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Use of omeprazole in patients with Zollinger-Ellison syndrome

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Abstract

Omeprazole, a substituted benzimidazole, has been shown to be a potent inhibitor of gastric acid secretion in patients with Zollinger-Ellison syndrome (ZES). We review our experience, as well as the published data on 210 patients with ZES who have required omeprazole for control of gastric acid hypersecretion over the past seven years. The dose of omeprazole required in individual patients ranged from 10 to 180 mg/24 hr with 20–60% requiring a split dosage regimen. Omeprazole was effective in approximately 99% of the patients over a period ranging from 0.5 to 54 months. Twenty-four percent of patients required an increase in omeprazole dose, while 26% required a decrease in dose. Adverse effects attributable to omeprazole were reported in 2% of patients, and in all cases, they were mild (ie, rash, constipation, headache). There was no effect of omeprazole on serum gastrin concentration or on gastric endocrine cells in three studies. Although one patient with multiple endocrine neoplasia, type-I syndrome (MEN-I) in this series developed a gastric carcinoid while taking omeprazole, evidence is presented that suggests the presence of MEN-Iper se may be important in determining the development of gastric carcinoid in patients with ZES. It is concluded that omeprazole is safe and effective in patients with ZES, and in these patients, it is the drug of choice for the management of gastric acid hypersecretion. However, yearly assessment is indicated to clearly evaluate the long-term risk of gastric carcinoid as well as therapy directed at the gastrinoma itself.

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References

  1. Zollinger RM, Ellison EH: Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann Surg 142:709–723, 1955

    Google Scholar 

  2. Jensen RT, Maton PN, Gardner JD: Current management of Zollinger-Ellison syndrome. Drugs 32:188–196, 1986

    Google Scholar 

  3. Jensen RT, Doppman JL, Gardner JD: Gastrinoma.In The Exocrine Pancreas: Biology, Pathobiology, Disease. VLW Go, JD Gardner, FP Brooks, E Lebenthal, EP Dimagno, G Scheele, (eds), New York: Raven Press, 1986, pp. 727–744.

    Google Scholar 

  4. Fox PS, Hofmann JW, Wilson SD, DECosse JJ: Surgical management of the Zollinger-Ellison syndrome. Surg Clin North Am 54:395–407, 1974

    Google Scholar 

  5. Bonfils S, Mignon M, Gratton J: Cimetidine treatment of acute and chronic Zollinger-Ellison syndrome. World J Surg 3:597–604, 1979

    Google Scholar 

  6. Jensen RT, Collen MJ, McArthur KE, Howard JM, Maton PN, Cherner JA, Gardner JD: Comparison of the effectiveness of ranitidine and cimetidine in inhibiting acid secretion in patients with gastric hypersecretory states.In Ranitidine: Therapeutic Advances. JJ Misiewicz, JR, Wood (eds). Amsterdam, Excerpta Medica, 1984; pp 168–198.

    Google Scholar 

  7. Vinayek R, Howard JM, Maton PN, Wank SA, Slaff JI, Gardner JD, Jensen RT: Famotidine in the therapy of gastric hypersecretory states. Am J Med 81 (4B):49–60, 1986

    Google Scholar 

  8. Wolfe MM, Jensen RT: Zollinger-Ellison syndrome. N Engl J Med 317:1200–1209, 1987

    Google Scholar 

  9. Bonfils S, Jensen RT, Malagelada J, Stadil F: Zollinger-Ellison syndrome management: A protocol for strategy. Gastroenterol Int 2:9–15, 1989

    Google Scholar 

  10. Zollinger RM, Ellison EC, Fabri PJ, Johnson J, Sparks J, Carey LC: Primary peptic ulcerations of the jejunum associated with islet cell tumors: Twenty-five year appraisal. Ann Surg 192:422–430, 1980

    Google Scholar 

  11. Thompson JC, Lewis BG, Wiener I, Townsend CM Jr: The role of surgery in the Zollinger-Ellison syndrome. Ann Surg 197:594–607, 1983

    Google Scholar 

  12. Maton PN, Frucht H, Vinayek R, Wank SA, Gardner JD, Jensen RT: Medical management of patients with Zollinger-Ellison syndrome who have had previous gastric surgery: A prospective study. Gastroenterology 94:294–299, 1988

