eMedicine Specialties > Gastroenterology > Systemic Disease

Familial Adenomatous Polyposis: Treatment & Medication

Author: Mohammad Wehbi, MD, Assistant Professor of Medicine, Associate Program Director, Department of Gastroenterology, Atlanta Veterans Affairs Medical Center, Emory University School of Medicine
Coauthor(s): Nicole M Griglione, MD, Staff Physician, Department of Medicine, Emory University School of Medicine; Vincent W Yang, MD, PhD, R Bruce Logue Professor, Director, Division of Digestive Diseases, Department of Medicine, Professor of Hematology and Oncology, Winship Cancer Institute, Emory University School of Medicine; Kamil Obideen, MD, Assistant Professor of Medicine, Division of Digestive Diseases, Emory University School of Medicine; Consulting Staff, Division of Gastrointestinal Endoscopy, Atlanta Veterans Affairs Medical Center; Jae W Nam, MD, Fellow in Gastroenterology, Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine; Consulting Staff, Department of Critical Care, Decatur Hospital; John M Carethers, MD, Professor of Medicine, Chief, Division of Gastroenterology, Department of Medicine, University of California at San Diego
Contributor Information and Disclosures

Updated: Jul 30, 2008

Treatment

Medical Care

Medical care is mainly based on endoscopic surveillance to detect the onset of polyposis. Consequently, surgery would prevent the development of colon cancer. However, in view of the increased risk for the development of other cancers, continued medical follow-up is required with a number of surveillance tests, as colectomy would only address the potential risk of colon cancer.

A number of drugs (eg, celecoxib, sulindac) have been used successfully to reduce the number and the size of polyps in patients with FAP. However, they are insufficient as a primary modality of therapy.

  • Endoscopic surveillance
    • Flexible sigmoidoscopy should be performed every 1-2 years starting at age 10-12 years in patients with FAP to document the onset of polyposis.
    • Sigmoidoscopic surveillance and ablation of any polyps in the retained rectum or ileal pouch should be performed every 3-6 months in patients with FAP who have undergone colonic (total or subtotal) resection. There is an increased risk for adenomas and carcinomas in the ileal pouch, as there is increased epithelial cell proliferation at this site as compared to the afferent ileal loop.4
    • Once polyps are detected, colonoscopic surveillance is recommended to remove large polyps in patients who have not had an operation. This is important because surgery (colectomy) is usually deferred until an appropriate psychological age is reached (usually late teenaged years to early twenties). However, if the polyps have advanced histologic features, then early surgery is recommended.
    • Front- and side-view esophagogastroduodenoscopy should be performed every 1-3 years once the diagnosis is made and after surgical therapy. The front-view esophagogastroduodenoscopy allows for the detection of gastric and duodenal polyps. The side-view duodenoscope allows for the examination of the ampulla of Vater. 
    • Capsule endoscopy is useful for the surveillance of jejunal-ileal polyps in selected patients but is not recommended for duodenal or ampullary surveillance.  Some patients who are at high risk may benefit from screening with endoscopic ultrasound for periampullary and ampullary tumors.5
  • Drugs used in the treatment of FAP include sulindac and celecoxib.
    • Because of the association between cyclooxygenase 2 (COX-2) inhibitors (celecoxib is a member of this drug family) and coronary artery disease, celecoxib is no longer widely used.
    • These drugs have no primary role as sole therapy for patients with FAP who have not had surgical therapy. However, in patients with FAP who have had colectomy with ileoanal anastomosis, sulindac or celecoxib may be beneficial in reducing the size and the number of adenomatous polyps in the remaining rectum.
    • The use of other nonsteroidal anti-inflammatory drugs (NSAIDs) and similar drugs is being studied.
    • Cancers of the rectum (in patients who have had subtotal colectomy with ileorectal anastomosis) have been reported with sulindac and celecoxib therapy. Because of the inability to control polyps medically, eventual rectal resection is usually necessary. This is why subtotal colectomy with ileorectal anastomosis (IRA) is not the preferred surgical procedure.
  • Screening of family members of patients with FAP should begin by age 12 years. Flexible sigmoidoscopy every 1-2 years until the patient is aged 35 years is adequate, then every 3 years thereafter. Genetic testing may eliminate the need for surveillance in some family members.
  • Desmoid tumors (intra-abdominal) may respond to antiestrogen therapy (tamoxifen) and sulindac because estrogen appears to promote their growth.
  • Chemotherapy with doxorubicin and dacarbazine may be attempted if no response is observed with other therapies.

