出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2018/05/27 13:06:02」(JST)
| Colorectal cancer | |
|---|---|
| Synonyms | Colon cancer, rectal cancer, bowel cancer |
| Diagram of the lower gastrointestinal tract | |
| Specialty | Oncology |
| Symptoms | Blood in the stool, change in bowel movements, weight loss, feeling tired all the time[1] |
| Causes | Old age, lifestyle factors, genetic disorders[2][3] |
| Risk factors | Diet, obesity, smoking, lack of physical activity, alcohol use[2][4] |
| Diagnostic method | Tissue biopsy during a sigmoidoscopy or colonoscopy[1] |
| Prevention | Screening from age of 50 to 75[5] |
| Treatment | Surgery, radiation therapy, chemotherapy, targeted therapy[6] |
| Prognosis | Five-year survival rate 65% (USA)[7] |
| Frequency | 9.4 million (2015)[8] |
| Deaths | 832,000 (2015)[9] |
Colorectal cancer (CRC), also known as bowel cancer and colon cancer, is the development of cancer from the colon or rectum (parts of the large intestine).[6] A cancer is the abnormal growth of cells that have the ability to invade or spread to other parts of the body.[10] Signs and symptoms may include blood in the stool, a change in bowel movements, weight loss, and feeling tired all the time.[1]
Most colorectal cancers are due to old age and lifestyle factors with only a small number of cases due to underlying genetic disorders.[2][3] Some risk factors include diet, obesity, smoking, and lack of physical activity.[2][3] Dietary factors that increase the risk include red and processed meat as well as alcohol.[2][4] Another risk factor is inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis.[2] Some of the inherited genetic disorders that can cause colorectal cancer include familial adenomatous polyposis and hereditary non-polyposis colon cancer; however, these represent less than 5% of cases.[2][3] It typically starts as a benign tumor, often in the form of a polyp, which over time becomes cancerous.[2]
Bowel cancer may be diagnosed by obtaining a sample of the colon during a sigmoidoscopy or colonoscopy.[1] This is then followed by medical imaging to determine if the disease has spread.[6] Screening is effective for preventing and decreasing deaths from colorectal cancer.[5] Screening, by one of a number of methods, is recommended starting from the age of 50 to 75.[5] During colonoscopy, small polyps may be removed if found.[2] If a large polyp or tumor is found, a biopsy may be performed to check if it is cancerous. Aspirin and other non-steroidal anti-inflammatory drugs decrease the risk.[2][11] Their general use is not recommended for this purpose, however, due to side effects.[12]
Treatments used for colorectal cancer may include some combination of surgery, radiation therapy, chemotherapy and targeted therapy.[6] Cancers that are confined within the wall of the colon may be curable with surgery while cancer that has spread widely are usually not curable, with management being directed towards improving quality of life and symptoms.[6] The five-year survival rate in the United States is around 65%.[7] The individual likelihood of survival depends on how advanced the cancer is, whether or not all the cancer can be removed with surgery, and the person's overall health.[1] Globally, colorectal cancer is the third most common type of cancer, making up about 10% of all cases.[13] In 2012, there were 1.4 million new cases and 694,000 deaths from the disease.[13] It is more common in developed countries, where more than 65% of cases are found.[2] It is less common in women than men.[2]
The signs and symptoms of colorectal cancer depend on the location of the tumor in the bowel, and whether it has spread elsewhere in the body (metastasis). The classic warning signs include: worsening constipation, blood in the stool, decrease in stool caliber (thickness), loss of appetite, loss of weight, and nausea or vomiting in someone over 50 years old.[14] While rectal bleeding or anemia are high-risk features in those over the age of 50,[15] other commonly described symptoms including weight loss and change in bowel habit are typically only concerning if associated with bleeding.[15][16]
Greater than 75–95% of colorectal cancer occurs in people with little or no genetic risk.[17][18] Risk factors include older age, male gender,[18] high intake of fat, alcohol, red meat, processed meats, obesity, smoking, and a lack of physical exercise.[17][19] Approximately 10% of cases are linked to insufficient activity.[20] The risk from alcohol appears to increase at greater than one drink per day.[21] Drinking 5 glasses of water a day is linked to a decrease in the risk of colorectal cancer and adenomatous polyps.[22] Streptococcus gallolyticus is associated with colorectal cancer.[23] Some strains of Streptococcus bovis/Streptococcus equinus complex are consumed by millions of people daily and thus may be safe.[24] 25 to 80% of people with Streptococcus bovis/gallolyticus bacteremia have concomitant colorectal tumors.[25] Seroprevalence of Streptococcus bovis/gallolyticus is considered as a candidate practical marker for the early prediction of an underlying bowel lesion at high risk population.[25] It has been suggested that the presence of antibodies to Streptococcus bovis/gallolyticus antigens or the antigens themselves in the bloodstream may act as markers for the carcinogenesis in the colon.[25]
