Improving cost-effectiveness of endoscopic surveillance for Barrett's esophagus by reducing low-value care: a review of economic evaluations.

BACKGROUND: Individuals with Barrett's esophagus are believed to be at 30-120× risk of developing esophageal adenocarcinoma (EAC). Early detection and endoscopic treatment of dysplasia/early cancer confers a significant advantage to patients under surveillance; however, most do not progress past the non-dysplastic state of Barrett's esophagus (NDBE), which is potentially an inefficient distribution of health care resources. OBJECTIVES: This article aimed to review the outcomes of cost-effectiveness studies reducing low-value care in the context of endoscopic surveillance for non-dysplastic Barrett's esophagus (NDBE). METHODS: A systematic search was conducted by two reviewers in accordance with PRISMA guidelines. INCLUSION CRITERIA: cost-utility analyses of endoscopic surveillance of NDBE patients with at least one treatment strategy focused on reduction of surveillance. A narrative synthesis of economic evaluations was undertaken, along with an in-depth analysis of input parameters contributing to stated Incremental cost-effectiveness ratios (ICER). Study appraisal was performed using the consolidated health economic evaluation reporting standards (CHEERS) tool. RESULTS: 10 Studies met inclusion criteria. There was significant variation in cost-model structures, input parameters, ICER values, and willingness-to-pay thresholds between studies. All studies except one concluded guideline-specified endoscopic surveillance for NDBE patients was not cost-effective. Studies that explored a modified surveillance by deselection of low-risk NDBE patients found it to be a cost-effective strategy. CONCLUSION: Guideline specified endoscopic surveillance for NDBE was not found to be cost-effective in the studies examined. A modified endoscopic surveillance strategy removing individuals with the lowest risk for progression from NDBE to adenocarcinoma is likely to be cost-effective but is dependent on risk profile of patients excluded from surveillance.

Association of Common Use Pharmaceuticals in Reducing Risk of Esophageal Adenocarcinoma: A SEER-Medicare Analysis.

Barrett's esophagus (BE), a recognized risk factor for esophageal adenocarcinoma (EAC), is routinely managed with proton pump inhibitors (PPIs) when symptomatic. Several lines of evidence suggest that PPIs may prevent malignant transformation. Chronic use of other common drugs, namely, statins nonsteroidal anti-inflammatory drugs (NSAIDs) and metformin, may also interfere with BE carcinogenesis, but confirmatory evidence is lacking. We identified 1,943 EAC cases and 19,430 controls (matched 10:1) between 2007 and 2013 that met our specified inclusion criteria in the SEER-Medicare database. Conditional logistic regression was used to generate odds ratios (OR) and 95% confidence intervals (95% CI). Wald χ2 tests were used to assess significance of covariates. Compared with controls, EAC cases had a higher prevalence of BE (26.2%). Use of PPIs, NSAIDs, statins, or metformin reduced the odds of EAC (PPIs: 0.10; 95% CI, 0.09-0.12; NSAIDs: 0.62; 95% CI, 0.51-0.74; statins: 0.15; 95% CI, 0.13-0.17; metformin: 0.76; 95% CI, 0.62-0.93). When stratified by BE, these associations persisted, though no association was found between NSAID use and EAC risk for participants with BE. Dual use of PPIs with NSAIDs or statins, and NSAID, statin, or metformin use alone also showed significant EAC risk reduction among all participants and those without BE. Use of PPIs alone and with NSAIDs, statins, or metformin was associated with reduced risk of EAC; however, a history of BE may diminish drug efficacy. These results indicate that common pharmacologic agents alone or in combination may decrease EAC development.Prevention Relevance: The use of common drugs, such as proton pump inhibitors, statins, non-steroidal anti-inflammatory drugs, or metformin, may reduce one's risk of developing esophageal adenocarcinoma. These results suggest that repurposing agents often used for common chronic conditions may be a new strategy for cancer prevention efforts.

