Adenomatous polyps are, by definition, neoplastic. Although benign, they are the direct precursors of adenocarcinomas and follow a predictable cancerous temporal course unless interrupted by treatment. They can be either pedunculated or sessile. Polyps are generally asymptomatic but may occasionally ulcerate and bleed; uncommonly, they may result in obstruction if very large.
Adenomas are divided into 3 subtypes based on histologic criteria, as follows: (1) tubular, (2) tubulovillous, and (3) villous. According to World Health Organization (WHO) criteria, villous adenomas are composed of greater than 80% villous architecture. Tubular adenomas are encountered most frequently (80-86%). Tubulovillous adenomas are encountered less frequently (8-16%), and villous adenomas are encountered least frequently (5%).
Villous adenomas are associated more often with larger adenomas and more severe degrees of dysplasia. These adenomas occur more frequently in the rectum and rectosigmoid, although they may occur anywhere in the colon. They generally are sessile structures that appear as velvety or cauliflowerlike projections. See the images below.
View Image | Endoscopic view of a sessile polyp, which histology studies revealed to be a villous adenoma. Courtesy of H. Chaun, MD. |
View Image | Endoscopic view of a sessile polyp histologically determined to be a villous adenoma. Courtesy of R. Enns, MD. |
Although rare, villous adenomas of the duodenum and the small bowel, particularly at the ampulla, can occur. Villous adenomas are of concern primarily because of the risk of malignant transformation (approximately 15-25% overall but higher once >2 cm). The primary focus of this article is colonic villous adenomas. Where appropriate, certain aspects of small bowel villous adenomas are addressed.
Adenomas are believed to have an abnormal process of cell proliferation and apoptosis. The proliferative component is not confined to the crypt base and accumulates onto the surface and infolds downward. In villous adenomas, mesenchymal proliferation results in longer projections and larger polyps.
Clinical, autopsical, and epidemiological studies provide evidence of adenoma-to-carcinoma progression. The mean age of adenoma diagnosis is 10 years earlier than with carcinoma, and progression to carcinoma takes a minimum of 4 years. Multiple sources have provided evidence for an adenoma-to-carcinoma progression: one third of operative specimens containing colon cancer contain one or more synchronous adenomas. The risk of colon cancer is increased with the number of adenomatous polyps. Adenomatous tissue is frequently found contiguous to frank carcinoma. Patients who refuse polypectomy for adenomas develop colon cancer at a rate of about 4% after 5 years and 14% after 10 years.
Molecular genetic studies also describe an adenoma-to-carcinoma sequence through accumulation of lesions in a variety of genes, with activation of oncogenes and inactivation of tumor suppressor genes. Genetic mutations lead to progressively disordered local DNA replication. The progressive accumulation of multiple genetic mutations results in the transition from normal mucosa to adenoma to severe dysplasia and finally to carcinoma. The K-ras oncogene is described in 9% of small adenomas, 58% of adenomas larger than 1 cm, and 46% of colorectal carcinomas. Inactivation of tumor suppressor genes on arms 5q, 18q, and 17p are thought to be essential in tumorigenesis. The APC gene, on 5q, has an important role in adenoma formation. The gene is mutated in 30-60% of persons with sporadic adenomas and adenocarcinomas. Mutations in the APC gene occur early in adenoma development and are often found in aberrant crypt foci, the earliest identifiable dysplastic crypts.
Mutation on the TP53 gene, on 17p, results in malignant transformation of adenomas. The loss of TP53 is frequent in patients with adenomas (50%) and occurs in more than 75% of patients with adenocarcinomas.
The loss of the DCC (deleted in colon cancer) gene, on 18q, occurs in 50% of patients with adenomas and 70% of patients with carcinomas. The loss of the normal DCC gene is important in the transition from an intermediate adenoma to a late adenoma.
United States
The prevalence of adenomas closely parallels the risk of colorectal cancer in a region. Adenomas are found in 30-40% of persons aged 60 years or older; in some areas, as many as 50% have adenomas.
International
In regions of low risk for colon carcinoma (eg, Costa Rica, Columbia), prevalence rates are 12%. This rate increases drastically in high-risk regions (eg, United States, Canada, western Europe, Argentina, New Zealand, Australia) to 30-40%. In some areas, rates approach 50%.
In Austrian patients undergoing colonoscopy screening, the prevalence for advanced adenomas was comparable between men aged 45 to 49 years and women aged 55 to 59 years.[1]
The immediate risks of adenomas include hemorrhage, obstruction with intussusception, and, possibly, torsion. However, the main concern is malignant progression of the villous adenoma. Studies have defined the risk of progression of adenomas to adenocarcinoma. Note the following:
Race is not an independent factor for adenoma prevalence, although region is considered to be a factor. Note the following:
Generally, adenoma risk is independent of sex, although some authorities suggest a slight male predominance.
