Friday, February 29, 2008

Polyposis Syndromes, Colon

A GI polyp is defined as
a mass of the mucosal surface protruding into the lumen of the bowel.
Polyps can be
· neoplastic,
· non-neoplastic, or
· submucosal.
GI polyposis is characterized by multiple polyps within the GI tract.
A variety of polyposis syndromes can affect the GI tract. These polyposis syndromes may be classified as
· familial inherited (autosomal dominant) or
· nonfamilial.
The inherited polyposis syndromes can be further subdivided into 2 groups depending on whether the polyps are
· adenomas or
· hamartomas.
The adenomatous polyposis syndromes include the classic
· familial adenomatous polyposis (FAP),
· Gardner syndrome, and
· Turcot syndrome.
Hamartomatous familial polyposis syndromes include
· Peutz-Jeghers syndrome,
· juvenile polyposis syndrome,
· Cowden disease, and
· Ruval-Caba-Myhre-Smith syndrome.
The non-inherited polyposis syndromes include
· Cronkhite-Canada syndrome,
· and a variety of miscellaneous non-familial polyposis.
From a prognostic viewpoint, these syndromes must be recognized, because the adenomatous polyps are premalignant. These syndromes should be considered when an intestinal polyp is recognized in the young, when 2 or more polyps are seen in any patient, when colonic carcinoma is discovered in patients younger than 40 years, and when extraintestinal manifestations associated with these syndromes are discovered.
GI polyps may be asymptomatic, but may also occur with rectal bleeding and diarrhea. The urgency of case tracing and genetic counseling is related not so much to the symptoms of the disease but to the potential for the development of a colonic carcinoma. It is probable that patients with familial polyposis, if untreated, will develop a colonic carcinoma.
Pathophysiology:
FAP coli
FAP coli is characterized by polyposis of the colon and the eventual development of colonic carcinoma. The syndrome is transmitted in an autosomal dominant manner. Some have suggested that Gardner syndrome may represent a spectrum of the same genetic disease as FAP, with a shared locus at 5q21-q22. Therefore, diagnosis is possible by means of linked DNA markers in the asymptomatic patient.
Approximately two thirds of patients with this disease give a family history of FAP or colonic cancer. In a third of the patients the disease occurs as spontaneous mutation. The colonic polyps are numerous and present as a carpet of polyps ranging from 1-2 mm to 1 cm or larger. In all cases, large numbers of adenomas carpet the colon, occurring initially in the left colon and then eventually spreading to involve the entire colon.
The number of polyps markedly varies between kindreds and even between affected individuals within 1 family with the exact same germline mutation. All affected family members exhibit polyps by the age of 35 years. The number of polyps ranges from 150 to over 1000. The disease is usually diffuse, but segmental involvement may occur.
FAP is associated with hamartomatous polyps in the stomach (49%), adenomatous polyps of the duodenum (25%) and periampullary carcinomas. Histologically, the polyps are adenomatous lesions indistinguishable from sporadic nonfamilial colonic polyps. Colonic cancers usually develop in all patients with FAP within 20 years after the diagnosis.
Another variant of FAP is attenuated adenomatous polyposis coli syndrome. This variant is associated with fewer polyps (<100), and patients may present with as few as 5-10 polyps. Patients with this syndrome have mutations in the extreme 5' and 3' ends of the APC gene. Gardner syndrome Gardner syndrome probably has the same genotype as FAP coli. FAP and Gardner syndrome may occur in the same family. As in FAP, the colonic polyps are histologically adenomatous, and malignant transformation occurs in 100% of patients. Fibrous tissue in patients with Gardner syndrome has a desmoplastic tendency resulting in desmoid tumors, keloids, mesenteric fibrosis and peritoneal adhesions, retroperitoneal fibrosis and mammary fibromatosis. Fibroblast cultures derived skin biopsy specimens in patients with Gardner syndrome have shown abnormalities that may predate the onset of the characteristic features of the disease elsewhere (Kopelovich, 1977). A diffuse form of spontaneous mesenteric fibrosis may occur and is thought to be a response to surgery or unrecognized trauma. It may result in an inoperable bowel obstruction. A variety of benign and malignant neoplasms and abnormal dentition are associated with Gardner syndrome, including the following: Soft-tissue tumors Epidermoid inclusion cysts of the skin Dermoid tumors Fibroma Lipoma Lipofibroma Neurofibroma Leiomyoma Mammary fibromatosis Intra-abdominal desmoid tumors and peritoneal fibromas GI tumors Colonic polyposis (100%) (Colonic carcinoma eventually develops.) Gastric adenomatous polyps (5-68%) Gastric hamartomatous polyps Duodenal adenomatous polyps (90%) (Malignant transformation occurs in 12% of patients.) Periampullary carcinoma (2-12%) Hepatoblastoma Pancreatic carcinoma Lymphoid hyperplasia of the terminal ileum Osseous abnormalities Usually involving the membranous bones (50%), mandible (81%), calvarium, maxilla, ribs, and long bones Self-limited benign exostosis Bone islands and periosteal thickening Endocrine tumors Thyroid carcinoma (This is commonly papillary, and it may be multicentric with a female preponderance. This may predate other manifestation of Gardner syndrome.) Carcinoid tumors of the small bowel Parathyroid adenoma Adrenal adenoma/carcinoma Pituitary chromophobe adenoma Central nervous system medulloblastoma Abnormal dentition Supernumerary teeth Impacted teeth Odontoma Hypercementosis Teeth more prone to carries Peutz-Jeghers syndrome Peutz and Jeghers independently described a syndrome consisting of multiple intestinal hamartomatous polyps associated with mucocutaneous melanotic pigmentation. The skin lesions are · 2-5 mm, · black or brown · macules that · sometimes coalesce on the lips, oral mucosa, nose, fingers, cheek, palms, toes, forehead, and abdomen. · Although the mucosal pigmentation is permanent, the skin lesions may fade at puberty. The hamartomatous polyps · have a smooth muscle core, · which arise from the muscularis mucosa and · extend into the polyp. Mutation analysis of the STK11 gene (with a chromosomal locus at 19p13.3) reveals disease-causing mutations in about 70% of familial cases and 30-70% of sporadic cases (depending on the study). Such testing is available clinically. Regarding the distribution of GI polyps and non-GI polyps, · the stomach and duodenum is involved in 25% patients; o the involvement is usually diffuse, o with multiple polyps. · The small bowel is involved in more than 95% of patients. · The polyps may be broad-based and separated by wide areas of normal mucosa, · a carpet of polyps varying from millimeters to several centimeters in diameter. · Some of the polyps may be large and multilobulated. Colonic and rectal polyps represent 25% of the polyps. · They are usually multiple varying from millimeters to 3 cm in size. · Carpeting usually does not occur in the colon and rectum. · Polyps may occur in the nose, larynx, and bronchial tree. · Polyps and/or adenomas may occur within the urinary tract, particularly the urinary bladder. · Polyps in the gallbladder and bile ducts are rare. Malignant degeneration of these polyps is rare, but the risk of developing other neoplasm is reported to be 18 times