Surgery Section - Transesophageal Endoscopic Therapies for Gastroesophageal Reflux Disease

IMPORTANT REMINDER

Regence Medical Policies are developed to provide guidance for members and providers regarding coverage in accordance with contract terms. Benefit determinations are based in all cases on the applicable contract language. To the extent there may be any conflict between the Medical Policy and contract language, the contract language takes precedence.

PLEASE NOTE: Contracts exclude from coverage, among other things, services or procedures that are considered investigational or cosmetic. Providers may bill members for services or procedures that are considered investigational or cosmetic. Providers are encouraged to inform members before rendering such services that the members are likely to be financially responsible for the cost of these services.

DESCRIPTION

Transesophageal endoscopic therapies are a group of minimally invasive antirefulx procedures being investigated as alternatives to medical management or fundoplication surgery in the treatment of gastroesophageal reflux disease (GERD). Each procedure uses an oral/endoscopic approach to alter structures at the junction between the stomach and the esophagus (gastroesophageal junction) to prevent reflux of gastric contents into the esophagus. There are three outpatient endoluminal procedures and one inpatient procedure being investigated for the management of GERD:

POLICY/CRITERIA

Transesophageal endoscopic therapies are considered investigational for the treatment of  gastroesophageal reflux disease (GERD). These procedures include but are not limited to the following:

POSITION STATEMENT

• Current published evidence is insufficient to establish the long-term safety and effectiveness of transesophageal endoscopic antireflux procedures for the treatment of gastroesophageal reflux disease (GERD).
• It is uncertain whether transesophageal endoscopic antireflux procedures can reliably decrease the need for medications to manage symptoms, decrease acid exposure to the esophagus, improve the extent of esophagitis, or improve overall health outcomes in the long-term in patients with GERD.
• It is unknown whether transesophageal endoscopic antireflux procedures are at least as effective as medical management or standard open or laparoscopic Nissen fundoplication.
• Published clinical practice guidelines concluded that current clinical trial data has neither established the safety, effectiveness and durability of these procedures, nor identified clear indications and patient selection criteria. (2-6)

Effectiveness

Transesophageal Endoscopic Gastroplasty and Transoral Incisionless Fundoplication 

There are four randomized, controlled studies comparing  transesophageal endoscopic gastroplasty or plication procedures to sham or other endoscopic procedures.(7-11) Though these studies showed a promising decrease in PPI use and symptom control at three to 12 months, they do not allow conclusions regarding long-term health outcomes, safety or durability of the procedure in patients with GERD for one or more of the following reasons:

1. Insufficient study durations – Only short-term follow-up of three to 12 months is available which does not address the long-term safety and durability of the procedures.(8-11) For example, there may be suture loss over time. One study reported up to 29 % of study subjects required a second procedure at 12 month follow-up.(8) Of these patients, 72% of sutures were still present but only 19% were judged functional. A second  study noted marked loss of sutures with 67% remaining at 12 months.(10)
2. Small sample size – Given the prevalence of GERD in the general population, available randomized trials include very small sample sizes. The largest study of 159 patients had an almost 10% loss in reported data with an intention to treat analysis that did not include these patients.(7) All other studies include sample sizes of 60 or fewer patients. It is unclear if these studies are adequately powered. (8,10,11)
3. Unreliable endpoints – The use of subjective, point in time GERD questionnaires as a primary endpoint may give variable results depending upon symptoms present at the time the subject completes the questionnaire.(8,9)

There are currently no randomized trials of the transoral incisionless fundoplication (TIF) procedure.

Observational case series of inpatient and outpatient plication procedures do not allow conclusions about their long-term effectiveness and durability.( 12-24) While some nonrandomized case series show a  promising decrease in acid exposure, use of PPIs or severity of symptoms, these trials are inherently prone to bias that favors the intervention. Long-term follow-up from well-designed clinical trials are needed to establish the clinical benefit of plication procedures.

