Colorectal Cancer

Colorectal Cancer

Colorectal Cancer

What is Colorectal Cancer?

The colon and rectum are the vital parts of the gastrointestinal (digestive) system. Colon is a muscular coiled tube stretching for the first 4 to 5 feet of the large intestine and rectum is about 12 cm long tube that constitutes the last part of the large intestine. The colon connects the small intestine and the rectum whilst the rectum connects the colon to the anus. The colon and rectum are highly specialized organs responsible for processing waste out of the body in a convenient way.

Functions

  • The main function of the colon is to absorb the remaining fluids and process waste products before preparing for its elimination.
  • Billions of bacteria that coat the colon break down the remaining material. Then the colon pushes the leftover material into the rectum.
  • Stool moves from the colon into the rectum, where it is stored temporarily before being expelled from the body.

What is colorectal cancer?

Colorectal cancer

Colorectal cancer, also known as bowel cancer occurs when cells lining the colon or rectum turn abnormal and continue to grow uncontrollably. If cancer originates in the colon then it is specified as colon cancer else if the site of origin is detected to be the rectum then it is rectal cancer. Due to the similarities in the features of both colon and rectal cancer, they are together cited as colorectal cancer.

The cancer cells can eventually grow and invade the nearby healthy tissues, in a process called metastasis. This results in a more serious, less treatable condition.

Types of Colorectal Cancer

  • Adenocarcinomas: Adenocarcinomas occurs in the cells that generate mucus to lubricate the interiors of the colon and rectum. Most colorectal cancers (92-95 %) are adenocarcinomas.
  • Lymphoma: It is cancer of immune system cells that typically start in lymph nodes, but they can also start in the colon, rectum, or other organs. It accounts for 1.3% of colorectal cancer.
  • Carcinoid: It starts from specialized hormone-making cells in the intestine and accounts for 0.4% colorectal cancer.
  • Sarcoma: It can start in blood vessels, muscle layers, or other connective tissues in the wall of the colon and rectum. Sarcomas of the colon or rectum are rare and account for 0.3% colorectal cancer.

Occurrence Rate

According to WHO and CDC, colorectal cancer is the second most common cancer. Approximately 40% of people diagnosed with colorectal cancer are at an advanced stage thus making it the third most common cause of cancer-related death.

However, it might bring a sigh of relief to know that colorectal cancer has the lowest incidence in India compared to the western world and other countries. Among all digestive cancers, colorectal cancer carries the best prognosis largely due to the multidisciplinary treatment options that have dramatically improved over the last decade. Low and stable incidence and mortality rates from colorectal cancers were observed in India in both men and women.

Anatomy of Colorectal Cancer

Colorectal

What are the general symptoms of Colorectal Cancer?

Generally, colorectal cancer does not cause any notable symptom in the early stages, but symptoms may develop as the cancer advances. Gastrointestinal problems are the most common symptoms. Also, the signs and symptoms of colorectal cancer depend on the location of the tumor in the bowel and the spread of the tumor. Some common complaints that might act as a symptom are:

  • Diarrhea or constipation
  • Frequent urination
  • Rectal bleeding or blood in the stool
  • Abdominal pain, cramps, bloating, or gas
  • Pain during bowel movements
  • Continual urges to defecate
  • Weakness and fatigue
  • A feeling of fullness in the abdomen
  • Unaccountable weight loss, vomiting, fatigue
  • Irritable bowel syndrome (IBS)
  • Iron deficiency, anaemia

However, the root cause of these symptoms is not always colorectal cancer. They may indicate some other illness or conditions. Hence, it is very important to consult the doctor for a proper diagnosis before jumping to conclusions. Experiencing any of these symptoms for four weeks calls for a visit to the doctor.

What are the general causes of Colorectal Cancer?

Normally, cells follow a systematic pattern of growth, division, and death. Cancer happens when this process is interrupted and the cells continue to grow and divide uncontrollably, without dying.