greater than that of the general population. A variety of malignant tumors are associated with Peutz-Jeghers syndrome. The risk of carcinoma in the pancreaticoduodenal region is 2-3% and not necessarily associated with polyps. · Pancreatic carcinoma is a complication of the disease in 13% of cases. · Breast carcinoma develops in a minority of patients and is commonly bilateral and ductal. · The risk of ovarian cysts and a variety of ovarian neoplasms (5%), including ovarian sex cord tumor, mucinous cystic tumor, cystadenoma, and granulosa cell tumor is increased. · Other non-GI neoplasms include neoplasms of the thyroid, lung, skin, uterus (endometrial cancer, adenoma malignum of cervix), and testicles (feminizing Sertoli cell tumor). Turcot syndrome Turcot et al first described an association between colonic polyps and tumors. · The colonic/rectal polyps are adenomatous, usually multiple, and 1-30 mm in diameter. · Most central nervous tumors are supratentorial glioblastoma with occasional medulloblastoma. · Other reported abnormalities include sebaceous cysts, papillary carcinoma of the thyroid, leukemia, and spinal cord tumors. A recent study of 14 families with a history of both colon and brain tumors revealed mutations in 2 types of genes known to cause inherited forms of colon cancer. · Ten of the families had alterations of the APC gene, a tumor suppressor gene associated with FAP. In 2 additional families, a mutation of 1 of 2 mismatch repair genes, hMLH1 and hPMS2, were identified. Those who inherit a defective mismatch repair gene tend to be mutation prone, and they are at higher risk of developing cancer. Both hMLH1 and hPMS2 are involved in the development hereditary nonpolyposis colorectal cancer, which is believed to be the most common inherited disease in humans. Recent studies have revealed that patients with FAP are about 90 times more likely to develop brain tumors than the general population. · Turcot syndrome may be more prevalent then previously thought. · Recently, Turcot syndrome has been subdivided into 2 groups. · In the first group, the association of o adenomatous polyposis with malignant brain tumors constitutes the rare disease of Crail syndrome; o patients with this disease usually have mutations in the APC gene. · A second group of patients o have mutations in the DNA repair genes; o these patients have hereditary nonpolyposis colon cancer (Turcot syndrome). Cronkhite-Canada syndrome Cronkhite-Canada syndrome includes · generalized GI polyposis in association · with neuroectodermal changes consisting of o alopecia, o hyperpigmentation, and o atrophy of the nails. · Electron microscopic studies of the skin reveals increased numbers of melanin granules in keratinocytes, increased numbers of melanosomes in melanocytes, increased melanocyte numbers, compact hyperkeratosis, and perivascular inflammation and exocytosis. · A number of hematologic, neurologic, and metabolic abnormalities are associated with Cronkhite-Canada syndrome.
Juvenile polyposis syndrome
Juvenile polyposis syndrome is
· a rare disease, but it is
· the most common cause of colonic polyposis in children.
· Inherited in an autosomal dominant manner with variable penetrance,
· it may be familial or nonfamilial.
· The 3 forms of juvenile polyposis are
o based on the location of the polyps:
§ familial juvenile polyposis coli,
· in which the polyps are confined to the colon;
§ familial juvenile polyposis of the stomach;
§ and generalized juvenile polyposis,
· in which polyps are distributed throughout the GI tract in any age group.
· This disorder is associated with variable penetrance so that one affected family member may have 200 polyps,
o whereas another affected member may only have a single hamartomatous polyp.
The syndrome is associated with
o hamartomatous GI polyps,
o but adenomas may coexist.
· The polyps are solitary in 75% of patients,
o but may be multiple.
· Most of the polyps are located in the rectosigmoid (80%), and
o polyps in the stomach and small bowels are rare.
· The polyps are smooth of rounded contour, and they may vary from 1 mm in size to several centimeters in diameter.
The polyps are invariably on a stalk of differing lengths.
Histologically, the polyps are characterized by
· hyperplasia of mucous glands,
· retention cysts, and
· obstruction of the gland orifices associated with an edematous, inflamed, and expanded lamina propria but
· little or no smooth muscle.
Cowden syndrome
Cowden is the family name of the original reported patient, Rachel Cowden. Cowden syndrome is a rare disorder that is inherited in autosomal dominant manner with intra-familial and inter-familial differences in the expressivity of symptoms. Germline mutations in a candidate tumor suppresser gene, PTEN, have been identified with Cowden syndrome.
· PTEN is involved in a wide variety of cancers, including those of the brain, breast, and prostrate.
Cowden syndrome is characterized by
· multiple hamartomas and neoplasms of endodermal, ectodermal, and mesodermal origin.
· The associated GI polyps may be juvenile;
· hamartomatous;
· and hyperplastic;
· lymphomatous; inflammatory;
· or adenomatous (rare).
Cowden syndrome is associated with Lhermitte-Duclos disease and Down syndrome. It is also associated with an increased severity and earlier onset of symptoms in subsequent generations.
A variety of lesions have been associated with the syndrome, including the following:
Mucocutaneous lesions
Multiple facial papules, papillomatosis of the lips, gums, and tongue and oral fibromas
Acral keratosis, palmoplantar keratosis, acral verrucoid lesions, skin tags, dermal fibromas, lipomas, and skin malignancies
Soft tissue tumors including lipomas, fibroangiomas, angiolipomas, and cavernous hemangiomas
Head and neck abnormalities
Macrocephaly, hypoplasia of the mandible and maxilla associated with microstomia
Cysts of the scalp
Cataracts, angioid streaks, myopia and congenital blood vessel anomalies, and glaucoma
Goiter, thyroid adenoma, hyperthyroidism, hypothyroidism, thyroiditis, thyroglossal duct cyst, and follicular thyroid carcinoma (3-4%).
Vocal cord polyps
Breast lesions
Fibrocystic disease, fibroadenomas, virginal hyperplasia, and benign gynecomastia (in males)
Breast cancer (often bilateral, ductal in 20-30%)
GI lesions
GI polyps
Diverticula of the colon
Ganglioneuromas, neuromas, epithelioid leiomyoma of the rectosigmoid, and adenocarcinoma of the colon
Hamartoma of the liver
Genitourinary involvement
Menstrual irregularity, miscarriages, and still births
Ovarian cysts
Uterine leiomyomas
Vaginal and vulvar cysts
Adenocarcinoma of the uterus
Cervical carcinoma
Ovarian cancer
Transitional cell carcinomas of the renal collecting system and bladder
Varicoceles
Central nervous system involvement
Reduced intellect
Seizures
Intention tremors
Cutaneous nerve neuromas
Neurofibromas
Meningiomas
Hearing loss
Musculoskeletal involvement
Supernumerary digits
Pectus excavatum
Scoliosis/kyphosis
Bone cysts
Ruval-Caba-Myhre-Smith syndrome
Ruval-Caba-Myhre-Smith syndrome is inherited in autosomal dominant manner, with some sporadic cases. The syndrome is characterized by macrocephaly, pigmented genital lesions, subcutaneous and visceral lipomas, and hemangiomas and GI hamartomatous polyps. Mesodermal hamartomas can affect the subcutaneous, intracranial, visceral, intestinal, thoracic, and osseous tissues. Hydrocephalus and diffuse thickening of the corpus callosum have also been described.
