What is Colo-rectum?

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 colo-rectum 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 Colo-Rectal 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 Colo-rectal Cancer?

Colo-rectal cancer is the third most most lethal cancer in the United States, after lung and breast cancer, with 156,000 new cases and 60,000 deaths in 1996 . Of these deaths, 52,000 are from colon cancer and 8,000 are from rectal cancer. 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 Colo-rectal 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 Colo-rectal 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 ashift toward the right colon in the past 2 decades.

How can Colo-Rectal 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 Colo-rectal 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, persistent 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, andpencil-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 colo-rectal 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.

How is Colo-rectal cancer Detected and Evaluated?

It may be detected before symptoms with screening, or after symptoms cause the patient to seek medical care:

Screening has been shown to lower the death rate from this cancer, especially if polyps are detected, and removed with a "polypectomy." Patients at higher risk, such as having a family history of colon cancer, should get colonoscopy (where a doctor puts a tube up into the colon to examine it under light anesthesia) every 3 years after age 40. The regular-risk patients should get a yearly digital rectal exam and test for occult blood in the stool every year after age 40, along with their annual physical exam. "Occult blood" in the stool means quantities to small to be noted by the patient; a specially treated card ("guiac test") allows the doctor to smear a little stool on this card, and use a developer which turns the stool smear blue if blood is present. To be sure the test is "negative" (i.e. normal-- no blood present) several consecutive stool samples should be tested. If any test shows blood, the fuller evaluation (below) must be done.

Full physical examination, including digital rectal exam, with the doctor's gloved finger, can feel 80% ofrectal cancers. The doctor tests the retained stool on his examining glove for occult blood. This test also detects prostate enlargement in men. For women, it is appropriate to do a full pelvic exam, since gynecological cancers can cause bowel symptoms. Other things the doctor looks for in physical exam areenlarged glands ("lymph nodes") which can sometimes be felt on rectal exam, in the groin region or even in the arm-pit ("axilla"). Cancer tends to spread to these glands, and they enlarge. Note, however, just having gland enlargement does not prove cancer is causing it, as many infective or inflammatory processes can also cause enlargement. The physician also does a thorough abdominal exam to look for masses or organ swelling (especially in the liver) which may represent cancer spread, and listens for altered bowel sounds which may mean impending obstruction.

Procto-sigmoidoscopy for lower cancer, or full colonoscopy for higher cancers (such as in the ascending or transverse colon). This is basically putting a tube up through the anus and visualizing the rectum and colon, under a light anesthesia (demerol and valium). The bowel must obviously be cleaned out, or "prepped" with enemas prior to this procedure. If a polyps are seen, they can often be cut out using the scissors on the end of the colonoscope.

Barium enema, with "double-contrast" (both barium and air) can detect polyps. "Adenomatous" polyps, or "Hamartomatous" polyps are the most common type and are rarely cancerous, but ones with "Villous" or "Dysplastic" changes are pre-cancerous and must be totally removed ("polypectomy"). Polyps on "stalks" are called "pendunculated" and are the easiest to remove with clipping. They are also less likely to be cancerous compared to polyps which are ulcerated or flat ("sessile") or ulcerate into the bowel. An open surgical procedure is often needed to remove these types.

Trans-rectal Ultrasound uses sound waves to see how deeply the cancer penetrates the rectal wall and if lymph glands in the area are enlarged, which suggests (but doesn't prove) spread of cancer to them. Enlargement for lymph glands means they are bigger than 1 cm. (about 1/2 inch).

CT scan of the abdomen and pelvis is used to pre-plan radiation therapy and to see if there is apparent spread to other organs. It can also show whether enlarged lymph nodes are present in the abdomen or pelvis, and give an idea of how deeply a cancer penetrates into the intestinal wall. CT with contrast means injecting some "radio-opaque" material into an arm vein, this helps to highlight blood vessels around the tumor and make the scan easier to read. Insist upon "omnipaque" or equivalent contrast, which is more expensive but also more comfortable and less likely to cause an allergic reaction or kidney damage. A plain Chest X-ray is usually enough to obviate ("rule-out") any spread to the lungs. If it is suspicious then a CT scan of the chest will then be ordered, possibly in conjunction with a fine-needle sampling of a lung "spot" abnormality to prove or disprove cancer spread there. This procedure is done in the radiology department under local anesthesia, and is ~85% accurate for determining whether cancer has spread to the lung or not. The main risk from fine-needle sampling ("biopsy") is collapse of the lung, which will cause the patient marked shortness of breath. The risk of lung collapse approaches 20% depending upon how experienced the radiologist is. If the lung does collapse, a "chest tube" will need to be placed through a hole made in the chest wall, and suction applied to re-expand the lung. This usually only required an overnight hospital stay, after which the chest-tube is removed.

