Colon Cancer – Risk factors, Complications, and Diagnosis.

Introduction

Colon cancer is also called as colorectal cancer. Colorectal cancer is caused by the abnormal growth of epithelial cells which form the lining of the colon or rectum. These small growths (known as polyps) are often benign, although some have the potential to develop and become cancerous. It is estimated that up to two thirds of colorectal polyps are pre-malignant and associated with a risk of colorectal cancer.

 

Normal colon and cancer colon

Structure of colon

The colon is also called the large intestine. The ileum (last part of the small intestine) connects to the cecum (first part of the colon) in the lower right abdomen. The rest of the colon is divided into four parts:

• The ascending colon travels up the right side of the abdomen.
• The transverse colon runs across the abdomen.
• The descending colon travels down the left abdomen.
• The sigmoid colon is a short curving of the colon, just before the rectum.

 

The colon removes water, salt, and some nutrients forming stool. Muscles line the colon’s walls, squeezing its contents along. Billions of bacteria coat the colon and its contents, living in a healthy balance with the body.

Staging

Staging determines how advanced the cancer is and whether it has spread to other parts of the body. It helps to identify the most appropriate treatment options for the patient. Staging in colorectal cancer can be confirmed by:

• Blood tests to look for tumour markers
• Biopsies, analysing tissue samples taken during a colonoscopy or sigmoidoscopy
• Imaging tests (CT scans, chest x-rays, ultrasound, MRI scans)
• Surgery

The most common staging for colorectal cancer is defined by the tumour, node, and metastasis (TNM) staging system, which classes a patient into stages I-IV according to the level of invasion or spread of the tumour to other organs (metastasis).

Stages of colorectal cancer

Using the TNM staging, the progression of the original primary tumour is denoted by the letter T (tumour); N (node) indicates whether the tumour has spread to lymph nodes; M (metastasis) represents whether the tumour has metastasised to distant organs in the body, most commonly the liver or lungs. T, N and M are followed by numbers giving further information on the stage of the disease: increasing numbers signify later stages.

Stage	Classification
Stage 1	The tumour is localised to the lining of the colon. T1-T2, N0, M0
Stage 2	The tumour grows into the outer lining of the colon or surrounding tissue. T3-T4, N0, M0
Stage 3	The cancer has metastasised to the lymph nodes. Any T, N1-N2, M0
Stage 4	The cancer has metastasised to distant organs in the body. Any T, Any N, M1

Epidemiological view of colon cancer

Colorectal cancer (CRC) is a formidable health problem worldwide. It is the third most common cancer in men (663000 cases, 10.0% of all cancer cases) and the second most common in women (571000 cases, 9.4% of all cancer cases). Almost 60% of cases are encountered in developed countries. The number of CRC-related deaths is estimated to be approximately 608000 worldwide, accounting for 8% of all cancer deaths and making CRC the fourth most common cause of death due to cancer.

In India, the annual incidence rates (AARs) for colon cancer and rectal cancer in men are 4.4 and 4.1 per 100000, respectively. The AAR for colon cancer in women is 3.9 per 100000. Colon cancer ranks 8th and rectal cancer ranks 9th among men. For women, rectal cancer does not figure in the top 10 cancers, whereas colon cancer ranks 9^th. In the 2013 report, the highest AAR in men for CRCs was recorded in Thiruvananthapuram (4.1) followed by Banglore (3.9) and Mumbai (3.7). The highest AAR in women for CRCs was recorded in Nagaland (5.2) followed by Aizwal.

Causes and Risk factors

• Family history: A person’s risk doubles if a direct relative has previously had the disease. There is an even greater risk if more than one relative has had colorectal cancer.
• Genetics: Individuals with inherited disorders such as familial adenomatous polyposis (FAP), where an individual is prone to polyp formation, have a higher risk of developing colorectal cancer.
• Colorectal polyps or inflammatory bowel diseases: A history of polyps or inflammatory bowel disease, where the bowel is inflamed for many years, increases the risk of colorectal cancer.
• Age: Although a person can develop colorectal cancer at any age, the risk increases greatly with age. Over 90% of colorectal cases are diagnosed in patients over the age of 50.
• Lifestyle: A sedentary lifestyle is associated with a higher risk of colorectal cancer. Studies have also linked obesity, lack of exercise, smoking and excessive alcohol consumption to a greater risk of colorectal cancer.
• Potential protective agents: Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, have been associated with a reduced risk of colorectal cancer. A healthy, fibre containing diet and hormone replacement therapy in women are also possible protective factors.

