Endoscopic and endoluminal techniques for the control of gastroesophageal reflux: Are they ready for widespread clinical application?

Abstract

Gastroesophageal reflux disease (GERD) is one of the most common conditions GI endoscopists are called on to evaluate. Lifestyle modifications and excellent medical therapy control symptoms for most patients, but lifelong therapy is generally required. One alternative is anti-reflux surgery, which has become less invasive with the shift to laparoscopic techniques. Therapeutic efficacy rates of laparoscopic fundoplication are high, with control of regurgitation and heartburn obtained in greater than 85% of patients. Many patients with GERD undergo diagnostic upper GI endoscopy. If a relatively simple, minimally invasive therapy could be simultaneously applied, this would seem ideal. If, as a result, symptoms and medication use decreased even by half, this would be major progress in the treatment of GERD.Fig. 2Standard acid reflux test (SART) data before and after treatment. The difference between the number of pre-treatment and posttreatment reflux episodes is significant at the p = 0.009 level (reprinted from O'Connor et al. Gastrointest Endosc 1988;34:109.)View Large Image Figure ViewerDownload Hi-res image Download (PPT)Table 1Features of ideal implant for the treatment of GERDLow viscosity (i.e., easy to inject through) Standard 5F catheter/25-gauge needleBiologically inert (implant site and metastatic)Non-carcinogenic/allergenic/immunogenicLow side-effect profileNon-biodegradableHigh persistence at implant siteLow costCapable of resisting mechanical strainSterileFavorable elasticity/plasticityNo adverse effect on adjacent muscle. Open table in a new tab Table 2Endoluminal anti-reflux techniquesInjection/bulkingEscharificationSuturingStaplingProsthetic valve Open table in a new tab Fig. 3Heartburn symptom score.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Radiofrequency induction of localized thermal injury at the LES or cardia was a treatment for GERD initiated in the late 1990s. In the botulinum toxin weakened LES pig model,9Utley DS Kim M Vierra MA Triadafilopoulos G. Augmentation of lower esophageal sphincter pressure and gastric yield pressure after radiofrequency energy delivery to the gastroesophageal junction: a porcine model.Gastrointest Endosc. 2000; 52: 81-86Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar radiofrequency therapy was associated with a numerical increase in basal LES pressure from 11.8 to 14.4 mm Hg (p > 0.05) and a statistically significant increase in gastric yield pressure compared with control animals (24.9 vs. 43.4 mm Hg, p = 0.0007). The technique requires endoscopic observation and measurement of the oral to cardia/squamocolumnar junction distance followed by passage of a 30F non-visualizing balloon probe (Curon Medical Inc, San Diego, Calif.). Four electrodes are penetrated into the esophageal wall and current is applied with balloon inflation. The mucosa is cooled by water irrigation to prevent surface injury. Data from a multi-center U.S. trial involving 44 patients with 6 months' follow-up were presented at the DDW 2000 meeting10Triadafilopoulos G Utley DS DiBaise J Nostrant T Stollman NH Rabine J et al.Radiofrequency energy application to the gastroesophageal junction for the treatment of gastroesophageal reflux disease.Gastrointest Endosc. 2000; 51 ([abstract]): AB223Google Scholar and submitted to the FDA for approval to market the product. For patients with GERD, there was a statistically significant improvement in quality of life, heartburn score, and 24-hour pH score. There was also evidence in this limited study of numerically fewer transient LES relaxations11DiBaise JK Akromis I Quigley EM. Efficacy of radiofrequency energy delivery to the lower esophageal sphincter in the treatment of GERD [abstract.Gastrointest Endosc. 