Fine Needle biopsy can also be done for a liver abnormality to "rule-out" cancer there. The main risk of this procedure is excessive bleeding from the liver, if this happens the patient may need emergency surgery to stem to bleeding. Magnetic Resonance Imaging("MRI") uses magnetism instead of ionizing radiation and is excellent for showing enlarged lymph nodes and spread into the bowel wall. It can also be given with intravenous contrast ("gadolinium") to highlight the blood vessels and areas of tumor spread, which characteristically have some swelling ("edema") around them well shown by MRI. However, it is about three times as expensive as CT scan (~$1000) and isn't routine. Bone Scans or Brain CT scans are only gotten if there is suspected spread there. If a test will not change the intended therapy depending upon it's result, in general it will not help the patient and should not be ordered.

Other routine tests are blood tests ("CBC") for anemia and infection. The Iron-Deficiency anemia common in bowel cancers shows red blood cells with a small volume (low "MCV"), pale and washed-out appearing. Infection is shown on a CBC by an increase in the White Blood Cell count (>12,000). Also, we want a blood chemistry panel ("SMA") which tells sodium, potassium, glucose, cholesterol, liver and kidney function, and suggests if the cancer has gone to bone (by the "alkaline phosphatase" enzyme released from destroyed bone). In more advanced cancer, blood calcium may be high ("hypercalcemia"). There is a special blood test for bowel cancers, the Carcino-Embryonic Antigen ("CEA") which is produced by the cancer itself- this is called a "tumor marker" and is useful to detect recurrence after treatment (if it was elevated before the treatment and went down with the treatment). Unfortunately, it is not specific for bowel cancer and can be raised by other conditions . An Electrocardiogram ("EKG") is standard before any surgery, to see if there is recent heart damage. If major surgery is contemplated, we commonly get "clotting studies"(PT/PTT and bleeding time) to see how quickly the patients blood clots. If the patient has been a long-time smoker or has asthma, "Lung Function Tests" may be gotten in the "pulmonology" laboratory to see how good their breathing is.

Biopsy, that is sampling a piece of the tumor, is the only way to absolutely make a diagnosis of colo-rectal cancer, or any other cancer for that matter. A piece of the tumor is sent to a "pathologist," a physician who specializes in diagnoses of disease from tissue samples. The pathologist examines the biopsy sample under the microscope and often uses special stains to help identify the tumor's origin. If cancer is detected, the pathologist will identify the type and specify the "grade," that is how aggressive and malignant the cancer looks. Grades are usually specified as I to III, with "I" being low grade (indolent) and "III" meaning high grade (very aggressive). Grade "II" is in between. The higher the grade, the less the cancer resembles it's normal tissue counterpart, (in this case the bowel lining cells) and the more likely it is to metastasize. It is not necessarily more resistant to local treatment, however. When a diagnosis of colo-rectal cancer is made, the next step is to assign the "stage."

How is the extent of Colo-Rectal Cancer Gauged?

To know how extensive the cancer is, the above evaluation assigns the Stage" :

Stage 0 or"CIS" means the cancer is microscopic only, and doesn't invade.
Stage I or "A" means a superficial cancer limited to the bowel wall.
Stage II or"B" means penetration through the bowel wall.
Stage III or"C" means that local lymph nodes are involved.
Stage IV or "D" means that the cancer has spread to other organs, such as the bones, liver, lung, skin or brain.

The Roman numeral staging is from the American Joint Cancer Committee ("AJCC"). The corresponding letter staging is the older "Dukes" system, which has been updated and is used by many colo-rectal surgeons.

What is the overall survival of Colo-Rectal Cancer?

The survival for cancers of the colon and rectum are about equal at 50% at 5 years. More specifically, survival will depend upon the above stages. On average, survival at 5 years:

Of course, survival and quality of life depends upon the treatment selected, and the response of the particular cancer to that treatment. The above textbook numbers include death from all causes, including heart attack, accident, and some other cancer. No one can predict just how long any individual will live with cancer . Many patients with colo-rectal cancer are elderly and have other severe ("comorbid") medical conditions they will succumb to first. Bear in mind that many people live for many years with incurable cancer!

