AUTHOR AND EDITOR INFORMATION

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• Treatment
• Medication
• Follow-up
• Miscellaneous
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INTRODUCTION

Section 2 of 11  

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Background

The term intestinal polyp is used to describe any projection arising from flat mucosa into the intestinal lumen. Polyps can be broadly classified as neoplastic and nonneoplastic. Neoplastic polyps can be further classified as either adenomatous (premalignant) or malignant. Approximately 95% of all colorectal carcinomas are believed to arise from adenomas, a finding that underscores the importance of treatment and surveillance of adenomas of the gastrointestinal tract.

Adenomas represent approximately 60% of all polyps removed during colonoscopic examination of the colon. The cancer risk of adenomas is related to their macroscopic appearance (ie, size, attachment, location) as well as their microscopic architecture and degree of dysplasia. These descriptors are used clinically to predict the malignant potential of a polyp and to guide both treatment and future surveillance intervals.

Pathophysiology

The colonic mucosa is a self-renewing epithelium that is a very tightly regulated balance between cell proliferation at the base of a crypt, maturation as colonocytes migrate up the crypt, and extrusion of senescent and/or apoptotic cells from the upper crypt into the lumen. This entire process takes approximately 3-6 days.

Adenomatous cells are characterized by loss of normal growth control. They continue to proliferate as they reach the top of the crypt, and they are not extruded into the lumen. Instead, they multiply and eventually fold back into the surrounding normal mucosa, inducing a response in the mesenchymal tissue that helps shape the microscopic architecture of the adenoma. The rate of growth and progression of adenomas to cancer is variable, but, typically, this occurs in 5-10 years. Patients with heritable forms of the disease, such as familial adenomatous polyposis (FAP) or hereditary nonpolyposis colorectal cancer (HNPCC), can have a more rapid rate of adenoma formation and progression to cancer.

The larger the index polyp, the more likely there may already be a focus of cancer. Barium enema studies suggest that the risk of developing cancer at the polyp site is as follows: at 5 years, 2.5%; at 10 years, 8%; and at 20 years, 24%. These growth characteristics are used to base the formulation of recommendations for surveillance after the index polyp has been found. When one adenoma is found, over one third of colons will have at least one more adenoma. The risk of cancer is increased with the number of polyps.

The adenoma-carcinoma sequence is thought to be a genetically driven process characterized by the occurrence over time of successive cycles of somatic mutation and clonal expansion of cells that have acquired a survival advantage. The first mutation in this process often involves inactivating mutations of the adenomatous polyposis coli (APC) tumor suppressor gene (inherited mutations in the APC gene cause FAP, and somatic mutations in the APC gene occur in about 80% of sporadic adenomas). Additional and progressive mutations occur in cells of the adenoma, including activating mutations of the oncogenes (Ki-ras) and inactivating mutations of tumor suppressor genes (ie, TP53) and/or DNA repair genes (ie, MSH2, MLH1). Epigenetic silencing of tumor suppressor and DNA repair genes by methylation may also contribute to this molecular process.

Some of these individual mutations lead to clones of cells that have acquired a survival advantage over surrounding cells, leading to a clone of mutant cells. Subsequent cycles of mutation and clonal expansion ultimately lead to adenoma growth, increased severity of dysplasia, and, ultimately, acquisition of the invasive and metastatic characteristics of an adenocarcinoma.

Frequency

United States

Colonoscopic and autopsy series suggest an overall prevalence of adenomatous polyps of 40-50% by age 50-60 years. The prevalence of colonic adenomas increases with age and varies depending on the inherent risk of colorectal cancer in a given population.

International

Significant geographic variation occurs throughout the world. For example, 2 different ethnic groups from genetically homogeneous regions in Japan have as much as a 20% difference in the prevalence of adenomas in people aged 50 years.

Mortality/Morbidity

Except for the rare adenoma that causes a clinically significant hemorrhage or obstruction, morbidity and mortality are primarily related to the carcinoma that can arise from an adenoma. The National Polyp Study, a large multicenter trial, has demonstrated that detection and removal of adenomas can be expected to substantially decrease the incidence of colorectal cancer.

