Intestinal Polypoid Adenomas Workup
- Author: Swati G Patel, MD, MS; Chief Editor: BS Anand, MD more...
2015 ACG guidelines on genetic testing and management of hereditary gastrointestinal cancer syndromes
The American College of Gastroenterology (ACG) released the following recommendations for the management of patients with hereditary gastrointestinal cancer syndromes—and they specifically discuss genetic testing and management of Lynch syndrome, familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP), MUTYH-associated polyposis (MAP), Peutz-Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, serrated (hyperplastic) polyposis syndrome, hereditary pancreatic cancer, and hereditary gastric cancer :
The initial assessment is the collection of a family history of cancers and premalignant gastrointestinal conditions and should provide enough information to develop a preliminary determination of the risk of a familial predisposition to cancer.
Age at diagnosis and lineage (maternal and/or paternal) should be documented for all diagnoses, especially in first- and second-degree relatives.
When indicated, genetic testing for a germline mutation should be done on the most informative candidate(s) identified through the family history evaluation and/or tumor analysis to confirm a diagnosis and allow for predictive testing of at-risk relatives.
Genetic testing should be conducted in the context of pre- and post-test genetic counseling to ensure the patient's informed decision making.
Patients who meet clinical criteria for a syndrome as well as those with identified pathogenic germline mutations should receive appropriate surveillance measures in order to minimize their overall risk of developing syndrome-specific cancers.
Complete blood cell (CBC) count may be helpful because patients with an adenoma occasionally can present with a microcytic (iron deficiency) anemia due to chronic occult blood loss.
Iron studies may be needed because low serum iron and ferritin and an increased total iron-binding capacity (TIBC) can occasionally be observed as a result of blood loss in some patients with colonic adenomas and carcinomas.
Guaiac-based fecal occult blood testing (FOBT)
A small proportion of large adenomas may bleed intermittently. Depending on the age of the patients tested, 10% to 40% of asymptomatic patients with a positive result on a fecal occult blood test have an advanced adenoma. Three fresh, separate, nonhydrated stool specimens are used. FOBT screening programs are intended for the early detection of colorectal cancer (CRC) and have demonstrated decreased cancer-related and all-cause mortality.[33, 34, 35, 36]
Fecal immunochemical test (FIT)
Immunochemical testing for human globin has higher sensitivity for CRC and adenomas than traditional FOBT and is increasingly replacing guaiac-based tests as the recommended FOBT for CRC screening. In one study using 3 consecutive samples and a hemoglobin threshold of 75 ng/mL, sensitivity was 94.1% and specificity was 87.5% for cancer. Using the same testing parameters, sensitivity and specificity were 67% and 91.4%, respectively, for clinically significant neoplasia (advanced adenoma [defined as adenoma >1 cm or with villous features or high-grade dysplasia] and cancer).
Many of the clinically available FITs recommend using only 1 test and a hemoglobin threshold of 100 ng/mL. This approach has been shown to still have a greater than 50% sensitivity for CRC and is associated with higher compliance than the 3-day guaiac-based testing regimens. Several issues should be considered when choosing a FIT regimen.
It is important to establish the relationship between a given quantity of hemoglobin detected in the stools and the pathology detected on colonoscopy in those with positive tests.
In CRC screening, different positivity thresholds need to be established for the immunochemical-based screening strategies. Depending on the threshold in terms of the amount of blood detected, the rates of adenoma and CRC detection vary. The positivity threshold influences the number needed to scope (NNS) to find a CRC or advanced adenoma by colonoscopy in an individual with positive FIT results.
Large differences exist in the diagnostic performance among various FITs, and the different test variances need to be carefully evaluated.
FITs increase the detection rates of advanced adenoma and CRC without generating an unacceptable number of false-positive results, which would lead to unnecessary colonoscopies.
A large, Dutch, population-based, randomized controlled trial has shown that FITs detected 2.5 times as many advanced adenomas and CRC compared with the guaiac-based FOBT, despite similar colonoscopy rates for positive screening tests. Thus, FITs appear to be superior to guaiac-based FOBTs for CRC screening.
Quantitative testing of stool for blood
This has been tried, but it does not appear to have a role for screening or diagnosis of colonic adenomas at this time.
Stool testing for genetic alterations
The analysis of fecal DNA represents an emerging area for early detection, and studies have reported 62% to 91% sensitivity for CRC and 26% to 73% sensitivity for adenomas, with a specificity ranging from 93% to 100%.[38, 39] The major drawback of current fecal DNA testing is the high cost and limited availability.
Fecal calprotectin and tumor M2-PK protein detection in stool
This test may also have better performance characteristics than guaiac-based FOBTs, but these newer tests also have low sensitivity and poor specificity.
Biomarkers in blood or urine for the detection of CRC and advanced neoplasia, such as measurement of septin 9 levels in blood and the urinary metabolite of prostaglandin E2, are being developed but are not yet ready for routine use.
Barium enema imaging of the colon
Barium enema (BE) imaging can detect polyps and colorectal cancer (CRC). Air-contrast BE is more sensitive than the single-contrast technique for the 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 smaller than 1 cm, 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 the evaluation of the entire colon.
