Review Article: Endoscopic Antireflux Procedures - An Unfulfilled Promise?
Review Article: Endoscopic Antireflux Procedures - An Unfulfilled Promise?
Background: Most published reviews concerning the endoscopic treatment of gastro-oesophageal reflux disease date back to 2005.
Aim: To provide an updated review that includes all papers published up to 2007.
Methods: A Medline search from January 2005 to June 2007 was performed regarding endoscopic procedures aiming at treating gastro-oesophageal reflux disease. In addition, we retrieved the abstracts presented at Digestive Disease Week during the last 3 years. We included in the review both ‘mechanistic' studies - that is, papers exploring the potential mechanism of action of the procedure/device - and studies trying to assess its clinical efficacy.
Results: During the last 3 years, the number of published papers has declined, and some devices are not available any more. The alleged mechanism(s) of action of the various devices or procedures is (are) still not completely elucidated; however, some concerns have arisen as far as durability and potential detrimental effects. Moreover, all the aspects of endoscopic therapy, except for its safety, are either insufficiently explored or not investigated at all, or assessed only in particularly selected patient subgroups.
Conclusions: None of the proposed antireflux therapies has fulfilled the criteria of efficacy, safety, cost, durability and, possibly, of reversibility. There is at present no definite indication for endoscopic therapy of gastro-oesophageal reflux disease. We suggest a list of recommendations to be followed when a new endoscopic therapeutic procedure is to be assessed for use in clinical practice.
The chronic nature of gastro-oesophageal reflux disease (GERD) and the frequent need for long-term treatment have become increasingly apparent in the past 15 years. Acid suppression, in particular achieved by proton pump inhibitors (PPIs), is an effective therapy in most patients, although it does not address the main abnormality: the impaired function of the lower oesophageal sphincter. Surgical fundoplication has shown to be an effective and durable option for control of GERD symptoms. Its appeal has increased since the introduction of minimally invasive techniques. Nevertheless, the benefit should be balanced against the reported 0.5-1% risk of mortality, the experience of the surgeon and a possible decline of efficacy overtime.
These caveats have fueled the interest for endoscopic antireflux procedures (EARPs) in the last decade. Following the pioneer experience of the group of Swain with an endoluminal sewing device, three different approaches have been carried out: endoscopic suturing, intraluminal radio-frequency delivering and injection of bulking agents in the muscle layers of the lower oesophagus. More technical details on these procedures are presented in the following sections. However, what is peculiar for all these devices has been the prompt delivering on the market based on few preliminary data on safety and clinical efficacy, without any controlled trial. This has become possible because of the profound difference of requirements between device and drugs adopted by regulatory agencies like Food and Drug Administration (FDA) and European Agency for Medicinals Evaluation. Whereas pharmaceuticals undergo wide scrutiny and subsequent marketing practices, medical devices are regulated under a risk-based system. Devices with a low-moderate risk (as the endoscopic devices were classified) enter the market through a process requiring only supporting data of ‘equivalence' to an existing device or procedure. In the case of radiofrequency device, (Stretta, Curon Medical Inc., Sunnyvale, CA, USA) for example, the accepted evidence of FDA was an open-label study involving 47 patients, demonstrating shorter hospital stay and recovery time compared with that in published data on fundoplication. Subsequent events (i.e. some deaths potentially associated with the use of Enteryx [Boston Scientific Inc., Natick, MA, USA] and Stretta) have overcome the enthusiasm to the point that one device has been voluntarily withdrawn (Enteryx) and two others are no longer marketed (Wilson-Cook's ESD, Cook Medical, Inc., Bloomington, IN, USA and Medtronic's Gatekeeper, Medtronic Inc., Minneapolis, MN, USA) by the relative companies. Three others are still available [Stretta, EndoCinch (Bard Inc., Billerica, MA, USA), and the Plicator (NDO Surgical Inc., Mansfield, MA, USA)], although it appears that their sales in the 2006 were decreasing compared with 2005. These considerations have reinforced the claim of many authors that data in support of the endoscopic antireflux devices were not sufficient to merit their routine use outside the research setting. Despite these considerations, a considerable number of recent studies have appeared in the Literature, and we aimed at updating already existing reviews by adding those papers published between 2005 and 2007.