Race

Although substantial variations in adenoma risk occur among different populations, race itself does not appear to be an independent determinant of risk. Dietary and environmental factors may have a role in explaining some of the differences observed throughout the world; Hawaiian-Japanese men have a high prevalence of adenomas, whereas some Japanese men have low risk. Similarly, blacks in New Orleans have a high risk for adenomas, while South African rural blacks are at low risk for developing adenomas.

Sex

Some studies suggest that adenoma prevalence can be up to 30% higher in men than in women.

Age

The prevalence of adenomas increases progressively with age. Adenomas are uncommon in people younger than 30 years unless associated with a significant family history or familial syndrome. Most studies suggest that sporadic adenoma prevalence begins to increase substantially in people aged 40-50 years and continues to increase through age 80 years.

CLINICAL

Section 3 of 11  

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History

Most adenomas are asymptomatic and are identified primarily by colorectal cancer screening tests or by colonic imaging tests ordered for unrelated reasons.

The most common symptoms and signs, usually occurring from large adenomas, include the following:

• Rectal bleeding, overt and occult
• Change in bowel habits
• Abdominal pain
• Rectal prolapse
• Occasional bowel obstruction from a large adenoma
• Intussusception
• A large villous adenoma causing a profuse watery diarrhea (rare)

The patient may have no symptoms and request colon cancer screening.

Physical

Physical examination findings are usually benign. A large rectal polyp or flat adenoma can sometimes be detected on digital rectal examination.

Causes

• Genetic predisposition: Two autosomal dominantly inherited forms of colon cancer that arise in adenomatous polyps have been well described and are thought to account for about 3% of all colorectal cancers. In addition, adenomatous change can occur in the hamartomatous polyposis syndromes.
  
  
  • FAP is caused by inheritance of a germ line mutation in the APC gene. FAP is characterized by the appearance of hundreds to thousands of adenomas of the colon during adolescence (average age at polyp formation is approximately 15 y) and a nearly 100% risk of colon cancer (average age at cancer development is approximately 40 y) if the colon is not removed. FAP accounts for less than 1% of the total colorectal cancer risk in the United States.
  • HNPCC is caused by inheritance of a germ line mutation in one of several DNA repair genes (eg, MSH2, MLH1, MSH6, PMS1, PMS2). Only a few colon adenomas develop in patients with HNPCC, but those that do occur appear to have a very high rate of progression to colorectal cancer. The cancers in HNPCC occur at a younger age (mean age is 44 y), occur more commonly in the proximal colon (60-70% proximal to splenic flexure), and more commonly are multiple rather than sporadic colorectal cancers.
  • Multiple hamartomas of the intestine occur in the rare autosomal dominant syndromes of Peutz-Jeghers syndrome and familial juvenile polyposis. Adenomatous change can occur within the hamartomas and lead to adenocarcinoma, most commonly of the colon and small intestine.
• Family history: Any patient with a first-degree relative who has a colorectal adenoma or cancer is at a moderately increased (ie, 1.5- to 2-fold) risk for developing an adenoma.

• Diet and/or lifestyle: Obesity; diabetes mellitus; coronary heart disease; lack of physical activity; diets high in total calories, fat, and meat; and diets low in vegetables, fruit, and fiber are associated with a moderately increased risk of colorectal adenomas and cancer. Alcohol use and cigarette smoking also increase the risk of adenomas. Acromegaly and ureterosigmoidostomy are both associated with increased risk of adenomas.

DIFFERENTIALS

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Other Problems to be Considered

The differential diagnosis of adenomas includes the other polypoid lesions of the gastrointestinal tract. Usually, neoplastic and nonneoplastic mucosal lesions can be endoscopically differentiated from the submucosal polypoid lesions.