People with inflammatory bowel disease (ulcerative colitis and Crohn's disease) are at increased risk of colon cancer.[26][27] The risk increases the longer a person has the disease,[28] and the worse the severity of inflammation.[29] In these high risk groups, both prevention with aspirin and regular colonoscopies are recommended.[28] People with inflammatory bowel disease account for less than 2% of colon cancer cases yearly.[29] In those with Crohn's disease 2% get colorectal cancer after 10 years, 8% after 20 years, and 18% after 30 years.[29] In those with ulcerative colitis approximately 16% develop either a cancer precursor or cancer of the colon over 30 years.[29]
Those with a family history in two or more first-degree relatives (such as a parent or sibling) have a two to threefold greater risk of disease and this group accounts for about 20% of all cases. A number of genetic syndromes are also associated with higher rates of colorectal cancer. The most common of these is hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome) which is present in about 3% of people with colorectal cancer.[18] Other syndromes that are strongly associated with colorectal cancer include Gardner syndrome,[30] and familial adenomatous polyposis (FAP). For people with these syndromes, cancer almost always occurs and makes up 1% of the cancer cases.[31] A total proctocolectomy may be recommended for people with FAP as a preventative measure due to the high risk of malignancy. Colectomy, removal of the colon, may not suffice as a preventative measure because of the high risk of rectal cancer if the rectum remains.[32]
Most deaths due to colon cancer are associated with metastatic disease. A gene that appears to contribute to the potential for metastatic disease, metastasis associated in colon cancer 1 (MACC1), has been isolated.[33] It is a transcriptional factor that influences the expression of hepatocyte growth factor. This gene is associated with the proliferation, invasion and scattering of colon cancer cells in cell culture, and tumor growth and metastasis in mice. MACC1 may be a potential target for cancer intervention, but this possibility needs to be confirmed with clinical studies.[34]
Epigenetic factors, such as abnormal DNA methylation of tumor suppressor promoters play a role in the development of colorectal cancer.[35]
Colorectal cancer is a disease originating from the epithelial cells lining the colon or rectum of the gastrointestinal tract, most frequently as a result of mutations in the Wnt signaling pathway that increase signaling activity. The mutations can be inherited or acquired, and most probably occur in the intestinal crypt stem cell.[36][37][38] The most commonly mutated gene in all colorectal cancer is the APC gene, which produces the APC protein. The APC protein prevents the accumulation of β-catenin protein. Without APC, β-catenin accumulates to high levels and translocates (moves) into the nucleus, binds to DNA, and activates the transcription of proto-oncogenes. These genes are normally important for stem cell renewal and differentiation, but when inappropriately expressed at high levels, they can cause cancer. While APC is mutated in most colon cancers, some cancers have increased β-catenin because of mutations in β-catenin (CTNNB1) that block its own breakdown, or have mutations in other genes with function similar to APC such as AXIN1, AXIN2, TCF7L2, or NKD1.[39]
Beyond the defects in the Wnt signaling pathway, other mutations must occur for the cell to become cancerous. The p53 protein, produced by the TP53 gene, normally monitors cell division and kills cells if they have Wnt pathway defects. Eventually, a cell line acquires a mutation in the TP53 gene and transforms the tissue from a benign epithelial tumor into an invasive epithelial cell cancer. Sometimes the gene encoding p53 is not mutated, but another protective protein named BAX is mutated instead.[39]
Other proteins responsible for programmed cell death that are commonly deactivated in colorectal cancers are TGF-β and DCC (Deleted in Colorectal Cancer). TGF-β has a deactivating mutation in at least half of colorectal cancers. Sometimes TGF-β is not deactivated, but a downstream protein named SMAD is deactivated.[39] DCC commonly has a deleted segment of a chromosome in colorectal cancer.[40]
Approximately 70% of all human genes are expressed in colorectal cancer, with just over 1% of having increased expression in colorectal cancer compared to other forms of cancer.[41] Some genes are oncogenes: they are overexpressed in colorectal cancer. For example, genes encoding the proteins KRAS, RAF, and PI3K, which normally stimulate the cell to divide in response to growth factors, can acquire mutations that result in over-activation of cell proliferation. The chronological order of mutations is sometimes important. If a previous APC mutation occurred, a primary KRAS mutation often progresses to cancer rather than a self-limiting hyperplastic or borderline lesion.[42] PTEN, a tumor suppressor, normally inhibits PI3K, but can sometimes become mutated and deactivated.[39]