2000; 51: AB96Google Scholar in humans after radiofrequency therapy. Partial denervation is therefore one proposed mechanism of action.Additional trials of LES implantation of an inert biopolymer (Enteryx; Enteric Technologies, Inc, Foster City, Calif.) are now underway. Initial studies in animals confirmed that the technique is safe in terms of local and systemic effects. Initial studies in humans in Europe, with more than 30 patients treated to date, have a maximum follow-up of 14 months. The injected implant tracked circumferentially around the cardia in a portion of patients to form a fluoroscopically visible ring. Preliminary data on efficacy have not been published to date, but the results appear to rival those obtained with radiofrequency and endoscopic sewing techniques.As a result of widespread media coverage of these new treatments for GERD and increasingly available Internet information, many endoscopists are receiving requests for this potential therapy. Now that two techniques are commercially available in the United States and soon to be available in other parts of the world, should the endoscopists take steps to offer this therapy to their patients?Many factors come into play in the decision to use a new therapy: Data reported to date on efficacy indicate that the rate of control of GERD symptoms with these new techniques is 60% to 70%. Regurgitation is controlled better than heartburn; 24-hour pH probe scores improve, but normalization to less than 4% total acid exposure time at a pH of less than 4 occurs in fewer than one quarter of patients. Half to two thirds of patients note a major reduction in the use of medication. Strict scientific proof of efficacy will require data from prospective randomized placebo- (sham-) controlled trials. These are in progress for both sewing and radiofrequency therapy. The medium-term efficacy (1- to 3-year data) is largely unknown in trials conducted in the United States. Potential patients must be made aware of that efficacy demonstrated to date is modest and the long-term outcome is uncertain.Table 3Optimal technique issues1. Site of therapy: LES vs. cardia2. Magnitude of therapy: number/volume3. Depth: submucosal vs. deeper intramural4. Configuration of treatment sites Open table in a new tab Attitudes of individual physicians and surgeons vary greatly with regard to adopting new treatment modalities. The cautious, conservative individual will recall the Garren anti-obesity bubble, gastric freezing, and certain drugs withdrawn from the market after initial FDA approval. Alternatively, failure to aggressively apply effective endoscopic therapies such as endoscopic bile duct stone extraction, endoscopic treatment of bleeding ulcers with injection or cautery techniques, and banding of esophageal varices may lead to increased morbidity or the need for more invasive alternative therapy. The equipment required for endotherapies for GERD varies widely depending on the technique. Injection techniques, usually with a modified sclerotherapy needle catheter, will likely be least expensive. The radiofrequency “control unit” is currently marketed at approximately $20,000 (U.S.). The sewing machine is intermediate in cost. Additional per-patient costs for materials/probes for suturing and radiofrequency techniques are approximately $1000 (U.S.). Physician reimbursement data and specific billing codes are unavailable at present. Cost efficacy studies are awaited.Suturing appears to be the most technically demanding of the several techniques. Injection techniques appear to be simplest. There are no data as to the number of procedures in animals or supervised procedures in humans needed to become competent at sewing techniques. The radiofrequency technique seems to be relatively simple with automated electronics.Whatever endoluminal technique is ultimately applied, it should leave the LES/cardia/fundic anatomy relatively unaltered so that standard surgical treatment remains an option if necessary. All current techniques appear to meet this criteria.In summary, because current techniques have undergone limited testing and appear to be only modestly effective, I recommend a conservative approach in their application in clinical practice. If you get involved, do so by contributing data to a national database so that efficacy and safety can be further defined. Better yet, participate in future research trials that aim to improve techniques.After a relatively slow start, research in the area of endoscopic therapy for GERD has greatly increased. Improved sewing methods are being evaluated. The application of limited multipolar coagulation between sewn plications improves plication persistence in animal models.12Filipi CJ Dunne D Sweeney S Dieselman K Baluyut A Lehman GA. Endoscopic gastroesophageal suturing: does addition of cautery aid plication persistence [abstract]?.Gastrointest Endosc. 