colon rectal cancer

8/14/2019 Colon Rectal Cancer

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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, orrectum, makes up this group. The colon and rectum are continuous, but the differing treatmentsfor cancers arising in different parts of the intestinal tract makes it useful to distinguish them bylocation. The colon is also known as the "large intestine," and starts where the small intestineends, in the area of the lower right portion of the abdomen. The area where the small intestinebecomes the colon is called the"cecum," and the fingerlike "appendix" is located nearby. Thecolon is shaped like an arch. The right leg of the arch is called the "ascending colon," and runs upthe right side of the abdomen, bending under the liver.

The arching portion is the "transverse colon," and it runs under the pancreas and stomach, endingunder the spleen. The left portion of the arch is the "descending colon" running down the leftside of the abdomen. The descending colon connects to the "sigmoid colon," which is shaped likean "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," wherebowel movements actually leave the body. Since the lining cells inside the colon and rectum aresimilar, and produce mucous, the cancers that arise in this part of the digestive system are alsosimilar, and considered together. However, the cells lining the inside of the anal canal aredifferent, 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 thebody'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"). Thebowel can become infarcted from a blood clot in the mesenteric blood vessels, becoming twistedupon 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 theliver ("portal vein") to extract and process digested fats, proteins and sugars. The processedblood is then returned to the heart by the large vein draining the liver ("inferior vena cava"). Thepoint is that infection or cancer cells can travel from the bowel up into the liver, and from therethrough the regular bloodstream to other areas . If a cancer spreads ("metastasizes") via thebloodstream, it is called "hematogenous metastasis." Initially, single cancer cells traveling in thebloodstream will "seed" other areas ("micrometastasis"), and eventually (if unchecked) grow intolarge 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, andhelp fight infection in the bowel. The bowel has an inner lining of specialized cells (see below)


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called the "mucosa," but it's walls are made of "muscle layers." These muscle layers allow thebowel to move ("peristalsis") so digesting food is passed through. Just underneath the delicatemucosal 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 withWhite Blood Cells. The purpose of the lymph nodes is to filter and purify the blood, trappinggerms 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 asa conduit for spread of infections or cancer ("lymphogenous metastasis"). Commonly, but notalways, 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 uponthemselves) to form glands, and the type of cancer which most commonly arises from glands iscalled "adenocarcinoma." As with all cells in the body, the production of new cells lining theintestine is under tight control from the "genes" within each cell, which are themselves composedof the basic genetic material "DNA." In the growing child, the cells divide quickly to form theenlarging intestines, but in the adult cells are only produced to replace those that die of injury orlost to old age. Colon cancer, like any cancer, starts in a single cell . This cell loses control of it'sdivision and then starts to reproduce in a haphazard, uncontrolled manner to form a "tumor." Atumor 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; itcannot go to other areas of the body and so is not cancer. In contrast, a "malignant" tumor iscapable 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 processis called "malignant degeneration" and happens in some polyps. Most polyps, however, willnever become cancerous. If cancer does arise and is not effectively treated, the will ultimatelyspread to other crucial body areas and kill the patient. Advanced colon cancer most often kills bycausing anemia, debility, infection, and organ failure. This is why it is critical to diagnose andtreat 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% ofAmericans will develop a colo-rectal cancer at some point. The disease is rare (3% of cases) inthose under 40 years old. Men are effected slightly more often than women. The disease is morecommon in the Western World than in Asia. However, if an Asian person moves to the UnitedStates, there chance for getting colon cancer increases. In the United States, the highest risk areasare in the Northeast, and the lowest in the Southwest. The incidence of colo-rectal cancer hasbeen going up over the past 3 decades, but the death rate peaked in 1985, owing to earlierdetection and better treatments.


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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 becomingcancerous. If a polyp is less than 1 cm. across, it has only a 1% chance of being cancerous, but ifit is larger than 2 cm. across, the chance of cancer rises to almost 50% . Polpys become muchmore 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 thoughtdue 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 thecolon to move food through quickly, and lessen the chance for polyps to form. Colo-rectal canceris rare in societies that eat mostly fruits and vegetables, and the vitamins in these (especiallyvitamins A and E ) may be protective. This is a reason that colon cancer is rarer in the Far Eastwhere less dietary fat is consumed.

2) Family Predisposition Certain cancers, namely colo-rectal, breast, uterine and ovarian, tend tooccur with alteration of the same genes, known as the "family cancer syndrome" genes. Whilenot all people with these inherited genes get cancer, many do. Around 15% of new patients withcolo-rectal cancer have close family members with disease.3) Hereditary syndromes causing multiple polyps in the digestive tract. For example, 100% ofFamilial 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 acancerous one to arise. Other rarer syndromes include "Turcot's," where there are associatedbrain tumors, and "Gardner's," with tumors in other glandular areas. The Peutz- Jegherssyndrome 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 bevery aggressive. The average patient is 60 years old. This goes along with more polyp formationas 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 ofdeveloping colon cancer with ulcerative colitis is about 2% per year. In these conditions, thereare many more new intestinal cells being produced to replace those lost through inflammationand 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 50years 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 byradiation is more likely to be a muscle, bone or cartilage tumor ("sarcoma") than the much morecommon adenocarcinoma of the colo-rectum.