Surgical Care

Because of the diffuse nature of the polyposis and the inevitability of colorectal cancer, surgical therapy is ultimately required. Surgical therapy should be performed before the typical onset of cancer.

  • Colectomy with mucosal proctectomy and ileoanal pouch pull-through (proctocolectomy with ileal pouch-anal anastomosis/IPAA) is the procedure of choice at many centers.
    • This procedure allows retention of rectal function.
    • Other options include subtotal colectomy with ileoanal anastomosis and total proctocolectomy with ileostomy.
  • If medical therapy and endoscopic therapy do not control polyp growth, rectal resection may be needed in patients who have a retained rectum (such as in subtotal colectomy). Desmoid tumors may be resected with adequate margins. This generally is reserved for patients with ureteral or intestinal obstruction.

Consultations

  • A gastroenterologist familiar with FAP should supervise follow-up care. This is important because appropriate surveillance should be pursued to detect and treat other cancers/complications of FAP after surgery.
  • Appropriate genetic counseling for both the patients and their family members should be initiated.

Medication

The goal of pharmacotherapy is to reduce morbidity and to prevent complications.

Nonsteroidal anti-inflammatory drugs

These agents are used to reduce the number and the size of adenomatous polyps that remain in the rectum or ileal pouch after colectomy in patients with FAP. Celecoxib is not widely used because of the association between COX-2 inhibitors (celecoxib is a member of this drug family) and coronary artery disease.


Sulindac (Clinoril)

Sulfoxide nonsteroidal anti-inflammatory agent 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 the regression of adenomatous polyps.

Adult

150 mg PO bid

Pediatric

Not established

Probenecid and lithium may increase concentrations and possibly toxicity of NSAIDs; effect of loop diuretics may decrease when administered concurrently; PT may increase when coadministered with anticoagulants; monitor PT closely and instruct patients to watch for signs and symptoms of bleeding; concurrent administration with phenytoin may increase pharmacologic and toxic effects of phenytoin

Documented hypersensitivity; patients in whom aspirin, iodides, or other NSAIDs induce hypersensitivity; GI bleed and renal insufficiency

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Category D in third trimester of pregnancy; acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in preexisting renal disease or compromised renal perfusion; low WBC counts occur rarely and usually return to normal in ongoing therapy; discontinuation of therapy may be necessary if persistent leukopenia, granulocytopenia, or thrombocytopenia is present; caution in anticoagulation defects or those receiving anticoagulant therapy


Celecoxib (Celebrex)

Primarily inhibits COX-2. COX-2 is considered an inducible isoenzyme, induced during pain and inflammatory stimuli. COX-2 is overexpressed in colonic adenomas, which may contribute to adenoma growth, and inhibition of COX-2 may be the mechanism for polyp regression.

Adult

400 mg PO bid

Pediatric

Not established

Coadministration with fluconazole may cause increase in celecoxib plasma concentrations because of inhibition of celecoxib metabolism; coadministration with rifampin may decrease celecoxib plasma concentrations

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May cause fluid retention and peripheral edema; caution in compromised cardiac function, hypertension, and conditions predisposing to fluid retention; severe heart failure and hyponatremia because may deteriorate circulatory hemodynamics; NSAIDs may mask usual signs of infection; caution in the presence of existing controlled infections; evaluate symptoms and signs suggesting liver dysfunction or with abnormal liver lab results

More on Familial Adenomatous Polyposis

Overview: Familial Adenomatous Polyposis
Differential Diagnoses & Workup: Familial Adenomatous Polyposis
Treatment & Medication: Familial Adenomatous Polyposis
Follow-up: Familial Adenomatous Polyposis
Multimedia: Familial Adenomatous Polyposis
References
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References

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  2. Ponti G, Losi L, Pellacani G, Rossi GB, Presutti L, Mattioli F, et al. Wnt pathway, angiogenetic and hormonal markers in sporadic and familial adenomatous polyposis-associated juvenile nasopharyngeal angiofibromas (JNA). Applied Immunohistochemistry & Molecular Morphology [serial online]. January 25, 2008;Available from: Pubmed. Accessed March 15, 2008. Available at http://www.appliedimmunohist.com/.

