Nonsteroidal antiinflammatory drugs and cyclooxygenase inhibition in the gastrointestinal tract: A trip from peptic ulcer to colon cancer

American Journal of the Medical Sciences

Volumn 338, Issue 2, 2009, Pages 96-106

  Lanas, Angel ^a  

^a HOSPITAL CLÍNICO UNIVERSITARIO LOZANO BLESA   (Spain)

Author keywords

Aspirin; Chemoprevention; Colon cancer; Cyclooxygenase; Gastrointestinal bleeding; NSAIDs; Peptic ulcer

Indexed keywords

ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; CELECOXIB; CLOPIDOGREL; CORTICOSTEROID; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; CYCLOOXYGENASE 2 INHIBITOR; DICLOFENAC; FENAMIC ACID DERIVATIVE; IBUPROFEN; KETOPROFEN; LANSOPRAZOLE; LORNOXICAM; LUMIRACOXIB; MELOXICAM; MISOPROSTOL; NAPROXEN; NONSTEROID ANTIINFLAMMATORY AGENT; OMEPRAZOLE; PLACEBO; PROSTAGLANDIN SYNTHASE INHIBITOR; PROTON PUMP INHIBITOR; RIFAXIMIN; ROFECOXIB; SALAZOSULFAPYRIDINE; SEROTONIN UPTAKE INHIBITOR; STOMACH SECRETION INHIBITOR; SULINDAC; UNINDEXED DRUG;

ABDOMINAL DISEASE; ATROPHIC GASTRITIS; BLEEDING; CAPSULE ENDOSCOPY; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CLINICAL TRIAL; COLON CANCER; COLON INJURY; COLON POLYP; COLONOSCOPY; DIARRHEA; DIGESTIVE SYSTEM ULCER; DRUG FATALITY; DRUG MEGADOSE; DRUG WITHDRAWAL; DUODENUM ULCER; DYSPEPSIA; EDEMA; ENTERIC COATED TABLET; ENTERITIS; ENTEROPATHY; ERYTHEMA; ESOPHAGEAL ADENOCARCINOMA; ESOPHAGITIS; ESOPHAGUS CANCER; GASTROINTESTINAL DISEASE; GASTROINTESTINAL SYMPTOM; GASTROINTESTINAL TRACT; GENETIC SUSCEPTIBILITY; HELICOBACTER INFECTION; HELICOBACTER PYLORI; HOSPITALIZATION; HUMAN; HYPOALBUMINEMIA; INTESTINE INJURY; INTESTINE MUCOSA PERMEABILITY; IRON DEFICIENCY ANEMIA; LOW DRUG DOSE; MALABSORPTION; MUCOSAL BLEEDING; NONHUMAN; OBSERVATIONAL STUDY; PEPTIC ULCER; PROSTATE CANCER; RECURRENCE RISK; REVIEW; RHEUMATOID ARTHRITIS; RISK FACTOR; RISK REDUCTION; STOMACH CANCER; STOMACH EROSION; STOMACH ULCER; TREATMENT DURATION; ULCERATIVE COLITIS; UPPER GASTROINTESTINAL TRACT;

EID: 69349087916     PISSN: 00029629     EISSN: None     Source Type: Journal    
DOI: 10.1097/MAJ.0b013e3181ad8cd3     Document Type: Article

References (146)

1. Wallace JL. Nonsteroidal anti-inflammatory drugs and gastroenteropathy: the second hundred years. Gastroenterology 1997;112:1000-1016
2. Kujubu DA, Fletcher BS, Varnum BC, et al. TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue. J Biol Chem 1991;266:12866-12872
3. O'Banion MK, Sadowski HB, Winn V, et al. A serum- and glucocorticoid-regulated 4-kilobase mRNA encodes a cyclooxygenase-related protein. J Biol Chem 1991;266:23261-23267 (Pubitemid 21908788)
4. FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med 2001;345:433-442
5. Doherty GA, Murray FE. Cyclooxygenase as a target for chemoprevention in colorectal cancer: lost cause or a concept coming of age? Expert Opin Ther Targets 2009;13:209-218
6. Lanas A, Hunt R. Prevention of anti-inflammatory drug-induced gastrointestinal damage: benefits and risks of therapeutic strategies. Ann Med 2006;38:415-428 (Pubitemid 44484879)
