SAGES Society of American Gastrointestinal and Endoscopic Surgeons http://www.sagescms.org Endoluminal Treatments for Gastroesophageal Reflux Disease (GERD) Edward D. Auyang, Patrice Carter, Thomas Rauth, Robert D. Fanelli and the SAGES Guidelines Committee Preamble The following clinical spotlight review regarding the endoluminal treatment of gastroesophageal reflux disease is intended for physicians who manage and treat GERD. It is meant to critically review these techniques and the available evidence supporting their safety and efficacy. Based on the level of evidence, recommendations may or may not be given for their use in clinical practice. Disclaimer Guidelines for clinical practice and spotlight reviews are intended to indicate preferable approaches to medical problems as established by experts in the field. These recommendations will be based on existing data or a consensus of expert opinion when little or no data are available. Spotlight reviews are applicable to all physicians who address the clinical problem(s) without regard to specialty training or interests, and are intended to convey recommendations based on a focused topic; within the defined scope of review, they indicate the preferable, but not necessarily the only acceptable approaches due to the complexity of the healthcare environment. Guidelines and recommendations are intended to be flexible. Given the wide range of specifics in any health care problem, the surgeon must always choose the course best suited to the individual patient and the variables in existence at the moment of decision. Guidelines, spotlight reviews, and recommendations are developed under the auspices of the Society of American Gastrointestinal Endoscopic Surgeons and its various committees, and approved by the Board of Governors. Each clinical spotlight review has been systematically researched, reviewed and revised by the guidelines committee, and, when appropriate, reviewed by an appropriate multidisciplinary team. The recommendations are therefore considered valid at the time of production based on the data available. Literature Review A systematic literature search was performed using PubMed for each of the technologies discussed in this Clinical Spotlight Review. The literature was reviewed through the dates as listed below for the individual technologies (June – September, 2012). The volume of literature available for each procedure varied, mostly depending on the length of existence of each device. Strength and level of evidence therefore is variable too, and is determined by review of available literature. 1 / 22 SAGES Society of American Gastrointestinal and Endoscopic Surgeons http://www.sagescms.org Levels of Evidence/Definitions Both the quality of the evidence and the strength of the recommendation for each of the guidelines were assessed according to the GRADE system. This uses a 4-tiered system for denoting the quality of evidence (very low (+), low (+ +), moderate (+ + +), or high (+ + + +)) and a 2-tiered system for strength of recommendation (weak, or strong) 1, 2. I. Introduction Gastroesophageal reflux disease (GERD) is a complex disorder resulting from multiple contributing factors, including acid production, lower esophageal sphincter tone and location, and anatomic barriers to reflux created by the angle of His and the diaphragmatic hiatus. GERD is a common problem that affects approximately 30-40% of the adult population with at least 20% of Americans reporting weekly symptoms. 1,2 GERD symptoms can be bothersome, resulting in interference with quality of life, and treatment can result in lifelong lifestyle changes and inadequate symptom relief. The estimated US population cost according to the American Gastroenterology Association is approximately 24 billion dollars annually, the majority of which stems from loss of work productivity.2 Symptoms can range from a simple episode of heartburn, to regurgitation, persistent cough, and dysphagia.1 Some symptoms easily are overcome using over-the-counter antacids. Persistent symptoms, however, often require lifelong treatment. The downstream risks of esophagitis, esophageal stricture, Barrett esophagus, and adenocarcinoma of the esophagus are significant causes for concern, and justify effective therapy for patients with GERD. Although a mainstay of GERD therapy for many patients, a discussion of long-term pharmacologic therapy, and its hazards, falls outside the scope of this document. Instead, the remainder of this review will focus on techniques designed to impact the anatomic mechanisms associated with GERD and its remedy. Laparoscopic fundoplication remains the gold standard in interventions for GERD in both adults and children. Multiple studies document the long term success of laparoscopic Nissen fundoplication.3,4 Notwithstanding the successes of surgical fundoplication, patients and providers continue to search for increasingly less invasive approaches to GERD, especially emphasizing techniques that seek to reduce the risks of dysphagia, bloating, and adverse