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| | __NOTOC__ |
| | {{Colon cancer}} |
| | To view familial adenomatous polyposis (FAP), click [[Familial adenomatous polyposis|'''here''']]<br> |
| | To view hereditary nonpolyposis colorectal cancer (HNPCC), click [[Hereditary nonpolyposis colorectal cancer|'''here''']]<br><br> |
| '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' | | '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' |
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| {{DiseaseDisorder infobox | | | {{CMG}}; {{AE}} Saarah T. Alkhairy, M.D |
| Name = Colorectal cancer |
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| ICD10 = {{ICD10|C|18||c|15}}-{{ICD10|C|20||c|15}} |
| | {{SK}} Colon cancer; bowel cancer |
| ICD9 = {{ICD9|153.0}}-{{ICD9|154.1}} |
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| ICDO = {{ICDO|8140|3}} (95% of cases) |
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| OMIM = 114500 |
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| OMIM_mult = |
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| MedlinePlus = 000262 |
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| DiseasesDB = 2975 |
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| }}
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| {{Colon cancer}}
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| '''Editor(s)-in-Chief:''' [[C. Michael Gibson]], M.S.,M.D. [mailto:mgibson@perfuse.org] Phone:617-632-7753; Elliot B. Tapper, M.D., Beth Israel Deaconess Medical Center
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| ==[[Colorectal cancer overview|Overview]]== | | ==[[Colorectal cancer overview|Overview]]== |
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| ==[[Colorectal cancer history and symptoms|History & Symptoms]]== | | ==[[Colorectal cancer historical perspective|Historical Perspective]]== |
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| ==[[Colorectal cancer risk factors|Risk factors]]== | | ==[[Colorectal cancer pathophysiology|Pathophysiology]]== |
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| ==[[Colorectal cancer screening|Screening]] == | | ==[[Colorectal cancer causes|Causes]]== |
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| == Diagnosis == | | ==[[Colorectal cancer differential diagnosis|Differentiating Colorectal cancer from other Diseases]]== |
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| :[[Colorectal cancer history and symptoms| History and Symptoms]] | [[Colorectal cancer physical examination | Physical Examination]] | [[Colorectal cancer staging | Staging]] | [[Colorectal cancer laboratory studies | Lab Studies]] | [[Colorectal cancer electrocardiogram|Electrocardiogram]] | [[Colorectal cancer x ray|X Ray]] | [[Colorectal cancer MRI|MRI]] | [[Colorectal cancer CT|CT]] | [[Colorectal cancer echocardiography|Echocardiography]] | [[Colorectal cancer other imaging findings|Other imaging findings]]
| | ==[[Colorectal cancer epidemiology and demographics|Epidemiology and Demographics]]== |
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| ==Pathology== | | ==[[Colorectal cancer risk factors|Risk factors]]== |
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| The [[pathology]] of the tumor is usually reported from the analysis of tissue taken from a biopsy or surgery. A pathology report will usually contain a description of [[histology|cell type]] and grade. The most common colon cancer cell type is [[adenocarcinoma]] which accounts for 95% of cases. Other, rarer types include [[lymphoma]] and [[squamous cell carcinoma]].
| | ==[[Colorectal cancer screening|Screening]] == |
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| Cancers on the right side (ascending colon and [[cecum]]) tend to be exophytic, that is, the tumour grows outwards from one location in the bowel wall. This very rarely causes obstruction of [[feces]], and presents with symptoms such as [[anemia]]. Left-sided tumours tend to be circumferential, and can obstruct the bowel much like a napkin ring.
