Portal de Periódicos da CAPES

The Rise and Fall (and Rise?) of Endoscopic Anti-Reflux Procedures

2006; Elsevier BV; Volume: 131; Issue: 3 Linguagem: Inglês

10.1053/j.gastro.2006.07.030

1528-0012

Nicholas J. Shaheen,

Dysphagia Assessment and Management

See “Endoscopic full-thickness plication for the treatment of GERD: a randomized, sham-controlled trial” by Rothstein R, Filipi CJ, Caca K, et al, on page 704.The report of my death was an exaggeration. —Mark Twain, after reading his own obituary, May, 1897.The role of endoscopic anti-reflux procedures in the treatment of gastroesophageal reflux disease (GERD) remains unclear. Patients and physicians continue to yearn for treatment options that do not involve a lifelong medication requirement or surgical intervention. However, because of the safety and effectiveness of antacid medications, any replacement therapy must meet a high standard before equivalency with medical therapy can be claimed. Additionally, because laparoscopic Nissen fundoplication is a generally safe, often effective procedure that allows repair of any hiatal hernia, as well as augmentation of lower esophageal sphincter tone, it, too, is an attractive option for the appropriately chosen patient. Squeezed between the options of chronic medical therapy, and laparoscopic anti-reflux surgery, sits endoscopic anti-reflux therapy. Beyond patient preferences, the guidelines for who should get what are not well demarcated.On this backdrop, Rothstein et al report in this issue of Gastroenterology a sham-controlled study of the Plicator device (NDO Surgical, Inc, Mansfield, MA).1Rothstein R. Filipi C.J. Caca K. Pruitt R. Mergener K. Torquati A. Haber G. Chen Y. Chang K. Wong D. Deviere J. Pleskow D. Lightdale C. Ades A. Kozarek R. Richards W. Lembo A. Endoscopic full-thickness plication for the treatment of Gastroesophageal Reflux Disease: a randomized, sham-controlled trial.Gastroenterology. 2006; 131: 704-712Google Scholar This device creates a full-thickness plication in the anterior gastric cardia, by retracting a flap of tissue into the “jaws” of the device, which are then closed. A single pledgeted suture is deployed, leaving the 2 serosal surfaces of the tissue firmly apposed. Anyone who has seen this device in action will attest to the fact that the flap created is substantial and that the architecture of the hiatus is quite changed by the procedure.The patients selected for this study had a history of heartburn or regurgitation responsive to and requiring chronic proton pump inhibitor (PPI) therapy, as well as abnormal pH studies. Subjects with large hiatal hernias, as well as those with significant erosive esophagitis, were excluded. The primary outcome variable was a disease-specific health-related quality of life (HRQL) measure, the GERD-HRQL. The investigators demonstrated that symptom scores and medication usage were positively impacted by the procedure. Perhaps most interestingly, they also demonstrate that esophageal acid exposures improved at 3 months in the group treated with Plicator compared with the sham arm (time with pH < 4, 7% vs. 10% at baseline in the plicator group and 10% in sham group; P < .001). The authors conclude that the full-thickness plication more effectively reduced GERD symptoms, PPI use, and acid exposures than sham, and “preliminary data are encouraging that it is a treatment option for patients with mild symptomatic nonerosive GERD who do not wish to remain on acid suppressive medications, and who do not currently wish to undergo a surgical procedure.”This is a seminal study for multiple reasons. The authors provide sham-controlled data for a device that, to date, had only uncontrolled data to support its use. Additionally, the study was rigorously done, with attention to detail not commonly seen in research of this type. For instance, the operators “talked through” the use of the device even for those in the sham arm, so that subjects with some memory of the procedure would be unable to discern their group assignment based on the dialogue in the room. All analysis was intention-to-treat, and outcomes and side effects were documented in minute detail.Beside the methodologic rigor of the study, the results are also notable because they are the first sham-controlled data of an endoscopic anti-reflux device to demonstrate an improvement in objective data compared with sham. Previous sham-controlled studies of 2 devices, the Stretta device (Curon Medical Inc, Fremont, CA)2Corley D.A. Katz P. Wo J.M. Stefan A. Patti M. Rothstein R. Edmundowicz S. Kline M. Mason R. Wolfe M.M. Improvement of gastroesophageal reflux symptoms after radiofrequency energy: a randomized, sham-controlled trial.Gastroenterology. 2003; 125: 668-676Google Scholar and the Enteryx system,3Deviere J. Costamagna G. Neuhaus H. Voderholzer W. Louis H. Tringali A. Marchese M. Fiedler T. Darb-Esfahani P. Schumacher B. Nonresorbable copolymer implantation for gastroesophageal reflux disease: a randomized sham-controlled multicenter trial.Gastroenterology. 2005; 128: 532-540Abstract Full Text Full Text PDF Scopus (118) Google Scholar demonstrated improvement in subjective measures, such as symptom scores, but not in more objective measures, such as esophageal acid exposure. The demonstration of changes in objective measures here is important because all 3 sham-controlled trials demonstrated more adverse events (such as chest pain or shoulder pain) in the treatment group than the sham group. This differential side effect profile almost certainly partially unblinded the study groups as to their allocation—the patients, who had a previous endoscopy, were able to guess their allocation based on side effects of the procedure. If subjects in these studies correctly guessed that they had undergone the intervention, an alternative explanation for the improvement in subjective but not objective measures in the previous 2 studies is placebo response: the subjects receiving the intervention were more likely to report improved symptoms, but in fact, esophageal acid exposures had not been truly altered from baseline. It is comforting in