Barrett's Esophagus Patients Research Articles

Analytical Validation of Esopredict, an Epigenetic Prognostic Assay for Patients with Barrett's Esophagus.

EsopredictTM is a prognostic assay that risk-stratifies Barrett's esophagus patients to predict future progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). Established based on foundational studies at Johns Hopkins University, a risk algorithm was developed and clinically validated in two independent studies (n = 320). EsopredictTM is currently offered as a clinical test under the Clinical Laboratory Improvement Amendments (CLIA) guidelines. Here we present the analytical validation by repeated testing of FFPE tissues (n = 26 patients), cell lines, and contrived DNA controls to determine assay performance regarding analytical sensitivity (as defined by the limit of detection (LOD)), analytical specificity (as defined by the limit of blank (LOB)), accuracy as determined from the average positive and negative agreement, repeatability, and reproducibility. The LOD for the assay at 1.5% DNA methylation was significantly higher than the LOB, as determined by an unmethylated DNA control (0% methylated DNA). Inter- and intra-assay average positive agreement (APA) were 88% and 94%, respectively, while average negative agreement (ANA) values were 90% and 94%, respectively. Average inter- and intra-assay precision were <9% and <5% coefficient of variation (CV), respectively. These results confirm that EsopredictTM is a highly reproducible, sensitive, and specific risk categorization assay for the prediction of progression to HGD or EAC within 5 years.

Hypoxia-inducible factor-1α mediates reflux-induced epithelial-mesenchymal plasticity in Barrett’s oesophagus patients

IntroductionEpithelial-mesenchymal plasticity (EMP), the process through which epithelial cells acquire mesenchymal features, is needed for wound repair but also might contribute to cancer initiation. Earlier, in vitro studies showed that...

Development and validation of a novel Barrett's oesophagus patient reported outcome measure (B-PROM)

Patients with Barrett's oesophagus (BO) carry significant cancer worry, burden of symptoms, and lack disease-specific knowledge. Currently there is no validated BO patient reported outcome measure (PROM) to measure these factors for use in clinical practice and research, hence the aim of this study was to devise a novel, validated BO-specific tool, B-PROM. Literature review, quantitative and qualitative research informed the initial item generation. The item bank was refined through a modified Delphi process between May and August 2021. The PROM was then tested through cognitive interviews and validated via multicentre testing between September 2021 and February 2023 with the aim to create a succinct tool which addresses the key important factors to BO patients and has strong psychometric properties. B-PROM covers key themes of disease-specific knowledge, trust in clinicians, burden of symptoms, cancer worry and burden of surveillance. Validation results from 387 participants (response rate 40.8%) showed 93.3% of participants completed >95% of B-PROM. All individual items scored a completion rate of >95%. Mean completion time was 5mins 34s for a sample group. Nineteen items showed a ceiling effect, 3 items showed a floor effect. Internal consistency overall demonstrated a Cronbach Alpha of 0.846, while predetermined subsections showed Cronbach alphas of 0.335, 0.718, 0.736, and 0.896. Inter-item analysis found 2 pairs of items with strong correlation, with only 6 items correlating weakly. Item-total correlation showed 19 items correlated well. Exploratory Factor analysis (EFA) with principal component analysis produced 5 components with Eigenvalues >1 of which 4/5 had satisfactory Cronbach alphas. Test-retest reliability showed no significant differences across single and average measures (p ≤ 0.001). B-PROM is the first BO-specific PROM to be systematically evaluated. Validation findings show strong internal consistency, short completion time, low missingness and excellent test-retest reliability. Medtronic Limited ISR-2016-1077.

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

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

On-chip Raman spectroscopy of live single cells for the staging of oesophageal adenocarcinoma progression.

The absence of early diagnosis contributes to oesophageal cancer being the sixth most common cause of global cancer-associated deaths, with a 5-year survival rate of < 20%. Barrett's oesophagus is the main pre-cancerous condition to adenocarcinoma development, characterised by the morphological transition of oesophageal squamous epithelium to metaplastic columnar epithelium. Early tracking and treatment of oesophageal adenocarcinoma could dramatically improve with diagnosis and monitoring of patients with Barrett's Oesophagus. Current diagnostic methods involve invasive techniques such as endoscopies and, with only a few identified biomarkers of disease progression, the detection of oesophageal adenocarcinoma is costly and challenging. In this work, single-cell Raman spectroscopy was combined with microfluidic techniques to characterise the development of oesophageal adenocarcinoma through the progression of healthy epithelial, Barrett's oesophagus and oesophageal adenocarcinoma cell lines. Principal component analysis and linear discriminant analysis were used to classify the different stages of cancer progression. with the ability to differentiate between healthy and cancerous cells with an accuracy of 97%. Whilst the approach could also separate the dysplastic stages from healthy or cancer with high accuracy-the intra-class separation was approximately 68%. Overall, these results highlight the potential for rapid and reliable diagnostic/prognostic screening of Barrett's Oesophagus patients.