What is the Conventional Treatment for Colo-Rectal Cancer?

The conventional treatments for cancers of the colo-rectum have been Surgery, Radiation Therapy, andChemotherapy. All of these are still used today, but important advances have been made in each. In particular, we have learned to COMBINE the conventional therapies to improve results. This is called"multi-modality" treatment, described below as "Latest Effective Therapy." Firstly, we look in detail at each conventional treatment, along with it's common side-effects and results.

Surgery is the historic treatment for cancer of both the colon and rectum, requiring an operation to open the abdomen ("laparotomy"). This surgery is standardly performed by a surgical specialist-- a "colo-rectal" or "bowel" surgeon . This subspecialty has it's own Boards and requires ~2 years of special training after qualifying as a "general surgeon." If the patient is medically suited for surgery (for colon cancer) the abdomen is "explored" to determine how feasible it is to remove the tumor ("resectability"), to determine the extent of spread, and to search for other "primary" cancers. About 2% of patients will be found to have another "metachronous" bowel cancer arising independently. The surgeon must be careful not to spread the disease by unnecessarily moving the diseased bowel about, or by allowing cut through edges to contact other abdominal areas. The "primary site" (where the cancer started IS usually removable at surgery, and surgery is a crucial life-extending procedure if the bowel has become obstructed. If a patient initially "presents" with obstruction, the surgeon will cut out the obstructed area and bring the cut bowel edge out through an opening cut in the abdominal wall. This is called a colostomy ( to which a collection bag for stool is attached to the abdomen). In the past, nearly all colon cancer patients ended up with a permanent colostomy, with it's problems of hygiene, unpleasant smell, sexual and psychological worries. Today, as will be seen, fewer patients require permanent colostomy.

The most common operation for colo-rectal cancer was an "abdomno-peritoneal resection" or "APR."This involved 2 incisions, one in the abdomen and one in the groin region, to remove the cancer, with placement of a permanent colostomy. This aggressive operation had about 10% death rate from complications of the surgery, such as infection or blood clots. Obviously, the import of having a colostomy cannot be underestimated, as both self-image and sexual function have been shown to suffer. Although colostomy care techniques have been improved, it is indisputably a major alteration and adjustment. Thus, research was started to work on "sphincter preservation" - that is reconnecting to bowel to preserve normal anal emptying. The technical name for this procedure is a "primary reanastomosis" - which just means linking the remaining bowel back together. This was simpler up in the abdomen, since a "good margin" (of about 5 cm. on each side) could be cut away from the primary tumor, and the bowel could be reconnected with sutures or special stapling devices. The patient could then progress to having normal bowel movements again. For rectal cancer that is "reanastomosed" to avoid a colostomy, the operation is called a "Low Anterior Resection" and is possible down to about 4 cm. to the anus.

Besides for the worry of a permanent colostomy, other possible side-effects of major abdominal surgery include a 3% risk of death in the "peri-operative" period (around the time of the operation), infection (10%), heart attack, stroke, blood clots or pneumonia complications (total ~10%), chance of the would splitting open ("dehiscence") of 5%, and later bowel obstruction caused by scarring ("adhesions") from the surgery (5%). There is also the risk (averaging 10%) of spreading or "seeding" the cancer around at surgery. All of these risks are lower when the patient is in generally good health and the operation performed by a very experienced "colo-rectal" surgeon . Of course, the worst complication is return of the cancer, which with surgery alone averages nearly 50% once the muscle wall or local lymph nodes have been invaded. The healing time after surgery averages 3 weeks, after which time the scar has returned to 75% of normal tissue strength. After 3 weeks heavy weight lifting is again possible. The results of surgery for bowel cancer depend upon how extensive it is; for colon cancer which is confined to the inner lining and has not penetrated the muscle layer, surgery can be ~100% curative. If the disease is confined to the inner lining, the chance of invasion of local lymph nodes is remote, but these should always be sampled anyway at surgery. If the disease has penetrated into the muscle of the of the bowel wall, then the chance for lymph node (and distant) spread goes up dramatically, depending upon the timeframe and the size and grade of the primary (original) cancer. The chance for cure with muscle wall invasion (Duke's "C"), with surgery only, averages 60% at 5 years. For rectal cancer, results are somewhat poorer, averaging 10% less. This is because it is harder to get a "clear margin" around a cancer in the rectum. Thus, for muscle invading rectal cancer, the survival with surgery at 5 years averages 50%.

