EVIDENCE-BASED ANSWER
Some patients who have been diagnosed with Barrett’s esophagus will develop dysplasia and, in some cases, esophageal carcinoma (strength of recommendation [SOR]: A, based on consistent cohort studies). Endoscopic surveillance is recommended for all patients with Barrett’s esophagus as it is superior to other methods for detecting esophageal cancer (SOR: B, based on systematic review). The degree of dysplasia noted on biopsy specimens correlates with the risk of esophageal carcinoma development and should guide the frequency of subsequent evaluations (SOR: B, based on consistent cohort studies). The optimal frequency of endoscopy has yet to be determined in any randomized trial.
Recommendations from the 2002 American College of Gastroenterology (ACG) Practice Guideline provide guidance as to the frequency of endoscopy surveillance but were not based on an explicit systematic review of the literature (SOR: C, based on expert opinion; see TABLE 1).
CLINICAL COMMENTARY
Reduced monitoring for most patients with Barrett’s esophagus appears safe
Paul Crawford, MD
USAF–Eglin Family Practice Residency, Eglin Air Force Base, Fla
Family physicians have long been at the mercy of expert opinion when considering how to monitor patients with Barrett’s esophagus. This review of the evidence clearly shows that the days of yearly EGD for all Barrett’s esophagus patients are over.
Unlike other conditions—such as cervical dysplasia, where monitoring and therapies to remove dysplasia are proven to save lives—Barrett’s esophagus progresses slowly and unpredictably. Thus, until technological advances allow identification of higher risk Barrett’s esophagus patients, an EGD every 3 years for those without dysplasia seems to be a reasonable monitoring interval. Perhaps most importantly, family physicians can reassure Barrett’s esophagus patients in the community that they are likely to live a normal lifespan and die of something other than esophageal cancer.
Evidence summary
Barrett’s esophagus has been defined as “a change in the esophageal epithelium of any length that can be recognized at endoscopy and is confirmed to have intestinal metaplasia by biopsy of the tubular esophagus.”1 Intestinal metaplasia is a premalignant lesion for adenocarcinoma of the esophagus. Surveillance by serial endoscopy with biopsy has been recommended in an effort to find high-grade dysplasia or carcinoma in an early, asymptomatic, and potentially curable stage.1-4 Approximately 75% of patients involved in a Barrett’s esophagus surveillance program will present with resectable tumors, compared with only 25% of those not receiving surveillance.4
A recent systematic review assessing screening tools for esophageal carcinoma found standard endoscopy to be superior (90%–100% sensitivity) to other less invasive methods such as questionnaire (60%–70%), and fecal occult blood testing (20%).4 Additional endoscopy tools such as brush and balloon cytology increased the cost of surveillance without any improvement in diagnostic yield.
The degree of dysplasia on esophageal biopsy in Barrett’s esophagus patients is currently the best indicator of risk of progression to esophageal carcinoma. The data reviewed by the ACG for the practice guideline was drawn from several prospective studies and one available registry. In sum, a total of 783 Barrett’s esophagus patients were followed for a mean of 2.9 to 7.3 years. Esophageal carcinoma developed in 2% of patients with no dysplasia, 7% of patients with low-grade dysplasia (LGD) and 22% of patients with high-grade dysplasia (HGD).1 The ACG recommendations regarding frequency of esophagogastroduodenoscopy (EGD) were not based on an explicit critical appraisal of the literature. Recent cohort studies are consistent with recommendations for graded surveillance frequency. A randomized clinical trial to determine optimal endoscopic frequency and benefit has not been reported.
Several concerns have been raised regarding the utility of degree of dysplasia in determining optimal frequency of endoscopic surveillance. First, the progression of esophageal lesions over time is unpredictable. Skacel et al5 reported a series of 34 patients with LGD at initial pathologic examination. On subsequent surveillance endoscopy with repeat biopsy, 73% no longer demonstrated dysplasia. Such patients can be allowed to return to having surveillance every 3 years.
In addition to the non-linear progression of dysplasia, inter-rater reliability of the interpretation of pathology specimens varies substantially. Adequate reliability has been demonstrated among pathologists assigning results to 2 categories (either no dysplasia and LGD or HGD and carcinoma) (κ=0.7). Assignment to four distinct pathologic grades, however, was not reliable (κ=0.46, where 1.0 is complete agreement).1 In order to make a diagnosis of HGD or carcinoma, interpretation must be independently confirmed by 2 expert pathologists.1-3
Recommendations for frequent endoscopic surveillance are also weakened by the overall low rate of mortality from esophageal carcinoma noted in Barrett’s esophagus patients. A recent population based study demonstrated that there was no difference in overall mortality in those with a Barrett’s esophagus diagnosis compared with the general population.6 An increased risk of death from esophageal carcinoma was seen in patients with Barrett’s esophagus (4.7% seen in Barrett’s esophagus patients compared with 0.8% predicted in the general population; P<.05). The overall increased effect on mortality, however, was relatively small. Esophageal carcinoma accounted for less then 5% of deaths in Barrett’s esophagus patients reported during the study’s 6-year follow-up period.