Colorectal cancer

From Wikipedia, the free encyclopedia

Colorectal cancer

Classification and external resources

Diagram of the stomach, colon, and rectum

ICD-10

C18.-C20.

ICD-9

153.0-154.1

ICD-O:

M8140/3 (95% of cases)

OMIM

114500

DiseasesDB

2975

MedlinePlus

000262

eMedicine

med/413 med/1994ped/3037

Colorectal cancer, also called colon cancer or large bowel cancer, includes cancerous growths in the colon, rectum and appendix. With 655,000 deaths worldwide per year, it is the fourth most common form of cancer in the United States and the third leading cause of cancer-related death in the Western world.[1][2] Colorectal cancers arise from adenomatous polyps in the colon. These mushroom-shaped

growths are usually benign, but some develop into cancer over time. Localized colon cancer is usually diagnosed through colonoscopy. Invasive cancers that are confined within the wall of the colon (TNM stages I and II) are curable with surgery. If untreated, they spread to regional lymph nodes (stage III), where up to 73% are curable by surgery and chemotherapy. Cancer that metastasizes to distant sites (stage IV) is usually not curable, although chemotherapy can extend survival, and in rare cases, surgery and chemotherapy together have seen patients through to a cure.[3] Radiation is used with rectal cancer. On the cellular and molecular level, colorectal cancer starts with a mutation to theWnt signaling pathway. When Wnt binds to a receptor on the cell, that sets in motion a chain of molecular events that ends with catenin moving into the nucleus and activating a gene on DNA. In colorectal cancer, genes along this chain are damaged. Usually, a gene called APC, which is a "brake" on the Wnt pathway, is damaged. Without a working APC brake, the Wnt pathway is stuck in the "on" position.[3]
Contents
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1 Signs and symptoms

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1.1 Local 1.2 Constitutional

2 Risk factors

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2.1 Alcohol

3 Pathogenesis 4 Diagnosis

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4.1 Other screening methods 4.2 Monitoring 4.3 Pathology 4.4 Staging 

5 Prevention

4.4.1 Dukes system

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5.1 Surveillance 5.2 Lifestyle and nutrition 5.3 Chemoprevention 

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5.3.1 Aspirin chemoprophylaxis 5.3.2 Calcium

5.4 Vitamin D

6 Management

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6.1 Surgery

7 Aspirin 6. [edit]Local Local symptoms are more likely if the tumor is located closer to the anus.1 Follow-up 8 Epidemiology 9 Society and culture o 9.1 Notable patients 10 See also 11 References 12 External links [edit]Signs and symptoms The symptoms of colorectal cancer depend on the location of tumor in the bowel.o o o o o o o o 6. A large left colonic tumour may compress the left ureter and cause hydronephrosis.3 Radiation therapy 6. This situation is characterized by constipation. may indicate colorectal cancer.6 Treatment of liver metastases 6. Most of the symptoms may occur in other diseases as well.2 Chemotherapy 6. including the passage of bright red blood in the stool. Symp toms and signs are divided into local. but is sometimes encountered in colorectal cancer when the disease is located in the beginning of the large bowel. tenesmus and change in stool shape are both characteristic of rectal cancer. black stool with a tarry appearance. and a feeling of incomplete defecation (rectal tenesmus) and reduction in diameter of stool. There may be a change in bowel habit (new-onset constipation or diarrhea in the absence of another cause). A tumor that is large enough to fill the entire lumen of the bowel may cause bowel obstruction. .5 Cancer Vaccine 6. and hence none of the symptoms mentioned here is diagnostic of colorectal cancer. This occasionally leads to the obstructed and distended bowel perforating and causing peritonitis.8 Cimetidine 6. and whether it has spread elsewhere in the body (metastasis). Melena.4 Immunotherapy 6. constitutional (affecting the whole body) and metastatic (caused by spread to other organs). Lower gastrointestinal bleeding. abdominal distension and vomiting. as may the increased presence ofmucus. abdominal pain. normally occurs in upper gastrointestinal bleeding (such as from a duodenal ulcer).9 Support therapies 7 Prognosis o 7.