Neoplastic lesions

Adenoma
Carcinoma

Nonneoplastic lesions

Normal mucosa
Hyperplastic polyp
Inflammatory polyp
Juvenile polyp
Hamartomatous polyp

Submucosal lesions

Carcinoid
Lipomas
Lymphoid

Other conditions

Pneumatosis cystoides intestinalis
Colitis cystica profunda

WORKUP

Section 5 of 11  

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Lab Studies

• Fecal occult blood test: A small proportion of large adenomas may bleed intermittently. Depending on the age of the patients tested, 10-40% of asymptomatic patients with a positive result on a fecal occult blood test have an adenoma. Quantitative testing of stool for blood has been tried, but it does not appear to have a role in screening or diagnosis of colonic adenomas at this time. Newer immunologically based tests designed to detect only human blood in stool are becoming available and are expected to increase the specificity of the test. Three fresh separate nonhydrated stools are used.
• Stool testing for genetic alterations: Stool testing for genetic alterations that occur in adenomas is being studied. Thus far, the stool tests are more sensitive for cancers and advanced adenomas than for small tubular adenomas; these tests are expensive and may not yet be widely available.
• CBC count: Patients with an adenoma occasionally can present with a microcytic (iron deficiency) anemia due to chronic blood loss.
• Iron studies: Low serum iron and ferritin and an increased total iron-binding capacity (TIBC) can be observed because of blood loss in some patients with colonic adenomas and carcinomas.

Imaging Studies

• Barium enema (BE) imaging of the colon can detect polyps, but they are usually found when the test is ordered for another indication. Air contrast barium enema (ACBE) is more sensitive than single contrast technique for detection of polyps. BE is included as an acceptable screening or surveillance test for colorectal cancer in the recommendations of the American Cancer Society and other organizations, but prospective controlled studies of its use in a screening program are lacking. BE is generally regarded as less sensitive than colonoscopy in detecting adenomas less than 1 cm in size, and some studies indicate that it is not as accurate as colonoscopy for even larger lesions. As a result, BE is usually considered an alternative to colonoscopy for evaluation of the entire colon.
• CT or magnetic resonance (MR) CT colonography (virtual colonoscopy) is being evaluated for the detection of adenomas and carcinomas of the colon. Thus far, virtual colonoscopy has lower sensitivity than optical colonoscopy for small (<1 cm) adenomas and has a false-positive rate, but the technology is improving rapidly and may soon be the test of choice for screening purposes, with optical colonoscopy only being performed to obtain biopsy samples and to remove clinically significant lesions identified on CT colonoscopy. Procedure volume and attenuation thresholds may be important with MRCT computer-aided polyp detection. The advantages of virtual colonoscopy include the lack of need for sedation, the short commitment of time for the test, and the potential of the patient not needing to take a cathartic bowel preparation.

Other Tests

• New stool screening technology aimed at detecting some of the more common genetic alterations found in adenomas is being investigated. Currently, the stool DNA testing is more sensitive for colon cancers and advanced adenomas than for small tubular adenomas.
• Biomarkers for the detection of advanced neoplasia, such as the measurement of the urinary metabolite of prostaglandin E_2, are not yet ready.

Procedures

• Adequate bowel cleansing is necessary prior to many procedures. Several preparations are marketed for bowel cleansing (eg, polyethylene glycol 3350 [GoLYTELY, NuLYTELY], magnesium citrate [Citroma], senna [X-Prep]) in preparing patients for surgery or gastrointestinal procedures, such as endoscopy, colonoscopy, and barium x-ray studies. Bowel cleansing preparations may be used with various dietary preparations (eg, clear liquid diet 1-2 d before surgery or procedure) and are convenient to administer on an outpatient basis.
  
  
  • Guidelines vary about screening for colorectal cancer. Flexible sigmoidoscopy can be used to visualize the left colon, where about half of all colonic adenomas and cancers are located. It is more available and less expensive, and it has a lower risk than colonoscopy. Flexible sigmoidoscopy screening of the average-risk population older than 50 years could decrease the colorectal cancer mortality rate by about 40-50% and incidence by 30-40%. If an adenoma is found on sigmoidoscopy, colonoscopy should then be performed.
  • Colonoscopic screening for colorectal cancer and adenomas is generally recommended for high-risk individuals, such as those with 2 or more first-degree relatives with colorectal cancer or those with a single first-degree relative with colorectal cancer occurring at a young age (ie, <50 y).
    