Opportunistic upper endoscopy during colonoscopy as a screening strategy for countries with intermediate gastric cancer risk.

BACKGROUND AND AIM: Screening upper endoscopy can detect esophagogastric (OG) cancers early with improved outcomes. Recent cost-utility studies suggest that opportunistic upper endoscopy at the same setting of colonoscopy might be a useful strategy for screening of OG cancers, and it may be more acceptable to the patients due to cost-saving and convenience. We aim to study the diagnostic performance of this screening strategy in a country with intermediate gastric cancer risk. METHODS: A retrospective cohort study using a prospective endoscopy database from 2015 to 2017 was performed. Patients included were individuals age > 40 who underwent opportunistic upper endoscopy at the same setting of colonoscopy without any OG symptoms. Neoplastic OG lesions are defined as cancer and high-grade dysplasia. Pre-neoplastic lesions include Barrett's esophagus (BE), intestinal metaplasia (IM), and atrophic gastritis (AG). RESULTS: The study population involved 1414 patients. Neoplastic OG lesions were detected in five patients (0.35%). Pre-neoplastic lesions were identified in 174 (12.3%) patients. IM was found in 146 (10.3%) patients with 21 (1.4%) having extensive IM. The number needed to scope to detect a neoplastic OG lesion is 282.8 with an estimated cost of USD$141 400 per lesion detected. On multivariate regression, age ≥ 60 (RR: 1.84, 95% CI: 1.29-2.63) and first-degree relatives with gastric cancer (RR: 1.64, 95% CI: 1.06-2.55) were independent risk factors for neoplastic or pre-neoplastic OG lesion. CONCLUSION: For countries with intermediate gastric cancer risk, opportunistic upper endoscopy may be an alternative screening strategy in a selected patient population. Prospective trials are warranted to validate its performance.

Low-dose aspirin and risk of gastric and oesophageal cancer: A population-based study in the United Kingdom using The Health Improvement Network.

There is increasing interest regarding potential protective effects of low-dose aspirin against various gastrointestinal cancers. We aimed to quantify the association between use of low-dose aspirin and risk of gastric/oesophageal cancer using a population-based primary care database in the UK. Between January 2005 and December 2015, we identified a cohort of 223 640 new users of low-dose aspirin (75-300 mg/day) and a matched cohort of nonusers at the start of follow-up from The Health Improvement Network. Cohorts were followed to identify incident cases of gastric/oesophageal cancer. Nested case-control analyses were conducted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for current vs nonuse of low-dose aspirin using logistic regression. Current use was defined as when low-dose aspirin lasted 0 to 90 days before the index date (event date for cases, random date for controls) and previous duration was ≥1 year. We identified 727 incident cases of gastric cancer and 1394 incident cases of oesophageal cancer. ORs (95% CIs) were 0.46 (0.38-0.57) for gastric cancer and 0.59 (0.51-0.69) for oesophageal cancer. The effect remained consistent with no clear change seen between previous duration of low-dose aspirin use of 1-3, 3-5 or >5 years. The reduced risks was seen with 75 mg/day, and effects were consistent in lag-time analyses. In conclusion, our results indicate that use of low-dose aspirin is associated with a 54% reduced risk of gastric cancer and a 41% reduced risk of oesophageal cancer as supported by mechanistic data.

Age at Initiation and Frequency of Screening to Prevent Esophageal Squamous Cell Carcinoma in High-risk Regions: an Economic Evaluation.

