Despite the low incidence of adenocarcinoma in people with Barrett's esophagus (BE) — an annual risk of 0.12 to 0.13 percent according to recent studies — BE remains the single most important risk factor for esophageal cancer.
Current guidelines recommend periodic surveillance endoscopy with biopsies to detect high-grade dysplasia and early cancer, but this approach has several limitations. One is inconsistent histopathological interpretation. Another is the patchy nature of dysplasia, which requires a series of random biopsies — typically four quadrant biopsies every 2 centimeters along the length of the Barrett's epithelium.
Because only a few patients develop dysplasia each year and not all progress to cancer, standard surveillance results in a large number of biopsies with low yields, notes Michael B. Wallace, M.D., of Mayo Clinic in Florida. But, he says, better options exist. New endoscopic imaging technologies, including high-definition white-light endoscopy (HD-WLE), narrow band imaging (NBI) and probe-based confocal laser endomicroscopy (pCLE), in particular, may make surveillance endoscopy more efficient and eliminate random biopsies for some patients.
HD-WLE, which significantly improves image quality, is already widely used in surveillance endoscopy. NBI better detects dysplasia by providing a broad view of the Barrett's segment. And pCLE offers unprecedented dynamic views of the mucosa in real time, enabling cellular visualization. Until recently, though, the accuracy of pCLE and the comparative sensitivities of enhanced endoscopic procedures in general had not been fully evaluated.
So researchers at Mayo Clinic in Florida, in collaboration with colleagues at four other international academic centers, undertook the first prospective, randomized controlled trial of the three technologies.
The primary aim was to determine whether the addition of pCLE to regular endoscopic procedures would improve the detection of high-grade dysplasia and early cancer in Barrett's esophagus. Secondary aims included individual evaluation of each imaging technology.
In all, 101 people with BE participated in the study. Most were men, and the mean age was 65.1 years. Each patient underwent all three procedures: HD-WLE, NBI and pCLE.
Results showed that high-definition white-light endoscopy had a sensitivity and specificity of 34.2 percent and 92.7 percent, respectively, for the detection of dysplasia and early cancer. Using pCLE in combination with HD-WLE doubled sensitivity to 68.3 percent with only a slight decrease in specificity, leading to the identification of 41 additional neoplastic areas.
Narrow-band imaging alone had a sensitivity of 45 percent and specificity of 88 percent. But combining NBI with both white light and pCLE increased sensitivity to 76 percent.
In addition to significantly improving the ability to detect neoplasia in Barrett's esophagus, pCLE proved easy to use, with a short learning curve. "A published learning curve was part of the run-in for this study," Dr. Wallace says. "We found that inexperienced endoscopists could attain the skill level of someone who had looked at hundreds of images in a matter of two or three hours."
Dr. Wallace points out that these findings have important implications for patients with BE. "In this study, we were able to show that the negative predictive value of pCLE combined with white light was 91 percent, and 95.6 percent when combined with both white light and NBI," he says. "This high level of confidence can help us make better decisions about when tissue should be sampled."
He suggests that one strategy would be to evaluate BE using all three imaging tools. If no abnormalities were found, no biopsies would be taken. But if an abnormality were seen using any method, doctors would biopsy both targeted and random areas.
"This would avoid biopsies in 39 percent of patients," he says. "And since pathology is expensive, there would likely be a reduction in cost, which would be offset somewhat by the cost of the technology itself. We're crunching the numbers right now to determine exactly what the cost savings are."
There would likely be further savings if the number of surveillance endoscopies were also reduced.
"Current guidelines call for two initial surveillance endoscopies, one year apart. The purpose of the second endoscopy is to find any areas of missed dysplasia," Dr. Wallace says. "But if we were certain there were no missed dysplasia, then we might be able to avoid repeat endoscopies for as much as five years. This is purely theoretical right now. But as we get better imaging technologies and more confident that we can exclude dysplasia, we should be able to endoscopy less."
New endoscopic techniques have the potential to do more than cut down on procedures. They may also change the way disease is diagnosed.
"We are increasingly seeing technologies that improve the detection of precancerous growths and allow us to make decisions in vivo," Dr. Wallace says. "We are getting away from the algorithm that we have had for 100 years where we remove tissue, send it to a pathology lab, and they tell us what it is."