7. Wallander MA, Johansson S, Ruigómez A, et al. Dyspepsia in general practice: incidence, risk factors, comorbidity and mortality. Fam Pract 2007;24:403-411 (Pubitemid 350142636)
8. Weil J, Colin-Jones D, Langman M, et al. Prophylactic aspirin and risk of peptic ulcer bleeding. BMJ 1995;310:827-830
9. Lanas AI, Arroyo MT, Esteva F, et al. Aspirin related gastrointestinal bleeders have an exaggerated bleeding time response due to aspirin use. Gut 1996;39:654-660 (Pubitemid 26426464)
10. Piazuelo E, Fuentes J, Garcfa-González MA, et al. A case-control study of the association between polymorphisms of the endothelial nitric oxide synthase and glycoprotein IIIa genes and upper gastrointestinal bleeding in users of low-dose aspirin. Clin Ther 2008;30:121-130 (Pubitemid 351836067)
11. Hirschowitz BI, Lanas A. Intractable upper gastrointestinal ulceration due to aspirin in patients who have undergone surgery for peptic ulcer. Gastroenterology 1998;114:883-892 (Pubitemid 28217553)
12. Lanas A, Remacha B, Sáinz R, et al. Study of outcome after targeted intervention for peptic ulcer resistant to acid suppression therapy. Am J Gastroenterol 2000;95:513-519 (Pubitemid 30106186)
13. Lanas A, Hirschowitz BI. Significant role of aspirin use in patients with esophagitis. J Clin Gastroenterol 1991;13:622-627
14. Singh G, Triadafilopoulos G. Epidemiology of NSAID induced gastrointestinal complications. J Rheumatol 1999;26(suppl 56):18-24. (Pubitemid 29183022)
15. Lanas A, Perez-Aisa MA, Feu F, et al. A nationwide study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with non-steroidal anti-inflammatory drug use. Am J Gastroenterol 2005;100:1685-1693 (Pubitemid 41648418)
16. Lanas A, García Rodriguez LA, Polo M, et al. Time trends of upper and lower gastrointestinal bleeding and perforation. Am J Gastroenteriol 2009;104:1633-1641
17. Pérez-Aisa MA, Del Pino D, Siles M, et al. Clinical trends in ulcer diagnosis in a population with high prevalence of Helicobacter pylori infection. Aliment Pharmacol Ther 2005;21:65-72.
18. Lanza FL, Chan FK, Quigley EM; Practice Parameters Committee of the American College of Gastroenterology. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol 2009;104:728-738
19. Chan FK, Chung SC, Suen BY, et al. Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med 2001;344:967-973
20. Laine L, Bombardier C, Hawkey CJ, et al. Stratifying the risk of NSAID-related upper gastrointestinal clinical events: results of a double-blind outcomes study in patients with rheumatoid arthritis. Gastroenterology 2002;123:1006-1012
21. Laine L. Proton pump inhibitor co-therapy with nonsteroidal antiinflammatory drugs - nice or necessary? Rev Gastroenterol Disord 2004;4(suppl 4):S33-S41.
22. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med 1999;340:1888-1899 (Pubitemid 29272670)
23. Lanas A, García-Rodríguez LA, Arroyo MT, et al. Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations. Gut 2006;55:1731-1738 (Pubitemid 44893570)
24. Hernández-Díaz S, García Rodríguez LA. Cardioprotective aspirin users and their excess risk of upper gastrointestinal complications. BMC Med 2006;4:22.
