COLON AND RECTAL CANCER TREATMENT INFORMATION

What is the Colon & Rectum?

The colon and the rectum are parts of the digestive system. A cancer originating in the colon, or
rectum, makes up this group. The colon and rectum are continuous, but the differing treatments
for cancers arising in different parts of the intestinal tract makes it useful to distinguish them by
location. The colon is also known as the "large intestine," and starts where the small intestine
ends, in the area of the lower right portion of the abdomen. The area where the small intestine
becomes the colon is called the"cecum," and the fingerlike "appendix" is located nearby. The
colon is shaped like an arch. The right leg of the arch is called the "ascending colon," and runs up
the right side of the abdomen, bending under the liver.

The arching portion is the "transverse colon," and it runs under the pancreas and stomach, ending
under the spleen. The left portion of the arch is the "descending colon" running down the left
side of the abdomen. The descending colon connects to the "sigmoid colon," which is shaped like
an "S," and moves toward the center of the pelvis. The sigmoid colon joins the "rectum" at the
"recto-sigmoid" junction; the rectum is about 7 inches long. The rectum becomes the"anal canal"
at the "ano-rectal" junction, this canal is about 2 inches long and terminates as the "anus," where
bowel movements actually leave the body. Since the lining cells inside the colon and rectum are
similar, and produce mucous, the cancers that arise in this part of the digestive system are also
similar, and considered together. However, the cells lining the inside of the anal canal are
different, so different cancers arise there, and this is a separate topic.

The colorectum has a rich blood supply ; this is needed to absorb nutrients from the bowel and
get them into the bloodstream. The "mesenteric" arteries arteries are large branches off of the
body's main artery (the "aorta"), and provide fresh blood with oxygen and nutrients to the bowel.
If that blood supply is cut off, the bowel will become "infarcted" (shut off from fresh blood),
painful, and ultimately die ("necrosis"). This will allow the bacteria normally within the bowel,
which solidify stool, to escape into the sterile abdomen causing infection ("peritonitis"). The
bowel can become infarcted from a blood clot in the mesenteric blood vessels, becoming twisted
upon itself ("torsion"), telescoping in upon itself ("volvulus"), or by a growing tumor.

Blood is drained from the bowel by the "mesenteric" veins, which send that blood through the
liver ("portal vein") to extract and process digested fats, proteins and sugars. The processed
blood is then returned to the heart by the large vein draining the liver ("inferior vena cava"). The
point is that infection or cancer cells can travel from the bowel up into the liver, and from there
through the regular bloodstream to other areas . If a cancer spreads ("metastasizes") via the
bloodstream, it is called "hematogenous metastasis." Initially, single cancer cells traveling in the
bloodstream will "seed" other areas ("micrometastasis"), and eventually (if unchecked) grow into
large tumors there.

The bowel also has within it a series of "patches" of clumps of White Blood Cells, called
"Peyer's Patches." These are called "lymphoid tissue," much like the tonsils in the throat, and
help fight infection in the bowel. The bowel has an inner lining of specialized cells (see below)
called the "mucosa," but it's walls are made of "muscle layers." These muscle layers allow the
bowel to move ("peristalsis") so digesting food is passed through. Just underneath the delicate
mucosal inner lining, but before the muscle layers, is an area of loose connective tissue called the
"submucosa." Within the submucosa exists a network of "lymph channels," which collect the
"tissue fluid" that has migrated out from the blood vessels, to bathe and nourish each cell.

These lymph channels drain to pea-sized "lymph nodes" around the bowel, which are filled with
White Blood Cells. The purpose of the lymph nodes is to filter and purify the blood, trapping
germs and cancer cells. When lymph nodes are invaded by infection or cancer, they swell
("lymphadenopathy") . Normal "lymph fluid" is eventually returned back into the blood stream,
after purification by the lymph nodes. The importance of this is that the lymph system can act as
a conduit for spread of infections or cancer ("lymphogenous metastasis"). Commonly, but not
always, the local lymph nodes are involved before more distant sites.

What is Colorectal Cancer?

The cells lining the inner colon and rectum are called "columnar epithelial cells," and also
"goblet cells" which secrete mucous to help keep the stool soft. These cells invaginate (fold upon
themselves) to form glands, and the type of cancer which most commonly arises from glands is
called "adenocarcinoma." As with all cells in the body, the production of new cells lining the
intestine is under tight control from the "genes" within each cell, which are themselves composed
of the basic genetic material "DNA." In the growing child, the cells divide quickly to form the
enlarging intestines, but in the adult cells are only produced to replace those that die of injury or
lost to old age. Colon cancer, like any cancer, starts in a single cell . This cell loses control of it's
division and then starts to reproduce in a haphazard, uncontrolled manner to form a "tumor." A
tumor merely means a swelling, it can be caused by most anything and is not necessarily cancer.