A large tumor is more likely to be noticed on feeling the abdomen. The lifetime risk of developing colon cancer in the United States is about 7%. The risk of developing colorectal cance increases with age. palpitations and noticed as pallor (pale appearance of the skin). usually deep vein thrombosis.[4] These include: Age.Certain local effects of colorectal cancer occur when the disease has become more advanced. especially in a close relative before the age of 55 or multiple relatives. Normal colorectal mucosa is seen on the right. Certain factors increase a person's risk of developing the disease. uterus. [edit]Constitutional If a tumor has caused chronic occult bleeding. generally due to a decreased appetite. this may be experienced as fatigue. The disease may invade other organs. particularly adenomatous polyps. and it may be noticed by a doctor onphysical examination. More unusual constitutional symptoms are an unexplained fever and one of several paraneoplastic syndromes. and may cause blood or air in the urine (invasion of the bladder) or vaginal discharge (invasion of the female reproductive tract). Women who have had cancer of the ovary. The removal of colon polyps at the time of colonoscopy reduces the subsequent risk of colon cancer. iron deficiency anemia may occur. or breast are at higher risk of developing colorectal cancer. Most cases occur in the 60s and 70s. The most common paraneoplastic syndrome is thrombosis.  History of cancer.[6]  Familial adenomatous polyposis (FAP) carries a near 100% risk of developing colorectal cancer by the age of 40 if untreated  Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome . Individuals who have previously been diagnosed and treated for colon cancer are at risk for developing colon cancer in the future. Colorectal cancer may also lead to weight loss.   Polyps of the colon. r [5] while cases before age 50 are uncommon unless a family history of early colon cancer is present. a type of colonic polyp and a precursor of colorectal cancer. H&E stain.  Heredity:  Family history of colon cancer. [edit]Risk factors Micrograph of a tubular adenoma (left of image). are a risk factor for colon cancer.

[19]  Alcohol.[12] Carbonic acid type surfactant easily combine with calcium ion and become detoxication. Individuals who frequently eat fish showed a decreased risk.[11] The nature of the relationship between dietary fiber and risk of colorectal cancer remains controversial. low-fiber diet was associated with other risk factors. Male smokers had more than a 30% increase in risk of dying from the disease compared to men who never had smoked.    Primary sclerosing cholangitis offers a risk independent to ulcerative colitis Low levels of selenium. as well as those low in fiber. little evidence of an influence of endogenous hormones on the risk of colorectal cancer."[7][8]  Diet. a study by the European Prospective Investigation into Cancer and Nutrition suggested that diets high in red and processed meat. Smokers are more likely to die of colorectal cancer than non-smokers. but less than that of patients with ulcerative colitis. Studies show that a diet high in red meat[9] and low in fresh fruit. In contrast. tamoxifen.[17]  red Environmental factors. other studies have cast doubt on the claim that diets high in fiber decrease the risk of colorectal cancer.   Physical inactivity.  Lithocholic acid. Virus. People who are physically active are at lower risk of developing colorectal cancer. Exposure to some viruses (such as particular strains of human papilloma virus) may be associated with colorectal cancer.[18] There is. rather.[15][16] About one percent of colorectal cancer patients have a history of chronic ulcerative colitis.[13][14] Inflammatory bowel disease. vegetables. Patients with colorectal Crohn's disease have a more than average risk of colorectal cancer. Drinking. In June 2005. An American Cancer Society study found that "Women who smoked were more than 40% more likely to die from colorectal cancer than women who never had smoked.[20] . It has been implicated in human and experimental animal carcinogenesis. may be a risk factor. there is evidence that exogenous estrogens such as hormone replacement therapy (HRT). It is made from chenodeoxycholic acid by bacterial action in the colon. are associated with an increased risk of colorectal cancer. poultry and fish increases the risk of colorectal cancer.  Gardner syndrome Smoking. The differences in the time trends in colorectal cancer in males and females could be explained by cohort effects in exposure to some gender -specific risk factor. leading to confounding. especially heavily. The risk of developing colorectal cancer varies inversely with the age of onset of the colitis and directly with the extent of colonic involvement and the duration of active disease. Lithocholic acid is a bile acid that acts as a detergent to solubilize fats for absorption. or oral contraceptives might be associated with colorectal tumors.[15] Industrialized countries are at a relatively increased risk compa to less developed countries that traditionally had high-fiber/low-fat diets. however. in the etiology of colorectal cancers. Studies of migrant populations have revealed a role for environmental factors.  Exogenous hormones.[10] However. particularly dietary. one possibility that has been suggested is exposure to estrogens.

