BarrettNET—a prospective registry for risk estimation of patients with Barrett's esophagus to progress to adenocarcinoma

SUMMARYRisk stratification in patients with Barrett's esophagus (BE) to prevent the development of esophageal adenocarcinoma (EAC) is an unsolved task. The incidence of EAC and BE is increasing and patients are still at unknown risk. BarrettNET is an ongoing multicenter prospective cohort study initiated to identify and validate molecular and clinical biomarkers that allow a more personalized surveillance strategy for patients with BE. For BarrettNET participants are recruited in 20 study centers throughout Germany, to be followed for progression to dysplasia (low-grade dysplasia or high-grade dysplasia) or EAC for >10 years. The study instruments comprise self-administered epidemiological information (containing data on demographics, lifestyle factors, and health), as well as biological specimens, i.e., blood-based samples, esophageal tissue biopsies, and feces and saliva samples. In follow-up visits according to the individual surveillance plan of the participants, sample collection is repeated. The standardized collection and processing of the specimen guarantee the highest sample quality. Via a mobile accessible database, the documentation of inclusion, epidemiological data, and pathological disease status are recorded subsequently. Currently the BarrettNET registry includes 560 participants (23.1% women and 76.9% men, aged 22–92 years) with a median follow-up of 951 days. Both the design and the size of BarrettNET offer the advantage of answering research questions regarding potential causes of disease progression from BE to EAC. Here all the integrated methods and materials of BarrettNET are presented and reviewed to introduce this valuable German registry.

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Clinical pathways and outcomes of patients with Barrett’s esophagus in tertiary care settings: a prospective longitudinal cohort study in Australia, 2008–2016

Diseases of the Esophagus ◽

10.1093/dote/doaa119 ◽

2020 ◽

Author(s):

Renhua Na ◽

Kyoko Miura ◽

Suzanne O’Brien ◽

Guy D Eslick ◽

Bradley J Kendall ◽

...

Keyword(s):

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Clinical Pathways ◽

Tertiary Care ◽

Incidence Rates ◽

Segment Length ◽

Low Grade ◽

Adjusted Incidence ◽

Prospective Longitudinal

Summary Background Clinical services for Barrett’s esophagus have been rising worldwide including Australia, but little is known of the long-term outcomes of such patients. Retrospective studies using data at baseline are prone to both selection and misclassification bias. We investigated the clinical characteristics and outcomes of Barrett’s esophagus patients in a prospective cohort. Methods We recruited patients diagnosed with Barrett’s esophagus in tertiary settings across Australia between 2008 and 2016. We compared baseline and follow-up epidemiological and clinical data between Barrett’s patients with and without dysplasia. We calculated age-adjusted incidence rates and estimated minimally and fully adjusted hazard ratios (HR) to identify those clinical factors related to disease progression. Results The cohort comprised 268 patients with Barrett’s esophagus (median follow-up 5 years). At recruitment, 224 (84%) had no dysplasia, 44 (16%) had low-grade or indefinite dysplasia (LGD/IND). The age-adjusted incidence of esophageal adenocarcinoma (EAC) was 0.5% per year in LGD/IND compared with 0.1% per year in those with no dysplasia. Risk of progression to high-grade dysplasia/EAC was associated with prior LGD/IND (fully adjusted HR 6.55, 95% confidence interval [CI] 1.96–21.8) but not long-segment disease (HR 1.03, 95%CI 0.29–3.58). Conclusions These prospective data suggest presence of dysplasia is a stronger predictor of progression to cancer than segment length in patients with Barrett’s esophagus.