outcomes sometimes associated with surgery. The endoscopic approach to treating GERD has been proposed by a number of devices and unique procedures, the majority of which are no longer available because ultimately, they failed to provide significant and durable relief from GERD symptoms or to effectively restore normal physiology. The review that follows considers two procedures based on an endoscopic platform that provide alternatives to the pharmacologic and surgical treatment of GERD. In considering the clinical application of these and other alternatives to the effective therapy provided by laparoscopic fundoplication for patients with GERD, the reader is asked to consider the degree of symptom relief and restoration of physiologic function provided by each therapy, and further, to consider the implications of treatment failures related to endoluminal therapies. Some endoluminal therapies may not offer the same degree of relief provided by surgery, but might still represent viable alternatives for patients seeking relief from lifelong dependence on pharmacologic 2 / 22 SAGES Society of American Gastrointestinal and Endoscopic Surgeons http://www.sagescms.org therapy, its cost, associated side effects, and long-term adverse outcomes. 1. Pohle T and Domschke. Results of short- and long-term medical treatment of gastroesophageal reflux disease (GERD). Langenbeck’s Archive of Surgery. 2000. 385: 317-323. 2. Brook RA, Wahlqvist P et al. Cost of gastro-oesophgeal reflux disease to the employer: a prospective from the United States. Alimentary Pharmacology and Therapeutics. 2007. 26. 889-898. 3. Papasavas PK, Keenan RJ et al. Effectiveness of laparoscopic fundoplication in relieving the symptoms of gastroesophageal reflux disease (GERD) and eliminating antireflux medical therapy. Surgical Endoscopy. 2003. 17. 1200 – 1205. 4. Dallemagne B, Weerts J et al. Clinical results of laparoscopic fundoplication at ten years after surgery. Surgical Endoscopy. 2006. 20. 159-165. II. Statement of Focus The intent of this Clinical Spotlight Review is to critically review literature related to currently available endoluminal therapies for GERD. The devices and techniques selected for this Clinical Spotlight Review include: EsophyX and Stretta. III. Endoluminal Treatments for GERD A. EsophyX EsophyX, developed by Endogastric Solutions (Redwood City, WA), is a device reported to create an incisionless fundoplication. Transoral Incisionless Fundoplication (TIF) was first approved for clinical use in the United States by the Food and Drug Administration in September of 2007.1 Once placed using the endoscopic approach, the instrument is deployed in the stomach and used to create a full thickness plication secured by “H-shaped” fasteners fashioned from polypropylene. The polypropylene stitch used as a fastener during TIF has been identified as one of the unique mechanisms of the device, and is thought to aid in the “serosa to serosa” fusion seen after completion of endoscopic fundoplication. The EsophyX device has gone through a number of revisions. The first technique was called endoluminal fundoplication (ELF) and used the TIF 1 device. The TIF 1 procedure produced a gastrogastric wrap at the level of the gastroesophageal junction (GEJ); critics likened this to a slipped fundoplication. The TIF 2 device was developed to more closely replicate laparoscopic fundoplication. H-fasteners are placed 3-5 cm above the GEJ resulting in creation of an esophagogastric fundoplication that more typifies what can be created surgically. (Figure 1) 3 / 22 SAGES Society of American Gastrointestinal and Endoscopic Surgeons http://www.sagescms.org (Bell & Cadiere. Transoral rotational esophagogastric fundoplication: technical, anatomical and safety considerations. Surgical Endoscopy. 2010.) Transoral Incisionless Fundoplication (TIF) (Literature Review through September, 2012) The TIF 1.0 protocol data first was collected in 2005 by Cadiere and colleagues, and published in Europe in 2006. Initially, the technique was called endoluminal fundoplication (ELF). This initial publication described the evolution and progression of the EsophyX device though its preclinical bench testing and animal studies, as well as its phase 1 and phase 2 clinical trials. At the time of this initial publication, the phase 2 clinical trial still was in progress. The phase 2 trial enrolled 17 patients. The study compared ELF to Laparoscopic Anti-Reflux Surgery (LARS) and a then existing competing Endoscopic Plication System (EPS); the authors did not specify the type of laparoscopic fundoplication performed. Six months after ELF, 80% of treated patients were reported to have stopped daily use of proton inhibitor medications (PPI); the reported cessation of PPI was 92-96% for patients treated using LARS, and 74% for patients treated with EPS. Esophageal pH was normalized in 67% of patients treated using ELF, 91 -96% of patients after LARS and 30% of patients after EPS.2 In 2008, Cadiere et al published a prospective clinical trial with one year follow-up; enrollment 4 / 22 SAGES Society of American Gastrointestinal and Endoscopic Surgeons http://www.sagescms.org began in 2005. Nineteen patients with chronic GERD lasting at least 6 months, grade A-C esophagitis per the LA classification, or chronic PPI dependence were enrolled. At 12 months, 16 patients were available for follow-up: 63% had a normal esophageal pH; 82% were off PPI medications; 53% improved pre-treatment HRQL scores by >50%. 