"Heavy alcohol use may also increase the risk of colorectal cancer". normally monitors cell division and kills cells if they have Wnt pathway defects. and others are acquired.[21] [edit]Alcohol The WCRF panel report Food. [31] however.)[3] Beyond the defects in the Wnt-APC-beta-catinin signaling pathway. In our sample. Vitamin B6 intake is inversely associated with the risk of colorectal cancer."[27][28][29] One study found that "While there was a more than twofold increased risk of significant colorectal neoplasia in people who drink spirits and beer. Some of the mutations are inherited. people who drank wine had a lower risk. then -catinin itself is.". The TP53 protein. -catinin moves into the nucleus.[25][26] Despite the large number of studies. produced by the p53 gene.[32] Drinking may be a cause of earlier onset of colorectal cancer. the National Cancer Institute does not list alcohol as a risk factor.[22] The NIAAA reports that: "Epidemiologic studies have found a small but consistent dose -dependent [23][24] association between alcohol consumption and colorectal cancer even when controlling for fiber and other dietary factors. and activates more proteins. Physical Activity and the Prevention of Cancer: a Global Perspective finds the evidence "convincing" that alcoholic drinks increase the risk of colorectal cancer in men.[34][35] The most commonly mutated gene in all colorectal cancer is the APC gene. Without APC. as a result of mutations along the 'Wnt signaling pathway. on another page it states. One study found that "People who drink more than 30 grams of alcohol per day (and especially those who drink more than 45 grams per day) appear to have a slightly higher risk for colorectal cancer. causality cannot be determined from the available data. people who drank more than eight servings of beer or spirits per week had at least a one in five chance of having [30] significant colorectal neoplasia detected by screening colonoscopy. Nutrition."[20] "Heavy alcohol use may also increase the risk of colorectal cancer" (NCI).[33] [edit]Pathogenesis Colorectal cancer is a disease originating from the epithelial cells lining the colon or rectum of the gastrointestinal tract. which produces the APC protein. binds to DNA. it's best to drink in moderation."[27] Another found that "The consumption of one or more alcoholic beverages a day at baseline was associated with approximately a 70% greater risk of colon cancer. Other research suggests that "to minimize your risk of developing colorectal cancer. The APC protein is the "brake" on the -catenin protein. Eventually."[20] On its colorectal cancer page. a cell line acquires a mutation in the p53 gene . however. (If APC is not mutated in colorectal cancer. other mutations must occur for the cell to become cancerous.

Thereare several different tests available for this purpose.e. TGF.[38] . can become mutated with mutations that make them oversignal the cell. RAF. The sensitivity of immunochemical testing is superior to that of chemical testing without an unacceptable redu ction in specifity.and DCC (Deleted in Colorectal Cancer). It only detects tumors large enough to be felt in the distal part of the rectum but is useful as an initial screening test. Sometimes TGF.[3] DCC commonly has deletion of its chromosome segment in colorectal cancer. PTEN normally inhibits PI3K. For example. Colorectal cancer can take many years to develop and early detection of colorectal cancer greatly improves the chances of a cure. but a downstream protein named SMAD is.[3] [edit]Diagnosis Endoscopic image of colon canceridentified in sigmoid colon on screeningcolonoscopy in the setting of Crohn's disease. colorectal cancer screening rates remain low.[37] Therefore.has a deactivating mutation in at least half of colorectal cancers.)[3] Other apoptotic proteins commonly deactivated in colorectal cancers are TGF. Two types of tests can be used for detecting occult blood in stools i. and PI3K.[36] Some genes are oncogenes -. gloved finger into the rectum to feel for abnormal areas. Despite this. which normally encourage the cell to divide in response to growth factors. screening for the disease is recommended in individuals who are at increased risk.is not deactivated.   Fecal occult blood test (FOBT): a test for blood in the stool. The National Cancer Policy Board of the Institute of Medicine estimated in 2003 that even modest efforts to implement colorectal cancer screening methods would result in a 29 percent drop in cancer deaths in 20 years. but another protective protein named BAX is. guaiac based (chemical test) and immunochemical.they are overexpressed in colorectal cancer.and transforms the tissue from an adenoma into an invasive carcinoma. but sometimes PTEN gets mutated. (Sometimes p53 is not mutated. Digital rectal exam (DRE): The doctor inserts a lubricated. RAS.

and an image is formed by measuring the emission of radiation from the sugar. The result is a thin layer of barium over the inner lining of the colon which is visible on X -ray films. Some cancers are found in CAT scans performed for other reasons.  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 radiologistto interpret. An enema containing barium sulfate is administered. and assess disease recurrence. [edit]Other screening methods  Double contrast barium enema (DCBE): First. the sugar collects in tissues with high metabolic activity. this can be used to differentiate benign and malignant tumors. such as hereditary nonpolyposis colorectal cancer (HNPCC) or familial adenomatous polyposis(FAP). and are not recommended for screening. This technique is approaching colonoscopy in sensitivity for polyps. CA19-9 and CA 242 biomarkers can indicate e-selectin related metastatic risks. and is a cost-effective way to differentiate resectable from nonresectable disease. However. colonoscopy or FOBT plus sigmoidoscopy are the preferred screening options.  Standard computed axial tomography is an x-ray method that can be used to determine the degree of spread of cancer. In particular.  Colonoscopy: A lighted probe called a colonoscope is inserted into the rectum and the entire colon to look for polyps and other abnormalities that may be caused by cancer. distending it.  Positron emission tomography (PET) is a 3-dimensional scanning technology where a radioactive sugar is injected into the patient. but is not sensitive enough to use for screening. These tests are frequently false positive or false negative.  Whole-body PET imaging is the most accurate diagnostic test for detection of recurrent colorectal cancer. Endoscopy:  Sigmoidoscopy: A lighted probe (sigmoidoscope) is inserted into the rectum and lower colon to check for polyps and other abnormalities. A colonoscopy has the advantage that if polyps are found during the procedure they can be removed immediately. high levels of carcinoembryonic antigen (CEA) in the blood can indicate metastasis of adenocarcinoma. This technique can miss the (less common) flat polyp.  Blood tests: Measurement of the patient's blood for elevated levels of certain proteins can give an indication of tumor load. then air is insufflated into the colon. PET is not used for screening and does not (yet) have a place in routine workup of colorectal cancer cases.  Genetic counseling and genetic testing for families who may have a hereditary form of colon cancer. an overnight preparation is taken to cleanse the colon. In the United States. it can be useful to assess disease recurrence. Tissue can also be taken for biopsy. A cancer or a precancerous polyp can be detected this way. help follow therapeutic progress. A PET scan . any polyps found must still be removed by standard colonoscopy. Because cancer cells often have very high metabolic rates.

