COLORECTAL CANCER DEFINITION

is a disease in which normal cells in the lining of the colon or rectum begin to change, start to grow uncontrollably, and no longer die. These changes usually take years to develop; however, in some cases of hereditary disease, changes can occur within months to years. Both genetic and environmental factors can cause the changes. Initially, the cell growth appears as a benign (noncancerous) polyp that can, over time, become a cancerous tumor. If not treated or removed, a polyp can become a potentially lifethreatening cancer. Recognizing and removing precancerous polyps before they become cancer can prevent colorectal cancer.

less formally known as bowel cancer, is a cancer characterized byneoplasia in the colon, rectum, or vermiform appendix.[citation needed] Colorectal cancer is clinically distinct from anal cancer, which affects the anus. Colorectal cancers start in the lining of the bowel. If left untreated, it can grow into the muscle layers underneath, and then through the bowel wall. Most begin as a small growth on the bowel wall: a colorectal polyp or adenoma. These mushroom-shaped growths are usually benign, but some develop into cancer over time. Localized bowel cancer is usually diagnosed throughcolonoscopy.

The colon is the part of the digestive system where the waste material is stored. The rectum is the end of the colon adjacent to the anus. Together, they form a long, muscular tube called the large intestine (also known as the large bowel). Tumors of the colon and rectum are growths arising from the inner wall of the large intestine. Benign tumors of the large intestine are called polyps. Malignant tumors of the large intestine are called cancers. Benign polyps do not invade nearby tissue or spread to other parts of the body. Benign polyps can be easily removed during colonoscopy and are not life-threatening. If benign polyps are not removed from the large intestine, they can become malignant (cancerous) over time. Most of the cancers of the large intestine are believed to have developed from polyps. Cancer of the colon and rectum (also referred to as colorectal cancer) can invade and damage adjacent tissues and organs. Cancer cells can also break away and spread to other parts of the body (such as liver and lung) where new tumors form. The spread of colon cancer to distant organs is called metastasis of the colon cancer. Once metastasis has occurred in colorectal cancer, a complete cure of the cancer is unlikely. Globally, cancer of the colon and rectum is the third leading cause of cancer in males and the fourth leading cause of cancer in females. The frequency of colorectal cancer varies around the world. It is common in the Western world and is rare in Asia and Africa. In countries where the people have adopted western diets, the incidence of colorectal cancer is increasing.

SIGNS AND SYMPTOMS

Signs and Symptoms: 1. Ascending (Right) Colon Cancer 2. Occult blood in stool Anemia Anorexia and weight loss Abdominal pain above umbilicus

Palpable mass Distal Colon/Rectal Cancer Rectal bleeding Changed in bowel habits Constipation or Diarrhea Pencil or ribbon shaped stool Tenesmus Sensation of incomplete bowel emptying

The symptoms of colorectal cancer depend on the location of tumor in the bowel, and whether it has spread elsewhere in the body (metastasis). Most of the symptoms may occur in other diseases as well, and hence none of the symptoms mentioned here is diagnostic of colorectal cancer. Symptoms and signs are divided into local, constitutional (affecting the whole body) and metastatic (caused by spread to other organs
LOCAL

Local symptoms are more likely if the tumor is located closer to the anus. There may be a change in bowel habit (new-onset constipation ordiarrhea in the absence of another cause), and a feeling of incomplete defecation (rectal tenesmus) . Lower gastrointestinal bleeding, including the passage of bright red blood in the stool, may indicate colorectal cancer, as may the increased presence of mucus. Melena, black stool with a tarry appearance, normally occurs in upper gastrointestinal bleeding (such as from a duodenal ulcer), but is sometimes encountered in colorectal cancer when the disease is located in the beginning of the large bowel. A tumor that is large enough to fill the entire lumen of the bowel may cause bowel obstruction. This situation is characterized by constipation,abdominal pain, abdominal distension and vomiting. This occasionally leads to the obstructed and distended bowel perforating and causingperitonitis. A large left colonic tumor may compress the left ureter and cause hydronephrosis.

Certain local effects of colorectal cancer occur when the disease has become more advanced. A large tumor is more likely to be noticed on feeling the abdomen, and it may be noticed by a doctor on physical examination. The disease may invade other organs, and may causeblood or air in the urine (invasion of the bladder) or vaginal discharge (invasion of the female reproductive tract). [edit]Constitutional If a tumor has caused chronic occult bleeding, iron deficiency anemia may occur; this may be experienced as fatigue, palpitations and noticed as pallor (pale appearance of the skin). Colorectal cancer may also lead to weight loss, generally due to a decreased appetite. More unusual constitutional symptoms are an unexplained fever and one of several paraneoplastic syndromes. The most common paraneoplastic syndrome is thrombosis, usually deep vein thrombosis.

