scholarly journals Detection of circulating BMP5 as a risk factor for Barrett’s esophagus

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ana C. P. Correia ◽  
Silvia Calpe ◽  
Nahid Mostafavi ◽  
Sanne Johanna Maria Hoefnagel ◽  
Maria del Carmen Sancho-Serra ◽  
...  
Keyword(s):  
High Risk ◽  
General Population ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Screening Programs ◽  
Non Invasive ◽  
Morphogenetic Protein ◽  
Increased Risk ◽  
Surveillance Programs ◽  
Invasive Method

Abstract Barrett’s esophagus (BE) predisposes for the malignant condition of esophageal adenocarcinoma (EAC). Since BE patients have few or no symptoms, most of these patients are not identified and not included in surveillance programs. These BE patients are at risk of developing advanced-stage EAC. At present, non-invasive tests to identify BE patients from the general population are lacking. We and others showed that Bone Morphogenetic Protein 4 (BMP4), and other BMPs are upregulated in BE. We aimed to determine if circulating BMPs can be identified and used as blood biomarkers to identify BE patients at high risk in the general population. In this study, we could detect the different BMPs in the blood of 112 BE patients and 134 age- and sex-matched controls. Concentration levels of BMP2, BMP4, and BMP5 were elevated in BE patients, with BMP2 and BMP5 significantly increased. BMP5 remained significant after multivariate analysis and was associated with an increased risk for BE with an OR of 1.49 (p value 0.01). Per log (pg/mL) of BMP5, the odds of having BE increased by 50%. Future optimization and validation studies might be needed to prove its utility as a non-invasive method for the detection of BE in high-risk populations and screening programs.

Use of optical biomarkers from nondysplastic metaplastic cells on the detection of high-grade dysplasia and adenocarcinoma from Barrett’s esophagus.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 14-14
Author(s):  
Randall Brand ◽  
Sumera Rizvi ◽  
Jon M. Davison ◽  
Rajan Bista ◽  
Kevin Staton ◽  
...  
Keyword(s):  
High Risk ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Statistical Significance ◽  
Optical Path Length ◽  
High Grade Dysplasia ◽  
High Grade ◽  
Novel Approach ◽  
Increased Risk ◽  
Protocol Biopsies

14 Background: Patients with Barrett’s esophagus (BE), defined as presence of intestinal metaplasia (IM) in the esophagus, require surveillance due to an increased risk of developing esophageal adenocarcinoma (EAC). The biggest challenge in the current surveillance methodology (i.e., Seattle protocol) is random sampling with the inability to identify those patients with non-dysplastic BE on surveillance who have occult high grade dysplasia (HGD) or will eventually progress to HGD or EAC. We propose a novel approach based on the concept of field effect to detect HGD or EAC through the analysis of non-dysplastic IM, thus identifying a high risk BE population. Our group uses a unique microscope – spatial-domain low-coherence quantitative phase microscopy (SL-QPM) to detect changes in nuclear structure as small as 0.9 nm, a scale 1000 times smaller than what conventional microscopy detects. We hypothesize that the SL-QPM-derived optical biomarkers of non-dysplastic IM would distinguish BE patients with EAC/HGD from those without neoplasia. Methods: We performed a retrospective study of 60 BE patients who underwent Seattle protocol biopsies: 33 BE patients with IM only and 27 BE patients with HGD or EAC (21 HGD, 6 EAC). H&E stained slides with non-dysplastic IM on review by an expert pathologist were used. The distance between the selected IM biopsy and HGD/EAC was 1 to 4 cm. Forty to 60 columnar cells from each case were analyzed. Results: We identified three optical biomarkers (nuclear optical path length, intra-nuclear uniformity, entropy) that can distinguish non-dysplastic BE from patients with HGD and EAC with statistical significance (P < 0.01). A prediction model combining all three optical biomarkers can distinguish BE patients with HGD/EAC from those with IM only at 89% sensitivity and 76% specificity (accuracy = 0.87). Conclusions: The accurate assessment of nanoscale optical biomarkers by SL-QPM is a promising approach for detecting dysplastic/neoplastic Barrett’s epithelium from non-dysplastic IM. This approach could potentially simplify BE surveillance by identifying a subset of high-risk BE patients that warrant intensive surveillance.

scholarly journals Esophageal abnormalities and the risk for gastroesophageal cancers—a histopathology-register-based study in Sweden

