Total Cancer Incidence and Overall Mortality Are Not Increased Among Patients With Barrett's Esophagus

doi:10.1016/j.cgh.2011.04.008

Clinical Gastroenterology and Hepatology

Volume 9, Issue 9, September 2011, Pages 754-761

https://doi.org/10.1016/j.cgh.2011.04.008 Get rights and content

Background & Aims

Barrett's esophagus (BE) increases risk for esophageal adenocarcinoma, but it is not clear how it affects risk for other cancers or overall mortality. We analyzed data from a population-based cohort of subjects with BE.

Methods

The Netherlands Cohort Study was initiated in 1986 and included 120,852 participants (55–69 years old at baseline). Until December 2002, 626 incident cases of BE (excluding nonintestinal metaplasia) were identified by record linkage with the nationwide Pathology Registry. This cohort was followed for a median period of 5.7 years; data on cancer and mortality were obtained from record linkage to the Netherlands Cancer Registry and Statistics Netherlands. The expected number of cases was calculated using national cancer incidence and mortality data.

Results

In the BE cohort, 13 individuals developed esophageal cancer and 5 developed gastric cancer. The ratio of observed:expected (O:E) incidence of esophageal and gastric cancer was 10.0 (95% confidence interval [CI], 5.3–17.1) and 1.8 (95% CI, 0.6–4.2), respectively. Total cancer incidence (excluding esophageal and gastric cancer) increased in the BE cohort, although not by a statistically significant amount (O:E, 1.3; 95% CI, 1.0–1.6). Of cancer subtypes, incidences of small intestinal and pancreatic cancer increased in subjects with BE, but not by a statistically significant amount, after exclusion of data from the first 6 months of follow-up. During the follow-up period, 225 individuals with BE died. Mortality from all causes (excluding esophageal and gastric cancer) was not increased among subjects with BE (O:E, 1.0; 95% CI, 0.9–1.2), nor was mortality from specific causes of death.

Conclusions

The incidence of esophageal cancer was increased in a population-based cohort of subjects with BE. However, when esophageal and gastric cancers were excluded, total cancer incidence and overall mortality were not increased among subjects with BE.

Section snippets

Study Design and Subjects

The Netherlands Cohort Study on Diet and Cancer was started in September 1986, when 58,279 Dutch men and 62,573 women aged 55 to 69 years were enrolled. The subjects were selected at random from 204 Dutch municipal population registries. All cohort members completed a self-administered questionnaire on dietary habits and other risk factors for cancer. The study design has been described previously in detail.¹⁴

BE cases in the total cohort were identified by computerized record-linkage to the

Results

The dataset for esophageal and gastric cancer incidence included 605 BE cases, the dataset for incidence of other cancers included 561 persons, while the dataset for mortality follow-up counted 626 persons (Figure 1, Table 1). The majority of the BE cases was male. In 73% to 74% of the BE cases, the histology was specified as intestinal metaplasia, while in the remaining cases the histology was unspecified. Dysplasia was reported not to be present in 81% of the cases, while high-grade dysplasia

Discussion

In this large population-based cohort, cases with BE are at an increased risk for esophageal adenocarcinoma with an O:E ratio of 10.0. Patients with nondysplastic BE have a risk of 2.7 and those with low-grade dysplasia have a risk of 3.7 per 1000 person years of progression to esophageal carcinoma. Total cancer incidence (excluding esophageal and gastric cancer) was increased in the BE cohort, although not by a statistically significant amount. Incidence of small intestinal and pancreatic

Acknowledgments

The authors are indebted to the participants of this study and further wish to thank the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA), the Netherlands Cancer Registry and Statistics Netherlands for supplying follow-up information. The authors also thank Dr W.J. Klokman (Netherlands Cancer Institute) for statistical advice; S. van de Crommert, H. Brants, J. Nelissen, C. de Zwart, M. Moll, W. van Dijk, M. Jansen, and A. Pisters for assistance; and H. van

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Cited by (37)