Identification of novel immune cell signature in gastroesophageal reflux disease: altered mucosal mast cells and dendritic cell profile.

Heartburn pathogenesis in GERD remains incompletely understood. We aimed to identify differences in the immune cell signature and sensory mucosal markers between reflux phenotypes and healthy asymptomatic subjects. Thirty-seven patients with heartburn symptoms were phenotyped endoscopically and with objective reflux studies into erosive reflux disease (ERD) (N=10), nonerosive reflux disease (NERD) (N=9), functional heartburn (FH) (N=9), and Barrett's esophagus (BO) (N=9). Bulk mRNA-sequencing(RNA-seq) was conducted on RNA extracted from endoscopic biopsies, and immune cell deconvolution analysis was performed using CIBERSORT. RNA-seq findings were validated by immunofluorescent staining for CD1a, nerve growth factor (NGF), and mast cell tryptase in corresponding patient biopsies. Transcriptomic analysis detected higher mast cell abundance in BO, ERD, and NERD compared to healthy controls (p<0.05), with decreased dendritic cell infiltration in BO, ERD, and NERD patients compared to healthy controls and FH patients. CD1a-positive dendritic cell infiltration was significantly higher in the healthy esophageal mucosa at protein level compared to BO (p=0.0005), ERD (p=0.0004), and FH patients (p=0.0096). Moreover, NGF co-expression on mast cells in GERD patients was significantly higher than in healthy controls (p=0.0094). The mucosa in patients with GERD had a significant increase in NGF expression on mast cells, suggesting an upregulation of signalling for neuronal sprouting in GERD. Moreover, decreased dendritic cell abundance in GERD esophageal mucosa may play a role in reduced oral tolerance and development of subsequent immune responses which may participate in esophageal sensitivity.

Incidence of Esophageal Adenocarcinoma, Mortality, and Esophagectomy in Barrett's Esophagus Patients Undergoing Endoscopic Eradication Therapy.

Endoscopic eradication therapy (EET) is the preferred treatment for Barrett's esophagus (BE)-related neoplasia patients. However, the impact of EET on critical outcomes, outside of clinical trials and registry data, remains scarcely studied. We aimed to assess real-world practice patterns and clinical outcomes among BE patients undergoing EET. TriNetX is a large research network comprising linked inpatient and outpatient electronic-health record-derived data from over 80,000,000 patients. Patients with a diagnosis of BE from 2015 to 2020 were identified and included if they underwent EET during the study period. The primary outcome was the progression to EAC after index EET. Secondary outcomes included rate of esophagectomy, and all-cause mortality. All outcomes were stratified by baseline histology. The incidence of EAC and all-cause mortality were reported in person-years and adjusted for age and sex. A total of 4114 patients were analyzed. Distribution of baseline histology was as follows: NDBE (11.8%), LGD (21.4%), HGD (26.4%), EAC (20.8%), and unspecified (19.6%). The total incidence of EAC after index EET was 6.01 per 1000 person-years (PY) for the entire cohort with the highest rate in HGD patients (12.9/1000 PY). The incidence of all-cause mortality was 13.23 per 1000 PY with the highest rates in EAC patients (25.1 per 1000 PY). Rates of esophagectomy were < 1% for all grades of dysplasia. The results of this study provide "real-world" data on critical outcomes for BE patients undergoing EET, demonstrating a low risk of incident EAC, all-cause mortality, and need for esophagectomy.

Adherence to guideline recommendations for Barrett's esophagus (BE) surveillance endoscopies: Effects of dedicated BE endoscopy lists.