| | ==[[Colorectal cancer natural history|Natural History, Complications and Prognosis]]== |
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| ''Histopathology'': Adenocarcinoma is a malignant epithelial tumor, originating from glandular epithelium of the colorectal mucosa. It invades the wall, infiltrating the [[muscularis mucosae]], the [[submucosa]] and thence the muscularis propria. Tumor cells describe irregular tubular structures, harboring pluristratification, multiple lumens, reduced stroma ("back to back" aspect). Sometimes, tumor cells are discohesive and secrete mucus, which invades the interstitium producing large pools of mucus/colloid (optically "empty" spaces) - ''mucinous (colloid)'' adenocarcinoma, poorly differentiated. If the mucus remains inside the tumor cell, it pushes the nucleus at the periphery - "signet-ring cell." Depending on glandular architecture, cellular pleomorphism, and mucosecretion of the predominant pattern, adenocarcinoma may present three degrees of differentiation: well, moderately, and poorly differentiated. <ref>[http://www.pathologyatlas.ro/Colon%20Cancer.html Pathology atlas (in Romanian)]</ref>
| | == Diagnosis == |
| | | [[Colorectal cancer staging|Staging]] | [[Colorectal cancer history and symptoms|History and Symptoms]] | [[Colorectal cancer physical examination|Physical Examination]] | [[Colorectal cancer laboratory tests|Laboratory Findings]] | [[Colorectal cancer x ray|X Ray]] | [[Colorectal cancer MRI|MRI]] | [[Colorectal cancer CT|CT]] | [[Colorectal cancer ultrasound|Ultrasound]] | [[Colorectal cancer other imaging findings|Other Imaging Findings]] | [[Colorectal cancer other diagnostic studies|Other Diagnostic Studies]] |
| [[Image:Colonic carcinoid (1) Endoscopic resection.jpg|thumb|left|Histopathologic image of colonic carcinoid stained by hematoxylin and eosin.]]
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| <br clear="left"/>
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| ==Staging== | |
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| 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 largely depend on the extent of local invasion, the degree of lymph node involvement and whether there is distant [[metastasis]].
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| Definitive staging can only be done after [[Colectomy|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]]. Adjuncts to staging of metastasis include [[Medical ultrasonography|Abdominal Ultrasound]], [[Computed tomography|CT]], [[Positron emission tomography|PET Scanning]], and other imaging studies.
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| ===Dukes' system===
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| Dukes' classification, first proposed by Dr Cuthbert E. Dukes in 1932, identifies the stages as:<ref>Dukes CE. The classification of cancer of the rectum. ''Journal of Pathological Bacteriology'' 1932;35:323.</ref>
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| * A - Tumour confined to the intestinal wall
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| * B - Tumour invading through the intestinal wall
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| * C - With lymph node(s) involvement
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| * D - With distant metastasis
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| ===TNM system===
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| {{main|TNM}}
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| The most common current staging system is the [[TNM]] (for tumors/nodes/metastases) system, though many doctors still use the older Dukes system. The [[TNM]] system assigns a number<ref>
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| {{cite book
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| |author=Wittekind, Ch; Sobin, L. H.
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| |title=TNM classification of malignant tumours
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| |publisher=Wiley-Liss
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| |location=New York
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| |year=2002
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| |pages= | |
| |isbn=0-471-22288-7
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| |oclc=
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| |doi=
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| }}</ref>:
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| * T - The degree of invasion of the intestinal wall
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| ** T0 - no evidence of tumor
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| ** Tis- cancer in situ (tumor present, but no invasion)
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| ** T1 - invasion through submucosa into lamina propria (basement membrane invaded)
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| ** T2 - invasion into the muscularis propria (i.e. proper muscle of the bowel wall)
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| ** T3 - invasion through the subserosa
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| ** T4 - invasion of surrounding structures (e.g. bladder) or with tumour cells on the free external surface of the bowel
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| * N - the degree of [[lymphatic]] node involvement
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| ** N0 - no [[lymph node]]s involved
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| ** N1 - one to three nodes involved
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| ** N2 - four or more nodes involved
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| * M - the degree of [[metastasis]]
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| ** M0 - no metastasis
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| ** M1 - metastasis present
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| === AJCC stage groupings ===
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| The 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.
