Barrett's Length Research Articles

Significance of Crypt Atypia in Barrett’s Esophagus: A Clinical, Molecular, and Outcome Study

The aim of this study was to characterize baseline morphologic features of crypts in nondysplastic Barrett's esophagus and correlate them with DNA content abnormalities and risk of progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). The morphologic features of nondysplastic crypts in baseline biopsy specimens from 212 BE patients (2956 biopsy specimens) were graded histologically using a 4-point scale (crypt atypia levels, 0-3). DNA content abnormalities were detected using flow cytometry. In patients who had dysplasia in their baseline biopsy specimens, dysplasia was associated significantly with increasing grades of crypt atypia in the background nondysplastic Barrett's esophagus (P < .001). In a subset of patients without dysplasia at baseline (N= 149), a higher grade of crypt atypia was associated with longer Barrett's esophagus segment length (5.5 vs 3.3 cm; P= .0095), and a higher percentage of cells with 4N DNA content (3.67 ± 1.27 vs 2.93 ± 1.22; P= .018). Crypt atypia was associated with the development of any neoplasia (low-grade dysplasia and HGD/EAC). Although no significant association was noted between the grade of crypt atypia and increased 4N, aneuploidy, or progression to HGD/EAC, only patients with grade 2 or 3 crypt atypia showed increased 4N, aneuploidy, or progression to HGD/EAC. Patients with Barrett's esophagus likely develop dysplasia via a progressive increase in the level of crypt atypia before the onset of dysplasia, and these changes may reflect some alteration of DNA content.

Location and appearance of dysplastic Barrett’s esophagus recurrence after endoscopic eradication therapy: no additional yield from random biopsy sampling neosquamous mucosa

Surveillance after complete remission of intestinal metaplasia (CRIM) is essential. Current recommendations are to sample visible lesions first, followed by random 4-quadrant biopsy sampling of the original Barrett's esophagus (BE) length. To inform post-CRIM surveillance protocols, we aimed to identify the anatomic location, appearance, and histology of BE recurrences. We performed an analysis of 216 patients who achieved CRIM after endoscopic eradication therapy for dysplastic BE at a Barrett's Referral Unit between 2008 and 2021. The anatomic location, recurrence histology, and endoscopic appearance of dysplastic recurrences were evaluated. After a median of 5.5 years (interquartile range, 2.9-7.2) of follow-up after CRIM, 57 patients (26.4%) developed nondysplastic BE (NDBE) recurrence and 18 patients (8.3%) developed dysplastic recurrence. From 8158 routine surveillance biopsy samplings of normal-appearing tubular esophageal neosquamous epithelium, the yield for recurrent NDBE or dysplasia was 0%. One hundred percent of dysplastic tubular esophageal recurrences were visible and in BE islands, whereas 77.8% of gastroesophageal junction dysplastic recurrences were nonvisible. Four distinct endoscopic features suspicious for recurrent advanced dysplasia or neoplasia were identified: buried or subsquamous BE, irregular mucosal pattern, loss of vascular pattern, and nodularity or depression. The yield of routine surveillance biopsy sampling of normal-appearing tubular esophageal neosquamous epithelium was zero. BE islands with indistinct mucosal or loss of vascular pattern, nodularity or depression, and/or signs of buried BE should raise clinician suspicion for advanced dysplasia or neoplasia recurrence. We suggest a new surveillance biopsy sampling protocol with a focus on meticulous inspection, followed by targeted biopsy sampling of visible lesions and random 4-quadrant biopsy sampling of the gastroesophageal junction.

Use of a Cytosponge biomarker panel to prioritise endoscopic Barrett's oesophagus surveillance: a cross-sectional study followed by a real-world prospective pilot.

SummaryBackgroundEndoscopic 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.

Barrett's esophagus surveillance in a prospective Dutch multi-center community-based cohort of 985 patients demonstrates low risk of neoplastic progression.