Comprehensive, genome-scale analysis has revealed that colorectal carcinomas can be categorized into hypermutated and non-hypermutated tumor types.[43] In addition to the oncogenic and inactivating mutations described for the genes above, non-hypermutated samples also contain mutated CTNNB1, FAM123B, SOX9, ATM, and ARID1A. Progressing through a distinct set of genetic events, hypermutated tumors display mutated forms of ACVR2A, TGFBR2, MSH3, MSH6, SLC9A9, TCF7L2, and BRAF. The common theme among these genes, across both tumor types, is their involvement in WNT and TGF-β signaling pathways, which results in increased activity of MYC, a central player in colorectal cancer.[43]
The term "field cancerization" was first used in 1953 to describe an area or "field" of epithelium that has been preconditioned (by what were largely unknown processes at the time) to predispose it towards development of cancer.[44] Since then, the terms "field cancerization", "field carcinogenesis", "field defect", and "field effect" have been used to describe pre-malignant or pre-neoplastic tissue in which new cancers are likely to arise.[45]
Field defects are important in progression to colon cancer.[46][47][48]
However, in most cancer research, as pointed out by Rubin[49] "The vast majority of studies in cancer research has been done on well-defined tumors in vivo, or on discrete neoplastic foci in vitro. Yet there is evidence that more than 80% of the somatic mutations found in mutator phenotype human colorectal tumors occur before the onset of terminal clonal expansion."[50] Similarly, Vogelstein et al.[51] pointed out that more than half of somatic mutations identified in tumors occurred in a pre-neoplastic phase (in a field defect), during growth of apparently normal cells. Likewise, epigenetic alterations present in tumors may have occurred in pre-neoplastic field defects.
An expanded view of field effect has been termed "etiologic field effect", which encompasses not only molecular and pathologic changes in pre-neoplastic cells but also influences of exogenous environmental factors and molecular changes in the local microenvironment on neoplastic evolution from tumor initiation to death.[52]
Epigenetic alterations are much more frequent in colon cancer than genetic (mutational) alterations. As described by Vogelstein et al.,[51] an average cancer of the colon has only 1 or 2 oncogene mutations and 1 to 5 tumor suppressor mutations (together designated “driver mutations”), with about 60 further “passenger” mutations. The oncogenes and tumor suppressor genes are well studied and are described above under Pathogenesis.
However, by comparison, epigenetic alterations in colon cancers are frequent and affect hundreds of genes. For instance, there are types of small RNAs called microRNAs that are about 22 nucleotides long. These microRNAs (or miRNAs) do not code for proteins, but they can target protein coding genes and reduce their expression. Expression of these miRNAs can be epigenetically altered. As one example, the epigenetic alteration consisting of CpG island methylation of the DNA sequence encoding miR-137 reduces its expression. This is a frequent early epigenetic event in colorectal carcinogenesis, occurring in 81% of colon cancers and in 14% of the normal appearing colonic mucosa adjacent to the cancers. The altered adjacent tissues associated with these cancers are called field defects. Silencing of miR-137 can affect expression of about 500 genes, the targets of this miRNA.[53]
Changes in the level of miR-137 expression result in changed mRNA expression of the target genes by 2 to 20-fold and corresponding, though often smaller, changes in expression of the protein products of the genes. Other microRNAs, with likely comparable numbers of target genes, are even more frequently epigenetically altered in colonic field defects and in the colon cancers that arise from them. These include miR-124a, miR-34b/c and miR-342 which are silenced by CpG island methylation of their encoding DNA sequences in primary tumors at rates of 99%, 93% and 86%, respectively, and in the adjacent normal appearing mucosa at rates of 59%, 26% and 56%, respectively.[54][55]
In addition to epigenetic alteration of expression of miRNAs, other common types of epigenetic alterations in cancers that change gene expression levels include direct hypermethylation or hypomethylation of CpG islands of protein-encoding genes and alterations in histones and chromosomal architecture that influence gene expression.[56][57] As an example, 147 hypermethylations and 27 hypomethylations of protein coding genes were frequently associated with colorectal cancers. Of the hypermethylated genes, 10 were hypermethylated in 100% of colon cancers, and many others were hypermethylated in more than 50% of colon cancers.[58] In addition, 11 hypermethylations and 96 hypomethylations of miRNAs were also associated with colorectal cancers.[58]
Recent evidence indicates that early epigenetic reductions of DNA repair enzyme expression likely lead to the genomic and epigenomic instability characteristic of cancer.[46][59][60][61]
As summarized in the articles Carcinogenesis and Neoplasm, for sporadic cancers in general, a deficiency in DNA repair is occasionally due to a mutation in a DNA repair gene, but is much more frequently due to epigenetic alterations that reduce or silence expression of DNA repair genes.