They include fatigue, weakness, shortness of breath, change in bowel habits, narrow stools, diarrhea or constipation, red or dark blood in stool, weight loss, abdominal pain, cramps, or bloating. Other conditions such as irritable bowel syndrome (spastic colon), ulcerative colitis, Crohn's disease, diverticulosis, and peptic ulcer disease can have symptoms that mimic colorectal cancer. Colon cancer can be present for several years before symptoms develop. Symptoms vary according to where in the large bowel the tumor is located. The right colon is spacious, and cancers of the right colon can grow to large sizes before they cause any abdominal symptoms. Typically, right-sided cancers cause iron deficiency anemia due to the slow loss of blood over a long period of time. Iron deficiency anemia causes fatigue, weakness, and shortness of breath. The left colon is narrower than the right colon. Therefore, cancers of the left colon are more likely to cause partial or complete bowel obstruction. Cancers causing partial bowel obstruction can cause symptoms of constipation, narrowed stool, diarrhea, abdominal pains, cramps, and bloating. Bright red blood in the stool may also indicate a growth near the end of the left colon or rectum.

HALLMARK SIGN TEST AND PROCEDURE

Exams and Tests

If you are having rectal bleeding or changes in your bowel movements, you will undergo tests to determine the cause of the symptoms.

Your health care provider may insert a gloved finger into your rectum through your anus. This test, called a digital rectal exam, is a quick screen to make sure that any bleeding is actually coming from your rectum. This is not painful, but it is mildly uncomfortable for some people. It takes only a few seconds.

You may have a test called a colonoscopy.

This is a test that allows a specialist in digestive diseases (a gastroenterologist) to look at the inside of your colon. This test looks for polyps, tumors, or other abnormalities. Colonoscopy is an endoscopic test. This means that a thin, flexible plastic tube with a tiny camera on the end will be inserted into your colon via your anus. As the tube is advanced further into your colon, the camera sends images of the inside of your colon to a video monitor. Colonoscopy is an uncomfortable test for most people. You will first be given a laxative solution to drink that will clear most of the fecal matter from your bowel. You will be allowed nothing to eat before the test. Whenever possible, you will be given medication before the procedure to relax you and relieve the discomfort. Flexible sigmoidoscopy is similar to colonoscopy but does not go as far into the colon. It uses a shorter endoscope to examine the rectum, sigmoid (lower) colon, and most of the left colon.

Air-contrast barium enema is a type of x-ray that can show tumors.

Before the x-ray is taken, a liquid is introduced into your colon and rectum via your anus. The liquid contains barium, which shows up solid on x-rays. This test highlights tumors and certain other abnormalities in the colon and rectum. Other types of contrast enemas are available.

Air-contrast barium enema frequently detects malignant tumors, but it is not as effective in detecting small tumors or those far up in your colon.

If a tumor is identified in the colon or rectum, you will probably undergo CT scan of your abdomen and a chest x-ray to make sure the disease has not spread.

When colon cancer is suspected, either a lower GI series (barium enema x-ray) or colonoscopy is performed to confirm the diagnosis and to localize the tumor. A barium enema involves taking x-rays of the colon and the rectum after the patient is given an enema with a white, chalky liquid containing barium. The barium outlines the large intestines on the x-rays. Tumors and other abnormalities appear as dark shadows on the xrays. For more information, please read the Lower Gastrointestinal Series (Barium Enema) article. Colonoscopy is a procedure whereby a doctor inserts a long, flexible viewing tube into the rectum for the purpose of inspecting the inside of the entire colon. Colonoscopy is generally considered more accurate than barium enema x-rays, especially in detecting small polyps. If colon polyps are found, they are usually removed through the colonoscope and sent to the pathologist. The pathologist examines the polyps under the microscope to check for cancer. While the majority of the polyps removed through the colonoscopes are benign, many are precancerous. Removal of precancerous polyps prevents the future development of colon cancer from these polyps. For more information, please read the Colonoscopy article. If cancerous growths are found during colonoscopy, small tissue samples (biopsies) can be obtained and examined under the microscope to confirm the diagnosis. If colon cancer is confirmed by a biopsy, staging examinations are performed to determine whether the cancer has already spread to other organs. Since colorectal cancer tends to spread to the lungs and the liver, staging tests usually include chest x-rays, ultrasonography, or a CAT scanof the lungs, liver, and abdomen. Sometimes, the doctor may obtain a blood test for CEA (carcinoembyonic antigen). CEA is a substance produced by some cancer cells. It is sometimes found in high levels in patients with colorectal cancer, especially when the disease has spread.

Invasive cancers that are confined within the wall of the colon (TNM stages I and II) are often curable with surgery,

Digital rectal exam (DRE): The doctor inserts a lubricated, gloved finger into the rectum

to feel for abnormal areas. It only detects tumors large enough to be felt in the distal part of the rectum but is useful as an initial screening test.