Till date, the exact cause of colorectal cancer resulting in a particular case could not be traced. However, there are several potential risk factors that have been identified. The major risk factors for colorectal cancer are family history, lifestyle and age of the person. Some other associated risk factors are discussed below:

  • Polyps: Colorectal cancer usually develops from precancerous polyps that exist in the large intestine. Adenomas are the most common polyps that lead to malignant cancer. Adenomas usually resemble the normal lining of the colon but may look different under a microscope. These polyps may turn to become cancerous over time, if they are not removed during the early stages of treatment.
  • Inflammatory bowel disease: Inflammatory bowel disease is another risk factor for colorectal cancer which includes Crohn's disease and ulcerative colitis. The risk increases with the increased tenure of the disease. People with inflammatory bowel disease account for less than 2% of colon cancer cases yearly.
  • Family History: Inherited genes increase colorectal cancer risks. The two most common inherited syndromes linked with colorectal cancers are Familial Adenomatous Polyposis (FAP) and Hereditary Non-Polyposis Colorectal Cancer (HNPCC). Other syndromes that may increase the risk of developing colorectal cancer include Lynch Syndrome, Turcot Syndrome and Peutz-Jeghers Syndrome. However, these represent less than 5% of cases.
  • Age and Lifestyle: Around 91% of cases of colorectal cancer consists of patients in the age group of over 50 years old. The risk is found to be increased in people following a sedentary lifestyle like those with obesity, less physical activity and those who smoke tobacco.
  • Dietary factors: Diets that are high in red and processed meats (e.g., beef, lamb, hot dogs) may increase colorectal cancer risks. Frying, grilling, broiling or other methods of cooking meats at very high temperatures create chemicals that may also contribute to an increased risk. Diets very high in animal protein, saturated fats, calories or alcohol possess a greater threat of colorectal cancer.
  • Smoking: Some cancer-causing substances associated with smoking may be swallowed, potentially increasing the risk of developing colorectal cancer. Studies revealed that smoking is significantly associated with an increased risk for colorectal cancer and death.
  • Certain other conditions: Some conditions and treatments have been associated with an increased risk of colorectal cancer. These include:
    • Diabetes
    • Obesity
    • Type II diabetes
    • Acromegaly, a growth hormone disorder
    • Exposure to ionizing radiation or asbestos
Can Colorectal Cancer be prevented?

Since colorectal cancer is associated with risk factors related to the lifestyle so altering to a healthy lifestyle offers some prevention against the same. Certain precautions to stay away from colorectal cancer are:

  • Maintaining a healthy diet: Including a variety of fruits, vegetables and whole grains may play a subtle role in cancer prevention. As the colon is part of the digestive system, so diet plays an important role in the prevention of colorectal cancer. Diets that are low in fiber and high in fat, calories, red meat, alcohol, and processed meats have been linked to a higher risk of colorectal cancer
  • Avoiding alcohol and Quitting Smoke: Alcohol should be consumed in moderation as consumption in excess amounts may lead to many complications including colorectal cancer. Smoking is associated with numerous cancers, so it is highly recommended to quit smoking and avoid the use of tobacco.
  • Maintaining a healthy weight: Following a healthy diet and maintaining a 30-minute workout regime every day has been shown to have a significant impact on lowering a person's risk of developing colorectal cancer.
  • Regular Screenings: If one is at a higher risk of developing colorectal cancer, then it is highly recommended to go for regular screenings at least once a year.
What are the stages of Colorectal Cancer?

Cancer staging is very important as the prognosis and outlook of the treatment largely depend on the stage of cancer. A common method used to describe the cancer stage is the TNM system.