However, for cancers of the rectum, more than surgery was necessary to get the same (or better) survival rates than APR or Low Anterior Resection. Fortunately, this has been a productive area of reseach by Drs. Moertel (posthumous) at the Mayo Clinic and more recently Dr. Minsky at the Memorial Sloan Kettering Institute in New York, and utilizes radiation therapy as seen below.

Radiation Therapy has been the treatment of choice for patients who could not tolerate surgery, usually due to other medical conditions like heart and lung disease. Although considered more palliative (symptom reducing) than curative, many patients have definitely been cured with radiation alone. Today, radiation is commonly used as part of a"multi-modality" approach (using multiple treatments for better success) . Radiation therapy is infrequently used, even today, for colon cancers (although is is believed to decrease the "risk of local recurrence" if properly administered, and it's role is being re-examined). The main use for radiation therapy is in rectal cancers, since the rectum tends to be a rather "tight area" bounded by other pelvic structures, and it is hard to get "clear surgical margins" (meaning removal of all of the cancer) in any case. If the colon proper is irradiated, the techniques are similar to those described below for rectal cancer.

Like surgery, radiation therapy is a local treatment, but a wider "field" may be radiated than removed surgically. Therapy can also help relieve ("palliate") the symptoms caused by distant spread of the disease. Treatment is administered under a "Radiation Oncologist," a cancer doctor who specializes in utilizing radiation. Radiation kills cancer cells by damaging their DNA, they die when they try to divide. Thus, damaged cancer cells die even after the treatment is complete. Radiation will also kill normal cells, which limits the amount that can be given. However, it usually takes more radiation to kill normal cells than cancer cells, and normal cells can often repair the radiation damage, while cancer cells can not. Nevertheless, it is important to be as exacting as possible in the administration and dose of radiation, so as to minimize the injury to adjacent normal cells. Particular areas of concern when radiating the rectum include the bladder and small bowel .

To receive therapy, a patient is first seen in "consult" by a radiation oncologist, who reviews the patients medical record, complaints, and radiology films. After explaining the possible benefits and side-effects of radiation, the patient is scheduled for a "simulation." This means the area to be treated is marked out on a replica treatment machine, and films are taken. Some barium contrast material is usually squirted up the patients rectum, which may outline the tumor. In females a "vaginal marker" (simply a tube of plastic) is often placed to help calculate the dose to the vagina. A "foley" catheter with some contrast may be placed into the bladder for the simulation to help calculate the dose their. Watercolor marks are painted on the patient to denote the treatment area, and eventually small, permanent tattoos are placed on the skin. Sometimes the patient is sent for a CT scan along with the simulation, the whole process takes less than 2 hours, and is painless. Information from the simulation and relevant scans is placed into a "treatment planning computer," which generates a "plan." This plan tells how much radiation is going to the tumor area, and how much to adjoining normal tissues. For rectal cancer, particular attention is paid for how much radiation is going to the bladder, rectum, and small intestine. Often, the beam is aimed from 4 directions (front, back, right and left sides) to uniformly dose the bladder. Higher energy treatment machines (over 15 Megavolts) also help smooth out the dose to the pelvis. The plan is reviewed by the radiation oncologist and also by a specially licensed Radiation Physicist prior to starting therapy. The patient then comes in for their"treatment start." They are placed on a hard, flat table in a specially shielded room and aligned with laser lights. The actual treatments are given by "Radiation Therapists," or "R.T.T's," who are first certified for diagnostic X-rays and then get additional training to deliver therapy. For the first treatment, "verification films" are taken to ensure proper positioning; they do not tell anything about the cancer.

The actual treatment only takes a couple of minutes and is given with a Linear Accelerator (or occasionally older Cobalt-60) which precisely aims a beam of photons at the treatment area. The head of the machine can swivel about the patient, to give the treatment from different angles. The patient needs only to lie still. Areas that are not to be treated can be "blocked" with special lead-type blocks in the head of the treatment machine. Normally, patients area treated 5 days a week, Monday through Friday, taking only several minutes each day. The usual dose for rectal cancer is 70 Gray (units of radiation) given at 10 Gray per week. If a treatment is missed, it is simply tacked on to the end so full prescribed dose it given. It is common to "cone down" off of the full pelvis after 50 Gray (since this is the tolerance dose for the small bowel) and shrink the field to treat the rectum proper only. This is called a "boost." Be aware that treatment normally covers the major lymph nodes in the pelvis.