Colorectal cancer diagnosis is performed by sampling of areas of the colon suspicious for possible tumor development, typically during colonoscopy or sigmoidoscopy, depending on the location of the lesion.[18] It is confirmed by microscopical examination of a tissue sample.
Disease extent is usually determined by a CT scan of the chest, abdomen and pelvis.[18] Other potential imaging tests such as PET and MRI may be used in certain cases.[18]
Colon cancer staging is done next and is based on radiology and pathology. As for all other forms of cancer, tumor staging is based on the TNM system which considers how much the initial tumor has spread, if and where there are lymph node metastasis and if there are metastases in more distant organs, usually liver.[18]
The microscopic cellular characteristics of the tumor are reported from the analysis of tissue taken from a biopsy or surgery. A pathology report contains a description of the microscopical characteristics of the tumor tissue, including both tumor cells and how the tumor invades into healthy tissues and finally if the tumor appears to be completely removed. The most common form of colon cancer is adenocarcinoma. Other, rarer types include lymphoma, adenosquamous and squamous cell carcinoma. Some subtypes have been found to be more aggressive.[62]
Cancers on the right side of the large intestine (ascending colon and cecum) tend to be exophytic, that is, the tumor 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 tumors tend to be circumferential, and can obstruct the bowel lumen, much like a napkin ring, and results in thinner caliber stools.
Adenocarcinoma is a malignant epithelial tumor, originating from superficial glandular epithelial cells lining the colon and rectum. It invades the wall, infiltrating the muscularis mucosae layer, the submucosa, and then 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. This occurs in mucinous adenocarcinoma, in which cells are poorly differentiated. If the mucus remains inside the tumor cell, it pushes the nucleus at the periphery, this occurs in "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.[63]
In cases where a metastasis from colorectal cancer is suspected, immunohistochemistry is used to ascertain correct diagnosis. Proteins that are more specifically expressed in colorectal cancer and can be used as diagnostic markers are cytokeratin 20, CDX2, SATB2 and CDH17. Most (50%) colorectal adenomas and (80–90%) colorectal cancer tumors are thought to over express the cyclooxygenase-2 (COX-2) enzyme.[64] This enzyme is generally not found in healthy colon tissue, but is thought to fuel abnormal cell growth.
Macroscopy
Appearance of the inside of the colon showing one invasive colorectal carcinoma (the crater-like, reddish, irregularly shaped tumor)
Gross appearance of a colectomy specimen containing two adenomatous polyps (the brownish oval tumors above the labels, attached to the normal beige lining by a stalk) and one invasive colorectal carcinoma (the crater-like, reddish, irregularly shaped tumor located above the label)
Endoscopic image of colon cancer identified in sigmoid colon on screening colonoscopy in the setting of Crohn's disease
PET/CT of a staging exam of colon carcinoma. Besides the primary tumor a lot of lesions can be seen. On cursor position: lung nodule.
Fungating carcinoma of the colon
Micrographs (H&E stain)
Cancer — Invasive adenocarcinoma (the most common type of colorectal cancer). The cancerous cells are seen in the center and at the bottom right of the image (blue). Near normal colon-lining cells are seen at the top right of the image.
