Endoscopic therapy for Barrett's oesophagus.
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SUBMITTER: Barr H
PROVIDER: S-EPMC1774518 | biostudies-literature | 2005 Jun
REPOSITORIES: biostudies-literature
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Project description:OBJECTIVE:Barrett's oesophagus is a premalignant condition that occurs in the context of gastro-oesophageal reflux. However, most Barrett's cases are undiagnosed because of reliance on endoscopy. We have developed a non-endoscopic tool: the Cytosponge, which when combined with trefoil factor 3 immunohistochemistry, can diagnose Barrett's oesophagus. We investigated whether a quantitative methylation test that is not reliant on histopathological analysis could be used to diagnose Barrett's oesophagus. DESIGN:Differentially methylated genes between Barrett's and normal squamous oesophageal biopsies were identified from whole methylome data and confirmed using MethyLight PCR in biopsy samples of squamous oesophagus, gastric cardia and Barrett's oesophagus. Selected genes were then tested on Cytosponge BEST2 trial samples comprising a pilot cohort (n=20?cases, n=10 controls) and a validation cohort (n=149?cases, n=129 controls). RESULTS:Eighteen genes were differentially methylated in patients with Barrett'soesophagus compared with squamous controls. Hypermethylation of TFPI2, TWIST1, ZNF345 and ZNF569 was confirmed in Barrett's biopsies compared with biopsies from squamous oesophagus and gastric cardia (p<0.05). When tested in Cytosponge samples, these four genes were hypermethylated in patients with Barrett's oesophagus compared with patients with reflux symptoms (p<0.001). The optimum biomarker to diagnose Barrett's oesophagus was TFPI2 with a sensitivity and specificity of 82.2% and 95.7%,?respectively. CONCLUSION:TFPI2, TWIST1, ZNF345 and ZNF569 methylation have promise as diagnostic biomarkers for Barrett's oesophagus when used in combination with a simple and cost effective non-endoscopic cell collection device.
| S-EPMC6176521 | biostudies-literature
Project description:BackgroundThe Coronavirus pandemic (COVID-19) curtailed endoscopy services, adding to diagnostic backlogs. Building on trial evidence for a non-endoscopic oesophageal cell collection device coupled with biomarkers (Cytosponge), an implementation pilot was launched for patients on waiting lists for reflux and Barrett's oesophagus surveillance.Aims(i) To review reflux referral patterns and Barrett's surveillance practices. (ii) To evaluate the range of Cytosponge findings and impact on endoscopy services.Design and methodsCytosponge data from centralized laboratory processing (trefoil factor 3 (TFF3) for intestinal metaplasia (IM), haematoxylin & eosin for cellular atypia and p53 for dysplasia) over a 2-year period were included.ResultsA total of 10 577 procedures were performed in 61 hospitals in England and Scotland, of which 92.5% (N = 9784/10 577) were sufficient for analysis. In the reflux cohort (N = 4074 with gastro-oesophageal junction sampling), 14.7% had one or more positive biomarkers (TFF3: 13.6% (N = 550/4056), p53: 0.5% (21/3974), atypia: 1.5% (N = 63/4071)), requiring endoscopy. Among samples from individuals undergoing Barrett's surveillance (N = 5710 with sufficient gland groups), TFF3-positivity increased with segment length (odds ratio = 1.37 per cm (95% confidence interval: 1.33-1.41, P < 0.001)). Some surveillance referrals (21.5%, N = 1175/5471) had ≤1 cm segment length, of which 65.9% (707/1073) were TFF3 negative. Of all surveillance procedures, 8.3% had dysplastic biomarkers (4.0% (N = 225/5630) for p53 and 7.6% (N = 430/5694) for atypia), increasing to 11.8% (N = 420/3552) in TFF3+ cases with confirmed IM and 19.7% (N = 58/294) in ultra-long segments.ConclusionsCytosponge-biomarker tests enabled targeting of endoscopy services to higher-risk individuals, whereas those with TFF3 negative ultra-short segments could be reconsidered regarding their Barrett's oesophagus status and surveillance requirements. Long-term follow-up will be important in these cohorts.
