Continuous treatment of Barrett's oesophagus patients with proton pump inhibitors up to 13 years: observations on regression and cancer incidence
J. C. GEARTY
Department of Pathology, City Hospital, Birmingham, UK
Search for more papers by this authorJ. C. GEARTY
Department of Pathology, City Hospital, Birmingham, UK
Search for more papers by this authorAbstract
Summary
Background
There is little evidence that treatment of patients with Barrett's oesophagus with proton pump inhibitors over periods up to 6 years results in major regression of Barrett's oesophagus.
Aim
To determine if longer periods of treatment with proton pump inhibitors lead to significant regression of Barrett's oesophagus, and to determine the incidence of oesophageal adenocarcinoma in the proton pump inhibitor-treated patients.
Methods
We analysed prospectively-collected data on Barrett's oesophagus patients treated with proton pump inhibitors for 1–13 years.
Results
188 patients with Barrett's oesophagus and intestinal metaplasia, were treated for 1–13 years with a proton pump inhibitor (966 years of treatment; mean 5.1 years). No change in length was seen during treatment but 48% of patients developed squamous islands (25% after 1–3 years; 100% at 12–13 years). Squamous islands correlated with treatment duration and male sex but not with proton pump inhibitor dose or patient age. Six patients developed dysplasia and three males developed adenocarcinoma during treatment (cancer incidence 0.31%).
Conclusions
Proton-pump inhibitor treatment over 1–13 years does not shorten the Barrett's oesophagus segment but squamous islands appear in many patients. The incidence of oesophageal adenocarcinoma was low in these proton pump inhibitor-treated patients compared with published series.
References
- 1 Iascone C, DeMeester TR, Little AG, Skinner DB. Barrett's esophagus; functional assessment, proposed pathogenesis and surgical therapy. Arch Surg 1983; 118: 543–9.
- 2 Cooper BT, Barbezat GO. Barrett's oesophagus. A clinical study of 52 cases. Q J Med 1987; 62: 97–108.
- 3 Tytgat GNJ, Hammeetman W, Onstenk RR, Scotberg R. The spectrum of columnar lined (Barrett's) oesophagus. Endoscopy 1989; 21: 177–85.
- 4 Paull A, Trier JS, Dalton MD, Camp RC, Loeb P, Goyal RK. The histological spectrum of Barrett's esophagus. N Engl J Med 1976; 295: 476–80.
- 5 Rothery GA, Patterson JE, Stoddard CJ, Day DW. Histological and histochemical changes in the columnar lined (Barrett's) oesophagus. Gut 1986; 27: 1062–8.
- 6 Skinner DB, Walther BC, Riddell RH, Schmid H, Iascone C, DeMeester TR. Barrett's esophagus. Comparison of benign and malignant cases. Ann Surg 1983; 198: 554–65.
- 7 Spechler SJ, Robbins AH, Rubin HB, et al. Adenocarcinoma and Barrett's esophagus. An overrated risk? Gastroenterology 1984; 87: 927–35.
- 8 Kerlin P, Mellow GD, van Deth A. Barrett's oesophagus. Clinical endoscopic and histologic spectrum in 50 cases. Aust N Z J Med 1986; 16: 198–205.
- 9 Reid BJ, Haggitt RG, Rubin CE, Rabinovitch PS. Barrett's esophagus. Correlation between flow cytometry and histology in detection of patients at risk of adenocarcinoma. Gastroenterology 1987; 93: 1–11.
- 10 Brand DL, Ylvisakar JF, Gelfand M, Pope CE. Regression of the columnar esophageal (Barrett's) epithelium after anti-reflux surgery. N Engl J Med 1980; 302: 844–8.
- 11 Skinner DB, Walther BC, Riddell RH, Schmidt H, Iascone C, DeMeester TR. Barrett's esophagus. Ann Surg 1983; 198: 554–65.
- 12 Starnes BA, Adkins RB, Ballinger JF. Barrett's esophagus: a surgical entity. Arch Surg 1984; 119: 563–7.
- 13 Williamson WA, Ellis FH, Gibb SP, Shahian DM, Aretz HT. Effects of anti-reflux operation on Barrett's mucosa. Ann Ther Surg 1990; 49: 537–42.
- 14 Barham CP, Jones RL, Biddlestone IR, et al. Photothermal laser ablation of Barrett's oesophagus: endoscopic and histological evidence of squamous re-epithelialisation. Gut 1997; 41: 281–4.
- 15 Basu KK, Pick B, Bale R, et al. Efficacy and one year follow up of argon plasma coagulation therapy for ablation of Barrett's oesophagus: factors determining persistence and recurrence of Barrett's epithelium. Gut 2002; 51: 776–80.