    Google Scholar 

  13. Maton PN, Vinayek R, Frucht H, McArthur KA, Miller LS, Saeed ZA, Gardner JD, Jensen RT: Long-term efficacy and safety of omeprazole in patients with Zollinger-Ellison syndrome: A prospective study. Gastroenterology 97:827–836, 1989

    Google Scholar 

  14. Raufman JP, Collins SM, Pandol SJ, Korman LY, Collen MJ, Cornelius MJ, Feld MK, McCarthy DM, Gardner JD, Jensen RT: Reliability of symptoms in assessing control of gastric acid secretion in patients with Zollinger-Ellison syndrome. Gastroenterology 84:108–113, 1983

    Google Scholar 

  15. McCarthy DM: Report on the United States experience with cimetidine in Zollinger-Ellison syndrome and other hypersecretory states. Gastroenterology 74:453–458, 1978

    Google Scholar 

  16. Malagelada JR, Edis AJ, Adson MA, Von Heerden KA, Go VLW: Medical and surgical options in the management of patients with gastrinoma. Gastroenterology 84:1524–1532, 1983

    Google Scholar 

  17. Howard JM, Chremos AN, Collen MJ, McArthur KE, Cherner JA, Maton PN, Ciarleglio CA, Cornelius MJ, Gardner JD, Jensen RT: Famotidine, a new, potent, long-acting histamine H2-receptor antagonist: Comparison with cimetidine and ranitidine in the treatment of Zollinger-Ellison syndrome. Gastroenterology 88:1026–1033, 1985

    Google Scholar 

  18. Jensen RT, Gardner JD, Raufman JP, Pandol SJ, Doppman JL, Collen MJ: Zollinger-Ellison syndrome. NIH Combined Clinical Staff Conference (RT Jensen, moderator). Ann Intern Med 98:59–75, 1983

    Google Scholar 

  19. McCarthy DM, Hyman PE: Effect of isopropamide on response to oral cimetidine in patients with Zollinger-Ellison syndrome. Dig Dis Sci 27:353–359, 1982

    Google Scholar 

  20. McCarthy DM, Olinger DM, May EJ, Long BW, Gardner JD: H2-histamine receptor blocking agents in the Zollinger-Ellison syndrome. Ann Intern Med 87:668–675, 1977

    Google Scholar 

  21. Collen MJ, Howard JM, McArthur KE, Raufman JP, Cornelius MJ, Ciarleglio CA, Gardner JD, Jensen RT: Comparison of ranitidine and cimetidine in the treatment of gastric hypersecretion. Ann Intern Med 100:52–58, 1984

    Google Scholar 

  22. Jensen RT, Collen MJ, Allende HD, Raufman JP, Bissonnette BM, Duncan WC, Durgin PL, Gillin JC, Gardner JD: Cimetidine-induced impotence and breast changes in patients with gastric hypersecretory states. N Engl J Med 308:883–887, 1983

    Google Scholar 

  23. Miller LS, Vinayek H, Frucht H, Gardner JD, Jensen RT, Maton PN: Reflux esophagitis in patients with Zollinger-Ellison syndrome. Gastroenterology 98:341–346, 1990

    Google Scholar 

  24. Larsson H, Carlsson E, Junggren U, Olbe L, Sjostrand SE, Skanberg I, Sundell G: Inhibition of gastric acid secretion by omeprazole in the dog and rat. Gastroenterology 85:900–907, 1983

    Google Scholar 

  25. Olbe L, Haglund U, Leth R, Lind T, Cederberg C, Ekenved G, Elander B, Fellenius E, Lundberg P, Wallmark B: Effects of substituted benzimidazole (H 149/94) on gastric acid secretion in humans. Gastroenterology 83:193–198, 1982

    Google Scholar 

  26. Fellenius E, Berglindh T, Brandstron A, Elander B, Helander HF, Olbe L, Sachs G, Sjostrand SE, Wallmark B: The inhibitory action of substituted benzimidazoles on isolated oxyntic glands and H+/K+-ATPase.In Hydrogen Ion Transport in Epithelia. I Schulz, G Sachs, J Forte, KJ Ullrich (eds). 1980, pp 193–202

  27. Fellenius E, Berglindh T, Sachs G, Olbe L, Elander B, Sjostrand SE, Wallmark B: Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+/K+)ATPase. Nature 290:159–161, 1981

    Google Scholar 

  28. Blanchi A, Delchier JC, Soule JC, Payen D, Bader JP: Control of acute Zollinger-Ellison syndrome with intravenous omeprazole. Lancet 2:1223–1224, 1982