Background and AimsBarrett's esophagus (BE) is accompanied by an increased risk of developing esophageal cancer. Accurate risk‐stratification is warranted to improve endoscopic surveillance. Most data available on risk factors is derived from tertiary care centers or from cohorts with limited surveillance time or surveillance quality. The aim of this study was to assess endoscopic and clinical risk factors for progression to high‐grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in a large prospective cohort of BE patients from community hospitals supported by an overarching infrastructure to ensure optimal surveillance quality.MethodsA well‐defined prospective multicenter cohort study was initiated in six community hospitals in the Amsterdam region in 2003. BE patients were identified by PALGA search and included in a prospective surveillance program with a single endoscopist performing all endoscopies at each hospital. Planning and data collection was performed by experienced research nurses who attended all endoscopies. Endpoint was progression to HGD/EAC.ResultsNine hundred eighty‐five patients were included for analysis. During median follow‐up of 7.9 years (IQR 4.1–12.5) 67 patients were diagnosed with HGD (n = 28) or EAC (n = 39), progression rate 0.78% per patient‐year. As a clinical risk factor age at time of endoscopy was associated with neoplastic progression (HR 1.05; 95% CI 1.03–1.08). Maximum Barrett length and low‐grade dysplasia (LGD) at baseline were endoscopic predictors of progression (HR 1.15; 95% CI 1.09–1.21 and HR 2.36; 95% CI 1.29–4.33).ConclusionRisk of progression to HGD/EAC in a large, prospective, community‐based Barrett's cohort was low. Barrett's length, LGD and age were important risk factors for progression.(www.trialregister.nl NTR1789)

A predictive Bayesian network that risk stratifies patients undergoing Barrett's surveillance for personalized risk of developing malignancy.

BackgroundBarrett’s esophagus is strongly associated with esophageal adenocarcinoma. Considering costs and risks associated with invasive surveillance endoscopies better methods of risk stratification are required to assist decision-making and move toward more personalised tailoring of Barrett’s surveillance.MethodsA Bayesian network was created by synthesizing data from published studies analysing risk factors for developing adenocarcinoma in Barrett’s oesophagus through a two-stage weighting process.ResultsData was synthesized from 114 studies (n = 394,827) to create the Bayesian network, which was validated against a prospectively maintained institutional database (n = 571). Version 1 contained 10 variables (dysplasia, gender, age, Barrett’s segment length, statin use, proton pump inhibitor use, BMI, smoking, aspirin and NSAID use) and achieved AUC of 0.61. Version 2 contained 4 variables with the strongest evidence of association with the development of adenocarcinoma in Barrett’s (dysplasia, gender, age, Barrett’s segment length) and achieved an AUC 0.90.ConclusionThis Bayesian network is unique in the way it utilizes published data to translate the existing empirical evidence surrounding the risk of developing adenocarcinoma in Barrett’s esophagus to make personalized risk predictions. Further work is required but this tool marks a vital step towards delivering a more personalized approach to Barrett’s surveillance.

Regression of Barrett's esophagus after magnetic sphincter augmentation: intermediate-term results.

Untreated gastroesophageal reflux disease (GERD) can lead to Barrett's esophagus and an increased risk for esophageal adenocarcinoma. Magnetic sphincter augmentation (MSA) isa safe and effectivemodality forthe treatment of GERD. Preliminary research on short-term outcomes after MSA demonstrated significant regression of Barrett's. Further investigation is required to evaluate the long-term effect of this treatment. A retrospective review of patients was conducted with biopsy-proven Barrett's esophagus who underwentMSAbetween 2007 and 2019. As a part oftheirpreoperative evaluation,patients underwent esophagogastroduodenoscopy (EGD) with biopsies of the distal esophagus and gastroesophageal junction including any abnormal-appearing segments, pH testing, andavideoesophagram. Patients were categorized according to the length of Barrett's identified (ultrashort < 1cm, short 1-3cm, long > 3cm). Improvement was defined asa decrease in length (e.g. long to short). There were 87 patients identified for study inclusion. 55 patients were male. Themedianbody mass indexwas 26.95. The median age was 61.81 (49.79-68.29). Mean follow-up time was 2.35 ± (1.57) years. 7 (8.0%)of these patients beganwith long segment Barrett's, 58 (66.7%) began with short segment disease, and 22 (25.3%) began with an ultrashort segment. Within this cohort, 74 (85.06%) had undergone postoperative biopsy. 7 out of 74 patients(9.46%)showed improvement in their intestinal metaplasia and 45/74(60.81%)showed complete regression. Fisher's exact test showed a significant decrease in Barrett's length following MSA (p = 0.002). No patients progressed to dysplasia or neoplasia. There was a statistically significant decrease in the median Demeester score from 34.00 to 13.70 after surgery (p < .001). MSA reducesesophageal acid exposure and can lead to reduction or resolution of Barrett's esophagus. MSAis also effective atpreventingprogression ofmetaplasiatodysplasia or neoplasia. This effectremains consistenteven after 2 years of follow-up.