- 16 Sampliner RE, Faigel D, Fennerty MB, et al. Effectiveness and safe endoscopic reversal of non dysplastic Barrett's esophagus with thermal electrocoagulation combined with high dose acid inhibition. Gastrointest Endosc 2001; 53: 554–8.
- 17 Overholt BF, Panjehpour M, Haydek JM. Photodynamic therapy for Barrett's esophagus: follow up of 100 patients. Gastrointest Endosc 1999; 49: 1–7.
- 18 Deviere J. Barrett's oesophagus: the new endoscopic modalities have a future. Gut 2005; 54: i33–8.
- 19 Berensen MM, Johnson TD, Markowitz NR, Samowitz WS. Restoration of squamous epithelium after ablation of Barrett's esophagus. Gastroenterology 1993; 104: 1686–91.
- 20 Cooper BT, Barbezat GO. Treatment of Barrett's with H2 blockers. J Clin Gastroenterol 1987; 9: 139–41.
- 21 Neumann CS, Iqbal TH, Cooper BT. Long term continuous omeprazole treatment of patients with Barrett's oesophagus. Aliment Pharmacol Ther 1995; 9: 451–4.
- 22 Peters FTM, Ganesh S, Kuipers EJ, et al. Endoscopic regression of Barrett's oesophagus during omeprazole therapy. Gut 1999; 45: 489–94.
- 23 Klinkenberg-Knoll EC, Festen HP, Jansen JB, et al. Long term treatment with omeprazole for erosive esophagitis. Ann Intern Med 1994; 121: 161–7.
- 24 Sharma P, Sampliner RE, Camargo E. Normalisation of esophageal pH with high dose proton pump inhibitor therapy does not result in regression of Barrett's esophagus. Am J Gastroenterol 1997; 92: 582–5.
- 25 Weinstein WF, Lieberman DA, Landis KJ, Weber LJ, Berger ML, Ippoliti AF. Omeprazole induced regression of Barrett's esophagus: a two year randomized controlled double blind trial. Gastroenterology 1996; 110: A294.
- 26 Cooper BT, Neumann CS, Cox MA, Iqbal TH. Continuous treatment with omeprazole 20 mg daily for up to 6 years in Barrett's oesophagus. Aliment Pharmacol Ther 1998; 12: 893–7.
- 27 Malesci A, Savarino V, Zentilin P, et al. Partial regression of Barrett's esophagus by long term therapy with high dose omeprazole. Gastrointest Endosc 1996; 44: 700–5.
- 28 Wilkinson SP, Biddlestone L, Gore S, Shepherd NA. Regression of columnar lined Barrett's oesophagus with omeprazole 40 mg daily: results of five years continuous therapy. Aliment Pharmacol Ther 1999; 13: 1205–9.
- 29 Weston AP, Badr AS, Hassanein RS. Prospective multivariate analysis of factors predictive of complete regression of Barrett's esophagus. Am J Gastroenterol 1999; 94: 3420–6.
- 30 Srinivasan R, Katz PO, Ramakrishnan A, Katzka DA, Vela MF, Castell DO. Maximal acid reflux control: feasible and effective. Aliment Pharmacol Ther 2001; 15: 519–24.
- 31 Howden CW, Horning CA. Do proton pump inhibitors induce regression in Barrett's esophagus? Gastroenterology 1997; 112: A152.
- 32 Jankowski JA, Provenzale D, Moayyeddi P. Esophageal adenocarcinoma arising from Barrett's metaplasia has regional variations in the west. Gastroenterology 2002; 122: 588–91.
- 33 Sampliner RE, Steinbronn K, Garewal HS, Riddell RH. Squamous mucosa overlying columnar epithelium in Barrett's esophagus in the absence of anti-reflux surgery. Am J Gastroenterol 1988; 83: 510–2.
- 34 Drewitz DJ, Sampliner RE, Garewal HS. The incidence of adenocarcinoma in Barrett's esophagus: a prospective study of 170 patients followed 4.8 years. Am J Gastroenterol 1997; 92: 212–5.
- 35 Shaheen NJ, Crosby MA, Bozymski EM, Sandler RS. Is there publication bias in the reporting of cancer risk in Barrett's esophagus? Gastroenterology 2000; 119: 333–8.
- 36 Jankowski JA, Anderson M. Review article: Management of oesophageal adenocarcinoma – control of acid, bile and inflammation in intervention strategies for Barrett's oesophagus. Aliment Pharmacol Ther 2004; 20 (Suppl. 5): 71–80.
- 37 Gladman L, Chapman W, Iqbal TH, Cooper BT. Barrett's oesophagus: an audit of surveillance over 15 years. Gut 2004; 53: A54.