The aim of this study was to identify the economic screening strategies for esophageal squamous cell carcinoma (ESCC) in high-risk regions. We used a validated ESCC health policy model for comparing different screening strategies for ESCC. Strategies varied in terms of age at initiation and frequency of screening. Model inputs were derived from parameter calibration and published literature. We estimated the effects of each strategy on the incidence of ESCC, costs, quality-adjusted life-year (QALY), and incremental cost-effectiveness ratios (ICERs). Compared with no screening, all competing screening strategies decreased the incidence of ESCC from 0.35% to 72.8%, and augmented the number of QALYs (0.002-0.086 QALYs per person) over a lifetime horizon. The screening strategies initiating at 40 years of age and repeated every 1-3 years, which gained over 70% of probabilities that was preferred in probabilistic sensitivity analysis at a $1,151/QALY willingness-to-pay threshold. Results were sensitive to the parameters related to the risks of developing basal cell hyperplasia/mild dysplasia. Endoscopy screening initiating at 40 years of age and repeated every 1-3 years could substantially reduce the disease burden and is cost-effective for the general population in high-risk regions.

Development of an Empirically Calibrated Model of Esophageal Squamous Cell Carcinoma in High-Risk Regions.

OBJECTIVE: This study constructs, calibrates, and verifies a mathematical simulation model designed to project the natural history of ESCC and is intended to serve as a platform for testing the benefits and cost-effectiveness of primary and secondary ESCC prevention alternatives. METHODS: The mathematical model illustrates the natural history of ESCC as a sequence of transitions among health states, including the primary health states (e.g., normal mucosa, precancerous lesions, and undetected and detected cancer). Using established calibration approaches, the parameter sets related to progression rates between health states were optimized to lead the model outputs to match the observed data (specifically, the prevalence of precancerous lesions and incidence of ESCC from the published literature in Chinese high-risk regions). As illustrative examples of clinical and policy application, the calibrated and validated model retrospectively simulate the potential benefit of two reported ESCC screening programs. RESULTS: Nearly 1,000 good-fitting parameter sets were identified from 1,000,000 simulated sets. Model outcomes had sufficient calibration fit to the calibration targets. Additionally, the verification analyses showed reasonable external consistency between the model-predicted effectiveness of ESCC screening and the reported data from clinical trials. CONCLUSIONS: This parameterized mathematical model offers a tool for future research investigating benefits, costs, and cost-effectiveness related to ESCC prevention and treatment.

Economic value of narrow-band imaging versus white light endoscopy for the diagnosis and surveillance of Barrett's esophagus: Cost-consequence model.

Barrett's esophagus (BE) is an abnormality arising from gastroesophageal reflux disease that can progressively evolve into a sequence of dysplasia and adenocarcinoma. Progression of Barrett's esophagus into dysplasia is monitored with endoscopic surveillance. The current surveillance standard requests random biopsies plus targeted biopsies of suspicious lesions under white-light endoscopy, known as the Seattle protocol. Recently, published evidence has shown that narrow-band imaging (NBI) can guide targeted biopsies to identify dysplasia and reduce the need for random biopsies. We aimed to assess the health economic implications of adopting NBI-guided targeted biopsy vs. the Seattle protocol from a National Health Service England perspective. A decision tree model was developed to undertake a cost-consequence analysis. The model estimated total costs (i.e. staff and overheads; histopathology; adverse events; capital equipment) and clinical implications of monitoring a cohort of patients with known/suspected BE, on an annual basis. In the simulation, BE patients (N = 161,657 at Year 1; estimated annual increase: +20%) entered the model every year and underwent esophageal endoscopy. After 7 years, the adoption of NBI with targeted biopsies resulted in cost reduction of £458.0 mln vs. HD-WLE with random biopsies (overall costs: £1,966.2 mln and £2,424.2 mln, respectively). The incremental investment on capital equipment to upgrade hospitals with NBI (+£68.3 mln) was offset by savings due to the reduction of histological examinations (-£505.2 mln). Reduction of biopsies also determined savings for avoided adverse events (-£21.1 mln). In the base-case analysis, the two techniques had the same accuracy (number of correctly identified cases: 1.934 mln), but NBI was safer than HD-WLE. Budget impact analysis and cost-effectiveness analyses confirmed the findings of the cost-consequence analysis. In conclusion, NBI-guided targeted biopsies was a cost-saving strategy for NHS England, compared to current practice for detection of dysplasia in patients with BE, whilst maintaining at least comparable health outcomes for patients.