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Endoscopic Mucosal Resection: Early Experience in British Columbia

Canadian Journal of Gastroenterology ◽

10.1155/2010/897473 ◽

2010 ◽

Vol 24 (4) ◽

pp. 239-244 ◽

Cited By ~ 6

Author(s):

Mayur Brahmania ◽

Eric Lam ◽

Jennifer Telford ◽

Robert Enns

Keyword(s):

British Columbia ◽

Barrett’S Esophagus ◽

Endoscopic Mucosal Resection ◽

Barrett's Esophagus ◽

Low Grade ◽

Complication Rates ◽

The Third ◽

Mucosal Resection ◽

The Mean

BACKGROUND: Endoscopic mucosal resection (EMR) has been proposed as a primary method of managing patients with dysplasia- or mucosal-based cancers of the esophagus.OBJECTIVES: To evaluate the use of EMR for the treatment of Barrett’s esophagus with dysplasia or early adenocarcinoma, assessing efficacy, complication rates and long-term outcomes.METHODS: All patients who underwent EMR at St Paul’s Hospital (Vancouver, British Columbia) were reviewed. Eligible patients were assessed with aggressive biopsy protocols. Detected cancers were staged with both endoscopic ultrasound imaging and computed tomography. Appropriate patients were offered EMR using a commercially available mucosectomy device. EMR was repeated at six- to eight-week intervals until complete. Patients with less than one year of follow-up or who were undergoing other ablative methods were excluded.RESULTS: Twenty-two patients (all men) with a mean (± SD) age of 67±10.6 years were identified. The mean duration of gastroesophageal reflux disease was 17 years (range four to 40 years) and all were receiving proton pump inhibitor therapy. The mean length of Barrett’s esophagus was 5.5±3.5 cm. One patient had no dysplasia (isolated nodule), three had low-grade dysplasia, 15 had high-grade dysplasia (HGD) and three had adenocarcinoma. A mean of 1.7±0.83 endoscopic sessions were performed, with a mean of 6±5.4 sections removed. Following EMR, three patients developed strictures; two of these patients had pre-existing strictures and the third required two dilations, which resolved his symptoms. There were no other complications. Three patients underwent esophagectomy. Two had adenocarcinoma or HGD in a pre-existing stricture. The third patient had an adenocarcinoma not amenable to EMR. One patient with a long segment of Barrett’s esophagus underwent radiofrequency ablation. At a median follow-up of two years (range one to three years), the remaining 18 patients (82%) had no evidence of HGD or cancer.CONCLUSION: Most patients with esophageal dysplasia can be managed with EMR. Individuals with pre-existing strictures require other endoscopic and/or surgical methods to manage their dysplasia or adenocarcinoma.

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Barrett’s Registry Collaboration of academic centers in Ireland reveals high progression rate of low-grade dysplasia and low risk from nondysplastic Barrett’s esophagus: report of the RIBBON network

Diseases of the Esophagus ◽

10.1093/dote/doaa009 ◽

2020 ◽

Vol 33 (10) ◽

Cited By ~ 3

Author(s):

Lisa M O’Byrne ◽

Jolene Witherspoon ◽

Roy J J Verhage ◽

Marie O’Brien ◽

Cian Muldoon ◽

...

Keyword(s):