3 A multi-center trial performed in 2008 enrolled 84 patients and reported on 79 patients available for 12 month follow-up. Additionally, the authors stratified results for 21 patients who maintained a grade 1 Hill Valve at 12 months after treatment. Within this subset, 48% had normal esophageal pH compared with 37% of the aggregated study group; 81% discontinued PPI use compared with 85% of the aggregated patients; and 86% improved their pre-treatment HRQL scores while 73% of the aggregated group had improved scores. Three procedure related complications were reported, including esophageal perforation (2 patients) and hemorrhage (1 patient) requiring transfusion; endoscopic control was reported as effective.1 Bergman and colleagues at Ohio State reported one of the first US studies of EsophyX. They published a retrospective review of 8 patients in 2008; patients were treated using the second generation EsophyX device that was applied in the same fashion as had been reported by Cadiere and associates during their trial of the first generation device. Mean follow-up was 60 days ± 44 which consisted of an office visit or a follow up telephone call. The interviewer recorded the HRQL survey, symptom severity score, and questions regarding GERD medication use, as well as any other pertinent data. Four patients reported taking the same PPI dose after treatment; 2 patients were taking ?50% of their pre-treatment dose, and 2 patents had stopped using PPI medications. The HRQL mean score was 8±8 and the mean symptom severity score was 17±15 at follow-up.4 This group went on to further report their findings on 26 additional patients; mean follow up was 10 months, and primary end points used were the Anvari and HRQL scores at 3 months, medication use, and patient satisfaction with procedure. At 3 months, 45% of patients improved pre-treatment HRQL scores ? 50%. At mean follow-up of 10 months, 68% of patients still were taking PPI; 45% of patients reported satisfaction with the procedure. There were two complications reported; both were hemorrhage requiring transfusion and therapeutic endoscopy. 5 In 2009, Cadiere et al published two year follow-up data for 14 patients initially enrolled in the original feasibility trial published in 2008. Follow-up data included HRQL survey, upper endoscopy, PPI and GERD medication use, diet, and lifestyle changes enacted. No esophageal pH assessment was performed. Determinants for success were cessation of PPI use, no interval development of hiatus hernia, absence of esophagitis, and relief of heartburn symptoms and regurgitation. Twenty-none percent of treated patients met these criteria for successful treatment at 2 year follow up. An additional fifty percent of patients were improved but reported occasional heartburn, regurgitation, or had developed a hiatus hernia or persistent esophagitis during follow up. Twenty-one percent of patients had ongoing symptoms and required daily PPI medication; they were deemed treatment failures. 6 A prospective trial of 20 patients treated using TIF was performed by Testoni and colleagues. GERD HRQL and GERD QUAL questionnaires were administered preoperatively, once with 5 / 22 SAGES Society of American Gastrointestinal and Endoscopic Surgeons http://www.sagescms.org patients on PPI medications, and again with the patient off PPI medication. Endoscopy and esophageal pH studies were performed preoperatively. All patients underwent the TIF 2.0 procedure. There were no operative complications reported. At six months, all patients underwent endoscopy, esophageal pH and impedance testing, and all were given both questionnaires again. PPI medication use was reduced in 22% of patients and eliminated entirely in 55%; 61% of patients no longer exhibited hiatus hernia after undergoing the procedure. No significant change in pre-operative and post-operative DeMeester scores was reported.7 Velanovich reported his experience with 26 patients; 20 reported typical GERD symptoms, 4 had been diagnosed with laryngopharyngeal reflux, and 4 reported recurrent GERD symptoms after prior Nissen fundoplication. The first ten procedures were done using the TIF 1.0 device; the remaining 16 were performed using the TIF 2.0 device. Velanovich explains the differences between the devices to include a smaller diameter main tube, a more flexible tissue mold, and multi-load H-fastener cartridges. Two procedures were aborted because of inability to pass the device through the pharynx; one complication, hemorrhage requiring transfusion and therapeutic endoscopy, was reported. Mean follow-up was 7 weeks. Thirteen