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A critical review of endoscopic therapy for gastroesophageal reflux disease
A Critical Review of Endoscopic Therapy for Gastroesophageal Reflux Disease Walter J. Hogan, MD, Reza Shaker, MD
The US Food and Drug Administration has approved 2 endoscopic devices for treating gastroesophageal reflux disease, and several thousand procedures have been performed to date. At least 6 other endoscopic devices designed to treat gastroesophageal reflux are in various stages of testing and may soon obtain approval for clinical use. Short-term follow-up studies uniformly report improvement in heartburn symptoms and quality-of-life scores, as well as decreases in use of antisecretory medications. However, esophageal acid reflux is not normalized after these treatments, nor is esophagitis improved. Although troubling efficacy and safety issues are currently unresolved, these techniques are becoming routine clinical procedures outside of clinical trials. Unless there is rigorous attention to scientific validation of these techniques, including comparative trials versus conventional treatments, there will remain a cloud of doubt and concern about their role and usefulness in clinical medicine. The rapid incursion of these devices into the clinical marketplace before they have undergone critical scientific scrutiny magnifies the urgency of addressing these issues. Am J Med. 2003;115(3A):201S–210S. © 2003 by Excerpta Medica, Inc.
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nique therapies delivered through an endoscope to treat gastroesophageal reflux disease (GERD) were first introduced clinically in 2000. The US Food and Drug Administration (FDA) has approved 2 endoscopic devices for treating GERD, and several thousand procedures have been performed to date on a relatively select group of patients with GERD. At least 6 other endoscopic devices designed to treat GERD are in various stages of testing and may soon receive FDA approval for clinical use. Peer-reviewed reports of the results of 3 open-trial clinical studies using endoscopic devices to treat patients with GERD were published in April 2000.1–3 Information concerning the remaining devices has been obtained from abstracts published at national meetings. The gastroesophageal junction (GEJ) is the designated target of all these therapeutic devices. The 2 endoscopic devices that have received widespread clinical use in the United States are the Stretta radiofrequency catheter (Curon Medical, Inc., Sunnyvale, CA) and the Bard EndoCinch sewing device (C.R. Bard, Inc., Billerica, MA). Significant concerns have arisen about the present and future clinical use of these proposed treatment modalities for GERD in regard to their safety, efficacy, and necessity. The rapid incursion of these devices into the clinical marketplace before they have undergone critical scientific scrutiny magnifies the urgency of addressing these issues. This article reviews current devices approved or undergoing evaluation in clinical trials.
ENDOSCOPIC THERAPIES FOR GASTROESOPHAGEAL REFLUX DISEASE
From the Medical College of Wisconsin, Milwaukee, Wisconsin, USA. Requests for reprints should be sent to Walter J. Hogan, MD, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226. © 2003 by Excerpta Medica, Inc. All rights reserved.
Approved Devices The Stretta radiofrequency energy delivery system device (Figure 1) consists of an 8-Fr catheter and a distal balloon with 4 externally attached 5.5-mm needle electrodes that deliver computer-regulated radiofrequency energy to the GEJ zone at 56 separate sites (Figure 2). The thermal lesions reportedly cause shrinkage and cellular response in the submucosal tissue surrounding the puncture sites, decreasing the frequency of gastric reflux and transient lower esophageal sphincter (LES) relaxations.4 The EndoCinch endoluminal gastric plication technique2 uses an endoscopic sewing device to create pleats through a series of sutures passed through adjoining folds at the proximal fundus. This treatment is designed to “tighten” the cardiac component of the LES and impose a barrier to acid reflux. 0002-9343/03/$22.00 201S doi:10.1016/S0002-9343(03)00224-9
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Figure 1. The Stretta catheter, with distal balloon assembly and operational handle.
Devices Under Investigation Using the Plexiglas (polymethylmethacrylate [PMMA]; Ro¨ hm GmbH & Co. KG, Darmstadt, Germany) implantation procedure, which has been described elsewhere,3 PMMA microspheres are injected by needle under high pressure into the submucosa of the proximal LES zone to provide “bulking” support to the sphincter. The Sew-Right (Wilson-Cook, Winston-Salem, NC) device is another “sewing machine” that forms plication folds between proximal gastrin rugae. This sewing procedure is reportedly simplified and requires fewer repetitive steps to place a suture compared with similar methods. 202S August 18, 2003
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With the biopolymer augmentation procedure (Enteryx; Enteric Medical Technologies),5,6 ethylene vinyl alcohol polymer (an inert biocompatible substance with tantalum marker) is injected deep into the submucosal zone beneath the LES during fluoroscopic monitoring. It forms a globular ringlike “bulking” zone to augment LES pressure and decrease transient LES relaxations. With the Full-Thickness Plicator (NDO Surgical, Mansfield, MA), a flexible tube (18 mm diameter) that is capable of retroflexing on itself within the stomach, performs a fundic fold fixation and plication with a single pretied suture implant delivered by 2 opposing jawlike
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clamps on its distal tip. A regular upper gastrointestinal endoscope passes through this large bore tube and enables the operator to view the entire process from within the stomach (Figure 3). Using the expandable hydrogel prosthesis (Gatekeeper Reflux Repair System; Medtronic, Inc., Minneapolis, MN),7 3 to 4 separate circumferential segments of mucosa within the GEJ are aspirated into the tip of a probe and dilated with injectable saline. Subsequently, small (15 ⫻ 6 mm) expandable hydrogel prostheses are placed through slits into these submucosa sites under direct vision to augment LES tone (Figure 4). The peroral endoscopic Nissen fundoplication technique, performed under direct visualization, places 2 bioabsorbable clips at 4 quadrants, causing invagination and fixation of the GEJ and creating a functional nipple valve at the LES.
OVERVIEW OF ENDOSCOPIC THERAPIES FOR GASTROINTESTINAL REFLUX DISEASE By midsummer 2002, an estimated 3,000 Stretta procedures and ⬎4,000 EndoCinch procedures had been performed. The public has been made aware of these new procedures to prevent GERD, primarily through advertising and the media. For example, an Orlando Sentinel advertising section accompanying the May 19, 2002 edition of the Chicago Tribune published an article under the headline “Non-surgical Heat Procedure Tames Reflux,” stating that 70% of patients were able to discontinue all heartburn medications.8 This article further noted that “approximately 15 locations in Orlando use the Stretta procedure.” These types of advertisements tend to increase consumer demand for a procedure that may or may not be appropriate for patients with GERD. Despite the publicity and the considerable numbers of procedures that have been performed to date, these endoscopic treatments of GERD have not been compared head-to-head with currently accepted treatments for the disease. Furthermore, treatment groups have been carefully selected. Clinical outcomes have been determined almost exclusively on the basis of short-term, open-label trials, and safety issues have arisen with these therapies. The cost-effectiveness of endoscopic treatment for GERD also remains to be defined. It has yet to be demonstrated that these novel endoscopic therapies for GERD fulfill an unmet need or compare favorably with the safety and efficacy of conventional therapy. At the time of this writing, although endoscopic treatments for GERD have been in the clinical marketplace for 2 years, there has been only 1 randomized, double-blind, sham-controlled study evaluating the efficacy of an endoscopic technique (Stretta).9 The remainder of results of endoscopic GERD treatment studies have been open-label trials or clinical series reports, and the majority have been published in abstracts.