The prevalence and distribution of adenomas varies with patient age. Note the following:
Note that the vast majority of patients are asymptomatic and have unremarkable laboratory findings. Approximately two thirds of colorectal polyps are asymptomatic. Any nonspecific intestinal symptoms are more likely to be coincidental. For example, bright red rectal bleeding in a patient in whom a small colonic polyp is eventually found is still most likely to be hemorrhoidal in origin. Polyps greater than 1 cm are more likely to produce symptoms, usually rectal bleeding, abdominal pain, and a change in bowel habits. Note the following:
Patients often have no findings on bedside physical examination.
Occasionally, a palpable mass is present upon digital rectal examination.
Jaundice may be present with villous adenoma of the ampulla.
Genetic factors
From the NPS data, relatives of patients with polyps have an increased risk of carcinoma. This includes siblings of patients with adenomas detected prior to age 60 years or siblings of patients with adenomas detected at any age if either parent has colorectal cancer. Offer these patients screening colonoscopy every 5 years after age 40 years.
Lifestyle and diet
Foods and vitamins that have a protective effect against adenomas include dietary fiber, plant foods, carbohydrates, and folate supplementation. Excess fat and alcohol are positively correlated with adenoma risk. A strong association exists between cigarette smoking and adenoma size. Supplemental vitamins C and E are not considered protective.
Acromegaly
Patients with acromegaly have an increased risk of adenomas and colon cancer. Prevalence rates of 14-35% for adenomas are reported. The mechanism for increased risk is not known.
Streptococcus bovis bacteremia
This causes an increased risk of adenomas, carcinomas, and, possibly, familial adenomatous polyposis (FAP). These patients should undergo colonoscopy. Patients with endocarditis from Streptococcus agalactiae infection are reported to have an increased risk of rectal villous adenoma and should be evaluated.
Atherosclerosis and cholesterol
Autopsy studies report a positive correlation between the degree of atherosclerosis and adenoma size, dysplasia, and multiplicity.
Uterosigmoidostomy sites
Patients who undergo urinary diversion procedures are at increased risk of developing polyps or carcinomas at uterosigmoidostomy sites as many as 38 years later. Prevalence rates of 29% are reported.
Inflammatory bowel disease (IBD)
In patients with IBD who develop carcinomas, 50% of the lesions are found to be juxtaposing serrated or villous adenomas. These possibly are the lesions from which the carcinomas originate. However, a dysplasia-associated lesion or mass is reported to be the premalignant lesion of adenocarcinoma in ulcerative colitis, in which the adenoma-carcinoma sequence is not preserved.
Other conditions
Historically, some conditions have been thought to be correlated with increased incidence of polyps. These conditions include acrochordons (skin tags), breast cancer, and cholecystectomy, for which no evidence exists of an increased risk for adenoma.
A low hemoglobin level and a classic low mean cell volume (MCV) suggest iron deficiency anemia, but these values can be within reference ranges or can be considered nonspecific findings if small polyps are present.
Obtain ferritin levels, serum iron levels, and transferrin saturation values. Patients with iron-deficiency anemia have low ferritin and serum iron levels and low transferrin saturation.
Only 20-40% of patients with adenomas have positive test findings, usually resulting from distal and larger polyps. Of those patients with fecal occult blood, 5-10% have colon cancer. Annual screening by fecal occult blood testing results in reduced mortality from colon cancer.
Fecal occult blood testing is demonstrated in the video below.
View Video | Fecal occult blood testing. Video courtesy of Therese Canares, MD; Marleny Franco, MD; and Jonathan Valente, MD (Rhode Island Hospital, Brown University). |
Genetic studies are not performed routinely in the evaluation of sporadic polyps.
DNA from colon cancer is shed into the fecal stream in greater quantities than DNA from normal colonic mucosa. Studies are ongoing for detection of multiarray assay for common mutations in colon cancer, including APC, p53, K-ras, and BAT-26 mutations. Unfortunately, most detected cases have been advanced tumors. This screening test has the potential of noninvasiveness and ease of use.
Double-contrast barium enemas have a higher sensitivity compared to single-contrast barium enemas. Sensitivity increases with polyp size.
Compared to colonoscopy, barium enema detected 32% of polyps smaller than 6 mm in diameter, 53% of polyps between 6 mm and 10 mm, and 48% of polyps larger than 10 mm. A false-positive rate of 5-10% is found because of improper cleaning of the bowel. Diverticulosis or redundant bowel can result in a false-negative rate of 10%, especially in the rectosigmoid. The accuracy of the procedure also can have an element of operator-dependence.