A "benign" tumor, also called a "polyp" within the intestines, only grows within it's local area; it
cannot go to other areas of the body and so is not cancer. In contrast, a "malignant" tumor is
capable of spreading to any area of the body, it is cancer. This process of spread is called
"metastasis." Sometimes previously benign tumors can become malignant over time, this process
is called "malignant degeneration" and happens in some polyps. Most polyps, however, will
never become cancerous. If cancer does arise and is not effectively treated, the will ultimately
spread to other crucial body areas and kill the patient. Advanced colon cancer most often kills by
causing anemia, debility, infection, and organ failure. This is why it is critical to diagnose and
treat any cancer as early as possible, when the chances for successful treatment are highest.

How common is Colorectal Cancer?

The American Cancer Society estimates that about 114,500 new cases of colon cancer and
42,880 new cases of rectal cancer will be diagnosed in 2008. Over their lifetimes, 5% of
Americans will develop a colo-rectal cancer at some point. The disease is rare (3% of cases) in
those under 40 years old. Men are effected slightly more often than women. The disease is more
common in the Western World than in Asia. However, if an Asian person moves to the United
States, there chance for getting colon cancer increases. In the United States, the highest risk areas
are in the Northeast, and the lowest in the Southwest. The incidence of colo-rectal cancer has
been going up over the past 3 decades, but the death rate peaked in 1985, owing to earlier
detection and better treatments.
How and Where Does Colorectal Cancer Start?

It usually starts from a polyp, which is a protrusion of gut tissue which starts as being non-
cancerous. These polyps are often screened for, and may be removed before becoming
cancerous. If a polyp is less than 1 cm. across, it has only a 1% chance of being cancerous, but if
it is larger than 2 cm. across, the chance of cancer rises to almost 50% . Polpys become much
more common as we grow older, over 80% of people over 70 years old have at least one polyp.
The risk for developing Colorectal cancer is increased with:

1) A high fat, low fiber diet. (The NCI noted 40 studies making this association). This is thought
due these foods taking longer to pass through the colon, thus allowing more contact with cancer-
inducing chemicals ("carcinogens") in these foods. In contrast, high fiber foods stimulate the
colon to move food through quickly, and lessen the chance for polyps to form. Colo-rectal cancer
is rare in societies that eat mostly fruits and vegetables, and the vitamins in these (especially
vitamins A and E ) may be protective. This is a reason that colon cancer is rarer in the Far East
where less dietary fat is consumed.
2) Family Predisposition Certain cancers, namely colo-rectal, breast, uterine and ovarian, tend to
occur with alteration of the same genes, known as the "family cancer syndrome" genes. While
not all people with these inherited genes get cancer, many do. Around 15% of new patients with
colo-rectal cancer have close family members with disease.
3) Hereditary syndromes causing multiple polyps in the digestive tract. For example, 100% of
Familial Polyposis patients will get colon cancer if the colon isn't removed. In this condition,
there are thousands of polyps in the colon, and the more polyps, the greater the chances for a
cancerous one to arise. Other rarer syndromes include "Turcot's," where there are associated
brain tumors, and "Gardner's," with tumors in other glandular areas. The Peutz- Jeghers
syndrome has lots of polyps throughout the intestinal tract, but they are the more benign type
("hamartomas") and the risk of cancer is low.
4) Age older than 40 years . Younger patients rarely develop this cancer, but if so it tends to be
very aggressive. The average patient is 60 years old. This goes along with more polyp formation
as we get older, and a greater risk that the polyps will be abnormal ("dysplastic") with age.
5) Inflammatory bowel disease, especially ulcerative colitis (less in Crohn's). The risk of
developing colon cancer with ulcerative colitis is about 2% per year. In these conditions, there
are many more new intestinal cells being produced to replace those lost through inflammation
and infection. The more new cells formed, the greater chance that a cancerous one will arise.
6) Radiation Exposure to the abdomen or pelvis may trigger cancer, but usually not for 10 to 50
years after the exposure. The chance of developing cancer from medical X-rays is remote,
estimated at about 6 cases per million X-ray procedures. Moreover, the type of cancer induced by
radiation is more likely to be a muscle, bone or cartilage tumor ("sarcoma") than the much more
common adenocarcinoma of the colo-rectum.
7) Chemical Exposure ("carcinogens") from foods or even from substances produced within our
own bodies. It is thought that eating burnt foods, nitrites, and various artificial additives and
preservatives may increase cancer risk, but it is hard to prove. The more fats a person eats, the
more bile salts their gall bladder releases, and these have been shown to promote polyp growth.
It is very hard to eat a pure, clean diet in America.
8) Possible link to depression, with decreased immune system response. Generally, digestive
diseases have been considered by psychiatry to result from "anger turned inward." It is now
known that normal people's immune systems are able to recognize and destroy tiny cancer cells
before they can spread. In the diseased or depressed person, the immune system does not
function efficiently and may allow cancer to start. The flip side is that a good positive attitude
helps cancer patients live longer and better. Over 50% of cancers are in the rectum or lowest
portion of the colon, the sigmoid. In the colon, 25% of cancers are in the ascending portion, 15%
in the transverse portion, and 10% in the descending portion. There has been a shift toward the
right colon in the past 2 decades.