Clinical trials with the various endoscopic technologies to treat GERD have involved a highly select patient population. Criteria for entry include the presence of both heartburn symptoms and regurgitation episodes, as well as at least a partial response to daily antisecretory medication. The patients cannot have a hiatal hernia ⬎2.0 cm, and esophageal inflammation is limited to grades 1 and 2, ruling out patients with higher grades of esophagitis. Esophageal acid exposure during 24-hour ambulatory pH monitoring is customarily documented before entry in many of the endoscopic GERD therapy studies. Because peer-reviewed published articles are scant, it is difficult to determine how investigators defined “heartburn,” or “response to medication.” It is also difficult to know the criteria by which esophagitis was graded in these studies. Thus, it is reasonable to wonder whether appropriate therapeutic adjustments to medication regimens have been attempted prior to trial enrollment. Endoscopists recognize the limitations inherent in accurately grading a hiatal hernia size, and the presence of a sliding hiatal hernia is often difficult to establish during endoscopy. Furthermore, available reports do not adequately describe patients’ symptoms at baseline or their less-than-adequate responses to treatment. For example, are patients dissatisfied, dyspeptic, or noncompliant, or are they truly patients with “refractive” GERD? A recent study reported that patients’ median drug requirement at baseline was equivalent to 40 mg omeprazole daily.10 However, some patients were taking as much as 120 mg of omeprazole daily plus 300 mg of ranitidine at night and apparently continued to have symptoms. Whether this is true refractive GERD or whether the symptoms originated from another source is unclear.
COMPARISON WITH NONENDOSCOPIC GASTROESOPHAGEAL REFLUX DISEASE THERAPIES Current conventional therapies for the treatment of GERD, both medical and surgical, have been used for decades. They are successful and unquestionably adequate for comparison with new endoscopic treatment modalities. Medical treatments with H2-receptor antagonist or proton pump inhibitor (PPI) drugs result in symptomatic improvement in 60% and 80% of patients with GERD, respectively, and heal esophagitis in 50% and 90% of patients, respectively.10 However, there are potential issues concerning medical therapy for GERD, including persistent regurgitation, patient compliance, intolerance of medications, desire to discontinue medications, and long-term costs of therapy. In 90% of cases, operative therapy for GERD is also effective in reducing symptoms and acid exposure. Additionally, fundoplication surgery markedly decreases regurgitation and resolves esophagitis. Nevertheless, operative therapy
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Figure 2.
also has its potential problems. Surgery requires general anesthesia and 1 to 2 days of hospitalization, and there is potential for immediate or later postoperative complications. 204S August 18, 2003
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Persistent dysphagia postoperatively, for example, has been reported to occur as frequently as in up to 15% of patients.11 These real and potential problems associated with existing
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Figure 2. Schema of Stretta procedure. (A) The catheter is placed at the gastroesophageal junction (GEJ), the balloon is inflated, the stylettes are deployed, and radiofrequency is applied to the esophageal wall. (B) Sagittal view of the zones at the GEJ that have received radiofrequency thermal burn (white spots). (C) Posttreatment sagittal view of the GEJ showing “thickening” of the lower esophageal sphincteric zone and adjacent structures.
treatments for GERD present an open invitation for newer therapies such as those that endoscopic techniques deliver. Efficacy of Endoscopic GERD Treatments Preliminary results of endoscopic GERD treatment have demonstrated initial decreases and, in some instances, complete elimination of the need for antisecretory medications in the short term. Long-term outcomes remain to be demonstrated, however, and there are a number of troubling aspects regarding efficacy that are embedded in the available data. To date the most comprehensive report on outcomes after endoscopic GERD therapy is the 6- to 12-month follow-up for 118 patients who underwent a Stretta procedure in a US open-label trial.12 In brief, 94 patients were available for the 12-month follow-up, and this group had improvements from baseline to follow-up in heartburn scores (4 and 1, respectively), GERD scores (27 and 9, respectively), and quality-of-life scores. Acid exposure had decreased significantly from a median duration of 10.2% to 6.4%. However, esophageal acid exposure did not normalize, nor did the grade of esophagitis improve, in the majority of patients. Importantly, at 6 months, 60% of patients were taking no medications; this rate had decreased to 40% at 1 year. In the randomized, sham-controlled clinical trial using the Stretta procedure, 64 patients were entered from 8 cen-
ters.9 At 6 months, the heartburn quality-of-life scores improved from 13 to 1, and heartburn symptoms decreased from 2 to 1. The short form 36 physical quality-of-life score improved from 0.1 to 7.6. However, the median acid-exposure (% time pH ⬍4) increased from 9.3% to 10.7%. At 6 months, the patients in the sham group were offered Stretta therapy, making a longer comparison impossible. Subsequently, both the crossover and original treatment groups apparently showed improvement. Additionally, although 47% of patients receiving Stretta treatment were off all therapy at 6 months, 37% of sham patients were also off medications. The overall effectiveness of the radiofrequency ablation technique for preventing GERD has not been substantiated, compared with placebo, in this first appropriately designed, randomized, controlled clinical trial. The results of therapeutic endoscopic trials using the Bard suture-plication technique have been reported in 2-year follow-up studies from 2 centers.13,14 Approximately one quarter of the patients treated by suture plication were off all PPIs, and slightly more than one quarter of patients were on less-than-baseline PPI therapy. However, in the report by Rothstein et al.,13 ⬎40% of patients were still on full-dose medications, whereas in the study by Haber et al.,14 7 of 23 patients (32%) eventually had an operative fundoplication. The long-term efficacy of these procedures appears to be problematic.
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Figure 3. (A) Advertisement brochure photograph of the Plicator (NDO Surgical Inc., Mansfield, MA), displaying retroflexion of the Plicator with jaws open and retroflexion of the viewing endoscope below. (B) Schema of plicator procedure: (top left) retroflexion of plicator within stomach; (top right) screwlike needle impales a fold beneath the GEJ; (middle) needle is retracted, pulling the fold toward the jaws of the Plicator; (bottom left) single pretied suture implant has been fixed by the opposing jawlike clamps; (bottom right) appearance of plicated gastric fold.