Fecal occult blood test (FOBT): a test for blood in the stool. Two types of tests can be

used for detecting occult blood in stools i.e. guaiac based (chemical test) and immunochemical. The sensitivity of immunochemical testing is superior to that of chemical testing without an unacceptable reduction in specifity.[40]

Endoscopy:

Sigmoidoscopy: A lighted probe (sigmoidoscope) is inserted into the rectum and Colonoscopy: A lighted probe called a colonoscope is inserted into the rectum

lower colon to check for polyps and other abnormalities.

and the entire colon to look for polyps and other abnormalities that may be caused by cancer. A colonoscopy has the advantage that if polyps are found during the procedure they can be removed immediately. Tissue can also be taken for biopsy. In the United States, colonoscopy or FOBT plus sigmoidoscopy are the preferred screening options. [edit]Other

screening methods

Double contrast barium enema (DCBE): First, an overnight preparation is taken to

cleanse the colon. An enema containing barium sulfateis administered, then air is insufflated into the colon, distending it. The result is a thin layer of barium over the inner lining of the colon which is visible on X-ray films. A cancer or a precancerous polyp can be detected this way. This technique can miss the (less common) flat polyp.

Virtual colonoscopy replaces X-ray films in the double contrast barium enema (above)

with a special computed tomography scan and requires special workstation software in order for the radiologist to interpret. This technique is approaching colonoscopy in sensitivity for polyps. However, any polyps found must still be removed by standard colonoscopy.

Standard computed axial tomography is an x-ray method that can be used to determine

the degree of spread of cancer, but is not sensitive enough to use for screening. Some cancers are found in CAT scans performed for other reasons.

Blood tests: Measurement of the patient's blood for elevated levels of

certain proteins can give an indication of tumor load. In particular, high levels

of carcinoembryonic antigen (CEA) in the blood can indicate metastasis of adenocarcinoma. These tests are frequently false positive or false negative, and are not recommended for screening, it can be useful to assess disease recurrence. CA19-9 and CA 242biomarkers can indicate e-selectin related metastatic risks, help follow therapeutic progress, and assess disease recurrence. Also the level of tissue inhibitor of metalloproteinases 1 (TIMP1) in the blood has been shown to correlate with the occurrence of colon cancer. ATIMP1 test can be helpful in an evaluation to assess the risk of having developed colorectal cancer. TIMP1 is particularly helpful as a marker for early identification of colorectal cancer, where it has been shown to have a high specificity and sensitivity.[41] The research ofTIMP1, as a marker for early identification of colorectal cancer, is particularly focused in Denmark as a collaboration between theUniversity of Copenhagen, the Technical University of Denmark, Rigshospitalet and Cancer Marker A/S, which is a Danish medico-company.

Cell free DNA - Blood: There is extensive literature describing DNA shed from tumors

circulating as cell free DNA in the blood.[42] Using highly sensitive assays, studies report the presence of DNA mutations [43] and DNA methylation tumor markers such as SEPT9 in the plasma of colon cancer patients.[44][45] In Europe, the SEPT9 methylation marker has been developed into the CE marked Epi proColon test (Epigenomics AG) and the ms9 test (Abbott Molecular). It is also the subject of a clinical trial[46] in the US, and has been licensed for the development of LDT tests by Quest Diagnostics and ARUP Laboratories in the US, and Warnex Laboratories [47] in Canada.[48]

Genetic counseling and genetic testing for families who may have a hereditary form of

colon cancer, such as hereditary nonpolyposis colorectal cancer (HNPCC) or familial adenomatous polyposis (FAP).

Positron emission tomography (PET) is a 3-dimensional scanning technology where a

radioactive sugar is injected into the patient, the sugar collects in tissues with high metabolic activity, and an image is formed by measuring the emission of radiation from the sugar. Because cancer cells often have very high metabolic rates, this can be used to differentiate benign and malignant tumors. PET is not used for screening and does not (yet) have a place in routine workup of colorectal cancer cases.

Whole-body PET imaging is the most accurate diagnostic test for detection of recurrent

colorectal cancer, and is a cost-effective way to differentiate resectable from nonresectable disease. A PET scan is indicated whenever a major management decision depends upon accurate evaluation of tumour presence and extent.

Stool DNA testing is an emerging technology in screening for colorectal cancer.

Premalignant adenomas and cancers shed DNA markers from their cells which are not

degraded during the digestive process and remain stable in the stool. Capture, followed by PCR amplifies the DNA to detectable levels for assay. Clinical studies have shown a cancer detection sensitivity of 71%91%.[49]

High C-Reactive Protein levels is risk marker.[50] miRNA-profiling-based screening for detection of early-stage colorectal cancer: The life

science and research company Exiqon A/S has developed a novel plasma miRNA screening assay for identifying early-stage colorectal cancer. Plasma miRNA has been shown to be a promising biomarker for many diseases including cancer. The goal of this technique is to select individuals for colonoscopy rather than to replace colonoscopy as the gold standard of colorectal cancer diagnosis. Blood plasma samples collected from patients with early, resectable (Stage II) colorectal cancer and sex-and age-matched healthy volunteers were profiled. So far potential biomarkers have shown promising specificity and sensitivity. The same technology can also be applied to patients who may be at higher risk of relapse and therefore in need for more aggressive adjuvant chemotherapy.[51][52][53]

