colorectal cancer

大腸癌

WordNet

1. type genus of the family Cancridae (同)genus Cancer
2. the fourth sign of the zodiac; the sun is in this sign from about June 21 to July 22 (同)Cancer the Crab, Crab
3. (astrology) a person who is born while the sun is in Cancer (同)Crab
4. a small zodiacal constellation in the northern hemisphere; between Leo and Gemini
5. any malignant growth or tumor caused by abnormal and uncontrolled cell division; it may spread to other parts of the body through the lymphatic system or the blood stream (同)malignant neoplastic disease
6. relating to or affecting the colon and the rectum; "most colorectal cancers arise from adenomatous polyps"

PrepTutorEJDIC

1. 〈U〉〈C〉『がん』 / 〈U〉〈C〉害悪 / 《Cancer》(星座の)カニ座

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/05/25 12:03:59」(JST)

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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
Causes	Old age, lifestyle factors, genetic disorders
Risk factors	Diet, obesity, smoking, lack of physical activity
Diagnostic method	Tissue biopsy during a sigmoidoscopy or colonoscopy
Prevention	Screening from age of 50 to 75
Treatment	Surgery, radiation therapy, chemotherapy, targeted therapy
Prognosis	Five year survival rates 65% (USA)
Frequency	9.4 million (2015)
Deaths	832,000 (2015)

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). A cancer is the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Signs and symptoms may include blood in the stool, a change in bowel movements, weight loss, and feeling tired all the time.

Most colorectal cancers are due to old age and lifestyle factors with only a small number of cases due to underlying genetic disorders. Some risk factors include diet, obesity, smoking, and lack of physical activity. Dietary factors that increase the risk include red and processed meat as well as alcohol. Another risk factor is inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis. 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. It typically starts as a benign tumor, often in the form of a polyp, which over time becomes cancerous.

Bowel cancer may be diagnosed by obtaining a sample of the colon during a sigmoidoscopy or colonoscopy. This is then followed by medical imaging to determine if the disease has spread. Screening is effective for preventing and decreasing deaths from colorectal cancer. Screening is recommended starting from the age of 50 to 75. During colonoscopy, small polyps may be removed if found. 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. Their general use is not recommended for this purpose, however, due to side effects.

Treatments used for colorectal cancer may include some combination of surgery, radiation therapy, chemotherapy and targeted therapy. 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. Five year survival rates in the United States are around 65%. This, however, depends on how advanced the cancer is, whether or not all the cancer can be removed with surgery, and the person's overall health. Globally, colorectal cancer is the third most common type of cancer making up about 10% of all cases. In 2012, there were 1.4 million new cases and 694,000 deaths from the disease. It is more common in developed countries, where more than 65% of cases are found. It is less common in women than men.

Signs and symptoms

Location and appearance of two example colorectal tumors

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. While rectal bleeding or anemia are high-risk features in those over the age of 50, other commonly described symptoms including weight loss and change in bowel habit are typically only concerning if associated with bleeding.

Cause

Greater than 75–95% of colorectal cancer occurs in people with little or no genetic risk. Risk factors include older age, male gender, high intake of fat, alcohol, red meat, processed meats, obesity, smoking, and a lack of physical exercise. Approximately 10% of cases are linked to insufficient activity. The risk from alcohol appears to increase at greater than one drink per day. Drinking 5 glasses of water a day is linked to a decrease in the risk of colorectal cancer and adenomatous polyps.

Inflammatory bowel disease

People with inflammatory bowel disease (ulcerative colitis and Crohn's disease) are at increased risk of colon cancer. The risk increases the longer a person has the disease, and the worse the severity of inflammation. In these high risk groups, both prevention with aspirin and regular colonoscopies are recommended. People with inflammatory bowel disease account for less than 2% of colon cancer cases yearly. In those with Crohn's disease 2% get colorectal cancer after 10 years, 8% after 20 years, and 18% after 30 years. In those with ulcerative colitis approximately 16% develop either a cancer precursor or cancer of the colon over 30 years.