Cancer — Histopathologic image of colonic carcinoid
Precancer — Tubular adenoma (left of image), a type of colonic polyp and a precursor of colorectal cancer. Normal colorectal mucosa is seen on the right.
Precancer — Colorectal villous adenoma
Staging is typically made according to the TNM staging system from the WHO organization, the UICC and the AJCC. The Astler-Coller classification (1954) and the Dukes classification (1932) are now less used.
The T stages of bowel cancer.
Dukes stage A bowel cancer; the cancer is only in the inner lining of the bowel.
Dukes stage B bowel cancer; the cancer has invaded the muscle.
Dukes stage C bowel cancer; the cancer has invaded the nearby lymph nodes.
Dukes stage D bowel cancer; the cancer has metastasized.
The most common metastasis sites for colorectal cancer are the liver, the lung and the peritoneum.[65]
Tumor budding in colorectal cancer is loosely defined by the presence of individual cells and small clusters of tumor cells at the invasive front of carcinomas. It has been postulated to represent an epithelial–mesenchymal transition (EMT). Tumor budding is a well-established independent marker of a potentially poor outcome in colorectal carcinoma that may allow for dividing people into risk categories more meaningful than those defined by TNM staging, and also potentially guide treatment decisions, especially in T1 and T3 N0 (Stage II, Dukes’ B) colorectal carcinoma. Unfortunately, its universal acceptance as a reportable factor has been held back by a lack of definitional uniformity with respect to both qualitative and quantitative aspects of tumor budding.[66]
It has been estimated that about half of colorectal cancer cases are due to lifestyle factors and about a quarter of all cases are preventable.[67] Increasing surveillance, engaging in physical activity, consuming a diet high in fiber, and reducing smoking and alcohol consumption decrease the risk.[68][69]
Current dietary recommendations to prevent colorectal cancer include increasing the consumption of whole grains, fruits and vegetables, and reducing the intake of red meat and processed meats.[19][70] Higher physical activity is also recommended.[19][71] Physical exercise is associated with a modest reduction in colon but not rectal cancer risk.[72][73] High levels of physical activity reduce the risk of colon cancer by about 21%.[74] Sitting regularly for prolonged periods is associated with higher mortality from colon cancer. The risk is not negated by regular exercise, though it is lowered.[75] The risk of colon cancer can be reduced by maintaining a normal body weight.[76] The evidence for any protective effect conferred by fiber and fruits and vegetables is, however, poor.[19][77]
Aspirin and celecoxib appear to decrease the risk of colorectal cancer in those at high risk.[78][79] Aspirin is recommended in those who are 50 to 60 years old, do not have an increased risk of bleeding, and are at risk for cardiovascular disease to prevent colorectal cancer.[80] It is not recommended in those at average risk.[81] There is tentative evidence for calcium supplementation, but it is not sufficient to make a recommendation.[82] Vitamin D intake and blood levels are associated with a lower risk of colon cancer.[83][84]
As more than 80% of colorectal cancers arise from adenomatous polyps, screening for this cancer is effective not only for early detection but also for prevention.[18][85] Diagnosis of cases of colorectal cancer through screening tends to occur 2–3 years before diagnosis of cases with symptoms.[18] Any polyps that are detected can be removed, usually by colonoscopy or sigmoidoscopy, and thus prevent them from turning cancerous. Screening has the potential to reduce colorectal cancer deaths by 60%.[86]
The three main screening tests are colonoscopy, fecal occult blood testing, flexible sigmoidoscopy.[87] Of the three, only sigmoidoscopy cannot screen the right side of the colon where 42% of malignancies are found.[88] Flexible sigmoidoscopy however has the best evidence for decreasing the risk of death from any cause.[89]
Other options may include virtual colonoscopy and stool DNA screening testing.[87] Virtual colonoscopy via a CT scan appears as good as standard colonoscopy for detecting cancers and large adenomas but is expensive, associated with radiation exposure, and cannot remove any detected abnormal growths like standard colonoscopy can.[18]
Fecal occult blood testing (FOBT) of the stool is typically recommended every two years and can be either guaiac-based or immunochemical.[18] If abnormal FOBT results are found, participants are typically referred for a follow-up colonoscopy examination. Yearly to every two year FOBT screening reduces colorectal cancer deaths by 16% and among those participating in screening colorectal cancer deaths can be reduced up to 23%, although it has not been proven to reduce all-cause mortality.[90] Immunochemical tests are accurate and do not require dietary or medication changes before testing.[91] The stool DNA screening test looks for biomarkers associated with colorectal cancer and precancerous lesions, including altered DNA and blood hemoglobin. A positive result should be followed by colonoscopy. If used, screening is recommended every 3 years, starting at age 50.[citation needed]