    Google Scholar 

  29. Oberg K, Lindstrom H: Reduction of gastric hypersecretion in Zollinger-Ellison syndrome with omeprazole. Lancet 1:66–67, 1983

    Google Scholar 

  30. Lamers CBHW, Lind T, Moberg S, Jansen JBMJ, Olbe L: Omeprazole in Zollinger-Ellison syndrome. Effects of a single dose and of long-term treatment in patients resistant to histamine H2-receptor antagonists. N Engl J Med 310:758–761, 1984

    Google Scholar 

  31. Vezzadini P, Tomassetti P, Toni R, Bonora G, Labo G: Omeprazole in the medical treatment of Zollinger-Ellison syndrome. Curr Ther Res 35:772–776, 1984

    Google Scholar 

  32. McArthur KE, Collen MJ, Maton PN, Cherner JA, Howard JM, Ciarleglio CA, Cornelius MJ, Jensen RT, Gardner JD: Omeprazole: Effective, convenient therapy for Zollinger-Ellison syndrome. Gastroenterology 88:939–944, 1985

    Google Scholar 

  33. Delchier JC, Soule JC, Mignon M, Goldfain D, Cortot A, Travers B, Isal JP, Bader JP: Effectiveness of omeprazole in seven patients wtih Zollinger-Ellison syndrome resistant to histamine H2-receptor antagonists. Dig Dis Sci 31:693–699, 1986

    Google Scholar 

  34. Bardram L, Stadil F: Omeprazole in the Zollinger-Ellison syndrome. Scand J Gastroenterol 21:374–378, 1986

    Google Scholar 

  35. Lloyd-Davies KA, Rutgersson K, Solvell L: Omeprazole the treatment of Zollinger-Ellison syndrome: A 4-year international study. Aliment Pharmacol Ther 2:13–32, 1988

    Google Scholar 

  36. Hirschowitz BI, Deren J, Raufman JP, LaMont B, Berman R, Humphries T: A multicenter US study of omeprazole treatment of Zollinger-Ellison syndrome (ZES). Gastroenterology 94:A188, 1988

    Google Scholar 

  37. Corleto J, Puoti M, Annibale B, Saggioro A, D'Ambra G, DiPaola M, Della Fave G: Loss of efficacy of famotidine (FMT) in the control of gastric acid secretion in patients with Zollinger-Ellison syndrome (ZES) reversed by omeprazole (OMP). Gastroenterology 94:A79, 1988

    Google Scholar 

  38. Vezzadini P, Tomassetti P, Marrano D, Labo G: Life threatening gastrointestinal hemorrhage with omeprazole. Dig Dis Sci 33:766–767, 1988

    Google Scholar 

  39. Lehy T, Mignon M, Cadiot G, Elouaer-Blanc L, Ruszniewski P, Levin MJM, Bonfils S: Gastric endocrine cell behavior in Zollinger-Ellison patients upon long-term antisecretory treatment. Gastroenterology 96:1029–1040, 1989

    Google Scholar 

  40. Jensen RT: The basis for cimetidine failure in Zollinger-Ellison syndrome. Dig Dis Sci 29:363–367, 1984

    Google Scholar 

  41. Brodgen RN, Lormine A, Neel C, Speight TM, Avery GS: Ranitidine: A review of its pharmacology and therapeutic use in peptic ulcer disease and other allied diseases. Drug 24:267–303, 1982

    Google Scholar 

  42. Hetzel DJ, Dent J, Reed WD, Narielvala FM, Mackinnon M, mcCarthy JH, Mitchell B, Beveridge BR, Laurence BH, Gibson CG, Grant AK, Shearman DJC, Whitehead R, Buckle PJ: Healing and relapse of severe peptic esophagitis after treatment with omeprazole. Gastroenterology 95:903–912, 1988

    Google Scholar 

  43. Fraker DL, Norton JA, Saeed ZA, Maton PN, Gardner JD, Jensen RT: A prospective study of perioperative and postoperative control of acid hypersecretion in patients with Zollinger-Ellison syndrome undergoing gastrinoma resection. Surgery 104:1054–1063, 1988

    Google Scholar 

  44. Norton JA, Cornelius MJ, Doppman JL, Maton PN, Gardner JD, Jensen RT: Effect of parathyroidectomy in patients with hyperparathyroidism, Zollinger-Ellison syndrome, and multiple endocrine neoplasia type I: A prospective study. Surgery 102:958–966, 1987

