Severe GERD Symptoms Inversely Linked to Esophageal Cancer

Laurie Barclay, MD

July 21, 2011

July 21, 2011 — The risk for esophageal adenocarcinogenesis is significantly higher in medically treated patients with mild or absent symptoms of gastroesophageal reflux disease (GERD) vs those with severe symptoms, according to the results of a cross-sectional study reported in the July issue of the Archives of Surgery.

"Screening for esophageal adenocarcinoma has focused on identifying Barrett esophagus (BE) in patients with severe, longstanding symptoms of ...GERD," write Katie S. Nason, MD, MPH, from the Division of Thoracic and Foregut Surgery, University of Pittsburgh in Pittsburgh, Pennsylvania, and colleagues. "Unfortunately, 95% of patients who develop esophageal adenocarcinoma are unaware of the presence of BE before their cancer diagnosis, which means they never had been selected for screening. One possible explanation is that no correlation exists between the severity of GERD symptoms and cancer risk."

The hypothesis tested by this study was that severe GERD symptoms are not associated with an increased prevalence of BE, dysplasia, or cancer among patients undergoing primary endoscopic screening. At a university hospital, 769 patients with GERD underwent primary screening endoscopy from November 1, 2004, through June 7, 2007. The primary study endpoint was esophageal adenocarcinogenesis, defined as BE, dysplasia, or cancer, as a function of symptom severity and proton pump inhibitor (PPI) therapy.

Esophageal adenocarcinogenesis was detected in 122 patients. Endoscopic findings of esophagitis correlated positively with an increasing number of severe GERD symptoms (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01 - 1.09). In contrast, the odds of adenocarcinogenesis were lower with increasing number of severe GERD symptoms (OR, 0.94; 95% CI, 0.89 - 0.98).

Among patients taking PPIs, those with no severe typical or atypical GERD symptoms were 61.3% and 81.5% more likely to have adenocarcinogenesis, respectively, than patients who reported that all symptoms were severe.

"Medically treated patients with mild or absent GERD symptoms have significantly higher odds of adenocarcinogenesis compared with medically treated patients with severe GERD symptoms," the study authors write. "This finding may explain the failure of the current screening paradigm in which the threshold for primary endoscopic examination is based on symptom severity."

Limitations of this study include cross-sectional design, inability to determine causality, failure to control for all known risk factors for BE and esophageal adenocarcinoma, and lack of validation of the symptom severity scale developed for this study.

"These findings ... suggest that, rather than recommending BE screening only in patients with long-standing, poorly controlled GERD, patients with long-standing but well-controlled symptoms of typical or atypical GERD may be a better population to target," the study authors conclude. "In addition, patients who present initially to the otolaryngology clinic with severe atypical-predominate symptoms should be strongly considered for primary screening endoscopy. Larger-scale prospective studies, ideally having a validated measure of symptom severity, will enable us to determine the prevalence of BE stratified by symptom duration, antisecretory medication use, and current symptoms severity and lead to stronger guidance in recommendations for screening endoscopy."

The Robert Anthony McHugh Research Fund for the Prevention and Early Detection of Esophageal Cancer, American Surgical Association Foundation Fellowship Award, and the National Institutes of Health supported this study. The study authors have disclosed no relevant financial relationships.

Arch Surg. 2011;146:851-858.

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