Colorectal cancer, also called or bowel cancer, includes cancerous growths in the colon, rectum and appendix. It is the third most common form of cancer and the second leading cause of death among cancers in the Western world. Colorectal cancer causes 655,000 deaths worldwide per year.1 Many colorectal cancers are thought to arise from adenomatous polyps in the colon. These mushroom-like growths are usually benign, but some may develop into cancer over time. The majority of the time, the diagnosis of localized is through colonoscopy. Therapy is usually through surgery, which in many cases is followed by chemotherapy.
Frequently, the patient may be asymptomatic. This is one reason why many organizations recommend periodic screening for the disease with fecal occult blood testing and colonoscopy. When symptoms do occur, they depend on the site of the lesion. Generally speaking, the nearer the lesion is to the anus, the more bowel symptoms there will be, such as:
Especially in the cases of cancer in the ascending colon, sometimes only the less specific constitutional symptoms will be found:
There may also be symptoms attributed to distant metastasis:
The lifetime risk of developing in the United States is about 7%. Certain factors increase a person's risk of developing the disease. These include:
On its colorectal cancer page, the National Cancer Institute does not list alcohol as a risk factor4: however, on another page it states, "Heavy alcohol use may also increase the risk of colorectal cancer" 5
The NIAAA reports that, "Epidemiologic studies have found a small but consistent dose-dependent association between alcohol consumption and colorectal cancer67even when controlling for fiber and other dietary factors.89 Despite the large number of studies, however, causality cannot be determined from the available data."10
"Heavy alcohol use may also increase the risk of colorectal cancer" (NCI). 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."1112 Another found that "The consumption of one or more alcoholic beverages a day at baseline was associated with approximately a 70% greater risk of ."131415
One study found that "While there was a more than twofold increased risk of significant colorectal neoplasia in people who drink spirits and beer, people who drank wine had a lower risk. In our sample, people who drank more than eight servings of beer or spirits per week had at least a one in five chance of having significant colorectal neoplasia detected by screening colonoscopy.".16
Other research suggests that "to minimize your risk of developing colorectal cancer, it's best to drink in moderation"10
Drinking may be a cause of earlier onset of colorectal cancer.17
Endoscopic image of identified in sigmoid colon on screening colonoscopy in the setting of Crohn's disease.
Colorectal cancer can take many years to develop and early detection of colorectal cancer greatly improves the chances of a cure. Therefore, screening for the disease is recommended in individuals who are at increased risk. There are several different tests available for this purpose.
In the United States, colonoscopy or FOBT plus sigmoidoscopy are the preferred screening options.
Histopathologic image of colonic carcinoid stained by hematoxylin and eosin.
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 cell type and grade. The most common cell type is adenocarcinoma which accounts for 95% of cases. Other, rarer types include lymphoma and squamous cell carcinoma.
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.
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. 1
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.
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. Adjuncts to staging of metastasis include Abdominal Ultrasound, CT, PET Scanning, and other imaging studies.
Dukes' classification, first proposed by Dr Cuthbert E. Dukes in 1932, identifies the stages as:19
The most common current staging system is the TNM system, though many doctors still use the older Dukes system. The TNM system assigns a number:
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 a likely worse outcome.
Colorectal cancer is a disease originating from the epithelial cells lining the gastrointestinal tract. Mutations in specific DNA sequences, among which are included the APC, K-Ras and p53 genes, lead to unrestricted cell division. Various causes for these mutations are inborn genetic aberrations, tobacco smoking, environmental, and possibly viral causes. 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.
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 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.
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.
In case of multiple metastases, palliative 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; 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 would do more harm than good to the patient.
Laparoscopic-assisted colectomy is a minimally-invasive technique that can reduce the size of the incision, minimize the risk of infection, and reduce post-operative pain.
As with any surgical procedure, colorectal surgery may result in complications including
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 trials to improve survival and/or reduce mortality rate and have been approved for use by the US Food and Drug Administration.
Radiotherapy is not used routinely in , as it could lead to radiation enteritis, and 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:
Sometimes chemotherapy agents are used to increase the effectiveness of radiation by sensitizing tumor cells if present.
Bacillus Calmette-Guerin (BCG) is being investigated as an adjuvant mixed with autologous tumor cells in immunotherapy for colorectal cancer.20
In November 2006, it was announced that a vaccine had been developed and tested with very promising results.(See 4) 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. Oxford BioMedica5 is the company behind the vaccine; it's a British company established as a spin-out from Oxford University and specialises in the development of gene-based treatments. Further vaccine trials are underway.
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 groups, 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.
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.
Follow-up aims at diagnosing metachronous lesion(s) or distant metastasis in the early stage. History taking and physical examination every 3 to 6 months for three years after surgery. CEA every 2 to 3 months for two or more years in patients who have had resection of liver metastasis. Colonoscopy looking for synchronise lesion(s) should be done shortly after surgery if preoperatively the scope cannot pass through the tumor; otherwise it should be done every 3 to 5 years. ASCO recommends against other routine follow-up tests such as Chest X-Ray, Ultrasound, CT, etc.
Most colorectal cancers should be preventable, through increased surveillance, improved lifestyle, and, probably, the use of dietary chemopreventative agents.
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.21
As per current guidelines under National Comprehensive Cancer Network at 6, in average risk individuals with negative family history of 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).
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, physical exercise, and eating plenty of fruits and vegetables would decrease cancer risk, probably because they contain protective phytochemicals. Accordingly, lifestyle changes could decrease the risk of colorectal cancer as much as 60-80%.22
More than 200 agents, including the above cited phytochemicals, and other food components like calcium or folic acid (a B vitamin), and NSAIDs 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"7 shows the results of all published scientific studies of chemopreventive agents, in people and in animals. 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) outweight the possible benefits.
National Cancer Institute
Cancer Information Service
Building 31, Room 10A16
31 Center Drive, MSC 2580
Bethesda, MD 20892–2580
Phone: 1–800–422–6237 or 301–496–6631
National Digestive Diseases Information Clearinghouse
The National Digestive Diseases Information Clearinghouse (NDDIC) is a service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The NIDDK is part of the National Institutes of Health of the U.S. Department of Health and Human Services. Established in 1980, the Clearinghouse provides information about digestive diseases to people with digestive disorders and to their families, health care professionals, and the public. The NDDIC answers inquiries, develops and distributes publications, and works closely with professional and patient organizations and Government agencies to coordinate resources about digestive diseases.
Publications produced by the Clearinghouse are carefully reviewed by both NIDDK scientists and outside experts.