Radiation to the pelvis area is painless, the patient does not become "radioactive," nauseated or lose their scalp hair. The patient can usually maintain normal activities, such as working, driving, and intake of alcoholic beverages. The side-effects of External Beam treatments are classified as "acute" (during treatment) or "late" (months to years after treatment). The most common acute symptoms are reddening of the skin in the treatment area, and anal area irritation. After several weeks of radiation therapy, it is common to develop frequent urination and diarrhea as the bladder and rectum (respectively) become irritated. Prescription of soothing steroid suppositories and anti-diarrheal medicine is usually all that's necessary to treat these acute effects; some dietary modification (less fruit and fiber) may also help. There is often a sense of greater fatigue while receiving radiation. As the dose "builds up" with successive treatments, more blood in the urine may be seen. In general, however, radiation treatments are very well tolerated, the expected side-effects are confined to the treatment area, and abate after completion of therapy. Of more concern are possible "late" effects, which tend to be long lasting or permanent if they occur. Specifically, impotence develops in about 50% of irradiated patients, bladder constriction ultimately requiring cystectomy in 10%, chronic diarrhea in 5%, and bowel or urethral obstruction requiring eventual surgery in 5%. Incontinence is rare (2%) as are second cancers caused by radiation (<1%). Giving the treatment as many fractions, instead of in one large dose, helps reduce the incidence of late reactions. The patient returns for follow-up after completion of treatments, seeing both their gastroenterologist and radiation oncologist. If all goes well, they are ultimately seen once or twice yearly for routine check. Overall, radiation treatments are safer than surgery. The results of radiation therapy alone for invasive rectal cancer show about 50% of patients surviving 5 years - which is the same as surgery! This is especially remarkable, as mentioned, since the irradiated patients are often sicker and have more advanced disease than the "surgerized" patients.

There is no question that local radiation is very valuable in relieving symptoms ('palliation") of bowel cancer, whether from pain from spread to nerves, bone, or lymph nodes. It can help relief urinary obstruction caused by the tumor, and chronic blood in the urine. It can be used to relieve neurological symptoms from spread to the brain, or dangerous pressure upon the spinal cord from metastasis. Thus, radiation therapy is almost always used in advanced cancer to relieve symptoms, with up to 90% effectiveness.

Chemotherapy has been proven valuable as an "adjuvant" (extra therapy) in bowel cancers, and is now considered "Conventional Treatment" for any bowel cancer that invades into the muscle wall. For both colon and rectal cancer, landmark study by the Gastrointestinal Research Group, published in the New England Journal of medicine, found that chemotherapy with 5-Fluoro-uracil (called 5-FU) after surgery significantly improved survival. Improvement has been greatest when 5-FU is given by "continuous infusion" instead of just a couple of times. For rectal cancer, this improvement was only noted when radiation therapy was given to the pelvis after surgery, in addition to 5-FU. The most common side-effects of 5-FU include lowered blood counts, some nausea and diarrhea, and occasionally painful mouth sores or a burning sensation in the hands and feet. These side-effects abate when the drug is discontinued.

What is the most modern, effective treatment for Colo-Rectal Cancer?

This depends upon the location of the cancer in the bowel. For colon cancer, radiation therapy has NOT been proven to increase survival, although it can decrease local relapse of the cancer. It is easier to get a good surgery to remove the cancerous colon than the cancerous rectum, since the rectum is so close to the pelvic wall while the colon floats freely in the abdomen.

A major consideration is preservation of bowel continence, that is avoidance of a permanent colostomy. The cancerous segment of colon can be cut out, and a "primary re-anastomosis" which means connecting the two healthy ends back together, can be performed with no compromise in survival compared to getting a colostomy. This often takes an expert bowel surgeon. The free-end of the colon can even be connected to the anus, if the rectum is removed, and a colostomy avoided this way! Again, this surgery is called "Low Anterior Resection with Primary Re-anastomosis." For rectal cancers, "pre-operative" radiation and chemotherapy may shrink down the tumor enough so that a colostomy is avoided. This is called a "sphincter-sparing" approach. Radiation is given for about 5 weeks, to about 50 Gray (units) along with infusional 5-FU chemotherapy. Then, several weeks later a "Low-Anterior resection" is performed. Only one incision is made, in the abdomen, for this surgery, and a colostomy is avoided. Low dose pre-operative radiation alone (<25 Gray), has NOT been shown to improve survival . If any pre-operative irradiation is done for colo-rectal cancer, it should be to at least 50 Gray to be effective.