    
    • Enthusiasm in the gastroenterology community is increasing for offering colonoscopy screening to average-risk persons (age 50 y or older) and to high-risk persons, such as those with a family history, especially if the relative was younger than 50 years. Medicare has recently added colorectal screening using colonoscopy every 10 years as a covered benefit for average-risk individuals. The entire colon can be visualized using colonoscopy, and mortality rates related to colorectal cancer could be reduced by up to 80% by the routine use of colonoscopic screening and removal of adenomas.
    • Widespread colonoscopic screening would be expensive, and the compliance rate for such a screening program is not known. In some countries, the number of trained endoscopists is insufficient to perform colonoscopy screening in the average-risk population. With the promise of newer equipment to facilitate colonoscopy, more primary care physicians and nurse endoscopists may assist in the screening process. 
  • Colonoscopic polypectomy is the procedure of choice for treatment of colonic adenomas, and colonoscopy is usually recommended for continued surveillance of patients with previously removed adenomas. The National Polyp Study showed that regular surveillance colonoscopy with polypectomy decreased the incidence of colorectal cancer by 76-90% compared to 3 historic control groups.
  • Chromoendoscopy using methylene blue with or without the use of a magnifying endoscope is being used in some centers to improve the accuracy of diagnosing colonic polyps and to identify small adenomas and aberrant crypt foci. The surface architecture of adenomas (ie, brainlike appearance with gyri) is different from that of hyperplastic polyps (ie, chickenwire fence–like). Thus, magnifying chromoendoscopy can potentially be used to distinguish these 2 types of colonic polyps.
  • Fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is being studied.

Histologic Findings

Adenomas are classified based on their size, architecture, and degree of dysplasia. Large size, villous content, and distal location are associated with severe dysplasia in colorectal adenomas.

• Size: Most adenomas are small (<1 cm). Large adenomas (>1 cm) tend toward more severe dysplasia and more worrisome architecture, and the risk of malignant potential is increased. However, small (5-10 mm) adenomas as well as diminutive adenomas (<4 mm) may have advanced histology, including carcinoma, in 10.1% and 1.7%, respectively. The term advanced adenoma is used for adenomas that are 1 cm or larger in diameter or that have tubulovillous or villous histologic features or high-grade dysplasia.  
  
  
  • The presence of 3 or more small adenomas or the presence of 1 or more advanced adenomas is associated with a 2- to 3-fold increased risk of metachronous adenomas.
  • Other features that may increase the risk of metachronous adenomas or colorectal cancer include an adenoma located proximal to the splenic flexure, male gender, older age, or a first-degree relative with colorectal cancer. 
• Architecture: Traditionally, adenomas are described as tubular, tubulovillous, or villous, primarily based on the overall percentage of villous component. Risk of malignancy increases with increased villous composition of the polyp.
  
  
  • Tubular adenomas are variously defined as those that contain 0-25% villous tissue. About 70-85% of all adenomas are tubular; they tend to be smaller than villous adenomas.
  • Tubulovillous adenomas contain approximately 25-75% villous tissue. These adenomas represent 10-25% of all adenomas; they tend to be intermediate in size.
  • Villous adenomas contain more than 75% villous tissue. These adenomas represent 5% of all adenomas; they tend to be larger and have the greatest malignancy potential.
  • Two other architectural types exist as well.
  • • Flat types are primarily in familial groups. They are not raised and are usually small erythematous plaques that are multiple, often have multiple foci of high-grade dysplasia, and can be associated with small adenocarcinomas.
    • Mixed hyperplastic (serrated) types make up less than 1% of all polyps. They have hyperplastic architecture with evidence of dysplasia and are associated with high frequency of high-grade dysplasia.

Staging

Dysplasia is a neoplastic change in histology. All adenomas are dysplastic; they display degrees of hyperchromasia, nucleolar prominence, nuclear pleomorphism, and increased mitoses. Dysplasias are classified as either low-grade or high-grade. Invasive carcinoma is distinguished from dysplasia by invasion of neoplastic tissue beyond the muscularis mucosa.

• Low-grade - Basal or stratified nuclei, crowded glands, less goblet cells and mucin
• High-grade - Loss of glandular architecture, increased mitoses (includes previously termed carcinoma in situ and intramucosal carcinoma)

• Sporadic adenoma in patients with ulcerative colitis is diagnosed only when the lesion is located proximal to the ulcerative colitis in an endoscopically and histologically normal mucosa. Otherwise, if the adenoma occurs in an area marked by ulcerated colitis, proctocolectomy is recommended.