2022 ◽  
Author(s):  
Isabella Ekheden ◽  
Jonas F. Ludvigsson ◽  
Li Yin ◽  
Peter Elbe ◽  
Weimin Ye
Keyword(s):  
General Population ◽  
Confidence Interval ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Population Based ◽  
Low Grade ◽  
Gastric Cardia Adenocarcinoma ◽  
Increased Risk ◽  
Columnar Metaplasia

Abstract Background The poor survival of patients with gastroesophageal cancers may improve if additional esophageal precursor lesions to Barrett’s esophagus and squamous dysplasia are identified. We estimated the risk for gastroesophageal cancers among patients with various histopathological abnormalities in the esophagus, including Barrett’s esophagus, subdivided by histopathological types. Methods Histopathology data from esophageal biopsies obtained 1979–2014 were linked with several national population-based registers in Sweden. Patients were followed from 2 years after the first biopsy date until cancer, death, emigration, esophagectomy/gastrectomy or end of follow-up, 31st of December 2016, whichever came first. We estimated standardized incidence ratios (SIRs) as measures of relative risk with the Swedish general population as reference. Results In total 367 esophageal adenocarcinoma (EAC) cases were ascertained during 831,394 person-years of follow-up. The incidence rate (IR) for EAC was 0.1 per 1000 person-years for normal morphology, 0.2–0.5 for inflammatory changes, and 0.8–2.9 for metaplasia. The IR was 1.0 per 1000 person-years (95% confidence interval 0.7–1.3) among patients with non-dysplastic intestinal metaplasia, 0.9 (0.8–1.1) in non-dysplastic gastric/glandular metaplasia and 2.9 (2.0–4.2) among columnar metaplasia patients with low-grade dysplasia. The SIRs were 11.7 (95% confidence interval 8.6–15.5), 12.0 (10.0–14.2) and 30.2 (20.5–42.8), respectively. The SIRs for gastric cardia adenocarcinoma (GCA) were moderately elevated. Conclusions For the first time, we demonstrate that patients with esophageal inflammatory and other metaplastic abnormalities than Barrett’s esophagus have an increased risk of EAC and GCA compared to the general population. Moreover, patients with different histopathologic subtypes of Barrett’s esophagus have a comparable risk for EAC.

scholarly journals Implications of Recent Revelations from Basic and Clinical Studies of Barrett’s Esophagus for Screening and Surveillance Strategies

2021 ◽  
Vol 1 (1) ◽  
pp. 86-92
Author(s):  
Stuart Jon Spechler ◽  
Rhonda F. Souza
Keyword(s):  
High Risk ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Prevention Strategies ◽  
Endoscopic Screening ◽  
Screening Practices ◽  
The Past ◽  
Screening And Surveillance ◽  
Gerd Symptoms ◽  
Current Screening

During the past several decades, while the incidence of esophageal adenocarcinoma (EAC) has risen dramatically, our primary EAC-prevention strategies have been endoscopic screening of individuals with GERD symptoms for Barrett’s esophagus (BE), and endoscopic surveillance for those found to have BE. Unfortunately, current screening practices have failed to identify most patients who develop EAC, and the efficacy of surveillance remains highly questionable. We review potential reasons for failure of these practices including recent evidence that most EACs develop through a rapid genomic doubling pathway, and recent data suggesting that many EACs develop from segments of esophageal intestinal metaplasia too short to be recognized as BE. We highlight need for a biomarker to identify BE patients at high risk for neoplasia (who would benefit from early therapeutic intervention), and BE patients at low risk (who would not benefit from surveillance). Promising recent efforts to identify such a biomarker are reviewed herein.

scholarly journals TissueCypher Barrett’s esophagus assay impacts clinical decisions in the management of patients with Barrett’s esophagus

2021 ◽  
Vol 09 (03) ◽  
pp. E348-E355
Author(s):  
David L. Diehl ◽  
Harshit S. Khara ◽  
Nasir Akhtar ◽  
Rebecca J. Critchley-Thorne
Keyword(s):  
High Risk ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Clinical Decision Making ◽  
Eradication Therapy ◽  
Low Risk ◽  
Management Approach ◽  
Low Grade ◽  
Management Decisions ◽  
The Impact