How can Colorectal cancer be Prevented?

Increased intake of fiber and Vitamin A, and decreased fat in the diet, are thought protective
against bowel cancers. For high risk patients, early detection with occult blood tests and periodic
colonoscopy and polyp removal is appropriate. For the rare very high risk patient, who has a
genetic disease with multiple polyps, prophylactic removal of the colon may be reasonable since
almost 100% of these patients will get colon cancer if it isn't removed. Any prolonged rectal
bleeding, whether bright and red or black and tarry must be promptly evaluated, and not just
ignored as "hemorrhoids."

What are the Symptoms of Colorectal Cancer?

The most common symptom is blood in the stool . This is bright red with cancers of the rectum
and sigmoid colon, but is usually thick, black, and "tarry" if the cancer is higher up in the
digestive tract. This type thick tarry blood is called "melena," and is the result of the blood being
partially digested. It is important to note that most blood found in the stool is not due to a cancer,
but rather a benign condition such as ulcers, bleeding polyps, hemorrhoids or fissures in the anal
canal. Nonetheless, persistant bleeding must never be ignored. With any prolonged slow
bleeding, It is common to develop Iron-Deficiency anemia, manifested by weakness and
paleness, and eventual shortness of breath. This bleeding may be so slow that the patient doesn't
even realize it, yet comes to their doctor with anemia. Subsequent evaluation of this bleeding
may prove a bowel cancer.

Changes in the stool are often seen. These are chronic diarrhea in many right-sided colon
cancers, and pencil-thin stools in left sided or rectal cancer. A feeling of incomplete emptying of
the rectum, called "tenesmus" is frequent with rectal cancer.Pain usually occurs only later in the
disease, usually due to painful spasms of the intestine, and invasion of the cancer into nerves. If a
cancer grows large enough, it can completely block the bowel, causing "bowel obstruction."
Symptoms of total bowel obstruction include no appetite, no bowel movements, abdominal pain,
bloating, vomiting. This is an emergency and must be treated with surgery.

Every colorectal surgeon has had the experience of first detecting cancer at the time of this
emergency surgery. Other common later symptoms include abdominal masses as the tumor
grows, weight loss, liver enlargement and bone pain with spread to those organs. Nearly all
untreated colon cancer will eventually spread to the liver, since this follows the course of the
draining (venous) blood from the colon . The liver provides an ideal spongy, blood-rich area for
cancer "seeds" to implant and grow. Less than 10% of colon cancers spread to the brain, but a
change in motor skills, judgement, memory or sensation is occasionally the first sign noted.

Sometimes, the first sign is spread of the cancer to another body area, and the original tumor
cannot even be found (but may have been from the digestive tract). This "cancer of unknown
origin" is a well described clinical entity, and a different topic.

Cancer of the lower digestive tract is very common in the U.S.A, and was historically treated
with drastic operations. The patient was often left with a bag on the abdomen to drain stool (a
"colostomy"). Unfortunately, the death rate from the cancer was high even with these debilitating
surgeries, and new research has shown some more effective ways of managing (and often curing)
these cancers. These newer treatments commonly allow maintainance of normal toilet activity by
avoiding colostomy. They are just as, if not more effective in producing a cure.
Q&A: Biologics in the Treatment of Metastatic Colorectal Cancer: Latest Data and Expert
Insights.

