Medically treated patients with mild or no symptoms of gastroesophageal reflux disease (GERD) are at higher risk for developing esophageal cancer than those with severe GERD symptoms, according to a University of Pittsburgh study published in the current issue of Archives of Surgery.

Many patients who develop adenocarcinoma, a common form of esophageal cancer, are unaware that they have Barrett's esophagus - a change in the cells lining the esophagus often due to repeated stomach acid exposure. In some cases, Barrett's esophagus develops into esophageal cancer.

"Typically, patients with severe GERD symptoms are screened for Barrett's esophagus, but those with mild or absent symptoms are not. Unfortunately, many patients who develop adenocarcinoma don't know that they have Barrett's esophagus until it has transformed into cancer and become advanced, leading to obstruction," said principal investigator Blair A. Jobe, M.D., professor and director of esophageal research and esophageal diagnostics and therapeutic endoscopy, Department of Cardiothoracic Surgery, Pitt School of Medicine.

The study included 769 GERD patients who presented for their first upper endoscopy, in which a flexible endoscopic camera is guided through the esophagus and stomach to look for tissue changes. Participants were separated into three groups: patients who were referred for upper endoscopy for any clinical indication regardless of symptoms; patients with typical GERD symptoms, such as heartburn, regurgitation and difficulty swallowing; and patients with atypical GERD symptoms, such as hoarseness, throat-clearing, mucus, coughing and a lump sensation in the throat.

All study participants underwent endoscopy and completed questionnaires and a detailed medication history. Endoscopy revealed that 122 of these patients, or 15.9 percent, had Barrett's esophagus or adenocarcinoma. Patients who were adequately managing their GERD symptoms with proton pump inhibitors (PPIs) were 61 percent more likely to have Barrett's esophagus or adenocarcinoma if they reported no severe GERD symptoms, compared to patients taking PPIs who reported severe symptoms. Patients with severe GERD symptoms often experienced irritation or swelling of the esophagus, but that was associated with decreased odds of having esophageal cancer.

"Our research indicates that even patients without severe symptoms may benefit from Barrett's esophagus screening," Dr. Jobe noted. "If GERD patients are screened early enough, there is a better chance that Barrett's esophagus can be identified before it becomes cancerous," he stated. "We are learning that the chronic and long-term use of PPIs may not be entirely without consequences and may lead to more insidious problems such as calcium malabsorption or cause one to be asymptomatic in the face of continued esophageal injury from GERD."

Dr. Jobe and his Pitt colleagues have established the Barrett's Esophagus Risk Consortium (BERC), in which primary care patients are being screened with in-office, small-caliber, unsedated endoscopy in an attempt to better understand risk factors for the condition as well as lower the threshold for screening. The multicenter effort is funded by the National Institutes of Health.

Study co-authors include Katie S. Nason, M.D., M.P.H., Omar Awais, M.D., Matthew J. Schuchert, M.D., and James D. Luketich, M.D., all from Pitt; and Promporn Paula Wichienkuer, M.D., M.P.H., Robert W. O'Rourke, M.D., John G. Hunter, M.D., and Cynthia D. Morris, Ph.D., M.P.H., all from Oregon Health and Science University.

The study was funded by the Robert Anthony McHugh Research Fund for the Prevention and Early Detection of Esophageal Cancer, David Gold and Irene Blumenkrantz Esophageal Cancer Research Fund, the Sampson Family Endowed Chair, the UPMC Heart, Lung and Esophageal Surgery Institute, the American Surgical Association Foundation Fellowship Award and grants from the National Institutes of Health.