Colon cancer
Definition
Cancer of the colon is the disease characterized by the development of malignant cells in the lining or epithelium of the first and longest portion of the large
Colon cancer
intestine. Malignant cells have lost normal control mechanisms governing growth. These cells may invade surrounding local tissue or they may spread throughout the body and invade other organ systems.
Synonyms for the colon include the large bowel or the large intestine. The rectum is the continuation of the
large intestine into the pelvis that terminates in the anus.
Description
The colon is a tubular organ beginning in the right lower aspect of the abdomen. Anatomically, it ascends on
the right side of the abdomen, traverses from right to left in the upper abdomen, descends vertically down the left
side, takes an S-shaped curve in the lower left abdomen, and then flows into the rectum as it leaves the abdomen
for the pelvis. These portions of the colon are named separately though they are part of the same organ.
• cecum, the beginning of the colon
• ascending colon, the right vertical ascent of the colon
• transverse colon, the portion traversing from right to left
• descending colon, the left vertical descent of the colon
• sigmoid colon, the s-shaped segment of colon above the pelvis
These portions of the colon are recognized anatomically based on the arterial blood supply and venous and
lymphatic drainage of these segments of the colon. Lymph, a protein-rich fluid that bathes the cells of the
body, is transported in small channels known as lymphatics that run alongside the veins of the colon. Lymph
nodes are small filters through which the lymph travels on its way back to the blood stream. Cancer can spread
elsewhere in the body by invading the lymph and vascular systems. Therefore, these anatomic considerations
become very important in the treatment of colon cancer.
The small intestine is the continuation of the upper gastrointestinal tract responsible for the transport of
ingested nutrients into the body. The waste left after the small intestine has completed absorption of nutrients
amounts to a few liters, (about the same as quart), of material per day and is directly delivered to the colon, (at
the cecum), for processing. Physiologically, the colon is responsible for the preservation of fluid and electrolytes
as it propels the increasingly solid waste towards the rectum and anus for excretion.
When cells lining the colon become malignant, they first grow locally and may invade partially or totally
through the wall of the bowel and even into adjacent structures and organs. In the process, the tumor can penetrate
and invade the lymphatics or the capillaries locally and it gains access to the circulation. As the malignant cells work their way to other areas of the body, they again become locally invasive in the new area to which
they have spread. These tumor deposits, originating from the colon primary tumor, are then known as metastases.
If metastases are found in the regional lymph nodes from the primary, they are known as regional metastases, or
regional nodal metastases. If they are distant from the primary tumor, they are known as distant metastases. The
patient with distant metastases has systemic disease. Thus the cancer originating in the colon begins locally
and, given time, can become systemic in its extent. By the time the primary tumor is originally detected
it is usually larger than one cm, (about 3/8 inches), in size and has over a million cells. This amount of growth
itself is estimated to take about three–seven years. Each time the cells double in number, the size of the tumor
quadruples. Thus like most cancers, the part that is identified clinically is later in the progression than would be
desired and screening becomes a very important endeavor to aid in earlier detection of this disease.
Demographics
There are about 94,000 cases of colon cancer diagnosed per year in the United States. Together, colon and
rectal cancers account for 10% of cancers in men and 11% of cancers in women. It is the second most common
site-specific cancer affecting both men and women.
Nearly 48,000 people died from colon cancer in the United States in 2000. In recent years the incidence of
this disease is decreasing very slightly, as has the mortality rate. It is difficult to tell if the decrease in mortality
reflects earlier diagnosis, less death related to the actual treatment of the disease, or a combination of both factors.
Cancer of the colon is thought to arise sporadically in about 80% of those who develop the disease. 20% of
cases are thought to have genetic predisposition that ranges from familial syndromes affecting 50% of the offspring
of a mutation carrier, to a risk of 6% when there is just a family history of colon cancer occurring in a first
degree relative. Development of colon cancer at an early age, or at multiple sites, or recurrent colon cancer suggests
a genetically transmitted form of the disease as opposed to the sporadic form.
Causes and symptoms
Causes
Causes of colon cancer are probably environmental in the sporadic cases, (80%), and genetic in the heredity
predisposed cases (20%). Since malignant cells have a changed genetic makeup, this means that in 80% of
cases, the environment spontaneously induces change, whereas in those born with a genetic predisposition, they
are either destined to get the cancer or it will take less environmental exposure to induce the cancer. Exposure
to agents in the environment that may induce mutation is the process of carcinogenesis and is caused by agents
known as carcinogens (cancer-causing agents). Specific carcinogens have been difficult to identify; however,
dietary factors seem to be involved. Colon cancer is more common in industrialized nations and diets high in fat, red meat, total calories, and alcohol seem to predispose. Diets high in fiber are associated with a decreased risk. The mechanism for protection by high-fiber diets may be related to less exposure of the colon lining to carcinogens from the environment, as the transit time through the bowel is faster with a highfiber diet than it is with a low fiber diet.
