eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology

Intestinal Polyposis Syndromes: Treatment & Medication

Author: Ann Scheimann, MD, MBA, Assistant Professor, Department of Pediatrics, Section of Nutrition and Gastroenterology, Baylor College of Medicine and Johns Hopkins Medical Institution
Contributor Information and Disclosures

Updated: Nov 27, 2007

Treatment

Medical Care

  • Gardner syndrome
    • Patients require medical care and management of cutaneous cysts, osteomas, fibromas, polyposis, and diligent surveillance for neoplasia.
    • Carcinoma may develop at any age, from late childhood through senior years.
    • Young children with gene mutations related to Gardner syndrome have an increased risk for development of hepatoblastoma. Hughes and Michels noted Gardner syndrome in 2 of 470 children who had parents with Gardner syndrome versus an incidence of 1 per 100,000 general population.34
    • Patients with Gardner syndrome are predisposed to the development of polyposis throughout the GI tract and to carcinomas of the stomach, periampullary region, biliary tract, and colon.
    • Women with Gardner syndrome have an increased risk of desmoid tumors and thyroid carcinoma.
    • Development of thyroid carcinoma is 100 times more likely among patients with Gardner syndrome.
    • Osteosarcomas and adrenal carcinomas (with Cushing syndrome) have been previously reported in patients with Gardner syndrome.
  • Turcot syndrome
    • Patients require medical intervention for complications of GI polyposis and carcinoma (eg, gastric, colonic), management of basal cell carcinomas, and treatment of CNS malignancies, including astrocytoma, glioblastoma, and medulloblastoma.
    • Patients with Turcot syndrome are predisposed to the development of hepatic focal nodular hyperplasia.
  • PJS
     
    • Patients require medical management for problems attributed to polyposis and for detection of malignancy.
    • Patients with PJS may develop significant GI bleeding, intussusception, and rectal prolapse requiring diagnosis and treatment, including endoscopy and surgical resection. 
    • Nasal endoscopy may be necessary in the presence of chronic sinusitis to exclude the presence of significant nasal polyps. 
    • Long-term surveillance strategies to monitor for GI malignancies, including bowel, pancreatic, and extraintestinal malignancies (eg, breast, gynecologic, testicular), are currently under development at several centers.
    • The use of the potassium titanyl phosphate (KTP) laser to treat mucocutaneous melanosis of the lips and hands in a patient with PJS has been reported in the United Kingdom.
  • BRR syndrome
    • Patients require medical therapy for CNS abnormalities, complications of lipomas and arteriovenous malformations, treatment of Hashimoto thyroiditis, and surveillance for malignancy.
    • Children with BRR exhibit hypotonia, developmental delay, and mild mental retardation requiring coordinated speech and occupational and physical therapies to maximize potential.
    • Significant lipomatous or vascular lesions (hemangiomas, arteriovenous malformations) have resulted in CNS complications (eg, seizures), amputations, and premature death.
    • Patients with BRR appear to have an increased risk for CNS tumors.
    • Increased incidences of Hashimoto thyroiditis, along with abnormalities of the PTEN gene (tumor suppressor gene), enhance the likelihood for development of neoplasia, especially thyroid and breast.
  • GS
    • Patients may require medical attention for craniofacial, vertebral, dental, and ophthalmologic abnormalities, in addition to diagnosis and treatment of potential neoplasia.
    • Bale reported that 3% of patients with GS presented with cleft lip and palate at birth.31
    • Scoliosis is commonly associated with GS. 
    • Jaw cysts are noted in more than 50% of patients, accompanied by symptoms of optic nerve compression, abnormalities of taste, and facial paresthesias.
    • Fibrosarcomas of the jaw have been encountered in patients with GS.
    • Glaucoma and cataracts have been described in patients with GS.
    • Patients with GS are predisposed to the development of neoplasia of the CNS, skin, and reproductive organs. 
    • In childhood, medulloblastomas have been reported in 5% of patients with GS.
    • Basal cell carcinomas may present in patients younger than 10 years, especially with prior history of exposure to ionizing radiation. Nearly all patients with GS develop basal cell carcinomas by the fourth decade of life.
    • Individuals with GS may present with abdominal symptoms that arise from abnormalities of the GI (lymphatic, mesenteric cysts) and gynecologic systems. Young girls with GS may develop ovarian fibromas (predisposed to torsion) and fibrosarcomas. Khalifa et al reported endometrial adenocarcinoma in a 37-year-old woman with GS.
  • Cowden disease
    • Patients require medical attention for management of complications of hamartomatous polyps, thyroid disease, scoliosis, and CNS abnormalities (eg, seizures, increased intracranial pressure).
    • Patients require careful monitoring for the development of malignancies within the cerebellum, breast, skin (Merkel cell), and kidneys (renal cell adenocarcinoma).