For all structural evaluations of the large bowel, use sigmoidoscopy with a barium enema.
Computed tomographic colonography is a newer method that is not as sensitive as colonoscopy, although it has the advantage of being less invasive. This scanning still requires bowel preparation.
A large variability exists in the effectiveness of computed tomographic colonoscopy as a screening tool. Differences in studies are due in part to differing computed tomographic technologies. When compared to colonoscopy, computed tomographic colonography was able to identify 55-93.8% of all polyps larger than 1 cm, 71-88.7% of polyps between 0.5 cm and 0.9 cm, and only 39% of polyps smaller than 0.6 cm. More studies comparing colonoscopy with virtual colonoscopy are needed before making firm recommendations regarding the role of virtual colonoscopy in screening for colon polyps.
These studies detect small bowel adenomas and can help investigate the small bowel for polypoid lesions beyond the reach of the conventional upper endoscope. They also help detect mass abnormality in 50-80% of patients and can help successfully define neoplasms in 30-44% of patients.
Video capsule endoscopy has provided an increasingly effective method to assess the small bowel. Video capsule endoscopy is not used as a screening tool for colonic polyps.
Endoscopy is the most sensitive method of diagnosing polyps, and it also allows therapeutic intervention. See the images below.
View Image | Endoscopic view of a sessile polyp, which histology studies revealed to be a villous adenoma. Courtesy of H. Chaun, MD. |
View Image | Endoscopic view of a sessile polyp histologically determined to be a villous adenoma. Courtesy of R. Enns, MD. |
View Image | Endoscopic view of injection of saline into the base of a sessile polyp histologically determined to be a villous adenoma. This enables an easier poly.... |
View Image | Polypectomy with a snare around a sessile polyp base (villous adenoma) injected with saline. Courtesy of R. Enns, MD. |
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.
Colonoscopy is the most accurate method for detection of polyps and is the first-line procedure of choice. The sensitivity for detecting polyps by colonoscopy compared to double-contrast barium enema is 94% and 67%, respectively. Although accuracy is operator-dependent, colonoscopy is regarded as the criterion standard.[4, 5, 6]
Villous adenomas at colonoscopy are usually bulky, sessile, soft, velvety, and friable. However, colonoscopic appearance is not diagnostic of histology.
Chromoendoscopy and magnifying endoscopy techniques use dye or magnification to identify and classify the pit pattern of small lesions. This allows a more predictive model on the final histology.[7, 8]
Difficulties with colonoscopy include patient discomfort, the need for patient sedation, and material risks of complications (eg, perforation, hemorrhage). Colonoscopy also costs more to perform than barium enema. Note that the accuracy of colonoscopy findings is operator-dependent, with reports of missing up to 15% of small polyps (< 8 mm) in a tandem study. No large polyps were missed in this study.
Risk of perforation is less than 0.1%. After colonoscopic polypectomy, the risks of perforation and significant bleeding are 0.2% and 1%, respectively.
Esophagogastroduodenoscopy is used to help investigate for small bowel adenomas. Visualization of the duodenum is limited.
Enteroscopy is used to help investigate for small bowel adenomas. Visualization beyond the conventional endoscope (occasionally up to the ileum) depends on the skill of the operator.
Endoscopic retrograde cholangiopancreatography is used to help investigate for adenomas at the ampulla of Vater and allows for biopsy and therapeutic procedures if biliary obstruction is a concern. The risk of complicating pancreatitis is reportedly 3-5%.
Flexible sigmoidoscopy allows for evaluation of the distal bowel to 60 cm. Compared to the previously used rigid sigmoidoscope, the flexible one can detect up to 3 times more adenomas, primarily because it can be inserted further.
Some guidelines recommend flexible sigmoidoscopy every 3-5 years in conjunction with annual FOBT for the screening of colon cancer. Overall, the role of flexible sigmoidoscopy is becoming increasingly limited in the screening and diagnosis of colon cancer. Patients do not require full bowel preparation.
Adenomatous epithelium has abnormal cellular differentiation with hypercellularity and variable amounts of mucin. The predominant cell type is columnar epithelium, and immature goblet cells may be observed. The dysplastic cells demonstrate elongated nuclei, are hyperchromatic, and have a picket-fence appearance.
Villous histology is characterized by glands arranged in long fingerlike fronds from the polyp surface down to the polyp stroma. Projections usually extend straight down with minimal or no branching. See the images below.
