Medical Care
In several of the polyposis syndromes, medical care encompasses screening and intervention for malignant transformation. Particularly in the case of familial adenomatous polyposis (FAP), in which an inevitable progression to colorectal cancer occurs by age 35-40 years, [24] screening of patients and family members has led to an improvement in cumulative survival and a 55% reduction in colorectal cancer at diagnosis of FAP. [67] Approximately 50% of patients with familial juvenile polyposis (FJP) develop GI cancer. [68]
Familial adenomatous polyposis
Unless a family history of early and aggressive disease is noted, children at risk for FAP should be screened twice yearly starting at age 10-12 years. Flexible sigmoidoscopy is sufficient because the adenomas are distributed throughout the colon. The American Gastroenterological Association recommends an annual sigmoidoscopy or colonoscopy for patients with a genetic diagnosis of FAP or for at-risk family members who have not undergone genetic testing. [69] Narrow-band imaging can identify higher numbers of duodenal adenomas, but it did not lead to a clinically relevant upgrade in stage when compared with high-resolution endoscopy. [70]
If the patient undergoes prophylactic colectomy, the ileal pouch is at risk for developing adenomatous carcinoma and should be screened with endoscopy on a yearly basis. Gastric and duodenal lesions occur in 45% of patients with the APC mutation, and upper endoscopy should begin when colonic adenomas are identified or at age 20-25 years. A study of pediatric patients with APC mutations suggests that upper endoscopy should begin even earlier. [71]
The risk of developing malignancy in these lesions is lower than the risk from colonic lesions but is still approximately 12%. Depending on the polyp burden, front and/or side-viewing endoscopies of the stomach, duodenum, and periampullary region should occur every 6 months to 4 years. The risk of periampullary tumors is increased in these patients. The tumors are best viewed with both side-viewing and end-viewing instruments. [72] Current options for management include endoscopy, chemoprevention, duodenectomy, the Whipple procedure, and ampullectomy, none of which have been especially successful.
Patients with the APC gene mutation at codon 1309 are at risk for a more aggressive phenotype, and early screening and colectomy is advocated for in children with this mutation. [71]
Postcolectomy, mesenteric or abdominal wall desmoids can develop and may cause fatal complications from sepsis or hemorrhage. They are more common in females and can cause obstruction of the mesenteric blood supply, intestines, or urinary tract. [4]
Gardner syndrome
In addition to the above recommendations for FAP, patients with Gardner syndrome 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. [73]
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
As with Gardner syndrome, in addition to the above recommendations for FAP, patients with Turcot syndrome require 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.
Peutz-Jeghers syndrome
Patients require medical management for problems attributed to polyposis and for detection of malignancy.
Patients with Peutz-Jeghers syndrome (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 periampullary malignancies. Colonoscopy is recommended every 3 years starting when symptoms occur or in the early teenage years in asymptomatic patients. At age 10 years, twice yearly upper endoscopies and barium imaging of the upper GI tract are recommended. [72]
Long-term surveillance to monitor for extraintestinal malignancies (eg, breast, gynecologic, testicular) is indicated.
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.
PTEN-hamartomatous syndromes
If a patient remains asymptomatic, a first colonoscopy is recommended between the ages of 35-40 years, with follow-up determined by number and type of polyps found on screening. [74]
Patients require medical therapy for CNS abnormalities, complications of lipomas and arteriovenous malformations, treatment of Hashimoto thyroiditis, and surveillance for malignancy.
Children may exhibit hypotonia, developmental delay, and mild mental retardation that requires coordinated speech and occupational and physical therapies to maximize potential. Development of pediatric nonmedullary thyroid cancer should raise clinical suspicion for PHTS. [74]
Significant lipomatous or vascular lesions (hemangiomas, arteriovenous malformations) have resulted in CNS complications (eg, seizures), amputations, and premature death.
Patients appear to have an increased risk for CNS tumors.
Increased incidence of Hashimoto thyroiditis, along with abnormalities of the PTEN gene (tumor suppressor gene), enhance the likelihood for development of neoplasia, especially thyroid and breast.