  3. Bianchi LK, Burke CA, Bennett AE, et al. Fundic gland polyp dysplasia is common in familial adenomatous polyposis. Clin Gastroenterol Hepatol. Feb 2008;6(2):180-5. [Medline].

  4. Friederich P, van Heumen BW, Nagtegaal ID, et al. Increased epithelial cell proliferation in the ileal pouch mucosa of patients with familial adenomatous polyposis. Virchows Arch. Sep 2007;451(3):659-67. [Medline]. [Full Text].

  5. Iaquinto G, Fornasarig M, Quaia M, et al. Capsule endoscopy is useful and safe for small-bowel surveillance in familial adenomatous polyposis. Gastrointest Endosc. Jan 2008;67(1):61-7. [Medline].

  6. Bresalier RS. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. 2006;2759-2810.

  7. Brosens LA, Keller JJ, Offerhaus GJ, et al. Prevention and management of duodenal polyps in familial adenomatous polyposis. Gut. Jul 2005;54(7):1034-43. [Medline].

  8. Burke CA, Beck GJ, Church JM, et al. The natural history of untreated duodenal and ampullary adenomas in patients with familial adenomatous polyposis followed in an endoscopic surveillance program. Gastrointest Endosc. Mar 1999;49(3 Pt 1):358-64. [Medline].

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  14. Giardiello FM, Hamilton SR, Krush AJ, et al. Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med. May 6 1993;328(18):1313-6. [Medline].

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Further Reading

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Keywords

familial adenomatous polyposis, FAP, adenomatous polyposis syndrome, adenomatous polyps, colon cancer, colorectal cancer, adenomatous polyposis coli, colorectal carcinoma, colonic polyps, colonic neoplasia, rectal bleeding, adenomatous polyposis coli gene, APC gene, Gardner syndrome, Turcot syndrome, attenuated adenomatous polyposis coli, AAPC, desmoid tumors, intestinal polyposis, colectomy, rectal resection, duodenal adenocarcinoma, periampullary adenocarcinoma, medulloblastoma, hepatoblastoma, thyroid cancers, adrenal cancers, upper gastrointestinal cancers

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Contributor Information and Disclosures

Author

Mohammad Wehbi, MD, Assistant Professor of Medicine, Associate Program Director, Department of Gastroenterology, Atlanta Veterans Affairs Medical Center, Emory University School of Medicine
Mohammad Wehbi, MD is a member of the following medical societies: American College of Physicians, American Gastroenterological Association, and American Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Nicole M Griglione, MD, Staff Physician, Department of Medicine, Emory University School of Medicine
Nicole M Griglione, MD is a member of the following medical societies: American Medical Association and Illinois State Medical Society
Disclosure: Nothing to disclose.

Vincent W Yang, MD, PhD, R Bruce Logue Professor, Director, Division of Digestive Diseases, Department of Medicine, Professor of Hematology and Oncology, Winship Cancer Institute, Emory University School of Medicine
Vincent W Yang, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Gastroenterological Association, American Society for Clinical Investigation, and Association of American Physicians
Disclosure: Nothing to disclose.

Kamil Obideen, MD, Assistant Professor of Medicine, Division of Digestive Diseases, Emory University School of Medicine; Consulting Staff, Division of Gastrointestinal Endoscopy, Atlanta Veterans Affairs Medical Center
Kamil Obideen, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.

Jae W Nam, MD, Fellow in Gastroenterology, Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine; Consulting Staff, Department of Critical Care, Decatur Hospital
Jae W Nam, MD is a member of the following medical societies: American College of Gastroenterology
Disclosure: Nothing to disclose.

John M Carethers, MD, Professor of Medicine, Chief, Division of Gastroenterology, Department of Medicine, University of California at San Diego
John M Carethers, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Gastroenterology, American College of Physicians, and American Gastroenterological Association
Disclosure: Nothing to disclose.

Medical Editor

John Gunn Lee, MD, Director of Pancreaticobiliary Service, Associate Professor, Department of Internal Medicine, Division of Gastroenterology, University of California at Irvine School of Medicine
John Gunn Lee, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Simmy Bank, MD, Chair, Professor, Department of Internal Medicine, Division of Gastroenterology, Long Island Jewish Hospital, Albert Einstein College of Medicine
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Assistant Dean for Medical Curriculum, Associate Professor of Medicine, Division of General Internal Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
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