An investigator group has evaluated concurrent cautery coaptation of fundic folds after stitch insertion to maintain suture stability.15 The small size of the patient population that has been studied is troubling as well. The majority of the new endoscopic techniques to treat GERD have been performed in small patient groups with brief follow-up and have been published primarily in the United States in preliminary or abstract reports. For example, the only publication on the results of the Plexiglas microsphere injection 206S August 18, 2003
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technique involved only 10 patients.3 The initial report of the results of the biopolymer injection into the lower esophageal muscle involved a small group of 15 patients.5 Results to date indicate that these endoscopic techniques to treat GERD do not normalize esophageal acid exposure, nor do they appear to reverse esophageal inflammation. The majority of short-term benefits appear to be related to improving symptoms of GERD and health-related quality-of-life. Interestingly, whereas the health-related quality-of-life survey has been validated as a clinical
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Figure 4. Schema of Gatekeeper Reflux Repair System (Medtronics Inc., Minneapolis, MN), showing the expandable hydrogel prosthesis inserted into the gastroesophageal junction. The hydrogel prosthesis is shown before and after expansion (inset).
outcomes measurement tool, results were somewhat contrary in a recent survey of 936 GERD subjects with heartburn.16 Similar to previous surveys, patients with heartburn symptoms showed higher health-related quality-oflife scores in all categories ranging from emotional distress to physical and social functioning. The disturbing feature of this study was that patients who reported infrequent heartburn symptoms had higher scores than those who reported frequent heartburn.
SAFETY OF ENDOSCOPIC GASTROESOPHAGEAL REFLUX DISEASE TREATMENTS Complications Actual and potential complications arising from endoscopic therapies are perhaps the most troubling aspect of this discussion. In a postmarketing evaluation of ⬎1,200 cases, there have been 2 deaths associated with the Stretta procedure (Table 1). Other complications included bleeding (0.17%), mucosal ulcerations (0.08%), pleural
effusions (0.08%), and perforations (0.33%), resulting in an overall complication rate of 0.83%.17 The frequency of complications appears to have decreased with the introduction of a guidewire to introduce the balloon catheter. However, a recent preliminary report using Stretta treatment on 118 patients describes 13 patients with chest discomfort for 2 to 5 days, 7 patients with mild transient nonobstructive dysphagia, and 2 patients with delayed bleeding (1 to 3 weeks postprocedure) that did not require transfusions. The total morbidity reported in this study was 1.7%.18 In reports describing the EndoCinch procedure, 1 perforation and 2 bleeding episodes have been reported; the major disadvantage with this technique is the length of the procedure, which requires prolonged sedation. The use of an overtube and an average of 8 steps per plication placement were necessary during the introduction of the EndoCinch procedure. In the initially reported study,2 17% of patients required general anesthesia, for a mean procedure time of 68 minutes. Other safety concerns with
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this procedure are the lack of suture permanency and incidence of repeat procedures. The radiofrequency ablation technique and the gastroplication procedure also have long procedure times and require multiple steps. The former took 1 hour to perform in initial reports. Procedure time and technical complexity have improved somewhat since the initial introduction of the endoscopic GERD therapies, because these procedures now require fewer steps; some concerns remain, however. The Enteryx study5 reported “mild” retrosternal pain for 1 to 3 days in 8 of 15 patients, whereas 1 patient developed dysphagia for 2 weeks. The majority of patients demonstrated at least 50% of retained polymer at 4 to 12 months, suggesting that polymer loss through migration is a potential problem. Potential Safety Issues There are a number of potential safety concerns with endoscopic GERD therapies (Table 2). Many relate to the motility of the esophageal structures. In particular, the GEJ is not static but is, in fact, quite dynamic, shortening 1 to 2 cm with respiration and swallowing. Additionally, there is often anatomic angulation of the distal esophagus, and luminal contractions frequently obliterate the squamocolumnar junction during endoscopy. The stylettes attached to the Stretta balloon are deployed blindly based on prior endoscopic measurements. The 5.5-mm needles are at least the depth of the esophageal wall and are deployed for periods of 120 seconds during esophageal movement. The presence of a sliding hiatal hernia complicates this scenario. A similar situation is encountered during injection therapy of microspheres or hydrogel prosthesis. Any endoscopist who has injected Botox (botulinum toxin type A; Allergan Inc., Irvine, CA) or other substances into the distal esophagus can appreciate the difficulties encountered in accurately delivering materials in a uniform distribution pattern around the entire periphery of the GEJ. Although fluoroscopy was used to monitor the appropriate placement of Enteryx biopolymer, which is mixed with a radiopaque contrast agent, a “ring” of polymer was not obtained in all cases.5 Another important concern is the learning curve required to perform these somewhat difficult procedures. Training has not been standardized, nor has technical competence been guaranteed. For example, in the multicenter gastroplication study,19 all but 1 of the clinical investigators were performing endoscopic suturing on humans for the first time. As with most procedures, complications decrease as experience increases. There are no guarantees that novices will receive adequate training to perform these procedures. Potential Long-Term Safety Issues In theory, endoscopic treatments for GERD may be a cause for potential long-term problems (Table 3). Radiofrequency ablation appears to result in neurolysis, leading 208S August 18, 2003
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Table 1. Postmarketing Complications for the Stretta Procedure in ⬎1,200 Cases Complication Bleeding Mucosal ulcerations Pleural effusions Perforation Aspiration/death Total
Rate (%) 0.17 0.08 0.08 0.33 0.17 0.83
Reprinted with permission from Stollman.17
to improvements in the frequency of transient LES relaxations and heartburn scores. However, it is possible that the loss of sensation will place the patient at future risk for reflux insult without experiencing the warning sensation of heartburn. It is likewise possible that this treatment may impair the belch reflex or the dynamic function of the diaphragmatic crus. Fundoplication surgery after failed radiofrequency ablation has been performed without apparent disruption or fusion of tissue planes. However, our group has experienced a situation in which significant tissue disruption from radiofrequency ablation was reported at the time of subsequent fundoplication operation, causing difficulties in freeing up the structures at the anatomic hiatus for appropriate plication (personal communication). Tissue damage to the GEJ may be associated with radiofrequency ablation, and reports of perforations appear to support this assumption. Microspheres used in PMMA treatment are supposedly treated to avoid foreign body reaction, migration, or impairment of phagocytosis. It is too early to tell how safe these implants are. On the other hand, the Enteryx biopolymer material has been noted to erode out of the esophageal tissue in 25% of patients, and the Gatekeeper hydrogel prosthesis apparently erodes from initial submucosal placement in a quarter of patients. These are serious concerns. Finally, the Plicator technique has been reported in only a small group of patients. The instrument is large in diameter (18 mm), and impaction of the instrument after plication is certainly possible. Postprocedure dysphagia occurs after operative fundoplication. Dysphagia following the Plicator procedure is also likely to be an associated problem.