25. Bombardier C, Laine L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000;343:1520-1528 (Pubitemid 30844348)
26. Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 2000;284:1247-1255 (Pubitemid 30691365)
27. Schnitzer TJ, Burmester GR, Mysler E, et al. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial. Lancet 2004;364:665-674 (Pubitemid 39140622)
28. Emery P, Zeidler H, Kvien TK, et al. Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison. Lancet 1999;354:2106-2111 (Pubitemid 30008893)
29. Rostom A, Muir K, Dubé C, et al. Gastrointestinal safety of cyclooxygenase-2 inhibitors: a Cochrane Collaboration systematic review. Clin Gastroenterol Hepatol 2007;5:818-828 (Pubitemid 47031062)
30. Singh G, Fort JG, Goldstein JL, et al. Celecoxib versus naproxen and diclofenac in osteoarthritis patients: SUCCESS-I Study. Am J Med 2006;119:255-266 (Pubitemid 43255067)
31. Laine L, Maller ES, Yu C, et al. Ulcer formation with low-dose enteric-coated aspirin and the effect of COX-2 selective inhibition: a double-blind trial. Gastroenterology 2004;127:395-402. (Pubitemid 39091887)
32. Rahme E, Bardou M, Dasgupta K, et al. Hospitalization for gastrointestinal bleeding associated with non-steroidal anti-inflammatory drugs among elderly patients using low-dose aspirin: a retrospective cohort study. Rheumatology (Oxford) 2007;46:265-272 (Pubitemid 46189787)
33. Rahme E, Nedjar H, Bizzi A, et al. Hospitalization for gastrointestinal adverse events attributable to the use of low-dose aspirin among patients 50 years or older also using non-steroidal anti-inflammatory drugs: a retrospective cohort study. Aliment Pharmacol Ther 2007;26:1387-1398 (Pubitemid 350045614)
34. Goldstein JL, Cryer B, Amer F, et al. Celecoxib plus aspirin versus naproxen and lansoprazole plus aspirin: a randomized, double-blind, endoscopic trial. Clin Gastroenterol Hepatol 2007;5:1167-1174 (Pubitemid 47488966)
35. Cannon CP, Curtis SP, FitzGerald GA, et al. Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet 2006;368:1771-1781 (Pubitemid 44739003)
36. Farkouh ME, Kirshner H, Harrington RA, et al. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomised controlled trial. Lancet 2004;364:675-684 (Pubitemid 39140623)
37. Huang JQ, Sridhar L, Hunt RH. Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis. Lancet 2002;359:14-22.
38. Chan FK, Sung JJ, Chung SC, et al. Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers. Lancet 1997;350:975-979
39. Chan FK, To KF, Wu JC, et al. Eradication of Helicobacter pylori and risk of peptic ulcers in patients starting long-term treatment with non-steroidal anti-inflammatory drugs: a randomised trial. Lancet 2002;359:9-13.
40. Labenz J, Blum AL, Bolten WW, et al. Primary prevention of diclofenac associated ulcers and dyspepsia by omeprazole or triple therapy in Helicobacter pylori positive patients: a randomised, double blind, placebo controlled, clinical trial. Gut 2002;51:329-335
41. Lanas A, Fuentes J, Benito R, et al. Helicobacter pylori increases the risk of upper gastrointestinal bleeding in patients taking low-dose aspirin. Aliment Pharmacol Ther 2002;16:779-786
42. Hawkey CJ, Tulassay Z, Szczepanski L, et al. Randomised controlled trial of Helicobacter pylori eradication in patients on nonsteroidal anti-inflammatory drugs: HELP NSAIDs study. Helicobacter eradication for lesion prevention. Lancet 1998;352:1016-1021 (Pubitemid 28438573)
43. Chan FK, Hung LC, Suen BY, et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med 2002;347:2104-2110 (Pubitemid 36015122)
44. Chan FK, Ching JY, Hung LC, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med 2005;352:238-244 (Pubitemid 40110812)
45. Lai KC, Lam SK, Chu KM, et al. Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. N Engl J Med 2002;346:2033-2038 (Pubitemid 34680594)
46. Chan F, Ching J, Suen B, et al. Eradication of H. pylori for the prevention of recurrent ulcer bleeding in high-risk aspirin users: a 4-year prospective cohort study. Gastroenterology 2005;128(4 pt 2):835.