Frequency:
In the US: FAP is inherited in an autosomal dominant manner with 80% penetrance but sporadic occurrence has been recorded in one third of patients. The gene for FAP is located on chromosome 5. The prevalence is quoted as 1 in 7,000-24,000 live births.
Gardner syndrome probably has the same genotype as FAP coli. It is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. The estimated prevalence is 1 in 14,000 population (Pierce, 1970).
Peutz-Jeghers syndrome has a prevalence of 1 in 7,000 live births with a half familial and half sporadic distribution.
Cronkhite-Canada syndrome has no hereditary factors, and 100 cases have been published as of 1994.
Turcot syndrome is inherited in an autosomal recessive manner. Approximately 100 cases of Cowden's syndrome have been reported in literature.
Ruval-Caba-Myhre-Smith syndrome is rare, and the exact incidence is not known.
Internationally: To the authors' knowledge, no available data suggest that the frequency of polyposis syndromes is different from that in the United States.
Mortality/Morbidity: In FAP, malignant transformation may occur in the stomach; small bowel; or colon, the most common site. Cancers develop in 12% of patients at 5 years after the diagnosis, in 30% at 10 years, and in 100% at 20 years. The carcinomas are multiple in 48%. Carcinomas develop in patients aged 20-40 years.
Periampullary carcinoma is the leading cause of death in patients with FAP who have undergone prophylactic colectomy.
In Gardner syndrome, colonic carcinoma develops in all patients by the age of 41 years.
Peutz-Jeghers syndrome is often associated with abdominal cramps due to subacute obstruction or small-bowel intussusception. The incidence of non-GI cancer is 18 times higher than that of the general population. The life expectancy is decreased, with the risk of cancer approaching 40% by the age of 40 years.
The prognosis in patients with Turcot syndrome is poor because of its association with supratentorial glioblastomas. Death from brain tumor occurs in the second or third decade of life. Malignant transformation of the colonic polyps occurs in almost all patients.
Cronkhite-Canada syndrome is rapidly fatal in women within 6-18 months from the onset of cachexia, with a tendency toward remission in men.
Regarding patients with Cowden syndrome, by the time women reach their 40s, 50-75% develop breast cancer.
Race: There is no racial predilection for colonic polyps.
The international incidences of colonic cancer reflect dietary differences in fat and fiber intake rather than racial differences.
When the population of a developing country adopts a Western diet, rates of colon cancer increase.
Similarly, among immigrants from a low-incidence country, the incidence rate soon approximates the rate of their adopted country.
Sex: No sex predominance is reported in FAP coli, Gardner syndrome, or Peutz-Jeghers syndrome. However, the papillary thyroid carcinoma associated with Gardner syndrome has a female preponderance.
Cronkhite-Canada syndrome is more common in males, although the exact male-to-female ratio is unknown.
For juvenile polyposis of infancy, the male-to-female ratio is 3:2.
Cowden syndrome mostly affects women. Regarding patients with Cowden syndrome, by the time women reach their 40s, 50-75% develop breast cancer.
Age: In FAP, the polyps are not present at birth and usually appear at puberty, although the age at onset varies greatly. In all cases, large numbers of adenomas carpet the colon, occurring initially at an average age of 15 years in the left colon. Eventually, these polyps spread to involve the entire colon. The average patient age at the onset of symptoms is 32 years, but the first symptoms may appear at any age between 5 and 55 years. A gap of 10 years usually occurs between the recognition of disease and the onset of symptoms.
Patients with Gardner syndrome are typically aged 15-30 years.
The average patient age at presentation of Peutz-Jeghers syndrome is 25 years.
Patients with juvenile polyposis of infancy are aged 4-6 years, with an age range of 1-10 years, whereas colonic or generalized polyposis usually present at 20 years of age.
Patients with Turcot syndrome are symptomatic during the second decade.
Cronkhite-Canada syndrome affects patients with an average age of 62 years (age range, 42-75 y).
The age of onset of Cowden syndrome is in the first to third decades.
Anatomy:
Clinical Details: The groups of symptoms that are shared by all polyposis syndromes include vague abdominal pain, rectal bleeding, mild diarrhea, passage of mucus, intussusception, rectal prolapse, and bowel obstruction.
GI symptoms of rectal bleeding and abdominal pain usually develop in the third decade in FAP.
Turcot syndrome
The presentation is that of FAP associated with café-au-lait spots and central nervous system tumors. Patients may present with seizures and diarrhea.
Gardner syndrome
Gardner syndrome is characterized by early mild diarrhea associated with small amount of mucus and blood. Some patients are asymptomatic. In 15-20 years after the onset of GI symptoms, the polyps undergo malignant transformation, and the associated symptoms are then those of an underlying GI malignancy.
A variety of other tumors can develop, including bone tumors and soft tissue tumors, such as multiple epidermoid cysts, dermoid tumors, fibromas, and neurofibromas. Patients can also have benign exostosis; osteomatosis, which is mostly confined to the face and skull, and multiple impactions of the supernumerary teeth.
Gardner syndrome is frequently associated with retinal pigment epithelium hypertrophy. Patients with Gardner syndrome often seek medical advice because of facial cosmetic deformity associated with soft tissue or bony abnormality. The diagnosis may be first suggested when dental abnormalities are detected or when patients present with sinusitis secondary to osteomas that affect the paranasal sinuses.
Peutz-Jeghers syndrome
Peutz-Jeghers syndrome is associated with brown or black freckles of the lips, buccal mucosa, face, palms, and soles. Hamartomatous polyps occur in the entire GI tract, where they may cause recurrent abdominal pain, rectal bleeding, and anemia. The polyps may form a nidus for intussusception and rectal prolapse. Malignant degeneration within the polyps is rare, but the incidence of both GI and non-GI neoplasms in patients with this syndrome is 18 times that of the general population.
Cronkhite-Canada syndrome
Cronkhite-Canada syndrome may occur with loss of the sense of taste and with xerostomia, glossitis, anorexia, dysphagia, vomiting, abdominal pain, protein-loosing enteropathy, and diarrhea.
A number of hematologic and metabolic abnormalities are associated with Cronkhite-Canada syndrome. These include anemia, thromboembolic episodes, hypocalcemia, hypomagnesemia, hypokalemia, electrolyte depletion, and weight loss. Fatty degeneration may cause abnormal liver function test results. Cronkhite-Canada syndrome is also associated with transient ischemic episodes, tetany, cataracts, peripheral neuropathy, systemic lupus erythematosus, finger clubbing, and hypothyroidism. The GI polyps are hamartomatous and have no malignant potential.
Symptoms appear in middle and old age. A rare infantile form has been described; this is characterized by macrocephaly, finger clubbing, alopecia, dystrophic nails, hypotonia, anemia, hepatosplenomegaly, and protein-loosing enteropathy. Most polyps are seen in the stomach and colon (100%), and the small bowel is affected in over 50% of patients.