COST-EFFECTIVENESS OF ENDOSCOPIC THERAPIES An estimated physician and facility cost and a Current Procedural Terminology code have been developed for the Stretta procedure. The Curon Company mailed information concerning approximate fees for the Stretta procedure in early 2002.20 Physician reimbursement for the procedure is estimated to be $525.53 by Medicare and $830.64 for managed care. Hospital costs were reported
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Table 2. Potential Procedural Problems Associated with Endoscopic Gastroesophageal Reflux Disease Therapies Variable Gastroesophageal junction anatomy
Potential Problems ● Potential injury due to: —Esophageal motility during procedure —Presence of hiatal hernia —Obstructed view during procedure
Treatment duration
● Prolonged procedure time, compared with laparoscopic procedures
Sedation
● Prolonged conscious sedation time ● Need to use general anesthesia
Training
● Need to learn a range of sophisticated techniques ● Relatively short training experience ● Relatively long learning curve
Table 3. Potential Long-Term Problems Associated with Endoscopic Gastroesophageal Reflux Disease Therapies Variable
Potential Problems
Neurologic injury
● Loss of heartburn sensation ● Loss of belching reflex ● Crus impairment ● Loss of endoluminal compliance
Plication efficacy
● Stitches may not hold ● Potential for injury due to depth of tissue penetration ● Need for cautery to secure stitches
Implantation safety
● Foreign body reaction ● Migration of foreign material
Wrap formation
● Instruments may impact ● Need to repeat procedure ● Dysphagia; wrap disruption; too tight
to be $1,804.30 and $2,250, respectively. A recent abstract compared the cost of gastroplication treatment to conventional medical treatment.21 For 142 patients with a small hiatal hernia, preplication medical expenses averaged $3,057 per year. Postplication procedure medical costs decreased to $214 per year, an annual savings of $2,843 per patient. If lowered cost is shown to be maintained for the long term, it will certainly increase the use of this procedure. However, suture disruption and repeat procedures that may be associated with it must be taken into account in any cost analysis. Furthermore, a cost analysis is best conducted once efficacy has been established.22
SUMMARY Endoscopic treatments for GERD have been in clinical use for 2 years, yet only 1 randomized, sham-controlled study, which critically evaluated a single technique, has been reported. The remainder of therapeutic trials have
been open label. Short-term follow-up studies uniformly report improvement in heartburn symptoms and healthrelated quality-of-life scores as well as decreases in the use of antisecretory medications. However, esophageal acid reflux is not normalized following these treatments, and esophagitis is not improved. To date, these endoscopic techniques have been confined to a stratified group of patients who had no or mild esophagitis and only small hiatal hernias. There are many new and developing endoscopic therapies to treat GERD. We feel it is unfortunate that the current FDA-approved endoscopic techniques have been in clinical use for 2 years without appropriate scientific validation of efficacy and long-term effectiveness. It could be tragic if newcomers to the field of endoscopic therapies for GERD are not subjected to more rigorous evaluation of efficacy and safety before they become standard clinical treatments.23 Issues of durability of effect require reasonable periods of follow-up after treatment.
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Therefore, more patients should be studied for longer than 6 months to 2 years. Furthermore, endoscopic GERD therapies should be compared head-to-head with existing medical and surgical therapies to determine their role and effectiveness in treating this disorder. Finally, it is appropriate to insist that endoscopic treatment of GERD should be applicable to all patients with GERD, not a carefully stratified minority. Unless there is rigorous attention to the tenets of scientific validation of endoscopic techniques for GERD treatment, there will remain a cloud of doubt and concern about their role and usefulness in clinical medicine.
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REFERENCES 1. Triadafilopoulous G, Baese JK, Nostrant TT, et al. Radiofrequency energy delivery to the gastroesophageal junction for the treatment of gastroesophageal reflux diseases. Gastrointest Endosc. 2001;53:407–415. 2. Filipi CJ, Lehman GA, Rothstein RI, et al. Transoral flexible endoscopic suturing for treatment of gastroesophageal reflux disease: a multicenter trial. Gastrointest Endosc. 2001; 53:416 –422. 3. Feretis C, Benakis P, Dimopoulos C, et al. Endoscopic implantation of Plexiglas (PMMA) microspheres for treatment of gastroesophageal reflux disease. Gastrointest Endosc. 2001;53:423–426. 4. Kim MS, Dent J, Holloway R, Utley DS. Radiofrequency energy delivery to the gastric cardia inhibits triggering of transient lower esophageal sphincter relaxation in a canine model [abstract]. Gastroenterology. 2000;118:A860. 5. Deviere J, Pastorelli A, Louis H, et al. Endoscopic implantation of a biopolymer in the lower esophageal sphincter for gastroesophageal reflux: a pilot study. Gastrointest Endosc. 2002;53:335–341. 6. Lehman GA, Eisenberg J, Cohen LB, et al. Enteryx solution, a minimally invasive injectable treatment for GERD: international multicenter trial results [abstract]. Gastroenterology. 2002;12:67. 7. Lehman GA, Watkins JL, Hieston K. Endoscopic gastroesophageal reflux disease (GERD) therapy with Gatekeeper™ system. Initiation of a multicenter prospective randomized trial [abstract]. Gastroenterology. 2002;122: 248. 8. Suriano R. Non-surgical heat procedure tames reflux: Orlando Sentinel special to Chicago Tribune. May 19, 2002. 9. Corley DA, Katz P, Wo J, et al. Radiofrequency energy to the gastroesophageal junction for treatment of GERD (the Stretta
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procedure): a randomized, sham-controlled, multicenter clinical trial [abstract]. Gastroenterology. 2002;122:67. Kahrilas PJ. Management of GERD: medical versus surgical. Semin Gastrointest Dis. 2001;12:3–15. Lufullarde T, Watson DI, Jamieson GG, et al. Laparoscopic Nissen fundoplication: five-year results and beyond. Arch Surg. 2001;136:180 –184. Triadafilopoulos G, Debase JK, Nostrant TT, et al. Longterm experience with the Stretta procedure for the treatment of GERD; 6 and 12-month follow-up of the US open label trial. Gastrointest Endosc. 2002;55:149 –156. Rothstein RI, Pohl H, Grave M, et al. Endoscopic gastric plication for the treatment of GERD: two-year follow-up results [abstract]. Am J Gastroenterol. 2001;S36:A107. Haber GB, Marcon NE, Kortan P, et al. A 2-year follow-up of 25 patients undergoing endoluminal gastric plication (ELGP) for gastroesophageal reflux disease (GERD) [abstract]. Gastrointest Endosc. 2001;53:AB116. Lehman GA, Dunne DP, Hiestenk, Dieselman K, Dimberio D. Suturing plication of cardia with Endocinch device: effect of supplemental cautery; a human prospective randomized trial [abstract]. Gastroenterology. 2002;122. Madisch A, Weihs C, Schland M, et al. Impact on healthrelated quality of life (HRQL) in subjects with gastroesophageal reflux disease (GERD): results of a nationwide informing campaign— based on telephone hotline in Germany [abstract]. Gastroenterology. 2002;122:214. Stollman N. GERD: the case for endoluminal treatment. Paper presented at Digestive Diseases Week, May 2002, San Francisco. Noar M, Knight S, Bidlack D. Long-term experience with the Stretta procedure in medically refractory GERD patients: the first 14 months [abstract]. Gastroenterology. 2002;112:4. Filipi CJ. Why endoscopic suturing for GERD is appropriate [letter]. Gastrointest Endosc. 2002;55:300 –301. Stretta Reimbursement Guide. Sunnyvale, CA: Curon Medical; 2002. Raijman I, Ben-Menachem T, Starpoli A, et al. Endoluminal gastroplication (ELGP) improves GERD symptoms in patients with large hiatal hernias [abstract]. Gastroenterology. 2002;122:283. Thiny MT, Shaheen NJ. Is Stretta ready for prime time? Selected summaries. Gastroenterology. 2002;123:643– 644. Hogan WJ. Endoscopic treatments for gastroesophageal reflux disease: not ready for prime time technology. Clin Perspect Gastroenterol. 2002;5:149 –153.