Genetics

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. Other syndromes that are strongly associated with colorectal cancer include Gardner syndrome, and familial adenomatous polyposis (FAP). For people with these syndromes, cancer almost always occurs and makes up 1% of the cancer cases. 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.

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. 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.

Epigenetic factors, such as abnormal DNA methylation of tumor suppressor promoters play a role in the development of colorectal cancer.

Pathogenesis

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. 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.

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.

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. DCC commonly has a deleted segment of a chromosome in colorectal cancer.

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. PTEN, a tumor suppressor, normally inhibits PI3K, but can sometimes become mutated and deactivated.

Comprehensive, genome-scale analysis has revealed that colorectal carcinomas can be categorized into hypermutated and non-hypermutated tumor types. 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.

Field defects

Longitudinally opened freshly resected colon segment showing a cancer and four polyps. Plus a schematic diagram indicating a likely field defect (a region of tissue that precedes and predisposes to the development of cancer) in this colon segment. The diagram indicates sub-clones and sub-sub-clones that were precursors to the tumors.

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. 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.

Field defects are important in progression to colon cancer.

However, in most cancer research, as pointed out by Rubin "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." Similarly, Vogelstein et al. 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.

Epigenetics

Epigenetic alterations are much more frequent in colon cancer than genetic (mutational) alterations. As described by Vogelstein et al., 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.

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.

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. 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. In addition, 11 hypermethylations and 96 hypomethylations of miRNAs were also associated with colorectal cancers.

Recent evidence indicates that early epigenetic reductions of DNA repair enzyme expression likely lead to the genomic and epigenomic instability characteristic of cancer.

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.

Diagnosis

Colon cancer with extensive metastases to the liver

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. Disease extent is usually determined by a CT scan of the chest, abdomen and pelvis. Other potential imaging tests such as PET and MRI may be used in certain cases. Colon cancer staging is done next, based on the TNM system which considers how much the initial tumor has spread, if and where lymph nodes are involved and the extent of metastatis.

The microscopic cellular characteristics of the tumor are usually reported from the analysis of tissue taken from a biopsy or surgery. A pathology report usually contains a description of cell type and grade. The most common colon cancer cell type is adenocarcinoma (98% of cases). Other, rarer types include lymphoma and squamous cell carcinoma.

Macroscopy

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.

Microscopy

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.

Immunochemistry

Most (50%) colorectal adenomas and (80–90%) colorectal cancer tumors are thought to over express the cyclooxygenase-2 (COX-2) enzyme. 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

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.

Tumor budding

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.

Prevention

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. Increasing surveillance, engaging in physical activity, consuming a diet high in fiber, and reducing smoking and alcohol consumption decrease the risk.

Lifestyle

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. Higher physical activity is also recommended. Physical exercise is associated with a modest reduction in colon but not rectal cancer risk. High levels of physical activity reduce the risk of colon cancer by about 21%. 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. The evidence for any protective effect conferred by fiber and fruits and vegetables is, however, poor. The risk of colon cancer can be reduced by maintaining a normal body weight.

Medication

Aspirin and celecoxib appear to decrease the risk of colorectal cancer in those at high risk. 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. It is not recommended in those at average risk. There is tentative evidence for calcium supplementation but it is not sufficient to make a recommendation. Vitamin D intake and blood levels are associated with a lower risk of colon cancer.

Screening

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. Diagnosis of cases of colorectal cancer through screening tends to occur 2–3 years before diagnosis of cases with symptoms. Any polyps that are detected can be removed, usually by colonoscopy or sigmoidoscopy, and thus prevented from turning cancerous. Screening has the potential to reduce colorectal cancer deaths by 60%.

The three main screening tests are fecal occult blood testing, flexible sigmoidoscopy, and colonoscopy. Of the three, only sigmoidoscopy cannot screen the right side of the colon where 42% of malignancies are found. Other options may include virtual colonoscopy and stool DNA screening testing. 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.

Fecal occult blood testing (FOBT) of the stool is typically recommended every two years and can be either guaiac based or immunochemical. If abnormal FOBT results are found, participants are typically referred for a follow-up colonoscopy examination. Annual to biennial FOBT screening reduce colorectal cancer mortality by 16% and among those participating in screening colorectal cancer mortality can be reduced up to 23%, although it has not been proven to reduce all-cause mortality. Immunochemical tests are highly accurate and do not require dietary or medication changes before testing. 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.