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| * Stage 0
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| ** Tis, N0, M0
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| * Stage I
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| ** T1, N0, M0
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| ** T2, N0, M0
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| * Stage IIA
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| ** T3, N0, M0
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| * Stage IIB
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| ** T4, N0, M0
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| * Stage IIIA
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| ** T1, N1, M0
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| ** T2, N1, M0
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| * Stage IIIB
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| ** T3, N1, M0
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| ** T4, N1, M0
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| * Stage IIIC
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| ** Any T, N2, M0
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| * Stage IV
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| ** Any T, Any N, M1
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| ==Pathogenesis==
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| Colorectal cancer is a disease originating from the [[epithelium|epithelial cells]] lining the [[gastrointestinal tract]]. [[Hereditary disease|Hereditary]] or [[somatic cell|somatic]] [[mutation]]s in specific [[DNA]] sequences, among which are included [[DNA replication]] or [[DNA repair]] [[gene]]s<ref>{{cite journal |author=Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M|title=Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis|journal=Nature|volume=363|issue=6429|pages=558-61|year=1993|url=http://dx.doi.org/10.1038/363558a0|pmid=8505985}}</ref>, and also the [[Adenomatous polyposis coli|APC]], [[Ras|K-Ras]], [[NOD2]] and [[p53]] genes, lead to unrestricted cell division. The exact reason why (and whether) a diet high in fiber might prevent colorectal cancer remains uncertain. Chronic inflammation, as in [[inflammatory bowel disease]], may predispose patients to malignancy. | |
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| ==Treatment== | | ==Treatment== |
| | [[Colorectal cancer medical therapy|Medical Therapy]] | [[Colorectal cancer surgery|Surgery]] | [[Colorectal cancer metastasis treatment|Metastasis Treatment]] | [[Colorectal cancer primary prevention|Primary prevention]] | [[Colorectal cancer secondary prevention|Secondary prevention]] | [[Colorectal cancer follow up|Follow-up]] | [[Colorectal cancer cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Colorectal cancer future or investigational therapies|Future or Investigational Therapies]] |
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| The treatment depends on the staging 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 [[metastasis|metastases]] are present) it is less likely to be curable.
| | ==Case Studies== |
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| Surgery remains the primary treatment while chemotherapy and/or radiotherapy may be recommended depending on the individual patient's staging and other medical factors.
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| ===Surgery=== | |
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| Surgeries can be categorised into curative, palliative, bypass, fecal diversion, or open-and-close.
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| '''Curative''' [[Surgery|Surgical]] treatment can be offered if the tumor is localized.
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| * Very early cancer that develops within a [[polyp]] can often be cured by removing the polyp (i.e., polypectomy) at the time of [[colonoscopy]].
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| * 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 node]]s to reduce local recurrence (i.e., colectomy). If possible, the remaining parts of colon are [[anastomosis|anastomosed]] together to create a functioning colon. In cases when anastomosis is not possible, a [[stoma (medicine)|stoma]] (artificial orifice) is created.
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| * Curative surgery on rectal cancer includes [[total mesorectal excision]] ([[lower anterior resection]]) or [[abdominoperineal excision]].
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| In case of multiple metastases, '''palliative''' (non curative) [[resection]] of the primary tumor is still offered in order 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.
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| 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 (medicine)|stoma]].
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| The worst case would be an '''open-and-close''' surgery, when surgeons find the tumor unresectable and the small bowel involved; any more procedures would 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.
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| [[Laparoscopic surgery|Laparoscopic]]-assisted [[colectomy]] is a [[Minimally invasive procedure|minimally-invasive]] technique that can reduce the size of the incision, minimize the risk of infection, and reduce post-operative pain.
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| [[Cleveland Clinic]] colorectal surgeons developed the “no touch” technique to prevent the spread of cancer cells during colorectal surgery.<ref>[http://www.universitycircle.org/content/healthcare.asp University Circle Inc<!-- Bot generated title -->]</ref>
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| As with any surgical procedure, colorectal surgery may result in complications including
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| * wound [[infection]], Dehiscence (bursting of wound) or hernia
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| * anastomosis breakdown, leading to abscess or fistula formation, and/or peritonitis
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| * bleeding with or without [[hematoma]] formation
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| * [[Adhesion (medicine)|adhesions]] resulting in [[bowel obstruction]] (especially small bowel)
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| * [[blind loop syndrome]] as in bypass surgery.
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| * adjacent organ injury; most commonly to the small intestine, ureters, spleen, or bladder
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| * Cardiorespiratory complications such as [[myocardial infarction]], [[pneumonia]], [[arrythmia]], [[pulmonary embolism]] etc
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| ===Chemotherapy===
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| [[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 (neo-adjuvant), or as the primary therapy if surgery is not indicated (palliative). The treatments listed here have been shown in [[clinical trial]]s to improve survival and/or reduce mortality rate and have been approved for use by the US Food and Drug Administration.