A cost-effectiveness analysis of endoscopic eradication therapy for management of dysplasia arising in patients with Barrett's oesophagus in the United Kingdom.

BACKGROUND AND AIMS: Endoscopic eradication therapy (EET) is the first line approach for treating Barrett's oesophagus (BE) related neoplasia globally. The British Society of Gastroenterology (BSG) recommend EET with combined endoscopic resection (ER) for visible dysplasia followed by endoscopic ablation in patients with both low and high grade dysplasia (LGD and HGD). The aim of this study is to perform a cost-effectiveness analysis for EET for treatment of all grades of dysplasia in BE patients. METHODS: A Markov cohort model with a lifetime time horizon was used to undertake a cost-effectiveness analysis. A hypothetical cohort of UK patients diagnosed with BE entered the model. Patients in the treatment arm with LGD and HGD received EET and patients with non-dysplastic BE (NDBE) received endoscopic surveillance only. In the comparator arm, patients with LGD, HGD and NDBE received endoscopic surveillance only. A UK National Health Service (NHS) perspective was adopted and the incremental cost-effectiveness ratio (ICER) was calculated. Sensitivity analysis was conducted on key input parameters. RESULTS: EET for patients with LGD and HGD arising in BE is cost-effective compared to endoscopic surveillance alone (lifetime ICER £3006 per quality adjusted life year [QALY] gained). The results show that, as the time horizon increases, the treatment becomes more cost-effective. The 5 year financial impact to the UK NHS of introducing EET is £7.1m. CONCLUSIONS: EET for patients with low and high grade BE dysplasia, following updated guidelines from the BSG, has been shown to be cost-effective for patients with BE in the UK.

A suggested framework for conducting esophageal cancer screening in China.

Esophageal cancer is one of the most prevalent malignant tumors worldwide. Because of its challenging clinical characteristics, esophageal cancer is a major disease burden on the economy, society, and individuals. There is an urgent need to establish a beneficial policy to reduce the burden and to improve the health-related quality of life of patients. Primary prevention with smoking cessation and reduction of drinking alcohol are highly recommended. Screening, early diagnosis and treatment are suggested. This study intended to establish a modified future screening model from the social perspective that deploys different strategies for different populations. Risk assessment and community-based screening are proposed for high-risk populations. Health education in low-risk areas could help promote primary prevention to mitigate lifestyle factors and to increase public awareness and potentially to increase screening and early detection.

The African Esophageal Cancer Consortium: A Call to Action.

Esophageal cancer is the eighth most common cancer worldwide and the sixth most common cause of cancer-related death; however, worldwide incidence and mortality rates do not reflect the geographic variations in the occurrence of this disease. In recent years, increased attention has been focused on the high incidence of esophageal squamous cell carcinoma (ESCC) throughout the eastern corridor of Africa, extending from Ethiopia to South Africa. Nascent investigations are underway at a number of sites throughout the region in an effort to improve our understanding of the etiology behind the high incidence of ESCC in this region. In 2017, these sites established the African Esophageal Cancer Consortium. Here, we summarize the priorities of this newly established consortium: to implement coordinated multisite investigations into etiology and identify targets for primary prevention; to address the impact of the clinical burden of ESCC via capacity building and shared resources in treatment and palliative care; and to heighten awareness of ESCC among physicians, at-risk populations, policy makers, and funding agencies.

A survey study with assessment of esophageal screening and genetic counseling in patients with Howel-Evans syndrome.