47. Scheiman JM, Fendrick AM. Summing the risk of NSAID therapy. Lancet 2007;369:1580-1581
48. Bresalier RS, Sandler RS, Quan H, et al; Adenomatous Polyp Prevention on Vioxx (APPROVe) Trial Investigators. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 2005;352:1092-1102
49. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA 2006;296:1633-1644 (Pubitemid 44511610)
50. Chan FK, Wong VW, Suen BY, et al. Combination of a cyclooxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial. Lancet 2007;369:1621-1626
51. Catella-Lawson F, Reilly MP, Kapoor SC, et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med 2001;345:1809-1817 (Pubitemid 34940862)
52. Ho PM, Maddox TM, Wang L, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009;301:937-944
53. Bhatt DL, Scheiman J, Abraham NS, et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2008;52:1502-1517
54. Lai K, Hui W, Wong B, et al. Lansoprazole but not rofecoxib reduced dyspeptic symptoms of patients on NSAIDs. Gastroenterology 2005;128(4 pt 2):137.
55. Hawkey C, Talley NJ, Yeomans ND, et al. Improvements with esomeprazole in patients with upper gastrointestinal symptoms taking non-steroidal antiinflammatory drugs, including selective COX-2 inhibitors. Am J Gastroenterol 2005;100:1028-1036 (Pubitemid 40769038)
56. Laine L, Smith R, Min K, et al. Systematic review: the lower gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 2006;24:751-767 (Pubitemid 44244899)
57. Whittle BJR. Mechanisms underlying intestinal injury induced by anti-inflammatory COX inhibitors. Eur J Pharmacol 2004;500:427-439
58. Smecuol E, Bai JC, Sugai E, et al. Acute gastrointestinal permeability responses to different non-steroidal anti-inflammatory drugs. Gut 2001;49:650-655 (Pubitemid 32989201)
59. Fortun PJ, Hawkey CJ. Nonsteroidal anti-inflammatory drugs and the small intestine. Curr Opin Gastroenterol 2005;21:169-175 (Pubitemid 40316198)
60. Reuter BK, Davies NM, Wallace JL. Nonsteroidal anti-inflammatory drug enteropathy in rats: role of permeability, bacteria, and enterohepatic circulation. Gastroenterology 1997;112:109-117
61. Bjarnason I, Hayllar J, Macpherson AJ, et al. Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology 1993;104:1832-1847 (Pubitemid 23235480)
62. Lanas A, Panés J, Piqué JM. Clinical implications of COX-1 and/or COX-2 inhibition for the distal gastrointestinal tract. Curr Pharm Des 2003;9:2253-2266 (Pubitemid 37139098)
63. Sigthorsson G, Simpson RJ, Walley M, et al. COX-1 and 2, intestinal integrity and pathogenesis of nonsteroidal anti-inflammatory drug enteropathy in mice. Gastroenterology 2002;122:1913-1923.
64. Davies NM. Non-steroidal anti-inflammatory drug-induced gastrointestinal permeability. Aliment Pharmacol Ther 1998;12:303-320 (Pubitemid 28182211)
65. Lanas A, Sopeña F. Nonsteroidal anti-inflammatory drugs and lower gastrointestinal complications. Gastroenterol Clin North Am 2009;38:333-352
66. Chmaisse HM, Antoon JS, Kvietys PR, et al. Role of leukocytes in indomethacin-induced small bowel injury in the rat. Am J Physiol 1994;266:G239-G246. (Pubitemid 24094782)
67. Stadnyk AW, Dollard C, Issekutz TB, et al. Neutrophil migration into indomethacin induced rat small intestinal injury is CD11a/CD18 and CD11b/CD18 codependent. Gut 2002;50:629-635 (Pubitemid 34407488)
68. Hagiwara M, Kataoka K, Arimochi H, et al. Role of unbalanced growth of gram-negative bacteria in ileal ulcer formation in rats treated with a nonsteroidal anti-inflammatory drug. J Med Invest 2004;51:43-51. (Pubitemid 38899321)
69. Scarpignato C. NSAID-induced intestinal damage: are luminal bacteria the therapeutic target? Gut 2008;57:145-148
70. Lanas A, Scarpignato C. Microbial flora in NSAID induced intestinal damage: a role for antibiotics? Digestion 2006;73(suppl 1):36-50.