the present study to see subjective and objective measures of reflux traffic together, and this finding strengthens the authors’ claim that the treatment truly was better than sham.Tough Times for Endoscopic Anti-Reflux DevicesThese data are especially interesting in what must be considered tough times for endoscopic anti-reflux devices. As with many innovations, initial enthusiasm for the procedures has been tempered by experience with the devices in practice. Concerns about safety and efficacy have arisen, and the appropriate parameters for patient selection remain unclear. Because the available data on the devices were generally not extensive when they were brought to market, and because long-term data were scarce, much of what we know about durability of the effects has come after the devices were disseminated into clinical practice. Additionally, new information regarding the safety of these devices outside of research protocols has become available.We have seen the voluntary removal of 1 device (Enteryx; Boston Scientific, Inc, Natick, MA), and the discontinuation of marketing of 2 others (Wilson-Cook’s ESD endoscopic sewing device (Cook Medical, Inc, Bloomington, IN) and Medtronic’s Gatekeeper (Medtronic Inc, Minneapolis, MN)). Three others, Curon’s Stretta, Bard’s Endo-Cinch (Davol Inc, Cranston, RI), and the Plicator, continue to be marketed. However, Curon’s first quarter report for 2006 notes sales to be down 37% from first quarter of 2005, and reports the sales of only 5 control modules and 316 catheters worldwide in the first quarter of 2006 (available: www.curonmedical.com/Company_Info/Media/may_15b_2006.html). Endo-Cinch has also faced challenges. Recent publications raise concerns regarding durability. Publications report up to a 90% loss of sutures at 1 year.4Schiefke I. Zabel-Langhennig A. Neumann S. Feisthammel J. Moessner J. Caca K. Long term failure of endoscopic gastroplication (EndoCinch).Gut. 2005; 54: 752-758Google Scholar, 5Abou-Rebyeh H. Hoepffner N. Rosch T. Osmanoglou E. Haneke J.H. Hintze R.E. Wiedenmann B. Monnikes H. Long-term failure of endoscopic suturing in the treatment of gastroesophageal reflux: a prospective follow-up study.Endoscopy. 2005; 37: 213-216Google ScholarConcurrent with these evolving data about endoscopic anti-reflux procedures, there have been changes in the academic community’s interest in these devices. In assessing abstracts accepted to DDW for 2003–2006, there is the suggestion that interest in research of these devices may have plateaued and is decreasing. Using the searchable CD-ROM abstract databases from 2003 to 2006, we compiled a list of abstracts assessing endoscopic anti-reflux procedures in either animal models or humans. We used the following search terms in either the title or abstract: endoscopic suturing, endoscopic sewing, plication, gastroplication, ELGP, Endocinch, Plicator, His-Wiz, full-thickness, ESD, Enteryx, copolymer, Gatekeeper, hydrogel, Stretta, radiofrequency, radio frequency, and radio-frequency. Decision analyses, cost-effectiveness analyses, secondary data analysis, and nonesophageal applications of the technologies were excluded. Abstracts retrieved were reviewed and classified into the following categories: endoscopic plicators, Stretta research, and Enteryx research.Figure 1 demonstrates the number of accepted abstracts on endoscopic anti-reflux procedures from 2003–2006. After 3 years with 27–42 abstracts per year, the number of pertinent abstracts fell to 16 in 2006, fewer than half that of the previous year. Abstracts reporting results from plicating devices, Stretta and Enteryx were all fewer in number than the previous year.To be sure, these data are hardly a comprehensive snapshot of research in the area. There are other scientific meetings to present such data. Additionally, the lack of research presented at DDW does not necessarily mean that this research was not pursued—it may just mean that the reviewers grading the abstracts did not feel that the submitted abstracts on the topic merited presentation. Even with these caveats, the data suggest that interest in clinical research in these endoscopic anti-reflux procedures may be waning.What Has Hindered Acceptance of Endoscopic Anti-Reflux Devices?Multiple authors, myself included, have previously suggested that data in support of the endoscopic anti-reflux devices were not sufficient to merit their routine use outside of the research setting.6Hogan W.J. Clinical trials evaluating endoscopic GERD treatments: is it time for a moratorium on the clinical use of these procedures?.Am J Gastroenterol. 2006; 101: 437-439Google Scholar, 7Shaheen N.J. Raising the bar in studies of endoscopic anti-reflux procedures.Gastroenterology. 2005; 128: 779-782Google Scholar, 8Lee T.J. Kahrilas P.J. Endoluminal therapy for gastroesophageal reflux disease: is the evidence for efficacy any stronger?.Curr Gastroenterol Rep. 2005; 7: 202-206Google Scholar, 9Kahrilas P.J. Lee T.J. Gatekeeper reflux repair system; a mechanistic hypothesis.Gut. 2005; 54: 179-180Google Scholar While a detailed description of the concerns regarding these devices can be found in the publications referenced herein, in short, the argument against the devices in general is as follows: 1Safety: Deaths have been reported in association with Stretta and Enteryx in the FDA’s Manufacturer and User Facility Device Experience Database (MAUDE; available: www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/search.cfm?searchoptions=1). The present study1Rothstein R. Filipi C.J. Caca K. Pruitt R. Mergener K. Torquati A. Haber G. Chen Y. Chang K. Wong D. Deviere J. Pleskow D. Lightdale C. Ades A. Kozarek R. Richards W. Lembo A. Endoscopic full-thickness plication for the treatment of Gastroesophageal Reflux Disease: a randomized, sham-controlled trial.Gastroenterology. 