Juvenile polyposis syndrome
Juvenile polyposis syndrome can subdivided into 2 types. The first is juvenile polyposis, which affects children aged 4-6 years, who usually present with protein-loosing enteropathy, diarrhea, hemorrhage rectal prolapse, and intestinal obstruction due to intussusception. The second type is colonic and generalized polyposis with an average age of presentation by 20 years present with rectal bleeding, rectal prolapse and anemia.
The most common presenting symptom may be anemia, at an average age of 18 years. Another typical presentation is a child who has a rectal polyp and presents with bleeding, obstruction, or intussusceptions. Other features of the syndrome may include macrocephaly; mental retardation; and breast lesions, including fibroadenomas. Approximately one half of the patients who present with juvenile polyposis have no family history of the disease. The risk of colorectal cancer in juvenile polyposis is approximately 40%; however, some families develop gastric cancer rather than colon cancer.
Cowden syndrome
Patients with Cowden syndrome presents with a birdlike facies, a small mandible and maxilla, and microstomia. The palate is high and arched. Skin lesions are common and seen as multiple facial papules, keratosis, and a scrotal tongue. Female patients may present with menstrual irregularities, miscarriages, and stillbirths. Central nervous system symptoms may predominate and include an intention tremor and seizure often associated with impaired intellect. Cataracts, myopia hearing loss, and thyroid disorders are well-recognized features. A variety of tumors have been described.
Ruval-Caba-Myhre-Smith syndrome
Patients with Ruval-Caba-Myhre-Smith syndrome may present with macrocephaly, increased birth weight, and postnatal growth retardation. Central nervous system symptoms may the dominant symptoms. These include a delay in achieving the milestones of development, impaired intellect, speech delay, prolonged drooling, seizures, strabismus, and amblyopia. The palate is arched, and the syndrome is associated with pectus excavatum and hyperextensibility of joints. The presentation may reflect the effects of a colonic polyp or subcutaneous, intracranial, visceral, thoracic, or skeletal hamartomas.
Preferred Examination:
Imaging examinations
For polyps larger than 1 cm, the sensitivity of single- and double-contrast barium enema (DCBE) examination is 90-95%. DCBE is more sensitive in the detection of polyps smaller than 1 cm.
When combined with a sodium chloride enema technique, sonography can be used to detect colonic polyps as small as 7 mm in 91% of patients. However, the technique is cumbersome and not widely practiced. At present, this approach cannot replace a barium enema study or colonoscopy. Still, ultrasonography is an invaluable tool in the screening of patients with polyposis syndromes and in the screening of their families for associated cancers, such as those of the thyroid, breast, liver, ovaries, and uterus.
CT and magnetic resonance (MR) colonography (virtual colonoscopy) are new techniques being developed for the imaging of colorectal polyps and cancer. The limited data presently available show that the sensitivity of both CT and MR colonography for polyps larger than 1 cm is 75-90%; however, the detection rate decreases precipitously for smaller polyps. Both CT and MR colonography allow an analysis in both the cross-sectional and virtual endoscopic formats. New developments, such as fecal tagging, are likely to increase the sensitivity of the techniques, and the noninvasive nature of the procedures increase patient acceptability.
CT and MR techniques have the added advantage that both offer the capability of imaging extra-intestinal disease associated with many of the colon polyposis syndromes.
Genetic counseling, screening, and surveillance
Identified genes
In the majority of patients, colon cancer is sporadic, and they have no family history of bowel cancer. However, a growing number of genes have been identified; these increase the risk of colon cancer. Three genes with a strong link with colon cancer include the gene for FAP and two genes associated with hereditary non-polyposis colorectal cancer; these are designated MSH2 and MLH1.
The FAP gene is best understood because of its mode of its autosomal dominant inheritance and complete penetrance. Although polyp formation usually begins in the second decade of life, genetic testing is available for the APC gene, which is located on chromosome 5q. Current assays detect approximately 82% of cases tested. The FAP gene, known as APC, has been localized to the long arm of chromosome 5, and mutations are usually associated with the progressive development of multiple colonic polyps with a potential for malignant transformation.
For patients with inherited FAP, the lifetime risk for developing colon cancer is almost 100%. Genetic detection and counseling is available to at-risk families and can significantly improve the lives of noncarriers. Therefore, a person found not to carry the FAP gene can be spared further surveillance, which is usually undertaken in individuals at high risk.
Testing for potentially affected families usually starts with analysis of an affected family member, to identify the mutation responsible for the disease. Importantly, 20-30% of newly diagnosed adenomatous polyposis patients have de novo mutations, being the first patients in the family to present with colonic polyposis.
In patients who have inherited the disease, the condition is treatable and even curable with screening colonoscopy and surgical resection.
Screening and surveillance for patients with adenomatous polyposis syndromes
Screening and surveillance in this group includes flexible sigmoidoscopy of first-degree relatives starting at puberty (10-12 y), or sooner in symptomatic patients. Families should be screened annually for polyposis until adenomas are detected, until they have undergone genetic testing along with the index patient, or until are found not to have the mutant gene that caused the disease in the index case. Genetic testing can be performed as early as age 10 years. If genetic testing is not available or not performed, first-degree relatives who have no evidence of polyps by the age of 25 years may undergo flexible sigmoidoscopy every 2 years until the age of 35 years.
Because FAP has 100% penetrance, virtually all affected members will exhibit polyps by 35 years of age. Upper GI polyps develop in the majority of patients with FAP. Most common are benign polyps in the stomach, as well as adenomas that develop in the duodenum and ampulla.
The risk of gastric or nonduodenal small-bowel cancers appears to be low (0.5%) in patients with FAP. However, the lifetime risk of duodenal, ampullary, and/or pancreatic cancer is increased, at 5-10%. For this reason, most authorities recommend upper GI side-viewing endoscopy every 1-4 years in patients with FAP, starting at 20-25 years of age. Patients should be evaluated for polyps of the stomach or duodenum at least once a year, and biopsy samples of suspicious lesions should be obtained. No screening is normally recommended in first-degree relatives in whom polyposis has not been diagnosed.
Surveillance for extra-GI tumors can be performed by means of yearly physical examination supplemented by laboratory examination. Desmoid tumors affect 10% of patients with FAP. Although these tumors are benign, they have an aggressive behavior and can be lethal, as they encase and constrict the abdominal organs and vessels. Desmoids are more common in women than in men, and they appear to cluster in families. The tumors are provoked by surgery and childbirth.
In patients with FAP, the lifetime risk of thyroid cancer is increased by 2-3%, and patients usually present in the third decade. Some authorities recommend thyroid screens, perhaps by means of ultrasonography, while others regard physical examination as sufficient.
Patients with Crail syndrome and their potentially affected family members should undergo screening similar to that used in FAP. However, in addition, careful neurologic assessment is indicated. Screening for brain tumors may include CT but preferably MRI of the head. Hepatoblastomas and embryonal liver tumors are known to be associated with FAP in young children. Because these liver cancers are potentially curable, screening with serum alpha-fetoprotein testing and with a consideration of liver imaging (perhaps sonography) may be warranted in children younger than 5 years.