71. Adebayo D, Bjarnason I. Is non-steroidal anti-inflammatory drug (NSAID) enteropathy clinically more important than NSAID gastropathy? Postgrad Med J 2006;82:186-191
72. Bjarnason I, Williams P, Smethurst P, et al. Effect of non-steroidal anti-inflammatory drugs and prostaglandins on the permeability of the human small intestine. Gut 1986;27:1292-1299 (Pubitemid 17175676)
73. Bjarnason I, Zanelli G, Prouse P, et al. Blood and protein loss via small intestinal inflammation induced by nonsteroidal antiinflammatory drugs. Lancet 1987;2:711-714 (Pubitemid 17125695)
74. Bjarnason I, Smethurst P, Macpherson A, et al. Glucose and citrate reduce the permeability changes caused by indomethacin in humans. Gastroenterology 1992;102:1546-1550
75. Sigthorsson G, Crane R, Simon T, et al. COX-2 inhibition with rofecoxib does not increase intestinal permeability in healthy subjects: a double blind crossover study comparing rofecoxib with placebo and indomethacin. Gut 2000;47:527-532
76. Morris AJ, Madhok R, Sturrock RD, et al. Enteroscopic diagnosis of small bowel ulceration in patients receiving non-steroidal antiin- flammatory drugs. Lancet 1991;337:520.
77. Moore RA, Derry S, McQuay HJ. Faecal blood loss with aspirin, nonsteroidal anti-inflammatory drugs and cyclo-oxygenase-2 selective inhibitors: systematic review of randomized trials using autologous chromium-labelled erythrocytes. Arthritis Res Ther 2008;10:R7. (Pubitemid 351189041)
78. Bjarnason I, Zanelli G, Smith T, et al. The pathogenesis and consequence of non steroidal anti-inflammatory drug induced small intestinal inflammation in man. Scand J Rheumatol Suppl 1987;64:55-62. (Pubitemid 18047195)
79. Freeman HJ. Sulindac-associated small bowel lesion. J Clin Gastroenterol 1986;8:569-571
80. Etienney I, Beaugerie L, Viboud C, et al. Non-steroidal antiinflammatory drugs as a risk factor for acute diarrhoea: a case cross-over study. Gut 2003;52:260-263 (Pubitemid 36115069)
81. Costamagna G, Shah SK, Riccioni ME, et al. A prospective trial comparing small bowel radiographs and video capsule endoscopy for suspected small bowel disease. Gastroenterology 2002;123:999-1005.