TREATMENT

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Medical Care

Excision and complete removal of adenomatous tissue during colonoscopy is considered the treatment of choice and the ultimate goal of therapy in an attempt to decrease the risk for development of colorectal carcinoma. Several techniques for removal are used, including biopsy forceps and snare excision (with and without electrocautery) as well as simple fulguration and piecemeal excision of large polyps.

Sulindac, a nonsteroidal anti-inflammatory drug (NSAID), has been shown to significantly reduce the number and size of adenomas in patients with FAP. The selective cyclooxygenase-2 (COX-2) inhibitor celecoxib has also been shown to cause modest regression of colonic adenomas in patients with FAP, and the Food and Drug Administration (FDA) has approved it for the treatment of FAP adenomas.

Several case-control and cohort studies indicate that the regular use of aspirin or other NSAIDs is associated with a lower rate of colorectal cancer mortality, but whether the association is causal is unclear. Trials are underway to determine if aspirin or other NSAIDs can prevent new adenoma formation, but none of these studies is complete yet. As a result, NSAIDs are not currently recommended for either treatment or prevention of sporadic colonic adenomas.

Surgical Care

Surgical intervention is usually not required in the management of adenomatous polyps. Rarely, a large (>2 cm) sessile adenoma may not be amenable to endoscopic resection or adequate biopsy and may require surgery. Large rectal adenomas can be removed via intraoperative transanal resection. More proximal lesions may require laparoscopy or laparotomy with segmental colonic resection and evaluation of lymph nodes.

Consultations

Most colonoscopy and polyp treatment is performed by gastroenterologists or colorectal surgeons who work closely with primary care physicians and pathologists to coordinate diagnosis, treatment, and follow-up of adenomas.

Diet

Observational epidemiologic studies have implicated several dietary factors as potentially modulating the prevalence of adenomas.

A recent summary by the American College of Gastroenterology makes the following recommendations: a low-fat (25-30% of total calories) high-fiber (20-30 g/d) diet with 5 servings per day of fruits and vegetables, maintenance of normal body weight, no excessive use of alcohol, total abstinence from tobacco, and calcium carbonate supplementation (3 g/d).

Obesity is now recognized as a risk factor, and achieving a normal body mass index (BMI) is a further goal to reduce the risk of colorectal cancer.

• Fat: Consumption of dietary fat is associated with the prevalence of adenomas in several epidemiological studies. Consuming more than 40% of calories from fat is associated with increased risk, while consuming less than 15% of calories from fat is associated with a decreased risk of adenomas. Intervention trials have thus far failed to demonstrate a beneficial effect of a low-fat diet for the prevention of colonic adenomas. The underlying pathophysiology, demonstrated in animal models, likely involves increased production of cholesterol and bile acids by the liver, producing larger amounts of these substances in the colon. Bacterial flora subsequently convert the excess fat-derived substances into oxidized bile acids and cholesterol metabolites, which may exert a tumorigenic effect on colonic epithelium.
• Fiber: High-fiber diets are associated with a decreased incidence of adenomas in observational studies, but intervention trials have thus far failed to show a benefit of fiber supplements for the prevention of new adenomas. The focus of recent attempts to explain the effect of fiber on adenoma formation has centered on fermentation of poorly soluble fiber by colonic bacterial flora. This process produces short-chain fatty acids, which are important substrates for colonic epithelial metabolism as well as potential inhibitors of tumorigenesis.
• Dietary supplements: Multiple studies assessing the effects of supplements such as vitamins A, C, and E; folate; and selenium show no benefit in reducing the risk of adenoma formation in patients with previous adenomas. The only supplement recommended, 3 g daily of calcium carbonate, is shown to be associated with a 24% reduction of recurrent adenomas in patients with one or more previously resected adenomas. Daily supplementation with 1 mg folic acid may be protective.
• Increased BMI is associated with colorectal cancer and polyps.

Activity

Multiple epidemiologic studies suggest a protective effect of regular physical activity on colonic cancer risk. No intervention studies have directly evaluated the relationship between physical activity and adenoma or carcinoma risk.