Independent Validation of a Tissue Systems Pathology Assay to Predict Future Progression in Nondysplastic Barrett's Esophagus: A Spatial-Temporal Analysis.

INTRODUCTION:An automated risk prediction assay has previously been shown to objectively identify patients with nondysplastic Barrett's esophagus (NDBE) who are at increased risk of malignant progression. To evaluate the predictive performance of the assay in 76 patients with NDBE of which 38 progressed to high-grade dysplasia/esophageal adenocarcinoma (progressors) and 38 did not (nonprogressors) and to determine whether assessment of additional (spatial) levels per endoscopy and/or multiple (temporal) time points improves assay performance.METHODS:In a blinded, nested case-control cohort, progressors and nonprogressors were matched (age, sex, and Barrett's esophagus length). All random biopsy levels from the baseline endoscopy (spatial samples) and all available previous endoscopies back to 10 years before progression (temporal samples) were assayed. Because the 1:1 ratio of progressors to nonprogressors does not reflect the real-world Barrett's population, negative and positive predictive values were adjusted for prevalence.RESULTS:Seventy-six patients (58 men), mean age of 63 ± 9 years, were studied. A high-risk score was associated with a prevalence-adjusted annual progression rate of 6.9%. The assay identified 31% of progressors when assessing a single biopsy level from the baseline endoscopy. Sensitivity increased to 50% and 69% in spatial and temporal analyses, respectively, while specificity remained at 95%.DISCUSSION:The assay identified a significant subset of NDBE patients who progress at a rate comparable with published estimates for expert-confirmed low-grade dysplasia. Assessing additional spatial and temporal biopsies increased the predictive accuracy, allowing for identification of most future progressors. Additional studies will evaluate the predictive performance of the assay in low-prevalence settings.

Safety and histologic outcomes of endoscopic submucosal dissection with a novel articulating knife for esophageal neoplasia

Treatment of large esophageal neoplasia is gradually evolving from piecemeal to en bloc resections. Endoscopic submucosal dissection (ESD) is known to achieve more complete resections than piecemeal EMR for large lesions, yet it remains underused in the West because of technical and safety concerns withtraditional electrosurgical knives. We aimed to evaluate a novel endoscopic articulating knife used with ESD (ESD-AR) to determine its safety and efficacy for large esophageal neoplasms in comparison with EMR. We retrospectively studied clinically indicated cases of ESD-AR and EMR for esophageal lesions that were 15mm or greater. All EMR cases had at least 3 simultaneous EMRs to adequately compare resection area. Rates of perforation, GI bleeding, technical performance, and pre- and postendoscopic resection diagnoses were evaluated. Seventy-two ESD-AR and 72 widespread EMR cases were evaluated for Barrett's esophagus (56%), adenocarcinoma (36%), squamous nodularity (2%), and squamous cell carcinoma (6%). There were no statistical differences in age, sex, Barrett's esophagus length, and lesion or resection size between the 2 groups. No perforations occurred. Two adverse events were recorded with ESD-AR and none with EMR (3% vs 0%, P= .50); these were associated with anticoagulation use (P= .04) and greater resection area (P= .02). There were more upgraded diagnoses post-ESD versus EMR (27% vs 12%, P= .05). ESD-AR by an experienced endoscopist has a comparable safety profile with widespread EMR for large esophageal neoplasia and may have advantages for diagnostic staging.

External validation of a model to determine risk of progression of Barrett's oesophagus to neoplasia.

