Colorectal cancer overview
To view the overview of familial adenomatous polyposis (FAP), click here
To view the overview of hereditary nonpolyposis colorectal cancer (HNPCC), click here

# Overview
Colorectal cancer is the third most commonly diagnosed cancer in the world, and accounts for 8% of all cancer-related deaths annually. There are both genetic and environmental factors that can increase the risk of colorectal carcinoma (CRC). The pathogenesis of colorectal carcinoma (CRC) involves the molecular pathways for both sporadic and colitis-associated CRC. There are both genetic and environmental causes of colorectal carcinoma (CRC). Colorectal cancer may be differentiated from other diseases that cause unexplained weight loss, unexplained loss of appetite, nausea, vomiting, diarrhea, anemia, jaundice, and fatigue, such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), hemorrhoids, anal fissures, and diverticular disease. Current guidelines recommend that colonoscopy is the optimal screening tool for colon cancer since it detects 98-99% of the cases. The progression from an edematous polyp to colorectal cancer may take 10-15 years. Colorectal cancer staging is an estimate of the amount of penetration of the cancer. Staging is based on the TNM classification system which depends on the extent of local invasion, the degree of lymph node involvement, and whether there is distant metastasis. The history of a patient with colorectal cancer may include a family history of polyps/colorectal cancer or a history of inflammatory bowel disease. Some symptoms that are associated with colorectal cancer are change in bowel habits, hematochezia, and rectal pain. Metastatic symptoms include dyspnea, abdominal pain, fractures, and confusion. Generally, the most common signs of colorectal cancer are emaciation, lethargy, and pallor Other signs include low-grade fever, discomfort on palpation, ascites, rectal bleeding, rectal mass, and jaundice. The laboratory findings associated with colorectal carcinoma are the following: Complete Blood Count (CBC), Fecal Occult Blood Tests (FOBT), serum CEA and CA 19-9 concentration, serum iron concentrations, serum vitamin B12 and folate concentrations, liver function tests, and pulmonary function tests. Chest radiography (CXR) is the initial imaging modality used in the detection of suspected pulmonary metastasis. CT scan is used to determine the extent of involvement on colon cancer, most commonly in the abdomen and lungs. Other imaging tests that can be used for colorectal cancer are MRI, ultrasound, endoscopy, PET scan, barium study, and angiography. A biopsy and genetic testing can be performed when a suspected lesion is found on colonoscopy. Chemotherapy is used to reduce the likelihood of metastasis developing, shrink tumor size, and slow tumor growth. Surgery remains the primary treatment while chemotherapy and/or radiotherapy may be recommended depending on the individual patient's staging and other medical factors. When colorectal cancer metastasizes, there will be a different approach than with a localized tumor. The most common site of metastasis is the liver, and the second most common is the lung.

# Historical Perspective
Colorectal cancer can be dated back to an Egyptian mummy who had lived in the Dakleh Oasis during the Ptolemaic period (200-400 CE). Dr. Aldred Warthin (an American pathologist) studied a family in 1895 and published his first report on it in 1913, documenting a pattern of endometrial, gastric, and colon cancers. In 1971, Lynch and Krush updated the studies of the family which eventually became known as hereditary nonpolyposis colon cancer (HNPCC), also known as Lynch Syndrome. In February 2000, President Bill Clinton officially dedicated March as National Colon Cancer Awareness Month.

# Pathophysiology
The pathogenesis of colorectal carcinoma (CRC) involves the molecular pathways for both sporadic and colitis-associated CRC. Sporadic instability originates from the epithelial cells that line the colon or rectum. Colitis-associated CRC includes genetic instability, epigenetic alteration, chronic inflammation, oxidative stress, and intestinal microbiota. According to the World Health Organization (WHO) histological classification, most colorectal tumors are carcinomas of which almost 90% are adenocarcinomas.

# Causes
The cause of colorectal cancer has not been identified. To review risk factors for the development of colorectal cancer, click here.

# Differential Diagnosis
Colorectal cancer may be differentiated from other diseases that cause unexplained weight loss, unexplained loss of appetite, nausea, vomiting, diarrhea, anemia, jaundice, and fatigue, such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), hemorrhoids, anal fissures, and diverticular disease. There are less common conditions that may be confused as colorectal cancer such as infectious colitis and gastrointestinal lymphoma.

# Epidemiology and Demographics
Colorectal cancer is the third most commonly diagnosed cancer in the world, and accounts for 8% of all cancer-related deaths annually. In the United States, the prevalence of colorectal cancer is 376.3 per 100,000 persons, and the incidence is 42.9 per 100,000 persons. The incidence of colorectal cancer is higher in males, the elderly, and in the African American race.