Patients require careful monitoring for the development of malignancies within the cerebellum, breast, skin (Merkel cell), and kidneys (renal cell adenocarcinoma) with scheduled screening of mammograms, dermatological examinations, and appropriate imaging.
Familial juvenile polyposis
Esophagogastroduodenoscopy (EGD) and colonoscopy should be performed at age of onset of symptoms or at age 15 years in asymptomatic patients at risk. If no polyps are present, this should be repeated every 3 years. If polyps are seen, they should be removed and EGD and colonoscopy should be performed yearly until no polyps are seen. [75]
Cronkhite-Canada syndrome
Patients should be regularly screened for colorectal and gastric cancer because they are at higher risk of developing malignancy in these areas.
Gorlin syndrome
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 Gorlin syndrome (GS) presented with cleft lip and palate at birth. [59]
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.
Serrated polyposis syndrome
Patients with serrated polyposis syndrome (SPS) require regular screening colonoscopies to remove premalignant lesions that could lead to colorectal cancer. First-degree relatives of patients with SPS should begin screening 10 years prior to the index case. Screening should occur every 1-2 years with removal of all visualized polyps. [15]
Surgical Care
Familial adenomatous polyposis
The inevitable course is the development of colorectal cancer. To prevent this, surgical intervention is required, in the form of total proctocolectomy with ileoanal anastomosis, subtotal colectomy with ileorectal anastomosis, or total proctocolectomy with permanent ileostomy.
In patients who have subtotal colectomy with ileorectal anastomosis, the remaining rectal stump must be monitored for polyp recurrence. Timing of prophylactic colectomy or proctocolectomy has not been standardized, with most authors recommending that once polyposis is confirmed, severely affected patients should have prophylactic surgery as soon as possible. Mildly affected patients are recommended to have surgery within the year. [76]
Patients with Gardner syndrome require surgical treatment of the following:
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Cutaneous cysts
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Symptomatic dental anomalies and osteomas
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Biopsy and resection for malignancies, including hepatoblastoma, thyroid carcinoma, osteocarcinoma, gastric carcinoma, periampullary carcinoma, and biliary tract carcinoma
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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 and hepatic lesions.
Peutz-Jeghers syndrome
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 for potential malignancies (ie, antrectomy, duodenectomy).
PTEN-hamartomatous syndromes
Patients 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.
Later in age, these patients may 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
Familial juvenile polyposis
With the cumulative risk of malignancy greater than 50%, no guidelines have been established; however, some authors are recommending subtotal colectomy with ileorectal anastomosis in children with anemia, hypoproteinemia, and failure to thrive. [77]
Prophylactic colectomy with ileorectal anastomosis is recommended for children who have severe or repeated bleeding and adults with FJP. [78]
Gorlin syndrome
Patients with GS may require surgical management for the following:
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Craniofacial lesions (cleft lip and palate, jaw cysts, other mandibular lesions)
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Abdominal masses (mesenteric cysts, lymphatic cysts, ovarian fibromas)
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Diagnostic and therapeutic interventions for potential neoplasia within the CNS (medulloblastoma), skin (basal cell carcinoma), jaw (fibrosarcoma), ovaries (fibrosarcoma), and endometrium (adenocarcinoma)
Serrated polyposis syndrome
Prophylactic colectomy with ileorectal anastomosis is recommended for those with detection of cancer, inability of colonoscopy to control polyps, or patient preference. [79]
Consultations
Familial adenomatous polyposis
Patients with Gardner syndrome may require consultation with the following:
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Gastroenterologist - For monitoring and surveillance for malignancies
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Oncologist - For treatment of malignancies
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Surgeon - For biopsy or resection of suspicious areas
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Dentist or maxillofacial surgeon - For mandibular osteomas or dental anomalies
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Ophthalmologist - For evaluation for retinal anomalies
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Endocrinologist - For evaluation and management of thyroid carcinoma and adrenal carcinoma
Patients with Turcot syndrome may require medical consultation with the following:
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Gastroenterologist - For monitoring and surveillance for malignancies
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Oncologist - For monitoring and treatment of malignancies
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Dermatologist
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Surgeon - For management of CNS, cutaneous, and GI malignancies
Peutz-Jeghers syndrome
Patients with PJS may require consultation with the following:
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Gastroenterologist: Assistance from a gastroenterologist may localize sites of polyps or bleeding.
