Colorectal cancer

Colorectal cancer includes cancerous growths in the colon, rectum, anus, and appendix. It is the third most common form of cancer and the second leading cause of death among cancers in the United States.

Many colorectal cancers are thought to arise from polyps in the colon. These mushroom-like growths are usually benign, but some may develop into cancer over time.

Causes

Colorectal cancer is a disease resulting from mutations in epithelial cells of the gastrointestinal tract. Most of the known abnormalities involve the DNA which regulates cell growth. Though many of these effects are well known, there are likely environmental, hereditary, and viral causes for specific cell defects. Because the changes at the cell level may take years to develop into cancer, it is generally impossible to track the cause of specific cases of cancer. Thus efforts at prevention mostly focus on avoiding or identifying risk factors and early detection.

Risk Factors

Certain factors increase a person's risk of developing the disease. These include:

• Age. The risk of developing colorectal cancer increases with age
• History of cancer. Women who have had cancer of the ovary, uterus, or breast are at higher risk of developing colorectal cancer
• Familial adenomatous polyposis (FAP) carries 100% risk of developing cancer of the colon
• long-standing colitis ulcerosa or other chronic inflammatory diseases, very high risk after 25 years
• Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome
• Smoking. Smokers are more likely to die of colorectal cancer than non-smokers
• Diet. Some studies have shown that people who have diets high in fresh fruit and vegetables and low in red meat are at reduced risk of colorectal cancer.
• Virus. Exposure to some viruses (such as human papilloma virus) may be associated with colorectal cancer
• Physical inactivity. People who are physically active are at lower risk of developing colorectal cancer.

Symptoms

Symptoms of colorectal cancer include

• Change in bowel habits.
• Blood in stools.
• Unexplained weight loss.
• symptoms of anemia including tiredness, malaise, pallor

It is also possible that there will be no symptoms at all. This is one reason why screening for the disease is recommended.

Diagnostics, Screening and Monitoring

Colorectal cancer can take many years to develop and early detection of colorectal cancer greatly improves the chances of a cure. Therefore, screening for the disease is recommended in individuals who are at increased risk. There are several different tests available for this purpose.

• Digital rectal exam (DRE): The doctor inserts a lubricated, gloved finger into the rectum to feel for abnormal areas.
• Fecal Occult Blood Test (FOBT): A test for blood in the faeces.
• Sigmoidoscopy: A lighted probe (sigmoidoscope) is inserted into the rectum and lower colon to check for polyps and other abnormalities.
• Colonoscopy: A lighted probe called a colonoscope is inserted into the rectum and the entire colon to look for polyps and other abnormalities that may be caused by cancer. A colonoscopy has the advantage that if polyps are found during the procedure they can be immediately removed. Tissue can also be taken for biopsy.
• Double contrast barium enema (DCBE): An enema containing barium, which helps the outline of the colon and rectum stand out on X-rays, is given to the patient. The doctor then takes a series of X-rays of the colon and rectum.
• Computed axial tomography is used to determine the degree of spread of cancer. Though it is not generally used for screening, some cancers are found in CAT scans given for other reasons.
• Blood tests: Measurement of the patients blood for elevated levels of certain proteins can give an indication of tumor load. In particular, high levels of carcinoembryonic antigen CEA in the blood can indicate metastasis of adenocarcinoma.

Pathology

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 types include squamous cell carcinoma, etc.

Staging

Colon cancer staging is an estimate of the condition of a particular cancer for patient diagnostic and research purposes.

The systems for staging colorectal cancers largely depend on the extent of local invasion, the degree of lymph node involvement and whether there is distant metastases or not.

The most common currently used system for staging is the TNM system, though some doctors still use the older Duke's system. The TNM system assigns a number :

• T - The degree of invasion of the intestinal wall
  • T0 - no evidence of tumor
  • Tis- cancer in situ (tumor present, but no invasion)
  • T1 - tumor present but minimal invasion
  • T2 - invasion into the submucosa
  • T3 - invasion into the muscularis propria
• N - the degree of lymphatic node involvement
  • N0 - no lymph nodes involved
  • N1 - one to three nodes involved
  • N2 - four or more nodes involved
• M - the degree of metastasis
  • M0 - no metastasis
  • M1 - metastasis present

for example for a patient with no disease would be T0N0M0.