Transesophageal Radiofrequency Energy (i.e., the Stretta procedure)

There is one randomized trial comparing transesophageal radiofrequency (RF) energy with a sham procedure that involved balloon inflation but no needle deployment or RF energy delivery. (25) Results of this study failed to include 20% of the randomized patients in analysis of primary endpoints and no intention to treat analysis was provided. Therefore, reported results of improved heartburn symptoms and GERD quality of life scores are not reliable.

A small randomized trial compared RF to PPI therapy. (26) This trial showed promising short-term (six months) results, but does not permit conclusions about mid- to long-term effectiveness and durability.

Other clinical studies concerning transesophageal radiofrequency are limited to observational case series that do not allow conclusions about long-term effectiveness and durability.( 7, 27-36) Though two case series report 48 month outcomes, there was a significant loss to follow-up in these studies such that conclusions on durability and health outcomes cannot be made. Data are needed from controlled comparisons with other treatments for GERD such as Nissen fundoplication or medical therapy.

Injection or Implantation of biocompatible polymers

There is one randomized sham-controlled trial which reports results of patients randomized to receive either injection of Enteryx biopolymer or a sham procedure. (37) At three and six months follow-up, patients in the Enteryx group had greater reductions in PPI use and more improvement in GERD health-related quality of life heartburn scores.  However, the small size and short duration of the study limit interpretation of findings.

The FDA approval for Enteryx procedure was based on a prospective case series of 85 patients who had GERD that was controlled by medical therapy.  While 76.5% of the study subjects met the primary outcome of eliminating or reducing medication use compared with baseline, 22% of the patients underwent a repeat injection either due to lack of effectiveness or sloughing of the implanted material. ( 38,39) This raises concerns about the durability of the procedure.

Additionally, in September 2005 Enteryx was voluntarily removed from the market due to serious adverse effects.  It is unclear if or when this product will return to the market.(40)

Other data on injectable or implantable polymers consists of very small case series. (7,41) The small number of patients and lack of long-term follow-up precludes scientific analysis.

Safety

• The durability and replacement rate of all of the above procedures is unknown.
• Highly technical skill is required to perform these procedures. There is limited, manufacturer-sponsored credentialing in place for the performance of these procedures.
• The safety and efficacy of repeat procedures is unknown.
• The safety and efficacy of these devices in patients with highly erosive disease or large hiatal hernias is unknown.