Symptoms and signs

Colorectal cancer might not cause symptoms right away, but if it does, it may cause one or more of these symptoms:

• A change in bowel habits, such as diarrhea, constipation, or narrowing of the stool, that lasts for more than a few days
• A feeling that you need to have a bowel movement that is not relieved by having one
• Rectal bleeding with bright red blood
• Blood in the stool, which may make the stool look dark
• Cramping or abdominal (belly) pain
• Weakness and fatigue
• Unintended weight loss
• Colorectal cancers can often bleed into the digestive tract.
• Sometimes the blood can be seen in the stool or make it look darker, but often the stool looks normal.
• But over time, the blood loss can build up and can lead to low red blood cell counts (anemia).

Screening and diagnosis

In addition to a physical examination, the following tests may be used to diagnose colorectal cancer.

• As described in Screening, a colonoscopy allows the doctor to look inside the entire rectum and colon while a patient is sedated. If colorectal cancer is found, a complete diagnosis that accurately describes the location and spread of the cancer may not be possible until the tumor is surgically removed.
• A biopsy is the removal of a small amount of tissue for examination under a microscope. Other tests can suggest that cancer is present, but only a biopsy can make a definite diagnosis of colorectal cancer. A biopsy may be performed during a colonoscopy, or it may be done on any tissue that is removed during surgery. Sometimes, a CT scan or ultrasound is used to help perform a needle biopsy.
• Molecular testing of the tumor. Your doctor may recommend running laboratory tests on a tumor sample to identify specific genes, proteins, and other factors unique to the tumor. If you have metastatic or recurrent colorectal cancer, a sample of tissue from the area where it spread or recurred is preferred for testing, if available. Results of these tests will help decide whether your treatment options include a type of treatment called targeted therapy.
• 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 a cancer has spread to other parts of the body. A CEA test is most often used to monitor colorectal cancer for patients who are already receiving treatment. It is not useful as a screening test.
• Computed tomography (CT or CAT) scan. A CT scan can be used to measure the tumor’s size. Sometimes a special dye called a contrast medium is given before the scan to provide better detail on the image. This dye can be injected into a patient’s vein or given as a pill to swallow. In a person with colorectal cancer, a CT scan can check for the spread of cancer in the lungs, liver, and other organs. It is often done before surgery.
• MRI can also 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. This dye can be injected into a patient’s vein or given as a pill to swallow. MRI is the best imaging test to find where the colorectal cancer has grown.
• Endorectal ultrasound. is commonly used to find out how deeply rectal cancer has grown and can be used to help plan treatment. However, this test cannot accurately detect cancer that has spread to nearby lymph nodes or beyond the pelvis.
• Chest x-ray. An x-ray of the chest can help doctors find out if the cancer has spread to the lungs.

Treatment of colon cancer

Treatment options for patients vary and are assessed taking into account the following variables:

• Tumour size
• Stage of diagnosis
• The location of the tumour in the colon or rectum
• The risk of the cancer returning
• The physical health of the patient

In general the current treatment options for colorectal cancer are surgery, chemotherapy, and biological therapies. Radiotherapy is not often used to treat metastatic colorectal cancer due to side effects, although it can be used after surgery to destroy any residual cancer cells.

Surgery

• The majority of patients with early-stage colorectal cancer will undergo surgery to remove as much of the tumour as possible in a procedure known as ‘resection’.
• Resection is also a treatment option for some patients with later stage disease, particularly when the cancer has metastasised to the liver.
• A less invasive procedure known as laparoscopic resection, where the affected area of the colon is removed through keyhole surgery, can also be performed on patients with early-stage colorectal cancer.

Chemotherapy

• Patients diagnosed with advanced disease are usually treated with chemotherapy after surgery, known as ‘first-line’ treatment.
• This involves a combination of a fluoropyrimidine and most often fluorouracil (5-FU) with leucovorin (folinic acid or LV) and oxaliplatin, known as FOLFOX19 or with irinotecan, known as FOLFIRI.
• Some patients with advanced colorectal cancer who are not initially able to undergo surgery due to invasive tumours can be treated with chemotherapy before being considered for surgery (called neoadjuvant treatment).
• Many people with colorectal cancer initially respond to chemotherapy, but unfortunately, in the majority of cases the disease eventually progresses after first-line treatment.
• When this occurs the patient may undergo another round of chemotherapy, known as ‘second-line’ treatment.

Biological therapies

Several types of biological therapy are available to treat metastatic colorectal cancer including anti-angiogenics and the Epidermal Growth Factor Receptor (EGFR) inhibitors. Biological therapies are typically given in combination with chemotherapy

Prognosis of colon cancer

Cancer statistics often use an ‘overall 5-year survival rate’ to give a better idea of the longer term outlook for people with a particular cancer. The overall 5-year survival rate for colorectal cancer patients is 65%, although this differs greatly depending on how advanced the cancer is.

The 5-year survival rate for a patient diagnosed with stage I or II colorectal cancer, where the tumour is localised to the colon, is up to 90%. Approximately two fifths of patients are diagnosed at this stage. However the 5-year survival rate for patients diagnosed with stage IV disease, once the cancer has metastasised to other organs, is only 12%.