Monitoring
Carcinoembryonic antigen (CEA) is a protein found on virtually all colorectal tumors. CEA may be used to monitor and assess response to treatment in patients with metastatic disease. CEA can also be used to monitor recurrence in patients post-operatively.[citation needed] Tissue Inhibitor of Metalloproteinases 1 (TIMP1) is also possible to be used as a monitor and assess response to treatment of coloreactal cancer. Particular when it is combined with (CEA).
[41]

Constantly increased levels of TIMP1 during treatment identify patients with a very poor

prognosis.[54]

Digital rectal examination and stool occult blood testing It is recommended that all individuals over the age of 40 have yearly digital examinations of the rectum and their stool tested for hidden or "occult" blood. During digital examination of the rectum, the doctor inserts a gloved finger into the rectum to feel for abnormal growths. Stool samples can be obtained to test for occult blood (see below). The prostate gland can be examined at the same time. An important screening test for colorectal cancers and polyps is the stool occult blood test. Tumors of the colon and rectum tend to bleed slowly into the stool. The small amount of blood mixed into the stool is usually not visible to the naked eye. The commonly used stool occult blood tests rely on chemical color conversions to detect microscopic amounts of blood. These tests are both convenient and inexpensive. A small amount of stool sample is smeared on a special card for occult blood testing. Usually, three consecutive stool cards

are collected. A person who tests positive for stool occult blood has a 30% to 45% chance of having a colon polyp and a 3% to 5% chance of having a colon cancer. Colon cancers found under these circumstances tend to be early and have a better long-term prognosis. It is important to remember that having stool tested positive for occult blood does not necessarily mean the person has colon cancer. Many other conditions can cause occult blood in the stool. However, patients with a positive stool occult blood should undergo further evaluations involvingbarium enema x-rays, colonoscopies, and other tests to exclude colon cancer, and to explain the source of the bleeding. It is also important to realize that stool which has tested negative for occult blood does not mean the absence of colorectal cancer or polyps. Even under ideal testing conditions, at least 20% of colon cancers can be missed by stool occult blood screening. Many patients with colon polyps are tested negative for stool occult blood. In patients suspected of having colon tumors, and in those with high risk factors for developing colorectal polyps and cancer, flexible sigmoidoscopies or screening colonoscopies are performed even if the stool occult blood tests are negative. Flexible sigmoidoscopy and colonoscopy Beginning at age 50, a flexible sigmoidoscopy screening tests is recommended every three to five years. Flexible sigmoidoscopy is an exam of the rectum and the lower colon using a viewing tube (a short version of colonoscopy). Recent studies have shown that the use of screening flexible sigmoidoscopy can reduce mortality from colon cancer. This is a result of the detection of polyps or early cancers in people with no symptoms. If a polyp or cancer is found, a complete colonoscopy is recommended. The majority of colon polyps can be completely removed by colonoscopy without open surgery. Recently doctors are recommending screening colonoscopies instead of screening flexible sigmoidoscopies for healthy individuals starting at ages 50-55. Please read the Colon Cancer Screening article. Patients with a high risk of developing colorectal cancer may undergo colonoscopies starting at earlier ages than 50. For example, patients with family history of colon cancer are recommended to start screening colonoscopies at an age 10 years before the earliest colon caner diagnosed in a first-degree relative, or five years earlier than the earliest precancerous colon polyp discovered in a first-degree relative. Patients with hereditary colon cancer syndromes such as FAP, AFAP, HNPCC, and MYH are recommended to begin colonoscopies early. The recommendations differ depending on the genetic defect, for example in FAP; colonoscopies may begin during teenage years to look for the development of colon polyps. Patients with a prior history of polyps or colon cancer may also undergo colonoscopies to exclude recurrence. Patients with a long history (greater than 10 years) of chronic ulcerative colitis have an increased risk of colon cancer, and should have regular colonoscopies to look for precancerous changes in the colon lining.

Genetic counseling and testing Blood tests are now available to test for FAP, AFAP, MYH, and HNPCC hereditary colon cancer syndromes. Families with multiple members having colon cancers, members with multiple colon polyps, members having cancers at young ages, and having other cancers such as cancers of the ureters, uterus, duodenum, etc., should be referred for genetic counseling followed possibly by genetic testing. Genetic testing without prior counseling is discouraged because of the extensive family education that is involved and the complicated nature of interpreting the test results. The advantages of genetic counseling followed by genetic testing include: (1) identifying family members at high risk of developing colon cancer to begin colonoscopies early; (2) identifying high risk members so that screening may begin to prevent other cancers such as ultrasound tests for uterine cancer, urine examinations for ureter cancer, and upper endoscopies for stomach and duodenal cancers; and (3) alleviating concern for members who test negative for the hereditary genetic defects.