Ophthalmic examinations are performed to evaluate for congenital hypertrophy of the retinal pigment epithelium (CHRPE) in the index patient with FAP. If the index patient has CHRPE, it may be a useful clinical marker of Gardner syndrome in other first-degree relatives; when present, CHRPE has a predictive value of 100%. In screening first-degree relatives of a patient with Gardner syndrome, the absence of non-GI manifestations, such as bone or skin tumors, does not rule out Gardner syndrome.
In Ashkenazi Jews, a single mutation in the APC gene (I1307K) has been identified. This mutation seems to be associated with a 20-30% lifetime risk of colorectal cancer, but at this point, it is not associated with FAP. This mutation has been found in 28% of Ashkenazi Jews with a family history of colon cancer and in 6% of those with a negative family history of colorectal cancer. For carriers of the mutation who have a positive family history of colorectal cancer, the lifetime risk may approach 50%. Ashkenazi Jews with a family history of colon cancer may benefit from genetic testing for I1307K. If the results are positive for the mutation, individuals may be followed up with colonoscopy every 2 years, beginning at age 35 years. Genetic testing is available.
A unified policy of screening may be applied to hamartomatous polyposis, with some changes for individual syndromes such as juvenile polyposis, Cowden disease, and Peutz-Jeghers syndrome.
Peutz-Jeghers syndrome is inherited in an autosomal dominant manner. About one half of the patients have an affected parent, whereas one half of the cases appear to be sporadic. The LKB1/STK11 gene located on chromosome region 19p is associated with Peutz-Jeghers syndrome; however, genetic testing for this condition is not yet available. Of the sporadic cases, many appear to be caused by de novo mutations in STK11. Because the frequency of subtle signs of the disorder has not been thoroughly evaluated and because the molecular genetic data are insufficient to rule out Peutz-Jeghers syndrome in supposedly sporadic cases, parents should be advised that they might be at risk of having Peutz-Jeghers syndrome.
Prenatal testing is possible. However, prenatal diagnosis of diseases that typically manifest in adulthood poses a difficult situation, and careful genetic counseling is required.
Screening of the first-degree family members consists of colonoscopy and upper GI series with small-bowel follow-through study. Current recommendations for surveillance include colonoscopy, esophagogastroduodenoscopy, and small-bowel follow-through studies every 2 years after diagnosis. Affected individuals should also undergo an annual physical examination, and women should undergo annual mammograms. Some authorities recommend transvaginal ultrasonography for the surveillance of gynecologic or testicular tumors.
Screening of families potentially affected by juvenile polyposis
Screening in this group involves careful history taking and colonoscopic examination every 5 years, beginning at age 12 years. For families with familial juvenile polyposis of the stomach, esophagogastroscopy is substituted for colonoscopy. Patients with polyps should undergo endoscopic surveillance every 1-3 year. Colectomy is recommended for patients who have numerous polyps in the colon; however, surveillance of the ileal pouch should be continued because of the risk of malignant change.
No commercial genetic testing for juvenile polyposis is currently available. Recent studies have shown that the DPC4 gene located on chromosome arm 18q is constitutionally mutated in some patients with juvenile polyposis. In addition, chromosome arm 10q (PTEN gene) appears to be mutated in some patients.
Screening and surveillance for Cowden syndrome
Endoscopic screening is not necessary. However, because of the common association of non-GI cancers, the surveillance of affected individuals should include physical examination with special attention to the organs that are at risk, to thyroid function tests and/or scans, and to mammography every 6-12 months. No genetic test for Cowden syndrome is currently commercially available, although the disease has been linked to mutations in the PTEN gene on chromosome arm 10q.
Limitations of Techniques: The false-negative rate for the detection of polyps smaller than 1 cm is 7% with DCBE. Small sessile polyps are easily missed. Interpretive problems may occur because of overlapping bowel loops, air bubbles, spasm, diverticulae, a poorly prepared bowel, and barium flooding. Diverticulae impacted with feces, lobulated diverticulae seen en face, and edema of the diverticula neck due to inflammatory changes can also mimic polyps and contribute to the false-positive rates.
The screening and surveillance of patients with many of the colonic polyposis syndromes prolonged observation; however, barium enema studies are less acceptable for surveillance because of concerns about radiation exposure.
Ultrasonography remains operator dependent. Colonic and bowel gas and obesity degrade sonograms. The presence of feces and mucus also prevents the identification of colonic polyps. An assessment of the bowel thickness at the base of a polyp is important in identifying malignant transformation; however, this cannot always be evaluated by using the sodium chloride enema technique. Polyps smaller than 7 mm can be missed during ultrasonographic examination.
The main limiting factor for interpreting CT colonograms is time spent on reading the scans. For virtual colonoscopy to be a clinically feasible tool, the examination must be performed and the results interpreted in a time-efficient manner. For example, in a recent study, a large cohort of patients underwent both 2-dimensional (2D) and 3-dimensional (3D) imaging with antegrade and retrograde 3D navigation of the colon. Patients were in both the supine and prone positions. The median interpretation time for two radiologists was 31 minutes (2D imaging) and 27 minutes (3D imaging), respectively. In this study, the sensitivity for CT for polyps 10 mm or larger was over 90%.
The time issue is especially a problem with multisection CT colonography, with which nearly 1000 images can be obtained per patient, depending on the section collimation and degree of overlap.
MR colonography shares several limitations with its CT counterpart. Inadequate colon distension, contrast opacification, and the presence of air bubbles and fecal masses may potentially cause problems in interpretation.
None of the above techniques are useful in differentiating hamartomatous polyps from adenomatous polyps.
Findings: With DCBE, the features common to all the colon polyposis syndromes is the finding of multiple (usually 10 or more) polyps in the colon. The appearances of polyps on a DCBE study are dependent on the angle at which they are viewed and their relationship to the barium pool. When viewed en face, wide-based or sessile polyps exhibit the meniscus sign. This sign is a clearly defined inner border, which represents the base of the polyp; this fades into a less clearly defined outer border, which represents normal mucosa. When viewed tangentially or obliquely, both sessile and intermediate polyps can look like a bowler hat because the meniscus at the base and barium covering the surface of the polyp are seen. (The polyps exhibit features suggestive of pedunculated form.)
The target sign refers to the appearance of intermediate and pedunculated polyps seen en face. Adenomatous polyps can present as sessile, intermediate, or pedunculated forms. Hamartomatous polyps are commonly pedunculated; therefore, they can be large. Metaplastic polyps are often small and most commonly sessile. Malignancy is suggested when polyps have irregular, lobulated surface, when the base is wider than the height, and when the base of the polyp is retracted.
When a patient with FAP coli presents early, they may have more than 100 sessile adenomas measuring 1-5 mm and occurring throughout the whole length of the colon. Later in the disease process, contrast-enhanced examination usually reveals sessile and pedunculated adenomas that are 0.5-1 cm or larger. Malignant transformation in larger adenomas may be seen.