2006; 131: 704-712Google Scholar reports that 4 of 78 (5.1%) subjects in the treatment arm required hospitalization after the procedure, and that 1 underwent laparotomy and removal of the plication after adhesions were found between the gastric serosa and the left hemidiaphragm. It is unclear, especially in the PPI-responsive patient, whether the benefits of the procedures outweigh the risks.2Efficacy: None of the devices has been shown to be highly efficacious in erosive disease or among those with hiatal hernias. Sham-controlled studies of Stretta and Enteryx, as noted, demonstrated improvements in symptom scores but not esophageal acid exposures.2Corley D.A. Katz P. Wo J.M. Stefan A. Patti M. Rothstein R. Edmundowicz S. Kline M. Mason R. Wolfe M.M. Improvement of gastroesophageal reflux symptoms after radiofrequency energy: a randomized, sham-controlled trial.Gastroenterology. 2003; 125: 668-676Google Scholar, 3Deviere J. Costamagna G. Neuhaus H. Voderholzer W. Louis H. Tringali A. Marchese M. Fiedler T. Darb-Esfahani P. Schumacher B. Nonresorbable copolymer implantation for gastroesophageal reflux disease: a randomized sham-controlled multicenter trial.Gastroenterology. 2005; 128: 532-540Abstract Full Text Full Text PDF Scopus (118) Google Scholar No randomized data compare any of the devices to PPI therapy or surgery. Given that the devices are being marketed as an alternative to medical therapy, some evidence that they are better than, or at least as good as, medical therapy is essential.3Durability: Long-term data with Endocinch and ESD suggest issues with suture patency, as noted.4Schiefke I. Zabel-Langhennig A. Neumann S. Feisthammel J. Moessner J. Caca K. Long term failure of endoscopic gastroplication (EndoCinch).Gut. 2005; 54: 752-758Google Scholar, 5Abou-Rebyeh H. Hoepffner N. Rosch T. Osmanoglou E. Haneke J.H. Hintze R.E. Wiedenmann B. Monnikes H. Long-term failure of endoscopic suturing in the treatment of gastroesophageal reflux: a prospective follow-up study.Endoscopy. 2005; 37: 213-216Google Scholar, 10Schiefke I. Neumann S. Zabel-Langhennig A. Moessner J. Caca K. Use of an endoscopic suturing device (the “ESD”) to treat patients with gastroesophageal reflux disease, after unsuccessful EndoCinch endoluminal gastroplication: another failure.Endoscopy. 2005; 37: 700-705Google Scholar These issues may be averted with full-thickness plication,11Pleskow D. Rothstein R. Lo S. Hawes R. Kozarek R. Haber G. Gostout C. Lembo A. Endoscopic full-thickness plication for the treatment of GERD: 12-month follow-up for the North American open-label trial.Gastrointest Endosc. 2005; 61: 643-649Google Scholar but data are limited. Some data suggest long-term durability of Stretta,12Torquati A. Houston H.L. Kaiser J. Holzman M.D. Richards W.O. Long-term follow-up study of the Stretta procedure for the treatment of gastroesophageal reflux disease.Surg Endosc. 2004; 18: 1475-1479Google Scholar whereas others do not.13Holloway R.H. Ryan R.J. Sivanesan S. Tam W.C. Schoeman M.N. Dent J. Long-term 5-year follow-up of the Stretta procedure for the treatment of reflux disease.Gastroenterology. 2006; 130: W1105Google ScholarKnowing What We Don’t KnowCan an endoscopic anti-reflux device earn a place in the treatment algorithm for GERD? Although it is tempting to say that the problems noted above are insurmountable, it is never wise to bet against the evolution of technology. What data would aid in the effort to place a device in our clinical “tool box” for GERD? What essential data do we not know about the devices?Some head-to-head data with alternative treatment measures would be helpful. Sham-controlled trials like the present study are important because they provide proof of principle—they demonstrate that the intervention is better than no intervention. However, clinically, in the subject with PPI-responsive GERD, we are never choosing between an endoscopic anti-reflux device and nothing. The clinical decision we are generally facing is whether to use the endoscopic anti-reflux device, continue medical therapy, or consider surgery, and the presently available data are not sufficient to allow us to understand the utility of endoscopic interventions in that setting. To date, no study has truly compared the results of PPI therapy to endoscopic anti-reflux devices. The present study does note that the symptom profile of subjects in the Plicator arm was similar to that of the subjects when on PPI therapy prior to randomization. These data, although interesting, cannot be used as proof that the 2 treatments are equivalent. Only a true randomized study, with one half of the patients getting a sham procedure and PPIs, and the other half getting a real procedure and placebos, would answer this question.Also, longer term and more complete data on durability and complications of the procedures are necessary. It is difficult to understand the long-term utility of the devices based on 6- or 12-month data. Given the issues with durability brought to light by previous devices, the Plicator and future devices will face intense questions of durability. The need to demonstrate durable effect is especially challenging to small companies with a single product in its pipeline, because the immediate commercial need to get the product to market and show profitability is at odds with the scientific demands of sufficient follow-up to provide data regarding long-term effectiveness. The reporting of complications, too, needs improvement. The voluntary reporting system for complications with these devices is inadequate. Given that some devices have reached the market with little data available, it is quite possible that complications might not become evident until it is widely disseminated. If such a scenario occurs, many patients may be hurt who could have been protected if either the manufacturer or the government kept a systematic, publicly accessible record of complications with the devices.The present study adds fuel to a fire that was dim. However, we are still left with uncertainty as to where to position endoscopic anti-reflux procedures in the patient with GERD. Given the lack of data, it is premature to claim superiority, or even equivalency, of these devices to best medical or surgical therapy for GERD. Until the questions regarding safety, efficacy, and durability outlined above become clearer, the routine use of these devices in