New Research in Barrett’s Esophagus

Dr. Charles J. Lightdale

Barrett’s esophagus is a premalignant condition in which the normal squamous epithelium of the esophagus is replaced in varying degree by a metaplastic specialized columnar epithelium in about 5% of patients with gastroesophageal reflux disease (GERD).  The condition can be diagnosed only by endoscopy and endoscopic biopsy, and increases the risk of adenocarcinoma of the esophagus by 30 to 125 fold. One of the most important trends over the past 30 years has been the dramatic increase in adenocarcinoma of the esophagus; those with Barrett’s esophagus develop cancer at a rate of 0.5% per year. 

Because Barrett's esophagus is a major risk factor for developing esophageal cancer, Charles J. Lightdale, M.D., Professor of Clinical Medicine at Columbia University College of Physicians and Surgeons, and Attending Physician at the New York-Presbyterian Hospital, is conducting various ongoing investigations to determine more effective diagnostic techniques and treatments for this increasingly prevalent condition that affects approximately 700,000 people in the United States. 

Diagnostic Measures

In most patients with Barrett’s esophagus, the neoplastic process is believed to progress through stages that can be recognized on light microscopy of endoscopic biopsies as low-grade dysplasia, then high-grade dysplasia, and finally to adenocarcinoma.  These changes are accompanied by complex molecular events that take place over many months and years.  The relatively long time for progression from metaplasia to dysplasia to carcinoma offers a potential opportunity for intervention before the process evolves into carcinoma.

Currently, Dr. Lightdale is testing high magnification endoscopy to better identify dysplastic areas, including the use of a light imaging method called endoscopic optical coherence tomography, which provides images at near microscopic levels. 

High-frequency endoscopic ultrasonography is also being evaluated for staging the depth of abnormality in patients with high-grade dysplasia and early cancer.  In cooperation with Dr. Hanina Hibshoosh of the Department of Pathology, Dr. Lightdale is studying the expression of several biomarkers in biopsy specimens of Barrett’s esophagus, including p27 and cyclin D-1, during the metaplasia-dysplasia-carcinoma sequence.

Therapeutic Interventions

Alongside these diagnostic studies, Dr. Lightdale is also conducting therapeutic trials in patients with Barrett’s esophagus. Cyclo-oxygenase 2 (COX-2) is overexpressed in Barrett’s metaplasia, and increasing levels of COX-2 are present in the progression of Barrett’s metaplasia to low-grade dysplasia, high-grade dysplasia, and adenocarcinoma.  In a multicenter trial, sponsored by the National Cancer Institute (NCI), Dr. Lightdale is  testing the COX-2 inhibitor celecoxib in patients with Barrett’s esophagus and dysplasia. To learn more about this investigation, see Chemoprevention Trial of Celecoxib in Patients with Barrett's-associated Dysplasia.

Ablation of Barrett’s metaplasia without dysplasia is an early intervention that has also developed a great deal of interest.  Dr. Lightdale is Principal Investigator of a New York-Presbyterian Hospital team that received a grant from the NCI to study ablation of Barrett’s esophagus combined with acid suppression and COX-2 inhibition with celecoxib. The study will evaluate the effect of celecoxib on the regeneration of normal squamous epithelium rather than the specialized columnar epithelium, following ablation of the Barrett’s tissue using a new non-contact electrocautery method called argon plasma coagulation.

Treatment Alternatives

Patients with high-grade dysplasia and early cancer confined to the mucosa are usually treated with esophagectomy, but because of the mortality and morbidity associated with this surgery, particularly in older individuals, other methods of curative treatment are being actively evaluated.  Currently, Dr. Lightdale is studying photodynamic therapy (PDT) in patients with high-grade dysplasia.  PDT utilizes a sensitizing drug, porfimer sodium, which sensitizes tissues to light and concentrates in areas of neoplasia.  The drug is activated using an endoscopic laser, which shines a specific red light at the Barrett’s area, resulting in deep ablation of the abnormal mucosa.

Another study uses endoscopic mucosal resection (EMR) in patients with focal areas of high-grade dysplasia or early carcinoma that can be identified as nodules or slightly raised areas of abnormality within Barrett’s esophagus.  EMR is a treatment measure that involves lifting the abnormal area by injecting saline beneath it, and then using a special cap fitted endoscope and electrocautery snare to remove the lesion, similar to endoscopic polypectomy.  The advantage to this method is that an excellent pathology specimen is obtained and the completeness of the resection can be verified.  Both PDT and EMR are being performed on outpatients; the ongoing studies are designed to evaluate their potential to avoid esophagectomy in selected patients. 

For more information, please contact Kevin Bukowski, RN, at  212-305-3224 or e-mail kb416@columbia.edu. 

Editor’s note:

Charles J. Lightdale, M.D., Professor of Clinical Medicine at Columbia University College of Physicians and Surgeons, and Attending Physician at the New York-Presbyterian Hospital, has had a longstanding interest in the prevention and early detection of gastrointestinal cancer. A major focus of his research has been Barrett’s esophagus and esophageal cancer.