Age plays a definite role in the predisposition to colon cancer. Colon cancer is uncommon before age 40.
This incidence increases substantially after age 50 and doubles with each succeeding decade.
There is also a slight increase risk for colon cancer in the individual who smokes.
Patients who suffer from inflammatory diseases of the colon known as ulcerative colitis and Crohn’s colitis
are also at increased risk.
As for genetic predisposition, on chromosome 5, there is a gene called the APC gene associated with the familial
adenomatous polyposis syndrome. There are multiple different mutations that occur at this site, yet they all cause a
defect in tumor suppression that results in early and frequent development of colon cancer. This genetic aberration
is transmitted to 50% of offspring and each of those affected will develop colon cancer, usually at an early age. There is another syndrome, hereditary non-polyposis colon cancer (also known as Lynch syndrome), related to mutations in any of four genes responsible for DNA mismatch repair.
In patients with colon cancer, the p53 gene is mutated 70% of the time. When the p53 gene is mutated and ineffective, cells with damaged DNA escape repair or destruction. This allows for the damaged cell to perpetuate itself, and continued replication of the damaged DNA may lead to tumor development. Though these syndromes have a very high incidence of colon cancer, family history without the syndrome is also a substantial risk factor.
When considering first-degree relatives, history of one with colon cancer raises the baseline risk of 2% to 6%. (Most physicians think that this baseline is about 4%.) The presence of a second raises the risk to 17%. The development of polyps of the colon almost always precedes the development of colon cancer by five or more years. Polyps are benign growths of the colon lining. They can be unrelated to cancer, precancerous, or malignant. Polyps, when identified, are removed for diagnosis. If the polyps are benign, the patient should undergo careful surveillance for the development of more polyps or the development of colon cancer.
Symptoms
Colon cancer causes symptoms related to its local presence in the large bowel or by its effect on other
organs if it has spread. These symptoms may occur alone or in combination:
• a change in bowel habit
• blood in the stool
• bloating, persistent abdominal distention
• constipation
• a feeling of fullness even after having a bowel movement
• narrowing of the stool—so-called ribbon stools
• persistent, chronic fatigue
• abdominal discomfort
• unexplained weight loss
• and, very rarely, nausea and vomiting
Most of these symptoms are caused by the physical presence of the tumor mass in the colon. Similar symptoms
can be caused by other processes; these are not absolutely specific to colon cancer. The key is recognizing
that the persistence of these types of symptoms without ready explanation should prompt the individual to
seek medical evaluation.
Many of the symptoms are understood by remembering that the colon is a tubular conduit. If a tumor develops, as it reaches a certain size it will begin to cause symptoms related to the obstruction of that conduit. In addition, the tumor commonly oozes blood that is lost in the stool. (Often, this blood is not visible.) This phenomenon
results in anemia and chronic fatigue. Weight loss is a late symptom, often implying substantial obstruction
or the presence of systemic disease.
Diagnosis
Screening
Of all of the major cancers, only colorectal cancer can be prevented by screening. In all other cancers
(breast and prostate, for example), screening tests look for small, malignant lesions. Screening for colorectal
cancers, however, is the search for pre-malignant, benign polyps. This screening can be close to 100% effective in
preventing cancer development, not just in detecting small cancers.
Screening involves physical exam, simple laboratory tests, and the visualization of the lining of the colon. The
ways to visualize the colon epithelium are with x rays (indirect visualization), and endoscopy (direct visualization).
The physical examination involves the performance of a digital rectal exam (DRE). The DRE includes manual
examination of the rectum, anus and the prostate. During this examination, the physician examines the anus
and the surrounding skin for hemorrhoids, abscesses, and other irregularities. After lubricating the gloved finger
and anus, the examiner gently slides the finger into the anus and follows the contours of the rectum. The examiner
notes the tone of the anus and feels the walls and the edges for texture, tenderness and masses as far as the
examining finger can reach. At the time of this exam, the physician checks the stool on the examining glove with a
chemical to see if any occult (invisible), blood is present. At home, after having a bowel movement, the patient is
asked to swipe a sample of stool obtained with a small stick on a card. After 3 such specimens are on the card,
the card is then easily chemically tested for occult blood also. (The stool analysis mentioned here is known as a
fecal occult blood test, or FOBT, and, while it can be helpful, it is not 100% accurate—only about 50% of cancers
are FOBT-positive.) These exams are accomplished as an easy part of a routine yearly physical exam.