REFERENCES

1. BlueCross BlueShield Association Medical Policy Reference Manual, Policy No. 2.01.38
2. DeVault KR, Castell DO.  Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am J Gastroenterol 2005;100(1):190-200. Full text available online at: http://www.gi.org/physicians/guidelines/GERDTreatment.pdf (Verified 8/12/09)
3. Ip S, Bonis P, Tatisoni A et al.  Comparative Effectiveness of Management Strategies for Gastroesophageal Reflux Disease.  Evidence Report/Technology Assessment No. 1.  (Prepared by Tufts-new England Medical Center Evidence-based Practice Center)  Agency for Healthcare Research and Quality.  AHRQ Publication No. 06-EHC003-EF. http://effectivehealthcare.ahrq.gov/repFiles/GERD%20Final%20Report.pdf (Verified 8/12/09)
4. Lichtenstein DR, Cash BD, Davila R, et al.  Role of endoscopy in the management of GERD. American Society for Gastrointestinal Endoscopy. Gastrointest Endosc. 2007;66(2):219-24. Full text available online at www.asge.org (verified 8/12/09)
5. Kahrilas PJ, Shaheen NJ, Vaezi MF, et al. American Gastroenterological Association medical position statement on the management of gastroesophageal reflux disease.  Gastroenterology 2008;135(4):1383-91, 1391.e1-5. Full text available online at: http://www.gastro.org/user-assets/ Documents/02_Clinical_Practice/medical_position_statments/gerd_mps.pdf (Verified 8/13/09)
6. National Institute for Health and Clinical Excellence Guidance for care of the digestive system. Available online at: http://www.nice.org.uk/guidance/index.jsp?action=byTopic&o=7220 (Verified 8/112/09)
7. TEC Assessment: Transesophageal Endoscopic Treatment for Gastroesophageal Reflux Disease. 2003; BlueCross and BlueShield Association Technology Evaluation Center. Vol. 18, Tab 20
8. Schwartz MP, Wellink H, Gooszen HG et al. Endoscopic gastroplication for the treatment of gastroesophageal reflux disease: a randomized, sham controlled trial. Gut 2007;56:20-28
9. Rothstein R, Filipi C, Caca K et al. Endoscopic full-thickness plication for the treatment of gastroesophageal reflux disease: a randomized, sham-controlled trial. Gastroenterol 2006;131:704-12
10. Montgomery M, Hakanson B, Ljungqvist O et al. Twelve months’ follow-up after treatment with the EndoCinch endoscopic technique for gastro-oesophageal reflux disease: a randomized, placebo-controlled study. Scand J Gastroenterol 2006;41(12):1382-9
11. Domagk D, Menzel J, Seidel M et al. Endoluminal gastroplasty (EndoCinch) versus endoscopic polymer implantation (Enteryx) for treatment of gastroesophageal reflux disease: 6-month results of a prospective, randomized trial. Am J Gastroenterol 2006;101:422-30
12. Filipi CJ, Lehman GA, Rothstein RI et al. Transoral endoscopic suturing for treatment of GERD: a multicenter trial. Gastrointest Endosc 2001;53(4):416-22
13. Swain CP. Endoscopic suturing. Baillieres Best Pract Res Clin Gastroenterol 1999;13(1):97-108
14. Mahmood Z, McMahon BP, Arfin Q et al. EndoCinch therapy for gastro-esophageal reflux disease: a one year prospective follow-up. Gut 2003;52(1):34-9
15. Thomson M, Fritscher-Ravens A, Hall S et al.  Endoluminal gastroplication in children with significant gastro-oesophageal reflux disease.  Gut 2004;53(12):1745-50
16. Chadalavada R, Lin E, Swafford V et al.  Comparative results of endoluminal gastroplasty and laparoscopic antireflux surgery for the treatment of GERD.  Surg Endosc 2004;18(2):261-5
17. Abou-Rebyeh H, Hoepffner N, Rosch T et al.  Long-term failure of endoscopic suturing in the treatment of gastroesophageal reflux: a prospective follow-up study.  Endoscopy 2005;37(3):213-6
18. Schiefke I, Zabel-Langhennig A, Neumann S et al.  Long term failure of endoscopic gastroplication (EndoCinch).  Gut  2005;54:752-8
19. Pleskow D, Rothstein R, Kozarek R et al. Endoscopic full-thickness plication for the treatment of GERD: long-term multicenter results. Sur Endosc 2007;21(3):439-44
20. Mahmood Z, Byrne PJ, McMahon BP et al. Comparison of transesophageal endoscopic plication (TEP) with laparoscopic Nissen fundoplication (LNF) in treatment of uncomplicated reflux disease. Am J Gastroenterol 2006; 101(3):431-6