Sometimes, for small (<4 cm.), superficial cancers within 10 cm. of the anus, where suspicion of lymph node involvement is low, a "contact cone" of radiation can be administered through the rectum, called the"Papillon" technique. Survival is over 90% at 5 yrs. Bowel function usually remains normal, and this should be considered for older patients.

There is a trade-off to using pre-operative chemo-radiation therapy to avoid colostomy, that is that patients with early cancers may get unnecessary treatment. For those with stage I, chemotherapy and radiation has not been shown to improve survival, which is almost 100%. However, since the only real way of knowing whether the cancer has spread through the bowel wall (stage II) or involves lymph nodes (stage III) is to do an operation, the maximal chances to avoid a colostomy are with the preoperative method even at the cost of some unnecessary treatment.

It is has now been shown that giving adjuvant chemotherapy (New England Journal of Medicine June 1997) at the time of operation improves 10 year survival about 10% on average, to 60%. This is only when this chemotherapy (5-FU) is given by "portal vein infusion" (directly into the liver) for one week following the surgery, not when the chemotherapy is given into the general circulation (as from an arm vein).

This study showed the survival benefit for stages Dukes stages A, B, and C colon cancer. Another advancement is a recent Swedish study, also in the New England Journal of Medicine, which showed increased survival when pre-operative radiation to 25 Gray in 5 Gray per day increments was given to patients with "localized disease" (Previous trials of pre-operative therapy have not shown improvement over surgery alone, but this one did). However, post-operative (after operation) radiation therapy for rectal cancer, along with infusional chemotherapy, is now standard for all but the most superficial cancers.

What about locally advanced Colo-rectal cancer?

A fairly new method of radiation therapy, called "Intra-operative Radiation Therapy" or "IORT," has been shown to improve survival in locally advanced or recurrent cancer or the rectosigmoid. This treatment is electron beam therapy, usually 10 - 20 Gray, given during surgery in the operating room. This surgery usually follows pre-operative chemotherapy with 5-FU and pre-operative radiation to about 50 Gray in 5 weeks. At Massachusetts General Hospital, which used this technique, survival at 3 years was 70% for patients who had their cancer removed at surgery, and 30% for those who did not. Local recurrence was only 13% with IORT. The side effects of high dose IORT can include nerve damage and "fibrosis" (scarring) of the area around the aorta, or later bowel obstruction. Nonetheless, using IORT during surgery for organ cancers (including bowel, bladder, stomach, liver, pancreas, esophagus) is rapidly showing better control of the cancer, less relapse in the local area, and even better overall survival. It is not a complicated treatment, but is only offered at Academic Hospitals with the specially equipped operating room.

Spread of Colo-Rectal Cancer to the Liver

Since the blood from the intestinal veins is drained into the liver, it is the most common site of distant spread for colo-rectal cancers. This is considered Stage "D" or "IV" disease, but there ARE LONG TERM SURVIVORS, and possibly even CURES, for patients with distant spread ONLY to the liver. Any "seed" of colo-rectal cancer which gets into the bloodstream can readily get trapped in the liver, since it is a dense, fibrous organ. Once it gets trapped, it is encouraged to grow into a large tumor, since the liver has a rich blood supply and is readily expandable by a growing tumor. Usually, there are several sites of spread, or "metastasis" to the liver, and they are seen on a CT scan of the abdomen. These tumors can grow to very large sizes, stretch the liver capsule, and cause pain (the liver's nerves are in it's capsule). The liver is normally situated underneath the right chest ribcage. It can expand due to inflammation ("hepatitis") from an infection or having it's bile drainage blocked (by gallstones or tumor). Also, it can expand from any "infiltrative" process (something growing in the liver), such as fat cells ("steatosis"), fiber cells ("amyloid") or cancers. As the liver expands, it causes dull pain in the "right upper quadrant" (under the right ribcage) and it's edge starts poking down below the ribcage. This expansion is called "hepatomegaly" (which just means enlarged liver).

The liver is a remarkably resilient organ and only 10% of it's normal function is needed to survive. In fact part of the liver can be cut out of an adult, and it will actually regrow! This is a unique capability not seen in other human organs. The liver is an astounding laboratory sustaining metabolism. Among it's functions are purification of the blood, by detoxifying alcohol and drugs, controlling the body's sugar and cholesterol balance, making bile to digest fats, forming clotting factors for the blood and generating new blood cells. This myriad of functions makes clear why the liver is essential to life.