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Surgeon: Surgical intervention may include resection of symptomatic areas and biopsy for suspicious malignancy.
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Dermatologist: Some patients with PJS may initially present to the dermatologist for diagnosis of cutaneous lesions.
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Endocrinologist
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Gynecologist
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Urologist
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Otolaryngologist
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Oncologist: An oncologist directs appropriate therapy in the presence of intestinal or extraintestinal malignancy.
PTEN-hamartomatous syndromes
Patients with BRR may require consultation with the following:
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Dermatologist
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Developmental pediatrician: The developmental pediatrician manages seizures and develops strategies for neurodevelopmental stimulation.
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Endocrinologist: An endocrinologist treats Hashimoto thyroiditis and cryptorchidism.
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Gastroenterologist: A gastroenterologist evaluates for polyposis, manages symptoms of drooling, and establishes GI surveillance.
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Gynecologist: A gynecologist establishes surveillance strategies for breast neoplasia.
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Neurologist: The neurologist manages seizures and develops strategies for neurodevelopmental stimulation.
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Oncologist: An oncologist directs appropriate therapy if malignant transformation occurs.
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Surgeon: Consultation with a surgeon is indicated for treatment of increased intracranial pressure, cerebellar lesions, breast cancer, thyroid lesions, and renal carcinoma.
Gorlin syndrome
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).
Serrated polyposis syndrome
Patients with SPS may require subspecialty consultation from oncology and general surgery if colorectal cancer occurs.
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 FAP. Several controlled trials in adults have studied dietary interventions, including wheat bran, vitamin intake, and fiber on the rate of development of adenomatous polyps. [80]
Yang et al noted a decrease in colonic epithelial proliferation activity via increasing calcium intake to 1200 mg with low-fat dairy foods; [81] 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. [82] Fuchs et al also noted no protective effect of dietary fiber against colorectal adenomas and carcinoma in women. [83]
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 PTEN -hamartomatous syndromes or GS. Nutritional support is the mainstay of treatment of Cronkhite-Canada syndrome, especially in light of protein-losing enteropathy.
Activity
No limitation of activity is mandated for patients with Gardner syndrome, Turcot syndrome, PJS, and BRR syndrome unless other medical issues necessitate restrictions.
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.
Patients with GS should minimize exposure to ultraviolet light and ionizing radiation to reduce the risk of developing basal cell carcinomas.
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Familial adenomatous polyposis, total colectomy specimen. The colonic mucosa is studded with innumerable sessile and small pedunculated polyps, which involve the entire length of the specimen.
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Pedunculated tubular adenoma. Note the contrast between the goblet cell-rich glands along the pedicle of the polyp and in the underlying normal colonic mucosa at the bottom and the dysplastic glands in the polyp proper. The dysplastic glands are more crowded and exhibit decreased mucin production. (Hematoxylin and eosin stain; 1X magnification).
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Sessile tubular adenoma. The glands on the superficial aspect of the specimen are dysplastic and exhibit increased nuclear size, hyperchromasia, crowding, and decreased mucin production. (Hematoxylin and eosin stain, 4X magnification).
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Hamartomatous (Peutz-Jeghers) polyp, small bowel. This pedunculated polyp has a cerebriform appearance due to the arborizing frond-like growth with delicate finger-like projections of the stroma. (Hematoxylin and eosin stain, 1X magnification).
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Hamartomatous (Peutz-Jeghers) polyp, small bowel. Closer view of the fingerlike projections of the stroma demonstrates prominent smooth muscle fascicles between the glandular elements. (Hematoxylin and eosin stain, 4X magnification).
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Hamartomatous polyp, as seen in the stomach. (Endoscopic image).
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Colon in familial adenomatous polyposis (FAP). (Endoscopic image).
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Small bowel polyp. (Video capsule image).
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Multiple large polyps in the colon. The polyp in the center of the image is situated on a stalk. (Endoscopic image).
