Endoscopic Mucosal Resection for Barrett Esophagus–Related Dysplasia and Cancer

Progressive stages of malignant BE.

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Barrett esophagus (BE) is a premalignant metaplastic condition that has traditionally been challenging to diagnose, stage, and treat prior to the development of adenocarcinoma. An estimated 10% of patients with chronic reflux symptoms present with BE at endoscopy, and BE patients face a 30- to 125- fold increased risk of developing esophageal cancer in a progressive process that can be asymptomatic.

Early detection produces the best outcomes. But optimal diagnosis and management of cancers arising from BE have been hampered by the small size and unreliability of histologic samples available by traditional means of endoscopic biopsy. Missing an area of cancer or dysplasia is always a risk because the biopsy sample may not come from the most diseased area and most of the involved areas of advanced dysplasia or early cancer cannot be visually identified. Further complicating diagnosis is the distribution pattern of BE. It can occur diffusely over a large area, thus increasing the chances that a cancer may be misdiagnosed as dysplasia because too little cancerous tissue was evident in the limited traditional biopsy sample. Thus, one of the greatest weaknesses of managing BE by traditional means is the risk that even though the dysplasia is removed, high-grade dysplasia or even cancerous lesions are left behind.

EMR being performed with the cap technique.

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A New Approach

A new outpatient technique called endoscopic mucosal resection (EMR) overcomes the limits of traditional diagnosis and management of BE. Pioneered and used successfully in Japan since 1990, EMR enables physicians to take a much larger biopsy specimen: 3 cm2 as opposed to the traditional sample size of 6 mm2. In addition, EMR offers outpatient advantages of requiring no hospitalization versus at least 7 days of hospitalization after open surgical treatment, retaining the esophagus, and resuming a fairly normal lifestyle.

In as many as 70% of patients, removal of tissue in the EMR biopsy itself may be a cure. However, while dysplastic changes in the epithelial mucosa tend to occur in discrete locations that can be resected, the predisposing genetic abnormality is usually distributed throughout. This means that vigilant follow-up for recurrence is necessary because tissue that appears noncancerous after resectionhas a 15% to 30% chance of recurrence. In 2005, research from the Mayo Clinic Barrett's Esophagus Unit demonstrated that for early esophageal cancer, combination treatment with EMR and photodynamic therapy (PDT) to eliminate any residual lesions is feasible.

The addition of PDT ablation is a means of completely eliminating metaplastic mucosa.

Evidence of EMR Advantages

Mayo Clinic is one of the few US medical centers to offer the evolving technique of EMR. The physicians at all 3 Mayo Clinic sites combined have performed more EMR procedures than most other US institutions, with complication rates among the lowest. The perforation rate has been reported as 1% to 3%, but Mayo physicians have had no perforations in more than 1,000 EMRs. Mayo's gastrointestinal bleeding rate is less than 1% compared with rates of 5% to 10% reported in the literature.

Mayo's results with diagnosis, staging, and treatment support the safety and efficacy of EMR. In 1996, a Mayo Clinic study showed that an estimated 40% of the diagnoses of high-grade dysplasia obtained by surgical means were reclassified to a diagnosis of cancer after EMR biopsy. This is an important finding, given that the literature suggests that up to 50% of high-grade dysplasia patients have cancer. Also, when submucosal cancer is found, open surgical treatment is recommended.

Bigger is better. Diagnosis is facilitated by the much larger biopsy specimens available with EMR.

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In 2005, Mayo researchers demonstrated that for early esophageal cancer that did not invade the submucosa, combination therapy with EMR and PDT to eliminate any residual lesions is feasible. The addition of PDT ablation is a means of completely eliminating metaplastic mucosa. Five-year follow-up mortality data showed no cancer-related deaths.

In 2007, Mayo Clinic published the first US large-scale study on endoscopic therapy of highgrade dysplasia arising in patients with BE and demonstrated the ability of endoscopic therapy, including EMR, to treat this condition with mortality rates similar to those after esophagectomy.

Indications for Evaluation and Treatment by EMR

In general, any patient with superficial, high-grade dysplasia and early cancer is suitable for EMR evaluation, staging, and treatment. Indications for treatment by mucosal resection include the presence of small, mucosally based cancer, preferably less than 2 cm; no evidence of metastatic disease; and patient unwillingness or inability to undergo open surgery. EMR is not indicated for patients with submucosal malignant involvement.