MEDICATION

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The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Nonsteroidal anti-inflammatory drugs (NSAIDs)

Growing evidence suggests a protective role for NSAIDs against the development of colorectal cancer. In addition, a significant effect in reversing adenoma growth has been illustrated with the use of sulindac and celecoxib in patients with FAP. Aspirin may also be useful to reduce the recurrence of polyps or cancer, but because of the potential for these drugs to cause damage to the upper gastrointestinal tract, they are not routinely recommended for this purpose. The mechanism of NSAID-induced polyp regression is not known, but it may involve the selective induction of apoptotic cell death in the adenomatous mucosa.

Drug Name	Celecoxib (Celebrex)
Description	Inhibits primarily COX-2. COX-2 is considered an inducible isoenzyme, induced during pain and inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited, thus GI toxicity may be decreased. Multiple systemic effects, including analgesia, antipyretic, and anti-inflammatory, mostly mediated by selective inhibition of prostaglandin synthesis.
Adult Dose	400 mg PO bid for colonic adenomas in FAP
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity to NSAIDS or sulfonamides
Interactions	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
Pregnancy	B - Usually safe but benefits must outweigh the risks. D - Unsafe in pregnancy
Precautions	May cause fluid retention and peripheral edema; caution in compromised cardiac function, hypertension, and conditions predisposing to fluid retention; severe heart failure and hyponatremia may occur because circulatory hemodynamics may deteriorate; 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 laboratory results; COX-2 inhibitors may increase risk of cardiac deaths and stroke

FOLLOW-UP

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Further Inpatient Care

• Flexible sigmoidoscopy and colonoscopy generally are outpatient procedures. Inpatient care rarely is required for the diagnosis and treatment of adenomas.

Further Outpatient Care

• The interval between colonoscopy depends on the size, number, and histological type of polyp, as well as the patient's family history. Polyp recurrence rates are 20% at 5 years and 50% at 15 years, with even higher recurrence rates for multiple index polyps. Polyps may be missed at the index colonoscopy, and the presence of a polyp when colonoscopy is repeated at 1 year is about 33%.

• In general, a 3-year interval for surveillance colonoscopy, for the patient previously found to have an adenomatous polyp, is safe and cost-effective for most patients after removal of adenomas. Specific clinical scenarios dictate alterations from this general guideline.

• Postpolypectomy surveillance guidelines suggest the following:
• • Repeat colonoscopy every 3 years for high-risk persons, those with a polyp with a villous component or with high-grade dysplasia, or if there is a first-degree relative with colon cancer.

  • Large (>2 cm) sessile polyps or multiple (3 or more) adenomas, found on initial colonoscopy, warrant repeat colonoscopy 3-6 months after initial diagnosis to ensure complete removal of all adenomatous tissue.
  • If either the endoscopist or the pathologist is unsure that the polyp has been completely removed, a repeat colonoscopy in 3-6 months is recommended.
  • A suboptimal examination at colonoscopy or multiple (>4) adenomas indicates need for follow-up colonoscopy in 1 year or sooner.
  • If the 3-year follow-up examination reveals no recurrent adenomas, repeat colonoscopy is recommended every 5 years.
  • Follow-up of single tubular adenomas less than 1 cm is debated and patient-specific, depending primarily on comorbidities and age.
  • Repeat colonoscopy every 10 years for the low-risk person.

Deterrence/Prevention

• Observational epidemiologic studies have implicated several dietary factors as potentially modulating the prevalence of adenomas. A recent summary by the American College of Gastroenterology makes the following recommendations: a low-fat (25-30% of total calories) high-fiber (20-30 g/d) diet with 5 servings per day of fruits and vegetables, maintenance of normal body weight, no excessive use of alcohol, abstinence from tobacco, and calcium supplementation. 
• Antioxidant supplements do not have a significant beneficial effect on primary or secondary prevention of adenoma.
• The only intervention proven to decrease the incidence of recurrent sporadic adenomas is calcium carbonate (3 g/d).
• Growing evidence suggests a protective role for Coxibs, NSAIDs, and ASA against the development of colorectal cancer. For example, the Prevention of Colorectal Sporadic Adenomatous Polyps Trial (2006) studied celecoxib at a dose of 400 mg per day versus placebo. The cumulative rate of adenomas detected through year 3 was 33.6% in the celecoxib group versus 49.3% in the placebo group (relative risk, 0.64; 95% confidence interval, 0.56-0.75; P<0.001).² In addition, a significant effect in reversing adenoma growth has been illustrated with the use of sulindac and celecoxib in patients with FAP.
• The use of chemoprotection for primary or secondary polyp formation is not yet fully endorsed.
• Smoking tobacco (ie, cigarettes smoked per day, smoking duration, pack/years, recent use) increases the risk (odds ratio [OR]=6.2 [95% confidence interval, 4.7-5.3]) for both hyperplastic polyps and adenomatous polyps. 