The radiologic features in the colon are identical in Gardner syndrome, which is regarded as a variant of FAP with important extracolonic manifestations. These manifestations unusually include multiple osteomas of the skull and mandible, though these can be seen in any bone. In young persons, the symptoms of osteomas and other extracolonic manifestations often prompt an investigation of the large bowel.
In Turcot syndrome, the adenomatous polyps are fewer in number, though as many as 100 may be present, and they may be as large as 3 cm. The polyps of Peutz-Jeghers syndrome are hamartomatous, and they more commonly affect the small intestine and stomach than the colon. As mentioned earlier, the polyps may appear solitary, or they may be few in number, large, and pedunculated. This morphology commonly affects the colon; the lesions often become eroded, and this may be seen on contrast-enhanced examination. More commonly, multiple, small, sessile polyps resembling those of FAP may carpet the small intestine, and this is demonstrated on barium follow-through study and small-bowel enteroclysis.
Degree of Confidence: Because of the appearances of polyposis syndromes in the colon, there is often little doubt regarding the nature of the lesions, as demonstrated on optimal double-contrast examination in a well-prepared bowel. In young persons, who often have extracolonic manifestations of disease, multiplicity of polyps aids the diagnosis.
The radiographic detection of colonic polyps depends on the size of the lesion and the type of examination. For polyps 1 cm or larger, the sensitivity of single-contrast barium enema and DCBE studies is 90-95%. DCBE is more sensitive in the detection of polyps smaller than 1 cm. The false-negative rate for the detection of polyps smaller than 1 cm in size is 7% with DCBE study. These radiographic sensitivities for detection of polyps of larger than 1 cm are similar to those of colonoscopy.
False Positives/Negatives: Polyps may not be detectable for many reasons. Small, sessile polyps smaller than 1 cm can be missed. Overlapping loops of bowel, air bubbles, spasm of the bowel, poor image quality, diverticulae, poor bowel preparation (with feces or a wet colon), and excess barium can all compound the problem.
Diverticulae can be particularly troublesome. Diverticulae impacted with feces, lobulated diverticulae seen en face, and edema of the diverticular neck due to inflammatory changes can all mimic polyps. However, when multiple polyps are present, as in most of the polyposis syndromes, the diagnosis should rarely be missed. Double reporting of examination results also aids in diagnosis.

Findings:
Conventional CT
Conventional CT may show colonic polyps as intraluminal filling defects that cause deformation of the contrast material–filled lumen. Conventional abdominal CT is also a valuable tool in planning surgery for colonic cancer, which can be a complication of colonic polyposis. On CT scans, colonic cancer appears a soft tissue–attenuating mass that narrows the colonic lumen. Colonic cancer can also appear as focal bowel thickening and luminal narrowing. CT can also readily depict complications of colonic cancer, such as obstruction, perforation and fistula formation and liver, and lymph node and other distant metastasis. Extraluminal spread is depicted as the loss of fat planes between the colon and adjacent organs.
CT colonography (virtual CT colonoscopy)
CT colonography typically refers to the evaluation of a cleansed and gas-distended colon to detect polyps and masses. A low-dose CT is performed in both the supine and prone positions. The images are interpreted using specialized software by viewing the axial, multiplanar reconstruction (MPR) and 3D endoluminal images.
A strategy of stool opacification with barium and fluid opacification with water-soluble contrast may also be used. The stool opacified images may be viewed in axial and multiplanar reconstructed views. When stool and fluid opacification is used, an electronic subtraction program may be applied to permit a primary 3D or 2D interpretation of the subtracted images. Some investigators suggest using intravenous contrast in one view, particularly if there is a large amount of fluid that could hide polyps (even with the patient scanned both supine and prone) or when investigating a patient with a known obstructing carcinoma whose colonoscopy was incomplete.
Thorough colonic cleansing is required to eliminate false-positive scans caused by fecal residue. Dry preparation by using sodium chloride cathartics is preferred to a colonic lavage, to minimize retained fluid that might hide polyps. After colonic cleansing, the patient is placed in the left lateral decubitus position on the CT table. An endorectal tube is passed, and the large bowel is insufflated with air or carbon dioxide using either manual insufflation or a mechanical pump.
The use of spasmolytics may help with patient comfort and possibly with optimal large-bowel distension. In Europe, hyoscine-N-butyl bromide (Buscopan; Boehringer Ingelheim) is preferred, but this drug is not licensed for use in the United States, where glucagon hydrochloride is usually used. Some authorities do not use a bowel relaxant and argue that this minimizes cost and patient anxiety.
To minimize respiratory motion, a fast scanner is needed. Multidetector-row CT is the preferred imaging modality, but electron-beam CT also can be used. Even single-section helical CT can be used, but it may require multiple breath holds to scan the abdomen and pelvis. A CT scanogram is first obtained to allow the optimal areas to be covered and also to ensure that optimal distension of the colon has been achieved.
With multisection imaging, the typical CT parameters include a 4 X 1-mm section detector configuration, 120 kV, 0.5-second gantry rotation, and effective 50 mAs. A variable pitch between 6 and 7 is used so that the entire abdomen and pelvis can be covered within a 30-second breath-hold. This imaging results in 12 and 14 mm of coverage per second. If helical CT is used, satisfactory images can be obtained by using 5-mm beam collimation, a reformatting index of 2 mm, acquisition time of 1 second per revolution, a pitch of 1.25, 110 kVp, 200 mAs, and the smallest field of view to fit a 512 X 512 matrix. Most investigators do not recommend a beam collimation above 3 mm.
CT images are reconstructed as 1.25-mm-thick sections with a 1-mm reconstruction interval. Scans are usually obtained with the patient in both the supine and prone positions to obtain optimal views of all colonic segments by moving fluid, stool, and gas to facilitate the differentiation of feces and polyps. The images are networked to a workstation, where data interpretation can proceed. A wide variety of surface and volume-rendering packages are now commercially available. These can be used to obtain the virtual colonoscopic fly-through on a workstation.
The optimal evaluation of CT colonograms requires access to supine and prone images and 2D, 3D, and MPR images. Several workstations allow axial supine and prone images to be displayed adjacent to each other. The ability to quickly change window and/or level settings from wide to narrow facilitates data interpretation.
One major drawback of reading the 2D, MPR, and 3D reconstructed images is the time required to interpret them. However, as experience with 2D imaging as a primary interpretation technique has increased, the time to evaluate colonographic data has decreased. The reason for this is that, with experience, confidence in differentiating bulbous folds and fecal material from polyps increases; therefore, the utility of MPR and 3D is confined to problem solving.
The interpretation of primary 2D images requires an evaluation of the entire colon. The process is facilitated by access to a workstation that allows a rapid cine function so that scrolling through the colon is easy. Because the colon is a tortuous and rather redundant organ, scrolling should be performed so that the entire colon is evaluated.
A 12% incidence of incidental extracolonic findings is reported, even when low dose CT is used and intravenous contrast is not used.
Degree of Confidence: 3D virtual colonoscopic techniques have the appeal of truly simulating conventional colonoscopy. Several commercial workstations are incorporating an automated center line that allows the computer to automatically generate images and make cine images of the colon traversing this center line. With improvements in the software, one can then navigate through the colon and evaluate suspicious abnormalities.
