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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 distinctivefamilial 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 hereditarysyndromes 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 Westerncountries. 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 eatenwith 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, carcinogensproduced 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 asblockage or bleeding. This is why surveillance colonoscopy is extremely important todetect 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 isnot 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 rectumwith 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 willneed 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.

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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 ofinvasion 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 definethe 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 ofMRI (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 isdeemed 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 wallTis- 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

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N - The degree of lymphatic node involvement

N0 - no lymph nodes involved

N1 - one to three nodes involvedN2 - four or more nodes involved

M - The degree of metastasis, i.e., deposits of tumor at distant organs such as the liver

M0 - no metastasisM1 - metastasis present

Stage T N M 5 year

survival*

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% YesIII 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 atnearly 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 theirown growth through the growth of these new blood vessels. It is used in combination

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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, tinglingor numbness in fingers or toes