Medication Summary

The literature supports the use of NSAIDs in FAP syndrome, with regression of polyps already present. It has been demonstrated that COX-2 is up-regulated 2-50 times in most (85-90%) adenocarcinomas. The role for NSAIDs (including the newer COX-2 inhibitors) in nonfamilial adenomatous lesions is unclear. For sporadic polyps, NSAID use has not been proven to cause regression in already developed polyps, although evidence suggests a decreased incidence of polyps in persons already taking NSAIDs. Therefore, a potential role exists for NSAIDs as primary prophylaxis.

In patients who have had a history of colon cancer, patients undergoing therapy with aspirin at 325 mg daily have fewer polyps than those on placebo. In patients with a history of a colonic polyp, low-dose aspirin (81 mg) may have some benefit in decreased adenoma recurrence.^[9]

Studies with celecoxib have shown some regression in polyps in those patients with FAP. However, the routine use of COX-2 inhibitors for this indication may not be reasonable, especially in consideration of the recent documentation on cardiovascular toxicity/contraindications.

Class Summary

Mechanism of action is not known but may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions, also may exist.

Sulindac (Clinoril)

View full drug information

Sulfoxide NSAID that is metabolized to the anti-inflammatory sulfide metabolite and a sulfone metabolite. Sulfide metabolite is now known to have apoptotic activity on colonic epithelial cells and is presumed to be responsible for regression of adenomatous polyps. Primary route of excretion is via urine as both sulindac and its sulfone metabolite.

