Impact of endoscopic biopsy surveillance of Barrett's oesophagus on pathological stage and clinical outcome of Barrett's carcinoma.
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ABSTRACT:
SUBMITTER: van Sandick JW
PROVIDER: S-EPMC1727211 | biostudies-other | 1998 Aug
REPOSITORIES: biostudies-other
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Project description: Not available
| S-EPMC1774518 | biostudies-literature
Project description:Optical biopsy in Barrett's oesophagus (BE) using endocytoscopy (EC) could optimize endoscopic screening. However, the identification of dysplasia is challenging due to the complex interpretation of the highly detailed images. Therefore, we assessed whether using artificial intelligence (AI) as second assessor could help gastroenterologists in interpreting endocytoscopic BE images. First, we prospectively videotaped 52 BE patients with EC. Then we trained and tested the AI pm distinct datasets drawn from 83,277 frames, developed an endocytoscopic BE classification system, and designed online training and testing modules. We invited two successive cohorts for these online modules: 10 endoscopists to validate the classification system and 12 gastroenterologists to evaluate AI as second assessor by providing six of them with the option to request AI assistance. Training the endoscopists in the classification system established an improved sensitivity of 90.0% (+32.67%, p < 0.001) and an accuracy of 77.67% (+13.0%, p = 0.020) compared with the baseline. However, these values deteriorated at follow-up (-16.67%, p < 0.001 and -8.0%, p = 0.009). Contrastingly, AI-assisted gastroenterologists maintained high sensitivity and accuracy at follow-up, subsequently outperforming the unassisted gastroenterologists (+20.0%, p = 0.025 and +12.22%, p = 0.05). Thus, best diagnostic scores for the identification of dysplasia emerged through human-machine collaboration between trained gastroenterologists with AI as the second assessor. Therefore, AI could support clinical implementation of optical biopsies through EC.
| S-EPMC10093622 | biostudies-literature
Project description:Background & aimsAlthough patients with Barrett's esophagus commonly undergo endoscopic surveillance, its effectiveness in reducing mortality from esophageal/gastroesophageal junction adenocarcinomas has not been evaluated rigorously.MethodsWe performed a case-control study in a community-based setting. Among 8272 members with Barrett's esophagus, we identified 351 esophageal adenocarcinoma: 70 in persons who had a prior diagnosis of Barrett's esophagus (who were eligible for surveillance); 51 of these patients died, 38 as a result of the cancers (cases). Surveillance histories were contrasted with a sample of 101 living persons with Barrett's esophagus (controls), matched for age, sex, and duration of follow-up evaluation.ResultsSurveillance within 3 years was not associated with a decreased risk of death from esophageal adenocarcinoma (adjusted odds ratio, 0.99; 95% confidence interval, 0.36-2.75). Fatal cases were nearly as likely to have received surveillance (55.3%) as were controls (60.4%). A Barrett's esophagus length longer than 3 cm and prior dysplasia each were associated with subsequent mortality, but adjustment for these did not change the main findings. Although all patients should be included in evaluations of effectiveness, excluding deaths related to cancer treatment and patients who failed to complete treatment, changed the magnitude, but not the significance, of the association (odds ratio, 0.46; 95% confidence interval, 0.13-1.64).ConclusionsEndoscopic surveillance of patients with Barrett's esophagus was not associated with a substantially decreased risk of death from esophageal adenocarcinoma. The results do not exclude a small to moderate benefit. However, if such a benefit exists, our findings indicate that it is substantially smaller than currently estimated. The effectiveness of surveillance was influenced partially by the acceptability of existing treatments and the occurrence of treatment-associated mortality.
