Understanding Barrett's columnar lined oesophagus from the patients' perspective: qualitative analysis of semistructured interviews with patients.
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ABSTRACT:
SUBMITTER: Griffiths H
PROVIDER: S-EPMC5517223 | biostudies-other | 2011 Jul
REPOSITORIES: biostudies-other
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Project description:In several organ systems, the transitional zone between different types of epithelium is a hotspot for pre-neoplastic metaplasia and malignancy, but the cells of origin for these metaplastic epithelia and subsequent malignancies remain unknown. In the case of Barrett's oesophagus, intestinal metaplasia occurs at the gastro-oesophageal junction, where stratified squamous epithelium transitions into simple columnar cells. On the basis of a number of experimental models, several alternative cell types have been proposed as the source of this metaplasia but in all cases the evidence is inconclusive: no model completely mimics Barrett's oesophagus in terms of the presence of intestinal goblet cells. Here we describe a transitional columnar epithelium with distinct basal progenitor cells (p63+KRT5+KRT7+) at the squamous-columnar junction of the upper gastrointestinal tract in a mouse model. We use multiple models and lineage tracing strategies to show that this squamous-columnar junction basal cell population serves as a source of progenitors for the transitional epithelium. On ectopic expression of CDX2, these transitional basal progenitors differentiate into intestinal-like epithelium (including goblet cells) and thereby reproduce Barrett's metaplasia. A similar transitional columnar epithelium is present at the transitional zones of other mouse tissues (including the anorectal junction) as well as in the gastro-oesophageal junction in the human gut. Acid reflux-induced oesophagitis and the multilayered epithelium (believed to be a precursor of Barrett's oesophagus) are both characterized by the expansion of the transitional basal progenitor cells. Our findings reveal a previously unidentified transitional zone in the epithelium of the upper gastrointestinal tract and provide evidence that the p63+KRT5+KRT7+ basal cells in this zone are the cells of origin for multi-layered epithelium and Barrett's oesophagus.
| S-EPMC5831195 | biostudies-literature
Project description:OBJECTIVE:Barrett's oesophagus commonly presents as a patchwork of columnar metaplasia with and without goblet cells in the distal oesophagus. The presence of metaplastic columnar epithelium with goblet cells on oesophageal biopsy is a marker of cancer progression risk, but it is unclear whether clonal expansion and progression in Barrett's oesophagus is exclusive to columnar epithelium with goblet cells. DESIGN:We developed a novel method to trace the clonal ancestry of an oesophageal adenocarcinoma across an entire Barrett's segment. Clonal expansions in Barrett's mucosa were identified using cytochrome c oxidase enzyme histochemistry. Somatic mutations were identified through mitochondrial DNA sequencing and single gland whole exome sequencing. RESULTS:By tracing the clonal origin of an oesophageal adenocarcinoma across an entire Barrett's segment through a combination of histopathological spatial mapping and clonal ordering, we find that this cancer developed from a premalignant clonal expansion in non-dysplastic ('cardia-type') columnar metaplasia without goblet cells. CONCLUSION:Our data demonstrate the premalignant potential of metaplastic columnar epithelium without goblet cells in the context of Barrett's oesophagus.
| S-EPMC4893117 | biostudies-other
Project description:BACKGROUND:Barrett'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. SUMMARY:This review highlights the current risk factors associated with the development of BO. KEY MESSAGE:Primary 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 IMPLICATIONS:By 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:To investigate changes to eRNA transcripts in Barrett's oesophagus & OAC patients.
2024-09-25 | E-MTAB-14091 | biostudies-arrayexpress
Project description:KAS-seq of Barrett's oesophagus & OAC patients
| PRJEB75915 | ENA
Project description:BackgroundBarrett's oesophagus (BO), a precursor to oesophageal adenocarcinoma, requires long-term endoscopic surveillance. The rising incidence of this chronic disease has implications for service provision and patient burden. Few studies have explored BO patients' personal burden, care delivery experience and participation in health-care delivery decisions.ObjectiveTo identify and explore factors impacting BO patients' health-related quality of life, follow-up needs and views on new models of follow-up care.DesignAn exploratory qualitative approach was adopted using semi-structured, in-depth, one-to-one interviews, audio-recorded and transcribed verbatim. Patients undergoing BO surveillance, at a single NHS hospital, were recruited using purposive sampling with the aim of achieving maximum variation. Data were analysed using framework analysis approach, supported by NVivo Pro 11.ResultsData saturation occurred after 20 participant interviews. Ten subthemes and three main themes emerged from the analysis: (a) burden of disease-symptom control, worry of oesophageal cancer and surveillance endoscopy; (b) follow-up experiences-follow-up care, at this NHS hospital, was found to be inconsistent and often inadequate to meet patients' needs, in particular a lack of disease-specific information; and (c) follow-up needs-participants sought enhanced communication, organization and structure of care. They highly valued face-to-face interaction with a specialist, and the concept of direct secondary care access in-between endoscopies was reassuring to participants.ConclusionsThis qualitative research provides an in-depth account of the patients' perspective of BO, the effectiveness of follow-up care and patient opinion on new follow-up systems.