of 24 treated patients reported symptom resolution; 19 were satisfied with the procedure. The median GERD HRQL score decreased from 25 to 5. The 79% of patients who reported satisfaction with the procedure were no longer taking PPI medications.8 A retrospective review of 124 patients treated using a combination of the TIF 1.0 and TIF 2.0 technique has been published; median follow-up was 7 months. This review combined patients treated at 2 community hospitals; esophageal pH testing was unavailable at both institutions. Follow up data were available for 110 patients. All patients treated prior to TIF 2.0 exhibited moderate deterioration of their post-treatment gastroesophageal valves; 64% had hiatus hernias determined to be 2 or 3cm in size. Forty-three percent of study patients were ? than 65 years old, and 97% reported inadequate pre-treatment symptom relief on PPI therapy. One procedure was abandoned when a hematoma developed; this was reported to be related to patient failure to stop anticoagulant medication at the recommended time. Four percent of patients underwent laparoscopic Nissen fundoplication (LNF) within 2 months following TIF; treatment failure was the indication in each. PPI medication was stopped successfully in 93% of patients after TIF. Post-treatment endoscopy was performed in 53 patients; 89% exhibited a grade 1 Hill Valve, and 97% of pre-treatment hiatus hernias reduced during performance of TIF remained reduced at the time of post-treatment endoscopy. One new hiatus hernia was identified and 1 patient was found to have active esophagitis after TIF; the authors concluded that 79% of their patients had been treated successfully by TIF.9 Outcomes have varied by study, and untoward outcomes have been reported in a variety of studies. A multi-institutional study of 19 patients with mean follow up of 10.8 months published by Hoppo et al reported three complications; esophageal perforation in 1 patient; permanent numbness of the tongue in 1 patient; and hemorrhage requiring transfusion in 1 patient. Eventually 10 of these 19 patients went on to have surgical treatment for GERD, undergoing LNF. Hoppo determined that 68.4% of their patients experienced treatment failure.10 Bell and Freeman reported 37 patients with median 6 month follow-up after TIF, with 2 complications reported; one mediastinal abscess and 1 patient experiencing hemorrhage. PPI cessation was 6 / 22 SAGES Society of American Gastrointestinal and Endoscopic Surgeons http://www.sagescms.org reported in 82%, and 5 patients required additional treatment; 3 underwent LNF and 2 underwent repeat TIF. 11 Trad et al reported on 32 patients undergoing TIF, where 82% of the 28 patients available for follow up were off PPI medications; no complications were reported, and 1 patient underwent LNF six months post-treatment. 12 Narsule et al performed TIF for 46 patients, and during median follow up of 83 days, 2 patients underwent repeat TIF and 1 was converted to LNF.13 Testoni and colleagues treated 42 patients with TIF 2.0, and report mean follow up of 27 months ± 4.6 months. Thirty-five patients completed 6 month follow up assessment and 26 patients completed 24 month follow up assessment. At 6 months, 60% of patients had stopped using PPI medication; at 24 months, 42.3% of patients were off PPI. There was no significant difference between PPI use at 12 months and 24 months, and there was no significant change in DeMeester scores. Two patients developed pneumothorax related to TIF; 4 patients went on to have LNF.14 Svoboda and colleagues published the only randomized clinical trial comparing endoluminal fundoplication and LNF identified during this literature review. Initiated in 2007, patients were randomized to either full thickness plication using a then available endoscopic plication device, or to surgical treatment with LNF. When the plication device became unavailable because of insolvency of its manufacturer, patients were then randomized either to TIF or LNF. Fifty-two patients were enrolled; 18 were randomized to plication, 16 to TIF, and 18 to LNF. At 12 month follow up, there were no statistically significant differences between the endoscopic fundoplication group and the LNF.15 A recent modification of the approach to endoscopic fundoplication using the TIF device is the “hybrid” technique. Ihde and colleagues published one of very few reports to include patients who underwent combined laparoscopic repair of hiatus hernia followed immediately by the TIF procedure. These authors enrolled all patients with a hiatus hernia ? 