Metastatic cancers arise from a decades-long succession of increasingly virulent precursor lesions, each of which represents prospective targets for therapeutic intervention. This evolutionary process has been particularly vivid in esophageal adenocarcinoma (EAC), as this cancer and associated precursor lesions, including Barrett's esophagus (BE), low-grade dysplasia (LGD), and high-grade dysplasia (HGD), coexist in an accessible, 2-dimensional pattern in esophageal mucosa. Given the durability of these precursor lesions, it is likely that they, like EAC, rely on stem cells for their regenerative growth. To assess the role of stem cells in the evolution of EAC, we apply technology that selectively clones stem cells from the gastrointestinal tract to patient-matched endoscopic biopsies from each of the precursor lesions implicated in EAC.

Histologically validated, endoscopic biopsy series including EAC, HGD, LGD, BE, and normal esophageal mucosa were obtained from patients presenting with EAC. Rare (1:1000) cells from each of these lesions proved clonogenic and were assessed by in vitro differentiation, tumorigenicity in mice, and by molecular genetics.

Each of the lesions in the evolution of EAC possesses a discrete set of clonogenic cells marked by immaturity, enormous proliferative potential, and lesion-specific differentiation fate. DNA sequencing of these clones reveals intralesional heterogeneity and clonal resolution of the mutation progression within a given patient from BE, LGD, HGD, and EAC. High-throughput chemical screens against BE stem cells reveal drug combinations that are similarly effective against stem cells of LGD, HGD, and EAC.

All lesions in the evolution of EAC possess discrete populations of stem cells that are potential therapeutic targets.

Hybrid argon plasma coagulation (H-APC) is a novel technique for ablation of neoplastic Barrett's esophagus (BE), consisting in submucosal fluid injection and subsequent APC of visible BE. The aim of this study was to assess H-APC efficacy, safety, and tolerability.

We prospectively included patients undergoing H-APC ablation at four Italian Hospitals from September 2022 to March 2024. Patients with BE C3M5 maximum extent, low- or high-grade dysplasia (LGD, HGD) or residual BE after endoscopic resection (ER) of visible lesions were included. Patients who had undergone previous ablative treatments were excluded. The primary endpoints were complete eradication of intestinal metaplasia (CE-IM) and dysplasia (CE-D). Secondary endpoints were safety in terms of major and minor adverse events (AEs) and tolerability, assessed using pain (0-10) and dysphagia (0-5) scores within 7 days post-ablation (NCT05645679).

Among the 51 enrolled patients (mean circumferential 0.43 cm; standard deviation [SD] 0.72, mean maximum longitudinal 2.20 cm; SD 1.09) who completed treatment (80 H-APC sessions), 45.1% (23/51) had prior ER of visible lesions. All patients achieved both CE-IM and CE-D (51/51), requiring a mean of 1.51 sessions (SD 0.83). Only one case of fever and absolute dysphagia was observed (1/51; 1.96% AEs). Regarding tolerability, mean pain score was 1.3 (SD 1.99) whereas mean dysphagia score was 1.28 (SD 0.56).

The H-APC technique showed promising results in terms of effectiveness and safety with good tolerability in achieving initial CE-IM and CE-D in a selected population of BE patients.

Barrett's esophagus (BE) is described by the transformation of the normal squamous epithelium into metaplastic columnar epithelium, driven by chronic gastroesophageal reflux disease (GERD). BE is a recognized premalignant condition and the main precursor to esophageal adenocarcinoma (EAC). Understanding the molecular mechanisms underlying BE carcinogenesis is crucial for improving prevention, surveillance, and treatment strategies.

This narrative review examines the molecular abnormalities associated with the progression of BE to EAC.

This study highlights inflammatory, genetic, epigenetic, and chromosomal alterations, emphasizing key pathways and biomarkers. BE progression follows a multistep process involving dysplasia and genetic alterations such as TP53 and CDKN2A (p16) mutations, chromosomal instability, and dysregulation of pathways like PI3K/AKT/mTOR. Epigenetic alterations, including aberrant microRNA expression or DNA methylation, further contribute to this progression. These molecular changes are stage-specific, with some alterations occurring early in BE during the transition to high-grade dysplasia or EAC. Innovations in chemoprevention, such as combining proton pump inhibitors and aspirin, and the potential of antireflux surgery to halt disease progression are promising. Incorporating molecular biomarkers into surveillance strategies and advancing precision medicine may enable earlier detection and personalized treatments.

BE is the primary preneoplastic condition for EAC. A deeper understanding of its molecular transformation can enhance surveillance protocols, optimize the management of gastroesophageal reflux inflammation, and refine prevention and therapeutic strategies, ultimately contributing to a reduction in the global burden of EAC.

Barrett esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). We aimed to assess performance, safety, and tolerability of the EsoGuard (EG) assay on samples collected nonendoscopically with the EsoCheck (EC) device (EG/EC) for BE detection in the intended-use population meeting American College of Gastroenterology guideline criteria (chronic gastroesophageal reflux disease and 3+ additional risk factors).

We performed a prospective, multicenter study (NCT04293458) to assess EG performance (primary endpoint) on cells collected with EC, for detection of BE and EAC using esophagogastroduodenoscopy (EGD) and biopsies as the comparator. Twenty-four sites across the United States and Spain participated. EC safety and usability were assessed as secondary endpoints.