    Google Scholar 

  45. Clissold SP, Campoli-Richards DM: Omeprazole: A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in peptic ulcer disease and Zollinger-Ellison syndrome. Drugs 32:15–47, 1986

    Google Scholar 

  46. Regardh CG, Gabrielsson M, Hoffman K-J, Lofberg I, Skaberg I: Pharmacokinetics and metabolism of omeprazole in animals and man—an overview. Scand J Gastroenterol 29(suppl 108):79–94, 1985

    Google Scholar 

  47. Ekman L, Hansson E, Havu N, Carlsson E, Lundberg C: Toxicological studies on omeprazole. Scand J Gastroenterol 20(Suppl 108):53–69, 1985

    Google Scholar 

  48. Havu N: Enterochromaffin-like cell carcinoids of gastric mucosa in rats after life-long inhibition of gastric secretion. Digestion 35(suppl 1):42–55, 1986

    Google Scholar 

  49. Larson H, Carlson E, Mattsson H, Lundeu L, Sundler F, Sundeu G, Wallmark B, Watenabe T, hakanson R: Plasma gastrin and gastric enterochromaffin cell activation and proliferation—studies wtih omeprazole and ranitidine in intact and antrectomized rats. Gastroenterology 90:391–399, 1986

    Google Scholar 

  50. Wormsley KG: Assessing the safety of drugs for the longterm treatment of peptic ulcers. Gut 25:1416–1423, 1984

    Google Scholar 

  51. Solcia E, Bordi C, Creutzfeldt W, Dayal Y, Dayan AD, Falkmer S, Grimelius L, Havu N: Histopathological classification of nonantral gastric endocrine growths in man. Digestion 41:185–200, 1988

    Google Scholar 

  52. Carney JA, Go, VLM, Fairbanks VF, Moore SB, Alport EC, Nora FE: The syndrome of gastric argyrophil carcinoid tumors and nonantral gastric atrophy. Ann Intern Med 99:761–766, 1983

    Google Scholar 

  53. Solcia E, Capella C, Sessa F, Rindi G, Cornaggia M, Riva C, Villani L: Gastric carcinoids and related endocrine growths. Digestion 35(suppl 1):3–22, 1986

    Google Scholar 

  54. Goldfain D, LeBodic MF, Lavergne A, Galian A, Modigliani R: Gastric carcinoid tumors in patients with Zollinger-Ellison syndrome on long term omeprazole. Lancet 1:776–777, 1989

    Google Scholar 

  55. Solcia E, Capella C, Vassallo G: Endocrine cells of the stomach and pancreas in states of gastric hypersecretion. Rend R Gastroenterol 2:147–158, 1970

    Google Scholar 

  56. Solcia E, Capella C, Vassallo G, Buffa R: Endocrine cells of the gastric mucosa. Int Rev Cytol 42:223–286, 1975

    Google Scholar 

  57. Solcia E, Capella C, Buffa R, Frigerio B, Fiocca R: Pathology of the Zollinger-Ellison syndrome.In Progress in Surgical Pathology, Vol I. CM Fenoglio (ed) New York, Masson Publishing, 1980, pp 119–133

    Google Scholar 

  58. Bordi C, Cocconi G, Togni R, Vezzadini P, Missale G: Gastric endocrine cell proliferation association with Zollinger-Ellison syndrome. Arch Pathol 98:274–278, 1974

    Google Scholar 

  59. Bordi C, Ravazzola M, De Vita O: Pathology of endocrine cells in gastric mucosa. Ann Pathol 3:19–28, 1983

    Google Scholar 

  60. Larsson H, Carlsson E, Mattsson H, Lundell L, Sundler F, Sundell G, Wallmark B, Watanabe T, Hakanson R: Plasma gastrin and gastric enterochromaffin-like cell activation and proliferation: Studies with omeprazole and ranitidine in intact and antrectomized rats. Gastroenterology 90:391–399, 1986

    Google Scholar 

  61. Ryberg B, Hakanson R, Lundell L, Sundler F, Mattsson H: Trophic effects of continuous infusion of [Leu15]-gastrin-17 in the rat. Gastroenterology 98:33–38, 1990

    Google Scholar 

  62. Creutzfeldt W: The achlorhydria-carcinoid sequence: role of gastrin. Digestion 39:61–79, 1988

    Google Scholar 

  63. Mattsson H, Havu N, Carlsson K, Brautigam J, Lundell L, Carlsson E: Partial fundectomy results in hypergastrinemia and the development of gastric ECL cell carcinoids in the rat. Gastroenterology 96:A330, 1989