PPI-responsive patients, outside the realm of clinical studies cannot be recommended. See “Endoscopic full-thickness plication for the treatment of GERD: a randomized, sham-controlled trial” by Rothstein R, Filipi CJ, Caca K, et al, on page 704. See “Endoscopic full-thickness plication for the treatment of GERD: a randomized, sham-controlled trial” by Rothstein R, Filipi CJ, Caca K, et al, on page 704. See “Endoscopic full-thickness plication for the treatment of GERD: a randomized, sham-controlled trial” by Rothstein R, Filipi CJ, Caca K, et al, on page 704. The report of my death was an exaggeration. —Mark Twain, after reading his own obituary, May, 1897. The role of endoscopic anti-reflux procedures in the treatment of gastroesophageal reflux disease (GERD) remains unclear. Patients and physicians continue to yearn for treatment options that do not involve a lifelong medication requirement or surgical intervention. However, because of the safety and effectiveness of antacid medications, any replacement therapy must meet a high standard before equivalency with medical therapy can be claimed. Additionally, because laparoscopic Nissen fundoplication is a generally safe, often effective procedure that allows repair of any hiatal hernia, as well as augmentation of lower esophageal sphincter tone, it, too, is an attractive option for the appropriately chosen patient. Squeezed between the options of chronic medical therapy, and laparoscopic anti-reflux surgery, sits endoscopic anti-reflux therapy. Beyond patient preferences, the guidelines for who should get what are not well demarcated. On this backdrop, Rothstein et al report in this issue of Gastroenterology a sham-controlled study of the Plicator device (NDO Surgical, Inc, Mansfield, MA).1Rothstein R. Filipi C.J. Caca K. Pruitt R. Mergener K. Torquati A. Haber G. Chen Y. Chang K. Wong D. Deviere J. Pleskow D. Lightdale C. Ades A. Kozarek R. Richards W. Lembo A. Endoscopic full-thickness plication for the treatment of Gastroesophageal Reflux Disease: a randomized, sham-controlled trial.Gastroenterology. 2006; 131: 704-712Google Scholar This device creates a full-thickness plication in the anterior gastric cardia, by retracting a flap of tissue into the “jaws” of the device, which are then closed. A single pledgeted suture is deployed, leaving the 2 serosal surfaces of the tissue firmly apposed. Anyone who has seen this device in action will attest to the fact that the flap created is substantial and that the architecture of the hiatus is quite changed by the procedure. The patients selected for this study had a history of heartburn or regurgitation responsive to and requiring chronic proton pump inhibitor (PPI) therapy, as well as abnormal pH studies. Subjects with large hiatal hernias, as well as those with significant erosive esophagitis, were excluded. The primary outcome variable was a disease-specific health-related quality of life (HRQL) measure, the GERD-HRQL. The investigators demonstrated that symptom scores and medication usage were positively impacted by the procedure. Perhaps most interestingly, they also demonstrate that esophageal acid exposures improved at 3 months in the group treated with Plicator compared with the sham arm (time with pH < 4, 7% vs. 10% at baseline in the plicator group and 10% in sham group; P < .001). The authors conclude that the full-thickness plication more effectively reduced GERD symptoms, PPI use, and acid exposures than sham, and “preliminary data are encouraging that it is a treatment option for patients with mild symptomatic nonerosive GERD who do not wish to remain on acid suppressive medications, and who do not currently wish to undergo a surgical procedure.” This is a seminal study for multiple reasons. The authors provide sham-controlled data for a device that, to date, had only uncontrolled data to support its use. Additionally, the study was rigorously done, with attention to detail not commonly seen in research of this type. For instance, the operators “talked through” the use of the device even for those in the sham arm, so that subjects with some memory of the procedure would be unable to discern their group assignment based on the dialogue in the room. All analysis was intention-to-treat, and outcomes and side effects were documented in minute detail. Beside the methodologic rigor of the study, the results are also notable because they are the first sham-controlled data of an endoscopic anti-reflux device to demonstrate an improvement in objective data compared with sham. Previous sham-controlled studies of 2 devices, the Stretta device (Curon Medical Inc, Fremont, CA)2Corley D.A. Katz P. Wo J.M. Stefan A. Patti M. Rothstein R. Edmundowicz S. Kline M. Mason R. Wolfe M.M. Improvement of gastroesophageal reflux symptoms after radiofrequency energy: a randomized, sham-controlled trial.Gastroenterology. 2003; 125: 668-676Google Scholar and the Enteryx system,3Deviere J. Costamagna G. Neuhaus H. Voderholzer W. Louis H. Tringali A. Marchese M. Fiedler T. Darb-Esfahani P. Schumacher B. Nonresorbable copolymer implantation for gastroesophageal reflux disease: a randomized sham-controlled multicenter trial.Gastroenterology. 2005; 128: 532-540Abstract Full Text Full Text PDF Scopus (118) Google Scholar demonstrated improvement in subjective measures, such as symptom scores, but not in more objective measures, such as esophageal acid exposure. The demonstration of changes in objective measures here is important because all 3 sham-controlled trials demonstrated more adverse events (such as chest pain or shoulder pain) in the treatment group than the sham group. This differential side effect profile almost certainly partially unblinded the study groups as to their allocation—the patients, who had a previous endoscopy, were able to guess their allocation based on side effects of the procedure. If subjects in these studies correctly guessed that they had undergone the intervention, an alternative explanation for the improvement in subjective but not objective measures in the previous 2 studies is placebo response: the subjects receiving the intervention