If there are only a few discreet "metastasis" to the liver (four or less), and the patient is medically suitable for surgery, then survival is improved if these tumors are removed surgically, called a "metastastectomy." This was demonstrated in a large trial comparing surgical removal to "conservative therapy" (i.e. pain medicine) only. If those tumors cannot be removed surgically, then they may be shrunk by injecting ethyl alcohol into the tumors under radiographic ("fluoroscopy") guidance. Although unconfirmed in America, Japanese investigators have injected ethanol (ingestable alcohol) directly into the liver under ultrasound guidance (with a needle placed through the skin of the chest) and found a 5-year survival rate of nearly 80% in patients with local liver disease only. This was even more effective than surgery for patients with operable cancers invading the liver!

Radiation Therapy advances focus on delivering high dose treatment directly to the liver tumor. Unfortunately, the normal liver has a poor general tolerance for radiation. Also, the the nearby critical structures (lung and spinal cord) again don't tolerate high dose treatment, and this had limited the usefulness of the conventional "Exernal Beam" treatments given in standard Radiation Therapy departments. It can provide some relief from pain from capsule stretching by growing tumor, but with a dose limited to about 30 Gray cannot cure tumor spread to the liver. Also, there is usually lots of nausea and fatigue when treating large liver areas with radiation, making it very unpleasant. Furthermore, the liver can get "radiation hepatitis" from doses higher than about 25 Gray, with progressive liver failure as a result. Thus, conventional radiation is not considered a good option today for patients with spread of colo-rectal cancer to the liver.

While aggressive chemotherapy for advanced colo-rectal cancer is disappointing, a 20% improvement in disease-free survival at 4 years has been noted when the antiworm agent Levamisole is combined with 5-FU in stage III and IV colon cancer. Chemotherapy has been given directly into the main artery of the liver, the "hepatic artery," to treat metastasis, and has shown some impressive shrinkage of liver tumors. Unfortunately, it has not been proven that "Hepatic Arterial Infusion" (of 5-FU) extends survival compared to conventional administration of the drug into the veins. Large tumors in the liver may be stiffled by using "Embolization" techniques to block off their blood vessels, usually with Gelfoam.

Current exerimental therapies for advanced colo-rectal cancer include use of the chemotherapy drug "Gemcitabine" ("Gemzar") which was approved by the FDA in 1996 for advanced pancreatic cancer. There is a study at the University of Chicago using this drug sponsored by the American National Cancer Institute (NCI). Another interesting study for colo-rectal cancer metastatic to the liver is using the durg Flucyosine (5FC) with a "Replication Deficient Adenovirus Vector" containing the "Cytosine Deaminase Gene"-- this study is being done at Cornell University in New York for patients aged 18 to 70, and combines chemotherapy with gene therapy. Another study at the Mayo Clinic in Minneapolis, Minnesota is using a Seven Day course of an oral chemotherapy drug "Ethynyluracil" along with 5-FU in patients with unresectable or metastatic colo-rectal cancer, for patients aged 18 and over. This new drug is also being used at the University of Chicago along with Leukovorin calcium and 5-FU in an NCI sponsored study for advanced colo-rectal cancer.

Symptom Relief From Advanced Disease

Even if cure is no longer realistic, the patient should be made as comfortable as possible. There is absolutely no reason that today's patient should suffer pain, given the rapid advancement of pain-relieving technology. If the patient has the most advanced type of cancer with distant disease spread throughout the body, the objective is no longer cure but palliation (meaning relief of pain and other symptoms). Narcotic medicines like morphine (which the American medical pioneer Sir Wm. Osler called G-d's own medicine) should never be withheld for fear of causing "addiction." Using "Fentanyl Patches"applied to the skin helps give a continuous amount of narcotic, eliminating the problems of forgotten doses, "loss" of narcotics (certain people will steal them) and smoothing out the dosing for less disturbing "highs and lows."