82. Smecuol E, Pinto Sanchez MI, Suarez A, et al. A low-dose aspirin affects the small bowel mucosa: results of a pilot study with a multidimensional assessment. Clin Gastroenterol Hepatol 2009;7:524-529
83. Lanas A, Sekar MC, Hirschowitz BI. Objective evidence of aspirin use in both ulcer and non-ulcer upper and lower gastrointestinal bleeding. Gastroenterology 1992;103:862-869
84. Lanas A, Serrano P, Bajador E, et al. Evidence of aspirin use in both upper and lower gastrointestinal perforation. Gastroenterology 1997;112:683-689 (Pubitemid 27113792)
85. Zuccaro G. Epidemiology of lower gastrointestinal bleeding. Best Pract Res Clin Gastroenterol 2008;22:225-232
86. Kurahara K, Matsumoto T, Iida M, et al. Clinical and endoscopic features of nonsteroidal anti-inflammatory drug-induced colonic ulcerations. Am J Gastroenterol 2001;96:473-480
87. Felder JB, Korelitz BI, Rajapakse R, et al. Effects of nonsteroidal antiinflammatory drugs on inflammatory bowel disease: a case control study. Am J Gastroenterol 2000;95:1949-1954 (Pubitemid 30629292)
88. Forrest K, Symmons D, Foster P. Systematic review: is ingestion of paracetamol or non-steroidal anti-inflammatory drugs associated with exacerbations of inflammatory bowel disease? Aliment Pharmacol Ther 2004;20:1035-1043
89. Sandborn WJ, Stenson WF, Brynskov J, et al. Safety of celecoxib in patients with ulcerative colitis in remission: a randomized, placebo-controlled, pilot study. Clin Gastroenterol Hepatol 2006;4:203-211 (Pubitemid 43199691)
90. Lang J, Price AB, Levi AJ, et al. Diaphragm disease: pathology of disease of the small intestine induced by non-steroidal anti-inflammatory drugs. J Clin Pathol 1988;41:516-526 (Pubitemid 18126444)
91. Blandizzi C, Tuccori M, Colucci R, et al. Role of coxibs in the strategies for gastrointestinal protection in patients requiring chronic non-steroidal anti-inflammatory therapy. Pharmacol Res 2009;59:90-100.
92. Laine L, Connors LG, Reicin A, et al. Serious lower gastrointestinal clinical events with nonselective NSAID or coxib use. Gastroenterology 2003;124:288-292 (Pubitemid 36169245)
93. Goldstein JL, Eisen GM, Lewis B, et al. Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole, and placebo. Clin Gastroenterol Hepatol 2005;3:133-141 (Pubitemid 40220308)
94. Goldstein JL, Eisen GM, Lewis B, et al. Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole, as assessed by video capsule endoscopy. Aliment Pharmacol Ther 2007;25:1211-1222 (Pubitemid 46650300)
95. Maiden L, Thjodleifsson B, Seigal A, et al. Long-term effects of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 selective agents on the small bowel: a cross-sectional capsule enteroscopy study. Clin Gastroenterol Hepatol 2007;5:1040-1045
96. Langman MJ, Morgan L, Worrall A. Use of anti-inflammatory drugs by patients admitted with small or large bowel perforations and haemorrhage. Br Med J (Clin Res Ed) 1985;290:347-349 (Pubitemid 15115450)
97. Wilcox CM, Clark WS. Association of nonsteroidal antiinflammatory drugs with outcome in upper and lower gastrointestinal bleeding. Dig Dis Sci 1997;42:985-989 (Pubitemid 27239790)
98. Day TK. Intestinal perforation associated with osmotic slow release indomethacin capsules. Br Med J (Clin Res Ed) 1983;287:1671-1672
99. Lanas A. Update on gastrointestinal disorders associated with nonsteroidal anti-inflammatory drugs. Gastroenterol Hepatol 2008;31 (Supp 4):35-41.