Surgical Care

  • Patients with Gardner syndrome require surgical treatment of the following:
    • Cutaneous cysts
    • Symptomatic dental anomalies and osteomas
    • Biopsy and resection for malignancies, including hepatoblastoma, colonic carcinoma, thyroid carcinoma, osteocarcinoma, gastric carcinoma, periampullary carcinoma, and biliary tract carcinoma
    • Liver transplantation (may be required in patients with hepatoblastoma)
  • Patients with Turcot syndrome require surgical intervention for diagnosis and management of CNS lesions, gastric lesions, colonic polyposis, and hepatic lesions.
  • PJS
    • Patients may require surgical intervention for symptomatic GI lesions and biopsy of suspicious areas to exclude the possibility of malignancy.
    • Some patients with PJS develop manifestations of short-bowel syndrome secondary to long-term resections.
  • Patients with BRR may require surgical intervention for management of serious lipomatous, vascular lesions, and undescended testicles and biopsy of suggestive areas to exclude the possibility of occult malignancy.
  • Patients with GS may require surgical management for the following:
    • Craniofacial lesions (cleft lip and palate, jaw cysts, other mandibular lesions)
    • Abdominal masses (mesenteric cysts, lymphatic cysts, ovarian fibromas)
    • Diagnostic and therapeutic interventions for potential neoplasia within the CNS (medulloblastoma), skin (basal cell carcinoma), jaw (fibrosarcoma), ovaries (fibrosarcoma), and endometrium (adenocarcinoma)
  • Patients with Cowden disease require surgical intervention for management of symptomatic polyposis, scoliosis, and increased intracranial pressure.
    • Biopsy and resection of lesions within the cerebellum (dysplastic gangliocytomas), breast, and kidneys (renal cell adenocarcinoma) may be required.
    • Consideration of prophylactic mastectomy is recommended for women with Cowden disease.

Consultations

  • Patients with Gardner syndrome may require consultation with the following:
    • Gastroenterologist - For monitoring and surveillance for malignancies
    • Oncologist - For treatment of malignancies
    • Surgeon - For biopsy or resection of suspicious areas
    • Dentist or maxillofacial surgeon - For mandibular osteomas or dental anomalies
    • Ophthalmologist - For evaluation for retinal anomalies
    • Endocrinologist - For evaluation and management of thyroid carcinoma and adrenal carcinoma
  • Patients with Turcot syndrome may require medical consultation with the following:
    • Gastroenterologist - For monitoring and surveillance for malignancies
    • Oncologist - For monitoring and treatment of malignancies
    • Dermatologist
    • Surgeon - For management of CNS, cutaneous, and GI malignancies
  • Patients with PJS may require consultation with the following:
     
    • Gastroenterologist: Assistance from a gastroenterologist may localize sites of polyps or bleeding.
    • Surgeon: Surgical intervention may include resection of symptomatic areas and biopsy for suspicious malignancy.
    • Dermatologist: Some patients with PJS may initially present to the dermatologist for diagnosis of cutaneous lesions.
    • Endocrinologist
    • Gynecologist
    • Urologist
    • Otolaryngologist
    • Oncologist: An oncologist directs appropriate therapy in the presence of intestinal or extraintestinal malignancy.
  • Patients with BRR may require consultation with the following:
    • Dermatologist
    • Developmental pediatrician: The developmental pediatrician manages seizures and develops strategies for neurodevelopmental stimulation.
    • Endocrinologist: An endocrinologist treats Hashimoto thyroiditis and cryptorchidism.
    • Gastroenterologist: A gastroenterologist evaluates for polyposis, manages symptoms of drooling, and establishes GI surveillance. 
    • Gynecologist: A gynecologist establishes surveillance strategies for breast neoplasia.
    • Neurologist: The neurologist manages seizures and develops strategies for neurodevelopmental stimulation.
    • Oncologist: An oncologist directs appropriate therapy if malignant transformation occurs.
  • Patients with GS may require subspecialty support for treatment of craniofacial and ophthalmologic abnormalities, management of scoliosis, and surveillance and treatment of potential neoplasias (eg, medulloblastoma, basal cell carcinoma, ovarian fibromas and sarcomas, mesenteric cysts).
  • Patients with Cowden disease may benefit from the following consultations:
    • Neurologist - For seizures and tremors
    • Endocrinologist - For thyroid
    • Gastroenterologist - For hamartomatous polyps
    • Oncologist - For management and treatment of potential malignancies
    • Surgeon - For treatment of increased intracranial pressure, cerebellar lesions, breast cancer, thyroid lesions, and renal carcinoma