A review of the incidence of adenocarcinoma detected during surveillance for Barrett's esophagus
2019, Human Pathology
The objective of this study is to provide an up-to-date estimate of the incidence of adenocarcinoma detected during surveillance of Barrett's esophagus. Fifty-five longitudinal studies involving approximately 61 000 patients were reviewed. A general linear model analyses with Poisson link function was used to study how the number of cancer cases detected depended on study details. The studies seemed to follow the same statistical model, and the probability of developing Barrett's carcinoma during surveillance was found to depend on the following variables: how Barrett's metaplasia was defined, the number of patients studied, the mean time of follow-up, and the fraction of patients followed up for at least 5 years. The model derived from all the studies predicted that the per-person probability of developing cancer in 5 years of complete follow-up is approximately .0012.
Factors Associated With Progression of Barrett's Esophagus: A Systematic Review and Meta-analysis
2018, Clinical Gastroenterology and Hepatology
Endoscopic surveillance of patients with Barrett’s esophagus (BE) is inefficient. Risk stratification of patients might improve the effectiveness of surveillance. We performed a systematic review and meta-analysis to identify factors associated with progression of BE without dysplasia or BE with low-grade dysplasia (LGD) to high-grade dysplasia or esophageal adenocarcinoma.
We performed a systematic search of databases through May 2016 to identify cohort studies of patients with baseline BE without dysplasia or BE with LGD that reported predictors of progression. Pooled estimates (odds ratios) of associations of age, sex, smoking, alcohol use, obesity, baseline LGD, segment length, and medication use with progression were calculated.
We identified 20 studies, reporting 1231 events in 74943 patients. The studies associated BE progression with increasing age (12 studies; odds ratio [OR], 1.03; 95% CI, 1.01–1.05), male sex (11 studies; OR, 2.16; 95% CI, 1.84–2.53), ever smoking (current or past, 8 studies; OR, 1.47; 95% CI, 1.09–1.98), and increasing BE segment length (10 studies; OR, 1.25; 95% CI, 1.16–1.36), with a low degree of heterogeneity. LGD was associated with a 4-fold increase in risk of BE progression (11 studies; OR, 4.25; 95% CI, 2.58–7.0). Use of proton pump inhibitors (4 studies; OR, 0.55; 95% CI, 0.32–0.96) or statins (3 studies; OR, 0.48; 95% CI, 0.31–0.73) were associated with lower risk of BE progression. Alcohol use and obesity did not associate with risk of progression.
In a systematic review and meta-analysis, we associated older age, male sex, smoking, longer BE segment, and LGD with risk of progression of BE. Individuals with these features should undergo more intensive surveillance or endoscopic therapy. Smoking is a modifiable risk factor for cancer prevention in patients with BE.
A preliminary feasibility study: Narrow-band imaging targeted versus standard white light endoscopy non-targeted biopsies in a surveillance Barrett's population
2016, Digestive and Liver Disease
Citation Excerpt :
The published studies have proven a variable prevalence: Curvers [13] demonstrated a prevalence of LGD of 1.6%, but the prevalence obtained by Schnell [14] was up to 67.2%. Recent population studies [15,16] have shown a prevalence of LGD between 13 and 15%. The value obtained in our study is close to the one obtained by Hvid-Jensen [17] of 5.6%.
Narrow band imaging (NBI) is used in the detection of intestinal metaplasia (IM) and dysplasia in patients with Barrett's oesophagus (BE).
The study compared the usefulness of NBI with white-light standard endoscopy (WLSE) for the detection of dysplasia and IM in BE and determined the prediction of the histological diagnosis according to the mucosal and vascular patterns obtained by NBI.
A total of 84 patients were prospectively enrolled in the study. Every patient underwent a WLSE with random biopsies and after 4–6 weeks, a NBI examination was performed.
NBI detected significant more IM positive biopsies than WLSE (74.5% vs. 35.9%; p < 0.0001) and significant more patients with low grade dysplasia (LGD) (7.1% vs. 0%; p = 0.03). Taking biopsy samples from the villous pattern determined the diagnosis of IM (80%) and biopsies from the area covered by the irregular pattern lead to the identification of LGD in 45.4% of the cases and indefinite dysplasia (ID) in 18.2% of the cases.
A thorough analysis of NBI patterns may lead to real-time IM diagnosis in the absence of the histological examination and may require targeted biopsies from the areas with an irregular pattern for diagnosing dysplasia.
Incidence of Esophageal Adenocarcinoma and Causes of Mortality after Radiofrequency Ablation of Barrett's Esophagus
2015, Gastroenterology
Radiofrequency ablation (RFA) is commonly used to treat Barrett’s esophagus (BE). We assessed the incidence of esophageal adenocarcinoma (EAC) after RFA, factors associated with the development of EAC, and EAC-specific and all-cause mortality.
We collected data for outcomes of patients who underwent RFA for BE from July 2007 through July 2011 from US multicenter RFA Patient Registry. Patients were followed until July 2014. Kaplan-Meier curves of EAC incidence were stratified by baseline histology. Crude EAC incidence and mortality (all-cause and EAC-specific) were calculated, and adjusted all-cause mortality was assessed. Logistic regression models were constructed to assess predictors of EAC and all-cause mortality.
Among 4982 patients, 100 (2%) developed EAC (7.8/1000 person-years [PY]) and 9 patients (0.2%) died of EAC (0.7/1000 PY) in a mean 2.7 ± 1.6 years. The incidence of EAC in nondysplastic BE was 0.5/1000 PY. Overall, 157 patients (3%) died during follow-up (all-cause mortality, 11.2/1000 PY). On multivariate logistic regression, baseline BE length (odds ratio, 1.1/ cm) and baseline histology (odds ratios, 5.8 and 50.3 for low-grade dysplasia and high-grade dysplasia [HGD] respectively) predicted EAC incidence. Among 9 EAC deaths, 6 (67%) had baseline HGD, and 3 (33%) had baseline intramucosal EAC. The most common causes of death were cardiovascular (15%) and extraesophageal cancers (15%). No deaths were associated with RFA.
Based on analysis of a multicenter registry of patients who underwent RFA of BE, less than 1% died from EAC. The incidence of EAC was markedly lower in this study than in other studies of disease progression, with the greatest absolute benefit observed in patients with HGD.
Detection and characterization of early malignancy in the esophagus: What is the best management algorithm?
2015, Best Practice and Research: Clinical Gastroenterology
Barrett's esophagus is a known precursor for esophageal adenocarcinoma. Early detection of dysplasia provides a window of opportunity for curative intervention. Several image-enhanced technologies have been developed to improve visualization of neoplasia. These however have not been found to be superior to the standard four quadrant random biopsy protocol. Patients are risk-stratified based on the degree of dysplasia found on biopsies and undergo either surveillance or treatment. Endoscopic therapy has become the mainstay of treatment for early neoplasia.
Epidemiology of Barrett's Esophagus and Esophageal Adenocarcinoma
2015, Gastroenterology Clinics of North America