-NURSING RESPONSIBILITIES
1. Prepare the patient for surgery, as indicated. 2. Provide comfort measures and reassurance for patients undergoing radiation therapy. 3. Prepare the patient for the adverse effects of chemotherapy and take steps to minimize this effects. 4. Use strict aseptic technique when caring for I.V. catheters. 5. Have the patient wash his hands before and after meals and after going to the bathroom. 6. Listen to the patients fears and concerns, stay with him during periods of severe stress and anxiety. 7. Encourage the patient to identify actions and care measures that will promote his comfort and relaxation. 8. Monitor the patients bowel patterns. 9. Monitors the patients diet modification, and assess the adequacy of his nutrition intake. 10. Direct the patient to follow a high fiber diet. 11. Caution him to take laxatives or an antidiarrheal medications only as prescribed by the doctor. 12. Inform the patient about screening and early detection. 1. Prepare the patient for surgery, as indicated. 2. Provide comfort measures and reassurance for patients undergoing radiation therapy. 3. Prepare the patient for the adverse effects of chemotherapy and take steps to minimize this effects. 4. Use strict aseptic technique when caring for I.V. catheters.

5. Have the patient wash his hands before and after meals and after going to the bathroom. 6. Listen to the patients fears and concerns, stay with him during periods of severe stress and anxiety. 7. Encourage the patient to identify actions and care measures that will promote his comfort and relaxation. 8. Monitor the patients bowel patterns. 9. Monitors the patients diet modification, and assess the adequacy of his nutrition intake. 10. Direct the patient to follow a high fiber diet. 11. Caution him to take laxatives or an antidiarrheal medications only as prescribed by the doctor. 12. Inform the patient about screening and early detection.

PRIORITY TREATMENT -MEDICAL

Aspirin
A study published in 2009 found that aspirin reduces risk of colorectal neoplasia in randomized trials, and inhibits tumor growth and metastases in animal models. The influence of aspirin on survival after diagnosis of colorectal cancer is unknown.[90] Several reports, including a prospective cohort of 1,279 people diagnosed with stages I-III (nonmetastatic) colorectal cancer,
[91]

have suggested a significant improvement in cancer-specific survival in a subset of patients

using aspirin.[92]

Cimetidine
Cimetidine is being investigated in Japan as an adjuvant for adenocarcinomas,[93] including for stage III[94] and stage IV[95] colorectal cancers biomarked with overexpressed sialyl Lewis X and A epitopes. Multiple small trials suggest a significant survival improvement in the subset of patients with the sLeX and sLeA biomarkers that take cimetidine treatment perioperatively, through several mechanisms [1].
Support therapies

-SURGICAL
Surgery

Surgeries can be categorised into curative, palliative, bypass, fecal diversion, or open-andclose.

Curative surgical treatment can be offered if the tumor is localized.

Very early cancer that develops within a polyp can often be cured by removing the polyp In colon cancer, a more advanced tumor typically requires surgical removal of the

(i.e., polypectomy) at the time of colonoscopy.

section of colon containing the tumor with sufficient margins, and radical en-bloc resection of mesentery and lymph nodes to reduce local recurrence (i.e., colectomy). If possible, the remaining parts of colon are anastomosed to create a functioning colon. In cases when anastomosis is not possible, a stoma (artificial orifice) is created.

Curative surgery on rectal cancer includes total mesorectal excision (lower anterior

resection) or abdominoperineal excision. In case of multiple metastases, palliative (noncurative) resection of the primary tumor is still offered to reduce further morbidity caused by tumor bleeding, invasion, and its catabolic effect. Surgical removal of isolated liver metastases is, however, common and may be curative in selected patients; improved chemotherapy has increased the number of patients who are offered surgical removal of isolated liver metastases. If the tumor invaded into adjacent vital structures, which makes excision technically difficult, the surgeons may prefer to bypass the tumor (ileotransverse bypass) or to do a proximal fecal diversion through a stoma. The worst case would be an "open-and-close" surgery, when surgeons find the tumor unresectable and the small bowel involved; any more procedures are thought by some to do more harm than good to the patient. This is uncommon with the advent of laparoscopy and better radiological imaging. Most of these cases formerly subjected to "open and close" procedures are now diagnosed in advance and surgery avoided. Laparoscopic-assisted colectomy is a minimally invasive technique that can reduce the size of the incision and may reduce postoperative pain. As with any surgical procedure, colorectal surgery may result in complications, including

wound infection, dehiscence (bursting of wound) or hernia, anastomosis breakdown, leading to abscess or fistula formation, and/or peritonitis, bleeding with or without hematoma formation, adhesions resulting in bowel obstruction. A 5-year study of patients who had surgery in

1997 found the risk of hospital readmission to be 15% after panproctocolectomy, 9% after total colectomy, and 11% after ileostomy[77]

adjacent organ injury; most commonly to the small intestine, ureters, spleen, or bladder, cardiorespiratory complications, such as myocardial

and

infarction, pneumonia, arrythmia, pulmonary embolism, etc.