A risk prediction model containing sex, smoking history, Barrett's oesophagus length and presence of low-grade dysplasia was found to identify individuals at a higher risk of progression to oesophageal adenocarcinoma or high-grade dysplasia. To externally validate the model predicting risk of progression from Barrett's oesophagus to neoplasia and assess the predictive utility of additional factors. We conducted a retrospective cohort study among individuals from the population-based Northern Ireland Barrett's register with a histologically confirmed diagnosis of Barrett's oesophagus (with intestinal metaplasia) between 1993 and 2005. The association between a points based model and risk of progression to high-grade dysplasia or oesophageal adenocarcinoma until 2010 was assessed using Cox Proportional Hazards model. Model performance was assessed using area under the receiver operating characteristics curves (AUROC), sensitivity and specificity. We identified 1198 individuals with Barrett's oesophagus of whom 54 progressed. The model discriminated reasonably well between progressors and nonprogressors, with an AUROC of 0.70 (95% CI 0.63-0.78). When categorised into low, intermediate and high risk groups, the AUROC was 0.68 (95% CI 0.61-0.74). Compared to using data on dysplasia and segment length for risk stratification, the model resulted in a net reclassification improvement of 20.9%. This external validation provides further evidence that a model based on sex, smoking, Barrett's segment length and baseline low-grade dysplasia may help to risk stratify patients after an initial diagnosis of Barrett's oesophagus. The model also performed better than the use of low-grade dysplasia status alone for risk-stratification.

Esomeprazole and aspirin in Barrett's oesophagus (AspECT): a randomised factorial trial

SummaryBackgroundOesophageal adenocarcinoma is the sixth most common cause of cancer death worldwide and Barrett's oesophagus is the biggest risk factor. We aimed to evaluate the efficacy of high-dose esomeprazole proton-pump inhibitor (PPI) and aspirin for improving outcomes in patients with Barrett's oesophagus.MethodsThe Aspirin and Esomeprazole Chemoprevention in Barrett's metaplasia Trial had a 2 × 2 factorial design and was done at 84 centres in the UK and one in Canada. Patients with Barrett's oesophagus of 1 cm or more were randomised 1:1:1:1 using a computer-generated schedule held in a central trials unit to receive high-dose (40 mg twice-daily) or low-dose (20 mg once-daily) PPI, with or without aspirin (300 mg per day in the UK, 325 mg per day in Canada) for at least 8 years, in an unblinded manner. Reporting pathologists were masked to treatment allocation. The primary composite endpoint was time to all-cause mortality, oesophageal adenocarcinoma, or high-grade dysplasia, which was analysed with accelerated failure time modelling adjusted for minimisation factors (age, Barrett's oesophagus length, intestinal metaplasia) in all patients in the intention-to-treat population. This trial is registered with EudraCT, number 2004-003836-77.FindingsBetween March 10, 2005, and March 1, 2009, 2557 patients were recruited. 705 patients were assigned to low-dose PPI and no aspirin, 704 to high-dose PPI and no aspirin, 571 to low-dose PPI and aspirin, and 577 to high-dose PPI and aspirin. Median follow-up and treatment duration was 8·9 years (IQR 8·2–9·8), and we collected 20 095 follow-up years and 99·9% of planned data. 313 primary events occurred. High-dose PPI (139 events in 1270 patients) was superior to low-dose PPI (174 events in 1265 patients; time ratio [TR] 1·27, 95% CI 1·01–1·58, p=0·038). Aspirin (127 events in 1138 patients) was not significantly better than no aspirin (154 events in 1142 patients; TR 1·24, 0·98–1·57, p=0·068). If patients using non-steroidal anti-inflammatory drugs were censored at the time of first use, aspirin was significantly better than no aspirin (TR 1·29, 1·01–1·66, p=0·043; n=2236). Combining high-dose PPI with aspirin had the strongest effect compared with low-dose PPI without aspirin (TR 1·59, 1·14–2·23, p=0·0068). The numbers needed to treat were 34 for PPI and 43 for aspirin. Only 28 (1%) participants reported study-treatment-related serious adverse events.InterpretationHigh-dose PPI and aspirin chemoprevention therapy, especially in combination, significantly and safely improved outcomes in patients with Barrett's oesophagus.FundingCancer Research UK, AstraZeneca, Wellcome Trust, and Health Technology Assessment.