180 male subjects aged >50 years with chronic gastroesophageal reflux disease met eligibility criteria, of which 163 (90.6%) had EGD and successful EC administration. Mean age was 60.5 years, 34.4% were obese, 56.7% had tobacco history, and 3.9% had a 1st degree relative with BE or EAC. Of 122 samples analyzed, 93 contributed to the primary endpoint analysis. Eight subjects (8.6%) in the Primary Analysis Population had BE on EGD, none with dysplasia. Sensitivity of EG for BE was 87.5% (95% confidence interval [CI] 47.4-99.7), specificity was 81.2% (95% CI 71.2-88.8), positive predictive value was 30.4% (95% CI 13.2-52.9), and negative predictive value was 98.6% (95% CI 92.3-99.96). Mild esophageal abrasions were observed in 1.5%; no serious adverse events were reported.

This study in the intended-use population suggests that EG/EC is promising for BE screening. While future work is necessary to define its performance characteristics with more precision, this approach may provide a safe, accurate, and well-tolerated nonendoscopic alternative in high-risk patients.

Surveillance of nondysplastic Barrett's esophagus (NDBE) is recommended to identify progression to dysplasia; however, the most cost-effective strategy remains unclear. Mutation of TP53 or aberrant expression of p53 have been associated with the development of dysplasia in BE. We sought to determine if surveillance intervals for BE could be stratified based on p53 expression.

A Markov model was developed for NDBE. Patients with NDBE underwent p53 immunohistochemistry (IHC) and those with abnormal p53 expression underwent surveillance endoscopy at 1 year, while patients with normal p53 expression underwent surveillance in 3 years. Patients with dysplasia underwent endoscopic therapy and surveillance.

On base-case analysis, the strategy of stratifying surveillance based on abnormal p53 IHC was cost-effective relative to conventional surveillance and a natural history model, with an incremental cost-effectiveness ratio (ICER) of $8258 for p53 IHC-based surveillance. Both the conventional and p53-stratified surveillance strategies dominated the natural history model. On probabilistic sensitivity analysis, the p53 IHC strategy ($28 652; 16.78 quality-adjusted life years [QALYs]) was more cost-effective than conventional surveillance ($25 679; 16.17 QALYs) with a net monetary benefit of $306 873 compared with conventional surveillance ($297 642), with an ICER <$50 000 in 96% of iterations. The p53-stratification strategy was associated with a 14% reduction in the overall endoscopy burden and a 59% increase in dysplasia detection.

A surveillance strategy for BE based on abnormal p53 IHC is cost-effective relative to a conventional surveillance strategy and is likely to be associated with higher rates of dysplasia diagnosis.

Gastrointestinal cancers are a leading cause of cancer morbidity and mortality. Many gastrointestinal cancers develop from cancer precursor lesions, which are commonly found in individuals with hereditary cancer syndromes. Hereditary cancer syndromes have advanced our understanding of cancer development and progression and have facilitated the evaluation of cancer prevention and interception efforts. Common gastrointestinal hereditary cancer syndromes, including their organ-specific cancer risk and surveillance recommendations, are reviewed in this article. The management of common gastroesophageal, pancreatic, and colonic precursor lesions is also discussed, regardless of their genetic background. Further research is needed to advance chemoprevention and immunoprevention strategies.

Barrett's esophagus (BE) is a diagnosis of esophageal intestinal metaplasia, which can progress to esophageal adenocarcinoma (EAC), and guidelines recommend endoscopic surveillance for early detection and treatment of EAC. However, current practices have limited effectiveness in risk-stratifying patients with BE.

This study aimed to evaluate use of the TSP-9 test in risk-stratifying clinically relevant subsets of patients with BE in clinical practice.

TSP-9 results for tests ordered by 891 physicians for 8080 patients with BE with clinicopathologic data were evaluated. Orders were from nonacademic (94.3%) and academic (5.7%) settings for nondysplastic BE (NDBE; n=7586; 93.9%), indefinite for dysplasia (IND, n=312, 3.9%), and low-grade dysplasia (LGD, n=182, 2.3%).

The TSP-9 test scored 83.2% of patients with low risk, 10.6% intermediate risk, and 6.2% high risk, respectively, for progression to HGD/EAC within 5 years. TSP-9 provided significant risk-stratification independently of clinicopathologic features, within NDBE, IND, and LGD subsets, male and female, and short- and long-segment subsets of patients. TSP-9 identified 15.3% of patients with NDBE as intermediate/high-risk for progression, which was 6.4 times more than patients with a pathology diagnosis of LGD. Patients with NDBE who scored intermediate or high risk had a predicted 5-year progression risk of 8.1% and 15.3%, respectively, which are similar to and higher than published progression rates in patients with BE with confirmed LGD.

The TSP-9 test identified a high-risk subset of patients with NDBE who were predicted to progress at a higher rate than confirmed LGD, enabling early detection of patients requiring management escalation to reduce the incidence of EAC. TSP-9 scored the majority of patients with NDBE as low risk, providing support to adhere to 3- to 5-year surveillance per guidelines.