BACKGROUND: It is important to better understand the role that environmental risk factors play on the development of esophageal cancer in Howel-Evans families. Additionally, there is little published about appropriate esophageal cancer screening practices in families genetically confirmed to have this condition. METHODS: Surveys were distributed to 47 addresses of an American family with Howel-Evans syndrome, of which 29 responded and met inclusion criteria. Data was collected about demographics, environmental risk factors, and medical history of participants. RESULTS: We report characteristics of family members with tylosis, rates of esophageal cancer, rates of genetic counseling, and levels of environmental risk factors. Of the survey respondents, 43% reported features of tylosis, 71.4% were male and 28.6% were female and 28.6% reported leukoplakia. Only 21.4% of tylotic family members smoked, 65% drank alcohol, and 28.6% drank well water. More than half (57.1%) of the tylotic individuals had never had an esophagogastroduodenoscopy (EGD) and no one had been diagnosed with esophageal carcinoma. Only 3.4% of respondents had ever received genetic testing for Howel-Evans syndrome, despite genetic confirmation of their relatives. CONCLUSIONS: We encourage dermatologists to discuss smoking-cessation, genetic counseling, and early EGD with affected families.

How the pathologist can aid in the assessment of gastroesophageal reflux disease.

PURPOSE OF REVIEW: To provide new concepts regarding the early pathologic changes of gastroesophageal reflux disease (GERD) that are associated with damage to the lower esophageal sphincter (LES). RECENT FINDINGS: A body of evidence exists that cardiac mucosa is a metaplastic esophageal epithelium rather than a normal gastric epithelium. Recent studies in asymptomatic volunteers suggest a potential mechanism for cardiac metaplasia in the squamous epithelium of the esophagus. SUMMARY: The concept that cardiac mucosa is esophageal, not gastric, suggests that the widely accepted endoscopic definition of the gastroesophageal junction (GEJ) is incorrect. I propose that the true GEJ is the proximal extent of gastric oxyntic epithelium. If there is cardiac mucosa lining proximal rugal folds, that cardiac mucosa-lined region is the dilated distal esophagus, not the proximal stomach. The dilated distal esophagus is the pathologic expression of damage to the abdominal segment of the LES. This concept suggests a new test for measuring damage to the abdominal LES and a new understanding of the disease of GERD based on the measured amount of LES damage. This opens the door to new research and change in objectives in the management of reflux disease from control of symptoms to prevention of complications such as Barrett's esophagus and adenocarcinoma.

An explanatory and predictive model of the variation in esophageal cancer incidence on the basis of changes in the exposure to risk factors.

Variations in the exposure to risk factors may be used to explain past cancer trends and to predict its future burden. This study aimed to develop a model to describe and predict the variation of esophageal cancer incidence in 1995-2005, taking into account changes in exposures to risk factors. We adapted an existing model to calculate the expected variation in the number of esophageal cancer cases, between 1995 and 2005, in Australia, Japan, Italy, Portugal, the UK, and the USA, because of changes in exposures to risk factors, taking into account the corresponding lag times. Analyses were based on country-specific data of cancer incidence and exposures to risk factors. We computed 95% credibility intervals through Monte Carlo simulation methods. Absolute deviations between the number of cases predicted and those observed in 2005 ranged between 1.8% in Japan and 23.6% in the UK among men and 0.0% in Japan and 18.0% in Australia among women. In Italy and Japan, deviations did not exceed 3%. The UK registered the worst model performance. The variation in esophageal cancer incidence was mainly influenced by changes in fruit and red meat intake, and BMI. For nearly half of the sex-specific and histological type-specific predictions performed, credibility intervals included the observed number of cases. This study proposes a framework for the analysis of the contribution of changes in exposure to different factors to esophageal cancer incidence trends and for long-term predictions at a population level.

Barrett's oesophagus: Current controversies.

