What is appropriate medical systemic therapy for symptoms associated with BO?

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What is appropriate medical systemic therapy for symptoms associated with BO?

Introduction

Medical systemic therapy for patients with Barrett’s Oesophagus aims to control symptoms and reduce the risk of complications, including those related to peptic damage and (potentially) progression to adenocarcinoma. Uncomplicated Barrett’s Oesophagus itself is not a cause of symptoms, indeed patients with Barrett’s Oesophagus may have reduced sensitivity to oesophageal acidification, rather these are due to the effects of gastrooesophageal reflux on the squamous mucosa above the Barrett’s Oesophagus and to regurgitation of refluxate.[1] As a group, patients with Barrett’s Oesophagus have greater acid exposure than patients with less endoscopically severe reflux disease.[2][3] The general principles of medical systemic therapy for symptoms are essentially identical to treatment of the more severe forms of reflux oesophagitis without evidence of Barrett’s Oesophagus. The quality of evidence in the assessment of the control of symptoms specifically in patients with Barrett’s Oesophagus is poor, with few comparative randomised trials. Most information is derived from observational studies and medical treatment arms of comparative studies with surgical therapy or studies into other aspects of therapy (eg regression of metaplasia or control of intraoesophageal pH).

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Asymptomatic Barrett’s Oesophagus

A subpopulation of patients with Barrett’s Oesophagus have minimal or no typical reflux symptoms, but may still be at risk of complications. The value of medical systemic treatment in currently asymptomatic patients with Barrett’s Oesophagus and no macroscopic evidence of peptic oesophagitis diagnosed incidentally has not been examined. Patients with evidence of peptic oesophagitis should be treated to prevent the development of stricture.

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H2 Receptor Antagonist therapy

In the pre Proton Pump Inhibitor Therapy (PPI) era the use of cimetidine and ranitidine (+ antacid/other antisecretory agents) was shown to be effective in treating symptoms due to reflux in patients with Barrett’s Oesophagus.[4][5][6] These studies were small and selection of patients was not described. Up to 43% of patients may require higher doses than standard therapy to control symptoms,[7] but on an escalating dose regimen most patients’ symptoms can be controlled.[8]

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Proton Pump Inhibitor Therapy

Largely observational studies (sometimes the medical arm of a randomised study) show that most patients can be adequately controlled from a symptomatic point of view on PPI therapy,[6][9][10][11][12][13][14][15] although in a significant proportion treatment with higher doses of PPI is required.[16][17][18] Control of symptoms does not, however, equate to control of oesophageal acidification.[19][20][21]

Patients who achieve control of symptoms have a durable response over a period of years.[13][22][23][24]

Comparison of PPIs has not shown any PPI to be consistently superior to another in the control of symptoms in patients with Barrett’s Oesophagus.[25]

In patients with symptoms controlled on Ranitidine, changing to omeprazole did not result in better control.[26] Comparison of PPI to H2RA in a single trial showed that PPIs were superior in controlling symptoms.[6]

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Prokinetic Therapy

No studies have been performed to demonstrate that either prokinetic therapy alone, or its addition to acid suppression therapy has therapeutic value in the treatment of symptoms in patients with Barrett’s Oesophagus.

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Evidence summary and recommendations

Evidence summary Level References
Acid suppression with PPI is the most effective systemic therapy for reflux symptoms in patients with Barrett’s Oesophagus and can be expected to control symptoms in most patients with a durable effect over years II, IV [9], [6], [10], [11], [12], [13], [14], [15], [22], [23], [24]
Higher than standard doses of PPI may be required to control symptoms in a proportion of patients. IV [16], [17], [18]
Evidence-based recommendationQuestion mark transparent.png Grade
Symptomatic patients with Barrett’s Oesophagus should be treated with Proton Pump Inhibitor therapy (PPI), with the dose titrated to control symptoms.
C


