Definition of Colon Cancer
Colorectal cancer, commonly known as colon cancer or bowel cancer, is a cancer from uncontrolled cell growth in the colon or rectum (parts of the large intestine), or in the appendix. Genetic analysis shows that colon and rectal tumours are essentially genetically the same cancer. Symptoms of colorectal cancer typically include rectal bleeding and anemia which are sometimes associated with weight loss and changes in bowel habits.
Most colorectal cancer occurs due to lifestyle and increasing age with only a minority of cases associated with underlying genetic disorders. It typically starts in the lining of the bowel and if left untreated, can grow into the muscle layers underneath, and then through the bowel wall. Screening is effective at decreasing the chance of dying from colorectal cancer and is recommended starting at the age of 50 and continuing until a person is 75 years old. Localized bowel cancer is usually diagnosed through sigmoidoscopy or colonoscopy.
Cancers that are confined within the wall of the colon are often curable with surgery while cancer that has spread widely around the body is usually not curable and management then focuses on extending the person’s life via chemotherapy and improving quality of life.
Cause of Colon Cancer
Greater than 75-95% of colon cancer occurs in people with little or no genetic risk. Other risk factors include older age, male gender, high intake of fat, alcohol or red meat, obesity, smoking and a lack of physical exercise. Approximately 10% of cases are linked to insufficient activity. The risk for alcohol appears to increase at greater than one drink per day.
Inflammatory Bowel Disease
People with inflammatory bowel disease (ulcerative colitis and Crohn’s disease) are at increased risk of colon cancer. The risk is greater the longer a person has had the disease, and the worse the severity of inflammation. In these high risk groups both prevention with aspirin and regular colonoscopies are recommended. People with inflammatory bowel disease account for less than 2% of colon cancer cases yearly. In those with Crohn’s disease 2% get colorectal cancer after 10 years, 8% after 20 years, and 18% after 30 years. In those with ulcerative colitis approximately 16% develop either a cancer precursor or cancer of the colon over 30 years.
Those with a family history in two or more first-degree relatives have a two to threefold greater risk of disease and this group accounts for about 20% of all cases. A number of genetic syndromes are also associated with higher rates of colorectal cancer. The most common of these is hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome) which is present in about 3% of people with colorectal cancer. Other syndromes that are strongly associated include: Gardner syndrome, and familial adenomatous polyposis (FAP) in which cancer nearly always occurs and is the cause of 1% of cases
Signs and Symptoms of Colon Cancer
The symptoms and signs of colorectal cancer depend on the location of tumor in the bowel, and whether it has spread elsewhere in the body (metastasis). The classic warning signs include: worsening constipation, blood in the stool, weight loss, fever, loss of appetite, and nausea or vomiting in someone over 50 years old. While rectal bleeding or anemia are high-risk features in those over the age of 50, other commonly described symptoms including weight loss and change in bowel habit are typically only concerning if associated with bleeding.
Risk Factors for Colon Cancer
Factors that may increase your risk of colon cancer include:
- Older than 50
- A personal history of colorectal cancer or polyps
- Chronic inflammatory diseases of the colon, such as ulcerative colitis and Crohn’s disease
- Genetic syndromes like familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, which is also known as Lynch syndrome.
- Family history of colon cancer and colon polyps
- Low-fiber, high-fat diet
- A sedentary lifestyle
- Heavy use of alcohol
- Radiation therapy for cancer
Diagnosis of Colon Cancer
Diagnosis of colorectal cancer is via tumor biopsy typically done during sigmoidoscopy or colonoscopy. The extent of the disease is then usually determined by a CT scan of the chest, abdomen and pelvis. There are other potential imaging test such as PET andMRI which may be used in certain cases. Colon cancer staging is done next and based on the TNM system which is determined by how much the initial tumor has spread, if and where lymph nodes are involved, and if and how many metastases there are.
The pathology of the tumor is usually reported from the analysis of tissue taken from a biopsy or surgery. A pathology report will usually contain a description of cell type and grade. The most common colon cancer cell type is adenocarcinoma which accounts for 95% of cases. Other, rarer types include lymphoma and squamous cell carcinoma.
Cancers on the right side (ascending colon and cecum) tend to be exophytic, that is, the tumour grows outwards from one location in the bowel wall. This very rarely causes obstruction of feces, and presents with symptoms such as anemia. Left-sided tumours tend to be circumferential, and can obstruct the bowel much like a napkin ring.
