Surgery Section - Transesophageal Endoscopic Therapies for Gastroesophageal Reflux Disease

IMPORTANT REMINDER

This Medical Policy has been developed through consideration of medical necessity, generally accepted standards of medical practice, and review of medical literature and government approval status.

Benefit determinations should be based in all cases on the applicable contract language. To the extent there are any conflicts between these guidelines and the contract language, the contract language will control.

The purpose of medical policy is to provide a guide to coverage. Medical Policy is not intended to dictate to providers how to practice medicine. Providers are expected to exercise their medical judgment in providing the most appropriate care.

Description

Transesophageal endoscopic therapies are a group of minimally invasive 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

• The long-term safety and effectiveness of transesophageal endoscopic surgeries for the treatment of gastroesophageal reflux disease (GERD) has not been established.
• It is uncertain whether transesophageal endoscopic surgeries 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 surgeries are at least as effective as medical management or standard open or laparoscopic Nissen fundoplication.

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.(2-6) Though these studies show 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.(3-6) 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.(3) 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.(5)
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.(4) All other studies include sample sizes of 60 or fewer patients. It is unclear if these studies are adequately powered. (3,5,6)
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.(3,4)

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

Observational case series of inpatient and outpatient plication procedures do not allow conclusions about their long-term effectiveness and durability.(7-20) 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 concerning transesophageal radiofrequency energy. 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.

Other clinical studies concerning transesophageal radiofrequency are limited to observational case series that do not allow conclusions about long-term effectiveness and durability.(2, 22-30) Though two case series report 48 month outcomes, there is 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.(31) 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.(32,33) 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.(34)

Other data on injectable or implantable polymers consists of very small case series.(2,35) 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.

Published Guidelines 

In recent guidelines released by the American College of Gastroenterology (36), endoscopic therapies for reflux were stated to “control symptoms in selected patients with well-documented GERD,” with level III evidence, which are trials without randomization, single group prepost, cohort, time series, or matched case-controlled studies. Medical therapy with proton pump inhibitors and antireflux surgery are endorsed with higher levels of evidence in these guidelines.

In December 2005, the Agency for Healthcare Research and Quality released a report entitled “Comparative Effectiveness of Management Strategies for Gastroesophageal Reflux Disease.” (37) The report findings, as follows, are consistent with the policy conclusions above:

• Data on comparative endoscopic treatments with continued (or intensified) use of PPIs are needed to better understand their efficacy compared to an established standard.
• More efficacy and safety data on new endoscopic approaches tested against a sham procedure with adequate follow-up are needed.

References

1. BlueCross BlueShield Association Medical Policy Reference Manual, Policy No. 2.01.38
2. TEC Assessment: Transesophageal Endoscopic Treatment for Gastroesophageal Reflux Disease. 2003; BlueCross and BlueShield Association Technology Evaluation Center. Vol 18, Tab 20. http://blueweb.bcbs.com/global_assets/special_content/tec_assessments/ vol18/18_20.pdf  (Verified 05/26/08)
3. Schwartz MP, Wellink H, Gooszen HG et al. Endoscopic gastroplication for the treatment of gastrooeophageal reflux disease: a randomized, sham controlled trial. Gut 2007;56:20-28
4. Rothstein R, Filipi C, Caca K et al. Endoscopic full-thickness lacation for the treatment of gastroesophageal reflux disease: a randomized, sham-controlled trial. Gastroenterol 2006;131:704-12
5. 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
6. 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
7. 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
8. Swain CP. Endoscopic suturing. Baillieres Best Pract Res Clin Gastroenterol 1999;13(1):97-108
9. 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
10. 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
11. 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
12. 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
13. Schiefke I, Zabel-Langhennig A, Neumann S et al.  Long term failure of endoscopic gastroplication (EndoCinch).  Gut  2005;54:752-8
14. 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
15. 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
16. 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
17. Cadière GB, Rajan A, Germay O et al. Endoluminal fundoplication by a transoral device for the treatment of GERD: A feasibility study  Surg Endosc 2007 Dec 11 [Epub ahead of print]
18. Cadiere G, Buset M, Muls V et al. Antireflux transoral incisionless fundplicatoin using EsophyXTM  - six-month results of a prospective multicenter study. World Journal of Surgery (Transcript under review)
19. Cadiere G, Buset M, Muls V et al. Antireflux transoral incisionless fundopolicatoin using EsophyXTM  - twelve-month results of a prospective multicenter study. World Journal of Surgery (Transcript under review)
20. 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
21. 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
22. 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
23. 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
24. 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
25. Triadilopoulos G.  Stretta: an effective, minimally invasive treatment for gastroesophageal reflux disease.  Am J Med 2003;115(suppl 3A):192-200S
26. Vakil N, Sharma P.  Review article: endoscopic treatments for gastro-oesophageal reflux disease.  Aliment Pharmacol Ther 2003;17(12):1427-34
27. Houston H, Khaitan L, Holzman M et al.  First year experience of patients undergoing the Stretta procedure.  Surg Endosc 2003;17(3):401-4
28. 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
29. 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
30. 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
31. 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
32. www.fda.gov/cdrh/pdf2/p020006.html  (Verified 05/26/08)
33. 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
34. 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 05/26/08)
35. 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
36. DeVault KR, Castell DO.  Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease.  Am J Gastroenterol 2005;100(1):190-200
37. 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/synthesize/reports/finalGERD.cfm  (Verified 05/26/08)

Cross References

None

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