Recommendations

In the United States screening is typically recommended between the age of 50 and 75 years. For those between 76 and 85 years of age the decision to screen should be individualized. A number of 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. It is unclear which of these two methods is better. Colonoscopy may find more cancers in the first part of the colon but is associated with greater cost and more complications. 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. For people over 75 or those with a life expectancy of less than 10 years, screening is not recommended. It takes about 10 years after screening for one out of a 1000 people to benefit.

In Canada, among those 50 to 75 at normal risk, fecal immunochemical testing or FOBT is recommended every two years or sigmoidoscopy every 10 years. Colonoscopy is less preferred.

Some countries have national colorectal screening programs which offer FOBT screening for all adults within a certain age group, typically starting between age 50 and 60. Examples of countries with organised screening include the United Kingdom, Australia and the Netherlands.

Management

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. 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.

Surgery

If the cancer is found at a very early stage, it may be removed during a colonoscopy. 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. The colon may then be reconnected or a person may have a colostomy.

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.

• A diagram of a local resection of early stage colon cancer

• A diagram of local surgery for rectal cancer

Chemotherapy

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 patients 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.

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. Chemotherapy drugs for this condition may include capecitabine, fluorouracil, irinotecan, oxaliplatin and UFT. 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. 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.

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.

Radiation therapy

While a combination of radiation and chemotherapy may be useful for rectal cancer, its use in colon cancer is not routine due to the sensitivity of the bowels to radiation. Just as for chemotherapy, radiotherapy can be used in the neoadjuvant and adjuvant setting for some stages of rectal cancer.

Palliative care

Palliative care is medical care which focuses on treatment of symptoms from serious illness, like cancer, and improving quality of life. Palliative care is recommended for any person who has advanced colon cancer or has significant symptoms.

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.

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. Non-operative methods of symptomatic treatment include radiation therapy to decrease tumor size as well as pain medications.

Follow-up

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. 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 patients 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. A 2016 systematic review concluded that more intense surveillance and close follow-up does not provide additional survival benefits in non-metastatic colorectal cancers.

Exercise

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

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.

Prognosis

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.

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 is 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%.

According to American Cancer Society statistics in 2006, 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.

Epidemiology

Colon and rectum cancer deaths per million persons in 2012

  3-17

  18-21

  22-27

  28-36

  37-54

  55-77

  78-162

  163-244

  245-329

  330-533

Globally more than 1 million people get colorectal cancer every year resulting in about 715,000 deaths as of 2010 up from 490,000 in 1990.

As of 2012, it is the second most common cause of cancer in women (9.2% of diagnoses) and the third most common in men (10.0%) with it being the fourth most common cause of cancer death after lung, stomach, and liver cancer. It is more common in developed than developing countries. 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.

United States

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.

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. 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).

United Kingdom

In the UK about 41,000 people a year get colon cancer making it the fourth most common type.

Australia

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.

History

See also: Timeline of colorectal cancer

Rectal cancer has been diagnosed in an Ancient Egyptian mummy who had lived in the Dakhleh Oasis during the Ptolemaic period.

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.

Society and culture

In the United States, March is colorectal cancer awareness month.

Notable cases

Main article: List of people diagnosed with colorectal cancer

• Corazon Aquino, former president of the Philippines
• Pope John Paul II
• Ronald Reagan, actor and former President of the United States
• Harold Wilson, former Prime Minister of the United Kingdom
• Robin Gibb, musician and member of the Bee Gees
• Humayun Ahmed, Bengali writer and film maker
• J.B.S. Haldane, Geneticist; polymath, popular science author
• Stephen Sutton, Charity activist

Research

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.

Large-scale genome sequencing studies have been done to identify mutations in colorectal cancer patients' genome.

The bacteria clostridium novyi-NT, is also being studied.

• Mouse models of colorectal and intestinal cancer
• The Cancer Genome Atlas
• The Colorectal Cancer Atlas integrating genomic and proteomic data pertaining to colorectal cancer tissues and cell lines have been developed.