7) Chemical Exposure ("carcinogens") from foods or even from substances produced within ourown bodies. It is thought that eating burnt foods, nitrites, and various artificial additives andpreservatives may increase cancer risk, but it is hard to prove. The more fats a person eats, themore 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, digestivediseases have been considered by psychiatry to result from "anger turned inward." It is nowknown that normal people's immune systems are able to recognize and destroy tiny cancer cells


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before they can spread. In the diseased or depressed person, the immune system does notfunction efficiently and may allow cancer to start. The flip side is that a good positive attitudehelps cancer patients live longer and better. Over 50% of cancers are in the rectum or lowestportion 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 theright 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 protectiveagainst bowel cancers. For high risk patients, early detection with occult blood tests and periodiccolonoscopy and polyp removal is appropriate. For the rare very high risk patient, who has agenetic disease with multiple polyps, prophylactic removal of the colon may be reasonable sincealmost 100% of these patients will get colon cancer if it isn't removed. Any prolonged rectalbleeding, whether bright and red or black and tarry must be promptly evaluated, and not justignored 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 rectumand sigmoid colon, but is usually thick, black, and "tarry" if the cancer is higher up in thedigestive tract. This type thick tarry blood is called "melena," and is the result of the blood beingpartially 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 analcanal. Nonetheless, persistant bleeding must never be ignored. With any prolonged slowbleeding, It is common to develop Iron-Deficiency anemia, manifested by weakness andpaleness, and eventual shortness of breath. This bleeding may be so slow that the patient doesn'teven realize it, yet comes to their doctor with anemia. Subsequent evaluation of this bleedingmay prove a bowel cancer.

Changes in the stool are often seen. These are chronic diarrhea in many right-sided coloncancers, and pencil-thin stools in left sided or rectal cancer. A feeling of incomplete emptying ofthe rectum, called "tenesmus" is frequent with rectal cancer.Pain usually occurs only later in thedisease, usually due to painful spasms of the intestine, and invasion of the cancer into nerves. If acancer 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 thisemergency 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 alluntreated colon cancer will eventually spread to the liver, since this follows the course of thedraining (venous) blood from the colon . The liver provides an ideal spongy, blood-rich area forcancer "seeds" to implant and grow. Less than 10% of colon cancers spread to the brain, but achange 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 tumorcannot even be found (but may have been from the digestive tract). This "cancer of unknown


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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 treatedwith 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 debilitatingsurgeries, 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 byavoiding 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 ExpertInsights.

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

Answer:- All classes of antihypertensives have been used and all have shown efficacy, with noindications that one has superior efficacy compared with the others. In an analysis of data fromthe BRiTE study (Kozloff M et al. 14th European Cancer Conference [ECCO 2007]. Abstract3049.), 42.3% of the patients had hypertension at baseline and 18.7% developed increasedhypertension during treatment; but baseline hypertension did not increase the risk of developingincreased blood pressure with bevacizumab use. A number of different antihypertensive agentswere used, and all of them were equally effective. Greater than 70% of the patients needed onlyone 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 distinctionbetween responders and nonresponders to epidermal growth factor receptor (EGFR) inhibitortherapy?

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, AmadoRG et al. ECCO 2007. Abstract 7LB; Amado et al. 2008 American Society of Clinical OncologyGastrointestinal Cancers Symposium [ASCO-GI 2008]. Abstract 278; Hecht R et al. ASCO-GI2008. Abstract 279.), I suspect that this test will be widely used once it does become available.

Question:- How can we best combine agents with oxaliplatinfor instance, when we encountercumulative toxicities that force us to discontinue therapy early?

Answer:- The OPTIMOX2 study, a large phase 2 study conducted before the availability ofbevacizumab, randomized patients between an OPTIMOX1 arm (6 cycles ofFOLFOX7LV5FU2 until progressionreintroduction of FOLFOX7) and the OPTIMOX2 arm(6 cycles of FOLFOX7complete stop of chemotherapy and reintroduction of FOLFOX7before the tumor progression reached baseline measures). Latest data reported from theOPTIMOX2 trial (Maindrault-Goebel F et al. 43rd Annual Meeting of the American Society ofClinical Oncology [ASCO 2007].

Abstract 4013) suggested that the stop-and-go strategy that includes complete chemotherapy-freeintervals may be detrimental to overall survival and, therefore, is inferior to a stop-and-gostrategy that includes a maintenance phase with 5-FU/LV. Based on OPTIMOX2 and otherstudies, it has become clear that we should treat patients to progressive disease and not stop all


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therapy before. However, the cumulative toxicities related to oxaliplatin often do not allow us touse this drug continuously until patients progress; consequently, modifications in oxaliplatin-based therapy are required. When using oxaliplatin in combination with other agents, the key isnot to stop all therapy when neurotoxicity develops, but to only stop oxaliplatin for a necessaryperiod of time, while continuing treatment with other agents. For example, if FOLFOX is usedand oxaliplatin needs to be stopped, therapy with 5-FU/LV should continue. If therapy is startedwith FOLFOX + bevacizumab, oxaliplatin can be stopped if neutotoxicity develops, butbevacizumab and 5-FU/LV should be continued.

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

Answer:- At this time, there are no published data available to answer this. It can be speculatedthat patients at increased risk of toxicities may include older patients and those with poorperformance 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 rectalcancer. This can literally make the difference between life and death. Being knowledgable givesyou the peace-of-mind to know you have done everything possible to fight this diseasesuccessfully.

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 screeninginformation. We describe treatments including surgery, radiation, and chemotherapy, and theirresults. We tell you everything you need to know to help you make the right choices today for acolon 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 withcomprehensive, trustworthy information that may help you or someone you care about who hasbeen 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 thepeace-of-mind knowing that you have done everything possible to help fight Colorectal cancersuccessfully.

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