View Image | Histology of villous adenoma. Fingerlike projections stretching from the surface of a polyp downward with minimal branching. Courtesy of D. Owen, MD. |
View Image | Histology of villous adenoma. Low-grade dysplasia with loss of mucin, prominent nucleoli, and hyperchromatic and elongated cells. Courtesy of D. Owen,.... |
Dysplasia is subdivided into mild, moderate, and severe categories. Note the following:
A full colonoscopy is the accepted procedure of choice in North America for screening or investigation of possible adenomas. If possible, remove all polyps at endoscopy. Send polyps to a pathologist to assess for histological type, grade of dysplasia, and presence of carcinoma. Record the gross morphology, location, and size of each polyp.
Perform a full colonoscopy if sigmoidoscopy reveals an adenoma. Of patients with rectosigmoid adenomas, 40-50% have additional proximal polyps. From the NPS data, patients with left-sided adenomas had a 2.9-fold risk of also having right-sided polyps compared to patients with no left-sided polyps. Patients with only a hyperplastic polyp in the rectosigmoid do not require full colonoscopy.
Cautery snare is recommended for removal of larger polyps. For large sessile polyps, for which the risk of perforation is higher, injection of 1 mL or more of saline into the submucosa directly under the polyp is a useful technique. This lifts the flat polyp away from the muscular layer, creating a stalklike effect. A couple of drops of methylene blue added to the saline also allows the operator to determine if a perforation has occurred in the muscle layer, which would be seen as a break in the layer. Smaller sessile polyps should be removed or biopsied and ablated with hot-biopsy forceps or a minisnare.
After removal of a large (>2 cm) sessile polyp or if the possibility exists of incomplete removal of a large adenoma, a follow-up colonoscopy usually should be performed within 3-4 months.
In the case of malignant polyps, no further treatment is necessary if certain conditions are met, as published by the American College of Gastroenterology:
Surgical resection of a colorectal polyp may be required, especially if the polyp is larger than 2-3 cm and is sessile (as villous adenomas often are). Also, polyps encompassing 2 colonic folds often require surgical consideration. In such situations, the colonic wall can be marked with India ink for localization of the bowel segment at surgery.
If benign, duodenal villous adenomas can be treated by local transduodenal resection, although recurrence is common and may be malignant. Consider pancreaticoduodenectomy for duodenal malignant villous adenomas and for villous tumors of the ampulla of Vater.
A competent endoscopist should supervise care and follow-up.
Consultation with a surgeon may be required for resection of the polyp.
Dietary recommendations have been established to prevent colorectal cancer. Given the evidence for the adenoma-to-carcinoma sequence, these recommendations likely also apply to adenomas.
Limit total fat to 25-30% of energy intake. A fatty diet may increase biliary sterols, which are damaging.
Increase fruit and fiber intake to 5 servings daily. Increased fiber dilutes luminal contents and decreases the contact between carcinogenic substances and the lumen. Fruits and vegetables also contain minerals and vitamins that may impede carcinogenesis.
Ingest 20-30 g of fiber daily. In addition to the benefits of increased fruit and fiber intake, fiber may inhibit some harmful bacteria and prevent damaging effects of bile acids.
Dietary supplementation with 3 g of calcium carbonate is suggested based upon limited data.
Recommendations for activity include the following:
The literature supports the use of NSAIDs in FAP syndrome, with regression of polyps already present. It has been demonstrated that COX-2 is up-regulated 2-50 times in most (85-90%) adenocarcinomas. The role for NSAIDs (including the newer COX-2 inhibitors) in nonfamilial adenomatous lesions is unclear. For sporadic polyps, NSAID use has not been proven to cause regression in already developed polyps, although evidence suggests a decreased incidence of polyps in persons already taking NSAIDs. Therefore, a potential role exists for NSAIDs as primary prophylaxis.
In patients who have had a history of colon cancer, patients undergoing therapy with aspirin at 325 mg daily have fewer polyps than those on placebo. In patients with a history of a colonic polyp, low-dose aspirin (81 mg) may have some benefit in decreased adenoma recurrence.[9]
Studies with celecoxib have shown some regression in polyps in those patients with FAP. However, the routine use of COX-2 inhibitors for this indication may not be reasonable, especially in consideration of the recent documentation on cardiovascular toxicity/contraindications.
Clinical Context: Sulfoxide NSAID that is metabolized to the anti-inflammatory sulfide metabolite and a sulfone metabolite. Sulfide metabolite is now known to have apoptotic activity on colonic epithelial cells and is presumed to be responsible for regression of adenomatous polyps. Primary route of excretion is via urine as both sulindac and its sulfone metabolite.
Mechanism of action is not known but may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions, also may exist.
Surveillance colonoscopy (after initial colonoscopy and clearing of polyps) is recommended. Note the following:
Potential complications include the following:
Transformation to malignancy is a primary consideration in villous adenomas. Note the following:
Emphasize the importance of continued surveillance once polyps are identified.
Provide screening information for family members when appropriate.