References

External links

Classification	ICD-10: C18-C20/C21 ICD-9-CM: 153.0-154.1 OMIM: 114500 DiseasesDB: 2975
External resources	MedlinePlus: 000262 eMedicine: med/413 med/1994 ped/3037 Patient UK: Colorectal cancer

• Colorectal cancer at DMOZ

UpToDate Contents

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.

• 1. 大腸癌の臨床症状、診断、および病期分類 clinical presentation diagnosis and staging of colorectal cancer
• 2. 原発性大腸癌のマネージメントの概要 overview of the management of primary colon cancer
• 3. 大腸癌：疫学、危険因子、および防御因子 colorectal cancer epidemiology risk factors and protective factors
• 4. 大腸癌長期生存患者へのアプローチ approach to the long term survivor of colorectal cancer
• 5. 大腸癌の病理および予後決定因子 pathology and prognostic determinants of colorectal cancer

English Journal

• Immunohistochemical study of cyclooxygenase-2 in skin tumors.

• Amirnia M1, Babaie-Ghazani A, Fakhrjou A, Khodaeiani E, Alikhah H, Naghavi-behzad M, Zarrintan A.
• The Journal of dermatological treatment.J Dermatolog Treat.2014 Oct;25(5):380-7. doi: 10.3109/09546634.2012.674191. Epub 2012 Jun 5.
• INTRODUCTION: Anti-cancerous effects of cyclooxygenase-2 (COX-2) inhibitors have been reported in different cancers. High expression of COX-2 has been demonstrated in various neoplasms such as colorectal, gastric, esophageal, breast, non-small cell lung cancers, and pre-neoplastic lesions such as co
• PMID 22667343

• Discussion of First-Degree Relatives' Colorectal Cancer Risk: Survivors' Perspectives.

• Koskan AM1, Thomas-Purcell KB, Yu D, Quinn GP, Dessureault S, Shibata D, Jacobsen PB, Gwede CK.
• Health communication.Health Commun.2014 Sep;29(8):782-790. Epub 2013 Nov 14.
• Although screening reduces colorectal cancer (CRC) incidence and mortality, screening rates are low, particularly among CRC patients' first-degree relatives (FDRs). Little is known about discussion of family members' risk of CRC among patients and their health care providers or with their FDRs. The
• PMID 24229427

• Variation in promptness of presentation among 10,297 patients subsequently diagnosed with one of 18 cancers: Evidence from a National Audit of Cancer Diagnosis in Primary Care.

• Keeble S1, Abel GA, Saunders CL, McPhail S, Walter FM, Neal RD, Rubin GP, Lyratzopoulos G.
• International journal of cancer. Journal international du cancer.Int J Cancer.2014 Sep 1;135(5):1220-8. doi: 10.1002/ijc.28763. Epub 2014 Feb 25.
• Cancer awareness public campaigns aim to shorten the interval between symptom onset and presentation to a doctor (the 'patient interval'). Appreciating variation in promptness of presentation can help to better target awareness campaigns. We explored variation in patient intervals recorded in consul
• PMID 24515930

Japanese Journal

• Erratum to: Prognostic Factors in Colorectal Cancer with Peritoneal Metastases[J Tokyo Wom Med Univ 84:E351-E359, 2014]

• HAYASHIBARA Kaori,ITABASHI Michio,SHIMIZU Satoru,KAKEOKA Shingo,林原 香織,板橋 道朗,清水 悟,亀岡 信悟
• 東京女子医科大学雑誌 85(2), 70-70, 2015-04-25
• NAID 120005606871

• 修正:大腸癌同時性腹膜転移症例における予後因子の検討

• 林原 香織,板橋 道朗,清水 悟,亀岡 信悟
• 東京女子医科大学雑誌 85(2), 70-70, 2015-04-25
• NAID 110009900095

• α-Actinin-4 Enhances Colorectal Cancer Cell Invasion by Suppressing Focal Adhesion Maturation

• Fukumoto Miki,Kurisu Shusaku,Yamada Tesshi,Takenawa Tadaomi
• PLoS ONE 10(4), e0120616, 2015-04-10
• NAID 120005606038

Related Links

• Colorectal Cancer - National Cancer Institute

Information about colon and rectal cancer treatment, prevention, genetics, causes, screening, statistics and other topics from the National Cancer Institute. ... Colorectal cancer is cancer that starts in the colon or rectum. The colon ...