Background and study aims For non-dysplastic Barrett's Esophagus (BE) patients, guidelines recommend endoscopic surveillance every 3 to 5 years with four-quadrant random biopsies every 2 cm of BE length. Adherence to these guidelines is low in clinical practice. Pooling BE surveillance endoscopies on dedicated endoscopy lists performed by dedicated endoscopists could possibly enhance guideline adherence, detection of visible lesions, and dysplasia detection rates (DDRs). Patients and methods Data were used from the ACID-study (Netherlands Trial Registry NL8214), a prospective trial of BE surveillance in the Netherlands. BE patients with known or previously treated dysplasia were excluded. Guideline adherence, detection of visible lesions, and DDRs were compared for patients on dedicated and general endoscopy lists. Results A total of 1,244 patients were included, 318 on dedicated lists and 926 on general lists. Endoscopies on dedicated lists showed significantly higher adherence to the random biopsy protocol (85% vs. 66%, P <0.01) and recommended surveillance intervals (60% vs. 47%, P <0.01) compared to general lists. Detection of visible lesions (8.8% vs. 8.1%, P =0.79) and DDRs were not significantly different (6.9% and 6.6%, P =0.94). None (0.0%) of the patients scheduled on dedicated lists and 10 (1.1%) on general lists were diagnosed with esophageal adenocarcinoma ( P =0.07). In multivariable analysis, dedicated lists were significantly associated with biopsy protocol adherence and adherence to surveillance interval recommendations with odds ratios of 4.45 (95% confidence interval [CI] 2.07-9.57) and 1.64 (95% CI 1.03-2.61), respectively. Conclusions Dedicated endoscopy lists are associated with better adherence to the random biopsy protocol and surveillance interval recommendations.

Resident Esophageal Microbiota Dysbiosis Correlates with Cancer Risk in Barrett's Esophagus Patients and Is Linked to Low Adherence to WCRF/AICR Lifestyle Recommendations.

Esophageal adenocarcinoma (EAC) is the consequence of longstanding gastroesophageal reflux, which leads to inflammation and could cause Barrett's esophagus (BE), the main risk factor for EAC development. The 5 year survival rate of EAC is poor since the diagnosis occurs at the late stage of the disease. To improve patient management, a better comprehension of the mechanism undergoing the evolution through to adenocarcinoma is needed. Within this scenario, the resident microbiome investigation was studied. This study aimed to explore the esophageal microbial profile in patients affected by non-dysplastic BE, low- and high-grade dysplastic BE, and EAC to identify parameters characterizing cancer progression and to develop a score suitable for clinical practice to stratify cancer risk. The microbiota was investigated through the 16S rRNA gene sequencing of esophageal biopsies. The microbial composition was evaluated at each different taxonomic level along the disease progression. To further investigate bacteria potentially associated with cancer development, non-dysplastic and dysplastic/cancer patients were compared. The presence of the six significant microbial features with multivariate analysis was used to develop a multiparametric score (Resident Esophageal Microbial Dysbiosis Test) to predict the risk of progression toward EAC. Finally, the diagnostic ability of the test and its discrimination threshold for its ability to identify dysplastic/cancer patients were demonstrated. Since EAC has been related to obesity, the relationship between these microbial parameters and patients' diet/lifestyle habits was also investigated. Developing microbiome-based risk prediction models for esophageal adenocarcinoma onset could open new research avenues, demonstrating that the resident microbiome may be a valid cancer risk biomarker.

An Automated Tissue Systems Pathology Test can Standardize the Management and Improve Health Outcomes for Barrett's Esophagus Patients.

Low-grade dysplasia (LGD) in Barrett's esophagus (BE) is associated with an increased risk for progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). However, due to substantial interobserver variability in the diagnosis of LGD, a patient's management plan and health outcome depend largely on which pathologist reviews their case. This study evaluated the ability of a tissue systems pathology test that objectively risk stratifies patients with BE (TissueCypher, TSP-9) to standardize management in a manner consistent with improved health outcomes for BE patients. 154 BE patients with community-based LGD from the prospectively-followed screening cohort of the SURF trial were studied. Management decisions were simulated 500 times with varying generalist (n=16) and expert (n=14) pathology reviewers to determine the most likely care plan with or without use of the TSP-9 test for guidance. The percentage of patients receiving appropriate management based on the known progression/non-progression outcomes was calculated. The percentage of patients with 100% of simulations resulting in appropriate management significantly increased from 9.1% for pathology alone, to 58.4% when TSP-9 results were used with pathology, and further increased to 77.3% of patients receiving appropriate management when only TSP-9 results were used. Use of the test results also significantly increased the consistency of management decisions for patients when their slides were reviewed by different pathologists (P<0.0001). Management guided by the TSP-9 test can standardize care plans by increasing the early detection of progressors who can receive therapeutic interventions, while also increasing the percentage of non-progressors who can avoid unnecessary therapy and be managed by surveillance alone.