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| *'''Adjuvant''' (after surgery) chemotherapy. One regimen involves the combination of infusional [[5-fluorouracil]], [[leucovorin]], and [[oxaliplatin]] ([[FOLFOX]])
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| ** [[5-fluorouracil]] (5-FU) or [[Capecitabine]] (Xeloda®)
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| ** [[Leucovorin]] (LV, Folinic Acid)
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| ** [[Oxaliplatin]] (Eloxatin®)
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| *Chemotherapy for '''metastatic''' disease. Commonly used first line [[chemotherapy regimen]]s involve the combination of infusional [[5-fluorouracil]], [[leucovorin]], and [[oxaliplatin]] ([[FOLFOX]]) with [[bevacizumab]] or infusional [[5-fluorouracil]], [[leucovorin]], and [[irinotecan]] ([[FOLFIRI]]) with [[bevacizumab]]
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| ** [[5-fluorouracil]] (5-FU) or Capecitabine
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| ** [[Leucovorin]] (LV, Folinic Acid)
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| ** [[Irinotecan]] (Camptosar®)
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| ** [[Oxaliplatin]] (Eloxatin®)
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| ** [[Bevacizumab]] (Avastin®)
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| ** [[Cetuximab]] (Erbitux®)
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| ** [[Panitumumab]] (Vectibix)
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| *In clinical trials for treated/untreated metastatic disease. [http://saci.uthscsa.edu/ClinicalTrials/SelectedPhase1.html#PhINovel]
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| ** [[Bortezomib]] (Velcade®)
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| ** [[Oblimersen]] (Genasense®, G3139)
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| ** [[Gefitinib]] and [[Erlotinib]] (Tarceva®)
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| ** [[Topotecan]] (Hycamtin®)
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| ===Radiation therapy===
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| 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:
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| * Colon cancer
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| ** pain relief and palliation - targeted at [[metastasis|metastatic]] tumor deposits if they compress vital structures and/or cause pain
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| * Rectal cancer
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| ** neoadjuvant - given before surgery in patients with tumors that extend outside the rectum or have spread to regional lymph nodes, 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)
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| ** adjuvant - where a tumor perforates the rectum or involves regional lymph nodes (AJCC T3 or T4 tumors or Duke's B or C tumors)
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| ** palliative - to decrease the tumor burden in order to relieve or prevent symptoms
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| Sometimes chemotherapy agents are used to increase the effectiveness of radiation by sensitizing tumor cells if present.
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| ===Immunotherapy===
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| [[Bacillus Calmette-Guérin]] (BCG) is being investigated as an adjuvant mixed with autologous tumor cells in immunotherapy for colorectal cancer.<ref>Mosolits S, Nilsson B, Mellstedt H. ''Towards therapeutic vaccines for colorectal carcinoma: a review of clinical trials.'', Expert Rev. Vaccines, 2005;4:329-50. PMID 16026248.</ref>
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| ===Vaccine===
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| In November 2006, it was announced that a [[vaccine]] had been developed and tested with very promising results.<ref>[http://www.dailymail.co.uk/pages/live/articles/news/news.html?in_article_id=416006&in_page_id=1770 Wheldon, Julie. Vaccine for kidney and bowel cancers 'within three years' ''The Daily Mail'' [[2006-11-13]]]]</ref> The new vaccine, called [[TroVax]], works in a totally different way to existing treatments by harnessing the patient's own immune system to fight the disease. Experts say this suggests that [[gene therapy]] vaccines could prove an effective treatment for a whole range of cancers. [http://www.oxfordbiomedica.co.uk/ Oxford BioMedica] is a British spin-out from Oxford University specializing in the development of gene-based treatments. Phase III trials are underway for renal cancers and planned for colon cancers.<ref>[http://www.medscape.com/viewarticle/561321?src=mp Vaccine Works With Chemotherapy in Colorectal Cancer (Reuters) [[2007-08-13]]]</ref>
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| ===Treatment of colorectal cancer metastasis to the liver===
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| According to the American Cancer Society statistics in 2006 [http://www.cancer.org/docroot/PRO/content/PRO_1_1_Cancer_Statistics_2006_Presentation.asp]greater than 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%.<ref> Simmonds PC, et al. Surgical Resection of hepatic metastasis from colorectal cancer: A systemic review of published studies. Br J Surg. 2006;94:982-999. PMID 16538219 </ref>
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| Resectability of a liver met 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,non-anatomic "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 regimines. Lesions which are not amenable to surgical resection for cure can be treated with modalities including radio-frequency ablation (RFA), cryoablation, and chemoembolization.