The US Multi-Society Task Force (MSTF) offers double-contrast BE as an acceptable CRC screening tool; however, the US Preventative Services Task Force (USPSTF) does not.
Computed Tomography colonography (virtual colonoscopy)
This has emerged as a promising modality for the detection of adenomas and carcinomas of the colon. Thus far, computed tomography (CT) colonography has lower sensitivity than optical colonoscopy for small (<1 cm) adenomas, but the technology is improving rapidly. The advantages of virtual colonoscopy include the lack of need for sedation, the short commitment of time for the test, and its noninvasive nature. A positive test would need to be followed by a standard colonoscopy.
Most protocols still require cathartic bowel preparation, but CT colonography without bowel preparation may be possible in the future. The main disadvantages include cost, exposure to radiation, uncertainty in how to deal with extracolonic findings, and operator dependence.
The 2008 USPSTF guidelines state that there is insufficient evidence to support the use of CT colonography in routine polyp and CRC screening; however, the MSTF states CT colonography is an acceptable option.
Flexible sigmoidoscopy (FS) can be used to visualize the left colon, where over half of all colonic adenomas and cancers are located. If an adenoma is detected, a colonoscopy should then be performed. If no adenomas are detected, a repeat examination is not required for 5 years.
FS screening for average-risk patients is endorsed by all major society guidelines, including those by the US Multi-Society Task Force (MSTF) and the US Preventative Services Task Force (USPSTF). The Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial demonstrated a 26% reduction in overall colorectal cancer (CRC)–related mortality and a 21% reduction in CRC incidence with FS screening compared with standard care.
The main advantages to FS include that is more widely available and less expensive than colonoscopy, has a lower risk than colonoscopy, does not require sedation, and requires a less rigorous bowel preparation (usually enema preparation alone is recommended).
The disadvantages of FS are that it does not visualize the entire colon, it can be more uncomfortable for patients since they are not sedated, and it is 2-step procedure (requires subsequent colonoscopy) if adenomas are found.
Despite its efficacy in decreasing CRC incidence and mortality, FS is diminishing as a screening tool in the United States. Critics liken FS to undertaking mammography on only one breast.
Although there are several polyp and CRC screening options, colonoscopic screening has emerged as the dominant screening strategy in the United States for average-risk patients.
Colonoscopy is the recommended screening modality for high-risk individuals, such as those with first-degree relatives with colorectal cancer/advanced adenomas, those with a hereditary colorectal cancer syndrome, and for surveillance of those with a personal history of adenomas or CRC.
Colonoscopy carries the conceptual advantage of being a 1-time test that can both visualize the entire colon and remove any adenomas in a single session. A colonoscopy can be performed at longer (10-year) intervals if no adenomas are found, and there is minimal patient discomfort since the patient is sedated during the examination.
Endoscopically, polyps can be classified as pedunculated (mucosal stalk interposed between the polyp and the colonic wall), sessile (entire base is attached to the colonic wall), flat (polyp height less than one half the diameter of the polyp) or depressed (polyps with depression into the colonic mucosal wall. See the following images.
Disadvantages of colonoscopy are that it is an invasive examination with higher risk of complications than the other screening options (although low overall); it requires sedation; thus, patients would need to take time off work and would require a driver to and from the test. It requires a full bowel preparation and it is expensive. It is operator-dependent, and the quality of colonoscopy in the United States is highly variable. The procedure also can be time consuming. Furthermore, there is concern that the United States does not have enough trained endoscopists for all CRC screening-eligible patients to undergo high-quality colonoscopy as the primary screening tool. Complications associated with colonoscopy include perforation, bleeding, cardiopulmonary events related to sedation, and, rarely death.
Perforation rates vary depending on whether an intervention takes place (eg, polypectomy). Large database studies suggest rates ranging from 0.01% to 0.3%. Risk factors for perforation during diagnostic colonoscopy include advanced age, presence of diverticulosis, female sex, and a history of pelvic/abdominal surgery.
Bleeding rates range from 0.1% to 0.6%. Rates significantly depend on whether an intervention takes place (3.7 in 1000 for procedures without polypectomy and 8.7 in 1000 for procedures with polypectomy).
There is a 0.9% risk of a cardiopulmonary complication, usually associated with sedation.
The complication of death is extremely low, ranging from 0.007% to 0.03%.
No prospective randomized controlled trials available to date have demonstrated a beneficial effect of colonoscopy screening on CRC incidence or mortality. Despite this, colonoscopy is endorsed by all major society guidelines in the United States for CRC screening. The main support for the efficacy of colonoscopy lies in the conceptual advantage of visualizing the entire colon (compared to FS) and indirect evidence such as data from the National Polyp Study that showed a 76% to 90% reduction in CRC incidence after polypectomy compared with historic controls. Efficacy can also be extrapolated from randomized trials examining other screening modalities such as FOBT, since a positive test triggered a subsequent colonoscopy.
