Impact of Endoscopic Surveillance on Mortality From Barrett's Esophagus–Associated Esophageal Adenocarcinomas

doi:10.1053/j.gastro.2013.05.004

Gastroenterology

Volume 145, Issue 2, August 2013, Pages 312-319.e1

https://doi.org/10.1053/j.gastro.2013.05.004 Get rights and content

Background & Aims

Although patients with Barrett’s esophagus commonly undergo endoscopic surveillance, its effectiveness in reducing mortality from esophageal/gastroesophageal junction adenocarcinomas has not been evaluated rigorously.

Methods

We 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.

Results

Surveillance 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).

Conclusions

Endoscopic 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.

Section snippets

Source Population and Data Sources

The underlying study population was all adult (≥18 y) members of Kaiser Permanente, Northern California (KPNC) during the years 1995–2009. KPNC is an integrated health care delivery system with approximately 3.3 million current members who are approximately representative of the age, sex, and ethnic distributions of the underlying regional population.²¹ Patients with Barrett’s esophagus receive surveillance examinations through physician-directed recommendations.

Barrett’s Esophagus

Persons with Barrett’s esophagus

Results

We identified 8272 patients with a Barrett’s esophagus diagnosis using electronic coding (Figure 1), 351 of whom simultaneously or subsequently were diagnosed with an esophageal or gastroesophageal junction adenocarcinoma. Of these 351, 70 had their cancer diagnosed 6 months or more after their Barrett’s esophagus diagnosis, and 51 died during follow-up evaluation. Manual review excluded 13 patients: 5 patients whose cause of death could not be determined, 2 with deaths from other cancers, 3

Discussion

Surveillance for persons at high risk of a disease offers the potential to detect preclinical disease amenable to early treatment. To provide this benefit, the surveillance method must fulfill certain criteria.²⁰ First, the test must be able to detect a condition before it would present with symptoms. Second, treatment of this preclinical condition should yield a superior outcome to treatment of disease detected because of symptoms. Third, it should be feasible, available, and economically

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Cited by (203)