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| 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.
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| Poor pronostic factors of patients with liver metastasis include
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| * Synchronous (diagnosed simultaneously) liver and primary colorectal tumors
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| * A short time between detecting the primary cancer and subsequent development of liver mets
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| * Multiple metastatic lesions
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| * High blood levels of the tumor marker, carcino-embryonic antigen ('''CEA'''), in the patient prior to resection
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| * Larger size metastatic lesions
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| ===Support therapies===
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| Cancer diagnosis very often results in an enormous change in the patient's psychological wellbeing. Various support resources are available from hospitals and other agencies which provide [[counseling]], social service support, [[cancer support group]]s, and other services. These services help to mitigate some of the difficulties of integrating a patient's medical complications into other parts of their life.
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| ==Prognosis==
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| Survival is directly related to detection and the type of cancer involved. Survival rates for early stage detection is about 5 times that of late stage cancers. CEA level is also directly related to the prognosis of disease, since its level correlates with the bulk of tumor tissue.
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| ==Follow-up==
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| 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).
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| The U.S. [[National Comprehensive Cancer Network]] and [[American Society of Clinical Oncology]] provide guidelines for the follow-up of colon cancer.<ref name="NCCNguidelines">[http://www.nccn.org/professionals/physician_gls/PDF/colon.pdf NCCN Clinical Practice Guidelines in Oncology - Colon Cancer (version 1, 2008: September 19, 2007).]</ref><ref name="ASCOguidelines">{{cite journal |last=Desch CE, Benson AB 3rd, Somerfield MR, ''et al''; American Society of Clinical Oncology |first= |authorlink= |coauthors= |year=2005 |month= |title=Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology practice guideline |journal=J Clin Oncol |volume=23 |issue=33 |pages=8512-9 |id= |url=http://jco.ascopubs.org/cgi/reprint/JCO.2005.04.0063v1.pdf |accessdate= |quote= }}</ref> A [[medical history]] and [[physical examination]] are recommended every 3 to 6 months for 2 years, then every 6 months for 5 years. [[Carcinoembryonic antigen]] blood level measurements follow the same timing, but are only advised for patients with T2 or greater lesions who are candidates for intervention. A [[Computed tomography|CT-scan]] of the chest, abdomen and pelvis can be considered annually for the first 3 years for patients who are at high risk of recurrence (for example, patients who had poorly differentiated tumors or venous or lymphatic invasion) and are candidates for curative surgery (with the aim to cure). A [[colonoscopy]] can be done after 1 year, except if it could not be done during the initial staging because of an obstructing mass, in which case it should be performed after 3 to 6 months. If a villous polyp, polyp >1 centimeter or high grade dysplasia is found, it can be repeated after 3 years, then every 5 years. For other abnormalities, the colonoscopy can be repeated after 1 year.
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| Routine [[Positron emission tomography|PET]] or [[Medical ultrasonography|ultrasound scanning]], [[chest X-ray]]s, [[complete blood count]] or [[liver function tests]] are not recommended.<ref name="NCCNguidelines"/><ref name="ASCOguidelines"/> 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%.<ref name="Cochrane2002">{{cite journal |last=Jeffery M, Hickey BE, Hider PN|first=|authorlink= |coauthors=|year=2002 |month= |title=Follow-up strategies for patients treated for non-metastatic colorectal cancer |journal=Cochrane Database Syst Rev |volume= |issue= |pages= |id=CD002200 |url=http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD002200/frame.html |accessdate= |quote= }}</ref><ref name="BMJfollowup">{{cite journal |last=Renehan AG, Egger M, Saunders MP, O'Dwyer ST|first= |authorlink= |coauthors= |year=2002 |month= |title=Impact on survival of intensive follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomised trials |journal=BMJ |volume=324 |issue=7341 |pages=831-8 |id= |url=http://www.bmj.com/cgi/reprint/324/7341/813 |accessdate= |quote= }}</ref><ref name="BMCCancerFollowup">{{cite journal |last=Figueredo A, Rumble RB, Maroun J, ''et al''; Gastrointestinal Cancer Disease Site Group of Cancer Care Ontario's Program in Evidence-based Care. |first= |authorlink= |coauthors= |year=2003 |month= |title=Follow-up of patients with curatively resected colorectal cancer: a practice guideline. |journal=BMC Cancer |volume=3 |issue= |pages=26 |id= |url=http://www.biomedcentral.com/1471-2407/3/26 |accessdate= |quote= }}</ref>
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| ==Prevention==
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| Most colorectal cancers should be preventable, through increased surveillance, improved lifestyle, and, probably, the use of dietary chemopreventative agents.