• Colorectal Cancer | Cancer.Net

This is Cancer.Net’s Guide to Colorectal Cancer. Use the menu below to choose the Overview section to get started. Or, you can choose another section to learn more about a specific question you have. Each guide is reviewed by ...

Related Pictures

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★リンクテーブル★

リンク元	「大腸癌」「直腸癌」「colorectal neoplasm」「colorectal tumor」
拡張検索	「deleted in colorectal cancer」「hereditary non-polyposis colorectal cancer」「hereditary nonpolyposis colorectal cancer」
関連記事	「colorectal」「cancer」

「大腸癌」

　　[★]

英

large bowel cancer

同

結腸直腸癌, colorectal cancer, CRC, colorectal carcinoma、直腸結腸癌

関

結腸癌 colon cancer colonic cancer。大腸

• first aid step1 2006 p.277

概念

• 大腸に発生した悪性腫瘍の総称
• 結腸癌、直腸S状部癌、直腸癌を含む。

疫学

死亡率

• 日本

• 男性：第４位(肺＞胃＞肝＞大腸)
• 女性：第１位(大腸＞胃＞肺＞肝＞乳房＞子宮)

• 米

• 3rd most common cancer

リスクファクター(first aid step1 2006 p.277)

• colorectal villous adenomas
• chronic inflammatory bowel disease (especially ulcerative colitis)
• high-fat and low-fiber diets
• ↑ age
• 家族性大腸腺腫症 familial adenomatous polyposis (FAP)
• 遺伝性非ポリポーシス大腸癌 hereditary nonpolyposis colorectal cancer (HNPCC)
• DCC gene deletion
• personal and family history of colon cancer

×Peutz-Jeghers syndromeはリスクファクターではない

好発部位

• 直腸・S状結腸　＞　上行結腸・盲腸　＞　横行結腸　＞　下行結腸

直腸が50%、S状結腸25% (出典不明)

肉眼分類

• ボールマンの分類に基づく

早期癌

• 0型(表在型)

0-I型(隆起型)：Ip(隆起型)、Isp(亜有茎型)、Is(無茎型)

0-II型(表面型)：IIa(表面隆起型), IIc(表面陥凹型)

進行癌

• 1型(腫瘤型)
• 2型(潰瘍限局型)
• 3型(潰瘍浸潤型)
• 4型(びまん浸潤型)

頻度

• 進行癌：2型(潰瘍限局型) ＞ 3型(潰瘍浸潤型) ＞ 1型(腫瘤型) > 4型(びまん浸潤型)

早期癌を含めると、2型(潰瘍限局型)(80%)に次いで0型(表在型)が多い。

2型で外周の2/3週以上となると、注腸造影でapple core sign として認められる。

病期分類

Dukes分類

• A. 癌腫が腸管壁内に限局するもの　←　固有筋層まで(MP。つまりT2)
• B. 癌腫が腸壁を貫いて浸潤するが、リンパ節転移のないもの
• C. リンパ節転移があるもの

進行病期分類

stage	定義	治療
0	癌が粘膜にとどまっている。(M)	内視鏡
I	癌が大腸壁にとどまっている。(SM,MP)	SM軽度浸潤(＜2cm)では内視鏡、それ以外は手術療法
II	癌が大腸壁の外まで浸潤している。(SS,SE)	手術療法
III	リンパ節転移がある。	手術療法＋補助化学療法
IV	肝転移、肺転移または腹膜播種がある。	手術療法 and/or 化学療法 and/or 放射療法

大腸癌取り扱い規約 第7版(2009年)