Chemotherapy
Chemotherapy is used to reduce the likelihood of metastasis developing, shrink tumor size, or slow tumor growth. Chemotherapy is often applied after surgery (adjuvant), before surgery (neoadjuvant), or as the primary therapy (palliative). The treatments listed here have been shown in clinical trials to improve survival and/or reduce mortality rate, and have been approved for use by the US Food and Drug Administration. In colon cancer, chemotherapy after surgery is usually only given if the cancer has spread to the lymph nodes(Stage III).

Adjuvant (after surgery) chemotherapy

5-fluorouracil (5-FU) or capecitabine (Xeloda) Leucovorin (LV, folinic Acid) Oxaliplatin (Eloxatin)

Chemotherapy for metastatic disease. Commonly used first line chemotherapy

regimens involve the combination of infusional 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) with bevacizumab or infusional 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) withbevacizumab or the same chemotherapy drug combinations with cetuximab in KRAS wild type tumors

5-fluorouracil (5-FU) capecitabine (Xeloda) UFT or Tegafur-uracil Leucovorin (LV, folinic Acid) Irinotecan (Camptosar) Oxaliplatin (Eloxatin) Gemcitabine (Gemzar) Bevacizumab (Avastin) Cetuximab (Erbitux) Panitumumab (Vectibix)

In clinical trials for treated/untreated metastatic disease.[78]

Bortezomib (Velcade) Oblimersen (Genasense, G3139) Gefitinib and erlotinib (Tarceva) Topotecan (Hycamtin)

At the 2008 annual meeting of the American Society of Clinical Oncology, researchers announced that colorectal cancer patients that have a mutation in the KRAS gene do not respond to certain therapies, those that inhibit the epidermal growth factor receptor (EGFR)-namely Erbitux (cetuximab) and Vectibix (panitumumab).[79] Following recommendations by ASCO, patients should now be tested for the KRAS gene mutation before being offered these EGFR-inhibiting drugs.[80] In July 2009, the US Food and Drug Administration (FDA) updated the labels of two anti-EGFR monoclonal antibody drugs (panitumumab (Vectibix) and cetuximab (Erbitux)) indicated for treatment of metastatic colorectal cancer to include information about KRAS mutations.[81] However, having the normal KRAS version does not guarantee these drugs will benefit the patient.[79] The trouble with the KRAS mutation is that its downstream of EGFR, says Richard Goldberg, MD, director of oncology at the Lineberger Comprehensive Cancer Center at the University of North Carolina. It doesnt matter if you plug the socket if theres a short downstream of the plug. The mutation turns [EGFR] into a switch thats always on. But this doesnt mean that having normal, or wild-type, KRAS is a fail-safe. It isnt foolproof, cautions Goldberg. If you have wildtype KRAS, youre more likely to respond, but its not a guarantee. Tumors shrink in response to these drugs in up to 40 percent of patients with wild-type KRAS, and progression-free and overall survival is increased. The cost benefit of testing patients for the KRAS gene could potentially save about $740 million a year by not providing EGFR-inhibiting drugsto patients who would not benefit from the drugs. "With the assumption that patients with mutated Kras (35.6% of all patients) would not receive cetuximab (other studies have found Kras mutation in up to 46% of patients), theoretical drug cost savings would be $753 million; considering the cost of Kras testing, net savings would be $740 million."[82] [edit]Radiation

therapy

Radiotherapy is not used routinely in colon cancer, as it could lead to radiation enteritis, and it is difficult to target specific portions of the colon. It is more common for radiation to be used in

rectal cancer, since the rectum does not move as much as the colon and is thus easier to target. Indications include:

Colon cancer

pain relief and palliation - targeted at metastatic tumor deposits if they compress

vital structures and/or cause pain

Rectal cancer

neoadjuvant - given before surgery in patients with tumors that extend outside

the rectum or have spread to regional lymph nodes, to decrease the risk of recurrence following surgery or to allow for less invasive surgical approaches (such as a low anterior resection instead of an abdominoperineal resection). In locally advanced adenocarcinoma of middle and lower rectum, regional hyperthermia added to chemoradiotherapy achieved good results in terms of rate of sphincter-sparing surgery.
[83]

adjuvant - where a tumor perforates the rectum or involves regional lymph nodes palliative - to decrease the tumor burden to relieve or prevent symptoms

(AJCC T3 or T4 tumors or Duke's B or C tumors)

Sometimes chemotherapy agents are used to increase the effectiveness of radiation by sensitizing tumor cells, if present. ]Immunotherapy Bacillus Calmette-Gurin (BCG) is being investigated as an adjuvant mixed with autologous tumor cells in immunotherapy for colorectal cancer.[84] [edit]Cancer

Vaccine

TroVax, a cancer vaccine,[85] produced by Oxford BioMedica,[86] is in Phase III trials for renal cancers, and Phase III trials are planned for colon cancers.[87] [edit]Treatment

of liver metastases

According to the American Cancer Society statistics in 2006,[88] over 20% of patients present with metastatic (stage IV) colorectal cancer at the time of diagnosis, and up to 25% of this group will have isolated liver metastasis that is potentially resectable. Lesions which undergo curative resection have demonstrated 5-year survival outcomes now exceeding 50%.[89]