Cost-effectiveness Analysis of Radiofrequency Ablation in Patients With Barrett Esophagus and High-grade Dysplasia or Low-grade Dysplasia

PurposeClinical guidelines recommend radiofrequency ablation (RFA) for eradication of Barrett esophagus in patients with low-grade dysplasia (LGD) and high-grade dysplasia (HGD), but evidence on whether RFA provides good value for money is still sparse. This study evaluates the cost-effectiveness of RFA in Italy. MethodsA Markov model was used to estimate lifelong costs and consequences of disease progression with different treatments. RFA was compared with esophagectomy in the HGD group or endoscopic surveillance in the LGD group. Clinical and quality-of-life parameters were derived from a review of the literature and expert opinions, whereas Italian national tariffs were used as a proxy for costs. FindingsRFA dominated esophagectomy in patients with HGD with a probability of 83%. For patients with LGD, RFA was more effective and more costly than active surveillance (incremental cost-effectiveness ratio, €6276 per quality-adjusted life-year). At a cost-effectiveness threshold of €15,272, the probability of RFA being the optimal strategy in this population was close to 100%. Model results were sensitive to the cost of the interventions and utility weights used in the different disease states. ImplicationsRFA is likely to be the optimal choice for patients with LGD and HGD in Italy. Italy is discussing the implementation of a national program for the health technology assessment of medical devices, requiring more studies to prove value for money of emerging technologies.

651. LAPAROSCOPIC TOTAL FUNDOPLICATION IS SUPERIOR TO MEDICAL TREATMENT FOR REDUCING THE CANCER RISK IN BARRETT'S ESOPHAGUS: A LONG-TERM ANALYSIS

Abstract Background: The present study aims to compare the effectiveness of surgical and medical therapy in reducing the risk of cancer in Barrett's esophagus in a long-term evaluation. Methods: A prospective cohort was designed that compared Barrett's esophagus patients submitted to medical treatment with omeprazole or laparoscopic Nissen fundoplication. The groups were compared using propensity score matching paired by Barrett’s esophagus length. A total of 398 patients met inclusion criteria. There were 207 patients in the omeprazole group (Group A) and 191 in the total fundoplication group (Group B). After applying the propensity score matching paired by Barrett’s esophagus length, the Groups were 180 (Group A) and 190 (Group B). Median follow-up was 80 months. Group B was significantly superior for controlling GERD symptoms, in promoting Barrett’s esophagus regression or blocking its progression. Also was more efficient in preventing the development of dysplasia and cancer. Logistic regression was performed for the outcomes of adenocarcinoma and dysplasia, using age and BMI as covariates. Even after regression analysis, Group B was still superior to Group A to prevent esophageal adenocarcinoma or dysplasia transformation (OR: 0.51; 95% CI: 0.27 to 0.97, for adenocarcinoma or any dysplasia; and OR: 0.26; 95% CI: 0.08 to 0.81, for adenocarcinoma or high-grade dysplasia). Surgical treatment is superior to medical management, allowing for better symptom control, less need for reflux medication use, higher regression rate of the columnar epithelium and intestinal metaplasia, and lower risk for progression to dysplasia and cancer.

Prognostic, Diagnostic and Predictive Biomarkers in the Barrett's Oesophagus-Adenocarcinoma Disease Sequence.