Oesophageal adenocarcinoma is rapidly increasing in Western countries. This tumour frequently presents late in its course with metastatic disease and has a very poor prognosis. Barrett's oesophagus is an acquired condition whereby the native squamous mucosa of the lower oesophagus is replaced by columnar epithelium following prolonged gastro-oesophageal reflux and is the recognised precursor lesion for oesophageal adenocarcinoma. There are multiple national and society guidelines regarding screening, surveillance and management of Barrett's oesophagus, however all are limited regarding a clear evidence base for a well-demonstrated benefit and cost-effectiveness of surveillance, and robust risk stratification for patients to best use resources. Currently the accepted risk factors upon which surveillance intervals and interventions are based are Barrett's segment length and histological interpretation of the systematic biopsies. Further patient risk factors including other demographic features, smoking, gender, obesity, ethnicity, patient age, biomarkers and endoscopic adjuncts remain under consideration and are discussed in full. Recent evidence has been published to support earlier endoscopic intervention by means of ablation of the metaplastic Barrett's segment when the earliest signs of dysplasia are detected. Further work should concentrate on establishing better risk stratification and primary and secondary preventative strategies to reduce the risk of adenocarcinoma of the oesophagus.

The cost-effectiveness of radiofrequency ablation for Barrett's esophagus with low-grade dysplasia: results from a randomized controlled trial (SURF trial).

BACKGROUND AND AIMS: The Surveillance versus Radiofrequency Ablation (SURF) trial randomized 136 patients with Barrett's esophagus (BE) containing low-grade dysplasia (LGD), to receive radiofrequency ablation (ablation, n = 68) or endoscopic surveillance (control, n = 68). Ablation reduced the risk of neoplastic progression to high-grade dysplasia and esophageal adenocarcinoma (EAC) by 25% over 3 years (1.5% for ablation vs 26.5% for control). We performed a cost-effectiveness analysis from a provider perspective alongside this trial. METHODS: Patients were followed for 3 years to quantify their use of health care services, including therapeutic and surveillance endoscopies, treatment of adverse events, and medication. Costs for treatment of progression were analyzed separately. Incremental cost-effectiveness ratios (ICER) were calculated by dividing the difference in costs (excluding and including the downstream costs for treatment of progression) by the difference in prevented events of progression. Bootstrap analysis (1000 samples) was used to construct 95% confidence intervals (CIs). RESULTS: Patients who underwent ablation generated mean costs of U.S.$13,503 during the trial versus $2236 for controls (difference $11,267; 95% CI, $9996-$12,378), with an ICER per prevented event of progression of $45,066. Including the costs for treatment of progression, ablation patients generated mean costs of $13,523 versus $4,930 for controls (difference $8593; 95% CI, $6881-$10,153) with an ICER of $34,373. Based on the various ICER estimates derived from the bootstrap analysis, one can be reasonably certain (>75%) that ablation is efficient at a willingness to pay of $51,664 per prevented event of progression or $40,915 including downstream costs of progression. CONCLUSIONS: Ablation for patients with confirmed BE-LGD is more effective and more expensive than endoscopic surveillance in reducing the risk of progression to high-grade dysplasia/EAC. The increase in costs of ablation can be justified to avoid a serious event such as neoplastic progression. At a willingness to pay of $40,915 per prevented event of progression, one can be reasonably certain that ablation is efficient. (www.trialregister.nl number: NTR 1198.).

Screening for Barrett's esophagus.

Barrett's esophagus is the only known esophageal precursor for the development of esophageal adenocarcinoma. However, screening for Barrett's esophagus remains controversial. Although screening is advocated in selected populations, it is unclear how it should be implemented. In this review, the current definition of Barrett's esophagus will be discussed. There will be a review of the emerging evidence supporting the cost-effectiveness of screening and surveillance for Barrett's esophagus in preventing esophageal adenocarcinoma. The known risk factors for Barrett's esophagus and the development of esophageal adenocarcinoma, currently utilized to determine the appropriate populations to screen, will be reviewed. Finally we will review the standard techniques utilized to screen for Barrett's esophagus and examine new technologies that might improve the efficacy and availability of Barrett's esophagus screening.

Cost considerations in implementing a screening and surveillance strategy for Barrett's oesophagus.