The goal of this technique is to select individuals for colonoscopy rather than to replace colonoscopy as the gold standard of colorectal cancer diagnosis. [42] [43] . 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. [41]. Capture. CEA may be used to monitor and assess response to treatment in patients with metastatic disease. followed by PCR amplifies the DNA to detectable levels for assay. Plasma miRNA has been shown to be a promising biomarker for many diseases including cancer. irregularly shaped tumor located above the label). reddish. Blood plasma samples collected from patients with early.[39]   High C-Reactive Protein levels is risk marker [40] 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. [edit]Monitoring Carcinoembryonic antigen (CEA) is a protein found on virtually all colorectal tumors. . attached to the normal beige lining by a stalk) and one invasive colorectal carcinoma (the crater-like. CEA can also be used to monitor recurrence in patients post-operatively. resectable (Stage II) colorectal cancer and sex-and agematched healthy volunteers were profiled.  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.is indicated whenever a major management decision depends upon accurate evaluation oftumour presence and extent.[citation needed] [edit]Pathology Gross appearance of a colectomyspecimen containing two adenomatous polyps (the brownish oval tumors above the labels. So far potential biomarkers have shown promising specificity and sensitivity. Clinical studies have shown a cancer detection sensitivity of 71% ±91%.

The pathology of the tumor is usually reported from the analysis of tissue taken from a biopsy or surgery. Micrograph of an invasive adenocarcinoma (the most common type of colorectal cancer). The most common colon cancer cell type is adenocarcinoma which accounts for 95% of cases. Near normal colon -lining cells are seen at the top right of the image. Histopathologic image of colonic carcinoid stained by hematoxylin and eosin. A pathology report will usually contain a description of cell type and grade. the tumour grows outwards from one location in the bowel wall. that is. rarer types includelymphoma and squamous cell carcinoma. and can obstruct the bowel much like a napkin ring. . The cancerous cells are seen in the center and at the bottom right of the image (blue). Other.Gross appearance of a colectomyspecimen containing one invasive colorectal carcinoma (the crater -like. Cancers on the right side (ascending colon and cecum) tend to be exophytic. This very rarely causes obstruction of feces. irregularly shaped tumor). and presents with symptoms such as anemia. Left-sided tumours tend to be circumferential. reddish.

"T" denotes the degree of invasion of the intestinal wall. If the mucus remains inside the tumor cell."signet-ring cell. The most common staging system is the TNM (for tumors/nodes/metastases) system. "N" the degree of lymphatic node involvement. The broader stage of a cancer is usually quoted as a number I. PET Scanning. the submucosa and thence the muscularis propria. This enzyme is generally not found in healthy colon tissue. It invades the wall. cellular pleomorphism. and other imaging studies. II. cancer-in-situ Stage I T1 N0 M0 T1: Tumor invades submucosa Stage I T2 N0 M0 T2: Tumor invades muscularis propria . it pushes the nucleus at the periphery . multiple lume ns. and poorly differentiated. CT. Preoperative staging of rectal cancers may be done with endoscopic ultrasound. IV derived from the TNM value grouped by prognosis. The systems for staging colorectal cancers depend on the extent of local invasion. and "M" the degree of metastasis.Adenocarcinoma is a malignant epithelial tumor. reduced stroma ("back to back" aspect). harboring pluristratification. Adjunct staging of metastasis include Abdominal Ultrasound. Tumor cells describe irregular tubular structures. infiltrating the muscularis mucosae.[44] Most colorectal cancer tumors are thought to be cyclooxygenase-2 (COX-2) positive. the degree of lymph node nvolvement and i whether there is distant metastasis. from the American Joint Committee on Cancer (AJCC). Definitive staging can only be done after surgery has been performed and pathology reports reviewed. but is thought to fuel abnormal cell growth. Sometimes. tumor cells are discohesive and secrete mucus.mucinous (colloid) adenocarcinoma. and to determine the best method of treatment. An exception to this principle would be after a colonoscopic polypectomy of a malignant pedunculated polyp with minimal invasion. and mucosecretion of the predominant pattern. originating from glandular epithelium of the colorectal mucosa. III." Depending on glandular architecture. moderately. [edit]Staging Colon cancer staging is an estimate of the amount of penetration of a particular cancer. adenocarcinoma may present three degrees o f differentiation: well. Details of this system are in the graph below: AJCC stage TNM stage TNM stage criteria for colorectal cancer[45] Stage 0 Tis N0 M0 Tis: Tumor confined to mucosa. It is performed for diagnostic and research purposes. a higher number indicates a more advanced cancer and likely a worse outcome. The TNMsystem assigns a number based on three categories. poorly differentiated. which invades the interstitium producing large pools of mucus/colloid (optically "empty" spaces).