2000; 51: AB104Abstract Full Text PDF Google Scholar Trials involving humans will start soon. Additional LES/cardia implant material is being evaluated in animals. Novel therapies, such as the use of prosthetic valves, have been evaluated in limited trials in humans with esophageal cancer,13Dua KS Kozarek RA Kim JP Evans J Hogan WJ Shaker R. Anti-reflux self-expanding metal esophageal stent: clinical evaluation in patients.Gastrointest Endosc. 2000; 51 ([abstract]): AB118Google Scholar but may be too invasive for the treatment of GERD alone. Further refinement and development of relatively simple, therapeutically effective, cost effective methods will occur. In the not-too-distant future, endoluminal GERD therapy will be as routine as thermal probe therapy for bleeding peptic ulcers. Gastroesophageal reflux disease (GERD) is one of the most common conditions GI endoscopists are called on to evaluate. Lifestyle modifications and excellent medical therapy control symptoms for most patients, but lifelong therapy is generally required. One alternative is anti-reflux surgery, which has become less invasive with the shift to laparoscopic techniques. Therapeutic efficacy rates of laparoscopic fundoplication are high, with control of regurgitation and heartburn obtained in greater than 85% of patients. Many patients with GERD undergo diagnostic upper GI endoscopy. If a relatively simple, minimally invasive therapy could be simultaneously applied, this would seem ideal. If, as a result, symptoms and medication use decreased even by half, this would be major progress in the treatment of GERD. Radiofrequency induction of localized thermal injury at the LES or cardia was a treatment for GERD initiated in the late 1990s. In the botulinum toxin weakened LES pig model,9Utley DS Kim M Vierra MA Triadafilopoulos G. Augmentation of lower esophageal sphincter pressure and gastric yield pressure after radiofrequency energy delivery to the gastroesophageal junction: a porcine model.Gastrointest Endosc. 2000; 52: 81-86Abstract Full Text Full Text PDF PubMed Scopus (122) Google Scholar radiofrequency therapy was associated with a numerical increase in basal LES pressure from 11.8 to 14.4 mm Hg (p > 0.05) and a statistically significant increase in gastric yield pressure compared with control animals (24.9 vs. 43.4 mm Hg, p = 0.0007). The technique requires endoscopic observation and measurement of the oral to cardia/squamocolumnar junction distance followed by passage of a 30F non-visualizing balloon probe (Curon Medical Inc, San Diego, Calif.). Four electrodes are penetrated into the esophageal wall and current is applied with balloon inflation. The mucosa is cooled by water irrigation to prevent surface injury. Data from a multi-center U.S. trial involving 44 patients with 6 months' follow-up were presented at the DDW 2000 meeting10Triadafilopoulos G Utley DS DiBaise J Nostrant T Stollman NH Rabine J et al.Radiofrequency energy application to the gastroesophageal junction for the treatment of gastroesophageal reflux disease.Gastrointest Endosc. 2000; 51 ([abstract]): AB223Google Scholar and submitted to the FDA for approval to market the product. For patients with GERD, there was a statistically significant improvement in quality of life, heartburn score, and 24-hour pH score. There was also evidence in this limited study of numerically fewer transient LES relaxations11DiBaise JK Akromis I Quigley EM. Efficacy of radiofrequency energy delivery to the lower esophageal sphincter in the treatment of GERD [abstract.Gastrointest Endosc. 2000; 51: AB96Google Scholar in humans after radiofrequency therapy. Partial denervation is therefore one proposed mechanism of action. Additional trials of LES implantation of an inert biopolymer (Enteryx; Enteric Technologies, Inc, Foster City, Calif.) are now underway. Initial studies in animals confirmed that the technique is safe in terms of local and systemic effects. Initial studies in humans in Europe, with more than 30 patients treated to date, have a maximum follow-up of 14 months. The injected implant tracked circumferentially around the cardia in a portion of patients to form a fluoroscopically visible ring. Preliminary data on efficacy have not been published to date, but the results appear to rival those obtained with radiofrequency and endoscopic sewing techniques. As a result of widespread media coverage of these new treatments for GERD and increasingly available Internet information, many endoscopists are receiving requests for this potential therapy. Now that two techniques are commercially available in