Impact of surveillance for Barrett's oesophagus on tumour stage and survival of patients with neoplastic progression.

OBJECTIVE: Endoscopic surveillance for Barrett's oesophagus (BO) is under discussion given the overall low incidence of neoplastic progression and lack of evidence that it prevents advanced oesophageal adenocarcinoma (OAC). The aim of this study was to evaluate the impact of endoscopic BO surveillance on tumour stage and survival of patients with neoplastic progression. DESIGN: 783 patients with BO of at least 2 cm were included in a multicentre prospective cohort and followed during surveillance according to the American College of Gastroenterology guidelines. Cases of high-grade dysplasia and OAC were identified during follow-up. OAC staging was performed according to the 7th UICC-AJCC classification. Survival data were collected and crosschecked using death and municipal registries. Data from patients with OAC in the general population were obtained from the Dutch cancer registry. We compared survival of patients with BO with neoplastic progression during surveillance with those of patients without neoplastic progression and patients with OAC in the general population. RESULTS: 53 patients with BO developed high-grade dysplasia or OAC during surveillance. Thirty-five (66%) were classified as stage 0, 14 (26%) as stage 1 and 4 (8%) as stage 2. OAC was diagnosed at an earlier stage during BO surveillance than in the general population (p<0.001). Survival of patients with BO with neoplastic progression was not significantly worse than those of patients without neoplastic progression and similar to survival of patients with stage 0 or stage 1 OAC in the general population. CONCLUSIONS: OAC is detected at an earlier stage during BO surveillance than in the general population with good survival rates.

Surveillance in patients with long-segment Barrett's oesophagus: a cost-effectiveness analysis.

OBJECTIVE: Surveillance is recommended for Barrett's oesophagus (BO) to detect early oesophageal adenocarcinoma (OAC). The aim of this study was to evaluate the cost-effectiveness of surveillance. DESIGN: We included 714 patients with long-segment BO in a multicentre prospective cohort study and used a multistate Markov model to calculate progression rates from no dysplasia (ND) to low-grade dysplasia (LGD), high-grade dysplasia (HGD) and OAC. Progression rates were incorporated in a decision-analytic model, including costs and quality of life data. We evaluated different surveillance intervals for ND and LGD, endoscopic mucosal resection (EMR), radiofrequency ablation (RFA) and oesophagectomy for HGD or early OAC and oesophagectomy for advanced OAC. The incremental cost-effectiveness ratio (ICER) was calculated in costs per quality-adjusted life-year (QALY). RESULTS: The annual progression rate was 2% for ND to LGD, 4% for LGD to HGD or early OAC and 25% for HGD or early OAC to advanced OAC. Surveillance every 5 or 4 years with RFA for HGD or early OAC and oesophagectomy for advanced OAC had ICERs of €5.283 and €62.619 per QALY for ND. Surveillance every five to one year had ICERs of €4.922, €30.067, €32.531, €41.499 and €75.601 per QALY for LGD. EMR prior to RFA was slightly more expensive, but important for tumour staging. CONCLUSIONS: Based on a Dutch healthcare perspective and assuming a willingness-to-pay threshold of €35.000 per QALY, surveillance with EMR and RFA for HGD or early OAC, and oesophagectomy for advanced OAC is cost-effective every 5 years for ND and every 3 years for LGD.

Cyclooxygenase inhibitors use is associated with reduced risk of esophageal adenocarcinoma in patients with Barrett's esophagus: a meta-analysis.