Any T. in glands(circular/ovoid structures) and eosinophilic(bright pink). Stage III-B T3-4 N1 M0 N1: Metastasis to 1 to 3 regional lymph nodes. T3 or T4. H&E stain.With lymph node(s) involvement (this is further subdivided into C1 lymph node involvement where the apical node is not involved and C2 where the apical lymph node is involved)     D . M1 M1: Distant metastases present. N2 M0 N2: Metastasis to 4 or more regional lymph nodes. that predates the TNM system. Stage IV any T. Stage III-C any T.With distant metastasis A few cancer centers still use this staging system. Astler-Coller .Tumour invading through the intestinal wall C . [edit]Dukes system Micrograph of a colorectaladenocarcinoma metastasis to a lymph node. any N. The cancerous cells are at the top center-left of the image.Tumour confined to the intestinal wall B . any N.Stage II-A T3 N0 M0 T3: Tumor invades subserosa or beyond (without other organs involved) Stage II-B T4 N0 M0 T4: Tumor invades adjacent organs or perforates the visceral peritoneum Stage III-A T1-2 N1 M0 N1: Metastasis to 1 to 3 regional lymph nodes. Dukes classification is an older and less complicated staging system. T1 or T2. Any T. It identifies the stages as:[46] A .

a healthy body weight. the use of dietary chemopreventative agents. [edit]Lifestyle and nutrition The comparison of colorectal cancer incidence in various countries strongly suggests that sedentarity. probably. high caloric intake). and perhaps a diet high in meat (red or processed) could increase the risk of colorectal cancer. overeating (i.A: Tumor limited to mucosa. improved lifestyle.[47] As per current guidelines under National Comprehensive Cancer Network. Studies show this procedure would decrease by > 80% the risk of cancer death. and.e. physical fitness. Additional Staging venous invasion (v) v0 no venous invasion v1 microscopic venous invasion v2 macroscopic venous invasion    lymphatic invasion (l) l0 no lymphatic vessel invasion l1 lymphatic vessel invasion   histologic grade (G) g1 well differentiated g2 moderately differentiated g3 poorly differentiated g4 undiffererentiated     [edit]Prevention Most colorectal cancers should be preventable. [edit]Surveillance Most colorectal cancer arise from adenomatous polyps. carcinoma in situ B1: Tumor grows through muscularis mucosae but not through muscularis propria B2: Tumor grows beyond muscularis propria C1: Stage B1 with regional lymph node metastases C2: Stage B2 with regional lymph node metastases D: Distant metastases. and good nutrition decreases . in average risk individuals with negative family history of colon cancer and personal history negative for adenomas orInflammatory Bowel diseases. flexible sigmoidoscopy every 5 years with fecal occult blood testing annually or double contrast barium enema are other options acceptable for screening rather than colonoscopy every 10 years (which is currently the Gold-Standard of care). through increased sur veillance. In contrast. These lesions can be detected and removed during colonoscopy. provided it is started by the age of 50.. and repeated every 5 or 10 years.