Simple SummaryOesophageal adenocarcinoma (OAC) is a type of cancer of the oesophagus (food pipe) which is associated with poor patient outcomes. Barrett’s oesophagus (BO) is a precancerous condition of the oesophagus associated with chronic heartburn. Currently, surveillance programs exist which monitor patients with BO to prevent it from developing into OAC. However, these surveillance programs are expensive and unpleasant for patients. Prognostic biomarkers are signs which could be measured to determine the chance of someone with BO developing OAC, allowing more targeted surveillance. Similarly, diagnostic biomarkers are indicators which could be measured to see if someone has OAC. Developing new diagnostic biomarkers could allow wider population testing. Only a small proportion of patients with OAC respond to treatment before surgery. Predictive biomarkers could be measured to predict whether someone would respond to the treatments, allowing more individualized therapy. This review focuses on potential biomarkers which could improve patient outcomes in BO/OAC.Oesophageal adenocarcinoma (OAC) incidence has increased dramatically in the developed world, yet outcomes remain poor. Extensive endoscopic surveillance programs among patients with Barrett’s oesophagus (BO), the precursor lesion to OAC, have aimed to both prevent the development of OAC via radiofrequency ablation (RFA) and allow earlier detection of disease. However, given the low annual progression rate and the costs of endoscopy/RFA, improvement is needed. Prognostic biomarkers to stratify BO patients based on their likelihood to progress would enable a more targeted approach to surveillance and RFA of high-risk precursor lesions, improving the cost–risk–benefit ratio. Similarly, diagnostic biomarkers for OAC could enable earlier diagnosis of disease by allowing broader population screening. Current standard treatment for locally advanced OAC includes neoadjuvant chemotherapy (+/− radiotherapy) despite only a minority of patients benefiting from neoadjuvant treatment. Accordingly, biomarkers predictive of response to neoadjuvant therapy could improve patient outcomes by reducing time to surgery and unnecessary toxicity for the patients who would have received no benefit from the therapy. In this mini-review, we will discuss the emerging biomarkers which promise to dramatically improve patient outcomes along the BO-OAC disease sequence.

Multicenter Randomized Controlled Trial of Surveillance Versus Endoscopic Therapy for Barrett’s Esophagus With Low-grade Dysplasia: The SURVENT Trial: Study Rationale, Methodology, Innovation, and Implications

Multicenter Randomized Controlled Trial of Surveillance Versus Endoscopic Therapy for Barrett’s Esophagus With Low-grade Dysplasia: The SURVENT Trial: Study Rationale, Methodology, Innovation, and Implications

Measuring the Submucosal Depth of Invasion in Endoscopic Mucosal Resections for Barrett-associated Adenocarcinoma: Practical Issues and Relevance for the Decision for Esophagectomy.

Endoscopic mucosal resection (EMR) has made it possible for Barrett esophagus patients with superficial cancers to be treated without esophagectomy. Recent guidelines recommend measuring depth of invasion (DOI) in submucosal cancers based on reports that in low-risk cancers, submucosal invasion 500 μm or less is associated with low nodal metastasis rates. However, pathologists face challenges in reproducibly measuring DOI. To determine how often DOI measurements could impact treatment and to evaluate reproducibility in measuring submucosal DOI in EMR specimens. Consecutive adenocarcinoma EMR cases were identified, including cases of "low histologic risk" submucosal cancer, as follows: those with negative deep margins, no high-grade histology (G3), and no lymphovascular invasion. Submucosal DOI was measured by 7 pathologists according to guidelines. Of 213 cancer EMR cases, 46 were submucosa invasive and 6 cases were low histologic risk submucosal cancers for which measurement could impact decision-making. Of these low histologic risk cases, 3 were categorized as superficial, indicating that measurement would be a clinically actionable decision point in only 1.4% of adenocarcinoma EMRs. Interobserver agreement for in-depth categorization between 7 pathologists was moderate (κ = 0.42), and the range of measurements spanned the 500-μm relevant threshold in 40 of 55 measured samples (72.7%). While therapeutic decisions would rarely have depended on DOI measurements alone in our cohort, interobserver variability raises concerns about their use as a sole factor on which to offer patients conservative therapy. Responsibly reporting and clinically using submucosal DOI measurements will require practical experience troubleshooting common histologic artifacts, as well as multidisciplinary awareness of the impact of variable specimen-handling practices.

Image-Enhanced Endoscopy and Molecular Biomarkers Vs Seattle Protocol to Diagnose Dysplasia in Barrett’s Esophagus