Recently, several improvements in CT colonographic technique have increased its diagnostic performance. These improvements include the abilities to maximize colonic distension, to obtain data in the supine and prone positions, and to perform CT colonography in patients with well-prepared clean colons.
Virtual colonoscopy does not yet compete with colonoscopy in the demonstration of small colonic polyps, although one recent trial (Pickhardt et al) using stool/fluid opacification and electronic subtraction with a primary 3D read achieved results comparable to optical colonoscopy for 1 cm polyps. Currently, CT is not the examination of choice for examining the colon in polyposis syndromes. With good oral preparation and gaseous distension, CT colonography with scanning in the prone and supine positions reliably depicts larger polyps.
Polyps smaller than 1 cm may not be detected, even with prone and supine scanning. CT has good sensitivity for the detection of clinically important polyps. CT may be helpful in the less mobile and or older persons, as well as those in whom malignant transformation is suspected; therefore, it is a useful adjunct to a contrast-enhanced examination.
Although CT colonography is a relatively noninvasive imaging procedure, some aspects of the procedure may produce some anxiety and potential discomfort for patients; examples include bowel preparation and colonic insufflation. Most studies have shown a small to significant patient preference for CT colonography over optical colonoscopy, particularly when patients are asked how frequently they would be willing to be re-evaluated at various intervals.
Performing both supine and prone imaging doubles the patient radiation dose. However, this is essential to optimize bowel distension; redistribution of residual fluid; and differentiation of fecal material from polyps, since visualization of mobility of a filling defect implies residual fecal material. With high contrast at the air-mucosa interface, the milliampere-second setting can be sufficiently reduced to limit the patient radiation dose to levels comparable to that of a barium enema study or less. Ongoing research continues on the use of very low doses (20-50 mAs).
False Positives/Negatives: Adequate bowel preparation is absolutely vital for confident detection of significant lesions because residual fecal material may be indistinguishable from polyps or neoplasms, or it may obscure polyps, making their detection impossible.
Other problems in detection of polyps with CT colonoscopy arise with small, sessile polyps (<1 cm). Distinguishing polyps from haustral folds can also be difficult; thus, a clean, well-distended colon visualized prone and supine is important. Flat polyps, flat cancers, mobile pedunculated polyps, and mobile loops of colon can be causes of false-negative results. A review of the images in a soft tissue window/level setting helps detect foci of wall thickening.
With workstations incorporating a center path line, problems are encountered when segments of the colon are not well distended and the center line cannot be generated. Also, in overdistended bowel segments, the center line may jump to an adjacent distended loop. Problems with the workstation may also occur with a 3D-viewing facility, which does not always ensure that the entire colonic surface is evaluated.
Further limitations of both primary 2D and primary 3D techniques are that they cannot be used as the sole technique for image interpretation. Use of the 3D technique alone may result in many false-positive results. Just as 3D imaging and MPR are used for problem solving when 2D imaging is the primary interpretation technique, 2D imaging must be used as a problem-solving method for 3D imaging. This is to aid in the evaluation of the attenuation characteristics of a lesion and to determine if a filling defect is a mural abnormality or an extrinsic defect.
Often, lesions are detected by using 3D CT colonographic techniques that demonstrate morphology consistent with a polyp or neoplasm. When these same areas are investigated with 2D CT, a variety of normal structures may be found, including fecal material and extrinsic defects.
Finally, as stated above, the amount of time for data evaluation with these 3D techniques may limit its usefulness in a clinical setting. Primary 3D imaging techniques need to become quicker and more automated, with easier navigation, before they can become a primary viewing technique. However, given these limitations, polyps smaller than 5 mm can be routinely detected by using 3D endoluminal imaging in both antegrade and retrograde fashion.
One recent study has involved the use of axial images, as well as complete 3D endoluminal navigation in antegrade and retrograde directions in both the supine and prone position. The results showed that the detection of polyps smaller than 5 mm was 59%. This rate compares favorably to a recent report in which only 2D imaging was used as the primary data interpretation technique. Another recent study showed that 68% of polyps 5 mm or smaller that were missed with a primary 2D technique were either hyperplastic or normal colon, as determined at pathology.
MRI

Findings: GI polyps in patients with polyposis syndrome may be visualized on MRIs by using breath-hold T1-weighted and breathing-independent snapshot T2-weighted techniques.
In their recently published work, Semelka and Marcos describe MR findings in a small series of patients with GI polyposis syndromes. The study included six patients; three with FAP, one with Peutz-Jeghers syndrome, one with Gardner syndrome, and one with neurofibromatosis. The investigators used breath-hold T1-weighted sequences, both standard and with fat suppression, prior to and after the administration of gadolinium-based contrast agent. They also performed breath independent single-shot half-Fourier rapid acquisition with relaxation enhancement (RARE) T2-weighted sequences.
In all patients, polypoid lesions exhibited signal intensity comparable to that of bowel on nonenhanced images, and they showed enhancement similar to that of bowel on early and late enhanced images. Polyp enhancement on gadolinium-enhanced images is an important finding that should distinguish polyps from bowel contents.
Polyps larger than 2 cm were observed in 1 patient with FAP and in 1 patient with Gardner syndrome. Both these polyps showed mild heterogeneity on late gadolinium-enhanced fat-suppressed images. Multiple colonic polyps ranging in size from 5 mm to 3 cm were observed in 1 patient with FAP. A solitary polyp associated with enteroenteric intussusception was observed in the patient with Peutz-Jeghers syndrome. Gastric polyps sized 5 mm to 6 cm were observed in Gardner syndrome, 1- to 2-cm polyps were found within the duodenum and jejunum in the patient with neurofibromatosis.
Virtual MR colonoscopy
Studies have recently been shown that MR-based endoluminal assessment of the colon is possible. Patient preparation is similar to that of CT colonoscopy. After thorough cleansing of the colon, the patient is positioned prone on the imaging table, and the colon filled with 1500-2000 ml of water and 15-20 ml of 0.5 M gadopentetate dimeglumine via an endorectal tube. Colonic filling is monitored by means of a 2D spoiled gradient-echo sequence with the acquisition of 1 image every 2 seconds. When the entire colon is filled with contrast agent, a 3D Fourier transform gradient-echo sequence is used to image the colon. As with CT colonoscopy, the images are transferred to a workstation and interpreted in both multiplanar reformatted and virtual colonoscopic views.
Degree of Confidence: Like with CT, virtual MR colonoscopy does not yet compete with colonoscopy for the demonstration of small colonic polyps. The overall experience with the technique is limited. However, the lack of adverse affects and the lack of ionizing radiation warrant further consideration of MR colonography as a tool for GI polyp screening. The limited experience so far suggests that polyps as small as 6 mm in size can be assessed, as can the inner wall itself.
False Positives/Negatives: Inadequate colonic distension, contrast opacification, and air bubbles and fecal masses may present potential problems in the interpretation of the images.
Findings: GI polyps in patients with polyposis syndrome may be visualized on MRIs by using breath-hold T1-weighted and breathing-independent snapshot T2-weighted techniques.