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| ===Surveillance===
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| Most colorectal cancer arise from adenomatous polyps. These lesions can be detected and removed during [[colonoscopy]]. Studies show 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.<ref>Winawer SJ, Zauber AG, Ho MN, O'Brien MJ, Gottlieb LS, Sternberg SS, Waye JD, Schapiro M, Bond JH, Panish JF, Ackroyd F, Shike M, Kurtz RC, Hornsby-Lewis L, Gerdes H, Stewart ET, The National Polyp Study Workgroup. ''Prevention of colorectal cancer by colonoscopic polypectomy.'' [[N Engl J Med]] 1993;329:1977-81. PMID 8247072.</ref>
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| 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).
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| ===Lifestyle & Nutrition===
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| 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%.<ref>{{cite journal|last=Cummings |first=JH |coauthors=Bingham SA |title=Diet and the prevention of cancer |journal=[[British Medical Journal|BMJ]] |year=1998|issue317|pages=1636-40 |url=http://bmj.bmjjournals.com/ |id=PMID 9848907}}</ref>
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| 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. <ref>{{cite journal |title=Dietary Fiber and the Risk of Colorectal Cancer and Adenoma in Women |journal=New England Journal of Medicine |year=1999 |issue=340 |pages=169-76 |url=http://content.nejm.org/cgi/content/full/340/3/169}}</ref> A 2005 meta-analysis study further supports these findings.<ref>{{cite journal |title=Dietary Fiber and Colorectal Cancer: An Ongoing Saga |journal=Journal of the American Medical Association |year=2005 |issue=294(22) |pages=2904 - 2906 |url=http://jama.ama-assn.org/cgi/content/extract/294/22/2904 |id=PMID 16352792}}</ref>
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| The Harvard School of Public Health states:
| | [[Colorectal cancer case study one|Case #1]] |
| "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." <ref>{{cite web|title=Health Effects of Eating Fiber |url=http://www.hsph.harvard.edu/nutritionsource/fiber.html}}</ref>
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| ===Chemoprevention=== | | ==Related Chapters== |
| More than 200 agents, including the above cited phytochemicals, and other food components like calcium or folic acid (a B vitamin), and [[NSAID]]s like aspirin, are able to decrease carcinogenesis in preclinical 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. Calcium, aspirin and celecoxib supplements, given for 3 to 5 years after the removal of a polyp, decreased the recurrence of polyps in volunteers (by 15-40%). The "chemoprevention database" shows the results of all published scientific studies of chemopreventive agents, in people and in animals.<ref>{{cite web |url=http://www.inra.fr/reseau-nacre/sci-memb/corpet/indexan.html |title=Colorectal Cancer Prevention: Chemoprevention Database |accessdate=2007-08-23 |format= |work=}}</ref>
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| ====Aspirin chemoprophylaxis====
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| 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 (300mg or more) outweigh the possible benefits.<ref>{{cite web |title=Task Force Recommends Against Use of Aspirin and Non-Steroidal Anti-Inflammatory Drugs to Prevent Colorectal Cancer |url=http://www.ahrq.gov/news/press/pr2007/aspnsaidpr.htm |author=Agency for Healthcare Research and Quality | accessdate=2007-05-07 |date=2007-03-05 |publisher=United States Department of Health & Human Services }}</ref>