- 38 Basu KK, de Caestecker JS. Audit of a Barrett's epithelium surveillance database. Eur J Gastroenterol Hepatol 2004; 16: 171–5.
- 39 Murray L, Watson P, Johnston B, Sloan J, Mainie IML. Risk of adenocarcinoma in Barrett's oesophagus: a population based study. BMJ 2003; 327: 534–5.
- 40 Solaymani-Dodaran M, Logan RFA, West J, Card T, Coupland C. Risk of oesophageal cancer in Barrett's oesophagus and gastro-oesophageal reflux. Gut 2004; 53: 1070–4.
- 41 Hammeetman W, Tytgat GNJ, Houthoff HJ, van den Tweel JG. Barrett's esophagus: development of dysplasia and adenocarcinoma. Gastroenterology 1989; 96: 1249–56.
- 42 Reid BJ, Blount PL, Rubin CE, Levine DS, Haggitt RC, Rabinovitch PS. Flow cytometry and histological progression to malignancy in Barrett's esophagus. Gastroenterology 1992; 102: 1212–9.
- 43 Vieth M, Stolte M. Barrett's esophagus and neoplasia. Gastroenterology 2002; 122: 590.
- 44 Fitzgerald RC. Barrett's oesophagus and oesophageal adenocarcinoma: how does acid interfere with cell proliferation and differentiation? Gut 2005; 54: i21–6.
- 45 Fitzgerald RC, Omary MB, Triadafilopoulos G. Dynamic effects of acid on Barrett's esophagus: an ex vivo differentiation and proliferation model. J Clin Invest 1996; 68: 2120–8.
- 46 Souza RF, Shewmake K, Terada LS, et al. Acid exposure activates mitogen activated protein kinase pathways in Barrett's esophagus. Gastroenterology 2002; 122: 299–307.
- 47 Wilson KT, Fu S, Ramanujam KS, et al. Increased expression of inducible nitric oxide synthase and cyclo-oxygenase 2 in Barrett's esophagus and associated adenocarcinoma. Cancer Res 1998; 58: 2929–34.
- 48 Shirvani V, Ouatu-Luscar R, Kaur B, et al. Cyclo-oxygenase 2 expression in Barrett's esophagus and adenocarcinoma: ex vivo induction by bile salts and acid exposure. Gastroenterology 2000; 118: 467–96.
- 49 Ouatu-Luscar R, Fitzgerald RC, Triadafilopoulos G. Differentiation and proliferation in Barrett's esophagus and the effects of acid suppression. Gastroenterology 1999; 117: 327–5.
- 50 Umansky M, Yasui W, Hallak A, et al. Proton pump inhibitors reduce cell cycle abnormalities in Barrett's esophagus. Oncogene 2001; 20: 7987–91.
- 51 Kaur BS, Khamnehei N, Iravani M, et al. Rofecoxib inhibits cyclo-oxygenase 2 expression and activity and reduces cell proliferation in Barrett's esophagus. Gastroenterology 2002; 123: 60–7.
- 52 Spechler S, Lee E, Ahnen D, et al. Long term outcome of medical and surgical treatments for gastro-esophageal disease: follow up of a randomised trial. J Am Med Assoc 2001; 285: 2331–8.
- 53 Ye W, Chow WH, Lagergren J, et al. Risk of adenocarcinomas of the esophagus and gastric cardia in patients with gastro-esophageal diseases and after anti-reflux surgery. Gastroenterology 2001; 121: 1286–93.
- 54 Luostarinen M, Isolauri J, Laitinen J, et al. Fate of Nissen fundoplication after 20 years. A clinical, endoscopical and functional analysis. Gut 1993; 34: 1015–20.
- 55 Hillman LC, Chiragakis L, Shadbolt B, Kaye GL, Clarke AC. Proton pump inhibitor therapy and the development of dysplasia in patients with Barrett's oesophagus. Med J Aust 2004; 180: 387–91.
- 56 Farrow DC, Vaughan TL, Hansten PD, et al. Use of aspirin and other non-steroidal anti-inflammatory drugs and the risk esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prev 1998; 7: 97–102.
- 57 Basetti C, Talamini R, Franceschi SS, et al. Asprin use and cancers of the upper aerodigestive tract. Br J Cancer 2003; 88: 672–4.
- 58 Castell DO. Successful elimination of reflux symptoms does not ensure adequate control of acid reflux in patients with Barrett's esophagus. Am J Gastroenterol 1994; 89: 989–91.
- 59 Ouatu-Lascar R, Triadafilopoulos G. Complete elimination of reflux symptoms does not guarantee normalisation of intra-esophageal acid reflux in patients Barrett's esophagus. Am J Gastroenterol 1998; 93: 711–6.