were more likely to report improved symptoms, but in fact, esophageal acid exposures had not been truly altered from baseline. It is comforting in the present study to see subjective and objective measures of reflux traffic together, and this finding strengthens the authors’ claim that the treatment truly was better than sham. Tough Times for Endoscopic Anti-Reflux DevicesThese data are especially interesting in what must be considered tough times for endoscopic anti-reflux devices. As with many innovations, initial enthusiasm for the procedures has been tempered by experience with the devices in practice. Concerns about safety and efficacy have arisen, and the appropriate parameters for patient selection remain unclear. Because the available data on the devices were generally not extensive when they were brought to market, and because long-term data were scarce, much of what we know about durability of the effects has come after the devices were disseminated into clinical practice. Additionally, new information regarding the safety of these devices outside of research protocols has become available.We have seen the voluntary removal of 1 device (Enteryx; Boston Scientific, Inc, Natick, MA), and the discontinuation of marketing of 2 others (Wilson-Cook’s ESD endoscopic sewing device (Cook Medical, Inc, Bloomington, IN) and Medtronic’s Gatekeeper (Medtronic Inc, Minneapolis, MN)). Three others, Curon’s Stretta, Bard’s Endo-Cinch (Davol Inc, Cranston, RI), and the Plicator, continue to be marketed. However, Curon’s first quarter report for 2006 notes sales to be down 37% from first quarter of 2005, and reports the sales of only 5 control modules and 316 catheters worldwide in the first quarter of 2006 (available: www.curonmedical.com/Company_Info/Media/may_15b_2006.html). Endo-Cinch has also faced challenges. Recent publications raise concerns regarding durability. Publications report up to a 90% loss of sutures at 1 year.4Schiefke I. Zabel-Langhennig A. Neumann S. Feisthammel J. Moessner J. Caca K. Long term failure of endoscopic gastroplication (EndoCinch).Gut. 2005; 54: 752-758Google Scholar, 5Abou-Rebyeh H. Hoepffner N. Rosch T. Osmanoglou E. Haneke J.H. Hintze R.E. Wiedenmann B. Monnikes H. Long-term failure of endoscopic suturing in the treatment of gastroesophageal reflux: a prospective follow-up study.Endoscopy. 2005; 37: 213-216Google ScholarConcurrent with these evolving data about endoscopic anti-reflux procedures, there have been changes in the academic community’s interest in these devices. In assessing abstracts accepted to DDW for 2003–2006, there is the suggestion that interest in research of these devices may have plateaued and is decreasing. Using the searchable CD-ROM abstract databases from 2003 to 2006, we compiled a list of abstracts assessing endoscopic anti-reflux procedures in either animal models or humans. We used the following search terms in either the title or abstract: endoscopic suturing, endoscopic sewing, plication, gastroplication, ELGP, Endocinch, Plicator, His-Wiz, full-thickness, ESD, Enteryx, copolymer, Gatekeeper, hydrogel, Stretta, radiofrequency, radio frequency, and radio-frequency. Decision analyses, cost-effectiveness analyses, secondary data analysis, and nonesophageal applications of the technologies were excluded. Abstracts retrieved were reviewed and classified into the following categories: endoscopic plicators, Stretta research, and Enteryx research.Figure 1 demonstrates the number of accepted abstracts on endoscopic anti-reflux procedures from 2003–2006. After 3 years with 27–42 abstracts per year, the number of pertinent abstracts fell to 16 in 2006, fewer than half that of the previous year. Abstracts reporting results from plicating devices, Stretta and Enteryx were all fewer in number than the previous year.To be sure, these data are hardly a comprehensive snapshot of research in the area. There are other scientific meetings to present such data. Additionally, the lack of research presented at DDW does not necessarily mean that this research was not pursued—it may just mean that the reviewers grading the abstracts did not feel that the submitted abstracts on the topic merited presentation. Even with these caveats, the data suggest that interest in clinical research in these endoscopic anti-reflux procedures may be waning. These data are especially interesting in what must be considered tough times for endoscopic anti-reflux devices. As with many innovations, initial enthusiasm for the procedures has been tempered by experience with the devices in practice. Concerns about safety and efficacy have arisen, and the appropriate parameters for patient selection remain unclear. Because the available data on the devices were generally not extensive when they were brought to market, and because long-term data were scarce, much of what we know about durability of the effects has come after the devices were disseminated into clinical practice. Additionally, new information regarding the safety of these devices outside of research protocols has become available. We have seen the voluntary removal of 1 device (Enteryx; Boston Scientific, Inc, Natick, MA), and the discontinuation of marketing of 2 others (Wilson-Cook’s ESD endoscopic sewing device (Cook Medical, Inc, Bloomington, IN) and Medtronic’s Gatekeeper (Medtronic Inc, Minneapolis, MN)). Three others, Curon’s Stretta, Bard’s Endo-Cinch (Davol Inc, Cranston, RI), and the Plicator, continue to be marketed. However, Curon’s first quarter report for 2006 notes sales to be down 37% from first quarter of 2005, and reports the sales of only 5 control modules and 316 catheters worldwide in the first quarter of 2006 (available: www.curonmedical.com/Company_Info/Media/may_15b_2006.html). Endo-Cinch has also faced challenges. Recent publications raise concerns regarding durability. Publications report up to a 90% loss of sutures at 1 year.4Schiefke I. Zabel-Langhennig A. Neumann S. Feisthammel J. Moessner J. Caca K. Long term failure of endoscopic gastroplication (EndoCinch).Gut. 2005; 54: 752-758Google Scholar, 5Abou-Rebyeh H. Hoepffner N. Rosch T. Osmanoglou E. Haneke J.H. Hintze R.E. Wiedenmann B. Monnikes H. Long-term failure of endoscopic suturing in the treatment of gastroesophageal reflux: a prospective follow-up study.Endoscopy. 