100. Chan FK, Hung LC, Suen BY, et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med 2002;26:2104-2110 (Pubitemid 36015122)
101. Laine L, Curtis SP, Langman M, et al. Lower gastrointestinal events in a double-blind trial of the cyclo-oxigenase-2 selective inhibitor etoricoxib and the traditional nonsteroidal anti-inflammatory drug diclofenac. Gastroenterology 2008;135:1517-1525
102. Laine L, Curtis SP, Cryer B, et al; MEDAL Steering Committee. Assessment of upper gastrointestinal safety of etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet 2007;369:465-473
103. Combe B, Swergold G, McLay J, et al. Cardiovascular safety and gastrointestinal tolerability of etoricoxib vs diclofenac in a randomized controlled clinical trial (The MEDAL study). Rheumatology (Oxford) 2009;48:425-432
104. Krum H, Curtis SP, Kaur A, et al. Baseline factors associated with congestive heart failure in patients receiving etoricoxib or diclofenac: multivariate analysis of the MEDAL program. Eur J Heart Fail. 2009;11:542-550
105. Laine L, White WB, Rostom A, et al. COX-2 selective inhibitors in the treatment of osteoarthritis. Semin Arthritis Rheum 2008;38:165-187
106. Wilcox CM, Alexander LN, Cotsonis GA, et al. Nonsteroidal anti-inflammatory drugs are associated with both upper and lower gastrointestinal bleeding. Dig Dis Sci 199;42:990-997
107. Morris AJ, Murray L, Sturrock RD, et al. Short report: the effect of misoprostol on the anaemia of NSAID enteropathy. Aliment Pharmacol Ther 1994;8:343-346 (Pubitemid 24205535)
108. Davies NM, Saleh JY, Skjodt NM. Detection and prevention of NSAID-induced enteropathy. J Pharm Pharmaceut Sci 2000;3:137-155
109. Watanabe T, Sugimori S, Kameda N, et al. Small bowel injury by low-dose enteric-coated aspirin and treatment with misoprostol: a pilot study. Clin Gastroenterol Hepatol 2008;6:1279-1282
110. Hayllar J, Smith T, Macpherson A, et al. Nonsteroidal antiinflammatory drug-induced small intestinal inflammation and blood loss. Effects of sulfasalazine and other disease-modifying antirheumatic drugs. Arthritis Rheum 1994;37:1146-1150
111. Bjarnason I, Hayllar J, Smethurst P, et al. Metronidazole reduces intestinal inflammation and blood loss in non-steroidal anti-inflammatory drug induced enteropathy. Gut 1992;33:1204-1208
112. DuBois RN, Abramson SB, Crofford L, et al. Cyclooxygenase in biology and disease. FASEB J 1998;12:1063-1073
113. Shirvani VN, Ouatu-Lascar R, Kaur BS, et al. Cyclooxygenase-2 expression in Barrett's esophagus and esophageal adenocarcinoma: ex vivo induction by bile salts and acid exposure. Gastroenterology 2000;118:487-496 (Pubitemid 30140846)
114. Zhang F, Altorki NK, Wu YC, et al. Duodenal reflux induces cyclooxygenase-2 in the esophageal mucosa of rats: evidence for involvement of bile acids. Gastroenterology 2001;121:1391-1399 (Pubitemid 33140456)
115. Fosslien E. Molecular pathology of cyclooxygenase-2 in neoplasia. Ann Clin Lab Sci 2000;30:3-21.
116. Oshima M, Dinchuk JE, Kargman SL, et al. Suppression of intestinal polyposis in Apc delta 716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 1996;87:803-809 (Pubitemid 26404280)
117. Steinbach G, Lynch PM, Phillips RK, et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 2000;342:1946-1952 (Pubitemid 30419089)
118. Baron JA, Sandler RS, Bresalier RS, et al; APPROVe Trial Investigators. A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas. Gastroenterology 2006;131:1674-1682
119. Eberhart CE, Coffey RJ, Radhika A, et al. Upregulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 1994;107:1183-1188 (Pubitemid 24294584)
120. Fujita T, Matsui M, Takaku K, et al. Size and invasion dependent increase in cyclooxygenase 2 levels in human colorectal carcinomas. Cancer Res 1998;58:4823-4826 (Pubitemid 28503676)
121. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990;61:759-767
122. Clevers H. Colon cancer - understanding how NSAIDs work. N Engl J Med 2006;354:761-763 (Pubitemid 43247150)
123. Yamamoto Y, Yin M-J, Lin K-M, et al. Sulindac inhibits activation of the NF-kappaB pathway. J Biol Chem 1999;274:27307-27314 (Pubitemid 129520262)
124. He T-C, Chan TA, Vogelstein B, et al. PPARdelta is an APC regulated target of nonsteroidal anti-inflammatory drugs. Cell 1999;99:335-345 (Pubitemid 29519912)
125. Gately S, Kerbel R. Therapeutic potential of selective cyclooxygenase-2 inhibitors in the management of tumor angiogenesis. Prog Exp Tumor Res 2003;37:179-192 (Pubitemid 36767986)
126. Janne P, Mayer R. Chemoprevention of colorectal cancer. N Engl J Med 2000;342:1960-1968
127. Langman MJ, Cheng KK, Gilman EA, et al. Effect of antiinflammatory drugs on overall risk of common cancer: case-control study in general practice research database. BMJ 2000;320:1642-1646
128. Bosetti C, Gallus S, La Vecchia C. Aspirin and cancer risk: a summary review to 2007. Recent Results Cancer Res 2009;181:231-251
129. Harris RE, Beebe-Donk J, Alshafie GA. Similar reductions in the risk of human colon cancer by selective and nonselective cyclooxygenase-2 (COX-2) inhibitors. BMC Cancer 2008;8:237.