the United States and soon to be available in other parts of the world, should the endoscopists take steps to offer this therapy to their patients? Many factors come into play in the decision to use a new therapy: Data reported to date on efficacy indicate that the rate of control of GERD symptoms with these new techniques is 60% to 70%. Regurgitation is controlled better than heartburn; 24-hour pH probe scores improve, but normalization to less than 4% total acid exposure time at a pH of less than 4 occurs in fewer than one quarter of patients. Half to two thirds of patients note a major reduction in the use of medication. Strict scientific proof of efficacy will require data from prospective randomized placebo- (sham-) controlled trials. These are in progress for both sewing and radiofrequency therapy. The medium-term efficacy (1- to 3-year data) is largely unknown in trials conducted in the United States. Potential patients must be made aware of that efficacy demonstrated to date is modest and the long-term outcome is uncertain. Attitudes of individual physicians and surgeons vary greatly with regard to adopting new treatment modalities. The cautious, conservative individual will recall the Garren anti-obesity bubble, gastric freezing, and certain drugs withdrawn from the market after initial FDA approval. Alternatively, failure to aggressively apply effective endoscopic therapies such as endoscopic bile duct stone extraction, endoscopic treatment of bleeding ulcers with injection or cautery techniques, and banding of esophageal varices may lead to increased morbidity or the need for more invasive alternative therapy. The equipment required for endotherapies for GERD varies widely depending on the technique. Injection techniques, usually with a modified sclerotherapy needle catheter, will likely be least expensive. The radiofrequency “control unit” is currently marketed at approximately $20,000 (U.S.). The sewing machine is intermediate in cost. Additional per-patient costs for materials/probes for suturing and radiofrequency techniques are approximately $1000 (U.S.). Physician reimbursement data and specific billing codes are unavailable at present. Cost efficacy studies are awaited. Suturing appears to be the most technically demanding of the several techniques. Injection techniques appear to be simplest. There are no data as to the number of procedures in animals or supervised procedures in humans needed to become competent at sewing techniques. The radiofrequency technique seems to be relatively simple with automated electronics. Whatever endoluminal technique is ultimately applied, it should leave the LES/cardia/fundic anatomy relatively unaltered so that standard surgical treatment remains an option if necessary. All current techniques appear to meet this criteria. In summary, because current techniques have undergone limited testing and appear to be only modestly effective, I recommend a conservative approach in their application in clinical practice. If you get involved, do so by contributing data to a national database so that efficacy and safety can be further defined. Better yet, participate in future research trials that aim to improve techniques. After a relatively slow start, research in the area of endoscopic therapy for GERD has greatly increased. Improved sewing methods are being evaluated. The application of limited multipolar coagulation between sewn plications improves plication persistence in animal models.12Filipi CJ Dunne D Sweeney S Dieselman K Baluyut A Lehman GA. Endoscopic gastroesophageal suturing: does addition of cautery aid plication persistence [abstract]?.Gastrointest Endosc. 2000; 51: AB104Abstract Full Text PDF Google Scholar Trials involving humans will start soon. Additional LES/cardia implant material is being evaluated in animals. Novel therapies, such as the use of prosthetic valves, have been evaluated in limited trials in humans with esophageal cancer,13Dua KS Kozarek RA Kim JP Evans J Hogan WJ Shaker R. Anti-reflux self-expanding metal esophageal stent: clinical evaluation in patients.Gastrointest Endosc. 2000; 51 ([abstract]): AB118Google Scholar but may be too invasive for the treatment of GERD alone. Further refinement and development of relatively simple, therapeutically effective, cost effective methods will occur. In the not-too-distant future, endoluminal GERD therapy will be as routine as thermal probe therapy for bleeding peptic ulcers.