| S-EPMC10497181 | biostudies-literature
Project description:BackgroundBarrett's oesophagus (BO) is a premalignant condition associated with the development of oesophageal adenocarcinoma (OAC). Globally, the incidence of OAC is rising. Furthermore, the prognosis regarding the morbidity and mortality of OAC is bleak, with an estimated 5-year survival of 10-15%. Hence, detection of the premalignant phase is paramount. Endoscopy and biopsy sampling is the mainstay of diagnosis. Patients may present with symptoms of gastro-oesophageal reflux disease (GORD) or be completely asymptomatic. Therefore, symptomatology alone is a poor indicator of this condition.SummaryThis review highlights the current risk factors associated with the development of BO.Key messagePrimary risk factors for BO include male gender, increased age, a family history of the disease, long-standing GORD, smoking, obesity (specifically determined by the waist-to-hip ratio as opposed to BMI), and Caucasian race. Alcohol consumption and Helicobacter pylori are not associated with the condition.Practical implicationsBy ensuring an appropriate understanding of the risk factors, clinicians can discern at-risk patients for endoscopic diagnosis and surveillance.
| S-EPMC5121541 | biostudies-literature
Project description:BackgroundIntestinal metaplasia (IM) is pre-neoplastic with variable cancer risk. Cytosponge-TFF3 test can detect IM. We aimed to 1) assess whether quantitative TFF3 scores can distinguish clinically relevant Barrett's oesophagus (BO) (C≥1 or M≥3) from focal IM pathologies (C<1, M<3 or IM of gastro-oesophageal junction); 2) whether TFF3 counts can be automated to inform clinical practice.MethodsPatients from the Barett's oEsophagus Screening Trial 2 (BEST2) case-control and BEST3 randomised trials were used. For aim 1, TFF3-positive glands were scored manually and correlated with clinical diagnosis. For aim 2, machine learning approach was used to obtain TFF3 count and logistic regression with cross-validation was trained on the BEST2 dataset (n = 529) and tested in the BEST3 dataset (n = 158).FindingsPatients with clinically relevant BO had higher mean TFF3 gland count compared to focal IM pathologies (mean difference 4.14; 95% confidence interval, CI 2.76-5.52, p < 0.001). The mean class-balanced validation accuracy was 0.84 (95% CI 0.77-0.90), and precision of 0.95 (95% CI 0.87-1.00) for detecting clinically relevant BO. Applying this model on BEST3 showed precision of 0.91 (95% CI 0.85-0.97) for focal IM pathologies with a class-balanced accuracy of 0.77 (95% CI 0.69-0.84). Using this model, 55% of patients (87/158) in BEST3 would fall below the threshold for clinically relevant BO and could avoid gastroscopy, while only missing 5.1% of patients (8/158).InterpretationAutomated Cytosponge-TFF3 gland quantification may enable thresholds to be set to trigger confirmatory gastroscopy to minimize overdiagnosis of focal IM pathologies with very low cancer-associated risk.FundingCancer Research UK (12088/16893 and C14478/A21047).