2005; 37: 213-216Google Scholar Concurrent with these evolving data about endoscopic anti-reflux procedures, there have been changes in the academic community’s interest in these devices. In assessing abstracts accepted to DDW for 2003–2006, there is the suggestion that interest in research of these devices may have plateaued and is decreasing. Using the searchable CD-ROM abstract databases from 2003 to 2006, we compiled a list of abstracts assessing endoscopic anti-reflux procedures in either animal models or humans. We used the following search terms in either the title or abstract: endoscopic suturing, endoscopic sewing, plication, gastroplication, ELGP, Endocinch, Plicator, His-Wiz, full-thickness, ESD, Enteryx, copolymer, Gatekeeper, hydrogel, Stretta, radiofrequency, radio frequency, and radio-frequency. Decision analyses, cost-effectiveness analyses, secondary data analysis, and nonesophageal applications of the technologies were excluded. Abstracts retrieved were reviewed and classified into the following categories: endoscopic plicators, Stretta research, and Enteryx research. Figure 1 demonstrates the number of accepted abstracts on endoscopic anti-reflux procedures from 2003–2006. After 3 years with 27–42 abstracts per year, the number of pertinent abstracts fell to 16 in 2006, fewer than half that of the previous year. Abstracts reporting results from plicating devices, Stretta and Enteryx were all fewer in number than the previous year. To be sure, these data are hardly a comprehensive snapshot of research in the area. There are other scientific meetings to present such data. Additionally, the lack of research presented at DDW does not necessarily mean that this research was not pursued—it may just mean that the reviewers grading the abstracts did not feel that the submitted abstracts on the topic merited presentation. Even with these caveats, the data suggest that interest in clinical research in these endoscopic anti-reflux procedures may be waning. What Has Hindered Acceptance of Endoscopic Anti-Reflux Devices?Multiple authors, myself included, have previously suggested that data in support of the endoscopic anti-reflux devices were not sufficient to merit their routine use outside of the research setting.6Hogan W.J. Clinical trials evaluating endoscopic GERD treatments: is it time for a moratorium on the clinical use of these procedures?.Am J Gastroenterol. 2006; 101: 437-439Google Scholar, 7Shaheen N.J. Raising the bar in studies of endoscopic anti-reflux procedures.Gastroenterology. 2005; 128: 779-782Google Scholar, 8Lee T.J. Kahrilas P.J. Endoluminal therapy for gastroesophageal reflux disease: is the evidence for efficacy any stronger?.Curr Gastroenterol Rep. 2005; 7: 202-206Google Scholar, 9Kahrilas P.J. Lee T.J. Gatekeeper reflux repair system; a mechanistic hypothesis.Gut. 2005; 54: 179-180Google Scholar While a detailed description of the concerns regarding these devices can be found in the publications referenced herein, in short, the argument against the devices in general is as follows: 1Safety: Deaths have been reported in association with Stretta and Enteryx in the FDA’s Manufacturer and User Facility Device Experience Database (MAUDE; available: www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/search.cfm?searchoptions=1). The present study1Rothstein R. Filipi C.J. Caca K. Pruitt R. Mergener K. Torquati A. Haber G. Chen Y. Chang K. Wong D. Deviere J. Pleskow D. Lightdale C. Ades A. Kozarek R. Richards W. Lembo A. Endoscopic full-thickness plication for the treatment of Gastroesophageal Reflux Disease: a randomized, sham-controlled trial.Gastroenterology. 2006; 131: 704-712Google Scholar reports that 4 of 78 (5.1%) subjects in the treatment arm required hospitalization after the procedure, and that 1 underwent laparotomy and removal of the plication after adhesions were found between the gastric serosa and the left hemidiaphragm. It is unclear, especially in the PPI-responsive patient, whether the benefits of the procedures outweigh the risks.2Efficacy: None of the devices has been shown to be highly efficacious in erosive disease or among those with hiatal hernias. Sham-controlled studies of Stretta and Enteryx, as noted, demonstrated improvements in symptom scores but not esophageal acid exposures.2Corley D.A. Katz P. Wo J.M. Stefan A. Patti M. Rothstein R. Edmundowicz S. Kline M. Mason R. Wolfe M.M. Improvement of gastroesophageal reflux symptoms after radiofrequency energy: a randomized, sham-controlled trial.Gastroenterology. 2003; 125: 668-676Google Scholar, 3Deviere J. Costamagna G. Neuhaus H. Voderholzer W. Louis H. Tringali A. Marchese M. Fiedler T. Darb-Esfahani P. Schumacher B. Nonresorbable copolymer implantation for gastroesophageal reflux disease: a randomized sham-controlled multicenter trial.Gastroenterology. 2005; 128: 532-540Abstract Full Text Full Text PDF Scopus (118) Google Scholar No randomized data compare any of the devices to PPI therapy or surgery. Given that the devices are being marketed as an alternative to medical therapy, some evidence that they are better than, or at least as good as, medical therapy is essential.3Durability: Long-term data with Endocinch and ESD suggest issues with suture patency, as noted.4Schiefke I. Zabel-Langhennig A. Neumann S. Feisthammel J. Moessner J. Caca K. Long term failure of endoscopic gastroplication (EndoCinch).Gut. 2005; 54: 752-758Google Scholar, 5Abou-Rebyeh H. Hoepffner N. Rosch T. Osmanoglou E. Haneke J.H. Hintze R.E. Wiedenmann B. Monnikes H. Long-term failure of endoscopic suturing in the treatment of gastroesophageal reflux: a prospective follow-up study.Endoscopy. 2005; 37: 213-216Google Scholar, 10Schiefke I. Neumann S. Zabel-Langhennig A. Moessner J. Caca K. Use of an endoscopic suturing device (the “ESD”) to treat patients with gastroesophageal reflux disease, after unsuccessful EndoCinch endoluminal gastroplication: another failure.Endoscopy. 