| S-EPMC3767470 | biostudies-literature
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:BackgroundEndoscopic surveillance is recommended for patients with Barrett's oesophagus because, although the progression risk is low, endoscopic intervention is highly effective for high-grade dysplasia and cancer. However, repeated endoscopy has associated harms and access has been limited during the COVID-19 pandemic. We aimed to evaluate the role of a non-endoscopic device (Cytosponge) coupled with laboratory biomarkers and clinical factors to prioritise endoscopy for Barrett's oesophagus.MethodsWe first conducted a retrospective, multicentre, cross-sectional study in patients older than 18 years who were having endoscopic surveillance for Barrett's oesophagus (with intestinal metaplasia confirmed by TFF3 and a minimum Barrett's segment length of 1 cm [circumferential or tongues by the Prague C and M criteria]). All patients had received the Cytosponge and confirmatory endoscopy during the BEST2 (ISRCTN12730505) and BEST3 (ISRCTN68382401) clinical trials, from July 7, 2011, to April 1, 2019 (UK Clinical Research Network Study Portfolio 9461). Participants were divided into training (n=557) and validation (n=334) cohorts to identify optimal risk groups. The biomarkers evaluated were overexpression of p53, cellular atypia, and 17 clinical demographic variables. Endoscopic biopsy diagnosis of high-grade dysplasia or cancer was the primary endpoint. Clinical feasibility of a decision tree for Cytosponge triage was evaluated in a real-world prospective cohort from Aug 27, 2020 (DELTA; ISRCTN91655550; n=223), in response to COVID-19 and the need to provide an alternative to endoscopic surveillance.FindingsThe prevalence of high-grade dysplasia or cancer determined by the current gold standard of endoscopic biopsy was 17% (92 of 557 patients) in the training cohort and 10% (35 of 344) in the validation cohort. From the new biomarker analysis, three risk groups were identified: high risk, defined as atypia or p53 overexpression or both on Cytosponge; moderate risk, defined by the presence of a clinical risk factor (age, sex, and segment length); and low risk, defined as Cytosponge-negative and no clinical risk factors. The risk of high-grade dysplasia or intramucosal cancer in the high-risk group was 52% (68 of 132 patients) in the training cohort and 41% (31 of 75) in the validation cohort, compared with 2% (five of 210) and 1% (two of 185) in the low-risk group, respectively. In the real-world setting, Cytosponge results prospectively identified 39 (17%) of 223 patients as high risk (atypia or p53 overexpression, or both) requiring endoscopy, among whom the positive predictive value was 31% (12 of 39 patients) for high-grade dysplasia or intramucosal cancer and 44% (17 of 39) for any grade of dysplasia.InterpretationCytosponge atypia, p53 overexpression, and clinical risk factors (age, sex, and segment length) could be used to prioritise patients for endoscopy. Further investigation could validate their use in clinical practice and lead to a substantial reduction in endoscopy procedures compared with current surveillance pathways.FundingMedical Research Council, Cancer Research UK, Innovate UK.
| S-EPMC8803607 | biostudies-literature
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:ObjectivesTo review the benefit of an endoscopic surveillance programme for patients with Barrett's oesophagus.DesignObservational study.SettingUniversity teaching hospital.Participants409 patients in whom Barrett's oesophagus was identified during 1984-94; 143 were entered into the annual surveillance programme.Main outcome measuresDevelopment of dysplasia and cancer and mortality.ResultsThe average period of surveillance was 4.4 years; 55 patients were reassessed in 1994 but only eight remained in the programme in 1999, withdrawal being due to death (not from carcinoma of the oesophagus), illness, or frailty. Five of the patients who entered surveillance developed carcinoma of the oesophagus. Only one cancer was identified as a result of a surveillance endoscopy, the others being detected during endoscopy to investigate altered symptoms. Of the 266 patients who were not suitable for surveillance, one died from oesophageal cancer and 103 from other causes. Surveillance has resulted in 745 endoscopies and about 3000 biopsy specimens.ConclusionThe current surveillance strategy has limited value, and it may be appropriate to restrict surveillance to patients with additional risk factors such as stricture, ulcer, or long segment (>80 mm) Barrett's oesophagus.
| S-EPMC27527 | 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