In the United States, screening is typically recommended between ages 50 to 75 years.[5] For those between 76 and 85 years old, the decision to screen should be individualized.[5] Several screening methods can be used, including stool based tests every 3 years, sigmoidoscopy every 5 years and colonoscopy every 10 years. For those at high risk, screenings usually begin at around 40.[18][92] It is unclear which of these two methods is better.[93] Colonoscopy may find more cancers in the first part of the colon, but is associated with greater cost and more complications.[93] For people with average risk who have had a high-quality colonoscopy with normal results, the American Gastroenterological Association does not recommend any type of screening in the 10 years following the colonoscopy.[94][95] For people over 75 or those with a life expectancy of less than 10 years, screening is not recommended.[96] It takes about 10 years after screening for one out of a 1000 people to benefit.[97]
In Canada, among those 50 to 75 years old at normal risk, fecal immunochemical testing or FOBT is recommended every two years or sigmoidoscopy every 10 years.[98] Colonoscopy is less preferred.[98]
Some countries have national colorectal screening programs which offer FOBT screening for all adults within a certain age group, typically starting between ages 50 to 60. Examples of countries with organised screening include the United Kingdom,[99] Australia,[100] and the Netherlands.[101]
The treatment of colorectal cancer can be aimed at cure or palliation. The decision on which aim to adopt depends on various factors, including the person's health and preferences, as well as the stage of the tumor.[102] When colorectal cancer is caught early, surgery can be curative. However, when it is detected at later stages (for which metastases are present), this is less likely and treatment is often directed at palliation, to relieve symptoms caused by the tumour and keep the person as comfortable as possible.[18]
If the cancer is found at a very early stage, it may be removed during a colonoscopy.[6] For people with localized cancer, the preferred treatment is complete surgical removal with adequate margins, with the attempt of achieving a cure. This can either be done by an open laparotomy or sometimes laparoscopically.[18] The colon may then be reconnected or a person may have a colostomy.[6]
If there are only a few metastases in the liver or lungs they may also be removed. Sometimes chemotherapy is used before surgery to shrink the cancer before attempting to remove it. The two most common sites of recurrence of colorectal cancer are the liver and lungs.[18]
In both cancer of the colon and rectum, chemotherapy may be used in addition to surgery in certain cases. The decision to add chemotherapy in management of colon and rectal cancer depends on the stage of the disease.
In Stage I colon cancer, no chemotherapy is offered, and surgery is the definitive treatment. The role of chemotherapy in Stage II colon cancer is debatable, and is usually not offered unless risk factors such as T4 tumor or inadequate lymph node sampling is identified. It is also known that the people who carry abnormalities of the mismatch repair genes do not benefit from chemotherapy. For stage III and Stage IV colon cancer, chemotherapy is an integral part of treatment.[18]
If cancer has spread to the lymph nodes or distant organs, which is the case with stage III and stage IV colon cancer respectively, adding chemotherapy agents fluorouracil, capecitabine or oxaliplatin increases life expectancy. If the lymph nodes do not contain cancer, the benefits of chemotherapy are controversial. If the cancer is widely metastatic or unresectable, treatment is then palliative. Typically in this setting, a number of different chemotherapy medications may be used.[18] Chemotherapy drugs for this condition may include capecitabine, fluorouracil, irinotecan, oxaliplatin and UFT.[103] The drugs capecitabine and fluorouracil are interchangeable, with capecitabine being an oral medication while fluorouracil being an intravenous medicine. Some specific regimens used for CRC are FOLFOX, FOLFOXIRI, and FOLFIRI.[104] Antiangiogenic drugs such as bevacizumab are often added in first line therapy. Another class of drugs used in the second line setting are epidermal growth factor receptor inhibitors, of which the two FDA approved ones are cetuximab and panitumumab.[105]
The primary difference in the approach to low stage rectal cancer is the incorporation of radiation therapy. Often, it is used in conjunction with chemotherapy in a neoadjuvant fashion to enable surgical resection, so that ultimately as colostomy is not required. However, it may not be possible in low lying tumors, in which case, a permanent colostomy may be required. Stage IV rectal cancer is treated similar to stage IV colon cancer.