  • Tumor (T): It describes the growth of the tumor. It is categorized as:
    • TX: The primary tumor cannot be evaluated.
    • T0: There is no evidence of cancer in the colon or rectum.
    • Tis: Refers to carcinoma in situ.
    • T1: The tumor has grown into the submucosa.
    • T2: The tumor has grown into the muscularis propria, a thick layer of muscle.
    • T3: The tumor has grown into the subserosa, a thin layer of connective tissue or it has grown into tissues surrounding the colon or rectum.
    • T4a: The tumor has grown into the surface of the visceral peritoneum, which means it has grown through all layers of the colon.
    • T4b: The tumor has grown into or has attached to other organs or structures.
  • Node (N): Node is used to define the spread of the tumor.
    • NX: The regional lymph nodes cannot be evaluated.
    • N0: There is no spread to regional lymph nodes.
    • N1a: There are tumor cells found in 1 regional lymph node.
    • N1b: There are tumor cells found in 2 to 3 regional lymph nodes.
    • N1c: There are nodules made up of tumor cells found in the structures near the colon that do not appear to be lymph nodes.
    • N2a: There are tumor cells found in 4 to 6 regional lymph nodes.
    • N2b: There are tumor cells found in 7 or more regional lymph nodes.
  • Metastasis(M): It tells us if cancer has spread to other organs of the body.
    • MX: Distant metastasis cannot be evaluated.
    • M0: The disease has not spread to a distant part of the body.
    • M1a: The cancer has spread to 1 other part of the body beyond the colon or rectum.
    • M1b: The cancer has spread to more than 1 part of the body other than the colon or rectum.

Based on the analysis of several factors colorectal cancer is staged in categories from 0 till 4. Needless to say, the severity of the disease increases with each passing stage.

  • Stage 0 (Carcinoma in Situ): This is a very early stage of the cancer. In this stage, abnormal cells are found in the mucosa (innermost layer) of the colon or rectum. These abnormal cells may later become cancerous and spread to other parts.
    Colorectal stage0
  • Stage I: (T1 or T2, N0, M0) In this stage, cancer that had formed in the mucosa of the colon wall has now invaded the submucosa, the muscular layer of the colon or the rectum, but has not yet spread beyond the wall of the rectum or colon.
    Colorectal stage1
  • Stage II: At this stage, cancer has spread through the muscle layer of the colon wall to the serosa which is the outermost layer. However, it has not reached the nearby lymph nodes yet. This stage is further divided into stage IIA, stage IIB, and stage IIC.
    • Stage IIA (T3, N0, M0): Cancer has spread to the serosa or visceral peritoneum of the colon wall.
    • Stage IIB(T4a, N0, M0): Cancer has spread to the serosa or visceral peritoneum of the colon wall but has not spread to nearby lymph nodes or organs.
    • Stage IIC(T4b, N0, M0): Cancer has spread through the serosa of the colon wall to nearby organs.
      Colorectal stage2
  • Stage III: Cancer at this stage has spread from the mucosa to the submucosa and may have spread to the muscle layer, and has spread to one to three nearby lymph nodes or tissues near the lymph nodes.
    • Stage IIIA(T1 or T2, N1 or N1c, M0; or T1, N2a, M0): Cancer has spread through the mucosa of the colon wall to the submucosa. Anyone of the following conditions might hold true:
      • It may have spread to the muscle layer of the colon wall.
      • It has spread to at least one but not more than 3 nearby lymph nodes
      • Cancer cells have formed in tissues near the lymph nodes
      • Cancer has spread to at least 4 but not more than 6 nearby lymph nodes.
    • Stage IIIB(T3 or T4a, N1 or N1c, M0; T2 or T3, N2a, M0; or T1 or T2, N2b, M0): For stage IIIB cancer any of the following conditions might hold true:
      • Cancer has spread to the serosa but not to nearby organs.
      • Cancer has spread to one to three nearby lymph nodes or tissues near the lymph nodes.
      • Cancer has spread to the muscle layer or to the serosa, and to four to six nearby lymph nodes.
      • Cancer has spread through the mucosa to the submucosa and may have spread to the muscle layer.
      • Cancer has spread to seven or more nearby lymph nodes.
    • Stage IIIC(T4a, N2a, M0; T3 or T4a, N2b, M0; or T4b, N1 or N2, M0):
      • Cancer has spread through the serosa of the colon wall but has not spread to nearby organs. Cancer has spread to at least 4 but not more than 6 nearby lymph nodes.
      • Cancer has spread through the muscle layer of the colon wall to the serosa of the colon wall or has spread through the serosa but has not spread to nearby organs. Cancer has spread to 7 or more nearby lymph nodes.
      • Cancer has spread through the serosa of the colon wall and has spread to nearby organs. Cancer has spread to one or more nearby lymph nodes or cancer cells have formed in tissues near the lymph nodes.

