It is estimated that
Barretts esophagus is found in approximately 6% to 12% of patients undergoing endoscopy for symptoms of gastroesophageal reflux disease. Incidences have increased since the 1970s, but this parallels the increased use of diagnostic upper endoscopy. The evolving concept of short segment
Barretts esophagus may play a role in the increasing incidence of this disease, and data suggest that more short segment
Barrett’s esophagus is being found. An alternative attractive explanation is that as the population ages, this condition becomes more common and hence the population at risk f
or esophageal adenocarcinoma increases. Despite its increased incidence, autopsy data from Olmsted County, Minnesota, suggest that the majority of cases of
Barretts esophagus go undetected in the general population; and it is estimated that for every known case, 20 additional cases go unrecognized. Additional support for this concept comes from the fact that 95% of patients with esophageal adenocarcinoma do not have an antecedent diagnosis of
Barrett’s esophagus. However, in patient populations undergoing endoscopy for all possible indications, the prevalence of Barrett’s esophagus is much lower than that encountered in patients with symptomatic GERD: typically 1% or less.
This disease predominantly affects middle-aged white males and is more common in men than in women. When compared to GERD patients without Barretts esophagus, patients with the condition develop reflux symptoms at an earlier age, have an increased duration of symptoms, increased severity of nocturnal reflux symptoms, and increased complications of GERD such as stricture, ulcer and bleeding. Thus age of onset, symptom duration and presence of nocturnal symptoms or complications may be markers of increased risk for developing Barrett’s esophagus. Interestingly, similar clinical risk factors were recently identified for esophageal adenocarcinoma. Despite these observations, most patients have symptoms that are no different than those encountered in patients with gastroesophageal reflux disease uncomplicated by columnar metaplasia. It is well known that Barretts esophagus patients have an impaired sensitivity to esophageal acid perfusion. However, most patients are elderly, and part of this observation may be related to an age-related decrease in acid sensitivity. This observation emphasizes that impaired perception of acid may hamper our ability to screen patients for Barrett’s esophagus in the future if only GERD symptoms are used to guide us.
Could there be an inherited risk for development of Barrett’s esophagus? Several case series have reported on families with multiple affected relatives over successive generations. Furthermore, studies from the Mayo Clinic found a clear predisposition to reflux symptoms in parents and siblings of patients with Barrett’s esophagus and esophageal adenocarcinoma. Taken together, these studies suggest the possibility of a genetic predisposition in some settings. The search for a candidate gene is underway in several centers, including the Cleveland Clinic, as part of the Ohio Familial Barretts Esophagus Consortium.
Implications of Epidemiology on Screening for Barrett’s Esophagus
There has been a minor and clinically insignificant improvement in stage of disease at diagnosis and 5 year survival in patients with adenocarcinoma of the esophagus between 1973 and 1991. One potential strategy to decrease the mortality rate of esophageal adenocarcinoma further is to identify more patients at risk, namely those with Barrett’s esophagus. Published guidelines recommend just such an approach by looking for Barrett’s esophagus in patients at highest risk for this condition: those with long standing reflux symptoms.
The principle of screening is to apply a relatively simple and inexpensive investigation to identify individuals harboring cancer or who are at increased risk for developing it. Those found to be positive require further or continued investigation, for example continued endoscopic surveillance, whereas those found to be negative need no additional testing. Endoscopy with biopsy is the only validated technique to diagnose Barrett’s esophagus. However, it has clear limitations as a screening tool including cost, risk and complexity. If applied to the estimated 20% of the population with regular GERD symptoms, the cost implications would be staggering. However, the unsedated small caliber upper endoscopy and the "pill camera" may change the economics of endoscopic screening. Unsedated small caliber upper endoscopy is feasible, acceptable and accurate when compared to conventional sedated endoscopy. It also has the potential advantages of decreasing sedation-related complications and costs related to nursing and recovery room time, need for a driver and time away from work. However, regardless of cost issues, it is unclear if endoscopy without sedation will meet with patient acceptance given the cultural bias for sedation in the United States. More information on cost implications as well as patient acceptance of unsedated narrow caliber endoscopy is eagerly awaited.
Currently, there are no validated alternative techniques to screen for Barrett’s esophagus that overcome the cost and risks associated with endoscopy. Much work is underway to determine genetic risk factors for Barrett’s esophagus, but a genetic test is not yet available. It would be welcome as the ultimate noninvasive screening test for this disease.
Cost Issues and Screening
Despite the current practice guidelines, there are no data from randomized controlled trials or observational studies to evaluate the effectiveness or efficacy of screening. A recent decision analysis model by Inadomi et al. examined screenings of 50-year-old white men with chronic GERD symptoms for Barretts esophagus and found that one-time screening is probably cost-effective if subsequent surveillance is limited to patients with dysplasia on initial examination. This strategy would result in a cost of $10,440 per quality adjusted life year saved compared to a strategy of no screening or surveillance. Another modeling study also suggested that screening was a reasonable strategy, but only if the following conditions were met: a group of patients at high risk for Barretts esophagus, high-grade dysplasia or adenocarcinoma; high sensitivity and specificity of endoscopy with biopsy; and little or no reduction in quality of life with esophagectomy. Any variation of these ideal consitions quickly made this strategy cost-ineffective. The incremental cost-effectiveness of screening deteriorated rapidly once the prevalence of Barretts esophagus or high-grade dysplasia fell to less than 5 percent.
There is clearly a need to develop either a better profile of patients at high risk for Barretts esophagus and high-grade dysplasia or to develop a far less expensive tool to provide mass population screening. A simple questionnaire and monogram has been described in an effort to predict Barretts esophagus in patients with GERD symptoms. However, the sensitivity of this questionnaire for predicting Barretts esophagus was 77 percent with a specificity of only 63 percent. While clearly cost-saving, this model would obviously miss patients with Barretts esophagus with GERD symptoms and not account for individuals without any symptoms of GERD.
In the future, screening strategies will have to consider the following options: limiting screening to only high-risk patients; offering mass endoscopic screening to all adults over age 50 years as part of periodic health appraisal preventive strategy; or, doing nothing until clinical trials provide the evidence to support such a strategy. Problems inherent in demonstrating the utility of a screening program such as healthy volunteer bias, lead time bias, and length time bias will all need to be addressed.