Proteins are sometimes produced by cancers and these may be elevated in the patient’s blood. When this
occurs, the protein produced is known as a tumor marker.
There is a tumor marker for some cancers of the colon; it is known as carcinoembryonic antigen, or CEA. Unfortunately, this protein may be made by other adenocarcinomas as well, or it may not be produced by a particular colon cancer. Therefore, screening by chemical analysis for CEA has not been helpful. CEA has been helpful when used in a follow-up role for patients treated for colon cancer if their tumor makes the protein.
Indirect visualization of the colon may be accomplished by placing barium through the rectum and filling
the colon with this compound. Barium produces a white contrast image of the lining of the colon on x ray and
thus the contour of the lining of the colon may be seen. Detail can be increased if the barium utilized is thinned
and air also introduced. These studies are known as the barium enema (BE), and the double contrast barium
enema (DCBE).
Direct visualization of the lining of the colon is accomplished using a scope or endoscope. The physician
introduces the instrument through the rectum and passes it proximally, visualizing the colon epithelium in the
process. Older, shorter scopes were rigid. Today, utilizing fiberoptic technology, the scopes are flexible and can
reach much farther. If the left colon only is visualized, it is called flexible sigmoidoscopy. When the entire colon
is visualized, the procedure is known as colonoscopy.
Unlike the indirect visualizations of the colon (the BE and the DCBE), the endoscopic screeenings allow the
physician to remove polyps and biopsy suspicious tissue. (A biopsy is a removal of tissue for examination by a
pathologist.) For this reason, many physicians prefer endoscopic screening. All of the visualizations, the BE,
DCBE, and each type of endoscopy require pre-procedure preparation (evacuation) of the colon.
The American Cancer Society has recommended the following screening protocol for those of normal risk
over 50 years of age:
• yearly DRE with occult blood in stool testing
• flexible sigmoidoscopy at age 50
• flexible sigmoidoscopy repeated every 5 years
Many physicians, however, recommend full colonoscopy every five to seven years. Screening evaluations
should start sooner for patients who have predisposing factors, such as family history, history of polyps, or a
familial syndrome.
Evaluation of patients with symptoms
For those whose symptoms prompt them to visit their physician, and if their symptoms could possibly be related
to colon cancer, the entire colon will be inspected. The combination of a flexible sigmoidoscopy and double contrast
barium enema may be performed but the preferred evaluation of the entire colon and rectum is that of complete
colonoscopy. Colonoscopy allows direct visualization, photography, as well as the opportunity to obtain a biopsy of
any abnormality visualized. If, for technical reasons, the entire colon is not visualized endoscopically, a double contrast barium enema should complement the colonoscopy.
The diagnosis of colon cancer is actually made by the performance of a biopsy of any abnormal lesion in
the colon. When a tumor growth is identified, it could be either a benign polyp (or lesion) or a cancer; the biopsy
resolves the issue. The endoscopist may take many samples so as to exclude any sampling errors. If the patient presents with advanced disease, or has advanced disease at the time of diagnosis, areas where the tumor has spread (such as the liver) may be amenable to biopsy. Such biopsies are usually obtained using a special needle under local anesthesia.
Once a diagnosis of colon cancer has been established by biopsy, in addition to the physical exam, studies
will be performed to assess the extent of the disease. Blood studies include a complete blood count, liver function
tests, and a CEA. Imaging studies will include a chest x ray and a CAT scan (computed tomography
scan) of the abdomen. The chest x ray will determine if there is spread to the lung, the CAT scan will evaluate
potential spread to the liver as well as any local invasive characteristics of the primary tumor. If the patient has
any neurologic symptoms, a CAT scan of the brain will be performed, and if the patient is experiencing bone
pain, a bone scan will also be performed.
Treatment team
The surgeon and the medical oncologist each have a role in therapy that is dictated by the degree of progres-
sion of the disease. A radiation oncologist may also play a role on the team; however, radiation treatment is rare in
colon cancer.
Clinical staging, treatments, and prognosis
Clinical staging
Once the diagnosis has been confirmed by biopsy, the clinical stage of the cancer is assigned. Using the
characteristics of the primary tumor, its depth of penetration through the bowel, and the presence or absence of
regional or distant metastases, stage is derived. Often, the depth of penetration through the bowel or the presence of
regional lymph nodes can’t be assigned before surgery.
Colon cancer is assigned stages I through IV, based on the following general criteria:
• Stage I: the tumor is confined to the epithelium or has
not penetrated through the first layer of muscle in the
bowel wall.
• Stage II: the tumor has penetrated through to the outer
wall of the colon or has gone through it, possibly invading
other local tissue.
• Stage III: Any depth or size of tumor associated with
regional lymph node involvement.