Summary and Introduction
Summary
Background: Most published reviews concerning the endoscopic treatment of gastro-oesophageal reflux disease date back to 2005.
Aim: To provide an updated review that includes all papers published up to 2007.
Methods: A Medline search from January 2005 to June 2007 was performed regarding endoscopic procedures aiming at treating gastro-oesophageal reflux disease. In addition, we retrieved the abstracts presented at Digestive Disease Week during the last 3 years. We included in the review both ‘mechanistic' studies - that is, papers exploring the potential mechanism of action of the procedure/device - and studies trying to assess its clinical efficacy.
Results: During the last 3 years, the number of published papers has declined, and some devices are not available any more. The alleged mechanism(s) of action of the various devices or procedures is (are) still not completely elucidated; however, some concerns have arisen as far as durability and potential detrimental effects. Moreover, all the aspects of endoscopic therapy, except for its safety, are either insufficiently explored or not investigated at all, or assessed only in particularly selected patient subgroups.
Conclusions: None of the proposed antireflux therapies has fulfilled the criteria of efficacy, safety, cost, durability and, possibly, of reversibility. There is at present no definite indication for endoscopic therapy of gastro-oesophageal reflux disease. We suggest a list of recommendations to be followed when a new endoscopic therapeutic procedure is to be assessed for use in clinical practice.
Introduction
The chronic nature of gastro-oesophageal reflux disease (GERD) and the frequent need for long-term treatment have become increasingly apparent in the past 15 years. Acid suppression, in particular achieved by proton pump inhibitors (PPIs), is an effective therapy in most patients, although it does not address the main abnormality: the impaired function of the lower oesophageal sphincter. Surgical fundoplication has shown to be an effective and durable option for control of GERD symptoms. Its appeal has increased since the introduction of minimally invasive techniques. Nevertheless, the benefit should be balanced against the reported 0.5-1% risk of mortality, the experience of the surgeon and a possible decline of efficacy overtime.
These caveats have fueled the interest for endoscopic antireflux procedures (EARPs) in the last decade. Following the pioneer experience of the group of Swain with an endoluminal sewing device, three different approaches have been carried out: endoscopic suturing, intraluminal radio-frequency delivering and injection of bulking agents in the muscle layers of the lower oesophagus. More technical details on these procedures are presented in the following sections. However, what is peculiar for all these devices has been the prompt delivering on the market based on few preliminary data on safety and clinical efficacy, without any controlled trial. This has become possible because of the profound difference of requirements between device and drugs adopted by regulatory agencies like Food and Drug Administration (FDA) and European Agency for Medicinals Evaluation. Whereas pharmaceuticals undergo wide scrutiny and subsequent marketing practices, medical devices are regulated under a risk-based system. Devices with a low-moderate risk (as the endoscopic devices were classified) enter the market through a process requiring only supporting data of ‘equivalence' to an existing device or procedure. In the case of radiofrequency device, (Stretta, Curon Medical Inc., Sunnyvale, CA, USA) for example, the accepted evidence of FDA was an open-label study involving 47 patients, demonstrating shorter hospital stay and recovery time compared with that in published data on fundoplication. Subsequent events (i.e. some deaths potentially associated with the use of Enteryx [Boston Scientific Inc., Natick, MA, USA] and Stretta) have overcome the enthusiasm to the point that one device has been voluntarily withdrawn (Enteryx) and two others are no longer marketed (Wilson-Cook's ESD, Cook Medical, Inc., Bloomington, IN, USA and Medtronic's Gatekeeper, Medtronic Inc., Minneapolis, MN, USA) by the relative companies. Three others are still available [Stretta, EndoCinch (Bard Inc., Billerica, MA, USA), and the Plicator (NDO Surgical Inc., Mansfield, MA, USA)], although it appears that their sales in the 2006 were decreasing compared with 2005. These considerations have reinforced the claim of many authors that data in support of the endoscopic antireflux devices were not sufficient to merit their routine use outside the research setting. Despite these considerations, a considerable number of recent studies have appeared in the Literature, and we aimed at updating already existing reviews by adding those papers published between 2005 and 2007.