Significance of Crypt Atypia in Barrett's Esophagus: A Clinical, Molecular, and Outcome Study
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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.
DNA flow cytometry for detection of genomic instability as a cancer precursor in the gastrointestinal tract
2024, Methods in Cell Biology
One of the earliest applications of flow cytometry was the measurement of DNA content in cells. This method is based on the ability to stain DNA in a stoichiometric manner (i.e., the amount of stain is directly proportional to the amount of DNA within the cell). For more than 40 years, a number of studies have consistently demonstrated the utility of DNA flow cytometry as a potential diagnostic and/or prognostic tool in patients with most epithelial tumors, including pre-invasive lesions (such as dysplasia) in the gastrointestinal tract. However, its availability as a clinical test has been limited to few medical centers due to the requirement for fresh tissue in earlier studies and perceived technical demands. However, more recent studies have successfully utilized formalin-fixed paraffin-embedded (FFPE) tissue to generate high-quality DNA content histograms, demonstrating the feasibility of this methodology. This review summarizes step-by-step methods on how to perform DNA flow cytometry using FFPE tissue and analyze DNA content histograms based on the published consensus guidelines in order to assist in the diagnosis and/or risk stratification of many different epithelial tumors, with particular emphasis on dysplasia associated with Barrett's esophagus and inflammatory bowel disease.
Benefit of adjunctive wide-area transepithelial sampling with 3-dimensional computer-assisted analysis plus forceps biopsy based on Barrett's esophagus segment length
2023, Gastrointestinal Endoscopy
Wide-area transepithelial sampling with 3-dimensional computer-assisted analysis (WATS-3D) has been shown to increase the diagnostic yield of intestinal metaplasia (IM) and dysplasia within a segment of suspected or known Barrett’s esophagus (BE) when used as an adjunct to forceps biopsies. Few data are available regarding how segment length affects WATS-3D yield. The purpose of this study was to evaluate adjunctive WATS-3D use in patients with varying lengths of BE.
A total of 8471 patients (52.5% male; mean age, 63 years) enrolled in 2 registry studies were included in this study. All patients were being screened or surveyed for BE with both forceps biopsies and WATS-3D. The adjunctive and absolute yield of WATS-3D was calculated according to the length of the patient’s BE segment.
The overall adjunctive and absolute increased diagnostic yields with WATS-3D were 47.6% and 17.5%, respectively, for detection of IM, and 139% and 2.4% for detection of dysplasia. IM and dysplasia detection both increased with the use of WATS-3D regardless of segment length. Increase in IM diagnostic yield was significantly higher in short- versus long-segment cases but higher in long-segment cases for dysplasia detection.
This study shows that when WATS-3D is added as an adjunct to forceps biopsies, it is effective at increasing the diagnostic yield of both BE and associated dysplasia in patients with both short and long segments of esophageal columnar-lined epithelium.
Massively Parallel Sequencing of Esophageal Brushings Enables an Aneuploidy-Based Classification of Patients With Barrett's Esophagus
2021, Gastroenterology
Aneuploidy has been proposed as a tool to assess progression in patients with Barrett’s esophagus (BE), but has heretofore required multiple biopsies. We assessed whether a single esophageal brushing that widely sampled the esophagus could be combined with massively parallel sequencing to characterize aneuploidy and identify patients with disease progression to dysplasia or cancer.
Esophageal brushings were obtained from patients without BE, with non-dysplastic BE (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (EAC). To assess aneuploidy, we used RealSeqS, a technique that uses a single primer pair to interrogate ∼350,000 genome-spanning regions and identify specific chromosome arm alterations. A classifier to distinguish NDBE from EAC was trained on results from 79 patients. An independent validation cohort of 268 subjects was used to test the classifier at distinguishing patients at successive phases of BE progression.
Aneuploidy progression was associated with gains of 1q, 12p, and 20q and losses on 9p and 17p. The entire chromosome 8q was often gained in NDBE, whereas focal gain of 8q24 was identified only when there was dysplasia. Among validation subjects, a classifier incorporating these features with a global measure of aneuploidy scored positive in 96% of EAC, 68% of HGD, but only 7% of NDBE.
RealSeqS analysis of esophageal brushings provides a practical and sensitive method to determine aneuploidy in BE patients. It identifies specific chromosome changes that occur early in NDBE and others that occur late and mark progression to dysplasia. The clinical implications of this approach can now be tested in prospective trials.
Adequacy of EGD Reporting: a Review of 100 Reports from 100 Endoscopists
2021, Journal of Gastrointestinal Surgery
Esophagogastroduodenoscopy (EGD) is commonly performed in patients with gastroesophageal reflux disease (GERD). An EGD report should document pertinent findings such as esophagitis, a columnar-lined esophagus (CLE), the location of the squamo-columnar and gastroesophageal junctions, the size and type of a hiatal hernia and the number and location of any biopsies. The aim of this study was to evaluate how commonly these findings were noted in the EGD reports of patients referred for antireflux surgery.
A retrospective review was performed of patient charts from 2012 to 2015 to identify 100 consecutive EGD reports from different endoscopists in different patients. Each EGD report was reviewed for pertinent findings and the use of a classification system for esophagitis (Savory-Miller or Los Angeles) and for reporting a CLE (Prague).
In 100 EGD reports, esophagitis was noted in 33 patients, but was graded in only 14 (42%). A CLE was noted in 28 patients, but the length was reported in only 16 (57%) and no report used the Prague classification system. A hiatal hernia was noted in 61 patients, measured in 31 (51%) and the type classified in 26%. A biopsy was taken in 93 patients and the location noted in 86 patients (93%). The number of biopsies was recorded in only 20 patients (22%). In 12 patients the EGD was for Barrett’s surveillance, yet a Seattle biopsy protocol was reported to be used in only 3 patients.
Endoscopy reports frequently do not include the use of a grading system for esophagitis or the Prague system for CLE. This hampers the assessment of change with therapy or over time. The size of a hiatal hernia was typically reported in a subjective fashion and only infrequently was the type specified. Lack of clarity about the presence of a paraesophageal hernia can impede evaluation of acute symptoms. In patients with Barrett’s esophagus a standard biopsy protocol was infrequently reported to be used. These findings raise concern about the quality of upper endoscopy, both in the performance of the procedure and the documentation of findings. A consistent reporting system is recommended for routine use with upper endoscopy.
National Institute for Health and Care Excellence (NICE) guidance on monitoring and management of Barrett’s oesophagus and stage I oesophageal adenocarcinoma
2024, Gut

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: This article has an accompanying continuing medical education activity on page e14. Learning Objective: Upon completion of these questions, successful learners will be able to assess the evidence supporting routine endoscopic surveillance of patients with Barrett's esophagus.

: Conflicts of interest The authors disclose no conflicts.

: Funding Supported by US National Institutes of Health grant RO1 DK63616; the Kaiser Permanente Research Project on Genes, Environment and Health; and a Kaiser Permanente Community Benefits Grant.

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Original ResearchFull Report: Clinical—Alimentary TractImpact of Endoscopic Surveillance on Mortality From Barrett's Esophagus–Associated Esophageal Adenocarcinomas

Background & Aims

Methods

Results

Conclusions

Section snippets

Source Population and Data Sources

Barrett’s Esophagus

Results

Discussion

Am J Gastroenterol

Gastroenterology

Gastroenterology

Gastroenterology

Am J Gastroenterol

Clin Gastroenterol Hepatol

Lancet

Lancet

Gastrointest Endosc

Gastroenterology

Gastroenterology

Lancet

Gastrointest Endosc

Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's esophagus

Am J Gastroenterol

American Gastroenterological Association medical position statement on the management of Barrett's esophagus

Gastroenterology

Screening and surveillance for Barrett esophagus in high-risk groups: a cost-utility analysis

Ann Intern Med

Surveillance of Barrett's oesophagus: exploring the uncertainty through systematic review, expert workshop and economic modelling

Health Technol Assess

Mortality in Barrett's oesophagus: results from a population based study

Gut

Oesophageal cancer is an uncommon cause of death in patients with Barrett's oesophagus

Gut

Marked regional variation in adenocarcinomas of the esophagus and the gastric cardia in the United States

Cancer

Incidence of adenocarcinoma among patients with Barrett's esophagus

N Engl J Med

Original Research
Full Report: Clinical—Alimentary Tract
Impact of Endoscopic Surveillance on Mortality From Barrett's Esophagus–Associated Esophageal Adenocarcinomas