2005; 37: 700-705Google Scholar These issues may be averted with full-thickness plication,11Pleskow D. Rothstein R. Lo S. Hawes R. Kozarek R. Haber G. Gostout C. Lembo A. Endoscopic full-thickness plication for the treatment of GERD: 12-month follow-up for the North American open-label trial.Gastrointest Endosc. 2005; 61: 643-649Google Scholar but data are limited. Some data suggest long-term durability of Stretta,12Torquati A. Houston H.L. Kaiser J. Holzman M.D. Richards W.O. Long-term follow-up study of the Stretta procedure for the treatment of gastroesophageal reflux disease.Surg Endosc. 2004; 18: 1475-1479Google Scholar whereas others do not.13Holloway R.H. Ryan R.J. Sivanesan S. Tam W.C. Schoeman M.N. Dent J. Long-term 5-year follow-up of the Stretta procedure for the treatment of reflux disease.Gastroenterology. 2006; 130: W1105Google Scholar Multiple authors, myself included, have previously suggested that data in support of the endoscopic anti-reflux devices were not sufficient to merit their routine use outside of the research setting.6Hogan W.J. Clinical trials evaluating endoscopic GERD treatments: is it time for a moratorium on the clinical use of these procedures?.Am J Gastroenterol. 2006; 101: 437-439Google Scholar, 7Shaheen N.J. Raising the bar in studies of endoscopic anti-reflux procedures.Gastroenterology. 2005; 128: 779-782Google Scholar, 8Lee T.J. Kahrilas P.J. Endoluminal therapy for gastroesophageal reflux disease: is the evidence for efficacy any stronger?.Curr Gastroenterol Rep. 2005; 7: 202-206Google Scholar, 9Kahrilas P.J. Lee T.J. Gatekeeper reflux repair system; a mechanistic hypothesis.Gut. 2005; 54: 179-180Google Scholar While a detailed description of the concerns regarding these devices can be found in the publications referenced herein, in short, the argument against the devices in general is as follows: 1Safety: Deaths have been reported in association with Stretta and Enteryx in the FDA’s Manufacturer and User Facility Device Experience Database (MAUDE; available: www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/search.cfm?searchoptions=1). The present study1Rothstein R. Filipi C.J. Caca K. Pruitt R. Mergener K. Torquati A. Haber G. Chen Y. Chang K. Wong D. Deviere J. Pleskow D. Lightdale C. Ades A. Kozarek R. Richards W. Lembo A. Endoscopic full-thickness plication for the treatment of Gastroesophageal Reflux Disease: a randomized, sham-controlled trial.Gastroenterology. 2006; 131: 704-712Google Scholar reports that 4 of 78 (5.1%) subjects in the treatment arm required hospitalization after the procedure, and that 1 underwent laparotomy and removal of the plication after adhesions were found between the gastric serosa and the left hemidiaphragm. It is unclear, especially in the PPI-responsive patient, whether the benefits of the procedures outweigh the risks.2Efficacy: None of the devices has been shown to be highly efficacious in erosive disease or among those with hiatal hernias. Sham-controlled studies of Stretta and Enteryx, as noted, demonstrated improvements in symptom scores but not esophageal acid exposures.2Corley D.A. Katz P. Wo J.M. Stefan A. Patti M. Rothstein R. Edmundowicz S. Kline M. Mason R. Wolfe M.M. Improvement of gastroesophageal reflux symptoms after radiofrequency energy: a randomized, sham-controlled trial.Gastroenterology. 2003; 125: 668-676Google Scholar, 3Deviere J. Costamagna G. Neuhaus H. Voderholzer W. Louis H. Tringali A. Marchese M. Fiedler T. Darb-Esfahani P. Schumacher B. Nonresorbable copolymer implantation for gastroesophageal reflux disease: a randomized sham-controlled multicenter trial.Gastroenterology. 2005; 128: 532-540Abstract Full Text Full Text PDF Scopus (118) Google Scholar No randomized data compare any of the devices to PPI therapy or surgery. Given that the devices are being marketed as an alternative to medical therapy, some evidence that they are better than, or at least as good as, medical therapy is essential.3Durability: Long-term data with Endocinch and ESD suggest issues with suture patency, as noted.4Schiefke I. Zabel-Langhennig A. Neumann S. Feisthammel J. Moessner J. Caca K. Long term failure of endoscopic gastroplication (EndoCinch).Gut. 2005; 54: 752-758Google Scholar, 5Abou-Rebyeh H. Hoepffner N. Rosch T. Osmanoglou E. Haneke J.H. Hintze R.E. Wiedenmann B. Monnikes H. Long-term failure of endoscopic suturing in the treatment of gastroesophageal reflux: a prospective follow-up study.Endoscopy. 2005; 37: 213-216Google Scholar, 10Schiefke I. Neumann S. Zabel-Langhennig A. Moessner J. Caca K. Use of an endoscopic suturing device (the “ESD”) to treat patients with gastroesophageal reflux disease, after unsuccessful EndoCinch endoluminal gastroplication: another failure.Endoscopy. 2005; 37: 700-705Google Scholar These issues may be averted with full-thickness plication,11Pleskow D. Rothstein R. Lo S. Hawes R. Kozarek R. Haber G. Gostout C. Lembo A. Endoscopic full-thickness plication for the treatment of GERD: 12-month follow-up for the North American open-label trial.Gastrointest Endosc. 2005; 61: 643-649Google Scholar but data are limited. Some data suggest long-term durability of Stretta,12Torquati A. Houston H.L. Kaiser J. Holzman M.D. Richards W.O. Long-term follow-up study of the Stretta procedure for the treatment of gastroesophageal reflux disease.Surg Endosc. 2004; 18: 1475-1479Google Scholar whereas others do not.13Holloway R.H. Ryan R.J. Sivanesan S. Tam W.C. Schoeman M.N. Dent J. Long-term 5-year follow-up of the Stretta procedure for the treatment of reflux disease.Gastroenterology. 