histologic progression (HR 2.4, 95 %CI 1.7 - 3.4; P < 0.001). NLR predicted histologic progression in patients with BE. Patients with NDBE and NLR above 2.4 can be considered for specific surveillance programs with shorter intervals between sessions.

Systematic review of the published guidelines on Barrett's esophagus: should we stress the consensus or the differences?

Multiple guidelines on Barrett's esophagus (BE) have being published in order to standardize and improve clinical practice. However, studies have shown poor adherence to them. Our aim was to synthetize, compare, and assess the quality of recommendations from recently published guidelines, stressing similarities and differences. We conducted a search in Pubmed and Scopus. When different guidelines from the same society were identified, the most recent one was considered. We used the GRADE system to assess the quality of evidence. We included 24 guidelines and position/consensus statements from the European Society of Gastrointestinal Endoscopy, British Society of Gastroenterology, American Society for Gastrointestinal Endoscopy, American Gastroenterological Association, American College of Gastroenterology, Australian guidelines, and Asia-Pacific consensus. All guidelines defend that BE should be diagnosed when there is an extension of columnar epithelium into the distal esophagus. However, there is still some controversy regarding length and histology criteria for BE diagnosis. All guidelines recommend expert pathologist review for dysplasia diagnosis. All guidelines recommend surveillance for non-dysplastic BE, and some recommend surveillance for indefinite dysplasia. While the majority of guidelines recommend ablation therapy for low-grade dysplasia without visible lesion, others recommend ablation therapy or endoscopic surveillance. However, controversy exists regarding surveillance intervals and biopsy protocols. All guidelines recommend endoscopic resection followed by ablation therapy for neoplastic visible lesion. Several guidelines use the GRADE system, but the majority of recommendations are based on low and moderate quality of evidence. Although there is considerable consensus among guidelines, there are some discrepancies resulting from low-quality evidence. The lack of high-quality evidence for the majority of recommendations highlights the importance of continued well-conducted research in this field.

Tissue Systems Pathology Test Objectively Risk Stratifies Barrett's Esophagus Patients With Low-Grade Dysplasia.

Low-grade dysplasia (LGD) is the best predictor of neoplastic progression in Barrett's esophagus (BE). Most LGD cases are downstaged to nondysplastic (ND) BE on expert pathologist review, which is prone to interobserver variation and not widely available. Recent studies indicate that a risk prediction assay (TissueCypher) risk stratifies patients with NDBE for neoplastic progression. We aimed to investigate whether this risk prediction assay predicts neoplastic progression in BE patients with LGD. A blinded, retrospective cohort study was derived from the screening cohort of a randomized controlled trial of SURveillance vs RadioFrequency ablation for BE patients with LGD. Hematoxylin and eosin and p53 immunohistochemistry slides from the first endoscopy with LGD were independently reviewed by 3 expert pathologists and tested by the risk prediction assay. Revision diagnoses of NDBE were considered low risk, although indefinite for dysplasia, and LGD were considered high risk for progression. A total of 155 BE patients (123 men), mean age 61 ± 10 years, were analyzed. Thirty-four patients (22%) progressed to high-grade dysplasia/esophageal adenocarcinoma (median time 2.4 years) and 121 did not progress (median high-grade dysplasia/esophageal adenocarcinoma-free surveillance 7.9 years). The risk prediction assay sensitivity was 68% vs 76% for the 3 pathologists, and specificity was 79% vs 64%-77.0% for the pathologists. The assay detected 50%-56% of progressors that were downstaged to NDBE by the pathologists. The risk prediction assay provided significant risk stratification in BE patients with LGD and identified progressors that the experts downstaged to NDBE. This objective assay provides an effective solution to the lack of standardization of expert pathology review of LGD.

Can Genomic Sequencing Identify High-Risk Barrett’s Esophagus Earlier Than Pathologists?

Barrett's esophagus (BE) is a precursor to esophageal adenocarinoma, and screening for cancer risk focuses upon histologic assessment of dysplasia within endoscopic biopsies. A recent study in Nature Medicine contributes to growing evidence that genomic assessment of non-dysplastic BE samples can identify patients at greatest risk of progressing to cancer.

An Analysis of the GIQuIC Nationwide Quality Registry Reveals Unnecessary Surveillance Endoscopies in Patients With Normal and Irregular Z-Lines.

Population-based estimates of adherence to Barrett's esophagus (BE) guidelines are not available. Using a national registry, we assessed surveillance intervals for patients with normal and irregular Z-lines based on the presence or absence of intestinal metaplasia (IM) and among patients with suspected or confirmed BE. We analyzed data from the GI Quality Improvement Consortium Registry. Endoscopy data, including procedure indication, demographics, endoscopy and histology findings, and recommendations for further endoscopy, were assessed from January 2013 through December 2019. Patients with an indication of BE screening or surveillance or an endoscopic finding of BE were included. Biopsy and surveillance practices were assessed based on the length of columnar epithelium (0 cm, <1 cm, 1-3 cm, and >3 cm) and diagnosis based on histology findings. A total of 1,907,801 endoscopies were assessed; 135,704 endoscopies (7.1%) performed in 114,894 patients met the inclusion criteria (men 61.4%, Whites 91%, and mean age of 61.7 years [SD 12.5]). Among patients with normal Z-lines, surveillance endoscopy was recommended for 81% of patients with IM and 20% of individuals without IM. Among patients with irregular Z-lines, surveillance endoscopy was recommended for 81% with IM and 24% without IM. Approximately 30% of patients with confirmed nondysplastic BE (lengths 1-3 and >3 cm) had recommended surveillance intervals of <3 years. An analysis of data from a nationwide quality registry demonstrated that patients without BE are receiving recommendations for surveillance endoscopies and many patients with nondysplastic BE are reexamined too soon.