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The US Food and Drug Administration has approved 2 endoscopic devices for treating gastroesophageal reflux disease, and several thousand procedures have been performed to date. At least 6 other endoscopic devices designed to treat gastroesophageal reflux are in various stages of testing and may soon obtain approval for clinical use. Short-term follow-up studies uniformly report improvement in heartburn symptoms and quality-of-life scores, as well as decreases in use of antisecretory medications. However, esophageal acid reflux is not normalized after these treatments, nor is esophagitis improved. Although troubling efficacy and safety issues are currently unresolved, these techniques are becoming routine clinical procedures outside of clinical trials. Unless there is rigorous attention to scientific validation of these techniques, including comparative trials versus conventional treatments, there will remain a cloud of doubt and concern about their role and usefulness in clinical medicine. The rapid incursion of these devices into the clinical marketplace before they have undergone critical scientific scrutiny magnifies the urgency of addressing these issues. Am J Med. 2003;115(3A):201S–210S. © 2003 by Excerpta Medica, Inc.
U
nique therapies delivered through an endoscope to treat gastroesophageal reflux disease (GERD) were first introduced clinically in 2000. The US Food and Drug Administration (FDA) has approved 2 endoscopic devices for treating GERD, and several thousand procedures have been performed to date on a relatively select group of patients with GERD. At least 6 other endoscopic devices designed to treat GERD are in various stages of testing and may soon receive FDA approval for clinical use. Peer-reviewed reports of the results of 3 open-trial clinical studies using endoscopic devices to treat patients with GERD were published in April 2000.1–3 Information concerning the remaining devices has been obtained from abstracts published at national meetings. The gastroesophageal junction (GEJ) is the designated target of all these therapeutic devices. The 2 endoscopic devices that have received widespread clinical use in the United States are the Stretta radiofrequency catheter (Curon Medical, Inc., Sunnyvale, CA) and the Bard EndoCinch sewing device (C.R. Bard, Inc., Billerica, MA). Significant concerns have arisen about the present and future clinical use of these proposed treatment modalities for GERD in regard to their safety, efficacy, and necessity. The rapid incursion of these devices into the clinical marketplace before they have undergone critical scientific scrutiny magnifies the urgency of addressing these issues. This article reviews current devices approved or undergoing evaluation in clinical trials.
ENDOSCOPIC THERAPIES FOR GASTROESOPHAGEAL REFLUX DISEASE
From the Medical College of Wisconsin, Milwaukee, Wisconsin, USA. Requests for reprints should be sent to Walter J. Hogan, MD, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226. © 2003 by Excerpta Medica, Inc. All rights reserved.
Approved Devices The Stretta radiofrequency energy delivery system device (Figure 1) consists of an 8-Fr catheter and a distal balloon with 4 externally attached 5.5-mm needle electrodes that deliver computer-regulated radiofrequency energy to the GEJ zone at 56 separate sites (Figure 2). The thermal lesions reportedly cause shrinkage and cellular response in the submucosal tissue surrounding the puncture sites, decreasing the frequency of gastric reflux and transient lower esophageal sphincter (LES) relaxations.4 The EndoCinch endoluminal gastric plication technique2 uses an endoscopic sewing device to create pleats through a series of sutures passed through adjoining folds at the proximal fundus. This treatment is designed to “tighten” the cardiac component of the LES and impose a barrier to acid reflux. 0002-9343/03/$22.00 201S doi:10.1016/S0002-9343(03)00224-9
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Figure 1. The Stretta catheter, with distal balloon assembly and operational handle.
Devices Under Investigation Using the Plexiglas (polymethylmethacrylate [PMMA]; Ro¨ hm GmbH & Co. KG, Darmstadt, Germany) implantation procedure, which has been described elsewhere,3 PMMA microspheres are injected by needle under high pressure into the submucosa of the proximal LES zone to provide “bulking” support to the sphincter. The Sew-Right (Wilson-Cook, Winston-Salem, NC) device is another “sewing machine” that forms plication folds between proximal gastrin rugae. This sewing procedure is reportedly simplified and requires fewer repetitive steps to place a suture compared with similar methods. 202S August 18, 2003
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With the biopolymer augmentation procedure (Enteryx; Enteric Medical Technologies),5,6 ethylene vinyl alcohol polymer (an inert biocompatible substance with tantalum marker) is injected deep into the submucosal zone beneath the LES during fluoroscopic monitoring. It forms a globular ringlike “bulking” zone to augment LES pressure and decrease transient LES relaxations. With the Full-Thickness Plicator (NDO Surgical, Mansfield, MA), a flexible tube (18 mm diameter) that is capable of retroflexing on itself within the stomach, performs a fundic fold fixation and plication with a single pretied suture implant delivered by 2 opposing jawlike
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clamps on its distal tip. A regular upper gastrointestinal endoscope passes through this large bore tube and enables the operator to view the entire process from within the stomach (Figure 3). Using the expandable hydrogel prosthesis (Gatekeeper Reflux Repair System; Medtronic, Inc., Minneapolis, MN),7 3 to 4 separate circumferential segments of mucosa within the GEJ are aspirated into the tip of a probe and dilated with injectable saline. Subsequently, small (15 ⫻ 6 mm) expandable hydrogel prostheses are placed through slits into these submucosa sites under direct vision to augment LES tone (Figure 4). The peroral endoscopic Nissen fundoplication technique, performed under direct visualization, places 2 bioabsorbable clips at 4 quadrants, causing invagination and fixation of the GEJ and creating a functional nipple valve at the LES.