Abstract Background and study aims The TissueCypher Barrett’s Esophagus Assay is a novel tissue biomarker test, and has been validated to predict progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in patients with Barrett’s esophagus (BE). The aim of this study was to evaluate the impact of TissueCypher on clinical decision-making in the management of BE. Patients and methods TissueCypher was ordered for 60 patients with non-dysplastic (ND, n = 18) BE, indefinite for dysplasia (IND, n = 25), and low-grade dysplasia (LGD, n = 17). TissueCypher reports a risk class (low, intermediate or high) for progression to HGD or EAC within 5 years. The impact of the test results on BE management decisions was assessed. Results Fifty-two of 60 patients were male, mean age 65.2 ± 11.8, and 43 of 60 had long segment BE. TissueCypher results impacted 55.0 % of management decisions. In 21.7 % of patients, the test upstaged the management approach, resulting in endoscopic eradication therapy (EET) or shorter surveillance interval. The test downstaged the management approach in 33.4 % of patients, leading to surveillance rather than EET. In the subset of patients whose management plan was changed, upstaging was associated with a high-risk TissueCypher result, and downstaging was associated with a low-risk result (P < 0.0001). Conclusions TissueCypher was used as an adjunct to support a surveillance-only approach in 33.4 % of patients. Upstaging occurred in 21.7 % of patients, leading to therapeutic intervention or increased surveillance. These results indicate that the TissueCypher test may enable physicians to target EET for TissueCypher high-risk BE patients, while reducing unnecessary procedures in TissueCypher low-risk patients.

scholarly journals Vitamin D and Cardiovascular Disease: An Updated Narrative Review

2021 ◽  
Vol 22 (6) ◽  
pp. 2896
Author(s):  
Armin Zittermann ◽  
Christian Trummer ◽  
Verena Theiler-Schwetz ◽  
Elisabeth Lerchbaum ◽  
Winfried März ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Vitamin D ◽  
High Risk ◽  
General Population ◽  
Vitamin D Deficiency ◽  
Specific Gene ◽  
Vitamin D Status ◽  
Cvd Risk ◽  
Severe Vitamin ◽  
Increased Risk

During the last two decades, the potential impact of vitamin D on the risk of cardiovascular disease (CVD) has been rigorously studied. Data regarding the effect of vitamin D on CVD risk are puzzling: observational data indicate an inverse nonlinear association between vitamin D status and CVD events, with the highest CVD risk at severe vitamin D deficiency; however, preclinical data and randomized controlled trials (RCTs) show several beneficial effects of vitamin D on the surrogate parameters of vascular and cardiac function. By contrast, Mendelian randomization studies and large RCTs in the general population and in patients with chronic kidney disease, a high-risk group for CVD events, largely report no significant beneficial effect of vitamin D treatment on CVD events. In patients with rickets and osteomalacia, cardiovascular complications are infrequently reported, except for an increased risk of heart failure. In conclusion, there is no strong evidence for beneficial vitamin D effects on CVD risk, either in the general population or in high-risk groups. Whether some subgroups such as individuals with severe vitamin D deficiency or a combination of low vitamin D status with specific gene variants and/or certain nutrition/lifestyle factors would benefit from vitamin D (metabolite) administration, remains to be studied.

scholarly journals Probe-based confocal laser endomicroscopy and Barrett's esophagus – just a scientific toy or significant improvement in diagnosis?

2021 ◽  
Author(s):  
Luka Vranić ◽  
Tin Nadarević ◽  
Davor Štimac
Keyword(s):  
Diagnostic Accuracy ◽  
Real Time ◽  
Barrett’S Esophagus ◽  
Predictive Value ◽  
Barrett's Esophagus ◽  
High Reliability ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Imaging Method ◽  
Increased Risk

Background: Barrett’s esophagus (BE) requires surveillance to identify potential neoplasia at early stage. Standard surveillance regimen includes random four-quadrant biopsies by Seattle protocol. Main limitations of random biopsies are high risk of sampling error, difficulties in histology interpretation, common inadequate classification of pathohistological changes, increased risk of bleeding and time necessary to acquire the final diagnosis. Probe-based confocal laser endomicroscopy (pCLE) has emerged as a potential tool with an aim to overcome these obvious limitations. Summary: pCLE represents real-time microscopic imaging method that offers evaluation of epithelial and subepithelial structures with 1000-fold magnification. In theory, pCLE has potential to eliminate the need for biopsy in BE patient. The main advantages would be real-time diagnosis and decision making, greater diagnostic accuracy and to evaluate larger area compared to random biopsies. Clinical pCLE studies in esophagus show high diagnostic accuracy and its high negative predictive value offers high reliability and confidence to exclude dysplastic and neoplastic lesions. However, it still cannot replace histopathology due to lower positive predictive value and sensitivity. Key messages: Despite promising results, its role in routine use in patients with Barrett’s esophagus remains questionable primarily due to lack of well-organized double-blind randomized trials.

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