Evaluating clinical care through quality-related metrics is increasingly common. There are now numerous quality statements and indicators related to the medical management of benign and pre-malignant esophageal diseases. Expert consensus leveraging evidence-based recommendations from published society guidelines has been the most frequently used basis for developing esophageal quality statements. While surgical care of patients with esophageal malignancies, including squamous cell carcinoma, has also been developed, those related to benign esophageal disease now include domains of diagnosis, treatment, and monitoring for gastroesophageal reflux disease, eosinophilic esophagitis (EoE), achalasia, and Barrett's esophagus (BE). Several recent studies evaluating adherence to quality metrics affirm substantial variation in practice patterns with opportunities for improvement in care across esophageal diseases. In particular, patient education regarding treatment options in achalasia, frequency of esophageal biopsies among patients with dysphagia to evaluate for EoE, and endoscopic evaluation within a BE segment are areas identified to have need for improvement. As the management of esophageal diseases becomes more complex and interdisciplinary, adherence to quality metrics may be a source of standardization and improvement in delivery and ultimately patient outcomes. Indeed, the development of national quality databases has resulted in a significant growth in the use of these metrics for quality improvement activities and may form the basis for future inclusion in quality reporting and payment programs.

Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Endoscopic eradication therapy (EET) can be effective in eradicating BE and related neoplasia and has greater risk of harms and resource use than surveillance endoscopy. This clinical practice guideline aims to inform clinicians and patients by providing evidence-based practice recommendations for the use of EET in BE and related neoplasia.

The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients, conducted an evidence review, and used the Evidence-to-Decision Framework to develop recommendations regarding the use of EET in patients with BE under the following scenarios: presence of (1) high-grade dysplasia, (2) low-grade dysplasia, (3) no dysplasia, and (4) choice of stepwise endoscopic mucosal resection (EMR) or focal EMR plus ablation, and (5) endoscopic submucosal dissection vs EMR. Clinical recommendations were based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations.

The panel agreed on 5 recommendations for the use of EET in BE and related neoplasia. Based on the available evidence, the panel made a strong recommendation in favor of EET in patients with BE high-grade dysplasia and conditional recommendation against EET in BE without dysplasia. The panel made a conditional recommendation in favor of EET in BE low-grade dysplasia; patients with BE low-grade dysplasia who place a higher value on the potential harms and lower value on the benefits (which are uncertain) regarding reduction of esophageal cancer mortality could reasonably select surveillance endoscopy. In patients with visible lesions, a conditional recommendation was made in favor of focal EMR plus ablation over stepwise EMR. In patients with visible neoplastic lesions undergoing resection, the use of either endoscopic mucosal resection or endoscopic submucosal dissection was suggested based on lesion characteristics.

This document provides a comprehensive outline of the indications for EET in the management of BE and related neoplasia. Guidance is also provided regarding the considerations surrounding implementation of EET. Providers should engage in shared decision making based on patient preferences. Limitations and gaps in the evidence are highlighted to guide future research opportunities.

Whether gastric metaplasia (GM) of the oesophagus should be considered as Barrett's oesophagus (BO) is controversial. Given concern intestinal metaplasia (IM) may be missed due to sampling, the UK guidelines include GM as a type of BO. Here, we investigated whether the risk of misdiagnosis and the malignant potential of GM warrant its place in the UK surveillance.

We performed a thorough pathology and endoscopy review to follow clinical outcomes in a novel UK cohort of 244 patients, covering 1854 person years of follow-up. We complemented this with a comparative genomic analysis of 160 GM and IM specimens, focused on early molecular hallmarks of BO and oesophageal adenocarcinoma (OAC).

We found that 58 of 77 short-segment (<3 cm) GM (SS-GM) cases (75%) continued to be observed as GM-only across a median of 4.4 years of follow-up. We observed that disease progression in GM-only cases and GM+IM cases (cases with reported GM on some occasions, IM on others) was significantly lower than in the IM-only cases (Kaplan-Meier, p=0.03). Genomic analysis revealed that the mutation burden in GM is significantly lower than in IM (p<0.01). Moreover, GM does not bear the mutational hallmarks of OAC, with an absence of associated signatures and driver gene mutations. Finally, we established that GM found adjacent to OAC is evolutionarily distant from cancer.

SS-GM is a distinct entity from SS-IM and the malignant potential of GM is lower than IM. It is questionable whether SS-GM warrants inclusion in BO surveillance.

Early detection of dysplasia and effective management are critical steps in halting neoplastic progression in patients with Barrett's esophagus (BE). This review provides a contemporary overview of the BE-related dysplasia, its role in guiding surveillance and management, and discusses emerging diagnostic and therapeutic approaches that might further enhance patient management. Novel, noninvasive techniques for sampling and surveillance, adjunct biomarkers for risk assessment, and their limitations are also discussed.

Barrett's esophagus (BE), which has increased in prevalence worldwide, is a precursor for esophageal adenocarcinoma. Although there is a gap in the detection rates between endoscopic BE and histological BE in current research, we trained our artificial intelligence (AI) system with images of endoscopic BE and tested the system with images of histological BE.

To assess whether an AI system can aid in the detection of BE in our setting.

Endoscopic narrow-band imaging (NBI) was collected from Chung Shan Medical University Hospital and Changhua Christian Hospital, resulting in 724 cases, with 86 patients having pathological results. Three senior endoscopists, who were instructing physicians of the Digestive Endoscopy Society of Taiwan, independently annotated the images in the development set to determine whether each image was classified as an endoscopic BE. The test set consisted of 160 endoscopic images of 86 cases with histological results.

Six pre-trained models were compared, and EfficientNetV2B2 (accuracy [ACC]: 0.8) was selected as the backbone architecture for further evaluation due to better ACC results. In the final test, the AI system correctly identified 66 of 70 cases of BE and 85 of 90 cases without BE, resulting in an ACC of 94.37%.