OVERVIEW OF ENDOSCOPIC THERAPIES FOR GASTROINTESTINAL REFLUX DISEASE By midsummer 2002, an estimated 3,000 Stretta procedures and ⬎4,000 EndoCinch procedures had been performed. The public has been made aware of these new procedures to prevent GERD, primarily through advertising and the media. For example, an Orlando Sentinel advertising section accompanying the May 19, 2002 edition of the Chicago Tribune published an article under the headline “Non-surgical Heat Procedure Tames Reflux,” stating that 70% of patients were able to discontinue all heartburn medications.8 This article further noted that “approximately 15 locations in Orlando use the Stretta procedure.” These types of advertisements tend to increase consumer demand for a procedure that may or may not be appropriate for patients with GERD. Despite the publicity and the considerable numbers of procedures that have been performed to date, these endoscopic treatments of GERD have not been compared head-to-head with currently accepted treatments for the disease. Furthermore, treatment groups have been carefully selected. Clinical outcomes have been determined almost exclusively on the basis of short-term, open-label trials, and safety issues have arisen with these therapies. The cost-effectiveness of endoscopic treatment for GERD also remains to be defined. It has yet to be demonstrated that these novel endoscopic therapies for GERD fulfill an unmet need or compare favorably with the safety and efficacy of conventional therapy. At the time of this writing, although endoscopic treatments for GERD have been in the clinical marketplace for 2 years, there has been only 1 randomized, double-blind, sham-controlled study evaluating the efficacy of an endoscopic technique (Stretta).9 The remainder of results of endoscopic GERD treatment studies have been open-label trials or clinical series reports, and the majority have been published in abstracts.
Clinical trials with the various endoscopic technologies to treat GERD have involved a highly select patient population. Criteria for entry include the presence of both heartburn symptoms and regurgitation episodes, as well as at least a partial response to daily antisecretory medication. The patients cannot have a hiatal hernia ⬎2.0 cm, and esophageal inflammation is limited to grades 1 and 2, ruling out patients with higher grades of esophagitis. Esophageal acid exposure during 24-hour ambulatory pH monitoring is customarily documented before entry in many of the endoscopic GERD therapy studies. Because peer-reviewed published articles are scant, it is difficult to determine how investigators defined “heartburn,” or “response to medication.” It is also difficult to know the criteria by which esophagitis was graded in these studies. Thus, it is reasonable to wonder whether appropriate therapeutic adjustments to medication regimens have been attempted prior to trial enrollment. Endoscopists recognize the limitations inherent in accurately grading a hiatal hernia size, and the presence of a sliding hiatal hernia is often difficult to establish during endoscopy. Furthermore, available reports do not adequately describe patients’ symptoms at baseline or their less-than-adequate responses to treatment. For example, are patients dissatisfied, dyspeptic, or noncompliant, or are they truly patients with “refractive” GERD? A recent study reported that patients’ median drug requirement at baseline was equivalent to 40 mg omeprazole daily.10 However, some patients were taking as much as 120 mg of omeprazole daily plus 300 mg of ranitidine at night and apparently continued to have symptoms. Whether this is true refractive GERD or whether the symptoms originated from another source is unclear.
COMPARISON WITH NONENDOSCOPIC GASTROESOPHAGEAL REFLUX DISEASE THERAPIES Current conventional therapies for the treatment of GERD, both medical and surgical, have been used for decades. They are successful and unquestionably adequate for comparison with new endoscopic treatment modalities. Medical treatments with H2-receptor antagonist or proton pump inhibitor (PPI) drugs result in symptomatic improvement in 60% and 80% of patients with GERD, respectively, and heal esophagitis in 50% and 90% of patients, respectively.10 However, there are potential issues concerning medical therapy for GERD, including persistent regurgitation, patient compliance, intolerance of medications, desire to discontinue medications, and long-term costs of therapy. In 90% of cases, operative therapy for GERD is also effective in reducing symptoms and acid exposure. Additionally, fundoplication surgery markedly decreases regurgitation and resolves esophagitis. Nevertheless, operative therapy
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Figure 2.
also has its potential problems. Surgery requires general anesthesia and 1 to 2 days of hospitalization, and there is potential for immediate or later postoperative complications. 204S August 18, 2003
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Persistent dysphagia postoperatively, for example, has been reported to occur as frequently as in up to 15% of patients.11 These real and potential problems associated with existing
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Figure 2. Schema of Stretta procedure. (A) The catheter is placed at the gastroesophageal junction (GEJ), the balloon is inflated, the stylettes are deployed, and radiofrequency is applied to the esophageal wall. (B) Sagittal view of the zones at the GEJ that have received radiofrequency thermal burn (white spots). (C) Posttreatment sagittal view of the GEJ showing “thickening” of the lower esophageal sphincteric zone and adjacent structures.
treatments for GERD present an open invitation for newer therapies such as those that endoscopic techniques deliver. Efficacy of Endoscopic GERD Treatments Preliminary results of endoscopic GERD treatment have demonstrated initial decreases and, in some instances, complete elimination of the need for antisecretory medications in the short term. Long-term outcomes remain to be demonstrated, however, and there are a number of troubling aspects regarding efficacy that are embedded in the available data. To date the most comprehensive report on outcomes after endoscopic GERD therapy is the 6- to 12-month follow-up for 118 patients who underwent a Stretta procedure in a US open-label trial.12 In brief, 94 patients were available for the 12-month follow-up, and this group had improvements from baseline to follow-up in heartburn scores (4 and 1, respectively), GERD scores (27 and 9, respectively), and quality-of-life scores. Acid exposure had decreased significantly from a median duration of 10.2% to 6.4%. However, esophageal acid exposure did not normalize, nor did the grade of esophagitis improve, in the majority of patients. Importantly, at 6 months, 60% of patients were taking no medications; this rate had decreased to 40% at 1 year. In the randomized, sham-controlled clinical trial using the Stretta procedure, 64 patients were entered from 8 cen-
ters.9 At 6 months, the heartburn quality-of-life scores improved from 13 to 1, and heartburn symptoms decreased from 2 to 1. The short form 36 physical quality-of-life score improved from 0.1 to 7.6. However, the median acid-exposure (% time pH ⬍4) increased from 9.3% to 10.7%. At 6 months, the patients in the sham group were offered Stretta therapy, making a longer comparison impossible. Subsequently, both the crossover and original treatment groups apparently showed improvement. Additionally, although 47% of patients receiving Stretta treatment were off all therapy at 6 months, 37% of sham patients were also off medications. The overall effectiveness of the radiofrequency ablation technique for preventing GERD has not been substantiated, compared with placebo, in this first appropriately designed, randomized, controlled clinical trial. The results of therapeutic endoscopic trials using the Bard suture-plication technique have been reported in 2-year follow-up studies from 2 centers.13,14 Approximately one quarter of the patients treated by suture plication were off all PPIs, and slightly more than one quarter of patients were on less-than-baseline PPI therapy. However, in the report by Rothstein et al.,13 ⬎40% of patients were still on full-dose medications, whereas in the study by Haber et al.,14 7 of 23 patients (32%) eventually had an operative fundoplication. The long-term efficacy of these procedures appears to be problematic.