Diet

  • The benefits of low-fat/high-fiber diets and supplementation with either calcium or antioxidants, including ascorbic acid and alpha-tocopherol, is controversial in patients with Gardner syndrome. Several controlled trials in adults have studied dietary interventions, including wheat bran on the rate of development of adenomatous polyps.
    • In a 4-year Gardner syndrome trial, patients were randomized to either 4 g of ascorbic acid plus 400 mg of alpha-tocopherol alone or 22.5 g of daily fiber supplement.
    • Based on actual intake, the combined intervention diminished the rate of formation of rectal polyps.
    • The Australian polyp prevention trial noted a reduced incidence of adenoma formation with reduced fat and increased bran intake.
    • Yang et al noted a decrease in colonic epithelial proliferation activity via increasing calcium intake to 1200 mg with low-fat dairy foods; however, the Toronto polyp prevention trial found no difference in the incidence of polyp recurrence between a low-fat/high-fiber diet and a typical Western diet with placebo fiber.
    • Fuchs et al also noted no protective effect of dietary fiber against colorectal adenomas and carcinoma in women.35
  • No studies are currently available regarding dietary modification in patients with PJS. Development of short-bowel syndrome from repetitive intestinal resections requires special nutritional interventions, including vitamin and nutrient supplementation, continuous enteral feedings, or parenteral nutrition.
  • No studies are currently available regarding dietary modification in patients with BRR, Cowden disease, or GS.

Activity

  • No limitation of activity is mandated for patients with PJS, BRR, Gardner syndrome, or Turcot syndrome unless other medical issues necessitate restrictions.
  • Patients with GS should minimize exposure to ultraviolet light and ionizing radiation to reduce the risk of developing basal cell carcinomas.
  • No limitation of physical activity is mandated for patients with Cowden disease unless other physical conditions are present. Patients with Cowden disease have an increased risk for development of thyroid carcinoma and may wish to minimize exposure of the neck to ionizing radiation.

Medication

Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have been consistently associated with diminished risk of colorectal cancer. Sulindac has been reported to cause regression of adenomas in patients with Gardner syndrome. NSAIDs suppress cyclooxygenase-2 (COX-2), which affects epithelial proliferation and apoptosis.

Studies by Watanabe et al suggest an important role of antagonistic agents for the prostaglandin EP1 receptor for chemoprotection against the development of colon cancer.36

Nonsteroidal anti-inflammatory drugs (NSAIDs)

These agents have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action inhibits 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, may also occur.


Sulindac (Clinoril)

Has been reported to cause regression of adenomas in patients with Gardner syndrome (ie, FAP).

Adult

150 mg PO bid

Pediatric

Not established

May interact with PO anticoagulants and PO hypoglycemics; NSAIDs may enhance the tubular secretion of methotrexate and enhance toxicity; renal impairment may increase levels; simultaneous administration with cyclosporine may increase the toxicity of cyclosporine

Documented hypersensitivity, asthma; perioperative pain in setting of coronary artery bypass graft (CABG) surgery

Pregnancy

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

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

Precautions

Pregnancy category D in third trimester; pancreatitis may develop, requiring discontinuation of the drug; eye symptoms require ophthalmologic evaluation; may cause fluid retention and peripheral edema; caution in patients with hypertension or compromised cardiac function, conditions predisposing to fluid retention; may cause increased risk of serious CV thrombotic events, MI, and stroke; severe heart failure and hyponatremia, because may deteriorate circulatory hemodynamics; can cause renal papillary necrosis and GI bleeding

Cyclooxygenase-2 (COX-2) inhibitors

These agents inhibit COX-2, thus suppress production of prostaglandin E2 at inflammation sites.