| S-EPMC9297109 | biostudies-literature
Project description:Barrett's oesophagus (BE) is the precursor lesion to adenocarcinoma of the oesophagus. Understanding of the molecular alterations in this multistage process may contribute to improved diagnosis and treatment. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that modulates cell adhesion and growth. Alterations in SPARC expression have been observed in a variety of solid tumours. The aim of this study was to assess the prevalence and timing of SPARC mRNA expression in Barrett's multistage disease and to investigate the impact of SPARC alterations on the development and progression of this disease. SPARC mRNA expression was measured using a quantitative real-time RT-PCR method in 108 specimens from 19 patients with BE without carcinoma, 20 patients with Barrett's-associated adenocarcinoma (EA), and a control group (CG) of 10 patients without evidence of gastro-oesophageal reflux disease. The median SPARC mRNA expression was significantly upregulated in BE tissues compared to paired normal oesophagus (NE) tissues for the BE group (P=0.004) and for the EA group (P<0.001). The SPARC mRNA expression was significantly higher in adenocarcinoma of the oesophagus compared to matching NE tissue and compared to Barrett's tissues in the EA group (P<0.001). Furthermore, SPARC expression values were significantly different between metaplastic and dysplastic Barrett's tissues (P=0.014). In histologically normal squamous oesophagus tissues obtained from carcinoma patients (EA group), the SPARC mRNA expression was significantly higher compared to NE mucosa from the BE group and the CG group (P=0.03). These findings suggest that the upregulation of SPARC mRNA expression is an early event in the development and progression of BE and EA, and that high SPARC expression may be a clinically useful biomarker for the detection of occult adenocarcinoma, and that a widespread 'field effect' is present in the NE of patients with oesophageal adenocarcinoma.
| S-EPMC2394336 | biostudies-literature
Project description:BACKGROUND: The efficacy of endoscopic biopsy surveillance of Barrett's oesophagus in reducing mortality from oesophageal cancer has not been confirmed. AIMS: To investigate the impact of endoscopic biopsy surveillance on pathological stage and clinical outcome of Barrett's carcinoma. METHODS: A clinicopathological comparison was made between patients who initially presented with oesophageal adenocarcinoma (n = 54), and those in whom the cancer had been detected during surveillance of Barrett's oesophagus (n = 16). RESULTS: The surveyed patients were known to have Barrett's oesophagus for a median period of 42 months (range 6-144 months). Prior to the detection of adenocarcinoma or high grade dysplasia, 13 to 16 patients (81%) were previously found to have low grade dysplasia. Surgical pathology showed that surveyed patients had significantly earlier stages than non-surveyed patients (p = 0.0001). Only one surveyed patient (6%) versus 34 non-surveyed patients (63%) had nodal involvement (p = 0.0001). Two year survival was 85.9% for surveyed patients and 43.3% for non-surveyed patients (p = 0.0029). CONCLUSIONS: The temporal course of histological progression in our surveyed patients supports the theory that adenocarcinoma in Barrett's oesophagus develops through stages of increasing severity of dysplasia. Endoscopic biopsy surveillance of Barrett's oesophagus permits detection of malignancy at an early and curable stage, thereby potentially reducing mortality from oesophageal adenocarcinoma.
| S-EPMC1727211 | biostudies-other
Project description:Oesophageal adenocarcinoma is rapidly increasing in Western countries. This tumour frequently presents late in its course with metastatic disease and has a very poor prognosis. Barrett's oesophagus is an acquired condition whereby the native squamous mucosa of the lower oesophagus is replaced by columnar epithelium following prolonged gastro-oesophageal reflux and is the recognised precursor lesion for oesophageal adenocarcinoma. There are multiple national and society guidelines regarding screening, surveillance and management of Barrett's oesophagus, however all are limited regarding a clear evidence base for a well-demonstrated benefit and cost-effectiveness of surveillance, and robust risk stratification for patients to best use resources. Currently the accepted risk factors upon which surveillance intervals and interventions are based are Barrett's segment length and histological interpretation of the systematic biopsies. Further patient risk factors including other demographic features, smoking, gender, obesity, ethnicity, patient age, biomarkers and endoscopic adjuncts remain under consideration and are discussed in full. Recent evidence has been published to support earlier endoscopic intervention by means of ablation of the metaplastic Barrett's segment when the earliest signs of dysplasia are detected. Further work should concentrate on establishing better risk stratification and primary and secondary preventative strategies to reduce the risk of adenocarcinoma of the oesophagus.