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| A [[clinical practice guideline]] by the [http://www.ahrq.gov/clinic/uspstfix.htm U.S. Preventive Services Task Force (USPSTF)] recommended against taking [[aspirin]] ([http://www.ahrq.gov/clinic/3rduspstf/ratings.htm grade D recommendation]).<ref name="pmid17339621">{{cite journal |author= |title=Routine aspirin or nonsteroidal anti-inflammatory drugs for the primary prevention of colorectal cancer: U.S. Preventive Services Task Force recommendation statement |journal=Ann. Intern. Med. |volume=146 |issue=5 |pages=361-4 |year=2007 |id=pmid=17339621 |doi=}} PMID 17339621</ref> 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".<ref name="pmid17499602">{{cite journal |author=Flossmann E, Rothwell PM |title=Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies |journal=Lancet |volume=369 |issue=9573 |pages=1603-13 |year=2007 |pmid=17499602 |doi=10.1016/S0140-6736(07)60747-8}} PMID 17499602</ref> However, long-term doses over 81 mg per day may increase bleeding events.<ref name="pmid17488967">{{cite journal |author=Campbell CL, Smyth S, Montalescot G, Steinhubl SR |title=Aspirin dose for the prevention of cardiovascular disease: a systematic review |journal=JAMA |volume=297 |issue=18 |pages=2018-24 |year=2007 |pmid=17488967 |doi=10.1001/jama.297.18.2018}} PMID 17488967</ref>
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| ====Calcium====
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| A [[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.".<ref name="pmid16034903">{{cite journal |author=Weingarten MA, Zalmanovici A, Yaphe J |title=Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps |journal=Cochrane database of systematic reviews (Online) |volume= |issue=3 |pages=CD003548 |year=2005 |pmid=16034903 |doi=10.1002/14651858.CD003548.pub3}}</ref> Subsequently, one [[randomized controlled trial]] by the [[Women's Health Initiative]] (WHI) reported negative results.<ref name="pmid16481636">{{cite journal |author=Wactawski-Wende J, Kotchen JM, Anderson GL, ''et al'' |title=Calcium plus vitamin D supplementation and the risk of colorectal cancer |journal=N. Engl. J. Med. |volume=354 |issue=7 |pages=684-96 |year=2006 |pmid=16481636 |doi=10.1056/NEJMoa055222}}</ref> A second [[randomized controlled trial]] reported reduction in all cancers, but had insufficient colorectal cancers for analysis.<ref name="pmid17556697">{{cite journal |author=Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP |title=Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial |journal=Am. J. Clin. Nutr. |volume=85 |issue=6 |pages=1586-91 |year=2007 |pmid=17556697 |doi=|url=http://www.ajcn.org/cgi/content/full/85/6/1586}}</ref>
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| ==Mathematical modeling==
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| Colorectal cancer has been for years subject of mathematical modeling.<ref>{{cite journal | author = van Leeuwen I, Byrne H, Jensen O, King J | title = Crypt dynamics and colorectal cancer: advances in mathematical modelling. | journal = Cell Prolif | volume = 39 | issue = 3 | pages = 157-81 | year = 2006 | id = PMID 16671995}}[http://www.maths.nottingham.ac.uk/personal/pmzivl/LeeuByrn2006.html Full text]</ref> For a comprehensive overview of current computational approaches on colorectal cancer see the [http://www.maths.nottingham.ac.uk/personal/pmzivl/crc.html Integrative Biology] web page.
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| ==References==
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| {{Reflist|2}}
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| ==See also==
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| * [[Hereditary nonpolyposis colorectal cancer]] | | * [[Hereditary nonpolyposis colorectal cancer]] |
| * [[Diet and cancer]] | | * [[Diet and cancer]] |
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| == External links == | | ==External Links== |
| *[http://www.cancer.gov/cancerinfo/wyntk/colon-and-rectum National Cancer Institute (Cancer.gov)] colorectal cancer
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| *[http://clinicaltrials.gov/ct/search?term=colorectal+cancer Current clinical trials] | | *[http://clinicaltrials.gov/ct/search?term=colorectal+cancer Current clinical trials] |
| *[http://nccam.nih.gov/clinicaltrials/colorectalcancer.htm Complementary medical clinical trials]
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