While a combination of radiation and chemotherapy may be useful for rectal cancer,[18] its use in colon cancer is not routine due to the sensitivity of the bowels to radiation.[106] Just as for chemotherapy, radiotherapy can be used in the neoadjuvant and adjuvant setting for some stages of rectal cancer.
Immunotherapy with immune checkpoint inhibitors has been found to be useful for a type of colorectal cancer with mismatch repair deficiency and microsatellite instability.[107][108] Most people who do improve, however, still worsen after months or years.[108] Other types of colorectal cancer as of 2017 is still being studied.[107][108]
Palliative care is medical care which focuses on treatment of symptoms from serious illness, like cancer, and improving quality of life.[109] Palliative care is recommended for any person who has advanced colon cancer or has significant symptoms.[110]
Involvement of palliative care may be beneficial to improve the quality of life for both the person and his or her family, by improving symptoms, anxiety and preventing admissions to the hospital.[111]
In people with incurable colorectal cancer, palliative care can consist of procedures that relieve symptoms or complications from the cancer but do not attempt to cure the underlying cancer, thereby improving quality of life. Surgical options may include non-curative surgical removal of some of the cancer tissue, bypassing part of the intestines, or stent placement. These procedures can be considered to improve symptoms and reduce complications such as bleeding from the tumor, abdominal pain and intestinal obstruction.[112] Non-operative methods of symptomatic treatment include radiation therapy to decrease tumor size as well as pain medications.[113]
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).
The U.S. National Comprehensive Cancer Network and American Society of Clinical Oncology provide guidelines for the follow-up of colon cancer.[114][115] 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 people with T2 or greater lesions who are candidates for intervention. A CT-scan of the chest, abdomen and pelvis can be considered annually for the first 3 years for people who are at high risk of recurrence (for example, those 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, a 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.
Routine PET or ultrasound scanning, chest X-rays, complete blood count or liver function tests are not recommended.[114][115] A 2016 systematic review concluded that more intense surveillance and close follow-up does not provide additional survival benefits in non-metastatic colorectal cancers.[116]
Exercise may be recommended in the future as secondary therapy to cancer survivors. In epidemiological studies, exercise may decrease colorectal cancer-specific mortality and all-cause mortality. Results for the specific amounts of exercise needed to observe a benefit were conflicting. These differences may reflect differences in tumour biology and expression of biomarkers. Patients with tumors that lacked CTNNB1 expression (β-catenin), involved in Wnt signalling pathway, required more than 18 Metabolic equivalent (MET) hours per week, a measure of exercise, to observe a reduction in colorectal cancer mortality. The mechanism of how exercise benefits survival may be involved in immune surveillance and inflammation pathways. In clinical studies, a pro-inflammatory response was found in patients with stage II-III colorectal cancer who underwent 2 weeks of moderate exercise after completing their primary therapy. Oxidative balance may be another possible mechanism for benefits observed. A significant decrease in 8-oxo-dG was found in the urine of patients who underwent 2 weeks of moderate exercise after primary therapy. Other possible mechanisms may involve metabolic hormone and sex-steroid hormones, although these pathways may be involved in other types of cancers[117][118]
Another potential biomarker may be p27. Survivors with tumors that expressed p27 and performed greater and equal to 18 MET hours per week were found to have reduced colorectal-cancer mortality survival compared to those with less than 18 MET hours per week. Survivors without p27 expression who exercised were shown to have worse outcomes. The constitutive activation of PI3K/AKT/mTOR pathway may explain the loss of p27 and excess energy balance may up-regulate p27 to stop cancer cells from dividing.[118]
In Europe the five-year survival rate for colorectal cancer is less than 60%. In the developed world about a third of people who get the disease die from it.[18]