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Figure 3. (A) Advertisement brochure photograph of the Plicator (NDO Surgical Inc., Mansfield, MA), displaying retroflexion of the Plicator with jaws open and retroflexion of the viewing endoscope below. (B) Schema of plicator procedure: (top left) retroflexion of plicator within stomach; (top right) screwlike needle impales a fold beneath the GEJ; (middle) needle is retracted, pulling the fold toward the jaws of the Plicator; (bottom left) single pretied suture implant has been fixed by the opposing jawlike clamps; (bottom right) appearance of plicated gastric fold.
An investigator group has evaluated concurrent cautery coaptation of fundic folds after stitch insertion to maintain suture stability.15 The small size of the patient population that has been studied is troubling as well. The majority of the new endoscopic techniques to treat GERD have been performed in small patient groups with brief follow-up and have been published primarily in the United States in preliminary or abstract reports. For example, the only publication on the results of the Plexiglas microsphere injection 206S August 18, 2003
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technique involved only 10 patients.3 The initial report of the results of the biopolymer injection into the lower esophageal muscle involved a small group of 15 patients.5 Results to date indicate that these endoscopic techniques to treat GERD do not normalize esophageal acid exposure, nor do they appear to reverse esophageal inflammation. The majority of short-term benefits appear to be related to improving symptoms of GERD and health-related quality-of-life. Interestingly, whereas the health-related quality-of-life survey has been validated as a clinical
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Figure 4. Schema of Gatekeeper Reflux Repair System (Medtronics Inc., Minneapolis, MN), showing the expandable hydrogel prosthesis inserted into the gastroesophageal junction. The hydrogel prosthesis is shown before and after expansion (inset).
outcomes measurement tool, results were somewhat contrary in a recent survey of 936 GERD subjects with heartburn.16 Similar to previous surveys, patients with heartburn symptoms showed higher health-related quality-oflife scores in all categories ranging from emotional distress to physical and social functioning. The disturbing feature of this study was that patients who reported infrequent heartburn symptoms had higher scores than those who reported frequent heartburn.
SAFETY OF ENDOSCOPIC GASTROESOPHAGEAL REFLUX DISEASE TREATMENTS Complications Actual and potential complications arising from endoscopic therapies are perhaps the most troubling aspect of this discussion. In a postmarketing evaluation of ⬎1,200 cases, there have been 2 deaths associated with the Stretta procedure (Table 1). Other complications included bleeding (0.17%), mucosal ulcerations (0.08%), pleural
effusions (0.08%), and perforations (0.33%), resulting in an overall complication rate of 0.83%.17 The frequency of complications appears to have decreased with the introduction of a guidewire to introduce the balloon catheter. However, a recent preliminary report using Stretta treatment on 118 patients describes 13 patients with chest discomfort for 2 to 5 days, 7 patients with mild transient nonobstructive dysphagia, and 2 patients with delayed bleeding (1 to 3 weeks postprocedure) that did not require transfusions. The total morbidity reported in this study was 1.7%.18 In reports describing the EndoCinch procedure, 1 perforation and 2 bleeding episodes have been reported; the major disadvantage with this technique is the length of the procedure, which requires prolonged sedation. The use of an overtube and an average of 8 steps per plication placement were necessary during the introduction of the EndoCinch procedure. In the initially reported study,2 17% of patients required general anesthesia, for a mean procedure time of 68 minutes. Other safety concerns with
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this procedure are the lack of suture permanency and incidence of repeat procedures. The radiofrequency ablation technique and the gastroplication procedure also have long procedure times and require multiple steps. The former took 1 hour to perform in initial reports. Procedure time and technical complexity have improved somewhat since the initial introduction of the endoscopic GERD therapies, because these procedures now require fewer steps; some concerns remain, however. The Enteryx study5 reported “mild” retrosternal pain for 1 to 3 days in 8 of 15 patients, whereas 1 patient developed dysphagia for 2 weeks. The majority of patients demonstrated at least 50% of retained polymer at 4 to 12 months, suggesting that polymer loss through migration is a potential problem. Potential Safety Issues There are a number of potential safety concerns with endoscopic GERD therapies (Table 2). Many relate to the motility of the esophageal structures. In particular, the GEJ is not static but is, in fact, quite dynamic, shortening 1 to 2 cm with respiration and swallowing. Additionally, there is often anatomic angulation of the distal esophagus, and luminal contractions frequently obliterate the squamocolumnar junction during endoscopy. The stylettes attached to the Stretta balloon are deployed blindly based on prior endoscopic measurements. The 5.5-mm needles are at least the depth of the esophageal wall and are deployed for periods of 120 seconds during esophageal movement. The presence of a sliding hiatal hernia complicates this scenario. A similar situation is encountered during injection therapy of microspheres or hydrogel prosthesis. Any endoscopist who has injected Botox (botulinum toxin type A; Allergan Inc., Irvine, CA) or other substances into the distal esophagus can appreciate the difficulties encountered in accurately delivering materials in a uniform distribution pattern around the entire periphery of the GEJ. Although fluoroscopy was used to monitor the appropriate placement of Enteryx biopolymer, which is mixed with a radiopaque contrast agent, a “ring” of polymer was not obtained in all cases.5 Another important concern is the learning curve required to perform these somewhat difficult procedures. Training has not been standardized, nor has technical competence been guaranteed. For example, in the multicenter gastroplication study,19 all but 1 of the clinical investigators were performing endoscopic suturing on humans for the first time. As with most procedures, complications decrease as experience increases. There are no guarantees that novices will receive adequate training to perform these procedures. Potential Long-Term Safety Issues In theory, endoscopic treatments for GERD may be a cause for potential long-term problems (Table 3). Radiofrequency ablation appears to result in neurolysis, leading 208S August 18, 2003
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Table 1. Postmarketing Complications for the Stretta Procedure in ⬎1,200 Cases Complication Bleeding Mucosal ulcerations Pleural effusions Perforation Aspiration/death Total
Rate (%) 0.17 0.08 0.08 0.33 0.17 0.83
Reprinted with permission from Stollman.17
to improvements in the frequency of transient LES relaxations and heartburn scores. However, it is possible that the loss of sensation will place the patient at future risk for reflux insult without experiencing the warning sensation of heartburn. It is likewise possible that this treatment may impair the belch reflex or the dynamic function of the diaphragmatic crus. Fundoplication surgery after failed radiofrequency ablation has been performed without apparent disruption or fusion of tissue planes. However, our group has experienced a situation in which significant tissue disruption from radiofrequency ablation was reported at the time of subsequent fundoplication operation, causing difficulties in freeing up the structures at the anatomic hiatus for appropriate plication (personal communication). Tissue damage to the GEJ may be associated with radiofrequency ablation, and reports of perforations appear to support this assumption. Microspheres used in PMMA treatment are supposedly treated to avoid foreign body reaction, migration, or impairment of phagocytosis. It is too early to tell how safe these implants are. On the other hand, the Enteryx biopolymer material has been noted to erode out of the esophageal tissue in 25% of patients, and the Gatekeeper hydrogel prosthesis apparently erodes from initial submucosal placement in a quarter of patients. These are serious concerns. Finally, the Plicator technique has been reported in only a small group of patients. The instrument is large in diameter (18 mm), and impaction of the instrument after plication is certainly possible. Postprocedure dysphagia occurs after operative fundoplication. Dysphagia following the Plicator procedure is also likely to be an associated problem.