Follow-up

Ferlitsch M, Reinhart K, Pramhas S, et al. Sex-specific prevalence of adenomas, advanced adenomas, and colorectal cancer in individuals undergoing screening colonoscopy. JAMA. 2011 Sep 28. 306(12):1352-8. [QxMD MEDLINE Link].
Fairley KJ, Li J, Komar M, Steigerwalt N, Erlich P. Predicting the risk of recurrent adenoma and incident colorectal cancer based on findings of the baseline colonoscopy. Clin Transl Gastroenterol. 2014 Dec 4. 5:e64. [QxMD MEDLINE Link].
Wark PA, Wu K, van 't Veer P, Fuchs CF, Giovannucci EL. Family history of colorectal cancer: a determinant of advanced adenoma stage or adenoma multiplicity?. Int J Cancer. 2009 Jul 15. 125(2):413-20. [QxMD MEDLINE Link].
Terhaar Sive Droste JS, Craanen ME, et al. Colonoscopic yield of colorectal neoplasia in daily clinical practice. World J Gastroenterol. 2009 Mar 7. 15(9):1085-92. [QxMD MEDLINE Link]. [Full Text].
Martinez ME, Baron JA, Lieberman DA, et al. A pooled analysis of advanced colorectal neoplasia diagnoses after colonoscopic polypectomy. Gastroenterology. 2009 Mar. 136(3):832-41. [QxMD MEDLINE Link].
de Jonge V, Sint Nicolaas J, van Leerdam ME, Kuipers EJ, Veldhuyzen van Zanten SJ. Systematic literature review and pooled analyses of risk factors for finding adenomas at surveillance colonoscopy. Endoscopy. 2011 Jul. 43(7):560-72. [QxMD MEDLINE Link].
Denis B, Peters C, Chapelain C, et al. Diagnostic accuracy of community pathologists in the interpretation of colorectal polyps. Eur J Gastroenterol Hepatol. 2009 Oct. 21(10):1153-60. [QxMD MEDLINE Link].
Bokemeyer B, Bock H, Huppe D, et al. Screening colonoscopy for colorectal cancer prevention: results from a German online registry on 269000 cases. Eur J Gastroenterol Hepatol. 2009 Jun. 21(6):650-5. [QxMD MEDLINE Link].
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 Feb 18. 101(4):256-66. [QxMD MEDLINE Link].
Baron JA, Cole BF, Sandler RS, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med. 2003 Mar 6. 348(10):891-9. [QxMD MEDLINE Link].
Bond JH. Colon polyps and cancer. Endoscopy. 2001 Jan. 33(1):46-54. [QxMD MEDLINE Link].
Bond JH. Colorectal cancer update. Prevention, screening, treatment, and surveillance for high-risk groups. Med Clin North Am. 2000 Sep. 84(5):1163-82, viii. [QxMD MEDLINE Link].
Bond JH. Polyp guideline: diagnosis, treatment, and surveillance for patients with colorectal polyps. Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol. 2000 Nov. 95(11):3053-63. [QxMD MEDLINE Link].
Bond JH. Polyp guideline: diagnosis, treatment, and surveillance for patients with nonfamilial colorectal polyps. The Practice Parameters Committee of the American College of Gastroenterology. Ann Intern Med. 1993 Oct 15. 119(8):836-43. [QxMD MEDLINE Link].
Cotton PB, Durkalski VL, Pineau BC, et al. Computed tomographic colonography (virtual colonoscopy): a multicenter comparison with standard colonoscopy for detection of colorectal neoplasia. JAMA. 2004 Apr 14. 291(14):1713-9. [QxMD MEDLINE Link].
Day DW, Morson BC. The adenoma-carcinoma sequence. Morson BC, ed. The Pathogenesis of Colorectal Cancer. Philadelphia: WB Saunders; 1978. 58-71.
DuBois RN, Giardiello FM, Smalley WE. Nonsteroidal anti-inflammatory drugs, eicosanoids, and colorectal cancer prevention. Gastroenterol Clin North Am. 1996 Dec. 25(4):773-91. [QxMD MEDLINE Link].
Farnell MB, Sakorafas GH, Sarr MG, et al. Villous tumors of the duodenum: reappraisal of local vs. extended resection. J Gastrointest Surg. 2000 Jan-Feb. 4(1):13-21, discussion 22-3. [QxMD MEDLINE Link].
Gibbs ER, Walton GF, Kent RB 3rd, Laws HL. Villous tumors of the ampulla Vater. Am Surg. 1997 Jun. 63(6):467-71. [QxMD MEDLINE Link].
Heald RJ, Bussey HJ. Clinical experiences at St. Mark's Hospital with multiple synchronous cancers of the colon and rectum. Dis Colon Rectum. 1975 Jan-Feb. 18(1):6-10. [QxMD MEDLINE Link].
Itzkowitz SH, Kim YS. Colonic polyps and polyposis syndromes. Feldman M, Scharschmidt BF, Sleisenger MH, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, and Management. 6th ed. Philadelphia: WB Saunders; 1997. 467-71.
Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med. 1993 May 13. 328(19):1365-71. [QxMD MEDLINE Link].
Morson BC, Dawson IMP. Gastrointestinal Pathology. Oxford: Blackwell Scientific; 1972.
O'Brien MJ, Winawer SJ, Zauber AG, et al. The National Polyp Study. Patient and polyp characteristics associated with high-grade dysplasia in colorectal adenomas. Gastroenterology. 1990 Feb. 98(2):371-9. [QxMD MEDLINE Link].
Pickhardt PJ, Choi JR, Hwang I, et al. Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med. 2003 Dec 4. 349(23):2191-200. [QxMD MEDLINE Link].
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 Mar 6. 348(10):883-90. [QxMD MEDLINE Link].
Schrock TR. Colonoscopy for colorectal cancer: too much, too little, just right. ASGE Distinguished Lecture 1993. Gastrointest Endosc. 1993 Nov-Dec. 39(6):848-51. [QxMD MEDLINE Link].
Seitz U, Bohnacker S, Seewald S, et al. Is endoscopic polypectomy an adequate therapy for malignant colorectal adenomas? Presentation of 114 patients and review of the literature. Dis Colon Rectum. 2004 Nov. 47(11):1789-96; discussion 1796-7. [QxMD MEDLINE Link].
Stryker SJ, Wolff BG, Culp CE, Libbe SD, Ilstrup DM, MacCarty RL. Natural history of untreated colonic polyps. Gastroenterology. 1987 Nov. 93(5):1009-13. [QxMD MEDLINE Link].
Winawer SJ, Zauber AG, Fletcher RH, et al. Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society. Gastroenterology. 2006 May. 130(6):1872-85. [QxMD MEDLINE Link].
Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med. 1993 Dec 30. 329(27):1977-81. [QxMD MEDLINE Link].
Winawer SJ, Zauber AG, Ho MN, et al. The National Polyp Study. Eur J Cancer Prev. 1993 Jun. 2 Suppl 2:83-7. [QxMD MEDLINE Link].
Winawer SJ, Zauber AG, O'Brien MJ, et al. Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. The National Polyp Study Workgroup. N Engl J Med. 1993 Apr 1. 328(13):901-6. [QxMD MEDLINE Link].
Zauber AG, Winawer SJ. Initial management and follow-up surveillance of patients with colorectal adenomas. Gastroenterol Clin North Am. 1997 Mar. 26(1):85-101. [QxMD MEDLINE Link].
Jeong YH, Kim KO, Park CS, Kim SB, Lee SH, Jang BI. Risk factors of advanced adenoma in small and diminutive colorectal polyp. J Korean Med Sci. 2016 Sep. 31(9):1426-30. [QxMD MEDLINE Link].

Media Gallery

Endoscopic view of a sessile polyp, which histology studies revealed to be a villous adenoma. Courtesy of H. Chaun, MD.
Endoscopic view of a sessile polyp histologically determined to be a villous adenoma. Courtesy of R. Enns, MD.
Endoscopic view of injection of saline into the base of a sessile polyp histologically determined to be a villous adenoma. This enables an easier polypectomy. Courtesy of R. Enns, MD.
Polypectomy with a snare around a sessile polyp base (villous adenoma) injected with saline. Courtesy of R. Enns, MD.
Histology of villous adenoma. Fingerlike projections stretching from the surface of a polyp downward with minimal branching. Courtesy of D. Owen, MD.
Histology of villous adenoma. Low-grade dysplasia with loss of mucin, prominent nucleoli, and hyperchromatic and elongated cells. Courtesy of D. Owen, MD.
Fecal occult blood testing. Video courtesy of Therese Canares, MD; Marleny Franco, MD; and Jonathan Valente, MD (Rhode Island Hospital, Brown University).