21. Rothstein RI Endoscopic therapy of gastroesophageal reflux disease. Outcomes of the randomized –controlled trials done to date J Clin Gastroenterol 2008;42(5):594-602
22. Cadière GB, Rajan A, Germay O et al. Endoluminal fundoplication by a transoral device for the treatment of GERD: A feasibility study  Surg Endosc2008;22(2):333-42
23. Cadiere G, Buset M, Muls V et al. Antireflux transoral incisionless fundoplication using EsophyX^®: 12-month results of a prospective multicenter study. World J Surg 2008;32(8):1578-80
24. Pleskow D, Rothstein R, Kozarek R et al. Endoscopic full-thickness placation for the treatment of GERD:  Five-year long-term multicenter results. Surg Endosc.2008;22:326-32
25. Corley DA, Katz P, Wo JM et al. Improvement of gastroesophageal reflux symptoms after radiofrequency energy: a randomized sham-controlled trial. Gastroenterology 2003;125(3):668-76
26. Coron E, Sebille V, Cadiot G, et al. Clinical trial: Radiofrequency energy delivery in proton pump inhibitor-dependent gastro-oesophageal reflux disease patients. Aliment Pharmacol Ther. 2008;28(9):1147-58
27. Triadilopoulos G, DiBaise JK, Nostrant TT et al. The Stretta procedure for the treatment of GERD: 6 and 12 month follow-up of the U.S. open label trial. Gastrointest Endosc 2002;55(2):149-156
28. Richards WO, Scholz S, Khaitan L et al. Initial experience with the Stretta procedure for the treatment of gastroesophageal reflux disease. J Laparoendosc Adv Surg Tech A 2001;11(5):267-73
29. DiBaise JK, Brand RE, Quigley EM. Endoluminal delivery or radiofrequency energy to the gastroesophageal junction in uncomplicated GERD: efficacy and potential mechanism of action. Am J Gastroenterol 2002;97(4):833-42
30. Triadilopoulos G.  Stretta: an effective, minimally invasive treatment for gastroesophageal reflux disease.  Am J Med 2003;115(suppl 3A):192-200S
31. Vakil N, Sharma P.  Review article: endoscopic treatments for gastro-oesophageal reflux disease.  Aliment Pharmacol Ther 2003;17(12):1427-34
32. Houston H, Khaitan L, Holzman M et al.  First year experience of patients undergoing the Stretta procedure.  Surg Endosc 2003;17(3):401-4
33. Noar MD, Lotfi-Emran BS. Sustained improvement in symptoms of GERD and antisecretory drug use: 4-year follow-up of the Stretta procedure. Gastrointest Endosc 2007;65(3):367-72
34. Reymunde A, Santiago N. Long-term results of radiofrequency energy delivery for the treatment of GERD: sustained improvements in symptoms, quality of life, and drug use at 4-year follow-up. Gastrointest Endosc 2007;65(3):361-66
35. McClusky DA 3rd, Khaitan L, Swafford VA et al. Radiofrequency energy delivery to the lower esophageal sphincter (Stretta procedure) in patients with recurrent reflux after antireflux surgery: can surgery be avoided? Surg Endosc 2007;21(7):1207-11
36. Dundon JM, Davis SS, Hazey JW, et al, Radiofrequency energy delivery to the lower esophageal sphincter (Stretta procedure) does not provide long-term symptom control. Surg Innov. 2008;15(4):297-301
37. Deviere J, Costamagna G, Neuhaus H et al.  Nonresorbable copolymer implantation for gastroesophageal reflux disease: a randomized sham-controlled multicenter trial.  Gastroenterology  2005;128(3):532-40
38. www.fda.gov/cdrh/pdf2/p020006.html  (Verified 8/12/09)
39. Johnson DA, Ganz R, Aisenberg J et al. Endoscopic implantation of EnteryX^® for treatment of GERD: 12-month results of a prospective, multicenter trial. Am J Gastroenterol 2003;98(9):1921-30
40. FDA Preliminary Public Health Notification*: Recall of Boston Scientific ENTERYX® Procedure Kits and ENTERYX® Injector Single Packs for Treatment of Gastroesophageal Reflux Disease (GERD).  www.fda.gov/cdrh/safety/101405-enteryx.html  (Verified 8/12/09)
41. Feretis G, Benakis P, Dimopoulos C et al. Endoscopic implantation of Plexiglas (PMMA) microspheres for the treatment of GERD. Gastrointest Endosc 2001;53:423-6

Cross References

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