2006; 130: W1105Google Scholar Knowing What We Don’t KnowCan an endoscopic anti-reflux device earn a place in the treatment algorithm for GERD? Although it is tempting to say that the problems noted above are insurmountable, it is never wise to bet against the evolution of technology. What data would aid in the effort to place a device in our clinical “tool box” for GERD? What essential data do we not know about the devices?Some head-to-head data with alternative treatment measures would be helpful. Sham-controlled trials like the present study are important because they provide proof of principle—they demonstrate that the intervention is better than no intervention. However, clinically, in the subject with PPI-responsive GERD, we are never choosing between an endoscopic anti-reflux device and nothing. The clinical decision we are generally facing is whether to use the endoscopic anti-reflux device, continue medical therapy, or consider surgery, and the presently available data are not sufficient to allow us to understand the utility of endoscopic interventions in that setting. To date, no study has truly compared the results of PPI therapy to endoscopic anti-reflux devices. The present study does note that the symptom profile of subjects in the Plicator arm was similar to that of the subjects when on PPI therapy prior to randomization. These data, although interesting, cannot be used as proof that the 2 treatments are equivalent. Only a true randomized study, with one half of the patients getting a sham procedure and PPIs, and the other half getting a real procedure and placebos, would answer this question.Also, longer term and more complete data on durability and complications of the procedures are necessary. It is difficult to understand the long-term utility of the devices based on 6- or 12-month data. Given the issues with durability brought to light by previous devices, the Plicator and future devices will face intense questions of durability. The need to demonstrate durable effect is especially challenging to small companies with a single product in its pipeline, because the immediate commercial need to get the product to market and show profitability is at odds with the scientific demands of sufficient follow-up to provide data regarding long-term effectiveness. The reporting of complications, too, needs improvement. The voluntary reporting system for complications with these devices is inadequate. Given that some devices have reached the market with little data available, it is quite possible that complications might not become evident until it is widely disseminated. If such a scenario occurs, many patients may be hurt who could have been protected if either the manufacturer or the government kept a systematic, publicly accessible record of complications with the devices.The present study adds fuel to a fire that was dim. However, we are still left with uncertainty as to where to position endoscopic anti-reflux procedures in the patient with GERD. Given the lack of data, it is premature to claim superiority, or even equivalency, of these devices to best medical or surgical therapy for GERD. Until the questions regarding safety, efficacy, and durability outlined above become clearer, the routine use of these devices in PPI-responsive patients, outside the realm of clinical studies cannot be recommended. Can an endoscopic anti-reflux device earn a place in the treatment algorithm for GERD? Although it is tempting to say that the problems noted above are insurmountable, it is never wise to bet against the evolution of technology. What data would aid in the effort to place a device in our clinical “tool box” for GERD? What essential data do we not know about the devices? Some head-to-head data with alternative treatment measures would be helpful. Sham-controlled trials like the present study are important because they provide proof of principle—they demonstrate that the intervention is better than no intervention. However, clinically, in the subject with PPI-responsive GERD, we are never choosing between an endoscopic anti-reflux device and nothing. The clinical decision we are generally facing is whether to use the endoscopic anti-reflux device, continue medical therapy, or consider surgery, and the presently available data are not sufficient to allow us to understand the utility of endoscopic interventions in that setting. To date, no study has truly compared the results of PPI therapy to endoscopic anti-reflux devices. The present study does note that the symptom profile of subjects in the Plicator arm was similar to that of the subjects when on PPI therapy prior to randomization. These data, although interesting, cannot be used as proof that the 2 treatments are equivalent. Only a true randomized study, with one half of the patients getting a sham procedure and PPIs, and the other half getting a real procedure and placebos, would answer this question. Also, longer term and more complete data on durability and complications of the procedures are necessary. It is difficult to understand the long-term utility of the devices based on 6- or 12-month data. Given the issues with durability brought to light by previous devices, the Plicator and future devices will face intense questions of durability. The need to demonstrate durable effect is especially challenging to small companies with a single product in its pipeline, because the immediate commercial need to get the product to market and show profitability is at odds with the scientific demands of sufficient follow-up to provide data regarding long-term effectiveness. The reporting of complications, too, needs improvement. The voluntary reporting system for complications with these devices is inadequate. Given that some devices have reached the market with little data available, it is quite possible that complications might not become evident until it is widely disseminated. If such a scenario occurs, many patients may be hurt who could have been protected if either the manufacturer or the government kept a systematic, publicly accessible record of complications with the devices. The present study adds fuel to a fire that was dim. However, we are still left with uncertainty as to where to position endoscopic anti-reflux procedures in the patient with GERD. Given the lack of data, it is premature to claim superiority, or even equivalency, of these devices to best medical or surgical therapy for GERD. Until the questions regarding safety, efficacy, and durability outlined above become clearer, the routine use of these devices in PPI-responsive patients, outside the realm of clinical studies cannot be recommended.