Celecoxib (Celebrex)

Recently was approved by the FDA for treatment of Gardner syndrome as an adjunct to endoscopy and surgery. The mean reduction in the number of polyps was 28% with 400 mg PO bid and 12% with 100 mg PO bid (5% placebo).

Adult

100-400 mg PO bid

Pediatric

Not established

CYP 450 2C9 substrate; coadministration with fluconazole may cause increase in celecoxib plasma concentrations because of inhibition of celecoxib metabolism; coadministration of celecoxib with rifampin may decrease celecoxib plasma concentrations

Documented hypersensitivity; perioperative pain in setting of CABG surgery

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; as many as 15% of patients may experience an increase in transaminase levels; may cause fluid retention and peripheral edema; caution in compromised cardiac function, hypertension, conditions predisposing to fluid retention; may cause increased risk of serious CV thrombotic events, MI, and stroke; 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 in abnormal liver lab results

More on Intestinal Polyposis Syndromes

Overview: Intestinal Polyposis Syndromes
Differential Diagnoses & Workup: Intestinal Polyposis Syndromes
Treatment & Medication: Intestinal Polyposis Syndromes
Follow-up: Intestinal Polyposis Syndromes
References
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Further Reading

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Keywords

Gardner syndrome, familial adenomatous polyposis, FAP, Turcot syndrome, Peutz-Jeghers syndrome, polyps-and-spots syndrome, Cronkhite-Canada syndrome, polyposis, skin pigmentation, alopecia, fingernail changes, juvenile polyposis coli, inflammatory polyps, Cowden disease, multiple hamartoma syndrome, Bannayan-Riley-Ruvalcaba syndrome, BRR, macrocephaly, multiple lipomas, hemangiomata, Bannayan-Zonana syndrome, Riley-Smith syndrome, Ruvalcaba-Myrhe-Smith syndrome, Gorlin syndrome, GS, basal cell nevus syndrome, Gorlin-Goltz syndrome, colonic polyposis, periampullary adenomas, papillary carcinoma of the thyroid, hepatoblastoma, osteoma, epidermal cyst, desmoid tumor, glioblastoma multiforme, medulloblastoma, gynecomastia, hamartomatous polyps, macrocephaly, limpomas, hemangiomata, nevoid basal cell carcinoma, palmar pits, cerebelloparenchymal disorder, Lhermitte-Duclos disease, glycogenic acanthosis, orocutaneous hamartomas, pulmonary hamartomas

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Contributor Information and Disclosures

Author

Ann Scheimann, MD, MBA, Assistant Professor, Department of Pediatrics, Section of Nutrition and Gastroenterology, Baylor College of Medicine and Johns Hopkins Medical Institution
Ann Scheimann, MD, MBA is a member of the following medical societies: North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.

Medical Editor

Jayant Deodhar, MD, Associate Professor in Pediatrics, BJ Medical College, India; Honorary Associate Consultant, Departments of Pediatrics and Neonatology, King Edward Memorial Hospital, India
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Nothing to disclose.

Managing Editor

Stefano Guandalini, MD, Director, University of Chicago Celiac Disease Program, Section Chief of Gastroenterology, Hepatology and Nutrition; Professor, Department of Pediatrics, University of Chicago Comer Children's Hospital
Stefano Guandalini, MD is a member of the following medical societies: American Gastroenterological Association and North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.

CME Editor

Steven M Schwarz, MD, FAAP, FACN, AGAF, Professor of Pediatrics, State University of New York, Downstate Medical Center College of Medicine; Professor of Clinical Pediatrics, St George's University School of Medicine; Distinguished Lecturer, New York Medical College, School of Public Health; Chair and Consulting Staff, Department of Pediatrics, Long Island College Hospital
Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, American Gastroenterological Association, American Pediatric Society, Gastroenterology Research Group, New York Academy of Medicine, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine
Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

 
 
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