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Population Based ◽

First Year ◽

Progression Rate ◽

Low Grade ◽

Female Ratio ◽

Ablative Therapies ◽

Low Grade Dysplasia

Summary Barrett’s esophagus (BE) is the main pathological precursor of esophageal adenocarcinoma (EAC). Progression to high-grade dysplasia (HGD) or EAC from nondysplastic BE (NDBE), low-grade dysplasia (LGD) and indefinite for dysplasia (IND) varies widely between population-based studies and specialized centers for many reasons, principally the rigor of the biopsy protocol and the accuracy of pathologic definition. In the Republic of Ireland, a multicenter prospective registry and bioresource (RIBBON) was established in 2011 involving six academic medical centers, and this paper represents the first report from this network. A detailed clinical, endoscopic and pathologic database registered 3,557 patients. BE was defined strictly by both endoscopic evidence of Barrett’s epithelium and the presence of specialized intestinal metaplasia (SIM). A prospective web-based database was used to gather information with initial and follow-up data abstracted by a data manager at each site. A total of 2,244 patients, 1,925 with no dysplasia, were included with complete follow-up. The median age at diagnosis was 60.5 with a 2.1:1 male to female ratio and a median follow-up time of 2.7 years (IQR 1.19–4.04), and 6609.25 person years. In this time period, 125 (5.57%) progressed to HGD/EAC, with 74 (3.3%) after 1 year of follow-up and 38 (1.69%) developed EAC, with 20 (0.89%) beyond 1 year. The overall incidence of HGD/EAC was 1.89% per year; 1.16% if the first year is excluded. The risk of progression to EAC alone overall was 0.57% per year, 0.31% excluding the first year, and 0.21% in the 1,925 patients who had SIM alone at diagnosis. Low-grade dysplasia (LGD) progressed to HGD/EAC in 31% of patients, a progression rate of 12.96% per year, 6.71% with the first year excluded. In a national collaboration of academic centers in Ireland, the progression rate for NDBE was similar to recent population studies. Almost one in two who progressed was evident within 1 year. Crucially, LGD diagnosed and confirmed by specialist gastrointestinal pathologists represents truly high-risk disease, highlighting the importance of expertise in diagnosis and management, and providing indirect support for ablative therapies in this context.

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481 LONG-TERM FOLLOW-UP RESULTS OF A RANDOMIZED TRIAL COMPARING RADIOFREQUENCY ABLATION VERSUS ENDOSCOPIC SURVEILLANCE IN BARRETT'S ESOPHAGUS PATIENTS WITH LOW-GRADE DYSPLASIA

Gastrointestinal Endoscopy ◽

10.1016/j.gie.2018.04.090 ◽

2018 ◽

Vol 87 (6) ◽

pp. AB83 ◽

Cited By ~ 2

Author(s):

Esther Klaver ◽

K. Nadine Phoa ◽

Frederike G. van Vilsteren ◽

Bas L. Weusten ◽

Raf Bisschops ◽

...

Keyword(s):

Radiofrequency Ablation ◽

Randomized Trial ◽

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Endoscopic Surveillance ◽

Low Grade ◽

Long Term Follow Up ◽

Low Grade Dysplasia

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DIAGNOSIS, TREATMENT AND FOLLOW-UP OF BARRETT’S ESOPHAGUS: A SYSTEMATIC REVIEW

Arquivos de Gastroenterologia ◽

10.1590/s0004-2803.202000000-53 ◽

2020 ◽

Vol 57 (3) ◽

pp. 289-295

Author(s):

José Roberto ALVES ◽

Fabrissio Portelinha GRAFFUNDER ◽

João Vitor Ternes RECH ◽

Caique Martins Pereira TERNES ◽

Iago KOERICH-SILVA

Keyword(s):