Importantly, Radiation Treatment can help pelvic pain, urinary obstruction, bleeding and bone pain in over 90% of patients. It is also useful for reducing the symptoms, and even extending survival, in patients with spread to the brain. About 10% of colo-rectal cancer patients ultimately have spread to the brain. Sometimes radiation therapy is used as an emergency measure when the cancer spreads to the spinal column and threatens to cause paralysis by pressing upon the spinal cord. About 8% of patients with colo-rectal cancer will eventually experience this. Any patient with bladder cancer who experiences new weakness of the extremities, numbness, or loss of bowel or bladder function must be brought into the Emergency Room immediately to see whether the tumor is compressing the spinal cord causing these symptoms . Up to 60% of new back pain in a cancer patient is caused by spread of cancer there. The patient is given a painless Magnetic Resonance Imaging (MRI) scan to check for "epidural spinal cord compression." If this is caught early, and treatment is given, permanent paralysis may be prevented. It is unfortunately uncommon to reverse symptoms of paralysis once they have set it, however, so quick recognition is essential.

As mentioned, radiation treatment can be very helpful for metastatic bowel cancer. A relatively new method of radiation for spread to the brain (one of the most common areas of spread) is "Stereotactic Radiosurgery," where multiple beams of convergent radiation are aimed onto the area(s) of spread in brain, in a single painless session of one afternoon. This is usually followed by 10 to 20 treatments with conventional "External Beam" radiation. The advantage of Stereotactic Radiosurgery is that it can give a very high dose of radiation to areas of brain metastasis, and possibly enhance survival for these patients, without the risk of an open brain surgery from a neurosurgeon.

Other options for patients in severe pain for multiple areas of spread to bone include "hemi-body" radiation, and "strontium-89." Hemi-Body radiation uses a low dose (6 to 8 Gray) in a single treatment to the upper or lower body to treat multiple areas of bony involvement; some anti-nauseates are usually necessary and it lowers blood counts. It is over 90% effective for pain relief lasting an average of 6 months. Strontium-89 is an injected radioisotope that goes through the bloodstream to all bony areas, and is especially attracted to cancerous areas. It also lowers blood counts but is very effective at palliating pain. It can only be done once. If no relief is gotten from medications or radiation, neurological techniques to cut sensory nerves can usually afford relief, to this small population of patients. CancerAnswers has a transcript available on In-Depth Symptom Relief which you can order through our web-site . Committing suicide because of unrelieved pain should never be necessary with pain science today.

The patient diagnosed with colo-rectal cancer should not rely on any one therapy, but instead should use acombination approach to maximize the chance for success Specifically, besides the conventional medical therapies mentioned above, consider the use of a non-toxic, not over-expensive alternative therapy that you believe in, a program of spiritual renewal, "mind over cancer', nutritional therapy and exercise. Keep the most positive attitude possible-- research has shown this to be an important factor in survival.CancerAnswers has a transcript available on reasonable alternative treatments which you can order through our web-site . Using a true "multi-modality" approach will give the confidence that you have done everything possible for a happy outcome, and certainly improve the current quality of life.

New combinations of surgery, radiation and chemotherapy are giving better results for colo-rectal cancer, with less chance of a colostomy. Many new therapies are offered in the context of "Clinical Trials."These trials are first designed to show how toxic a new treatment is ("Phase I" studies), whether is works at all ("Phase II" studies), and if so just how well it works and is tolerated ("Phase III and IV" studies). The National Cancer Institute has protocols using mew chemotherapy agents that are available at the Major University Medical Centers. Also, Major Medical Centers often have their own "In House" trials designed and run by their own faculty.

If one wishes to join a Clinical Trial, there are "entrance criteria" (usually ensuring that the patient is in otherwise good health, and that they are NOT receiving any other therapy which could skew the Trial results) "disqualification factors" (for eliminating those who become too sick during the trial), and "early closure" factors (if it is obvious that the treatment either does or does not work). A patient may or may not be "accepted" into the Trial, and if they are then they are "randomized"to a particular "arm" (treatment), usually in a "double-blind" fashion (neither the patient nor the investigator knows if they are getting the new drug or a fake -"placebo" ). Obviously if a major surgery or radiation is involved in one arm but not another, the Study physicians and patients will know which treatments they are getting, but the initial "randomization" will still determine what patients will receive. Patients who do not wish to give up the autonomy for how they are treated should not enter Clinical Trials.

The National Cancer Institute keeps a listing of open cancer trials on their website (they change frequently). Especially look for ones listed as "Intergroup" studies, or in conjunction with the Radiation Oncology Therapy Group ("RTOG"). The future has never looked brighter for colo-rectal cancer patients.

This is the full transcript, offered freely in the spirit of internet sharing, of CancerAnswers' report on Colo-Rectal Cancer. Much more, including latest additional treatments for Colo-Rectal Cancer can be found on our order page. Thank you for using CancerAnswers as your information resource.