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References

  1. Johnson DA, Winters C, Spurling TJ, Chobanian SJ, Cattau EL Jr. Esophageal acid sensitivity in Barrett's esophagus. J Clin Gastroenterol 1987 Feb;9(1):23-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/3559107.
  2. Neumann CS, Cooper BT. 24 hour ambulatory oesophageal pH monitoring in uncomplicated Barrett's oesophagus. Gut 1994 Oct;35(10):1352-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7959184.
  3. Parrilla P, Ortiz A, Martinez de Haro LF, Aguayo JL, Ramirez P. Evaluation of the magnitude of gastro-oesophageal reflux in Barrett's oesophagus. Gut 1990 Sep;31(9):964-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/2210462.
  4. Wesdorp IC, Bartelsman J, Schipper ME, Tytgat GN. Effect of long-term treatment with cimetidine and antacids in Barrett's oesophagus. Gut 1981 Sep;22(9):724-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7297920.
  5. Humphries TJ. Effects of long-term medical treatment with cimetidine and bethanechol in patients with esophagitis and Barrett's esophagus. J Clin Gastroenterol 1987 Feb;9(1):28-32 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/2881958.
  6. 6.0 6.1 6.2 6.3 Sontag SJ, Schnell TG, Chejfec G, Kurucar C, Karpf J, Levine G. Lansoprazole heals erosive reflux oesophagitis in patients with Barrett's oesophagus. Aliment Pharmacol Ther 1997 Feb;11(1):147-56 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9042987.
  7. Collen MJ, Johnson DA. Correlation between basal acid output and daily ranitidine dose required for therapy in Barrett's esophagus. Dig Dis Sci 1992 Apr;37(4):570-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/1551347.
  8. Cooper BT, Barbezat GO. Treatment of Barrett's esophagus with H2 blockers. J Clin Gastroenterol 1987 Apr;9(2):139-41 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/2883213.
  9. 9.0 9.1 Malesci A, Savarino V, Zentilin P, Belicchi M, Mela GS, Lapertosa G, et al. Partial regression of Barrett's esophagus by long-term therapy with high-dose omeprazole. Gastrointest Endosc 1996 Dec;44(6):700-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8979061.
  10. 10.0 10.1 Ortiz A, Martínez de Haro LF, Parrilla P, Molina J, Bermejo J, Munitiz V. 24-h pH monitoring is necessary to assess acid reflux suppression in patients with Barrett's oesophagus undergoing treatment with proton pump inhibitors. Br J Surg 1999 Nov;86(11):1472-4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10583299.
  11. 11.0 11.1 Fass R, Sampliner RE, Malagon IB, Hayden CW, Camargo L, Wendel CS, et al. Failure of oesophageal acid control in candidates for Barrett's oesophagus reversal on a very high dose of proton pump inhibitor. Aliment Pharmacol Ther 2000 May;14(5):597-602 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10792123.
  12. 12.0 12.1 Yeh RW, Gerson LB, Triadafilopoulos G. Efficacy of esomeprazole in controlling reflux symptoms, intraesophageal, and intragastric pH in patients with Barrett's esophagus. Dis Esophagus 2003;16(3):193-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14641308.
  13. 13.0 13.1 13.2 Attwood SE, Lundell L, Hatlebakk JG, Eklund S, Junghard O, Galmiche JP, et al. Medical or surgical management of GERD patients with Barrett's esophagus: the LOTUS trial 3-year experience. J Gastrointest Surg 2008 Oct;12(10):1646-54; discussion 1654-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18709511.
  14. 14.0 14.1 Frazzoni M, Savarino E, Manno M, Melotti G, Mirante VG, Mussetto A, et al. Reflux patterns in patients with short-segment Barrett's oesophagus: a study using impedance-pH monitoring off and on proton pump inhibitor therapy. Aliment Pharmacol Ther 2009 Sep 1;30(5):508-15 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19519732.
  15. 15.0 15.1 Watson JT, Moawad FJ, Veerappan GR, Bassett JT, Maydonovitch CL, Horwhat JD, et al. The dose of omeprazole required to achieve adequate intraesophageal acid suppression in patients with gastroesophageal junction specialized intestinal metaplasia and Barrett's esophagus. Dig Dis Sci 2013 Aug;58(8):2253-60 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23824407.
  16. 16.0 16.1 Sharma P, Sampliner RE, Camargo E. Normalization of esophageal pH with high-dose proton pump inhibitor therapy does not result in regression of Barrett's esophagus. Am J Gastroenterol 1997 Apr;92(4):582-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9128303.
  17. 17.0 17.1 Basu KK, Bale R, West KP, de Caestecker JS. Persistent acid reflux and symptoms in patients with Barrett's oesophagus on proton-pump inhibitor therapy. Eur J Gastroenterol Hepatol 2002 Nov;14(11):1187-92 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12439112.
  18. 18.0 18.1 Frazzoni M, Manno M, De Micheli E, Savarino V. Efficacy in intra-oesophageal acid suppression may decrease after 2-year continuous treatment with proton pump inhibitors. Dig Liver Dis 2007 May;39(5):415-21 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17379591.
  19. Ouatu-Lascar R, Triadafilopoulos G. Complete elimination of reflux symptoms does not guarantee normalization of intraesophageal acid reflux in patients with Barrett's esophagus. Am J Gastroenterol 1998 May;93(5):711-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9625114.
  20. Katzka DA, Castell DO. Successful elimination of reflux symptoms does not insure adequate control of acid reflux in patients with Barrett's esophagus. Am J Gastroenterol 1994 Jul;89(7):989-91 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8017396.
  21. Sarela AI, Hick DG, Verbeke CS, Casey JF, Guillou PJ, Clark GW. Persistent acid and bile reflux in asymptomatic patients with Barrett esophagus receiving proton pump inhibitor therapy. Arch Surg 2004 May;139(5):547-51 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15136356.
  22. 22.0 22.1 Sampliner RE. Effect of up to 3 years of high-dose lansoprazole on Barrett's esophagus. Am J Gastroenterol 1994 Oct;89(10):1844-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7942680.
  23. 23.0 23.1 Parrilla P, Martínez de Haro LF, Ortiz A, Munitiz V, Molina J, Bermejo J, et al. Long-term results of a randomized prospective study comparing medical and surgical treatment of Barrett's esophagus. Ann Surg 2003 Mar;237(3):291-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12616111.
  24. 24.0 24.1 Zaninotto G, Parente P, Salvador R, Farinati F, Tieppo C, Passuello N, et al. Long-term follow-up of Barrett's epithelium: medical versus antireflux surgical therapy. J Gastrointest Surg 2012 Jan;16(1):7-14; discussion 14-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22086718.
  25. Frazzoni M, Manno M, De Micheli E, Savarino V. Intra-oesophageal acid suppression in complicated gastro-oesophageal reflux disease: esomeprazole versus lansoprazole. Dig Liver Dis 2006 Feb;38(2):85-90 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16289976.
  26. Peters FT, Ganesh S, Kuipers EJ, Sluiter WJ, Klinkenberg-Knol EC, Lamers CB, et al. Endoscopic regression of Barrett's oesophagus during omeprazole treatment; a randomised double blind study. Gut 1999 Oct;45(4):489-94 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10486353.

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Appendices


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