BACKGROUND: Esophageal adenocarcinoma (EAC) has high mortality and is increasing in incidence. Barrett's esophagus (BE) increases the risk for EAC. Studies have reported inconsistent findings on the association between use of cyclooxygenase (COX) inhibitors and the risk of neoplastic progression in BE patients. Therefore, we performed a meta-analysis to investigate this association. METHODS: A meta-analysis was undertaken among a total of 9 observational studies using fixed- and random-effects models, comprising 5446 participants; 605 had EAC or high-grade dysplasia (HGD). RESULTS: Overall, COX inhibitors use was associated with a reduced risk of EAC/HGD among BE patients (relative risk (RR)=0.64, 95% confidence interval (CI)=0.53-0.77). Aspirin use also reduced the risk of EAC/HGD (RR=0.63, 95% CI=0.43-0.94), as well as non-aspirin COX inhibitors (RR=0.50, 95% CI=0.32-0.78). The chemopreventive effect seemed to be independent of duration response. CONCLUSIONS: Cyclooxygenase inhibitors use is associated with a reduced risk of developing EAC in patients with BE. Both low-dose aspirin and non-aspirin COX inhibitors are associated with a reduced risk of neoplasia. More well-designed randomised controlled trials are needed to increase our understanding of the chemopreventive effect of COX inhibitors.

Predictors for neoplastic progression in patients with Barrett's Esophagus: a prospective cohort study.

OBJECTIVES: Patients with Barrett's esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EAC). As the absolute risk remains low, there is a need for predictors of neoplastic progression to tailor more individualized surveillance programs. The aim of this study was to identify such predictors of progression to high-grade dysplasia (HGD) and EAC in patients with BE after 4 years of surveillance and to develop a prediction model based on these factors. METHODS: We included 713 patients with BE (≥ 2 cm) with no dysplasia (ND) or low-grade dysplasia (LGD) in a multicenter, prospective cohort study. Data on age, gender, body mass index (BMI), reflux symptoms, tobacco and alcohol use, medication use, upper gastrointestinal (GI) endoscopy findings, and histology were prospectively collected. As part of this study, patients with ND underwent surveillance every 2 years, whereas those with LGD were followed on a yearly basis. Log linear regression analysis was performed to identify risk factors associated with the development of HGD or EAC during surveillance. RESULTS: After 4 years of follow-up, 26/713 (3.4%) patients developed HGD or EAC, with the remaining 687 patients remaining stable with ND or LGD. Multivariable analysis showed that a known duration of BE of ≥ 10 years (risk ratio (RR) 3.2; 95% confidence interval (CI) 1.3-7.8), length of BE (RR 1.11 per cm increase in length; 95% CI 1.01-1.2), esophagitis (RR 3.5; 95% CI 1.3-9.5), and LGD (RR 9.7; 95% CI 4.4-21.5) were significant predictors of progression to HGD or EAC. In a prediction model, we found that the annual risk of developing HGD or EAC in BE varied between 0.3% and up to 40%. Patients with ND and no other risk factors had the lowest risk of developing HGD or EAC (<1%), whereas those with LGD and at least one other risk factor had the highest risk of neoplastic progression (18-40%). CONCLUSIONS: In patients with BE, the risk of developing HGD or EAC is predominantly determined by the presence of LGD, a known duration of BE of ≥10 years, longer length of BE, and presence of esophagitis. One or combinations of these risk factors are able to identify patients with a low or high risk of neoplastic progression and could therefore be used to individualize surveillance intervals in BE.

Role of acid suppression in the development and progression of dysplasia in patients with Barrett's esophagus.

Barrett's esophagus (BE) usually develops in patients with gastroesophageal reflux disease and therefore it has been suggested that esophageal acid exposure plays an import role in the initiation of BE and its progression towards esophageal adenocarcinoma (EAC). The mechanisms whereby acid exposure causes BE are not completely revealed and the potential role of esophageal acid exposure in carcinogenesis is unclear as well. Since acid exposure is thought to play an important role in the progression of BE, therapies aimed at preventing the development of EAC have primarily focused on pharmacological and surgical acid suppression. In clinical practice, acid suppression is effective in relieving reflux symptoms and decreases esophageal acid exposure in most patients. However, in some individuals, pathological acid exposure persists and these patients continue to be at risk for developing dysplasia or EAC. To date, published trials suggest that acid suppression is able to prevent the development and progression of dysplasia in patients with BE, but definite and compelling proof is still lacking. This article reviews the mechanisms of acid-induced carcinogenesis in BE and the role of acid suppression in the prevention of neoplastic progression.