COST-EFFECTIVENESS OF ENDOSCOPIC THERAPIES An estimated physician and facility cost and a Current Procedural Terminology code have been developed for the Stretta procedure. The Curon Company mailed information concerning approximate fees for the Stretta procedure in early 2002.20 Physician reimbursement for the procedure is estimated to be $525.53 by Medicare and $830.64 for managed care. Hospital costs were reported
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Table 2. Potential Procedural Problems Associated with Endoscopic Gastroesophageal Reflux Disease Therapies Variable Gastroesophageal junction anatomy
Potential Problems ● Potential injury due to: —Esophageal motility during procedure —Presence of hiatal hernia —Obstructed view during procedure
Treatment duration
● Prolonged procedure time, compared with laparoscopic procedures
Sedation
● Prolonged conscious sedation time ● Need to use general anesthesia
Training
● Need to learn a range of sophisticated techniques ● Relatively short training experience ● Relatively long learning curve
Table 3. Potential Long-Term Problems Associated with Endoscopic Gastroesophageal Reflux Disease Therapies Variable
Potential Problems
Neurologic injury
● Loss of heartburn sensation ● Loss of belching reflex ● Crus impairment ● Loss of endoluminal compliance
Plication efficacy
● Stitches may not hold ● Potential for injury due to depth of tissue penetration ● Need for cautery to secure stitches
Implantation safety
● Foreign body reaction ● Migration of foreign material
Wrap formation
● Instruments may impact ● Need to repeat procedure ● Dysphagia; wrap disruption; too tight
to be $1,804.30 and $2,250, respectively. A recent abstract compared the cost of gastroplication treatment to conventional medical treatment.21 For 142 patients with a small hiatal hernia, preplication medical expenses averaged $3,057 per year. Postplication procedure medical costs decreased to $214 per year, an annual savings of $2,843 per patient. If lowered cost is shown to be maintained for the long term, it will certainly increase the use of this procedure. However, suture disruption and repeat procedures that may be associated with it must be taken into account in any cost analysis. Furthermore, a cost analysis is best conducted once efficacy has been established.22
SUMMARY Endoscopic treatments for GERD have been in clinical use for 2 years, yet only 1 randomized, sham-controlled study, which critically evaluated a single technique, has been reported. The remainder of therapeutic trials have
been open label. Short-term follow-up studies uniformly report improvement in heartburn symptoms and healthrelated quality-of-life scores as well as decreases in the use of antisecretory medications. However, esophageal acid reflux is not normalized following these treatments, and esophagitis is not improved. To date, these endoscopic techniques have been confined to a stratified group of patients who had no or mild esophagitis and only small hiatal hernias. There are many new and developing endoscopic therapies to treat GERD. We feel it is unfortunate that the current FDA-approved endoscopic techniques have been in clinical use for 2 years without appropriate scientific validation of efficacy and long-term effectiveness. It could be tragic if newcomers to the field of endoscopic therapies for GERD are not subjected to more rigorous evaluation of efficacy and safety before they become standard clinical treatments.23 Issues of durability of effect require reasonable periods of follow-up after treatment.
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Therefore, more patients should be studied for longer than 6 months to 2 years. Furthermore, endoscopic GERD therapies should be compared head-to-head with existing medical and surgical therapies to determine their role and effectiveness in treating this disorder. Finally, it is appropriate to insist that endoscopic treatment of GERD should be applicable to all patients with GERD, not a carefully stratified minority. Unless there is rigorous attention to the tenets of scientific validation of endoscopic techniques for GERD treatment, there will remain a cloud of doubt and concern about their role and usefulness in clinical medicine.
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procedure): a randomized, sham-controlled, multicenter clinical trial [abstract]. Gastroenterology. 2002;122:67. Kahrilas PJ. Management of GERD: medical versus surgical. Semin Gastrointest Dis. 2001;12:3–15. Lufullarde T, Watson DI, Jamieson GG, et al. Laparoscopic Nissen fundoplication: five-year results and beyond. Arch Surg. 2001;136:180 –184. Triadafilopoulos G, Debase JK, Nostrant TT, et al. Longterm experience with the Stretta procedure for the treatment of GERD; 6 and 12-month follow-up of the US open label trial. Gastrointest Endosc. 2002;55:149 –156. Rothstein RI, Pohl H, Grave M, et al. Endoscopic gastric plication for the treatment of GERD: two-year follow-up results [abstract]. Am J Gastroenterol. 2001;S36:A107. Haber GB, Marcon NE, Kortan P, et al. A 2-year follow-up of 25 patients undergoing endoluminal gastric plication (ELGP) for gastroesophageal reflux disease (GERD) [abstract]. Gastrointest Endosc. 2001;53:AB116. Lehman GA, Dunne DP, Hiestenk, Dieselman K, Dimberio D. Suturing plication of cardia with Endocinch device: effect of supplemental cautery; a human prospective randomized trial [abstract]. Gastroenterology. 2002;122. Madisch A, Weihs C, Schland M, et al. Impact on healthrelated quality of life (HRQL) in subjects with gastroesophageal reflux disease (GERD): results of a nationwide informing campaign— based on telephone hotline in Germany [abstract]. Gastroenterology. 2002;122:214. Stollman N. GERD: the case for endoluminal treatment. Paper presented at Digestive Diseases Week, May 2002, San Francisco. Noar M, Knight S, Bidlack D. Long-term experience with the Stretta procedure in medically refractory GERD patients: the first 14 months [abstract]. Gastroenterology. 2002;112:4. Filipi CJ. Why endoscopic suturing for GERD is appropriate [letter]. Gastrointest Endosc. 2002;55:300 –301. Stretta Reimbursement Guide. Sunnyvale, CA: Curon Medical; 2002. Raijman I, Ben-Menachem T, Starpoli A, et al. Endoluminal gastroplication (ELGP) improves GERD symptoms in patients with large hiatal hernias [abstract]. Gastroenterology. 2002;122:283. Thiny MT, Shaheen NJ. Is Stretta ready for prime time? Selected summaries. Gastroenterology. 2002;123:643– 644. Hogan WJ. Endoscopic treatments for gastroesophageal reflux disease: not ready for prime time technology. Clin Perspect Gastroenterol. 2002;5:149 –153.
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