Our AI system, which was trained by NBI of endoscopic BE, can adequately predict endoscopic images of histological BE. The ACC, sensitivity, and specificity are 94.37%, 94.29%, and 94.44%, respectively.

Although low-grade dysplasia (LGD) in Barrett's esophagus (BE) is a histopathological diagnosis based on different histological abnormalities, it is still problematic for different reasons. Patients without confirmed diagnosis of LGD undergo unnecessary and intensified follow-up where the risk of progression is low in the majority of cases. In contrast, the presence of confirmed LGD indicates a high risk of progression. In this article we try to address these reasons focusing on re-confirmation of LGD diagnosis, interobserver agreement, and persistent confirmed LGD. The progression risk of LGD to high-grade dysplasia and esophageal adenocarcinoma will also be reviewed.

Barrett's esophagus (BE) is the main precursor of esophageal adenocarcinoma (EAC). This study aimed to identify the risk factors associated with BE progression to dysplasia or EAC in a Latin population.

The study is a retrospective analysis of a single-center cohort of patients with BE, evaluated from 2002 to 2012.

We identified 420 patients with BE; 281 (66.9%) of them were men with a mean age of 57.2 ± 15.3 years. Among all BE patients evaluated, 81 (19.3%) had progression to some degree of dysplasia/EAC. The mean follow-up was 5.6 years. Multivariate analysis showed that age (OR = 1.03), cigarette smoking (OR = 3.05), long-segment BE (OR = 4.81), and a visible lesion on BE (OR = 6.94) were associated with progression to dysplasia/EAC.

In Latin patients with BE, age, cigarette smoking, long-segment BE, and the presence of lesions were associated with the presence of dysplasia/EAC.

Barrett's oesophagus is a pathological condition whereby the normal oesophageal squamous mucosa is replaced by specialised, intestinal-type metaplasia, which is strongly linked to chronic gastro-oesophageal reflux. A correct endoscopic and histological diagnosis is pivotal in the management of Barrett's oesophagus to identify patients who are at high risk of progression to neoplasia. The presence and grade of dysplasia and the characteristics of visible lesions within the mucosa of Barrett's oesophagus are both important to guide the most appropriate endoscopic therapy. In this review, we provide an overview on the management of Barrett's oesophagus, with a particular focus on recent advances in the diagnosis and recommendations for endoscopic therapy to reduce the risk of developing oesophageal adenocarcinoma.

Suppressor of mother against decapentaplegic (SMAD) family proteins are central to one of the most versatile cytokine signalling pathways in metazoan biology, the transforming growth factor-β (TGF-β) pathway. The TGF-β pathway is widely known for its dual role in cancer progression as both an inhibitor of tumour cell growth and an inducer of tumour metastasis. This is mainly mediated through SMAD proteins and their cofactors or regulators. SMAD proteins act as transcription factors, regulating the transcription of a wide range of genes, and their rich post-translational modifications are influenced by a variety of regulators and cofactors. The complex role, mechanisms, and important functions of SMAD proteins in tumours are the hot topics in current oncology research. In this paper, we summarize the recent progress on the effects and mechanisms of SMAD proteins on tumour development, diagnosis, treatment and prognosis, and provide clues for subsequent research on SMAD proteins in tumours.

The incidence of obesity is increasing in developed societies, and surgical treatment is one treatment option. The most common surgical treatment for obesity is laparoscopic sleeve gastrectomy (LSG). Gastroesophageal reflux disease (GERD) is a complication of both obesity and the surgical treatment of obesity.

In this study, the PubMed database was searched using the keywords "GERD" and "bariatric surgery", and 987 papers published between 1 July 2017 and 30 June 2022 were retrieved.

Nine papers met the inclusion criteria and were included in the meta-analysis. The articles were analyzed for the de novo occurrence of GERD after the treatment of its symptoms, the occurrence of erosive esophagitis, and Barrett's esophagus. In addition, interesting conclusions are presented from the papers that did not meet the inclusion criteria but shed light on the pathophysiology of GERD in obese patients undergoing LSG.

In conclusion, the authors draw attention to the need for endoscopic surveillance in patients undergoing LSG, even in the absence of clinical signs of GERD.

Endoscopic eradication therapy (EET) is an effective treatment for Barrett's esophagus (BE); however, disease recurrence remains problematic requiring surveillance post-treatment. While data regarding predictors of recurrence are limited, uncontrolled reflux may play a significant role. Our aim was to develop a scoring system based on histopathologic reflux in surveillance biopsies following EET to identify patients at high risk for recurrence of BE. Patients were identified from two centers in the treatment with resection and endoscopic ablation techniques for BE consortium. Hematoxylin and eosin-stained slides of surveillance biopsies post-EET were assessed for histologic changes associated with reflux from a cohort of patients who also underwent pH-metry (derivation cohort). We developed a novel scoring system (Recurrent Epithelial Changes from Uncontrolled Reflux [RECUR]) composed of dilated intercellular spaces, epithelial ballooning, basal cell hyperplasia, and parakeratosis, to identify patients with abnormal esophageal acid exposure. This scoring system was then used to grade surveillance biopsies from patients with or without recurrence of BE following EET (validation cohort). Of 41 patients in the derivation cohort, 19.5% had abnormal acid exposure times (AET) while on proton pump inhibitor therapy. The mean (SD) RECUR score for patients with AET <4% was 4.0 (1.6), compared with 5.5 (0.9) for AET ≥4% (P = 0.015). In the validation cohort consisting of 72 patients without recurrence and 64 patients with recurrence following EET, the RECUR score was the only significant predictor of recurrence (odds ratio: 1.36, 95% confidence interval: 1.10-1.69, P = 0.005). Histologic grading of surveillance biopsies using the RECUR scoring system correlates with BE recurrence following EET.