3 cm into the hybrid approach. Of 48 total patients with 6 month median follow up, 18 had undergone a hybrid approach that included laparoscopic posterior cruroplasty and standard TIF. Distal esophageal perforation in 1 patient was the only reported complication. Results were not stratified according to TIF alone or TIF plus laparoscopic cruroplasty. Sixty-seven percent of patients available for follow up reported cessation of daily PPI use; symptom severity scores were significantly reduced.16 Bell and colleagues published a multi-centered prospective trial of 100 patients undergoing the EsophyX2 procedure with mean six month follow-up. The centers involved in the study participated in the TIF registry. Included patients reported a one year or greater history of GERD, and at least 6 months of daily PPI use. Patients with a body mass index (BMI) > 35 or Barrett esophagus greater than 2 cm in length were excluded from this study. The majority of enrolled patients had been diagnosed with laryngeal pharyngeal reflux (LPR) (51%). The primary endpoint of the study was improvement in GERD symptoms as related to symptom severity monitored by various symptom surveys; GERD-HRQL (GERD – Health Related Quality of Life), RSI (Reflux Symptom Index), GERSS (GERD Symptom Score). Secondary endpoints included cessation of PPI use, improvement or normalization of esophageal pH, healing of esophagitis, and reduction in hiatus hernia size. For patients treated for typical GERD 7 / 22 SAGES Society of American Gastrointestinal and Endoscopic Surgeons http://www.sagescms.org symptoms, 66% recorded normalized HRQL scores, 87% recorded normalized regurgitation scores, and 71% were able to stop PPI use after TIF. For patients with LPR, 69% recorded normalized RSI scores, and 82% were able to stop PPI use after TIF. Overall, 80% of study patients stopped PPI use after TIF. Esophageal pH testing was reported for 44 of 100 patients; just 28 had esophageal pH testing both before and after TIF. This subgroup exhibited a significant reduction in percentage of esophageal acid exposure time, number of reflux episodes, and DeMeester scores. There were no untoward outcomes reported in this study.17 Considerations in the Pediatric Population The reader is advised that the EsophyX System is not approved by the FDA for use in pediatric patients, nor is the device recommended for use in children by its manufacturer. There is one available study that reports the use of the EsophyX system in the pediatric population. Chen et al. reported results for eleven patients who underwent transoral fundoplication for either primary GERD (6/11) or recurrent GERD following Nissen fundoplication (5/11) 18. The children had a mean age of 16 years and weighed 45 kg. The majority (9/11) were neurologically impaired. All required general anesthesia with a mean procedure time of 113 ± 31 minutes. Resolution of reflux was measured by the improvement in clinical symptoms, absence of reflux on upper GI or pH-probe study. Mean follow up was 8.2 ± 4.2 months. Overall, 7 patients underwent upper GI study and 3 underwent pH-probe all demonstrating the absence of reflux. The minority of patients had post-procedure gagging or feeding difficulties. There was one episode of recurrent reflux during the study period that ultimately went on to require gastroesophageal disconnect. This study is limited by its small size, short follow up, and uncontrolled patient selection. There was one device failure, and one hemorrhagic complication requiring a four unit blood transfusion and therapeutic endoscopy, reported in these 11 patients. Results were, on average, good though the study lacked a uniform objective measurement of post-procedure outcome. The device itself requires a delivery system of 54-French diameter, limiting application to patients larger than 25kg, excluding infants and toddlers from consideration for TIF. Presently, there is insufficient data to support the routine use of TIF in the pediatric population. Future controlled studies conducted under Institutional Review Board supervision are required before recommendations regarding its safety and efficacy in the pediatric population can be made. TIF Conclusions The EsophyX device has been studied across a broad range of adult patient populations, and reported in one adolescent study. Numerous published series have reported significant untoward events, although the safety profile for the procedure appears to be evolving in parallel with the procedural technique. Results appear mixed with some series reporting disappointing outcomes, and others reporting promising short-term results; yet, there still is a significant gap in the literature. The majority of available literature is significantly underpowered, mostly observational studies with routinely brief follow-up periods. There has been a paucity of sham controlled trials and studies that directly compare TIF with laparoscopic anti-reflux surgery. The device has been modified through multiple revisions, and the technique of the procedure has evolved as well; long term data that will be available in the near future will most likely be based upon the first generation device and the TIF 1.0 technique. The creation of the EsophyX 8 / 22 SAGES Society of American Gastrointestinal and Endoscopic Surgeons http://www.sagescms.org database and registry will aid in future research important to making more meaningful recommendations with respect to placement of TIF in the treatment of patients with GERD. Further study in the pediatric population will be necessary to consider TIF a treatment option for children. Recommendation: Long term data is not yet available for EsophyX. In short term follow-up, from 6 months to 2 years, EsophyX may be effective in patients with a hiatal hernia ? 