More recent studies have called into question the efficacy of colonoscopy efficacy. Several large retrospective studies from Canada[5, 42] and the United States have quantified the occurrence of CRC 6-36 months after reportedly a “negative” colonoscopy, ranging from 7.2% to 9% of all CRCs. In all of these studies, a significantly higher rate of postcolonoscopy CRC was seen in the right-sided compared with the left-sided colon (9.9% to 12.4% vs 4.5% to 6.8%) in these studies. A German study reported that previous colonoscopy was associated with a 67% reduction in advanced neoplasia in the left-sided colon, but no risk reduction in the right-sided colon. Multiple studies (tandem colonoscopy, CT colonography studies) have demonstrated considerable miss rates of colonoscopy ranging from 2% to 12% for large adenomas. These data have highlighted the importance of colonoscopy quality.
Even at centers of excellence, there is wide variability (3- to 5-fold) in adenoma detection rates between providers. Colonoscopy quality measures have emerged, although they are not uniformly tracked. All of these measures are geared towards adequate examination of the colon.
Colonoscopists or their institutions should develop a continuous quality improvement process to document quality assurance (eg, percentage of cases reaching the cecum, withdrawal time, polyp detection rate, adenoma detection rate, quality of bowel preparation).
A good bowel preparation is essential for adequate visualization of the colonic mucosa. A split-dosed bowel preparation (half of the volume the evening prior to the procedure, half of the volume on the morning of the procedure) is the preferred method of bowel cleansing and results in improved visualization of the colon during colonoscopy.
Withdrawal time is a widely accepted surrogate for colonoscopy quality and should be a minimum of 6 minutes according the American Society for Gastrointestinal Endoscopy. Colonoscopy reports should identify landmarks of the cecum as well as the colonoscopy withdrawal time.
The adenoma detection rate should be at least 25% among male patients and 15% among female patients undergoing screening colonoscopy. It is widely recognized, however, that these rates are likely well under the true adenoma prevalence rate and that higher thresholds may be considered in the future.
Three randomized controlled trials are currently under way to directly examine the efficacy of colonoscopy. The VA Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) trial and a Spanish trial are comparing colonoscopy with FIT, and the Nordic-European Initiative on Colorectal Cancer trial will compare colonoscopy with no screening.
Conclusions About Screening
Multiple screening options are available for colorectal polyps and colorectal cancer (CRC) in the average-risk patient, including stool-based tests (fecal occult blood test [FOBT], fecal immunochemical test [FIT]), imaging tests (barium enema [BE] imaging of the colon, computed tomography [CT] colonography), and endoscopic tests (flexible sigmoidoscopy [FS], colonoscopy).
FOBT and FS have been shown to decrease CRC-related mortality, but colonoscopy has emerged as the dominant screening modality in the United States because of its multiple conceptual advantages. Trials investigating colonoscopic screening are underway.
High-risk patients should undergo colonoscopic screening and surveillance.
Although colonoscopy is considered to be the criterion standard for screening for CRC by looking for adenomatous polyps, it is recognized that the miss rate for advanced adenomas and CRC with colonoscopy is sufficiently high to be of concern.
Screening and Surveillance Intervals
Average-risk individuals should begin screening at age 50 years.
Those at high risk have specific recommendations based on risk, such as the following:
Among persons with no colorectal neoplasia on initial screening colonoscopy, repeat screening is recommended in 10 years.
For those with 1-2 small adenomas (≤9 mm), repeat colonoscopy is recommended in 5-10 years.
For those with an adenoma larger than 1 cm, 3 or more adenomas of any size, or any adenoma with advanced histology (villous features, high-grade dysplasia), colonoscopy should be repeated in 3 years.
Adenomas are classified based on their size, architecture, and degree of dysplasia. Large size, villous content, and high-grade dysplasia in colorectal adenomas are all associated with a higher rate of finding a focus of colorectal cancer (CRC) within the adenoma. 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.
Most adenomas are small (<1 cm). Large adenomas (>1 cm) tend to have more severe dysplasia, more worrisome architecture, and increased risk of malignant potential. However, small (6-10 mm) and diminutive adenomas (≤5 mm) may have advanced histology or carcinoma, in up to 10.1% and 1.7%, respectively.
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% to 25% villous tissue. About 70% to 85% of all adenomas are tubular; they tend to be smaller than villous adenomas. See the image below.
Tubulovillous adenomas contain approximately 25% to 75% villous tissue. These adenomas represent 10% to 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.
Dysplasia is a neoplastic change in histology. All adenomas are dysplastic; they display varying degrees of hyperchromasia, nucleolar prominence, nuclear pleomorphism, and increased mitoses.
Dysplasia is classified as either low-grade or high-grade. High-grade dysplasia is associated with an increased risk of malignancy. Invasive carcinoma is distinguished from high-grade dysplasia by invasion of neoplastic tissue beyond the muscularis mucosa.
The histologic criteria used to differentiate low- and high-grade dysplasia are as follows:
Low-grade: Basal or stratified nuclei, crowded glands, less goblet cells and mucin (See the following image.)
High-grade: Loss of glandular architecture, increased mitoses (includes previously termed carcinoma in situ and intramucosal carcinoma) (See the image below.)
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