Over the last two decades, endoscopic eradication therapy has been established as the therapeutic strategy of choice for patients with Barrett's oesophagus-related dysplasia and early oesophageal adenocarcinoma. With a multimodal approach, ablative therapies have been highly effective in achieving remarkable eradication rates of metaplastic epithelium with an acceptable adverse event rate. Among ablative techniques, radiofrequency ablation is currently considered as the first-line option as its efficacy and safety are strongly supported by relevant data. Nevertheless, radiofrequency ablation is costly, and not universally available, or applicable to every situation. Moreover, primary failure and recurrence rates are not negligible. In the last few years, cryotherapy techniques and hybrid argon plasma coagulation have been increasingly assessed as potential novel ablative therapies. Preliminary data have been promising and suggest that they may even have a role as first-line options, alternatively to radiofrequency ablation. The aim of this review is to provide a practical guide for the ablation of Barrett's oesophagus, with emphasis on the different ablative options.

Endoscopic surveillance of Barrett's esophagus, aiming to detect prevalent dysplasia and adenocarcinoma, followed by effective endoscopic treatment, is an integral part of the esophageal adenocarcinoma prevention paradigm. However, several limitations, such as the subtle appearance of dysplasia, sampling error (inherent in current surveillance protocols), and noncompliance with surveillance recommendations, lead to missed dysplasia and neoplasia, reducing the effectiveness of surveillance as currently practiced. Careful endoscopic assessment with high-resolution white-light endoscopy, dye-based or electronic chromoendoscopy, and comprehensive sampling of the BE mucosa, remains the cornerstone of endoscopic surveillance. Emerging innovations in this area span the gamut of more efficient sampling methods, advanced imaging tools, artificial intelligence, and molecular marker-powered approaches as adjuncts, to identify prevalent and predict incident dysplasia or adenocarcinoma. Development and implementation of validated quality indicators will allow additional advancement of this critical field. These approaches will hopefully enable efficient and effective cancer prevention and treatment.

Barrett’s esophagus (BE) is a change in the distal esophageal mucosal lining, whereby metaplastic columnar epithelium replaces squamous epithelium of the esophagus. This change represents a pre-malignant mucosal transformation which has a known association with the development of esophageal adenocarcinoma. Gastroesophageal reflux disease is a risk factor for BE, other risk factors include patients who are Caucasian, age > 50 years, central obesity, tobacco use, history of peptic stricture and erosive gastritis. Screening for BE remains selective based on risk factors, a screening program in the general population is not routinely recommended. Diagnosis of BE is established with a combination of endoscopic recognition, targeted biopsies, and histologic confirmation of columnar metaplasia. We aim to provide a comprehensive review of the epidemiology, pathogenesis, screening and advanced techniques of detecting and eradicating Barrett’s esophagus.

Strong recruitment and retention into randomised controlled trials involving invasive therapies is a matter of priority to ensure better achievement of trial aims. The BRIDE (Barrett's Randomised Intervention for Dysplasia by Endoscopy) Study investigated the feasibility of undertaking a multicentre randomised controlled trial comparing argon plasma coagulation and radiofrequency ablation, following endoscopic resection, for the management of early Barrett's neoplasia. This paper aims to identify factors influencing patients' participation in the BRIDE Study and determine their views regarding acceptability of a potential future trial comparing surgery with endotherapy.

A semistructured telephone interview study was performed, including both patients who accepted and declined to participate in the BRIDE trial. Interview data were analysed using the constant comparison approach to identify recurring themes.

Interview participants were recruited from across six UK tertiary centres where the BRIDE trial was conducted.

We interviewed 18 participants, including 11 participants in the BRIDE trial and 7 who declined.

Four themes were identified centred around interviewees' decision to accept or decline participation in the BRIDE trial and a potential future trial comparing endotherapy with surgery: (1) influence of the recruitment process and participant-recruiter relationship; (2) participants' views of the design and aim of the study; (3) conditional altruism as a determining factor and (4) participants' perceptions of surgical risks versus less invasive treatments.

We identified four main influences to optimising recruitment and retention to a randomised controlled trial comparing endotherapies in patients with early Barrett's-related neoplasia. These findings highlight the importance of qualitative research to inform the design of larger randomised controlled trials.

Cryoablation is an interdisciplinary, widely used treatment approach for several types of solid tumors, making it difficult to obtain a comprehensive picture of its current status and popular research topics. This study aimed to use a bibliometric approach to understand important research themes and trends in cryoablation and oncology.

Literature studies on cryoablation and oncology from 2001 to 2020 were extracted from the Web of Science. A bibliometric analysis was performed based on the annual publication volume, several journal articles and local citation score, and distribution of keywords and trends in the literature using tools such as COOC version 9.94, VOSviewer version 1.6.17, and the bibliometrix version 3.1.3 R package.

This study included 2793 publications. Total yearly publications have plateaued over the last 20 years. Five research themes were presented in the keyword network, including clinical applications of cryoablation in liver, lung, kidney, prostate, and skin cancers and comparison of cryoablation with other energy ablations. After 2012, 2 new research topics emerged: synergy between cryoablation and immunotherapy in tumors and cryoablation of Barrett esophagus. The high cited literatures are dominated by studies related to cryoablation for renal and prostate cancer treatment, but they also reflect the recent increasing interest in immunotherapy and bone metastases. Twenty important journals were identified, with Cryobiology publishing the most articles.