Adenocarcinoma is a malignant epithelial tumor, originating from glandular epithelium of the colorectal mucosa. It invades the wall, infiltrating the muscularis mucosae, the submucosa and thence the muscularis propria. Tumor cells describe irregular tubular structures, harboring pluristratification, multiple lumens, reduced stroma (“back to back” aspect). Sometimes, tumor cells are discohesive and secrete mucus, which invades the interstitium producing large pools of mucus/colloid (optically “empty” spaces) -mucinous (colloid) adenocarcinoma, poorly differentiated. If the mucus remains inside the tumor cell, it pushes the nucleus at the periphery – “signet-ring cell.” Depending on glandular architecture, cellular pleomorphism, and mucosecretion of the predominant pattern, adenocarcinoma may present three degrees of differentiation: well, moderately, and poorly differentiated.
Most colorectal cancer tumors are thought to be cyclooxygenase-2 (COX-2) positive. This enzyme is generally not found in healthy colon tissue, but is thought to fuel abnormal cell growth.
Prevention from Colon Cancer
Most colorectal cancers should be preventable, through increased surveillance, improved lifestyle, and, probably, the use of dietary chemopreventative agents .
Current dietary recommendations to prevent colorectal cancer include increasing the consumption of whole grains, fruits and vegetables, and reducing the intake of red meat. The evidence for fiber and fruits and vegetables however is poor. Physical activity can moderately reduce the risk of colorectal cancer.
Aspirin and celecoxib appear to decrease the risk of colorectal cancer in those at high risk. However it is not recommended in those at average risk. There is tentative evidence for calcium supplementation but it is not sufficient to make a recommendation. Vitamin D intake and blood levels are associated with a lower risk of colon cancer
More than 80% of colorectal cancers arise from adenomatous polyps making this cancer amenable to screening. Diagnosis of cases of colorectal cancer through screening tends to occur 2–3 years before diagnosis of cases with symptoms. Screening has the potential to reduce colorectal cancer deaths by 60%.
The three main screening tests are fecal occult blood testing, flexible sigmoidoscopy and colonoscopy. Of the three, only sigmoidoscopy can not screen the right side of the colon where 42% of malignancies are found. Virtual colonoscopy via a CT scanappears as good as standard colonoscopy for detecting cancers and large adenomas but is expensive, associated with radiation exposure, and can not remove any detected abnormal growths like standard colonoscopy can.
A new screening method is the M2-PK Test. The enzyme biomarker M2-PK has been identified as a key enzyme in colorectal cancers and polyps. M2-PK does not depend on blood in the stool and is specifically related to changes in the tumour metabolism. It does not require any special preparation prior to testing. Only a small stool sample is needed. M2-PK features a high sensitivity for colorectal cancer and polyps and is able to detect bleeding and non-bleeding colorectal cancer and polyps. In the event of a positive result people would be asked to undergo further examination e.g. colonoscopy.
Fecal occult blood testing of the stool is typically recommended every two years and can be either guaiac based or immunochemical. Medical societies recommend screening between the age of 50 and 75 years with sigmoidoscopy every 5 years and colonoscopy every 10 years. For those at high risk, screenings usually begin at around 40. For people with average risk who have had a high-quality colonoscopy with normal results, the American Gastroenterological Association does not recommend any type of screening in the 10 years following the colonoscopy. For people over 75 or those with a life expectancy of less than 10 years, screening is not recommended.
Treatment of Colon Cancer
The treatment of colorectal cancer depends on how advanced it is. When colorectal cancer is caught early surgery can be curative. However, when it is detected at later stages (metastases are present), this is less likely and treatment is often directed more at extending life and keeping people comfortable.
For people with localized cancer the preferred treatment is complete surgical removal with the attempt of achieving a cure. This can either be done by an open laparotomy or sometimes laparoscopically. If there are only a few metastases in the liver or lungs they may also be removed. Sometimes chemotherapy is used before surgery to shrink the cancer before attempting to remove it. The two most common sites of recurrence if it occurs is in the liver and lungs.
Chemotherapy may be used in addition to surgery in certain cases as adjuvant therapy. If cancer has entered the lymph nodes, adding the chemotherapy agents fluorouracil or capecitabineincreases life expectancy. If the lymph nodes do not contain cancer, the benefits of chemotherapy are controversial. If the cancer is widely metastatic or unresectable, treatment is then palliative. Typically in this case, a couple of different chemotherapy medications are used. Chemotherapy drugs may include combinations of agents including fluorouracil, capecitabine, UFT, leucovorin,irinotecan, or oxaliplatin.
While a combination of radiation and chemotherapy may be useful for rectal cancer, its use in colon cancer is not routine due to the sensitivity of the bowels to radiation.
In people with incurable colorectal cancer, palliative care can be considered for improving quality of life. Surgical options may include non-curative surgical removal of some of the cancer tissue, bypassing part of the intestines, or stent placement. These procedures can be considered to improve symptoms and reduce complications such as bleeding from the tumor, abdominal pain and intestinal obstruction. Non-operative methods of symptomatic treatment include radiation therapy to decrease tumor size as well as pain medications.