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 |  موضوع: Colorectal cancer الأربعاء سبتمبر 07, 2011 9:55 pm | |
| Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth (neoplasia), 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 through colonoscopy.
Invasive cancers that are confined within the wall of the colon (TNM stages I and II) are often curable with surgery, For example, in England and Wales over 90% of patients diagnosed at this stage will survive the disease beyond 5 years.[1] However, if left untreated, the cancer can spread to regional lymph nodes (stage III). In England and Wales, around 48% of patients diagnosed at this stage survive the disease beyond five years.[1] Cancer that has spread widely around the body (stage IV) is usually not curable; approximately 7% of patients in England and Wales diagnosed at this stage survive beyond five years.[1]
Colorectal cancer is the third most commonly diagnosed cancer in the world, but it is more common in developed countries.[2] More than half of the people who die of colorectal cancer live in a developed region of the world.[3] GLOBOCAN estimated that, in 2008, 1.23 million new cases of colorectal cancer were clinically diagnosed, and that this type of cancer killed more than 600,000 people
Signs and symptoms
The symptoms of colorectal cancer depend on the location of tumor in the bowel, and whether it has spread elsewhere in the body (metastasis). While no symptom is diagnostic of colorectal cancer, rectal bleeding or anemia are high risk features.[4]
Local
Local symptoms are more likely if the tumor is located closer to the anus. There may be a change in bowel habit (such as unusual and unexplained constipation or diarrhea), 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 causing peritonitis. 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 cause blood or air in the urine (invasion of the bladder) or vaginal discharge (invasion of the female reproductive tract).
Constitutional
If a tumor has caused chronic bleeding in the bowel, iron deficiency anemia may occur, causing a range of symptoms that may include fatigue, palpitations and pale skin (pallor). Colorectal cancer may also lead to weight loss, generally due to a decreased appetite[citation needed].
There may be rarer symptoms including unexplained fever or thrombosis, usually deep vein thrombosis. Such symptoms, known as paraneoplastic syndrome, are due to the body's immune response to the cancer, rather than the tumor itself
Risk factors
The lifetime risk of developing colon cancer in the United States is about 7%. Certain factors increase a person's risk of developing the disease.[5] These include:
Age: The risk of developing colorectal cancer increases with age. Most cases occur in the 60s and 70s, while cases before age 50 are uncommon unless a family history of early colon cancer is present.[6]
Polyps of the colon, particularly adenomatous polyps, are a risk factor for colon cancer. The removal of colon polyps at the time of colonoscopy reduces the subsequent risk of colon cancer.
History of cancer. Individuals who have previously been diagnosed and treated for colon cancer are at risk for developing colon cancer in the future. Women who have had cancer of the ovary, uterus, or breast are at higher risk of developing colorectal cancer.
Heredity:
Family history of colon cancer, especially in a close relative before the age of 55 or multiple relatives.[7]
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
Gardner syndrome
Smoking: Smokers are more likely to die of colorectal cancer than nonsmokers. An American Cancer Society study found "Women who smoked were more than 40% more likely to die from colorectal cancer than women who never had smoked. Male smokers had more than a 30% increase in risk of dying from the disease compared to men who never had smoked."[8][9]
Diet: Studies show that a diet high in red meat[10] and low in fresh fruit, vegetables, poultry and fish increases the risk of colorectal cancer. In June 2005, a study by the European Prospective Investigation into Cancer and Nutrition suggested that diets high in red and processed meat, as well as those low in fiber, are associated with an increased risk of colorectal cancer. Individuals who frequently eat fish showed a decreased risk.[11] However, other studies have cast doubt on the claim that diets high in fiber decrease the risk of colorectal cancer; rather, low-fiber diet was associated with other risk factors, leading to confounding.[12] The nature of the relationship between dietary fiber and risk of colorectal cancer remains controversial.
Lithocholic acid: Lithocholic acid is a bile acid that acts as a detergent to solubilize fats for absorption. It is made from chenodeoxycholic acid by bacterial action in the colon. It has been implicated in human and experimental animal carcinogenesis.[13] Carbonic acid type surfactants easily combine with calcium ion and become detoxication products.
Physical inactivity: People who are physically active are at lower risk of developing colorectal cancer.
Viruses: Exposure to some viruses (such as particular strains of human papilloma virus) may be associated with colorectal cancer.[citation needed]
Primary sclerosing cholangitis offers a risk independent to ulcerative colitis.
