Endoscopic Treatment of Reflux (2005)

Gastroesophageal reflux disease (GERD) is the result of inappropriate exposure of the lining of the esophagus to gastric content. This is most easily treated by decreasing the noxious nature of the refluxate by lowering its acid content and volume with the use of acid-lowering agents. Proton pump inhibitor therapy brings esophageal acid exposure into the normal range in most patients when given once daily and in nearly all patients when given more than once daily.1 In addition, reflux symptoms and esophagitis can be controlled even with the most severe grades of esophagitis.2 Despite the fact that these medications control both esophagitis and symptoms, they do not address the basic pathophysiology of GERD, which is impairment of reflux competence at the low esophageal sphincter. Laparoscopic fundoplication addresses that pathophysiology by increasing the barrier function of the lower esophageal sphincter (LES) via augmentation of sphincter pressure and length with a resultant decrease in esophageal acid exposure. In a large survey, Carlson et al have shown that the mean time below pH 4 in the esophagus over 24 hours is decreased from 8.4% before surgery to 1% after surgery, returning to normal in more than 90% of patients.3 Surgery also provides excellence control of both reflux symptoms and esophagitis over many years.4 Surgery is therefore very effective but unfortunately is associated with occasional long-term side effects and a small but significant mortality and morbidity. This has led to the search for more simple methods of augmentation of LES function. Endoscopic suturing techniques and the application of radiofrequency energy have been developed, reported in the literature, and approved for use in patients. In open-label studies of both the suturing and radiofrequency techniques, symptoms and quality of life scores have improved out of proportion to either technique's ability to improve LES pressure and esophageal acid exposure.5,6 The injection of foreign materials at the LES has also been reported and approved for use in the United States with very impressive control of symptoms, but once again this is associated with a very modest improvement in esophageal physiology.7 In this edition of the Journal, Schumacher et al report on a multicenter European study in which medication dependency was decreased after the endoscopic injection of a polymer at the lowest esophageal sphincter.8 Their results are quite similar to those that have previously been reported showing good patient satisfaction with a significant decrease in the use of acid-lowering agents. In contrast to the symptom data, this study once again has reported minimal to no change in the LES pressure or esophageal pH. Indeed, in the study presented in this issue of the Journal, there was no significant change in manometry and pH at all. In addition, the severity of esophagitis actually increased! In reflux studies using proton pump inhibitors, it has been clear that the more effective the control of gastric and esophageal acid, the better the control of esophagitis and symptoms.9 It is therefore strange that the majority of these patients feel clinically better despite ongoing acid reflux into the esophagus. This could be explained by either a placebo effect or by the possibility that these manipulations at the LES have resulted in a decreased sensitivity of the esophagus to react to reflux. Most studies of endoscopic antireflux therapies have only accepted patients with mild disease, no large hiatal hernia, and no Barrett, so it is not surprising that a large placebo effect should be seen in this group of selected patients. One study of radiofrequency energy with a sham treatment arm reported a 37% placebo effect.10 A preliminary report of a sham-controlled trial of endoscopic suturing had a similarly high placebo response rate.11 Early concerns about the long-term effect of injected foreign material at the LES have not totally been resolved. Initially, some leaders expressed concern that significant esophageal dysfunction with an achalasia-like effect could result from these injections, although this has not been reported to this point. On the other hand, the possibility that the symptom improvement noted with these techniques is due to “neurolysis” and loss of sensory function in the lower esophagus must be respected. In a preliminary study, patients were noted to have a prolongation in time to symptom production with esophageal acid perfusion 6 months after a radiofrequency procedure.12 If there is indeed a decreased sensitivity of these patients to the refluxate, the long-term effect of undetected continuing reflux could be severe with the potential for complications such as strictures and Barrett's esophagus in the future. The results of this study should again make us question the wisdom of using a treatment that results in symptom improvement but does not affect the disease process itself. That having been said, what data should we demand prior to advocating the general use of these techniques outside of research studies? From a physiologic perspective, it is conceptually difficult to support a procedure that does not at least improve esophageal acid exposure and hopefully augment the LES either by increasing LES pressure or perhaps by decreasing transient LES relaxations. We certainly should demand that the clinical outcome be at least better than placebo, but we would contend that it also should be at least equal and preferably better than continued proton pump inhibitor therapy (this has not been studied to our knowledge). The complication rate of the procedure must certainly be equal to and again preferably less than laparoscopic fundoplication. Finally, the treatment must make economic sense. For example, it seems that these endoscopic treatments cost at least $3,000 in the United States. Proton pump inhibitor therapy is now available for around $30 per month using over-the-counter or generic preparations. This would indicate that patients will need to have at least 100 months of proton pump inhibitor to “break even.” It is no wonder that most insurance carriers have declined to provide coverage for endoscopic treatment of reflux! Despite our considerable reservations in regards to the currently available techniques, it is appropriate to search for a simple method to control reflux. The current study is commendable since it reports the results of patients treated under strict trial conditions. In general, these investigations should go forward, but it seems inappropriate for these methods to be in general use before their long-term efficacy and safety have been properly evaluated in well-designed, properly controlled clinical trials.