RANDOMIZED CONTROLLED TRIAL OF RADIOFREQUENCY ENERGY DELIVERY TO THE LOWER ESOPHAGEAL SPHINCTER FOR CHRONIC GASTROESOPHAGEAL REFLUX

a. Background Gastroesophageal reflux disease (GERD) is the most common disorder of the esophagus (0. It affects as much as 40% of the American adult population and up to 50% of these patients are afflicted with a chronic, relapsing syndrome (1). The quality of life with GERD has been reported as being comparable to that with angina or heart failure (2). There are a number of factors that contribute to the pathophysiology of this disorder, including lower esophageal sphincter (LES) incompetence, esophageal body dysmotility, and dysfunctional gastric secretion and emptying (1). Most medical therapies for GERD are directed at lowering the acidity of the refluxate. The most effective of these drug therapies is the proton pump inhibitor (PPI), which resolves symptoms in 80% of cases and heals esophagitis in 90 % (3-5). H2 blocker, which is much less efficacious, is sometimes helpful for nocturnal acid suppression (6). Unfortunately, with cessation of therapy, 80% of patients relapse and therefore many patients become committed to lifetime therapy (5). Therefore, many of the chronic patients face a dilemma of noncompliance with persistent symptoms or inconvenience and cost of indefinite medical therapy. Furthemore, although there is no suggestion epidemiologically of an association between long-term PPI therapy and gastric malignancies, there is also no definitive evidence that prolonged PPI treatment and its consequent elevated levels of gastrin are entirely benign (7) In fact in animal studies it has been shown to cause carcinoid tumors and enterochrornaffin cell hyperplasia (7). Also, omeprazole use has been associated with worsening of Helicobacter pylori-associated gastritis (8). Anti-reflux surgeries, such as open and laparoscopic Nissen fundoplication, are available as alternative treatments for GERD. These procedures are directed at mechanically improving the competence of the LES by wrapping the fundal stomach circumferentially around the sphincter. Studies have demonstrated that laparoscopic fundoplication reduces symptoms in76-98% of patients and decreases esophageal acid exposure time on pH monitoring in 90 % (9). Also, this procedure has been shown to be efficacious in improving quality of life, and even to outdo some medical therapies in similar measures (10, 11). Unfortunately, these procedures are not without risk. Although the laparoscopic approach has significantly reduced mortality, these invasive procedures can cause esophageal or gastric perforation, pneurnothorax and other complications associated with surgery and general anesthesia (1). A number of investigations have focused on endoscopic interventions, which are less invasive and do not require general anesthesia, to achieve overall similar LES improvements. Some of these are suturing, injecting bulking agents or sclerosing agents, and radiofrequency energy (RFE)delivery (12-16). Radiofrequency energy has been utilized for a number of clinical syndromes. Some of these applications include treatments for cardiac dysrhythmias and joint laxity (17, 18). These studies underscore the utility of RFE is in allowing targeted ablation of specific tissues and tissue tightening by thermally induced collagen contraction, collagen deposition, and wound healing (16). Recently, preliminary animal studies have suggested that RFE can be used as therapy for GERD (15, 16). In a canine model RFE reduced transient LES relaxation by 54% (15) and in a porcine model it increased the mean LES pressure and gastric yield pressure (gastric pressure required to induce reflux) (16). Similar effects were attained in a human study: RFE reduced transient relaxation of LES by 44% (14).