| S-EPMC5537175 | biostudies-other
Project description:BACKGROUND: Barrett's oesophagus is acquired by severe gastro-oesophageal reflux and is a premalignant condition. Acid suppression or anti-reflux surgery alone do not cause significant regression of the metaplastic mucosa nor reduce the malignant potential. Recent reports have suggested that the combination of mucosal ablation with acid suppression may result in squamous regeneration. AIMS: To destroy Barrett's mucosa by thermal ablation (in the setting of acid suppression) and so induce squamous regeneration. PATIENTS: Sixteen patients with non-dysplastic Barrett's oesophagus were recruited from a surveillance programme. All had been on a proton pump inhibitor. METHODS: At intervals, non-circumferential areas of columnar mucosa were ablated using the KTP laser. Acid suppression was obtained with 40 mg omeprazole daily. Multiple biopsy specimens were obtained for histological examination from ablated areas. RESULTS: Ablation of all areas of glandular mucosa resulted in squamous regeneration. The number of treatments required depended on the length of the Barrett's segment. In 11 patients there was evidence of squamous regeneration over remaining Barrett's glands (in some of the post-treatment biopsy specimens) whilst in nine patients squamous metaplasia was seen within Barrett's glands. CONCLUSION: Mucosal ablation of Barrett's oesophagus by laser, in the setting of acid suppression, results in squamous regeneration (though some burying of Barrett's glands did occur).
| S-EPMC1891489 | biostudies-other
Project description:Purpose of reviewThe targeted approach adopted for Barrett's oesophagus (BO) screening is sub-optimal considering the large proportion of BO cases that are currently missed. We reviewed the literature highlighting recent technological advancements in efforts to counteract this challenge. We also provided insights into strategies that can improve the outcomes from current BO screening practises.Recent findingsThe standard method for BO detection, endoscopy, is invasive and expensive and therefore inappropriate for mass screening. On the other hand, endoscopy is more cost-effective for screening a high-risk population. A consensus has however not been reached on who should be screened. Risk prediction algorithms have been tested as an enrichment pre-screening tool reporting modest AUC's but require more prospective evaluation studies. Less invasive endoscopy methods like trans-nasal endoscopy, oesophageal capsule endsocopy and non-endoscopic cell collection devices like the Cytosponge coupled with biomarker analysis have shown promise in BO detection with randomised clinical trial evidence.SummaryA three-tier precision cancer programme whereby risk prediction algorithms and non-endoscopic minimally invasive cell collection devices are used to triage test a wider pool of individuals may improve the detection rate of current screening practises with minimal cost implications.
| S-EPMC7962426 | biostudies-literature
Project description:Oncogene amplification on extrachromosomal DNA (ecDNA) drives the evolution of tumours and their resistance to treatment, and is associated with poor outcomes for patients with cancer1-6. At present, it is unclear whether ecDNA is a later manifestation of genomic instability, or whether it can be an early event in the transition from dysplasia to cancer. Here, to better understand the development of ecDNA, we analysed whole-genome sequencing (WGS) data from patients with oesophageal adenocarcinoma (EAC) or Barrett's oesophagus. These data included 206 biopsies in Barrett's oesophagus surveillance and EAC cohorts from Cambridge University. We also analysed WGS and histology data from biopsies that were collected across multiple regions at 2 time points from 80 patients in a case-control study at the Fred Hutchinson Cancer Center. In the Cambridge cohorts, the frequency of ecDNA increased between Barrett's-oesophagus-associated early-stage (24%) and late-stage (43%) EAC, suggesting that ecDNA is formed during cancer progression. In the cohort from the Fred Hutchinson Cancer Center, 33% of patients who developed EAC had at least one oesophageal biopsy with ecDNA before or at the diagnosis of EAC. In biopsies that were collected before cancer diagnosis, higher levels of ecDNA were present in samples from patients who later developed EAC than in samples from those who did not. We found that ecDNAs contained diverse collections of oncogenes and immunomodulatory genes. Furthermore, ecDNAs showed increases in copy number and structural complexity at more advanced stages of disease. Our findings show that ecDNA can develop early in the transition from high-grade dysplasia to cancer, and that ecDNAs progressively form and evolve under positive selection.
| S-EPMC10132967 | biostudies-literature