      Colorectal stage3A
      Colorectal stage3B
      Colorectal stage3C
  • Stage IV: At this stage, cancer has spread through the blood and lymph nodes to other parts of the body, such as the lung, liver, abdominal wall, or ovary. It is further subdivided into stage IVA and stage IVB.
      • Stage IVA(any T, any N, M1a): Cancer has spread to one organ that is not near the colon, such as the liver, lung, or ovary, or to a distant lymph node.
      • Stage IVB(any T, any N, M1b): Cancer has spread to more than one organ that is not near the colon or into the lining of the abdominal wall.

    Colorectal stage4
Survival rates of Colorectal Cancer?

Statistics on the outlook for a certain type and stage of cancer are often given as 5-year survival rates, but many people live longer and often surpass the 5 years time bond. The 5-year survival rate is the percentage of people who live at least 5 years after being diagnosed with cancer.

Stage 5 year survival rate
Stage I 92%
Stage IIA 87%
Stage IIB 63%
Stage IIIA 89%
Stage IIIB 69%
Stage IIIC 53%
Stage IV 11%
Can Colorectal Cancer be detected early?

Over the past few decades, the worldwide statistical report of colorectal cancer claims that there is a steady decline in the death rate caused by the disease. The main reason for this success in controlling death by colorectal cancer is improvements in colorectal cancer screening.

Screening is the process of looking for cancer or pre-cancer in people who have no symptoms of the disease. This process helps in detecting colorectal cancer early, even before symptoms develop. Screening can also sometimes find growths called polyps so they can be removed before they turn into cancer. Several screening tests have been developed to help find colorectal cancer early. Some tests that detect adenomas and polyps help diagnose the development of cancer earlier making way for effective action. Some of the tests to detect colon cancer are described below:

  • Physical examination and history : A physical examination of the body is conducted to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. The doctor also inquires about the history of the patient’s health habits and past illnesses along with family history of any major disease.
  • Flexible sigmoidoscopy: A sigmoidoscope i.e. a flexible, slender and lighted tube, is used to examine part of the rectum and sigmoid (the last part of the colon). If a polyps or colon cancer is detected then a colonoscopy is advised.
  • Colonoscopy: During colonoscopy, a tube like instrument called Colonoscope is used to look inside the rectum and colon. A colonoscopy helps find ulcers, colon polyps, tumors, and areas of inflammation or bleeding.
  • Digital rectal examination (DRE): The average finger can reach approximately 8 cm above the dentate line; rectal tumors can be assessed for size, ulceration, and presence of any pararectal lymph nodes.
  • Rigid proctoscopy: This examination helps to identify the exact location of the tumor in relation to the sphincter mechanism
  • Chest x-ray: An x-ray uses radiations to get a clear picture of the structures inside of the body. An x-ray of the chest can help doctors find out if the cancer has spread to the lungs.
  • High-sensitivity fecal occult blood tests (FOBT): Bleeding is a common phenomenon experienced in both polyps and colorectal cancers. FOBT checks for tiny amounts of blood in feces (stool) that cannot be seen visually. However, these tests are not 100% accurate, as it fails to detect cancers that do not bleed. Furthermore, a positive result of the test also does not ascertain the presence of cancer cells as bleeding may be attributed to some other illness or conditions as well.
    FOBT may be done by:
    • Guaiac FOBT: It uses a chemical to detect heme, a component of the blood protein hemoglobin. For this test certain dietary restrictions are adviced.
    • FIT: It uses antibodies to detect human hemoglobin protein specifically (4, 5).
  • Biopsy: Biopsy is the procedure of removal of a small amount of suspected tissue for examination under a microscope. A biopsy can make a definite diagnosis of colorectal cancer.
  • Molecular testing of the tumor: Molecular testing is also called biomarker testing or genetic testing. As the root of cancer is an abnormal change in the genes, molecular testing helps in checking structural changes within the gene, abnormal features of gene products, or biochemical effects of the tumor.
    Gene tests assess either one gene or a short piece of DNA. These tests look for extra gene copies, missing genes, or incorrectly placed genes. Also, gene tests can assess for small changes, such as an altered chemical "step" within the DNA "ladder," called gene mutations.
    In case of metastatic or recurrent colorectal cancer, a sample of tissue from the cancerous area is extracted to identify specific genes, proteins, and other factors unique to the tumor. Results of these tests help in deciding the most suitable treatment option.
  • Computed tomography (CT) scan: In a CT scan, multiple pictures of the interior of the body is taken through X-Rays from different angles and a 3-dimensional picture is created. A computer combines these images into a detailed, cross-sectional view that shows any abnormalities or tumors. A CT scan is helpful in knowing details like tumor’s size, location etc. Sometimes a special dye called a contrast medium is injected or swallowed before the scan to provide better detail on the image.
  • Magnetic resonance imaging (MRI): An MRI uses magnetic fields, to produce detailed images of the body. MRI can be used to measure the tumor’s size. A special dye called a contrast medium is given before the scan to create a clearer picture. MRI is the best imaging test to find where the colorectal cancer has grown.
  • Ultrasound: An ultrasound uses sound waves to create a picture of the internal organs to find out if cancer has spread.
  • Positron emission tomography scan: A PET scan is a way to create pictures of internal organs and tissues. A small amount of a radioactive sugar substance is injected into the patient’s body. This sugar substance is taken up by cells that use the most energy. Because cancer tends to use energy actively, it absorbs more of the radioactive substance. A scanner then detects this substance to produce images of the inside of the body.
  • Double-contrast barium enema(DCBE): It is another method of visualizing the colon from outside the body. In DCBE, a series of x-ray images of the entire colon and rectum is taken after the patient is given an enema with a barium solution. The barium helps to outline the colon and the rectum on the images. DCBE is rarely used for screening because it is less sensitive than colonoscopy in detecting small polyps and cancers. However, it may be used for people who cannot undergo standard colonoscopy—for example, because they are at particular risk for complications.
  • Blood tests: Because colorectal cancer often bleeds into the large intestine or rectum, people with the disease may become anemic. A test of the number of red cells in the blood, which is part of a complete blood count (CBC), can indicate that bleeding may be occurring. Another blood test detects the levels of a protein called carcinoembryonic antigen (CEA). High levels of CEA may indicate that cancer has spread to other parts of the body.
What are the Treatments available?

Due to the advancement in technology, today colon cancer is highly treatable and the mortality rate is steadily declining. Even when it spreads to nearby lymph nodes, surgical treatment followed by chemotherapy is highly effective. Constant research is going on to learn more and provide hope for people no matter what stage they are.

The different treatment options available to beat colorectal cancer include a combination of the any of the following:

  • Surgery: Surgery is the most common treatment for all stages of colorectal cancer. Any of the following surgery may be conducted depending on the stage of the cancer and the patient’s health:
    • Local excision: If the cancer is detected at a very early stage, then there is a possibility to remove it without cutting through the abdominal wall. Instead, a tube with a cutting tool is inserted through the rectum into the colon and the cancer cells are cut out.
    • Resection of the colon with anastomosis: If the cancer is larger, a partial colectomy may be performed, wherein the cancer and a small amount of healthy tissue around it are removed. It might be followed up by an anastomosis i.e. sewing the healthy parts of the colon together.
    • Resection of the colon with colostomy: Sometimes a stoma (opening) needs to be made on the outside of the body for waste to pass through. This procedure is called a colostomy. A bag is placed around the stoma to collect the waste.
    • Endoscopic mucosal resection: Removing larger polyps may require also taking a small amount of the lining of the colon in a procedure called endoscopic mucosal resection.
  • Radiofrequency ablation: In this process, a special probe with tiny electrodes is used to kill cancer cells.
  • Cryosurgery: In this process an instrument is used to freeze and destroy abnormal tissue. This type of treatment is also called cryotherapy
  • Chemotherapy: Chemotherapy is the use of drugs to inhibit the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemotherapy may be done either orally mouth or injected into a vein or muscle. The way the chemotherapy is given depends on the type and stage of the cancer being treated.
  • Radiation therapy: Radiation therapy is a cancer treatment that uses high-energy x-rays to kill cancer cells or keep them from growing. There are two types of radiation therapy:
    • External radiation: As the name suggests, radiation when given externally through a machine then it is said to be external radiation.
    • Internal radiation: In this therapy, a radioactive substance sealed in needles, seeds, wires, or catheters is placed directly into or near the cancer.

