Colorectal Cancer While colorectal cancer remains as the second most common cancer in the United States, striking

140,000 people annually, early detection has made it curable in most cases. Predisposing factors for colon cancer are polyps, ulcerative colitis, Crohns disease, previous radiation therapy involving the pelvis (uterine and cervical cancer, seminoma of the testicle), and history of colon cancer in family members. There are two distinctive familial forms of colorectal cancer, one associated with polyps: familial adenomatous polyposis (FAP), and the other one without polyps: hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome types I and type II). In people with these hereditary syndromes the colon cancer has special characteristics. When a hereditary form of colorectal cancer is suspected genetic testing can be done on the patient and first degree relatives. In most cases the exact cause is unknown. What is known is that in populations who consume a diet high in fiber and low in fat, such as Africans, the incidence of colon cancer is extremely low. Industrialization and mass production of foods since the late 1800s has reduced the amount of fiber in the diet through several generations in Western countries. Along with the reduction of fiber, the bulk of stool has been reduced, the bacterial flora has changed and the transit through the colon is slower. Markers eaten with food reach the stomach in seconds, are out of the stomach in 3 hours, travel through the small bowel another 3 hours to reach the colon. The first traces of these markers can be seen in stool in 24 hours and the last of them in 7 days. Therefore, carcinogens produced from bacterial transformation of some chemical ingested with foods have a long time to act on the lining of the colon. The small bowel is protected from these effects because it is devoid of bacteria and transit is quite fast. When colorectal cancer arises from a simple polyp (without the above mentioned risk factors) the progression is quite slow, taking many years to produce symptoms such as blockage or bleeding. This is why surveillance colonoscopy is extremely important to detect polyps before they become cancerous. It is generally recommended to stat having colonoscopies at the age of 50, unless one has predisposing factors which moves the starting age to 40. By the fact that colorectal cancer is a slow growing process surgery is not an emergency. Although the instinctive reaction of most people is to have surgery as soon as the diagnosis is made it is best to take all the necessary time to refine the diagnosis and best prepare for surgery than rush to the operating room. Surgery remains the main therapy for the cure of colorectal cancer. In some cases of rectal cancer chemotherapy and radiation therapy is given before surgery (neoadjuvant therapy) to make the operation more effective and avoid complete removal of the rectum with the anus. In colon cancer chemotherapy may be necessary following surgery (adjuvant therapy) if the staging of the cancer after pathological analysis suggests potential spread of the tumor. Less than 5% of patients with rectal colorectal cancer will need a permanent colostomy, which is the exteriorization of the colon through the abdominal wall to allow for feces to be collected in a plastic pouch. Cure of colorectal cancer is currently achieved in 90% of patients with early stages and 50% of those with advanced disease.

The decision for chemotherapy and radiation is based on staging the cancer. Staging of the cancer is done by the pathologists who analyses the surgical specimen for depth of invasion of the tumor across the wall of the intestine, the presence of tumor cells in lymph nodes and presence of tumor cells at distant organs such as the liver or lung, these are called metastasis. Nowadays pathologist include in the report other factors that define the behavior of the tumor such as the degree of differentiation of the cells (well differentiated are close to normal, poorly differentiated are very abnormal), presence of tumor cells within blood and lymphatic vessels, and genetic markers (oncogenes). Technological advancements have recently made possible to do a staging before surgery in patients with rectal cancer. Because of the accessibility and the fixed location this preoperative staging can be done with either transrectal ultrasound or a special form of MRI (magnetic resonance imaging). Similar to the pathological staging system the depth of penetration of the tumor and the presence of enlarged lymph nodes is what determines the staging of the tumor. If the tumor is at a favorable stage the surgery can be limited to a local excision through the anus (if reachable) or through the abdomen. If the tumor is deemed at an unfavorable stage neoadjuvant therapy is given before surgery. The most common pathological staging system is the TNM (for tumors/nodes/metastases) system. Patients are assigned into a stage according with the American Joint Committee on Cancer (AJCC).

T - The degree of invasion of the intestinal wall Tis- cancer in situ (tumor present, but no invasion) T1 - invasion through submucosa into lamina propria (basement membrane invaded) T2 - invasion into the muscularis propria (i.e. proper muscle of the bowel wall) T3 - invasion through the subserosa T4 - invasion of surrounding structures (e.g. bladder) or with tumor cells on the free external surface of the bowel

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, i.e., deposits of tumor at distant organs such as the liver M0 - no metastasis M1 - metastasis present Stage Adjuvant Chemotherapy Recommended O Tis N0 M0 100% No I T1 or 2 N0 M0 93% No II A T3 N0 M0 85% Usually not II B T4 N0 M0 72% Usually not III A T3 N1 M0 83% Yes III B T4 N1 M0 64% Yes III C Any T N2 M0 44% Yes IV Any T Any N M1 8% Yes * This figures represent the percentage of survivors at 5 years following surgery and is based on a study of the National Cancer Institute's SEER database, looking at nearly 120,000 people diagnosed with colon cancer between 1991 and 2000. Newer forms of therapy have significantly improved these figures but there is not enough data to build survival tables yet FOLFOX is the most common chemotherapy regimen for treatment of colorectal cancer. It consists of 3 drugs: FOL Folinic acid (leucovorin) F Fluorouracil (5-FU) OX Oxaliplatin (Eloxatin) FOLFOX4: Adjuvant treatment in patients with stage III colon cancer is recommended for 12 cycles, 2 days each cycle, every 2 weeks. Side-effects of oxaliplatin treatment can potentially include: Neuropathy, both an acute, reversible sensitivity to cold and numbness in the hands and feet and a chronic, possibly irreversible foot/leg, hand/arm numbness, often with deficits in proprioception (the sense of the relative position of neighboring parts of the body) fatigue, nausea, vomiting, and/or diarrheal, ototoxicity (hearing loss) In addition, some patients may experience an allergic reaction to platinum-containing drugs. Bevacizumab (Avastin) is new class of drugs used to treat metastatic colorectal cancer, stage IV, called anti-angiogenic agents. These drugs slow down the process of angiogenesis or growth of blood vessels. Tumors derive oxygen and nutrients for their own growth through the growth of these new blood vessels. It is used in combination T N M 5 year survival*

with some of the chemotherapeutic agents mentioned above. In addition to the side effects already mentioned for FOLFOX, Avastin can produce: Bleeding or bruising easily, loss of hair, mouth sores, rash on the hands and feet, tingling or numbness in fingers or toes