Resectability of a liver metastasis is determined using preoperative imaging studies (CT or MRI), intraoperative ultrasound, and by direct palpation and visualization during resection. Lesions confined to the right lobe are amenable to en bloc removal with a right hepatectomy (liver resection) surgery. Smaller lesions of the central or left liver lobe may sometimes be resected in anatomic "segments", while large lesions of left hepatic lobe are resected by a procedure called hepatic trisegmentectomy. Treatment of lesions by smaller, nonanatomic "wedge" resections is associated with higher recurrence rates. Some lesions which are not initially amenable to surgical resection may become candidates if they have significant responses to preoperative chemotherapy or immunotherapy regimens. Lesions which are not amenable to surgical resection for cure can be treated with modalities including radio-frequency ablation (RFA), cryoablation, and chemoembolization. Patients with colon cancer and metastatic disease to the liver may be treated in either a single surgery or in staged surgeries (with the colon tumor traditionally removed first) depending upon the fitness of the patient for prolonged surgery, the difficulty expected with the procedure with either the colon or liver resection, and the comfort of the surgery performing potentially complex hepatic surgery.

Surgery is the most common treatment for colorectal cancer. During surgery, the tumor, a small margin of the surrounding healthy bowel, and adjacent lymph nodes are removed. The surgeon then reconnects the healthy sections of the bowel. In patients with rectal cancer, the rectum is permanently removed. The surgeon then creates an opening (colostomy) on the abdomen wall through which solid waste in the colon is excreted. Specially trained nurses (enterostomal therapists) can help patients adjust to colostomies, and most patients with colostomies return to a normal lifestyle. The long-term prognosis after surgery depends on whether the cancer has spread to other organs (metastasis). The risk of metastasis is proportional to the depth of penetration of the cancer into the bowel wall. In patients with early colon cancer which is limited to the superficial layer of the bowel wall, surgery is often the only treatment needed. These patients can experience long-term survival in excess of 80%. In patients with advanced colon cancer, wherein the tumor has penetrated beyond the bowel wall and there is evidence of metastasis to distant organs, the fiveyear survival rate is less than 10%. In some patients, there is no evidence of distant metastasis at the time of surgery, but the cancer has penetrated deeply into the colon wall or reached adjacent lymph

nodes. These patients are at risk of tumor recurrence either locally or in distant organs. Chemotherapy in these patients may delay tumor recurrence and improve survival.

Chemotherapy is the use of medications to kill cancer cells. It is a systemic therapy, meaning that the medication travels throughout the body to destroy cancer cells. After colon cancer surgery, some patients may harbor microscopic metastasis (small foci of cancer cells that cannot be detected). Chemotherapy is given shortly after surgery to destroy these microscopic cells. Chemotherapy given in this manner is called adjuvant chemotherapy. Recent studies have shown increased survival and delay of tumor recurrence in some patients treated with adjuvant chemotherapy within five weeks of surgery. Most drug regimens have included the use of 5flourauracil (5-FU). On the other hand, chemotherapy for shrinking or controlling the growth of metastatic tumors has been disappointing. Improvement in the overall survival for patients with widespread metastasis has not been convincingly demonstrated. Chemotherapy is usually given in a doctor's office, in the hospital as a outpatient, or at home. Chemotherapy is usually given in cycles of treatment periods followed by recovery periods. Side effects of chemotherapy vary from person to person, and also depend on the agents given. Modern chemotherapy agents are usually well tolerated, and side effects are manageable. In general, anticancer medications destroy cells that are rapidly growing and dividing. Therefore, red blood cells, platelets, and white blood cells are frequently affected by chemotherapy. Common side effects include anemia, loss of energy, easy bruising, and a low resistance to infections. Cells in the hair roots and intestines also divide rapidly. Therefore, chemotherapy can cause hair loss, mouth sores, nausea, vomiting, and diarrhea. Radiation therapy in colorectal cancer has been limited to treating cancer of the rectum. There is a decreased local recurrence of rectal cancer in patients receiving radiation either prior to or after surgery. Without radiation, the risk of rectal cancer recurrence is close to 50%. With radiation, the risk is lowered to approximately 7%. Side effects of radiation treatment include fatigue, temporary or permanent pelvic hair loss, and skin irritation in the treated areas. Other treatments have included the use of localized infusion of chemotherapeutic agents into the liver, the most common site of metastasis. This involves the insertion of a pump into the blood supply of the liver which can deliver high doses of medicine directly to the liver tumor. Response rates for these treatments have been reported to be as high as eighty percent. Side effects, however, can be serious. Additional

experimental agents considered for the treatment of colon cancer include the use of cancer-seeking antibodies bound to cancer-fighting drugs. Such combinations can specifically seek and destroy tumor tissues in the body. Other treatments attempt to boost the immune system, the bodies' own defense system, in an effort to more effectively attack and control colon cancer. In patients who are poor surgical risks, but who have large tumors which are causing obstruction or bleeding, laser treatment can be used to destroy cancerous tissue and relieve associated symptoms. Still other experimental agents include the use of photodynamic therapy. In this treatment, a light sensitive agent is taken up by the tumor which can then be activated to cause tumor destruction.