Low levels of selenium[14][15]
Inflammatory bowel disease:[16][17] About one percent of colorectal cancer patients have a history of chronic ulcerative colitis. 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. Patients with colorectal Crohn's disease have a more than average risk of colorectal cancer, but less than that of patients with ulcerative colitis.[18]
Environmental factors.[16] Industrialized countries are at a relatively increased risk compared to less developed countries that traditionally had high-fiber/low-fat diets. Studies of migrant populations have revealed a role for environmental factors, particularly dietary, in the etiology of colorectal cancers.
Exogenous hormones. 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; one possibility that has been suggested is exposure to estrogens.[19] There is, however, little evidence of an influence of endogenous hormones on the risk of colorectal cancer. In contrast, there is evidence that exogenous estrogens such as hormone replacement therapy (HRT), tamoxifen, or oral contraceptives might be associated with colorectal tumors.[20]
Alcohol: Drinking, especially heavily, may be a risk factor.[21]
Vitamin B6 intake lowers the risk of colorectal cance
.
Diagnosis
Colorectal cancer can take many years to develop and early detection of colorectal cancer greatly improves the chances of a cure. 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. Despite this, colorectal cancer screening rates remain low.[40] Therefore, screening for the disease is recommended in individuals who are at increased risk. There are several different tests available for this purpose.
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.[41]
Endoscopy:
Sigmoidoscopy: A lighted probe (sigmoidoscope) is inserted into the rectum and lower colon to check for polyps and other abnormalities.
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. 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
Staging
Colon cancer staging is an estimate of the amount of penetration of a particular cancer. It is performed for diagnostic and research purposes, and to determine the best method of treatment. The systems for staging colorectal cancers depend on the extent of local invasion, the degree of lymph node involvement and whether there is distant metastasis.
Definitive staging can only be done after surgery has been performed and pathology reports reviewed. An exception to this principle would be after a colonoscopic polypectomy of a malignant pedunculated polyp with minimal invasion. Preoperative staging of rectal cancers may be done with endoscopic ultrasound. Adjunct staging of metastasis include Abdominal Ultrasound, CT, PET Scanning, and other imaging studies.
The most common staging system is the TNM (for tumors/nodes/metastases) system, from the American Joint Committee on Cancer (AJCC). The TNM system assigns a number based on three categories. "T" denotes the degree of invasion of the intestinal wall, "N" the degree of lymphatic node involvement, and "M" the degree of metastasis. The broader stage of a cancer is usually quoted as a number I, II, III, IV derived from the TNM value grouped by prognosis; a higher number indicates a more advanced cancer and likely a worse outcome. Details of this system are in the graph below
Prevention
Most colorectal cancers should be preventable, through increased surveillance, improved lifestyle, and, probably, the use of dietary chemopreventative agents.
Surveillance
Most colorectal cancers arise from adenomatous polyps. These lesions can be detected and removed during colonoscopy. A 1993 study suggested this procedure would decrease by > 80% the risk of cancer death, provided it is started by the age of 50, and repeated every 5 or 10 years.[60] A 2009 study published in the Annals of Internal Medicine[61] implies that colonoscopy screening prevents approximately two thirds of the deaths due to colorectal cancers on the left side of the colon, and is not associated with a significant reduction in deaths from right-sided disease.[62] The summary result suggested approximately a 37% reduction in net death rate from colorectal cancer.
As per current guidelines under National Comprehensive Cancer Network, in average risk individuals with negative family history of colon cancer and personal history negative for adenomas or inflammatory 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
):.
Management
The treatment depends on the stage of the cancer. When colorectal cancer is caught at early stages (with little spread), it can be curable. However, when it is detected at later stages (when distant metastases are present), it is less likely to be curable.
Surgery remains the primary treatment, while chemotherapy and/or radiotherapy may be recommended depending on the individual patient's staging and other medical factors.
Because colon cancer primarily affects the elderly, it can be a challenge to determine how aggressively to treat a particular patient, especially after surgery. Clinical trials suggest "otherwise fit" elderly patients fare well if they have adjuvant chemotherapy after surgery, so chronological age alone should not be a contraindication to aggressive management.[77]
Surgery
Surgeries can be categorised into curative, palliative, bypass, fecal diversion, or open-and-close.
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 (i.e., polypectomy) at the time of colonoscopy.
In colon cancer, a more advanced tumor typically requires surgical removal of the 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[78]
adjacent organ injury; most commonly to the small intestine, ureters, spleen, or bladder, and
cardiorespiratory complications, such as myocardial 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) with bevacizumab 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.[79]
Bortezomib (Velcade)
Oblimersen (Genasense, G3139)
Gefitinib and erlotinib (Tarceva)
Topotecan (Hycamtin) | |
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