# Risk Factors
There are both genetic and environmental factors that can increase the risk of colorectal carcinoma (CRC). Some of the genetic risk factors are familial adenomatous polyposis and hereditary non-polyposis colorectal cancer. Some environmental risk factors are personal/family history, history of inflammatory bowel disease, diet, alcohol, cigarette smoking, race, and gender.

# Screening
Early detection of premalignant colorectal masses or early-stage colorectal cancers is essential in treating these patients and possibly preventing cancer or colorectal cancer related death. According to the USPSTF (United States Preventive Services Task Force): Screening for colorectal cancer is recommended among adults older than 50 years of age and do not have an increased risk of developing the disease (average-risk adults).

# Natural History, Complications, and Prognosis
The progression from an adenomatous polyp to colorectal cancer may take 10-15 years. Complications may arise if the cancer is not eradicated or from the treatment itself. Complications include intestinal obstruction, gastrointestinal bleeding, metastasis, cancer recurrence, radiation therapy adverse effects, chemotherapy adverse effects, post-surgical complications, metachronous colon cancer, and death. The 5 years survival rate depends on the stage of colorectal cancer.

# Staging
Colorectal cancer staging is an estimate of the amount of penetration of the cancer. It is performed for diagnostic and research purposes and to determine the optimal method of treatment. Staging is based on the TNM classification system which depends on the extent of local invasion, the degree of lymph node involvement, and whether there is distant metastasis. The staging systems are called Duke's classification, TNM classification, and AJCC stage grouping.

# History and Symptoms
The history of a patient with colorectal cancer may include a family history of polyps/colorectal cancer or a history of inflammatory bowel disease. Some symptoms that are associated with colorectal cancer are change in bowel habits, hematochezia, and rectal pain. Metastatic symptoms include dyspnea, abdominal pain, fractures, and confusion.

# Physical Examination
Generally, the most common signs of colorectal cancer are emaciation, lethargy, and pallor. Other signs include low-grade fever, discomfort on palpation, ascites, rectal bleeding, rectal mass, and jaundice.

# Diagnostic Studies

## Laboratory Findings
The laboratory findings associated with colorectal carcinoma are the following: CBC, FOBT, serum CEA and CA 19-9 concentration, serum iron concentrations, serum vitamin B12 and folate concentrations, liver function tests, and pulmonary function tests.

## X-Ray
Chest radiography (CXR) is the initial imaging modality used in the detection of suspected pulmonary metastasis. It normally appears as peripheral, rounded nodules of variable size, scattered throughout both lungs. Atypical features include consolidation, cavitation, calcification, hemorrhage, and secondary pneumothorax.

## CT
CT scan is used to determine the extent of involvement of colon cancer, most commonly in the abdomen and lungs.

## MRI
MRI in colon cancer is used to determine the extent of the spread of the tumor to the liver, lung, brain and lymph nodes. MRI is also used for staging the cancer.

## Ultrasound
Abdominal ultrasound can be used to look for tumors in the liver, gallbladder, pancreas, or elsewhere in the abdomen, but it is insufficient in identifying colorectal cancer. The two special types of ultrasound exams that can be performed to evaluate colon and rectal cancers are endorectal ultrasound and intraoperative ultrasound.

## Other Imaging Findings
Other imaging tests that can be used for colorectal cancer are endoscopy, PET scan, barium study, and angiography.

## Other Diagnostic Studies
A biopsy and genetic testing can be performed when a suspected lesion is found on colonoscopy.

# Medical Therapy
Chemotherapy is used to reduce the likelihood of metastasis developing, shrink tumor size, and slow tumor growth. Chemotherapy is often applied after surgery (adjuvant), before surgery (neo-adjuvant), or as primary therapy if surgery is not indicated (palliative). Other therapies include radiation and support therapies.

# Surgery
Surgery remains the primary treatment while chemotherapy and/or radiotherapy may be recommended depending on the individual patient's staging and other medical factors.

# Metastases Treatment
When colorectal cancer metastasizes, a different approach is utilized as opposed to a localized tumor. The most common site of metastasis is the liver, and the second most common is the lung.

# Primary Prevention
Most colorectal cancers could be preventable through screening, maintaining an improved and healthy lifestyle.

# Secondary Prevention
Secondary prevention of colorectal cancer, as opposed to primary prevention, indicates that a person has already had the disease and there are steps being taken to prevent cancer recurrence, usually as metachronous tumors. This involves annual surveillance with colonoscopy after surgical removal and possibly an adjunct after the initial operation. The timing for secondary prevention is critical to prevent recurrent advanced disease.