壁深達度

• M：粘膜内まで
• SM：粘膜下層まで
• MP：固有筋層まで

漿膜を有する部位

• SS：MP越えているが漿膜下にとどまる
• SE：漿膜表面に露出
• SI：他臓器に直接浸潤

漿膜を有しない部位

• A：固有筋層を越えて浸潤
• AI：他臓器に直接浸潤

進行度

	N0	N1	N2	H1,H2,H3,M1 P1,P2,P3
M	0
SM MP	I	IIIa	IIIb	IV
SS,A SE SI,AI	II

リンパ節郭清

• 1群リンパ節郭清：D1：腫瘍付近のリンパ節（傍リンパ節）を切除
• 2群リンパ節郭清：D2：癌のある腸管を栄養する血管に沿うリンパ節（中間リンパ節）までを切除
• 3群リンパ節郭清：D3：栄養血管の根元にあるリンパ節（主リンパ節）までを切除

病理

• 95%が腺癌。高分化型が多い。

症状

腫瘍の局在	右側結腸	左側結腸	S状結腸・直腸
症状	自覚症状に乏しい（貧血、腹部腫瘤、腹痛、まれに腸重積)	イレウス多い、左下腹部痛	血便/粘結弁
	下痢	便秘、便通過障害(下血・血便)	便通異常(下痢・便秘、腹部膨満感、しぶり腹、輪状狭窄、糞柱の狭小化)

検査

血液検査

• Hb：貧血の徴候がないか

腫瘍マーカー

• CEA
• CA19-9
• TPA

便潜血

• 免疫学的便潜血反応：抗ヒトヘモグロビン法

単純X線検査

• apple core sign

診断

• 生検結果による(内視鏡生検)

治療

• 原則として以下の治療を選択するが、必要に応じて、手術療法、化学療法、放射線療法を組み合わせる。(SSUR.550)

Stage0,StageIの一部：内視鏡的切除

StageI,II：手術療法

StageIII：手術療法＋化学療法

StageIV：手術療法、化学療法、および放射線療法の組み合わせ

早期癌

内視鏡的治療

• 内視鏡的ポリペクトミー
• 内視鏡的粘膜切除術 EMR
• 内視鏡的粘膜下層剥離術 ESD

原則

• リンパ節メタなく、腫瘍を一括切除できること。

病期

• stage 0 ～ stage I and SM軽度浸潤 and 最大径 2cm以下

適応基準

• ( M or SM ) and ( 最大経≦2cm ) and ( 肉眼型は問わない )

進行癌

• 化学療法 (参考3)

• 補助化学療法：5-FU　＋　ロイコボリン、テガフール・ウラシル(UFT)　＋　ロイコボリン、カペシタビン capecitabine
• 切除不能進行再発大腸癌：

• FOLFIRI療法　→　FOLFOX療法　、　FOLFOX療法　→　FOLFIRI療法　。一次治療にはベバシズマブ、二次治療にはセツキシマブの併用を推奨

• FOLFOX療法：fluorouracil(5-FU)、levofolinate(L-LV)、oxaliplatin(L-OHP)
• FOLFIRI療法：fluorouracil(5-FU)、levofolinate(L-LV)、irinotecan(CPT-11)

• 放射線療法
• 手術療法

• stage I～IVで行われる。
• 原発巣の切除とリンパ節の郭清を行う
• 転移巣(肝臓、肺)、局所再発に対して：根治性が得られるなら切除。得られないのであれば姑息的治療(肝転移の場合なら、経カテーテル的肝動脈塞栓術
• (姑息的に？結腸癌の進展による直腸の狭窄が考慮される場合には)Hartmann手術をおこなう。
• (大腸癌の肝転移例に対する手術適応)原発巣が根治的に処理されている場合には積極的に肝切除を行う。肝切除ができない場合は経カテーテル的冠動脈塞栓術を施行(QB.A-194)

術式

結腸癌

• 結腸部分切除術
• 回盲部切除術
• 結腸右半切除術
• 結腸左半切除術
• S状結腸切除術
• 結腸全摘術

検診

スクリーニング

USPSTF

• 50-75歳の成人に便潜血・大腸内視鏡を推奨する(A)
• 85歳以上の高齢者には推奨しない(D)
• リスクが有る患者には40歳、ないし発症した親族の年齢の10年前から大腸内視鏡を5年ごとに行う