Systematic Review ◽

Randomized Controlled Trials ◽

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Endoscopic Surveillance ◽

Controlled Trials ◽

Low Grade ◽

Randomized Controlled ◽

Mesh Terms

ABSTRACT BACKGROUND: Barrett’s esophagus (BE) is a premalignant condition that raises controversy among general practitioners and specialists, especially regarding its diagnosis, treatment, and follow-up protocols. OBJECTIVE: This systematic review aims to present the particularities and to clarify controversies related to the diagnosis, treatment and surveillance of BE. METHODS: A systematic review was conducted on PubMed, Cochrane, and SciELO based on articles published in the last 10 years. PRISMA guidelines were followed and the search was made using MeSH and non-MeSH terms “Barrett” and “diagnosis or treatment or therapy or surveillance”. We searched for complete randomized controlled clinical trials or Phase IV studies, carried out with individuals over 18 years old. RESULTS: A total of 42 randomized controlled trials were selected after applying all inclusion and exclusion criteria. A growing trend of alternative and safer techniques to traditional upper gastrointestinal endoscopy were identified, which could improve the detection of BE and patient acceptance. The use of chromoendoscopy-guided biopsy protocols significantly reduced the number of biopsies required to maintain similar BE detection rates. Furthermore, the value of BE chemoprophylaxis with esomeprazole and acetylsalicylic acid was relevant, as well as the establishment of protocols for the follow-up and endoscopic surveillance of patients with BE based predominantly on the presence and degree of dysplasia, as well as on the length of the follow-up affected by BE. CONCLUSION: Although further studies regarding the diagnosis, treatment and follow-up of BE are warranted, in light of the best evidence presented in the last decade, there is a trend towards electronic chromoendoscopy-guided biopsies for the diagnosis of BE, while treatment should encompass endoscopic techniques such as radiofrequency ablation. Risks of ablative endoscopic methods should be weighted against those of resective surgery. It is also important to consider lifetime endoscopic follow-up for both short and long term BE patients, with consideration to limitations imposed by a range of comorbidities. Unfortunately, there are no randomized controlled trials that have evaluated which is the best recommendation for BE follow-up and endoscopic surveillance (>1 cm) protocols, however, based on current International Guidelines, it is recommended esophagogastroduodenoscopy (EGD) every 5 years in BE without dysplasia with 1 up to 3 cm of extension; every 3 years in BE without dysplasia with >3 up to 10 cm of extension, every 6 to 12 months in BE with low grade dysplasia and, finally, EGD every 3 months after ablative endoscopic therapy in cases of BE with high grade dysplasia.

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Systematic review and meta-analysis of the effectiveness of radiofrequency ablation in low grade dysplastic Barrett’s esophagus

Endoscopy ◽

10.1055/a-0588-5151 ◽

2018 ◽

Vol 50 (10) ◽

pp. 953-960 ◽

Cited By ~ 9

Author(s):

Gargi Pandey ◽

Mubashir Mulla ◽

Wyn Lewis ◽

Antonio Foliaki ◽

David Chan

Keyword(s):

Systematic Review ◽

Radiofrequency Ablation ◽

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Meta Analysis ◽

Low Grade ◽

Short Term ◽

Recurrence Rates ◽

Premalignant Condition

Abstract Background Barrett’s esophagus (BE) is a premalignant condition characterized by replacement of the esophageal lining with metastatic columnar epithelium, and its management when complicated by low grade dysplasia (LGD) is controversial. This systematic review and meta-analysis aimed to determine the efficacy of radiofrequency ablation (RFA) in patients with LGD. Methods MEDLINE, EMBASE, and Web of Science were searched for studies including patients with BE-associated LGD receiving RFA (January 1990 to May 2017). The outcome measures were complete eradication of intestinal metaplasia (CE-IM) and dysplasia (CE-D), rates of progression to high grade dysplasia (HGD) or cancer, and recurrence. Results Eight studies including 619 patients with LGD (RFA = 404, surveillance = 215) were analyzed. After a median follow-up of 26 months (range 12 – 44 months), the overall pooled rates of CE-IM and CE-D after RFA were 88.17 % (95 % confidence interval [CI] 88.13 % – 88.20 %; P < 0.001) and 96.69 % (95 %CI 96.67 % – 96.71 %; P < 0.001), respectively. When compared with surveillance, RFA resulted in significantly lower rates of progression to HGD or cancer (odds ratio [OR] 0.07, 95 %CI 0.02 – 0.22). The pooled recurrence rates of IM and dysplasia were 5.6 % (95 %CI 5.57 – 5.63; P < 0.001) and 9.66 % (95 %CI 9.61 – 9.71; P < 0.001), respectively. Conclusions RFA safely eradicates IM and dysplasia and reduces the rates of progression from LGD to HGD or cancer in the short term.