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: This article has an accompanying continuing medical education activity on page e98. Learning Objectives—At the end of this activity, the learner will know about the incidence of cancer and mortality in patients with Barrett’s esophagus.

: Conflicts of interest The authors disclose no conflicts.

: Funding This study was financially supported by grant UM 2006-3562 from the Dutch Cancer Society.

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Original article—alimentary tractTotal Cancer Incidence and Overall Mortality Are Not Increased Among Patients With Barrett's Esophagus

Background & Aims

Methods

Results

Conclusions

Section snippets

Study Design and Subjects

Results

Discussion

Acknowledgments

Lancet

Clin Gastroenterol Hepatol

J Clin Epidemiol

Gastroenterology

Gastroenterology

Am J Gastroenterol

Lancet

Risk of mortality and cancer incidence in Barrett's esophagus

Cancer Epidemiol Biomarkers Prev

The incidence of esophageal cancer and high-grade dysplasia in Barrett's esophagus: a systematic review and meta-analysis

Am J Epidemiol

Risk of malignant progression in patients with Barrett's oesophagus: a Dutch nationwide cohort study

Gut

Patients with nondysplastic Barrett's esophagus have low risks for developing dysplasia or esophageal adenocarcinoma

Clin Gastroenterol Hepatol

Risk of colorectal cancer in patients with Barrett's esophagus: a Dutch population-based study

Am J Gastroenterol

A systematic review of the association between Barrett's esophagus and colon neoplasms

Am J Gastroenterol

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

Gut

Original article—alimentary tract
Total Cancer Incidence and Overall Mortality Are Not Increased Among Patients With Barrett's Esophagus