130. González-Pérez A, García Rodríguez LA, López-Ridaura R. Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis. BMC Cancer 2003;3:28. (Pubitemid 38851321)
131. Elwood PC, Gallagher AM, Duthie GG, et al. Aspirin, salicylates, and cancer. Lancet 2009;373:1301-1309
132. Bresalier RS. Chemoprevention of intestinal polyposis by COX-2 inhibition: from mouse to man. Gastroenterology 2002;122:234-236
133. Cole BF, Logan RF, Halabi S, et al. Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. J Natl Cancer Inst 2009;101:256-266
134. Arber N, Eagle CJ, Spicak J, et al; PreSAP Trial Investigators. Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med 2006;355:885-895
135. Baron JA, Cole BF, Sandler RS, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med 2003;348:891-899 (Pubitemid 36297997)
136. Sandler RS, Halabi S, Baron JA, et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med 2003;348:883-890 (Pubitemid 36297996)
137. Benamouzig R, Deyra J, Martin A, et al. Daily soluble aspirin and prevention of colorectal adenoma recurrence: one-year results of the APACC trial. Gastroenterology 2003;125:328-336 (Pubitemid 36929412)
138. Logan RF, Grainge MJ, Shepherd VC, et al. Aspirin and folic acid for the prevention of recurrent colorectal adenomas. Gastroenterology 2008;134:29-38. (Pubitemid 350309319)
139. Chan AT, Giovannucci EL, Schernhammer ES, et al. A prospective study of aspirin use and the risk for colorectal adenoma. Ann Intern Med 2004;140:157-166
140. Flossmann E, Rothwell PM; Trial BDATatU-TA. Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies. Lancet 2007;369:1603-1613 (Pubitemid 46710123)
141. Chan AT, Giovannucci EL, Meyerhardt JA, et al. Aspirin dose and duration of use and risk of colorectal cancer in men. Gastroenterology 2008;134:21-28 (Pubitemid 350309311)
142. Lance P. Chemoprevention for colorectal cancer: some progress but a long way to go. Gastroenterology 2008;134:341-343 (Pubitemid 350309344)
143. Chan AT, Ogino S, Fuchs CS. Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med 2007;356:2131-2142 (Pubitemid 47010839)
144. Grau MV, Baron JA, Sandler RS, et al. Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial. J Natl Cancer Inst 2003;95:1765-1771 (Pubitemid 38008899)
145. McIlhatton MA, Tyler J, Burkholder S, et al. Nitric oxide-donating aspirin derivatives suppress microsatellite instability in mismatch repair-deficient and hereditary nonpolyposis colorectal cancer cells. Cancer Res 2007;67:10966-10975 (Pubitemid 350145926)
146. Kerr DJ, Dunn JA, Langman MJ, et al. Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer. N Engl J Med 2007;357:360-369 (Pubitemid 47124136)