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June 1, 2007

Reduction of Interleukin 8 Gene Expression in Reflux Esophagitis and Barrett's Esophagus With Antireflux Surgery

Author Affiliations

Author Affiliations: Departments of Surgery (Drs Oh, Vallbohmer, Hagen, Lipham, and T. R. DeMeester), Cardiothoracic Surgery (Dr S. R. DeMeester), Biochemistry and Molecular Biology (Drs Mori, Kuramochi, and P. V. Danenberg), and Pathology (Dr Chandrasoma), University of Southern California; and Response Genetics Inc (Ms K. D. Danenberg), Los Angeles, Calif.

Arch Surg. 2007;142(6):554-560. doi:10.1001/archsurg.142.6.554

Hypothesis  Chronic inflammation of esophageal mucosa secondary to refluxed gastric juice increases gene expression of interleukin 8 (IL-8). Antireflux surgery can reduce this overexpression.

Design  Prospective analysis of archival paraffin-embedded tissue.

Setting  Academic tertiary medical center.

Patients and Methods  One hundred eight patients with reflux symptoms were classified according to pH monitoring and endoscopic and histologic findings. Twenty patients did not have reflux or mucosal injury; 47 had reflux disease (16 esophagitis and 31 Barrett's esophagus), 20 had dysplasia, and 21 had adenocarcinoma. Microdissection was performed to exclude inflammatory cells and stromal tissue. After RNA isolation and reverse transcription, IL-8 messenger RNA expression was measured using quantitative real-time polymerase chain reaction. All patients with reflux disease had Nissen fundoplication with biopsies at matched levels within the esophagus preoperation and postoperation.

Results  Expression of IL-8 was increased in patients with reflux compared with those without reflux. Patients with the highest IL-8 expression were those with Barrett's dysplasia and adenocarcinoma (P<.001). In patients with reflux, Nissen fundoplication led to significantly decreased IL-8 expression compared with preoperative levels in esophagitis (P = .01) and Barrett's esophagus (P = .03).

Conclusions  Interleukin 8 messenger RNA expression increases during the progression of reflux disease from normal squamous mucosa to esophageal adenocarcinoma. Elimination of reflux with Nissen fundoplication significantly reduces IL-8 expression in both squamous and Barrett's mucosa. These results demonstrate that effective antireflux surgery can modulate the gene expression of esophageal mucosa and may impact the natural history of reflux disease.