Does the treatment of proton pump inhibitors reduce dysplasia or adenocarcinoma development in Barrett's esophagus?

Besides reducing the reflux symptoms, the benefit of proton pump inhibitors (PPI) in the treatment of Barrett's esophagus (BE) is not exactly known. The data in the literature show that although the PPI treatment does not reduce the Barrett's segment length, it can reduce dysplasia or the development of early-stage adenocarcinoma (odds ratio (OR): 0.46). Therefore, treatments with PPI may be considered in patients with a diagnosis of BE and at a high risk of adenocarcinoma, even though they are not symptomatic.

Barrett's esophagus: Ten years of experience at a tertiary care hospital center in Mexico

IntroductionThe prevalence of Barrett's esophagus has been calculated at between 1.3 and 1.6%. There is little information with respect to this in Mexico. AimTo determine the frequency and characteristics of Barrett's esophagus in patients that underwent endoscopy at a national referral center, within a 10-year time frame. Material and methodsThe databases of the pathology and gastrointestinal endoscopy departments of the Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” were analyzed, covering the period of January 2002 to December 2012. Patients with a histologic diagnosis of Barrett's esophagus were included. The variables of age, sex, the presence of dysplasia/esophageal adenocarcinoma, Barrett's esophagus length, and follow-up were analyzed. ResultsOf 43,639 upper gastrointestinal endoscopies performed, 420 revealed Barrett's esophagus, corresponding to a frequency of 9.6 patients for every 1,000 endoscopies. Of those patients, 66.9% (n=281) were men, mean patient age±SD was 57.2±15.3 years, 223 patients (53%) presented with long-segment Barrett's esophagus, and 197 (47%) with short-segment Barrett's esophagus. Dysplasia was not present in 339 patients (80.7%). Eighty-one (19.3%) patients had some grade of dysplasia or cancer: 48/420 (11.42%) presented with low-grade dysplasia, 20/420 (4.76%) with high-grade dysplasia, and 13/420 (3.1%) were diagnosed with esophageal cancer arising from Barrett's esophagus. Mean follow-up time was 5.6 years. ConclusionsThe frequency of Barrett's esophagus was 9.6 cases for every 1,000 upper gastrointestinal endoscopies performed. Dysplasia was not documented in the majority of the patients with Barrett's esophagus and they had no histopathologic changes during follow-up. A total of 19.3% of the patients presented with dysplasia or cancer.

Subsquamous intestinal metaplasia is common in treatment-naïve Barrett’s esophagus

Barrett's intestinal metaplasia may extend beneath normal squamous epithelium at the squamocolumnar junction (SCJ) and therefore escape surveillance biopsy sampling. The prevalence of subsquamous intestinal metaplasia (SSIM) in patients undergoing Barrett's esophagus (BE) surveillance is unknown. Our aim was to examine the prevalence and distribution of SSIM proximal to the SCJ in patients undergoing BE surveillance. We enrolled consecutive patients with biopsy specimen-proven BE. Biopsy specimens were obtained from the squamous epithelium at 5mm and 10mm above the SCJ. The primary outcomes were the proportion of patients with SSIM at each level. We further assessed factors associated with SSIM. We examined 515 squamous epithelial biopsy specimens from 106 BE patients (95% men; mean age, 66 years) with a mean Barrett's length of 3.0 cm. SSIM was present in 39% at 5mm (95% CI, 29.4-48.6) and 21% (95% CI, 11.7-32.1) at 10mm proximal to the SCJ. Among all biopsy specimens, 13% (95% CI, 10.6-16.6) contained SSIM: 17% (95% CI, 13-21.6) of biopsy samples at 5mm and 8% (95% CI, 4.3-12.2) at 10mm proximal to the SCJ. SSIM was more common in the anterior/right lateral position compared with the posterior/left lateral position (21% vs 11%, P= .001). None of the biopsy specimens showed dysplasia. Length of BE or duration of reflux symptoms were not associated with the presence of SSIM. This cross-sectional study found a surprisingly high proportion of SSIM in treatment-naïve patients proximal to the SCJ. These findings raise questions regarding BE management and the prevalence of SSIM in normal-appearing esophagus.