    Google Scholar 

  64. Maton PN, Lack E, Collen MJ, Cornelius MJ, David E, Gardner JD, Jensen RT: The effect of Zollinger-Ellison syndrome and omeprazole therapy on gastric endocrine cells. Gastroenterology 99:943–950, 1990

    Google Scholar 

  65. Bardram L, Thomsen P, Stadil F: Gastric endocrine cells in omeprazole-treated and untreated patients with Zollinger-Ellison syndrome. Digestion 35(suppl 1):116–122, 1986

    Google Scholar 

  66. D'Adda T, Corleto V, Pilato FP, Baggi MT, Robutti F, Delle Fave G, Bordi C: Quantitative ultrastructure of endocrine cells of oxyntic mucosa in Zollinger-Ellison syndrome. Gastroenterology 99:17–26, 1990

    Google Scholar 

  67. Rosai J: Stomach. Multiple carcinoid tumors. 7th Congress of the European Society of Pathology. Slide Seminar: Problems in diagnostic surgical pathology. Case 9.5. September 1979. Valencia, Spain. Quoted in ref. 53.

  68. Duggan M, Anderson C: Mixed type Zollinger-Ellison syndrome in a florid case of multiple endocrine neoplasia type I. Am J Clin Pathol 82:481–486, 1984

    Google Scholar 

  69. Mignon M, Lehy T, Bonnefond A, Ruszniewski P, Labeille D, Bonfils S: Development of gastric argyrophil carcinoid tumors in a case of Zollinger-Ellison syndrome with primary hyperparathyroidism during long term antisecretory treatment. Cancer 59:1959–1962, 1987

    Google Scholar 

  70. Solcia E, Capella C, Buffa R, Usellini L, Frigerio B, Fontana P: Endocrine cells of the gastrointestinal tract and related tumors. Pathobiol Ann 9:163–203, 1979

    Google Scholar 

  71. Dotevall G, Walan A: Gastric secretion after stimulation with pentagastrin and histamine.In Origin, Chemistry, Physiology and Pathophysiology of the Gastrointestinal Hormones. W Creutzfeldt (ed). Stuttgart, Schattauer, 1970, pp 240

    Google Scholar 

  72. Bordi C, Senatore S, Missale G: Gastric carcinoid following gastrojejunostomy. Am J Dig Dis 21:667–671, 1976

    Google Scholar 

  73. Solcia E, Capella C, Fiocca R, Cornaggia M, Bosi F: The gastroenteropancreatic endocrine system and related tumors. Gastroenterol Clin North Am 18:671–693, 1989

    Google Scholar 

  74. Mignon M, Ruszniewski P, Haffar S, Rigaud D, Rene E, Bonfils S: Current approach to the management of tumoral process in patients with gastrinoma. World J Surg 10:703–710, 1986

    Google Scholar 

  75. Borch K, Renvall H, Liedberg G: Gastric endocrine cell hyperplasia and carcinoid tumors in permicious anemia. Gastrenterology 88:638–648, 1985

    Google Scholar 

  76. Lehtola J, Karttunen T, Krekela I, Niemela S, Rasanen O: Gastric carcinoids with minimal or no macroscopic lesion in patients with pernicious anemia. Hepatogastroenterology 32:72–76, 1985

    Google Scholar 

  77. Stockbrugger RW, Menon GG, Beilby JO, Mason RR, Cotton PB: Gastroscopic screening in 80 patients with pernicious anaemia. Gut 24:1141–1147, 1983

    Google Scholar 

  78. Axelson J, Ekelund M, Sundler F, Hakanson R: Enhanced hyperplasia of gastric enterochromaffinlike cells in response to omeprazole-evoked hypergastrinemia in rats with portocaval shunts. Gastroenterology 99:635–640, 1990

    Google Scholar 

  79. Jensen RT, Maton PN: Zollinger-Ellison syndrome.In The Stomach. S. Gustavsson, D Kuman, DY Graham (eds). London, Churchill-Livingstone (in press)

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Frucht, H., Maton, P.N. & Jensen, R.T. Use of omeprazole in patients with Zollinger-Ellison syndrome. Digest Dis Sci 36, 394–404 (1991). https://doi.org/10.1007/BF01298865

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