Dysplasia in Barrett's esophagus often is invisible on high-resolution white-light endoscopy (HRWLE). We compared the diagnostic accuracy for inconspicuous dysplasia of the combination of autofluorescence imaging (AFI)-guided probe-based confocal laser endomicroscopy (pCLE) and molecular biomarkers vs HRWLE with Seattle protocol biopsies. Barrett's esophagus patients with no dysplastic lesions were block-randomized to standard endoscopy (HRWLE with the Seattle protocol) or AFI-guided pCLE with targeted biopsies for molecular biomarkers (p53 and cyclin A by immunohistochemistry; aneuploidy by image cytometry), with crossover to the other arm after 6 to 12 weeks. The primary end point was the histologic diagnosis from all study biopsies (trial histology). A sensitivity analysis was performed for overall histology, which included diagnoses within 12 months from the first study endoscopy. Endoscopists were blinded to the referral endoscopy and histology results. The primary outcome was diagnostic accuracy for dysplasia by real-time pCLE vs HRWLE biopsies. Of 154 patients recruited, 134 completed both arms. In the primary outcome analysis (trial histology analysis), AFI-guided pCLE had similar sensitivity for dysplasia compared with standard endoscopy (74.3%; 95% CI, 56.7-87.5 vs 80.0%; 95% CI, 63.1-91.6; P= .48). Multivariate logistic regression showed pCLE optical dysplasia, aberrant p53, and aneuploidy had the strongest correlation with dysplasia (secondary outcome). This 3-biomarker panel had higher sensitivity for any grade of dysplasia than the Seattle protocol (81.5% vs 51.9%; P &lt; .001) in the overall histology analysis, but not in the trial histology analysis (91.4% vs 80.0%; P= .16), with an area under the receiver operating curve of 0.83. Seattle protocol biopsies miss dysplasia in approximately half of patients with inconspicuous neoplasia. AFI-guided pCLE has similar accuracy to the current gold standard. The addition of molecular biomarkers could improve diagnostic accuracy.

P-OGC38 The Impact of the COVID-19 Pandemic on Barrett’s Oesophagus and Oesophago-gastric Cancer

BackgroundThe COVID-19 pandemic has placed an inexorable strain on endoscopy services worldwide, affecting the diagnosis of oesophago-gastric (OG) cancer and Barrett’s oesophagus (BO). As coronavirus infection rates rose many professional bodies advised that all endoscopy, except emergency and essential procedures be stopped immediately. We sought to quantify the decline in OG cancer and BO diagnoses following implementation of British Society of Gastroenterology (BSG) guidance related to COVID-19 and the psychosocial effects on BO patients.MethodsWe examined OG cancer and BO diagnoses in Northern Ireland from March-September 2020 and compared them with the three-year average number of patients during the same time period (corresponding to weeks 10-37) between 2017-2019 by utilising Northern Ireland Cancer Registry (NICR) data. The psychosocial impact of COVID-19 was assessed using an online survey, which included validated WHOQOL-BREF and EQ-5D-5L quality of life measures, and was completed by 24 BO patients from April-May 2020.ResultsBetween March and September 2020 in Northern Ireland, the proportion of OG cancer and BO diagnoses declined by 26.6% and 59.3%, respectively, compared to expected levels. In April, BO diagnoses fell by 95.5% but by September, whilst OG cancer rates had returned to baseline, BO cases remained supressed by approximately 20%. We estimate that these declines in diagnosis represent 53 ‘missed’ OG cancer and 236 ‘missed’ BO diagnoses. In the online survey sample, BO patients reported consistently lower quality of life scores than population norms, and highlighted a number of concerns with regard to their health and care.ConclusionsThe COVID-19 pandemic has resulted in an abrupt decline in OG cancer and BO diagnoses and has profoundly impacted the wellbeing of BO patients. Our study represents the first report of the impact of COVID-19 on the diagnosis of BO. Strategies to mitigate the ongoing effects of the pandemic are urgently required to preserve the ability to rapidly detect and diagnose cancer and pre-malignant conditions.

P-OGC95 Understanding the molecular age of Barrett’s oesophagus in a population-representative sample of patients