Survival is directly related to detection and the type of cancer involved, but overall is poor for symptomatic cancers, as they are typically quite advanced. Survival rates for early stage detection are about five times that of late stage cancers. People with a tumor that has not breached the muscularis mucosa (TNM stage Tis, N0, M0) have a five-year survival rate of 100%, while those with invasive cancer of T1 (within the submucosal layer) or T2 (within the muscular layer) have an average five-year survival rate of approximately 90%. Those with a more invasive tumor yet without node involvement (T3-4, N0, M0) have an average five-year survival rate of approximately 70%. Patients with positive regional lymph nodes (any T, N1-3, M0) have an average five-year survival rate of approximately 40%, while those with distant metastases (any T, any N, M1) have an average five-year survival rate of approximately 5%.[119]
According to American Cancer Society statistics in 2006,[120] over 20% of people with colorectal cancer come to medical attention when the disease is already advanced (stage IV), and up to 25% of this group will have isolated liver metastasis that is potentially resectable. In this selective group, those who undergo curative resection experience a five-year survival outcome in a third of the cases.[121]
Less than 600 genes are linked to outcomes in colorectal cancer.[41] These include both unfavorable genes, where high expression is related to poor outcome, for example the heat shock 70 kDa protein 1 (HSPA1A), and favorable genes where high expression is associated with better survival, for example the putative RNA-binding protein 3 (RBM3).[41]
Colon and rectum cancer deaths per million persons in 2012
Globally more than 1 million people get colorectal cancer every year[18] resulting in about 715,000 deaths as of 2010 up from 490,000 in 1990.[122]
As of 2012[update], it is the second most common cause of cancer in women (9.2% of diagnoses) and the third most common in men (10.0%)[123] with it being the fourth most common cause of cancer death after lung, stomach, and liver cancer.[124] It is more common in developed than developing countries.[125] Globally incidences vary 10-fold with highest rates in Australia, New Zealand, Europe and the US and lowest rates in Africa and South-Central Asia.[126]
Colorectal cancer is the second highest cause of cancer occurrence and death for men and women in the United States combined. An estimated 141,210 cases were diagnosed in 2011.[127]
Based on rates from 2007 to 2009, 4.96% of US men and women born today will be diagnosed with colorectal cancer during their lifetime.[128] From 2005 to 2009, the median age at diagnosis for cancer of the colon and rectum in the US was 69 years of age. Approximately 0.1% were diagnosed under age 20; 1.1% between 20 and 34; 4.0% between 35 and 44; 13.4% between 45 and 54; 20.4% between 55 and 64; 24.0% between 65 and 74; 25.0% between 75 and 84; and 12.0% 85+ years of age. Rates are higher among males (54 per 100,000 c.f. 40 per 100,000 for females).
In the UK about 41,000 people a year get colon cancer making it the fourth most common type.[129]
One in 19 men and one in 28 women in Australia will develop colorectal cancer before the age of 75; one in 10 men and one in 15 women will develop it by 85 years of age.[130]
Rectal cancer has been diagnosed in an Ancient Egyptian mummy who had lived in the Dakhleh Oasis during the Ptolemaic period.[131]
The Biblical king Jehoram of Judah was recorded in 2 Chronicles 21 to be cursed with an incurable disease of the bowel, leading to his death, due to his supposed evil deeds. Modern scholarship indicates that his condition was most likely colon cancer.[132]
In the United States, March is colorectal cancer awareness month.[86]
Preliminary in-vitro evidence suggests lactic acid bacteria (e.g., lactobacilli, streptococci or lactococci) may be protective against the development and progression of colorectal cancer through several mechanisms such as antioxidant activity, immunomodulation, promoting programmed cell death, antiproliferative effects, and epigenetic modification of cancer cells.[133]
Large-scale genome sequencing studies have been done to identify mutations in colorectal cancer patients' genome.[134]
The bacteria clostridium novyi-NT, is also being studied.[135]
2010/2011
| Classification |
D
|
|---|---|
| External resources |
|
| Wikimedia Commons has media related to Colorectal cancer. |
Diseases of the digestive system (primarily K20–K93, 530–579)
|
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Upper GI tract |
|
||||||||||
| Lower GI tract: Intestinal/ |
|
||||||||||
| GI bleeding/BIS |
|
||||||||||
| Accessory |
|
||||||||||
| Abdominopelvic |
|
||||||||||
Digestive system neoplasia (C15–C26/D12–D13, 150–159/211)
|
|||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| GI tract |
|
||||||||||||||||||
| Accessory |
|
||||||||||||||||||
| Peritoneum |
|
||||||||||||||||||
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
| リンク元 | 「結腸癌」 |
| 関連記事 | 「colonic」「colon」 |
| normal →→→→→ carcinoma | |||
| APC | K-RAS | SMAD4 | P53 |
| β-catenin | BRAF | TGFβII | |