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FA02.05: PROGRESSION RATE OF BARRETT’S ESOPHAGUS FROM NATIONAL REGISTRY OF EXPERT CENTERS IS MUCH GREATER THAN ANTICIPATED FROM POPULATION STUDIES

Diseases of the Esophagus ◽

10.1093/dote/doy089.fa02.05 ◽

2018 ◽

Vol 31 (Supplement_1) ◽

pp. 4-4

Author(s):

Lisa O'Byrne ◽

Roy Verhage ◽

Marie O'Brien ◽

Dermot O'Toole ◽

Cian Muldoon ◽

...

Keyword(s):

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Population Studies ◽

First Year ◽

Progression Rate ◽

Low Grade ◽

Risk Of Progression ◽

Low Grade Dysplasia ◽

One Year

Abstract Background Barrett's Esophagus (BE) is well established as the main pathological precursor for esophageal adenocarcinoma (EAC). Progression to high grade dysplasia (HGD) or EAC varies widely between population based studies and specialized BE registries from high volume centers. No such data existed from the Republic of Ireland until 2011 when a multicenter registry was established involving three centers to more accurately determine the risk of progression to EAC in the Irish population. Methods A detailed clinical, endoscopic and pathological database includes 3397 patients from January 2008 to July 2017, with BE defined by the presence of specialized intestinal metaplasia (SIM). A prospective web based database was used to gather information from three designated esophageal centers with initial and follow up data abstracted by a data manager and overseen by a project manager. Results 325 were excluded following a diagnosis of HGD or EAC at index biopsy, or being a tertiary referral, leaving 3072 with a median age of 61 and a 2.1:1 male to female ratio and a median follow up of 3 years, and 5024 person years. 127 (4%) cases progressed to HGD/EAC, 65 after one year of follow up. 55 (2%) developed EAC were identified, 30 of those within one year. The overall incidence HGD/EAC was 2.53% per year, 1.3% if the first year is excluded. The risk of progression to EAC alone was 1.09% per year, 0.5% excluding the first year. Low grade dysplasia (LGD) on index biopsy was associated with a progression rate of 11.7% per year, 4.2% with the first year excluded. Conclusion With strict data entry and pathologic quality assurance, progression rates for non-dysplastic BE was several fold higher than population studies, highlighting caution in abstracting from population data. True LGD, as evidenced in a recent report by Kestens et al.1 represent high risk disease, with most of the risk evident within the first year. Reference: 1. Kestens C, Offerhaus G, van Baal J, Siersema PD. Patients wtih Barrett's esophagus and persistent low-grade dysplasia have an increased risk for high- grade dysplasia and cancer. Clin Gastroenterol Hepatol. 2016;14:956–962 Disclosure All authors have declared no conflicts of interest.

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Non-thermal Resection Device for Ablation of Barrett’s Esophagus – a Feasibility and Safety Study

Endoscopy ◽

10.1055/a-1644-4326 ◽

2021 ◽

Author(s):

Annieke Willemien Gotink ◽

Yonne Peters ◽

Marco J. Bruno ◽

Peter D. Siersema ◽

Arjun Dave Koch

Keyword(s):

