Endoscopic management of dysplasia and early cancer in Barrett's esophagus
Two decades ago, the primary treatment for high-grade dysplasia and early cancer in Barrett's esophagus (BE) was esophagectomy — a complicated surgery associated with significant morbidity and mortality.
Since then, tremendous advances in the field have expanded the armamentarium considerably, providing doctors and patients with far less invasive options, says Kenneth K. Wang, M.D., of Mayo Clinic in Rochester, Minn. "Today, endoscopic management of esophageal dysplasia and early (stage T1a) adenocarcinomas is the standard of care for most people."
As an example, he points to radiofrequency ablation (RFA), which uses targeted thermal energy to destroy abnormal tissue. "RFA is a safe, effective and durable way to eradicate intestinal metaplasia and dysplasia in patients with BE. For many people, RFA, which usually requires two or three treatments, is preferable to long-term surveillance with multiple biopsies and certainly to surgery."
Arguably one of the most important advances in the Barrett's field, though, is the treatment of early stage cancers with organ-sparing endoscopic therapies — primarily endoscopic mucosal resection (EMR) but also, in some cases, endoscopic submucosal dissection.
EMR snares and removes well-contained, superficial cancer smaller than 0.6 to 0.8 inches (1.5 to 2 centimeters). Endoscopic submucosal dissection can meticulously dissect lesions up to 3.6 inches (9 centimeters). Both procedures show cure rates similar to esophagectomy in cohort studies, though no randomized trials have been performed.
"These are relatively simple outpatient procedures with a rapid recovery and few complications," Dr. Wang says.
On the other hand, in spite of improved techniques using robots and other minimal access procedures, the recovery for esophagectomy is lengthy and the complication rate remains high — as much as 50 percent.
"I want to emphasize how significant these developments are," Dr. Wang says. "We no longer have to treat early cancer the same way we treat advanced disease, which is like hunting mice with a cannon."
Optical imaging, molecular testing
Equally important are novel techniques that improve the detection of neoplastic changes. "The Achilles' heel in the diagnosis of esophageal cancers has been the sampling and unreliable interpretation of histologic specimens. The risk was always that there were small areas of malignancy that we simply couldn't find," Dr. Wang explains. "With the new techniques, we're better able to detect those areas."
Standard endoscopy, for instance, shows few details of the mucosal surface, but high-resolution magnifying endoscopes can enhance the appearance of the esophageal mucosa 300 times, revealing microvascular and pit patterns.
Also expanding the capabilities of endoscopy are optical imaging technologies — narrow band imaging, autofluorescence and optical coherence tomography among them — which better identify areas of dysplasia or scan large areas of the mucosa in a single pass. This allows for more-targeted biopsies, reducing the number of random samples needed and increasing diagnostic yield.
"We once had to take random biopsies every half-inch or so around the entire circumference of the esophagus to detect areas of neoplasia — and even that had many limitations," Dr. Wang says. "But the new imaging techniques take away the inconsistency by finding the right areas to biopsy."
Yet Dr. Wang is also convinced that finding alternatives to traditional biopsy is crucial. One technique with potential is confocal laser endomicroscopy, which relies on tissue fluorescence to examine mucosal histology in real time. "The confocal laser microscope probe magnifies 400 times, allowing us to obtain optical biopsies of any accessible surface in vivo," he says.
He anticipates even better results with emerging technologies such as angle-resolved low-coherence interferometry, which uses patterns of scattered light to locate abnormal cells in situ, while avoiding observer error.
A procedure currently in use that addresses the difficult problem of interpretation error is molecular testing. Fluorescent in situ hybridization (FISH), for instance, which bypasses the unreliability of histology by analyzing cytology specimens, uses fluorescent probes to detect abnormal genetic changes in cells.
"These tests are very valuable in helping identify patients with progressive neoplasia who will benefit from further treatment," Dr. Wang says.
He continues, "Pathology is a wonderful, but very old technique that depends on experts. What we are trying to do is develop tests like cytology that are easy for anyone to do. Tests and treatments that can only be performed in tertiary centers don't benefit patients or health care in general."
The goal: Better patient care
In addition to novel diagnostic and therapeutic options for BE and esophageal cancer, research on the etiology of these disorders is ongoing. "Barrett's research is moving very quickly now," Dr. Wang notes. "There is a concerted effort, much of it very promising, to figure this disease out."
What is especially rare, he points out, is the confluence of so many breakthroughs at the same time. "This is an incredibly exciting time to be in this field. I feel that for the first time, we can look patients in the eye and say, 'We can really help you.' " It was different two decades ago, he says.
"All I could offer patients with Barrett's-related adenocarcinoma was a difficult surgery, two weeks to a month in the hospital, a six-month recovery at home, lifelong dietary restrictions and a 50 percent chance of serious complications — and that was if everything went well. These days, we remove the cancer, the patient goes home the same day, is eating a regular diet the next and has a completely normal quality of life."
As great as the changes have been in the last 20 years, he foresees even greater advances in the next five. "We're increasingly certain of what we're looking at and what we need to do. This has led to an enormous improvement in patient care. I look at my patients, and every day, I see that this works."