Adverse Events After Radiofrequency Ablation in Patients With Barrett's Esophagus: A Systematic Review and Meta-analysis.

Radiofrequency ablation (RFA) with or without endoscopic mucosal resection (EMR) is routinely used for treatment of Barrett's esophagus with dysplasia. Despite the relative safety of this method, there have been imprecise estimates of the rate of adverse events. We performed a systematic review and meta-analysis to assess the rate of adverse events associated with RFA with and without EMR. We searched MEDLINE, Embase, Web of Science, and Cochrane Central through October 22, 2014. The primary outcome of interest was the overall rate of adverse events after RFA with or without EMR. We used forest plots to contrast effect sizes among studies. Of 1521 articles assessed, 37 met our inclusion criteria (comprising 9200 patients). The pooled rate of all adverse events from RFA with or without EMR was 8.8% (95% confidence interval [CI], 6.5%-11.9%); 5.6% of patients developed strictures (95% CI, 4.2%-7.4%), 1% had bleeding (95% CI, 0.8%-1.3%), and 0.6% developed a perforation (95% CI, 0.4%-0.9%). In studies that compared RFA with vs without EMR, the relative risk for adverse events was significantly higher for RFA with EMR (4.4) (P= .015). There was a trend toward higher proportions of adverse events in prospective studies compared with retrospective studies (11.3% vs 7.8%, P= .20). Other factors associated with adverse events included Barrett's esophagus and length and baseline histology. In a systematic review and meta-analysis, we found the relative risk for adverse events from RFA to be about 4-fold higher with EMR than without; we identified factors associated with these events. Endoscopists should discuss these risks with patients before endoscopic eradication therapy.

Length of Barrett's oesophagus and cancer risk: implications from a large sample of patients with early oesophageal adenocarcinoma

ObjectiveAlthough it is well understood that the risk of oesophageal adenocarcinoma increases with Barrett length, transition risks for cancer associated with different Barrett lengths are unknown. We aimed to estimate...

Derivation of genetic biomarkers for cancer risk stratification in Barrett's oesophagus: a prospective cohort study.

The risk of developing adenocarcinoma in non-dysplastic Barrett's oesophagus is low and difficult to predict. Accurate tools for risk stratification are needed to increase the efficiency of surveillance. We aimed to develop a prediction model for progression using clinical variables and genetic markers. In a prospective cohort of patients with non-dysplastic Barrett's oesophagus, we evaluated six molecular markers: p16, p53, Her-2/neu, 20q, MYC and aneusomy by DNA fluorescence in situ hybridisation on brush cytology specimens. Primary study outcomes were the development of high-grade dysplasia or oesophageal adenocarcinoma. The most predictive clinical variables and markers were determined using Cox proportional-hazards models, receiver operating characteristic curves and a leave-one-out analysis. A total of 428 patients participated (345 men; median age 60 years) with a cumulative follow-up of 2019 patient-years (median 45 months per patient). Of these patients, 22 progressed; nine developed high-grade dysplasia and 13 oesophageal adenocarcinoma. The clinical variables, age and circumferential Barrett's length, and the markers, p16 loss, MYC gain and aneusomy, were significantly associated with progression on univariate analysis. We defined an 'Abnormal Marker Count' that counted abnormalities in p16, MYC and aneusomy, which significantly improved risk prediction beyond using just age and Barrett's length. In multivariate analysis, these three factors identified a high-risk group with an 8.7-fold (95% CI 2.6 to 29.8) increased HR when compared with the low-risk group, with an area under the curve of 0.76 (95% CI 0.66 to 0.86). A prediction model based on age, Barrett's length and the markers p16, MYC and aneusomy determines progression risk in non-dysplastic Barrett's oesophagus.

Barrett's oesophagus length is established at the time of initial endoscopy and does not change over time: results from a large multicentre cohort

ObjectiveIt is unclear whether Barrett's oesophagus (BO) length changes over time or whether the full length of the segment is established at the onset of disease recognition. The objectives of...

