Large Intestine, Neoplastic: Adenocarcinoma

At a Glance

Most colon polyps and early stages of colon cancer are often asymptomatic until they are advanced and present with symptoms, such as gastrointestinal (GI) blood loss, which is the most common sign. Other clinical findings that may provide clues to the diagnosis include a positive fecal occult (hidden) blood test (FOBT), bright red blood per rectum (hematochezia), or hematologic abnormalities, such as iron-deficiency anemia. Iron deficiency anemia in an older man or post-menopausal woman, is GI cancer until proven otherwise.

Right-sided colon cancers are most often associated with fatigue and weakness due to iron deficiency anemia. Left-sided colon cancers are more likely to produce occult bleeding or changes in bowel habits. Unfortunately, obvious symptoms, such as anorexia, weight loss, or obstructive symptoms, such as a change in bowel habits or abdominal pain, occur late in the disease course.

Your patient may have an increased risk of acquiring colon cancer if he or she has any of the following risk factors:

  • Personal history of adenomas or colon cancer

  • Family history of colorectal adenoma or colon cancer

  • First-degree relative younger than 60 years of age or two first-degree relatives of any age with diagnosed colon cancer

  • Inherited colorectal cancer syndromes, such as hereditary nonpolyposis colorectal cancer (HNPCC) or familial adenomatous polyposis (FAP), MYH-associated polyposis (MAP), or inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn's disease

The diagnosis of colonic polyps or adenocarcinoma of the colon is often made when a patient presents with any of the mentioned symptoms or during routine colonoscopy screening as recommended by the American College of Gastroenterology. Since most adenocarcinomas of the large intestine arise from adenomas, which are precancerous lesions, early detection significantly increases patient survival.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

The most useful screening tests for the diagnosis of adenocarcinoma of the large intestine in average risk patients include a FOBT completed annually, a flexible sigoidoscopy, computed tomography (CT), or a barium enema performed at least every 5 years; or a colonoscopy performed every 10 years. In patients without any of the listed risk factors, screening should begin at age 50. However, in patients with high risk diseases such as FAP, HNPCC, or IBD, screening is recommended much earlier and eventually is recommended on an annual basis. For example, in patients with FAP screening should begin at puberty.

The gold standard test is colonoscopy, which is cost effective in average risk patients. Colon cancer is one of the few cancers in which early detection can be curative, and those that have undergone polypectomies have significantly (>90%) decreased rates of colorectal cancer development. Although other screening tests, such as FOBT and sigmoidoscopy, can be used initially, when positive results are obtained a follow-up colonoscopy is recommended.

Carcinoembryonic antigen (CEA) remains the prototypical solid tumor marker of colon cancer. Despite its lack of specificity, if used correctly, it is a valuable addition to clinical decision making in patients diagnosed with colon or rectal carcinoma. CEA is not an appropriate screening test, as values are not usually elevated in mild disease, but it may be used to monitor disease regression or reoccurrence after treatment when compared to baseline values. If CEA is not elevated in patients with advanced or recurrent cancer, sometimes another tumor marker, CA 19-9, can be used.

Are There Any Factors That Might Affect the Lab Results?

The FOBT test can have false-positive results if patients do not adhere to special diets (i.e., meat free and without certain vegetables, such as turnips and horseradish, that have peroxidase activity) and avoid excess levels (>250 mg/day) of vitamin C for at least 72 hours prior to testing. As mentioned, aspirin and other nonsteroidal anti-inflammatory drugs may cause bleeding in the GI tract and should be avoided for 7days prior to testing. Additionally, with this test, it can also be difficult to obtain patient compliance, as three separate stool specimens at least 1 day apart are recommended for optimal results. A positive FOBT is made by observing a color change in the presence of added hydrogen peroxide when the peroxidase in the fecal blood catalyzes the oxidation of guaiac.

The fecal immunochemical test, also called an immunochemical fecal occult blood test (iFOBT), is a newer test that also detects occult blood in the stool. This test is specific for human hemoglobin, which is found in red blood cells, and will not react with animal hemoglobin. The iFOBT is done essentially the same way as the FOBT, but patients may find it easier, because there are no dietary restrictions. However, patients should still refrain from ingesting aspirin and other nonsteroidal anti-inflammatory drugs. The iFOBT is also less likely to react to bleeding from parts of the upper GI tract, such as the stomach.

In recent years, there has been an increased incidence in colon cancers that involve the ascending colon. Therefore, use of flexible sigmoidoscopy, which is unable to examine the entire colon, is decreasing in use.

Barium enema, although it does allow visualization of the entire bowel, does not allow detection of small polyps, especially those located in the rectum.

CT is not recommended for normal screening purposes, because it is unable to detect smaller lesions, such as polyps, that are smaller the 5 mm in greatest dimension. However, this imaging modality often detects larger colonic lesions incidentally.

What Lab Results Are Absolutely Confirmatory?

As mentioned, the gold standard test is colonoscopy, followed by surgical biopsy and pathologic diagnosis if polyps are removed. All polyps need pathologic diagnosis to distinguish those without malignant potential (e.g., hyperplastic) from precancerous (e.g., tubular adenoma) lesions.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

The discussion of colon cancer would not be complete without discussing some of the molecular tests used to determine susceptibility to disease or, as with DNA testing, may be used for diagnosis in the future.

There are two molecular pathways that involve both genetic and epigenetic alternations that lead to development of colonic adenocarcinoma. The first is the classic adenoma-carcinoma sequence involving the APC/β-catenic/WNT pathway, which results in approximately 80% of sporadic cancers and 70% of FAP. The other is referred to as the microsatellite instability (MSI) pathway, which accounts for approximately 90% of cancer of patients with HNPCC and is associated with defect in DNA mismatch repair.

Mutations in genes that repair damaged DNA cause regions, called microsatellites, to get longer or shorter. Testing for MSI can help determine if a patient is likely to have a gene mutation that causes HNPCC cancer (also known as Lynch Syndrome). Testing for these mutations can be performed using several different methods, including polymerase chain reaction (PCR), RNA/DNA sequencing, or immunohistochemical techniques. Many of these tests can be performed on tumor tissue saved from biopsies or surgical procedures. These molecular methods are only recommended for patients who meet specific criteria; for example, those with first degree relatives with a confirmed diagnosis of FAP or HNPCC.

Stool DNA testing is another technique developed for diagnosis of colonic adenocarcinoma in fecal specimens and involves detecting DNA mutations, such as APC, KRAS, p53; markers of microsatellite instability caused by a loss of function of mismatch repair genes resulting in an accumulation of DNA sequence errors; and DNA methylation, an epigenetic alteration where gene promoter sites are hypermethylated. Although some clinical studies have had promising results, no stool DNA testinghas received FDA approval, and it is still considered an investigational device, thus is not widely used at this time.

Errors in test selection for Adenocarcinoma of the Large Intestine.

As mentioned, colonoscopy is the gold standard for diagnosis. Errors may be made if the bowel is not prepared properly, which can impede observation of the entire colonic mucosa. In addition, proximal colon polyps may be missed if flexible sigmoidoscopy is used for diagnosis.

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