There is increasing concern over the rising costs of healthcare leading to debate regarding the use of resources to implement preventive strategies. Oesophageal adenocarcinoma and its precursor, Barrett's oesophagus provides an excellent opportunity to highlight this issue since cancer is uncommon even among individuals with documented Barrett's oesophagus. This review provides a brief introduction to economic analysis in healthcare and summarizes published studies of the cost-effectiveness of strategies to reduce mortality from cancer. Current best estimates highlight the cost-effectiveness of endoscopic ablation among patients with Barrett's oesophagus and high-grade dysplasia and the low cost-effectiveness of ablation among patients without dysplasia. The cost-effectiveness of ablation among patients with Barrett's and low-grade dysplasia is poorly defined due to the ambiguity of diagnosing dysplasia, the unknown risk of cancer among patients with low-grade dysplasia, and the uncertain durability of ablation to maintain remission from metaplasia and dysplasia and prevent cancer.

Helicobacter pylori: friend or foe?

Helicobacter pylori (H. pylori) is a Gram-negative spiral bacterium that is present in nearly half the world's population. It is the major cause of peptic ulcer disease and a recognized cause of gastric carcinoma. In addition, it is linked to non-ulcer dyspepsia, vitamin B12 deficiency, iron-deficient anemia and immune thrombocytopenic purpura. These conditions are indications for testing and treatment according to current guidelines. An additional indication according to the guidelines is "anyone with a fear of gastric cancer" which results in nearly every infected person being eligible for eradication treatment. There may be beneficial effects of H. pylori in humans, including protection from gastroesophageal reflux disease and esophageal adenocarcinoma. In addition, universal treatment will be extremely expensive (more than $32 billion in the United States), may expose the patients to adverse effects such as anaphylaxis and Clostridium difficile infection, as well as contributing to antibiotic resistance. There may also be an as yet uncertain effect on the fecal microbiome. There is a need for robust clinical data to assist in decision-making regarding treatment of H. pylori infection.

Cost-effectiveness of chemoprevention with proton pump inhibitors in Barrett's esophagus.

BACKGROUND: Proton pump inhibitors (PPIs) may reduce the risk of esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus. PPIs are prescribed for virtually all patients with Barrett's esophagus, irrespective of the presence of reflux symptoms, and represent a de facto chemopreventive agent in this population. However, long-term PPI use has been associated with several adverse effects, and the cost-effectiveness of chemoprevention with PPIs has not been evaluated. AIM: The purpose of this study was to assess the cost-effectiveness of PPIs for the prevention of EAC in Barrett's esophagus without reflux. METHODS: We designed a state-transition Markov microsimulation model of a hypothetical cohort of 50-year-old white men with Barrett's esophagus. We modeled chemoprevention with PPIs or no chemoprevention, with endoscopic surveillance for all treatment arms. Outcome measures were life-years, quality-adjusted life years (QALYs), incident EAC cases and deaths, costs, and incremental cost-effectiveness ratios. RESULTS: Assuming 50% reduction in EAC, chemoprevention with PPIs was a cost-effective strategy compared to no chemoprevention. In our model, administration of PPIs cost $23,000 per patient and resulted in a gain of 0.32 QALYs for an incremental cost-effectiveness ratio of $12,000/QALY. In sensitivity analyses, PPIs would be cost-effective at $50,000/QALY if they reduce EAC risk by at least 19%. CONCLUSIONS: Chemoprevention with PPIs in patients with Barrett's esophagus without reflux is cost-effective if PPIs reduce EAC by a minimum of 19%. The identification of subgroups of Barrett's esophagus patients at increased risk for progression would lead to more cost-effective strategies for the prevention of esophageal adenocarcinoma.

Strategies to improve outcomes in esophageal adenocarcinoma.

Esophageal adenocarcinoma is one of the fastest rising cancers in Western society. Incidence has increased by 600% within the last 30 years. Rates of diagnosis and death run parallel due to the poor prognosis and a lack of effective treatments. Potentially curative treatments are followed by high rates of disease recurrence. For the majority of patients, who present with advanced disease, we have no effective treatment. We discuss the key areas of progress in this demanding field and offer our views on the direction of future research and treatment.