Negative surveillance endoscopy occurs frequently in patients with short-segment non-dysplastic Barrett's esophagus.

Surveillance endoscopy of non-dysplastic Barrett's esophagus (NDBE) that fails to detect intestinal metaplasia (IM), or negative surveillance, is known to occur in clinical practice, although the frequency and possible outcomes in a large cohort in clinical practice is not well described. The goals of this study were to define frequency in which negative surveillance occurs and endoscopic outcomes in a screening cohort of short segment NDBE. A retrospective cohort (n = 184) of patients newly diagnosed with short segment NDBE at an outpatient academic tertiary care center between 2003 and 2011 were reviewed. Only those with one or more surveillance endoscopies were included to define a frequency of negative surveillance. Included patients were further assessed if they had two or more surveillance endoscopies and were classified into groups as sampling error or negative IM on consecutive surveillances based on the results of their surveillance endoscopies. The frequency of a negative surveillance endoscopy in all short-segment NDBE patients was 19.66% (92 endoscopic exams were negative for IM of 468 total surveillance exams). A negative surveillance endoscopy occurred in 40.76% (n = 75) patients. Sampling error occurred in 44.12% and negative IM on consecutive surveillance endoscopies in 55.88% of those with ≥ 2 surveillance endoscopies and an initially negative surveillance exam. The frequency of negative IM on consecutive surveillances was 19.00% of all patients who had two surveillance endoscopies. When the index diagnostic Barrett's esophagus segment length was < 1 cm, 32.14% (18/56) of all patients (with ≥ 2 surveillance endoscopies) had negative IM on consecutive surveillance endoscopies. Negative surveillance occurs frequently in short-segment NDBE. When an initial negative surveillance endoscopy occurs, it may be due to either a sampling error or lack of detectable IM on surveillance exam. When a <1 cm segment of NDBE is diagnosed, a significant proportion of patients may go on to have continuously undetected IM on consecutive surveillance endoscopic exams without intervention.

Long-term recurrence of neoplasia and Barrett's epithelium after complete endoscopic resection

BackgroundCurrent endoscopic therapy for neoplastic Barrett's oesophagus (BO) consists of complete resection/ablation of all Barrett's tissue including neoplastic lesions. Recurrence seems to be frequent after thermal therapy, such as radiofrequency...

Management of Early‐stage Esophageal Neoplasia (MESEN) Consensus

Treatment of esophageal adenocarcinoma often involves surgical resection. Newer technologies in interventional endoscopy have led to a substantial paradigm shift in the management of early-stage neoplasia in Barrett's esophagus comprising high-grade dysplasia (HGD), intramucosal carcinoma, and, in some cases, submucosal carcinoma. However, there has been no consensus regarding the indications for esophageal preservation in these cases. In this work, consensus guidelines were established for the management of early-stage esophageal neoplasia considering clinically relevant aspects (age, comorbidities, and social environment) in each scenario. Seventeen experts were invited to participate based on their background and clinical expertise at high-volume centers. A questionnaire was created that included four clinical scenarios covering a wide range of situations within HGD and/or early esophageal neoplasia, particularly where controversies are likely to exist. Each of the clinical scenarios was open to discussion subdivided by patient age (20, 50, and 80 s). For each clinical scenario an expert was chosen to defend that position. Each defense triggered a subsequent discussion during a consensus meeting. Conclusions of that discussion together with an accompanying literature analysis allowed experts to confirm or change their original choices and served as the basis for the recommendations stated in this article. There was 100 % consensus supporting esophageal preservation in patients with HGD, independent of patient age or Barrett's length. In patients with T1a adenocarcinoma, consensus for preservation was not reached (65 %) for young and middle-aged individuals but was supported for elderly patients (100 %). For T1b adenocarcinoma, consensus was reached for surgical resection (90 %), leaving organ preservation for patients with very low risk of nodal invasion or poor surgical candidates. Advances in endoscopic imaging and therapy allow for organ preservation in most settings of early-stage neoplasia of the esophagus, provided that the patient understands the implications of this decision.