      The way the radiation therapy is given depends on the type and stage of the cancer being treated. External radiation therapy is used as palliative therapy to relieve symptoms and improve quality of life. However, radiation therapy has multiple side effects so various conditions need to be checked before applying radiation therapy.
  • Targeted therapy: In targeted therapy, drugs or other substances are used to identify and attack specific cancer cells without harming normal cells. Different types of targeted therapies used in the treatment of colorectal cancer include the following:
    • Monoclonal antibodies: Monoclonal antibodies are made from a single type of immune system cell. The antibodies attach and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion.
      • Bevacizumab and ramucirumab are monoclonal antibodies that bind to a protein called vascular endothelial growth factor (VEGF). This may prevent the growth of new blood vessels that aid the growth of tumors.
      • Cetuximab and panitumumab are types of monoclonal antibodies that bind to a protein called epidermal growth factor receptor (EGFR) on the surface of some types of cancer cells. This may stop cancer cells from growing and dividing.
      • Angiogenesis inhibitors: Angiogenesis inhibitors stop the growth of new blood vessels that aids tumor growth.
      • Ziv-aflibercept is a vascular endothelial growth factor trap that blocks an enzyme needed for the growth of new blood vessels in tumors.
    • Regorafenib is used to treat colorectal cancer that has spread to other parts of the body and has not gotten better with other treatment. It blocks the action of certain proteins, including vascular endothelial growth factor. This may help keep cancer cells from growing and may kill them. It may also prevent the growth of new blood vessels that tumors need to grow.
  • Supportive (palliative) care: Palliative care is specialized medical care that focuses on providing relief from pain and other symptoms of a serious illness.

Treating Metastatic or Stage IV cancers

Treatment of Metastatic cancer becomes very difficult as it has spread to distant organs of the body. When the cancer has spread to the other organs, the treatment depends on the location of metastasis. Colorectal cancer can spread to distant organs, such as the liver, lungs, the tissue called the peritoneum that lines the abdomen, or a woman’s ovaries.

Treatment plan for metastatic cancers may include a combination of surgery, radiation therapy, immunotherapy, and chemotherapy. Such treatment is often helpful in delaying the spread of the disease or shrinking the cancerous tumor. Palliative care will also be important to help relieve symptoms and side effects.

At this stage, surgery to remove the colon or portion of colon does not cure the cancer. However, it relieves the blockage of the colon and soothes the problems related to the cancer. Surgery may also be used to remove parts of other organs where the cancer has spread.

In case cancer has spread to liver the following procedures are usually used:

  • Surgery to remove the tumor (if possible).
  • Chemotherapy may be given before or after surgery, to shrink the tumor.
  • Cryosurgery or radiofrequency ablation.
  • Chemoembolization and/or systemic chemotherapy.
  • A clinical trial of chemoembolization combined with radiation therapy.

In the final stage of cancer, curing the cancer is often not possible. However, surgery may help in adding years to life and improving quality of life.

How frequently should one visit doctor for early diagnosis?

If one is at a higher risk to develop the disease, then it is recommended to go for regular screening at least once a year to facilitate early diagnosis. For those without any potential risk, it is advised to go for screening if they experience any of the symptom mentioned above.

How can I as a patient know it early?

Complete awareness about the disease and knowing one’s familial history related to any disease helps a person to detect the disease earlier.

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