this does not constitute sufficient evidence to recommend the general use of calcium supplements to prevent colorectal cancer.[52] [edit]Aspirin chemoprophylaxis Aspirin should not be taken routinely to prevent colorectal cancer. and other food components like calcium or folic acid (a B vitamin). are able to decrease carcinogenesis in pre-clinical development models: Some studies show full inhibition of carcinogen -induced tumours in the colon of rats.S. cereals. been thought to reduce the risk of colorectal cancer and adenoma. long-term doses over 81 mg per day may increase bleeding events. if any effect on colon cancer risk. vegetables.[48] A high intake of dietary fiber (from eating fruits. and constipation. one randomized controlled trial by the Women's Health Initiative (WHI) reported .[53] A clinical practice guideline of the U. diverticular disease. Despite what many people may think. until recently. Other studies show strong inhibition of spontaneous intestinal polyps in mutated mice (Min mice). even in people with a family history of the disease. and other high fiber food products) has.[49] A 2005 meta-analysis study further supports these findings. including heart disease.757 subjects tracked over 16 years). in people and in animals.[50] The Harvard School of Public Health states: "Health Effects of Eating Fiber: Long heralded as part of a healthy diet.[56] [edit]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 contribut e to a moderate degree to the prevention of colorectal adenomatous polyps. with a latency of about 10 years". lifestyle changes could decrease the risk of colorectal cancer as much as 60-80%.[55] However.[57] Subsequently. but "concluded that harms outweigh the bene of aspirin and NSAID use fits for the prevention of colorectal cancer".cancer risk in general. In the largest study ever to examine this theory (88. fiber probably has little. Chemoprevention clinical trials in human volunteers have shown smaller prevention. diabetes. it has been found that a fiber rich diet does not reduce the risk of colon cancer. because the risk of bleeding and kidney failure from high dose aspirin (300mg or more) outweigh the possible benefits. [54] The Task Force acknowledged that aspirin may reduce the incidence of colorectal cancer. A subsequent meta-analysisconcluded "300 mg or more of aspirin a day for about 5 years is effective in primary prevention of colorectal cancer in randomised controlled trials. but few intervention studies have been completed today."[51] [edit]Chemoprevention More than 200 agents. including the above cited phytochemicals.". fiber appears to reduce the risk of developing various conditions. however. Accordingly. and NSAIDs like aspirin. The "chemoprevention database" shows the results of all published scientific studies of chemopreventive agents. Preventive Services Task Force (USPSTF) recommended against taking aspirin (grade D recommendation).

  In colon cancer. when it is detected at later stages (when distantmetastases are present) it is less likely to be curable. however. Curative Surgical treatment can be offered if the tumor is localized.e. palliative.[60] A possible mechanism is inhibition of Hedgehog signal transduction. but had insufficient colorectal cancers for analysis. . Surgery remains the primary treatment while chemotherapy and/or radiotherapy may be recommended depending on the individual patient's staging and other medical factors. If possible. colectomy). Clinical trials suggest that "otherwise fit" elderly patients fare well if they have adjuvant chemotherapy after surgery.  Curative surgery on rectal cancer includes total mesorectal excision (lower anterior resection) or abdominoperineal excision. palliative (non curative) resection of the primary tumor is still offered in order to reduce further morbidity caused by tumor bleeding.[62] [edit]Surgery Surgeries can be categorised into curative.. common and may be curative in selected patients. fecal diversion. and its catabolic effect.negative results. Surgical removal of isolated liver metastases is. a more advanced tumor typically requires surgical removal of the section of colon containing the tumor with sufficient margins. When colorectal cancer is caught at early stages (with little spread) it can be curable. the remaining parts of colon are anastomosed together to create a functioning colon. it can be a challenge to determine how aggressively to treat a particular patient. or open -and-close. so chronological age alone shouldnot be a contraindication to aggressive management. Because colon cancer primarily affects the elderly. astoma (artificial orifice) is created. improved chemotherapy has increased the number of patients who are offered surgical removal of isolated liver metastases. and radical en-bloc resection of mesentery and lymph nodes to reduce local recurrence (i.[61] [edit]Management The treatment depends on the staging of the cancer. Very early cancer that develops within a polyp can often be cured by removing the polyp (i.[59] [edit]Vitamin D A scientific review undertaken by the National Cancer Institute found that vitamin D was beneficial in preventing colorectal cancer. In cases when anastomosis is not possible. In case of multiple metastases. polypectomy) at the time of colonoscopy. which showed an inverse relationship with blood levels of 80nmol/L or higher associated with a 72% risk reduction compared with lower than 50 nmol/L. However.e. invasion.[58] A second randomized controlled trial reported reduction in all cancers. especially after surgery. bypass..

and irinotecan (FOLFIRI) with bevacizumab or the same chemotherapy drug combinations with cetuximab in KRAS wild type tumors . colorectal surgery may result in complications including wound infection. ureters. Most of these cases formerly subjected to "open and close" procedures are now diagnosed in advance and surgery avoided. As with any surgical procedure. or as the primary therapy (palliative). and/or peritonitis bleeding with or without hematoma formation adhesions resulting in bowel obstruction. leucovorin. and 11% after ileostomy[63]       adjacent organ injury. In colon cancer.If the tumor invaded into adjacent vital structures which makes excision technically difficult. The worst case would be an open-and-close surgery. spleen. or slow tumor growth. This is uncommon with the advent of laparoscopy and better radiological imaging. [edit]Chemotherapy Chemotherapy is used to reduce the likelihood of metastasis developing.      5-fluorouracil (5-FU) or Capecitabine (Xeloda) Leucovorin (LV. any more procedures are thought by some to do more harm than good to the patient. Commonly used first line chemotherapy regimens involve the combination of infusional 5-fluorouracil. when surgeons find the tumor unresectable and the small bowel involved. Folinic Acid) Oxaliplatin (Eloxatin) Chemotherapy for metastatic disease. Adjuvant (after surgery) chemotherapy. A 5-year study of patients who had surgery in 1997 found the risk of hospital readmission to be 15% after panproctocolectomy. leading to abscess or fistula formation. most commonly to the small intestine. 9% after total colectomy. pneumonia. the surgeons may prefer to bypass the tumor (ileotransverse bypass) or to do a proximal fecal diversionthrough a stoma. 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. pulmonary embolism etc. leucovorin. chemotherapy after surgery is usually only given if the cancer has spread to the lymph nodes (Stage III). arrythmia. Chemotherapy is often applied after surgery (adjuvant). or bladder Cardiorespiratory complications such as myocardial infarction. Dehiscence (bursting of wound) or hernia anastomosis breakdown. before surgery (neo-adjuvant). and oxaliplatin (FOLFOX) with bevacizumabor infusional 5-fluorouracil. shrink tumor size. Laparoscopic-assisted colectomy is a minimally invasive technique that can reduce the size of the incision and may reduce post-operative pain.