2 cm with typical and atypical GERD. Further studies are required to define optimal techniques and most appropriate patient selection criteria, and to further evaluate device and technique safety. Quality of Evidence: (++). GRADE Recommendation: Weak Literature Cited 1. Cadiere GB, Buset M, Muls V et al. Antireflux Transoral Incisionless fundoplication using EsophyX: 12-Month Results of a prospective multicenter study. World Journal of Surgery. 2008. 32:1676-1688. 2. Cadiere GB; Rajan A et al. Endoluminal fundoplication (ELF) – evolution of EsophyX, a new surgical device for transoral surgery. Minimally invasive therapy. 2006. 15:6. 348-355. 3. Cadiere GB; Rajan A et al. Endoluminal fundoplication by a transoral device for the treatment of GERD: a feasibility study. Surgical Endoscopy. 2008. 22: 333-342. 4. Bergman S, Mikami J et al. Endoluminal fundoplication with EsophyX: The initial North American Experience. Surgical Innovation. 2008. 15:3. 166-170. 5. Demyttenaere S; Bergman S et al. Transoral Incisionless fundoplication for gastroesophageal reflux disease in an unselected patient population. Surgical Endoscopy. 2010. 24: 854-858. 6. Cadiere GB; Sante N et al. Two year results of a feasibility study on antireflux transoral incisionless using EsophyX. Surgical Endoscopy. 2009. 23:957 -964. 7. Testoni P; Corsetti M et al. Effect of transoral Incisionless fundoplication on symptoms, PPI use, and pH impedance refluxes of GERD patients. World Journal of Surgery. 2010. 34: 750-757. 8. Velanovich V. Endoscopic, endoluminal fundoplication for gastroesophageal reflux disease: initial experience and lessons learned. Surgery. 148. 4. 648-653. 9. Barnes, W; Hoddinott, K et al. Transoral Incisionless Fundoplication offers high patient satisfaction and relief of therapy-resistant typical and atypical symptoms of GERD in community practice. Surgical Innovation. 2011. 18. 10. Hoppo T; Immanuel A et al. Transoral Incisionless fundoplication 2.0 procedure using EsophyX for gastroesophageal reflux disease. Journal of Gastrointestinal Surgery. 2010. 9 / 22 SAGES Society of American Gastrointestinal and Endoscopic Surgeons http://www.sagescms.org 14: 1895-1901. 11. Bell R and Freeman K. Clinical and pH-metric outcomes of transoral esophogogastric fundoplication for the treatment of gastroesophageal reflux disease. Surgical Endoscopy. 2011. 25: 1975 – 1984. 12. Trad K; Turgeon D et al. Long term outcomes after transoral Incisionless fundoplication in patients with GERD and LPR symptoms. Surgical Endoscopy. 2012. 26: 650-660. 13. Narsule C; Burch M et al. Endoscopic Fundoplication for the treatment of gastroesophageal reflux disease: initial experience. The Journal of Thoracic and Cardiovascular Surgery. 2012: 143.1. 14. Testoni P; Vailati C et al. Transoral Incisionless fundoplication (TIF 2.0) with EsophyX for gastroesophageal reflux disease: long term results and findings affecting outcome. Surgical Endoscopy. 2011. 15. Svoboda P; Kantorova I et al. Our experience with transoral Incisionless plication of gastroesophageal reflux disease: NOTES Procedure. Hepatogastroenterology. 2011. 58: 1208-1213. 16. Ihde G; Besancon K et al. Short term safety and symptomatic outcomes of transoral Incisionless fundoplication with or without hiatal hernia repair in patients with chronic gastroesophageal reflux disease. The American Journal of Surgery. 2011. 202. 740-747. 17. Bell R; Mavrelis P et al. A prospective multicenter registry of patients with chronic gastroesophageal reflux disease receiving transoral incisionless fundoplication. Journal of the American College of Surgeons. 2012. 18. Chen S; Jarboe MD; Teitlebaum DH; Effectiveness of a transluminal endoscopic fundoplication for the treatment of pediatric gastroesophageal reflux disease. Pediatr Surg Int. 2012 28:229-234 B. Stretta Mederi Therapeutics Inc. (Greenwich CT) acquired all rights to the Stretta system for the radiofrequency treatment of GERD, including its specialized catheters and radiofrequency (RF) generators. The FDA originally cleared Stretta for use in 2000 and issued an updated clearance on the RF generator in 2011. The transoral Stretta catheter system uses a proprietary algorithmic application of low power (5 Watts) RF energy and generates low tissue temperatures (65C to 85C) during a series of one-minute treatment cycles. Stretta therapy remodels the musculature of the lower esophageal sphincter (LES) and gastric cardia. Clinical studies demonstrate that the Stretta RF treatment results in significant reductions in tissue compliance and transient LES relaxations. These mechanisms act to restore the natural barrier function of the LES as well as to significantly reduce spontaneous regurgitation caused by transient inappropriate relaxations of the sphincter. (Figure 2) 10 / 22