The stage of a cancer is usually quoted as a number I,II,III,IV derived from the TNM value grouped by prognosis; a higher number indicates a more advanced cancer and a likely worse outcome.

AJCC stage groupings

• Stage 0
  • Tis, N0, M0
• Stage I
  • T1, N0, M0
  • T2, N0, M0
• Stage IIA
  • T3, N0, M0
• Stage IIB
  • T4, N0, M0
• Stage IIIA
  • T1, N1, M0
  • T2, N1, M0
• Stage IIIB
  • T3, N1, M0
  • T4, N1, M0
• Stage IIIC
  • Any T, N2, M0
• Stage IV
  • Any T, Any N, M1

Treatment

The treatment depends on the staging of the cancer. When colorectal cancer is caught at early stages (with little spread) it can be curable. However when it is detected at later stages (when distant metastases are present) it is less likely to be curable.

Surgery remains the primary treatment while chemotherapy and/or radiotherapy may be recommended depending on the individual patient's staging and other medical factors.

Surgery

Surgical treatment is by far the most likely to result in a cure of colon cancer if the tumor is localized. The procedure consists of removal of the section of colon containing the tumor leaving sufficient margins to reduce likelihood of re-growth. If possible, the remaining parts of colon are anastomosed together to create a functioning colon. In cases when anastomosis is not possible, a stoma (artificial orifice) is created. Surgery is generally not offered if significant metastasis are present.

Laparoscopic assist resection of the colon for tumour can reduce the size of painful incision and minimize the risk of infection.

As with any surgical procedure, colorectal surgery can in rare cases result in complications. These may include Infection, Abscess, Fistula or Bowel obstruction.

Radiation therapy

Radiation therapy is used to kill tumor tissue before surgery or when surgery is not indicated. It is also used to sterilize the margins after surgery is performed. Sometimes chemotherapy agents are used to increase the effectiveness of radiation by sensitizing tumor cells if present.

Chemotherapy

Chemotherapy is used to reduce the likelihood of metastasis developing, shrink tumor size, or slow tumor growth. Chemotherapy often applied after surgery (adjuvant), before surgery (neo-adjuvant), or as the primary therapy if surgery is not indicated (palliative). The treatments listed here have been shown in clinical trials to improve survival and/or reduce mortality and have been approved for use by the US Food and Drug Administration.

• Standard first line Chemotherapy
  • 5-fluorouracil (5Fu)
  • Leucovorin
• Alternate first line Chemotherapy
  • capecitabine (Xeloda) - Roche Laboratories
• Other first line agents
  • Irinotecan (Camptosar, CPT-11) -
  • Oxaliplatin (Eloxatin) - Sanofi-Synthelabo

• Second Line Chemotherapy
  • cetuximab (erbitux)
  • bevacizumab (Avastin) - Genentech

Experimental Therapies

The treatments listed here are currently undergoing clinical trials and are not approved for general use by the US Food and Drug Administration.

• oxaliplatin (Eloratin) - Sanofi-Synthelabo

Alternative Therapies

The agents listed here are not proven in clinical trials but may be considered to have anti-colon cancer properties in in-vitro studies, the popular press, folk medicine or other sources.

• Ginger
• Circumin (Tumeric anti-angiogenesis factor)
• Mistletoe Extract (as solid tumor reducer)
• Acupuncture (symptom reduction)

Support Therapies

Cancer diagnosis very often results in an enormous change in the patients sociological wellbeing. Various support resources are available from, hospitals and other agencies which provide counseling, social service support, cancer support groups, and other services. These services help to mitigate some of the difficulties of integrating a patients medical complications into other parts of their life.