Bibliometric analysis of studies related to tumor cryoablation can help researchers rapidly comprehend popular topics and determine future trends, guiding future research directions.

Appropriate surveillance and treatment of Barrett's esophagus (BE) is vital to prevent disease progression and decrease esophageal adenocarcinoma (EAC)-related mortality. We sought to determine the variation in BE care and identify improvement opportunities. 275 physicians (113 general gastroenterologists, 128 interventional gastroenterologists, 34 gastrointestinal surgeons) cared for 3 simulated patients, one each from 3 BE clinical scenarios: non-dysplastic BE (NDBE), BE indefinite for dysplasia (IND), and BE with low grade dysplasia (LGD), and care scores were measured against societal guidelines. Overall quality-of-care scores ranged from 17% to 85% with mean of 47.9% ± 11.8% for NDBE, 50.8% ± 11.7% for IND, and 52.7% ± 12.2% for LGD. Participants appropriately determined risk of progression 20.3% of the time: 14.4% for NDBE cases, 19.9% for LGD cases, and 26.8% for IND cases (P = .001). Treatment and follow-up care scores averaged 12.9% ± 17.5% overall. For the LGD cases, guideline-recommended twice-daily PPI treatment was ordered only 24.7% of the time. Guideline-based follow-up endoscopic surveillance was done in only 27.7% of NDBE cases and 32.7% of IND cases. For the LGD cases, 45.4% ordered endoscopic eradication therapy while 25.1% chose annual endoscopic surveillance. Finally, participants provided counseling on lifestyle modifications in just 20% of cases. Overall care of patients diagnosed with BE varied widely and showed room for improvement. Specific opportunities for improvement were adherence to guideline recommended surveillance intervals, patient counseling, and treatment selection for LGD. Physicians would potentially benefit from additional BE education, endoscopic advances, and better methods for risk stratification.

Recommended surveillance intervals after complete eradication of intestinal metaplasia (CE-IM) after endoscopic eradication therapy (EET) are largely not evidence-based. Using recurrence rates in a multicenter international Barrett's esophagus (BE) CE-IM cohort, we aimed to generate optimal intervals for surveillance.

Patients with dysplastic BE undergoing EET and achieving CE-IM from prospectively maintained databases at 5 tertiary-care centers in the United States and the United Kingdom were included. The cumulative incidence of recurrence was estimated, accounting for the unknown date of actual recurrence that lies between the dates of current and previous endoscopy. This cumulative incidence of recurrence subsequently was used to estimate the proportion of patients with undetected recurrence for various surveillance intervals over 5 years. Intervals were selected that minimized recurrences remaining undetected for more than 6 months. Actual patterns of post-CE-IM follow-up evaluation are described.

A total of 498 patients (with baseline low-grade dysplasia, 115 patients; high-grade dysplasia [HGD], 288 patients; and intramucosal adenocarcinoma [IMCa], 95 patients) were included. Any recurrence occurred in 27.1% and dysplastic recurrence occurred in 8.4% over a median of 2.6 years of follow-up evaluation. For pre-ablation HGD/IMCa, intervals of 6, 12, 18, and 24 months, and then annually, resulted in no patients with dysplastic recurrence undetected for more than 6 months, comparable with current guideline recommendations despite a 33% reduction in the number of surveillance endoscopies. For pre-ablation low-grade dysplasia, intervals of 1, 2, and 4 years balanced endoscopic burden and undetected recurrence risk.

Lengthening post-CE-IM surveillance intervals would reduce the endoscopic burden after CE-IM with comparable rates of recurrent HGD/IMCa. Future guidelines should consider reduced surveillance frequency.

The risk of progression in Barrett's esophagus (BE) increases with development of dysplasia. There is a critical need to improve the diagnosis of BE dysplasia, given substantial interobserver disagreement among expert pathologists and overdiagnosis of dysplasia by community pathologists. We developed a deep learning model to predict dysplasia grade on whole-slide imaging.

We digitized nondysplastic BE (NDBE), low-grade dysplasia (LGD), and high-grade dysplasia (HGD) histology slides. Two expert pathologists confirmed all histology and digitally annotated areas of dysplasia. Training, validation, and test sets were created (by a random 70/20/10 split). We used an ensemble approach combining a "you only look once" model to identify regions of interest and histology class (NDBE, LGD, or HGD) followed by a ResNet101 model pretrained on ImageNet applied to the regions of interest. Diagnostic performance was determined for the whole slide.

We included slides from 542 patients (164 NDBE, 226 LGD, and 152 HGD) yielding 8596 bounding boxes in the training set, 1946 bounding boxes in the validation set, and 840 boxes in the test set. When the ensemble model was used, sensitivity and specificity for LGD was 81.3% and 100%, respectively, and >90% for NDBE and HGD. The overall positive predictive value and sensitivity metric (calculated as F1 score) was .91 for NDBE, .90 for LGD, and 1.0 for HGD.

We successfully trained and validated a deep learning model to accurately identify dysplasia on whole-slide images. This model can potentially help improve the histologic diagnosis of BE dysplasia and the appropriate application of endoscopic therapy.