[65] Following recommendations by ASCO.6% of all patients) would not receive cetuximab (other studies have found Kras mutation in up to 46% of patients). MD. The cost benefit of testing patients for the KRAS gene could potentially save about $740 million a year by not providing EGFR-inhibiting drugs to patients who would not benefit from the drugs. or wild-type. and progression-free and overall survival is increased. KRAS is a fail-safe. those that inhibit the epidermal growth factor receptor (EGFR)--namely Erbitux (cetuximab) and Vectibix (panitumumab).´ Tumors shrink in response to these drugs in up to 40 percent of patients with wild-type KRAS.         5-fluorouracil (5-FU) or Capecitabine UFT or Tegafur-uracil Leucovorin (LV. director of oncology at the Lineberger Comprehensive Cancer Center at the University of North Carolina. ³It isn¶t foolproof.[66] In July 2009.´ says Richard Goldberg. The mutation turns [EGFR] into a switch that¶s always on. considering the cost of Kras testing. having the normal KRAS version does not guarantee that these drugs will benefit the patient. ³If you have wild-type KRAS. G3139) Gefitinib and Erlotinib (Tarceva) Topotecan (Hycamtin) At the 2008 annual meeting of the American Society of Clinical Oncology.[65] ³The trouble with the KRAS mutation is that it¶s downstream of EGFR. ³It doesn¶t matter if you plug the socket if there¶s a short downstream of the plug. you¶re more likely to respond. theoretical drug cost savings would be $753 million.´ cautions Goldberg. "With the assumption that patients with mutated Kras (35. net savings would be $740 million. researchers announced that colorectal cancer patients that have a mutation in the KRAS gene do not respond to certain therapies. but it¶s not a guarantee. patients should now be tested for the KRAS gene mutation before being offered these EGFR-inhibiting drugs. Folinic Acid) Irinotecan (Camptosar) Oxaliplatin (Eloxatin) Bevacizumab (Avastin) Cetuximab (Erbitux) Panitumumab (Vectibix) In clinical trials for treated/untreated metastatic disease.[64]     Bortezomib (Velcade) Oblimersen (Genasense."[68] [edit]Radiation therapy .[67] However. 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.´ But this doesn¶t mean that having normal.

Indications include: Colon cancer   pain relief and palliation . and it is difficult to target specific portions of the colon. since the rectum does not move as much as the colon and is thus easier to target.Radiotherapy is not used routinely in colon cancer.[73] [edit]Treatment of liver metastases According to the American Cancer Society statistics in 2006. as it could lead to radiation enteritis.[71] produced by Oxford BioMedica. In locally advanced adenocarcinoma of middle and lower rectum.where a tumor perforates the rectum or involves regional lymph nodes (AJCC T3 or T4 tumors or Duke's B or C tumors)  palliative . while large .[74] 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. in order 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 abdomino-perineal resection). regional hyperthermia added to chemoradiotherapy achieved good results in terms of rate of sphincter sparing surgery. and phase III trials are planned for colon cancers. It is more common for radiation to be used in rectal cancer. and by direct palpation and visualization during resection.[75] Resectability of a liver metastasis is determined using preoperative imaging studies (CT or MRI). Lesions confined to the right lobe are amenable to en bloc removal with a right hepatectomy (liver resection) surgery.[70] [edit]Cancer Vaccine TroVax. intraoperative ultrasound.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 tumor burden in order to relieve or prevent symptoms Sometimes chemotherapy agents are used to increase the effectiveness of radiation by sensitizing tumor cells if present. Lesions which undergo curative resection have demonstrated 5-year survival outcomes now exceeding 50%. Smaller lesions of the central or left liver lobe may sometimes be resected in anatomic "segments". [edit]Immunotherapy Bacillus Calmette-Guérin (BCG) is being investigated as an adjuvant mixed with autologous tumor cells in immunotherapy for colorectal cancer.[69]   adjuvant . a cancer vaccine.[72] is in Phase III trials for renal cancers.