| S-EPMC6351418 | biostudies-literature
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: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:BackgroundThe proportions of patients with oesophageal adenocarcinoma (OAC) diagnosed by Barrett's oesophagus surveillance or with pre-existing Barrett's oesophagus are unclear.AimTo estimate the prevalence of prior and concurrent Barrett's oesophagus diagnosis among patients with OAC or oesophagogastric junction adenocarcinomas (OGJAC).MethodsWe searched PubMed and Embase to identify studies published 1966-1/8/2020 that examined the prevalence of prior (≥6 months) or concurrent Barrett's diagnosis (at cancer diagnosis) among OAC and OGJAC patients. Random effects models estimated overall and stratified pooled prevalence rates.ResultsA total of 69 studies, including 33 002 OAC patients (53 studies) and 2712 patients with OGJAC (28 studies) were included. The pooled prevalence of prior Barrett's oesophagus diagnosis in OAC was 11.8% (95% confidence interval [CI] 8.4%-15.6%). The prevalence of prior Barrett's oesophagus diagnosis was higher in single-centre resection studies (16.0%, 95% CI 8.7%-24.9%) than population-based cancer registry studies (8.4%, 95% CI 5.5%-11.9%). The prevalence of concurrent Barrett's oesophagus in OAC was 56.6% (95% CI 48.5%-64.6%). Studies with 100% early stage OAC had higher prevalence of concurrent Barrett's oesophagus (91.3%, 95% CI 82.4%-97.6%) than studies with <50% early OAC (39.7%, 95% CI 33.7%-45.9%). In OGJAC, the prevalence of prior and concurrent Barrett's oesophagus was 23.2% (95% CI 7.5%-44.0%) and 26.3% (95% CI 17.8%-35.7%), respectively.ConclusionsMost patients with OAC have Barrett's oesophagus. Our meta-analysis found ~12% of OAC patients had prior Barrett's diagnosis, but concurrent Barrett's oesophagus was found in ~57% at the time of OAC diagnosis. This represents a considerable missed opportunity for Barrett's oesophagus screening.
| S-EPMC7293564 | biostudies-literature
Project description:ObjectiveTo identify and characterise DNA methylation subtypes in oesophageal adenocarcinoma (EAC) and its precursor Barrett's oesophagus (BE).DesignWe performed genome-wide DNA methylation profiling on samples of non-dysplastic BE from cancer-free patients (n=59), EAC (n=23), normal squamous oesophagus (n=33) and normal fundus (n=9), and identified methylation subtypes using a recursively partitioned mixture model. We assessed genomic alterations for 9 BE and 22 EAC samples with massively parallel sequencing of 243 EAC-associated genes, and we conducted integrative analyses with transcriptome data to identify epigenetically repressed genes. We also carried out in vitro experiments treating EAC cell lines with 5-Aza-2'-Deoxycytidine (5-Aza-dC), short hairpin RNA knockdown and anticancer therapies.ResultsWe identified and validated four methylation subtypes of EAC and BE. The high methylator subtype (HM) of EAC had the greatest number of activating events in ERBB2 (p<0.05, Student's t-test) and the highest global mutation load (p<0.05, Fisher's exact test). PTPN13 was silenced by aberrant methylation in the HM subtype preferentially and in 57% of EACs overall. In EAC cell lines, 5-Aza-dC treatment restored PTPN13 expression and significantly decreased its promoter methylation in HM cell lines (p<0.05, Welch's t-test). Inhibition of PTPN13 expression in the SK-GT-4 EAC cell line promoted proliferation, colony formation and migration, and increased phosphorylation in ERBB2/EGFR/Src kinase pathways. Finally, EAC cell lines showed subtype-specific responses to topotecan, SN-38 and palbociclib treatment.ConclusionsWe identified and characterised methylator subtypes in BE and EAC. We further demonstrated the biological and clinical relevance of EAC methylator subtypes, which may ultimately help guide clinical management of patients with EAC.
| S-EPMC6565505 | biostudies-literature