NURSING DIAGNOSIS
Pain, related to surgical intervention Risk for impaired skin integrity (peristomal), related to fecal drainage and pouch adhesive Risk for constipation/diarrhea, related to effects of surgery on bowel function Risk for disturbed body image, related to colostomy Risk for sexual dysfunction, related to wide rectal incision, radiation therapy, and colostomy

NURSING CONSIDERATION
Provide analgesia as ordered, evaluating its effectiveness. Discuss foods that cause odor and gas. Teach colostomy care. Maintain consistent nursing personnel assignment to facilitate trust. Refer to the local United Ostomy Association. Provide a list of local medical supply companies for ostomy supplies. Provide for privacy when teaching and discussing concerns about ostomy.

PREVENTION
Most colorectal cancers should be preventable, through increased surveillance, improved lifestyle, and, probably, the use of dietary chemopreventative agents.

Unfortunately, colon cancers can be well advanced before they are detected. The most effective prevention of colon cancer is early detection and removal of precancerous colon polyps before they turn cancerous. Even in cases where cancer has already developed, early detection still significantly improves the chances of a cure by surgically removing the cancer before the disease spreads to other organs. Multiple world health organizations have suggested general screening guidelines.

Lifestyle and nutrition

The comparison of colorectal cancer incidence in various countries strongly suggests that sedentarity, overeating (i.e., high caloric intake), and perhaps a diet high in meat (red or processed) could increase the risk of colorectal cancer. In contrast, a healthy body weight, physical fitness, and good nutrition decreases cancer risk in general. Accordingly, lifestyle changes could decrease the risk of colorectal cancer as much as 60-80%.[62] A high intake of dietary fiber (from eating fruits, vegetables, cereals, and other high fiber food products) has, until recently, been thought to reduce the risk of colorectal cancer and adenoma. In the largest study ever to examine this theory (88,757 subjects tracked over 16 years), it has been found that a fiber rich diet does not reduce the risk of colon cancer.[63] A 2005 metaanalysis study further supports these findings.[64] The Harvard School of Public Health states: "Health Effects of Eating Fiber: Long heralded as part of a healthy diet, fiber appears to reduce the risk of developing various conditions, including heart disease, diabetes, diverticular disease, and constipation. Despite what many people may think, however, fiber probably has little, if any effect on colon cancer risk."[6

Chemoprevention

More than 200 agents, including the above cited phytochemicals, and other food components like calcium or folic acid (a B vitamin), andNSAIDs like aspirin, are able to decrease carcinogenesis in pre-clinical development models: Some studies show full inhibition of carcinogen-induced tumours in the colon of rats. Other studies show strong inhibition of spontaneous intestinal polyps in mutated mice (Min mice). Chemoprevention clinical trials in human volunteers have shown smaller prevention, but few intervention studies have been completed today. The "chemoprevention database" shows the results of all published scientific studies of chemopreventive agents, in people and in animals.[66]
Aspirin chemoprophylaxis

Aspirin should not be taken routinely to prevent colorectal cancer, even in people with a family history of the disease, because the risk of bleeding and kidney failure from high dose aspirin (300 mg or more) outweigh the possible benefits.[67] A clinical practice guideline of the U.S. Preventive Services Task Force (USPSTF) recommended against taking aspirin (grade D recommendation).[68] The Task Force acknowledged that aspirin may reduce the incidence of colorectal cancer, but "concluded that

harms outweigh the benefits of aspirin and NSAID use for the prevention of colorectal cancer". A subsequent meta-analysis concluded "300 mg or more of aspirin a day for about 5 years is effective in primary prevention of colorectal cancer in randomised controlled trials, with a latency of about 10 years".[69] However, long-term doses over 81 mg per day may increase bleeding events.

Calcium
The meta-analysis by the Cochrane Collaboration of randomized controlled trials published through 2002 concluded "Although the evidence from two RCTs suggests that calcium supplementation might contribute to a moderate degree to the prevention of colorectal adenomatous polyps, this does not constitute sufficient evidence to recommend the general use of calcium supplements to prevent colorectal cancer."[71]Subsequently, one randomized controlled trial by the Women's Health Initiative (WHI) reported negative results.[72] A second randomized controlled trial reported reduction in all cancers, but had insufficient colorectal cancers for analysis.[73]
Vitamin D

A scientific review undertaken by the National Cancer Institute found that vitamin D was beneficial in preventing colorectal cancer, which showed an inverse relationship with blood levels of 80 nmol/L or higher associated with a 72% risk reduction compared with lower than 50 nmol/L.[74] A possible mechanism is inhibition of Hedgehog signal transduction.[75]