Background and study aims  Barrett's esophagus (BE) is a precursor condition to esophageal adenocarcinoma (EAC), resulting in transformation of the squamous epithelium of distal esophagus to columnar-lined epithelium with intestinal metaplasia (IM). Liquid nitrogen spray cryotherapy (LNSC) is a non-contact method of BE eradication and has been used both as primary and salvage therapy. We conducted a systematic review and meta-analysis to assess the safety and efficacy of LNSC. Methods  We searched multiple databases from inception through December 2021 to identify studies on use of LNSC for Barrett's neoplasia. Pooled estimates were calculated using random-effects model and results were expressed in terms of pooled proportions with relevant 95 % confidence intervals (CIs) of complete eradication (CE) of dysplasia(D), high grade dysplasia (HGD) and IM. Results  Fourteen studies with 707 patients were included in our final analysis. Overall pooled rates of CE-D, CE-HGD and CE-IM were 80.8 % (CI 77.4-83.8; I ² 62), 90.3 % (CI 85.2-93.7; I ² 33) and 55.8 % (CI 51.7-59.8; I ² 73) with follow up ranging from 4.25 months to 69.7 months. In patients with follow up beyond 24 months, the rates of CE-D and CE-IM were 83.6 % (CI 77.6-88.2; I ² 60) and 54.7 % (CI 47.6-61.6; I ² 81). Among LNSC naïve patients with prior history of endoscopic resection, the rates were 79.9 % (CI 73.3-85.2; I ² 50) and 67.1 % (CI 59.5-73.8; I ² 0). Pooled rate of therapeutic failures, defined as lack of response to LNSC therapy, was 23.6 % (CI 19.4-28.3; I ² 73). Post LNSC strictures and perforation pooled rates were 4 % and 0.8 %, respectively, which are similar to those previously reported for RFA. Conclusions  Our analysis suggests that liquid nitrogen spray cryotherapy is an acceptable treatment for BE in both ablation naïve and experienced patients.

Endoscopic eradication therapy (EET) has become a standard of care for treatment of dysplastic Barrett's esophagus (BE) and early Barrett's neoplasia. EET mainly consists of removal of any visible lesions via endoscopic resection and eradication of all remaining Barrett's mucosa using endoscopic ablation. Endoscopic mucosal resection and endoscopic submucosal dissection are the two available resection techniques. After complete resection of all visible lesions, it is crucial to perform endoscopic ablation to ensure complete eradication of the remaining Barrett's segment. Endoscopic ablation can be done either with thermal techniques, including radiofrequency ablation and argon plasma coagulation, or cryotherapy techniques. The primary end point of EET is achieving complete remission of intestinal metaplasia (CRIM) to decrease the risk of dysplastic recurrence after successful EET. After CRIM is achieved, a standardized endoscopic surveillance protocol needs to be implemented for early detection of BE recurrence.

Many esophageal diseases can arise during development or throughout life. Therefore, well-characterized in vitro models and detailed methods are essential for studying human esophageal development, homeostasis and disease. Here, we (1) create an atlas of the cell types observed in the normal adult human esophagus; (2) establish an ancestrally diverse biobank of in vitro esophagus tissue to interrogate homeostasis and injury; and (3) benchmark in vitro models using the adult human esophagus atlas. We created a single-cell RNA sequencing reference atlas using fresh adult esophagus biopsies and a continuously expanding biobank of patient-derived in vitro cultures (n=55 lines). We identify and validate several transcriptionally distinct cell classes in the native human adult esophagus, with four populations belonging to the epithelial layer, including basal, epibasal, early differentiating and terminally differentiated luminal cells. Benchmarking in vitro esophagus cultures to the in vivo reference using single-cell RNA sequencing shows that the basal stem cells are robustly maintained in vitro, and the diversity of epithelial cell types in culture is dependent on cell density. We also demonstrate that cultures can be grown in 2D or as 3D organoids, and these methods can be employed for modeling the complete epithelial layers, thereby enabling in vitro modeling of the human adult esophagus.

Endoscopic eradication therapy (EET) is the standard of care for Barrett's esophagus (BE)-associated neoplasia. Previous data suggest the mean number of EET sessions required to achieve complete eradication of intestinal metaplasia (CE-IM) is 3. This study aimed to define the threshold of EET sessions required to achieve CE-IM.

The TREAT-BE Consortium is a multicenter outcomes cohort including prospectively enrolled patients with BE undergoing EET. All patients achieving CE-IM were included. Demographic, endoscopic, and histologic data were recorded at treatment onset along with treatment details and surveillance data. Kaplan-Meier analysis was performed to define a threshold of EET sessions, with 95 %CI, required to achieve CE-IM. A secondary analysis examined predictors of incomplete response to EET using multiple logistic regression and recurrence rates.

623 patients (mean age 65.2 [SD 11.6], 79.6 % male, 86.5 % Caucasian) achieved CE-IM in a mean of 2.9 (SD 1.7) EET sessions (median 2) and a median total observation period of 2.7 years (interquartile range 1.4-5.0). After three sessions, 73 % of patients achieved CE-IM (95 %CI 70 %-77 %). Age (odds ratio [OR] 1.25, 95 %CI 1.05-1.50) and length of BE (OR 1.24, 95 %CI 1.17-1.31) were significant predictors of incomplete response.

The current study found that a threshold of three EET sessions would achieve CE-IM in the majority of patients. Alternative therapies and further diagnostic testing should be considered for patients who do not have significant response to EET after three sessions.