In their recently published work, Semelka and Marcos describe MR findings in a small series of patients with GI polyposis syndromes. The study included six patients; three with FAP, one with Peutz-Jeghers syndrome, one with Gardner syndrome, and one with neurofibromatosis. The investigators used breath-hold T1-weighted sequences, both standard and with fat suppression, prior to and after the administration of gadolinium-based contrast agent. They also performed breath independent single-shot half-Fourier rapid acquisition with relaxation enhancement (RARE) T2-weighted sequences.
In all patients, polypoid lesions exhibited signal intensity comparable to that of bowel on nonenhanced images, and they showed enhancement similar to that of bowel on early and late enhanced images. Polyp enhancement on gadolinium-enhanced images is an important finding that should distinguish polyps from bowel contents.
Polyps larger than 2 cm were observed in 1 patient with FAP and in 1 patient with Gardner syndrome. Both these polyps showed mild heterogeneity on late gadolinium-enhanced fat-suppressed images. Multiple colonic polyps ranging in size from 5 mm to 3 cm were observed in 1 patient with FAP. A solitary polyp associated with enteroenteric intussusception was observed in the patient with Peutz-Jeghers syndrome. Gastric polyps sized 5 mm to 6 cm were observed in Gardner syndrome, 1- to 2-cm polyps were found within the duodenum and jejunum in the patient with neurofibromatosis.
Virtual MR colonoscopy
Studies have recently been shown that MR-based endoluminal assessment of the colon is possible. Patient preparation is similar to that of CT colonoscopy. After thorough cleansing of the colon, the patient is positioned prone on the imaging table, and the colon filled with 1500-2000 ml of water and 15-20 ml of 0.5 M gadopentetate dimeglumine via an endorectal tube. Colonic filling is monitored by means of a 2D spoiled gradient-echo sequence with the acquisition of 1 image every 2 seconds. When the entire colon is filled with contrast agent, a 3D Fourier transform gradient-echo sequence is used to image the colon. As with CT colonoscopy, the images are transferred to a workstation and interpreted in both multiplanar reformatted and virtual colonoscopic views.
Degree of Confidence: Like with CT, virtual MR colonoscopy does not yet compete with colonoscopy for the demonstration of small colonic polyps. The overall experience with the technique is limited. However, the lack of adverse affects and the lack of ionizing radiation warrant further consideration of MR colonography as a tool for GI polyp screening. The limited experience so far suggests that polyps as small as 6 mm in size can be assessed, as can the inner wall itself.
False Positives/Negatives: Inadequate colonic distension, contrast opacification, and air bubbles and fecal masses may present potential problems in the interpretation of the images.

ULTRASOUND

Findings: Ultrasonography is insensitive in the diagnosis of colonic polyps. However, with malignant transformation when the bowel wall is infiltrated, bowel wall thickening may be seen. If the bowel wall is thickened, compressed or obliterated a carcinoma should be suspected.
A target or an atypical target sign is generally seen with asymmetrical, hypoechoic thickening of the bowel wall. These occur in association of a central echogenic area due to the presence of intraluminal air and mucus.
The colon may be sonographically examined for polyps or colon carcinoma by means of the retrograde instillation of fluid (generally warm sodium chloride solution) into the colon. A warm isotonic sodium chloride enema may improve visualization of the rectosigmoid. Real-time examination of the colon can be performed with this technique.
Colonic polyps appear as hyperechoic structures projecting into the lumen of the colon. Endorectal ultrasonography can be used in the assessment of rectal carcinoma.
Degree of Confidence: With the sodium chloride enema technique, colonic polyps larger than 7 mm can be identified in 91% of patients. However, at present, ultrasonography cannot replace a barium enema study or colonoscopy for the detection of colonic polyps. Still, sonography is an invaluable tool in the screening of patients with polyposis syndromes and in the screening of their families for associated cancers, such as those of the thyroid, breast, liver, ovaries, and uterus.
False Positives/Negatives: Colonic polyps may be difficult to identify on sonograms obtained with the patient in the supine position because air normally collects anteriorly, causing distal acoustic shadowing that obscures the field. Moreover, the presence of feces and mucus also prevents the identification of colonic polyps. Adequate assessment of the bowel thickness at the base of the colonic polyp may not be possible by using the saline enema technique. Also polyps smaller than 7 mm usually cannot be identified by using the sodium chloride enema method.
NUCLEAR MEDICINE

Findings: Nuclear medicine has no role in the diagnosis of colonic polyps. However, associated abnormalities in some of the polyposis syndromes lend themselves to radionuclide imaging. One such example is Gardener syndrome, in which the osseous lesions, thyroid cancer, and small-bowel carcinoids can be imaged with radionuclides.
Intervention: For Gardner syndrome, the following may be performed: (1) biopsy of any skin and GI polyps and (2) subtotal colectomy with an ileorectal anastomosis and fulguration of residual rectal adenomas. Close follow-up of the rectum is required to destroy reappearing polyps. If a rectal carcinoma develops, abdominoperineal resection and a permanent ileostomy are required.
Prophylactic simple mastectomy may be undertaken in women with Cowden syndrome who have active cystic disease of the breasts.
The timing of prophylactic proctocolectomy is individualized for each patient with inherited polyposis, but the procedure is generally performed at the time of diagnosis in adults. In teenagers, proctocolectomy may be delayed until approximately 100 polyps develop, until multiple polyps are larger than 1 cm, or until polyps develop dysplastic features, whichever occurs first. Colectomy prior to the development of polyps in FAP is not indicated.
Patients who have undergone subtotal colectomy are at a markedly increased risk for rectal cancer, and therefore, close surveillance of the retained rectum is required every 6 months for the patient's lifetime or until this risk is eliminated after the patient undergoes proctocolectomy and ileal pouch–anal anastomosis. However, adenomatous polyps can form in the ileal-anal pouch, and they occasionally progress to cancer. Thus, some recommend periodic endoscopic surveillance of the pouch.
The nonsteroidal anti-inflammatory drug sulindac has been shown to cause a regression of polyps in FAP. In a randomized, double-blind, placebo-controlled study, sulindac was found to reduce the number and size of colonic adenomas, but the effect was incomplete. The role of sulindac in the prevention of upper GI adenomas is unclear, and at present, this treatment cannot replace screening or colectomy in affected patients.
In patients with Peutz-Jeghers, large polyps should be removed. If polyps larger than 1.5 cm cannot be removed endoscopically, they should be removed surgically.

Clinical suspicion should be raised in the following situations:
When a polyp is discovered in a young patient
When 2 or more polyps are found in any patient
When colonic cancer is discovered in a patient younger than 40 years
When a patient presents with an extraintestinal manifestation of one of the syndromes described in this article
A high index of clinical suspicion is imperative because a failure to recognize polyposis syndromes may lead to the premature death of the patient.
Affected relatives of the patient may be deprived of genetic counseling and screening and/or surveillance, as they may be unaware of the presence of the disease in their family.
It is equally important for the radiologist to be familiar with changes that may occur with the malignant transformation of a benign polyp.