• リスク：2人の大腸癌ないし腺腫性ポリープの家族歴あり

• 大腸内視鏡であれば10年毎でよいが、これをやらない場合には毎年の便潜血を。

参考

• 1. がん情報 - 結腸および直腸 Colon and Rectum（C18-C20）

http://ganjoho.ncc.go.jp/data/hospital/cancer_registration/odjrh3000000hrgr-att/20070723022_c18colon_and_rectum.pdf

• 2. 大腸低分化腺癌,印環細胞癌の臨床病理学的検討

山形県立中央病院外科

平井 一郎　池田 栄一　飯澤 肇　佐藤 敏彦　岡部 健二　石田 卓也　太田 陽一

最近11年間の大腸癌手術症例1,260例のうち,低分化腺癌(por)93例,印環細胞癌(sig)7例を臨床病理学的に検討した.また間質結合織の多寡で髄様型(med),中間型(int),硬性型(並1)に3分類した。por,sigはs(a2)以深の進行例が多く,早期癌203例中1例のみであり,癌発生直後より急速に進展すると考えられた。5生率は高分化:67.9%,中分化:423%,por,sig:37.4%で,por,sigは有意に予後不良であった。間質別5生率はmedで79.6%と極めて予後良好だったが,sciには3年生存例がなく,med,int,並i間に有意差が認められた。組織発生の検討では,intは分化型腺癌の浸潤先進部の分化度が低下し低分化部分が優勢となったもので,med,sciは発生初期から低分化腺癌の形態をとる症例が存在すると考えられた。大腸低分化腺癌,印環細胞癌の間質組合織の多寡による3分類は予後,癌組織発生の点で重要である。

http://journal.jsgs.or.jp/pdf/028040805.pdf

• 3. 大腸癌治療ガイドライン - 日本癌治療学会

http://www.jsco-cpg.jp/guideline/13.html

ガイドライン

• 大腸癌治療ガイドライン - 日本癌治療学会

http://www.jsco-cpg.jp/guideline/13.html

• 大腸癌治療ガイドライン　医師用　2010年版 - 大腸癌研究会 JSCCR

http://www.jsccr.jp/guideline2010/guideline02.html

「直腸癌」

　　[★]

英

rectal cancer, cancer of the rectum

ラ

carcinoma recti

関

大腸癌、直腸、colorectal cancer

治療

• 治療方針：

• イレウス状態になっている直腸癌に対しては

• 1. 経肛門的にイレウス管を挿入・減圧後、一期的手術　←　増えてきている。
• 2. 人工肛門造設、腫瘍摘出の二期的手術

手術療法

		粘膜内癌	粘膜下層癌	RS	Ra	Rb	P
内視鏡的粘膜切除術		○
内視鏡的粘膜下層剥離術		○	○
前方切除術	高位前方切除術			○
	低位前方切除術				○	○
超低位前方切除術	結腸肛門吻合術				？	？
	結腸嚢肛門吻合術				？	？
直腸切断術(Mile's手術)						○	○

• Hartmann手術：遺残直腸は閉鎖し、結腸口側を人工肛門とする。

国試

• 102B051、100F034(治療)

「colorectal neoplasm」

　　[★]

直腸結腸腫瘍、直腸結腸新生物

関

colorectal cancer、colorectal carcinoma、colorectal tumor

「colorectal tumor」

　　[★]

大腸腫瘍

関

colorectal cancer、colorectal carcinoma、colorectal neoplasm

「deleted in colorectal cancer」

　　[★]

ネトリン受容体

関

DCC、netrin receptor

「hereditary non-polyposis colorectal cancer」

　　[★] 遺伝性非ポリポーシス大腸癌 HNPCC

「hereditary nonpolyposis colorectal cancer」

　　[★] 遺伝性非ポリポーシス大腸癌 HNPCC

「colorectal」

　　[★]

• adj.

• 結腸直腸の

• ex.

• colorectal cancer 大腸癌

関

colorectum

　

「cancer」

　　[★]

同

癌腫

関

tumor