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Low Grade ◽

First Line ◽

Related Complication ◽

Median Percentage ◽

Ablation Therapy ◽

Ablation Technique ◽

Endoscopic Ablation

Background and study aims Several techniques exist for the eradication of Barrett’s esophagus (BE); however, all have limitations regarding successful conversion to squamous epithelium and a complication profile. We aimed to assess the feasibility and safety of a new non-thermal device, the EndoRotor, for the eradication of BE as a first-line ablation technique. Patients and methods Patients with BE were prospectively included in 2 tertiary referral centers in The Netherlands. Inclusion criteria: BE-length 2-5cm, with low-grade dysplasia, high-grade dysplasia or residual BE after endoscopic resection (ER) of a lesion containing early neoplasia. Exclusion criteria: previous ER >50% circumference, or previous ablation therapy. Follow-up endoscopy was performed after 3 months. Outcomes were the percentage of endoscopically visible BE surface regression and complications. Results Thirty patients (25 male, age 66 years [IQR: 59–73], median BE C0M3) were included. Eighteen patients underwent ER prior to ablation. Median percentage BE ablated was 100% (IQR: 94-100). Median visual BE surface regression at three-months follow-up was 80% (IQR: 68–95). Multiple residual Barrett’s islands were commonly seen. Six patients(20%) had a treatment-related complication requiring intervention, including one perforation(3%), one postprocedural hemorrhage(3%), and four strictures(13%). Post-procedural pain was reported in 18 patients(60%). Conclusions For the endoscopic ablation of BE, the EndoRotor procedure was found to be technically demanding with a longer procedure time compared to established ablation techniques and a high complication rate. Based on these results, we do not recommend the EndoRotor as a first-line ablation technique for the eradication of BE.

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Persistent indefinite for dysplasia in Barrett’s esophagus is a risk factor for dysplastic progression to low-grade dysplasia

Diseases of the Esophagus ◽

10.1093/dote/doaa015 ◽

2020 ◽

Vol 33 (9) ◽

Author(s):

Andrew J Henn ◽

Kevin Y Song ◽

Amy A Gravely ◽

Hector Mesa ◽

Shahnaz Sultan ◽

...

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

Risk Factor ◽

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Smoking History ◽

Low Grade ◽

Indefinite For Dysplasia ◽

Low Grade Dysplasia

Summary Patients with Barrett’s esophagus (BE) are at increased risk of esophageal adenocarcinoma (EAC). The risk is largely based on the degree of dysplasia. Dysplasia cannot always be differentiated from inflammatory changes, and therefore may be classified as indefinite for dysplasia (IND). The risk of progressive dysplasia in patients with IND is unclear. Our aim is to characterize the risk of progression in US veterans with BE-IND. We performed a single-center retrospective cohort study of patients with BE-IND between 2006 and 2016. All IND was diagnosed by consensus conference with an expert gastrointestinal (GI) pathologist or review by an expert GI pathologist and persistence was defined as IND present on subsequent endoscopic biopsy. The primary outcome was the incidence rate of high-grade dysplasia (HGD)/EAC. Secondary outcomes included any progression including incident low-grade dysplasia (LGD), any prevalent dysplasia and risk factors for dysplastic progression, namely persistent IND. Risk factors for progression were assessed using univariate and multivariate analysis with logistic regression. Among 107 patients with BE-IND, there were no incident cases of HGD/EAC. Twenty patients (18.7%) developed incident LGD during a median follow-up of 2.39 years (interquartile range, 1.13–5.17). The annual rate of progression to LGD was 5.95 per 100 patient-years (95% CI, 3.73–9.02). Prevalent dysplasia was common (9.3%). Eight patients had prevalent LGD, one patient had prevalent HGD and one patient had prevalent EAC. Twenty-eight patients (30.1%) were found to have persistent IND. Among those with persistent IND, 10 (36%) patients progressed to LGD (none to HGD/EAC). The progression rate to LGD for patients with persistent IND was 7.86 (95% CI, 3.99–14.02) cases per 100 patient-years versus 4.78 (95% CI, 2.48–8.52) for nonpersistent IND (P = 0.036). The odds ratio for progression to LGD in persistent IND was 3.06 (95% CI, 1.08–8.64). In multivariate analysis adjusting for age, smoking history, presence of hiatal hernia and BMI > 30, persistent IND remained significant (OR 3.23; 95% CI, 1.04–9.98). Regression to nondysplastic BE was very common. Seventy-one (61%) patients developed complete and sustained regression of all dysplastic changes at last follow-up. Persistent IND, present in one-third of patients with IND, is an independent risk factor for progression to LGD. Although no patients in this cohort developed HGD/EAC, prevalent dysplasia was common (9.3%). Taken together, patients with IND should receive close surveillance for both prevalent and incident dysplasia especially if IND is persistent.

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