while distant metastases (any T. the difficulty expected with the procedure with either the colon or liver resection. and chemoembolization. A more invasive tumor. yet without node involvement (T3-4. social service support.279 people diagnosed with stages I-III (non-metastatic) colorectal cancer[77] have suggested a significant improvement in cancer-specific survival in a subset of patients using aspirin. The influence of a spirin on survival after diagnosis of colorectal cancer is unknown. and the comfort of the surgery performing potentially complex hepatic surgery. through several mechanisms [3]. any N. N0. For example. Survival rates for early stage detection is about 5 times that of late stage cancers.[78] [edit]Cimetidine [79] Cimetidine is being investigated in Japan as an adjuvant for adenocarcinomas.[82] . and other services.[76] Several reports including a prospective cohort of 1. Treatment of c lesions by smaller. including for stage III [80] and stage IV[81] colorectal cancers biomarked with overexpressed sialyl Lewis X and A epitopes. M0) has an average 5-year survival of approximately 90%. Various support resources are available from hospitals and other agencies which providecounseling. M0) has an average 5-year survival of approximately 40%. These services help to mitigate some of the difficulties of integrating a patient's medical complications into other parts of their life. cancer support groups. a tumor that hasn't breached the muscularis mucosa (TNM stage T1-2. [edit]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. [edit]Prognosis Survival is directly related to detection and the type of cancer involved. Multiple small trials suggest a significant survival improvement in the subset of patients with the sLeX and sLeA biomarkers that take cimetidine treatment perioperatively.lesions of left hepatic lobe are resected by a procedure called hepati trisegmentectomy. non-anatomic "wedge" resections is associated with higher recurrence rates. 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. M1) has an average 5-year survival of approximately 5%. Lesions which are not amenable to surgical resection for cure can be treated with modalities including radio -frequency ablation (RFA). Some lesions which are not initially amenable to surgical resection may become candidates if they have significant responses to preoperative chemotherapy or immunotherapy regimens. cryoablation. N0. but overall is poor for symptomatic cancers as they are typically quite advanced. Positive regional lymph nodes (any T. [edit]Support therapies Cancer diagnosis very often results in an enormous change in the patient'spsychological wellbeing. N1-3. M0) has an average 5-year survival of approximately 70%.

[edit]Follow-up Micrograph of a colorectal villous adenoma.[83][84] Amedical history and physical examination are recommended every 3 to 6 months for 2 years. then every 5 years. The aims of follow-up are to diagnose in the earliest possible stage any metastasis or tumors that develop later but did not originate from the original cancer (metachronous lesions). polyp >1 centimeter or high grade dysplasia is found. Routine PET or ultrasound scanning. abdomen and pelvis can be considered annually for the first 3 years for patients who are at high risk of recurrence (for example. A colonoscopy can be done after 1 year.000 inhabitants in 2004. National Comprehensive Cancer Network and American Society of Clinical Oncology provide guidelines for the follow-up of colon cancer. complete blood count or liver function tests are not recommended.S. The U. H&E stain.[85][86][87] [edit]Epidemiology Age-standardized death from colorectal cancer per 100.[83][84] These guidelines are based on recent meta-analyses showing that intensive surveillance and close follow-up can reduce the 5-year mortality rate from 37% to 30%. If a villous polyp. but are only advised for patients with T2 or greater lesions who are candidates for intervention.CEA level is also directly related to the prognosis of disease. chest X-rays. except if it could not be done during the initial staging because of an obstructing mass. the colonoscopy can be repeated after 1 year. it can be repeated after 3 years. Carcinoembryonic antigenblood level measurements follow the same timing. [88] . patients who had poorly differentiated tumors or venous or lymphatic invasion) and are candidates for curative surgery (with the aim to cure). since its level correlates with the bulk of tumor tissue. These lesions are considered pre-cancerous. For other abnormalities. in which case it should be performed after 3 to 6 months. A CT-scan of the chest. then every 6 months for 5 years.

5-25 25-27. former Prime Minister of the United Kingdom[92] Rod Roddy. Pope John Paul II[90] Ronald Reagan[91] Harold Wilson.5 2.no data than 27.5-10 10-12. former president of the Philippines[89] Malcolm Marshall. a West Indian cricketer.5-5 5-7.5-20 20-22. second announcer on The Price is Right who became a spokesperson for early detection of cancer in his last years.5 more [edit]Society [edit]Notable and culture patients Main article: List of people diagnosed with colorectal cancer       Corazon Aquino.5 less than 2. primarily a fast bowler.5 7.5 22.5 17.5 12.5-15 15-17.[93]  Claude Debussy. a renowned French composer in the romantic .

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