Complications

• The primary complication associated with adenomas is the potential development of colorectal cancer. Less than 5% of all adenomas progress to cancer. The risk of progression to cancer rises with increasing size, villous component, and degree of dysplasia.
• Complications of colonoscopy include perforation and bleeding. A diagnostic colonoscopy carries a complication risk of about 0.1%; polypectomy substantially increases the risk of complications to up to 0.2% for perforation and 1% for bleeding.

Prognosis

• Almost all cases of colorectal cancer arise from an adenoma; excision of adenomas reduces the incidence of colorectal cancer. Adherence to guidelines for surveillance of adenomas is expected to substantially reduce the risk of developing colon cancer.

Patient Education

• A sustained public awareness campaign emphasizing the importance of early detection of adenomas in the prevention of colorectal cancer has been supported by all major gastroenterology associations.
• Dietary recommendations, such as those outlined in the Diet section, have been promoted by the National Cancer Institute, the American Cancer Society, and many other organizations.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Patients diagnosed with adenomas who are not properly followed with surveillance of a repeat colonoscopy have an increased risk of developing metachronous adenomas and/or colorectal cancer. Whatever the interval recommended for repeat colonoscopy, the patient must be cautioned to report any new bowel symptoms or bleeding, because of the concern that new pathology may have developed in the interim.
• The patient must be aware that there is a 6-12% miss rate for adenomas that are 1 cm or larger; the miss rate for smaller adenomas is up to 25%. Medical records must identify landmarks of the cecum as well as colonoscopy withdrawal time.
• The patient must be fully informed about the risks and the potential benefits of a colonoscopy.
• Patients with adenomatous polyps, a familial polyp syndrome, or colon cancer must be cautioned about the need for their first-degree relatives to undergo screening colonoscopy at an appropriate age.
• Colonoscopists or their institution have a continuous quality improvement process to document quality assurance (eg, percentage of cases reaching the cecum, withdrawal time, polyp detection rate).
• Colonoscopists, primary care physicians, and patients themselves are responsible for ensuring appropriate colonoscopic follow-up.
• While the US National Polyp Study (2006) and the Italian Multicentre Study Group (2001) reported 66-76% lower than registry-based reductions in the incidence of colorectal cancer among patients who underwent colonoscopic surveillance after the removal of colonic adenomas, not all studies have supported these findings. The role of colonoscopic surveillance to reduce the death rate from colon cancer awaits the results of ongoing studies. These considerations become especially important under circumstances where surveillance leads to a complication (eg, perforation, missed lesion).

MULTIMEDIA

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Media file 1:  Intestinal polypoid adenomas. Endoscopic view of pedunculated polyp.
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Media file 2:  Intestinal polypoid adenomas. Endoscopic view of sessile polyp.
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Media file 3:  Intestinal polypoid adenomas. Tubular adenoma, low-power view. Courtesy of G. Warren, MD, Rose Medical Center, Denver, Colo.
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Media file 4:  Intestinal polypoid adenomas. Villous adenoma, low-power view. Courtesy of G. Warren, MD, Rose Medical Center, Denver, Colo.
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Media file 5:  Intestinal polypoid adenomas. High-power view of adenomatous polyp with low-grade dysplasia. Courtesy of G. Warren, MD, Rose Medical Center, Denver, Colo.
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Media file 6:  Intestinal polypoid adenomas. Villous adenoma with grade IV invasive carcinoma. Courtesy of G. Warren, Rose Medical Center, Denver, Colo.
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REFERENCES

Section 11 of 11

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1. Alberts DS, Martínez ME, Roe DJ, Guillen-Rodriguez JM, Marshall JR, van Leeuwen JB, et al. Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. Phoenix Colon Cancer Prevention Physicians' Network. N Engl J Med. Apr 20 2000;342(16):1156-62. [Medline].
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Article Last Updated: Jul 11, 2007