• Stage IV: any of previous criteria associated with distant
Treatments
SURGERY. Surgical removal of the involved anatomic segment of colon (colectomy) along with its blood supply and regional lymph nodes is the primary therapy for colon cancer. Usually, on the basis of the blood supply,
the partial colectomies are separated into right, left, transverse, or sigmoid. The removal of the blood supply at its origin along with the regional lymph nodes that accompany it assures an adequate margin of normal colon on either side of the primary tumor. When the cancer lies in a position such that the blood supply and lymph drainage lies between two of the major vessels, both vessels are taken to assure complete radical resection,
or removal (extended radical right or left colectomy).
If the primary tumor penetrates through the bowel wall, any tissue adjacent to the tumor extension is also taken if feasible. Surgery is used as primary therapy for stages I through III colon cancer unless there are signs that local invasion will not permit complete removal of the tumor, as may occur in advanced stage III tumors. However, this
circumstance is very rare, and occurs in less than 2% of all colon cancer cases.
After the resection is completed, the ends of the remaining colon are reconstructed; the hook-up is called
an anastomosis. Once healing has occurred, there may be a slight increase in the frequency of bowel movements.
This effect usually lasts only for several weeks. Most patients go on to develop completely normal
bowel function.
Occasionally, the anastomosis would be risky and cannot be performed. (Most commonly, this occurs when the bowel could not be adequately evacuated in an emergency circumstance due to bowel obstruction.) When the
anastomosis cannot be performed, a colostomy is performed instead. A colostomy is performed by bringing
the end of the colon through the abdominal wall and sewing it to the skin. The patient will have to wear an
appliance (a bag) to manage the stool. The colostomy may be temporary and the patient may undergo a hookup
at a later, safer date, or the colostomy may be permanent. In most cases, emergent colostomies are not reversed and are permanent.
Clinical trials
Clinical trials are scientific studies in which new
therapies are compared to current standards in an effort
to identify therapies that give better results.
Agents being tested for efficacy in patients with
advanced disease include oxaliplatin and CPT-11.
Please see reference below for current information available
from the National Cancer Institute regarding these
clinical trials.
Prevention
There is not an absolute way of preventing colon
cancer. Still, there are steps an individual can take to dramatically
lessen the risk or to identify the precursors of
colon cancer so that it does not manifest itself. The
patient with a familial history can enter screening and
surveillance programs earlier than the general population.
High-fiber diets and vitamins, avoiding obesity, and
staying active lessen the risk. Avoiding cigarettes and
alcohol may be helpful. By controlling these environmental
factors, an individual can lessen risk and to this
degree prevent the disease.
By undergoing appropriate screening when uncontrollable
genetic risk factors have been identified, an
individual may be rewarded by the identification of
benign polyps that can be treated as opposed to having
these growths degenerate into a malignancy.
Special concerns
Polyps are growths of the epithelium of the colon.
They may be completely benign, premalignant or cancerous.
The association of colon cancers in patients with
certain types of polyps is such that it is thought that many
polyps begin as a benign growth and later acquire malignant
characteristics. There are two types of polyps,
pedunculated and sessile. This terminology comes from
their appearance; those that are pedunculated are on a
stalk like a mushroom, and the sessile polyps are broad
based and have no stalk. Unless a pedunculated polyp
gets large, malignant potential is very small. This type
may also be easily removed at colonoscopy, by a snaring
technique. (A snare is like a lasso introduced through the
endoscope to encircle the polyp at its base and amputate
it.) The sessile polyp is also known as a villous adenoma
and as many as 1/3 of these harbor a malignancy. Therefore,
the villous adenoma is considered premalignant.
Sessile polyps may or may not be able to be managed
with the colonoscope and may need surgical removal
because of their pre-malignant nature.
Polyps commonly present with occult blood in the
stool. Since they are associated with the development of
cancer, patients who have developed polyps need to enter
a program of careful surveillance.
There is an occasional patient who develops a pattern
of metastatic disease that is isolated to either the liver or the
lung and the deposit appears to be solitary. When patients
have this type of pattern of metastatic disease, especially if
there has been a long interval between the primary management
and the development of metastasis, they may be considered
for surgical resection of the isolated metastasis to
effect a cure. In carefully selected patients, long-term survival
approaching 20% has been achieved.
When a patient has developed metastatic cancer in
the liver alone, a technique of administering chemotherapy
directly to the liver is sometimes considered. This is
called hepatic arterial infusion and requires the placement
of a special device into the artery supplying the
liver. This method of utilizing chemotherapy has been
helpful in carefully selected patients only, and currently
is not used as a cure.
Random Posts
Leave a Reply
You must be logged in to post a comment.