Abstract Background The incidence of oesophageal adenocarcinoma (OAC) increases dramatically with patient age but only a small proportion of patients with diagnosed Barrett’s oesophagus (BO), the precursor to OAC, will develop dysplasia and/or cancer. Beyond chronological age, biomarkers of progression that capture biological aging offer largely untapped potential for objectively identifying BO patients at highest risk of progression, who could undergo personalised surveillance at shorter intervals. We have developed computational tools to determine tissue-specific aging using genome-wide methylation data as a “molecular clock” for estimating patient-specific BO dwell times at the time of incident diagnosis that cannot be clinically measured by other means. Methods Using the population-based Northern Ireland BO register in a retrospective study, we have identified 46 non-dysplastic BO patients who have 2-4 serial endoscopic biopsies each, and have not progressed to OAC (age range 29-77 years). FFPE biopsies for 10 age-matched patients who had prevalent HGD/OAC at index BO diagnosis were also retrieved. DNA has been extracted, quantified using fluorescence, quality checked through qPCR, and prepared for Illumina EPIC methylation arrays. We created a Python package called “MethylDrift” to determine genome-wide aging rates in patient data. Model outputs are used in the molecular clock for BO tissue age. Results We used MethylDrift to quantify aging rates in both cross-sectional data (population-level epigenetic drift) and longitudinal data within the same patients to obtain individual aging rates. Computational analyses using our previously developed Bayesian framework for the BO molecular clock will be applied to estimate the molecular age of BO in patients, i.e., how long the patient has been living with BO since onset of metaplasia. Results will be compared between age groups, birth cohorts, sex, and importantly between dysplastic and non-dysplastic BO to evaluate biomarker potential. Data analysis is ongoing, and the final results will be presented at the meeting. Conclusions Our results from this nested case-control study demonstrate feasibility and generate pilot data on molecular age as a proxy of BO duration at the time of incident diagnosis, in a large population-based registry of patients with BO. This will inform our computational tools for determining biological aging and can be applied in future work to investigate progression risk according to molecular age. Ultimately, this biomarker could inform surveillance frequency for BO patients, enable earlier detection of neoplastic progression, leading to improved patient outcomes and optimal distribution of limited endoscopy capacity for surveillance.

Studying the Role of IMP3 and P53 in Detection of Dysplastic Changes in Barrett's Esophagus

Abstract Background: Barrett's esophagus (BE) is an acquired metaplastic lesion with unpredictable potential for esophageal adenocarcinoma (EAC). Searching for immunohistochemical markers for predicting progression in Barrett's esophagus is of increasing interest. Aim of Study: The aim of this study is to detect early dysplastic changes in patients with BE for better management of diagnosed cases. Material and Methods: This retrospective study was carried upon 28 endoscopic biopsies of BE; 6 cases of Barrett's esophagus without dysplasia, 12 cases were Barrett's esophagus with low grade dysplasia and 10 cases with high grade dys-plasia. Cases were collected from archives of Pathology Department and Early Cancer Detection Unit (ECDU), Faculty of Medicine, Benha University during the years 2015-2020. IMP3 and P53 immunohistochemichal staining were performed and evaluated for each case. Results: IMP3 was positive with high expression in 80% of high grade dysplasia cases which was a statistically signif-icant relation between IMP3 expression and grade of dysplasia. P53 was a highly sensitive marker for early dysplastic changes, reporting 100% sensitivity to low grade dysplasia. P53 was also highly specific to high grade dysplasia (100%). IMP3 was found to be highly sensitive to high grade dysplastic changes (90%). Conclusion: Combination of both markers could be helpful in detection of early dysplastic changes in Barrett's esophagus patients who are at risk of malignancy to start a strict follow-up procedures. Both markers together could be useful in detection ofhigh grade dysplasiaand rapid intervention to prevent malignant transformation.

Systematic review with meta-analysis: association of Helicobacter pylori infection with gastro-oesophageal reflux and its complications.

Conflicting results exist on the association between Helicobacter pylori infection and gastro-oesophageal reflux (GOR), and its complications, such as erosive oesophagitis (EO) and Barrett's oesophagus (BO). To explore the association of H. pylori infection with GOR symptoms and their complications METHODS: We searched Embase, PubMed, Web of Science and Scopus databases through December 2020 for relevant articles. Regarding the association between H. pylori and GOR symptoms (heartburn, regurgitation or reflux), we included observational studies comparing the prevalence of GOR symptoms between H. pylori-positive and -negative individuals. Concerning the association between H. pylori and complications of GOR, we included studies comparing the prevalence of EO or BO between H. pylori-positive and -negative individuals. In total, 36 papers were eligible. Based on seven cross-sectional surveys, H. pylori infection was associated with a lower odds of GOR symptoms (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.61-0.90). However, in four case-control studies, H. pylori infection was not associated with odds of GOR symptoms (OR 1.10, 95% CI 0.85-0.1.43). In 26 cross-sectional studies in patients with GOR symptoms, the OR for EO was 0.70 (95% CI 0.58-0.84) in H. pylori-positive vs -negative cases. Based on nine cross-sectional studies in subjects with GOR complications, no significant association was found between H. pylori infection and either endoscopically-diagnosed (OR 1.84, 95% CI 0.67-5.02) or histologically confirmed (OR 0.85, 95% CI 0.60-1.20) BO. Helicobacter pylori infection appears to be associated with a decreased odds of GOR symptoms and EO. In contrast, H. pylori infection did not seem to affect the odds of BO in patients with GER complications.