Background and study aims  Radiofrequency ablation (RFA) for dysplastic Barrett's esophagus (BE) has resulted in a paradigm shift in the management of BE. Despite widespread adoption of RFA, the optimal surveillance interval of the ablated zone is unclear. Methods  A patient-level discrete time cycle Markov model was developed to model clinical surveillance strategies post-RFA for BE. Three surveillance strategies were examined: the American College of Gastroenterology (ACG) strategy based on ACG guidelines for post-RFA surveillance, the Cotton strategy based on data from the USA and UK RFA registries, and the UK strategy in line with surveillance strategies in UK centers. Monte-Carlo deterministic and probabilistic analyses were performed over 10,000 iterations (i. e., representing 10,000 patient journeys) and sensitivity analyses were carried out on the variables used in the model. Results  On base-case analysis, the ACG strategy was the most cost-effective strategy, at a mean cost of £ 11,733 ($ 16,396) (standard deviation (SD) 1520.15) and a mean effectiveness of 12.86 (SD 0.07) QALYs. Probabilistic sensitivity analysis demonstrated that the ACG model was the most cost-effective strategy with a net monetary benefit (NMB) of £ 5,136 ($ 7177) (SD 241) compared to the UK strategy and a NMB of £ 7017 ($ 9,806) (SD 379) compared to the Cotton strategy. At a willingness to pay (WTP) threshold of £ 20,000 ($ 27,949), the ACG model was superior to the other strategies as the most cost-effective strategy. Conclusions  A post-RFA surveillance strategy based on the ACG guidelines seems to be the most cost-effective surveillance option.

Long-term durability data for effectiveness of radiofrequency ablation (RFA) to prevent esophageal adenocarcinoma in patients with dysplastic Barrett's esophagus (BE) are lacking.

We prospectively collected data from 2535 patients with BE (mean length, 5.2 cm; range, 1-20) and neoplasia (20% low-grade dysplasia, 54% high-grade dysplasia, 26% intramucosal carcinoma) who underwent RFA therapy across 28 UK hospitals. We assessed rates of invasive cancer and performed detailed analyses of 1175 patients to assess clearance rates of dysplasia (CR-D) and intestinal metaplasia (CR-IM) within 2 years of starting RFA therapy. We assessed relapses and rates of return to CR-D (CR-D2) and CR-IM (CR-IM2) after further therapy. CR-D and CR-IM were confirmed by an absence of dysplasia and intestinal metaplasia on biopsy samples taken at 2 consecutive endoscopies.

Ten years after starting treatment, the Kaplan-Meier (KM) cancer rate was 4.1% with a crude incidence rate of .52 per 100 patient-years. CR-D and CR-IM after 2 years of therapy were 88% and 62.6%, respectively. KM relapse rates were 5.9% from CR-D and 18.7% from CR-IM at 8 years, with most occurring in the first 2 years. Both were successfully retreated with rates of CR-D2 of 63.4% and CR-IM2 of 70.0% 2 years after retreatment. EMR before RFA increased the likelihood of rescue EMR from 17.2% to 41.7% but did not affect the rate of CR-D, whereas rescue EMR after RFA commenced reduced CR-D from 91.4% to 79.7% (χ²P < .001).

RFA treatment is effective and durable to prevent esophageal adenocarcinoma. Most treatment relapses occur early and can be successfully retreated.

Oesophageal adenocarcinoma (OAC) develops from columnar metaplasia of the distal oesophagus, Barrett's oesophagus (BO), secondary to chronic gastro-oesophageal reflux disease (GORD). In the present review, the stepwise development of GORD, BO and OAC is presented and the evidence of OAC prevention, including treatment with proton pump inhibitors (PPIs). PPIs are the main treatment of GORD and BO, with some evidence of prevention of OAC in these patients. However, as about 40% of OAC patient do not report a history of GORD and fewer than 15% of OAC cases are detected in individuals during BO surveillance, prevention of OAC is limited by PPI use in GORD and BO patients.

Barrett’s esophagus (BE) is the precursor of esophageal adenocarcinoma (EAC). Dysplastic BE (DBE) has a higher progression risk to EAC compared to non-dysplastic BE (NDBE). However, the miss rates for the endoscopic detection of DBE remain high. Fluorescence molecular endoscopy (FME) can detect DBE and mucosal EAC by highlighting the tumor-specific expression of proteins. This study aimed to identify target proteins suitable for FME. Publicly available RNA expression profiles of EAC and NDBE were corrected by functional genomic mRNA (FGmRNA) profiling. Following a class comparison between FGmRNA profiles of EAC and NDBE, predicted, significantly upregulated genes in EAC were prioritized by a literature search. Protein expression of prioritized genes was validated by immunohistochemistry (IHC) on DBE and NDBE tissues. Near-infrared fluorescent tracers targeting the proteins were developed and evaluated ex vivo on fresh human specimens. In total, 1976 overexpressed genes were identified in EAC (n = 64) compared to NDBE (n = 66) at RNA level. Prioritization and IHC validation revealed SPARC, SULF1, PKCι, and DDR1 (all p < 0.0001) as the most attractive imaging protein targets for DBE detection. Newly developed tracers SULF1-800CW and SPARC-800CW both showed higher fluorescence intensity in DBE tissue compared to paired non-dysplastic tissue. This study identified SPARC, SULF1, PKCι, and DDR1 as promising targets for FME to differentiate DBE from NDBE tissue, for which SULF1-800CW and SPARC-800CW were successfully ex vivo evaluated. Clinical studies should further validate these findings.