Colorectal Cancer
last authored: Sept 2009, David LaPierre
Introduction
Colorectal cancer is the third most common cancer and the second most common cause of cancer deaths in men and women. Incidence increases dramatically after age 50. 1:18 men and 1:16 women (I think) develop colon cancer.
Industrialized countries are at greatest risk for colorectal cancer, with the notable exception of Japan.
Approximately 50% of cancers are between the rectum and the splenic flexture, with rates of more proximal cancers increasing with age.
Screening
Early detection through screening programs has the capacity to render this disease almost always curable, as well as reduce its incidence through the removal of premalignant adenomas.
Nova Scotia is beginning a Colon Cancer Screening Program.
Screening stratification:
Average risk
High risk: one first-degree relative with cancer, or with adenomatous polyp at age <60. Start screening at age 40, or 10 years younger than the index case. If two or more first-degree relatives with polyp or colon cancer at any age, start at age 40, and screen every 5 yea
colonoscopy every 5 years.
Fecal occult blood testing (FOBT) is good for the general population, due to its ease and cost. Recommended every two years. However, false positives can be due to many causes, including red meat, licorice, and other things. False negatives are also possible.
Air constrast barium enema (BE) is recommended every 5 years. False
Flexible sigmoidoscopy can be done up to the splenic flexture.
Periodic screeing should be done for people after age 50, flexible sigmoidoscopy, barium enema, or colonoscopy.
Colonoscopy should be done every 10 years. Gold standard. There is about a 10% miss rate
CT colonography and stool-based DNA testing show promise but are yet to be endorsed. Screeing for high risk people depend on risk factor but generally rely on colonoscopy at a younger age and at more frequent intervals. Surveillance is recommended for everyone with inflammatory bowel disease.
Virtual colonoscopy using CT can be done.
The Case of...
Causes and Risk Factors
Age is an important determinant of risk. Colorectal cancer is extremely uncommon in people under the age of 35, except in those with genetic syndromes such as Famililar Adenomatous Polyposis Coli (FAP) or Hereditary Non-Polyposis Coli Colorectal Cancer (HNPCC). Factors associated with decreased risk include physical activity and vegetable consumption. Smoking has been linked to colon cancer, among many others. People with inflammatory bowel disease, acromegaly, and potentially diabetes have higher rates of colorectal cancer.
Diet and obesity
There has been no direct cause identified.
onsumption of red meat and alcohol, and
Pathophysiology
Polyps can simply be hyperplastic or can be adenomas.
The majority of colorectal cancers are believed to arise from benign adenomas called polyps. While in the US, incidence of polyps averages 50% for older adults, only a minority of polyps progress to colon cancer. Observational studies suggest progression takes at least 10 years from normal tissue to cancer.
Of the adeomas, size (over 1 cm) and cell type (villous) increases risk.
Cancers can be sessile (flat) or pedunculated (stalklike), or can appear as stricures, fungated masses, or ulcerating masses.
Colorectal carcinogenesis is a well-theorized process involving the step-wise accumulation of various oncogenes and tumour suppressor genes. These include K-ras, APC/beta-catenin, DCC, SMAD4, SMAD2, p53, and DNA repair genes such as hMLH1 in some cases.
HNPCC is associated with mutations in DNA repair genes, and the microsatellite instability pathway. Important genes include hMSH2, hMLH1, hPMS1, and hPMS2. These cancers progress much faster, in perhaps 1-3 years.
Three family members with HNPCC cancer, 2 successive generations with cancer, and one perosn below 50 years. HNPCC is also associated with endometrium, SI, uterues, ovarian, renal ureter and pelvis, pancreas.
Screen folks whose family meets Amsterdam criteria for HNPCC with colonoscopy every 1-2 years.
For people with 1-2 adenomas
FAP: sigmoidoscopy at 10-12; once found, colectomy
AAPC attenuated adenopolyposis coli: on right side: colonoscopy at 16
Gardner syndrome: FAP can cause cancer at the biliary ampulla.
Signs and Symptoms
The majority of colorectal cancers are asymptomatic until advanced. Gastrointestinal bleeding is the most common symptom, and may appear as occult bleeding, hematochezia, or iron deficiency anemia. Other common symptoms can include abdominal pain from obstruction or invasion, change in bowel habits, or nonspecific symptoms of maligancy including anorexia, fatigue, or weight loss.
- history
- physical exam
History
Physical Exam
Investigations
- lab investigations
- diagnostic imaging
Lab Investigations
Diagnostic Imaging
Differential Diagnosis
Everyone with symptoms suggestive of colorectal cancer should undergo screeing by colonoscopy, which has greater accuracy at detecting early cancers than barium enemas.
Carcinoembryonic antigen (CEA) levels are measured preoperatively to establish a baseline to determine treatment success.
If cancer is found, an abdominal and pelvic CT is done to look for hepatic and lymphatic spread.
Treatments
Surgery alone is curative for early stage cancer. Surgery and postoperative radiation and 5-fluorocil, with or without leukovorin, are of benefit to people with stage II or III cancers. Palliative surgery, radiation, and chemotherapy are all used in treatment of stage IV cancers.
Consequences and Course
Survival is based on stage of disease. Almost 50% of patients are diagnosed at stage III or IV.
Obstruction is more common with distal malignancy, as the stool is harder, the lumen is smaller, and growths tend to grow in a napkin ring pattern vs polyp.
The Case of...
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