Question:- Has one class of antihypertensive drugs shown greater benefit in treating
bevacizumab-related hypertension than others?

Answer:- All classes of antihypertensives have been used and all have shown efficacy, with no
indications that one has superior efficacy compared with the others. In an analysis of data from
the BRiTE study (Kozloff M et al. 14th European Cancer Conference [ECCO 2007]. Abstract
3049.), 42.3% of the patients had hypertension at baseline and 18.7% developed increased
hypertension during treatment; but baseline hypertension did not increase the risk of developing
increased blood pressure with bevacizumab use. A number of different antihypertensive agents
were used, and all of them were equally effective. Greater than 70% of the patients needed only
one drug to manage the blood pressure, and 20% needed two classes of drugs to control it.

Question:- Where can one test for KRAS mutations if it indicates such a clear-cut distinction
between responders and nonresponders to epidermal growth factor receptor (EGFR) inhibitor
therapy?

Answer:- A test for KRAS mutations is not yet clinically available. However, I understand that
this may change within the next 8 months. Based on clinical data reported to date (eg, Amado
RG et al. ECCO 2007. Abstract 7LB; Amado et al. 2008 American Society of Clinical Oncology
Gastrointestinal Cancers Symposium [ASCO-GI 2008]. Abstract 278; Hecht R et al. ASCO-GI
2008. Abstract 279.), I suspect that this test will be widely used once it does become available.

Question:- How can we best combine agents with oxaliplatin—for instance, when we encounter
cumulative toxicities that force us to discontinue therapy early?

Answer:- The OPTIMOX2 study, a large phase 2 study conducted before the availability of
bevacizumab, randomized patients between an OPTIMOX1 arm (6 cycles of
FOLFOX7→LV5FU2 until progression→reintroduction of FOLFOX7) and the OPTIMOX2 arm
(6 cycles of FOLFOX7→complete stop of chemotherapy and reintroduction of FOLFOX7
before the tumor progression reached baseline measures). Latest data reported from the
OPTIMOX2 trial (Maindrault-Goebel F et al. 43rd Annual Meeting of the American Society of
Clinical Oncology [ASCO 2007].

Abstract 4013) suggested that the stop-and-go strategy that includes complete chemotherapy-free
intervals may be detrimental to overall survival and, therefore, is inferior to a stop-and-go
strategy that includes a maintenance phase with 5-FU/LV. Based on OPTIMOX2 and other
studies, it has become clear that we should treat patients to progressive disease and not stop all
therapy before. However, the cumulative toxicities related to oxaliplatin often do not allow us to
use this drug continuously until patients progress; consequently, modifications in oxaliplatin-
based therapy are required. When using oxaliplatin in combination with other agents, the key is
not to stop all therapy when neurotoxicity develops, but to only stop oxaliplatin for a necessary
period of time, while continuing treatment with other agents. For example, if FOLFOX is used
and oxaliplatin needs to be stopped, therapy with 5-FU/LV should continue. If therapy is started
with FOLFOX + bevacizumab, oxaliplatin can be stopped if neutotoxicity develops, but
bevacizumab and 5-FU/LV should be continued.

Question:- Have there been subgroup analyses in the PACCE or CAIRO2 studies to see which
patients might be more likely to benefit and who might have increased risk of toxicities from the
multidrug regimens?

Answer:- At this time, there are no published data available to answer this. It can be speculated
that patients at increased risk of toxicities may include older patients and those with poor
performance status, but this has not yet been confirmed.

It is crucial to be well eductated to make the proper choices in dealing with colon or rectal
cancer. This can literally make the difference between life and death. Being knowledgable gives
you the peace-of-mind to know you have done everything possible to fight this disease
successfully.
Our materials explain, in plain English, the definition, frequency, risk factors, symptoms,
evaluation, historic and latest effective treatments for colo-rectal cancer, as well as screening
information. We describe treatments including surgery, radiation, and chemotherapy, and their
results. We tell you everything you need to know to help you make the right choices today for a
colon or rectal cancer problem.

You won't find this combination of information anywhere else. It is easily accessible right here.
We invite you to read our review on Colorectal cancer so that you will be armed with
comprehensive, trustworthy information that may help you or someone you care about who has
been diagnosed with Colorectal cancer.

It is important to be knowledgable to make the right choices for the Colorectal cancer patient.
Making the right choice can literally mean the difference between life and death. You deserve the
peace-of-mind knowing that you have done everything possible to help fight Colorectal cancer
successfully.