Colon Cancer

The type of colon cancer depends on the cells in which the cancer arises. The most common variety of colon cancer is adenocarcinoma, cancer arising in the adenomatous gland cells that produce mucus and lubricate the mucosal lining of the inner colon wall. Adenocarcinoma also has sub-types. Signet cell and mucinous subtypes of adenocarcinoma have a particularly poor prognosis.

Other, less common, types of colon cancers include:

• Carcinoid colon tumours
• Gastrointestinal stromatolites tumours (GISTs)
• Sarcomas
• Lymphomas

In the early stages of colon cancer, there may be no noticeable symptoms and signs; however, some vague non-specific clinical features may be present. These features include, but may not be limited to:

• Constipation
• Diarrhea
• Changes in stool colour
• Changes in stool shape, such as narrowed stool
• Blood in the stool
• Bleeding from the rectum
• Excessive gas
• Abdominal cramps
• Abdominal pain

The appearance of any of these signs and symptoms should warrant a consultation with a doctor to rule out possible colon cancer and diagnose the underlying cause.

In advanced stages of colon cancer (stage 3 and stage 4), more clinical signs and symptoms can appear. These can include, but may not be limited to:

• Excessive fatigue
• Unexplained weakness
• Unintentional and significant weight loss (5-10% of the person’s starting weight)
• Changes in your stool that last longer than a month
• Tenesmus, a feeling that your bowels don’t empty completely during a bowel movement
• Vomiting
  
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Some signs and symptoms of metastasis (cancer spread to distant body parts through blood) can also appear in advanced stages of colon cancer. These signs and symptoms may include:

• Jaundice, or yellow eyes and skin, can appear due to metastatic cancer deposits in the liver, which under normal conditions metabolises bilirubin (excess of which produces the yellow colour)
• Swelling in the hands or feet
• Breathing difficulties can arise with metastatic deposits in the lungs
• Chronic headaches due to metastatic deposits in the brain
• Blurry vision
• Bone fractures due to metastasis to the bones

Although the exact cause of colon cancer is unknown, most evidence points to underlying genetic anomalies. These can include:

• Inherited genetic mutations: 
  • Familial adenomatous polyposis (FAP) due to an inherited adenomatous polyposis coli (APC) gene.
  • Lynch syndrome, also called hereditary non-polyposis colon cancer (HNPCC), is an inherited syndrome that can lead to colorectal cancer.
  • Peutz-Jeghers syndrome is caused by inherited changes in the STK11 (LKB1) gene that can cause colon cancer. Classical signs of this syndrome include hamartomatous intestinal polyps and bluish-grey patches on the gums and oral mucosa.
• Acquired genetic mutations: Various defects and changes to an individual’s DNA can be acquired during their lifetime. Some such mutations can lead to colorectal cancer. Smoking adds a considerable risk.

Certain risk factors increase the chances of developing colon cancer as well as accelerate the cancer spread or growth.

Fixed risk factors: In certain conditions, colon cancer can be an inevitable reality that will set in with age. The presence of any of these factors necessitates initiation of early screening, diagnosis and treatment. Some such factors include:

• A known history of colon polyps
• A previous history of bowel diseases
• A family history of colorectal cancer
• Some genetically inherited syndromes, like familial adenomatous polyposis (FAP) caused by the expression of the adenomatous polyposis coli (APC) gene, pose a near-certain risk of future colorectal cancer
• Some ethnicities like Eastern European Jewish or African descent are at greater risk
• Old age
• Inflammatory conditions of the intestines such as inflammatory bowel diseases (ulcerative colitis and Crohn’s disease)

Modifiable risk factors: Some factors that can lead to colon cancer are related to lifestyle and can be altered. Examples of such factors include, but are not limited to:

• BMI that suggests obesity or overweight
• Smoking
• Heavy alcohol consumption
• Type 2 Diabetes Mellitus
• Inactive sedentary lifestyle
• An unhealthy diet that includes excessive quantities of processed foods and red meat

The stages of colorectal cancer begin from stage 0, the earliest stage of cancer, and go up to stage 4, the most advanced stage.

• Stage 0 (carcinoma in situ): In this stage, abnormal cells are only in the inner lining of the colon or rectum. Carcinoma in situ means that the cancer has not spread from its site of origin.
• Stage 1: In this stage, the cancer has penetrated the lining of the colon or rectum and may have invaded the muscle layer as well. It hasn’t spread to nearby lymph nodes or to other parts of the body at this stage.
• Stage 2: The cancer has spread to the walls of the colon or rectum or through the walls to nearby tissue. The lymph nodes have not yet been breached by the cancer in this stage.
• Stage 3: The cancer has invaded the lymph nodes. Depending on the number and size of lymph nodes, the cancer may be staged into various sub-stages like 3A, 3B and so on. The cancer has not spread to other distant organs in the body yet.
• Stage 4: In this last and final stage, the cancer has spread to distant parts of the body by disseminating through the blood or lymph nodes. Common sites of spread include the lung, liver and brain. This phenomenon is called metastasis and has a poor prognosis.

History: The doctor will begin by taking a detailed medical history of the patient. After taking a thorough history of signs and symptoms (both current and past) and the sequence of their development, a special emphasis is laid on discovering potential lifestyle risk factors. Keen attention is paid to family history or a history or known pre-existing colonic polyps. In order to give an accurate diagnosis, the medical history taking is followed by a thorough physical examination, some special investigations with tools designed to visualise the colon lumen better, laboratory investigations and radiological imaging.

Physical examination: Following a medical history, the patient undergoes a thorough physical examination. A general medical examination is conducted in which many signs of an underlying disease like jaundice, anemia and fingernail clubbing can be noted. A systemic exam is conducted afterwards. Abdominal examination is of utmost importance to rule out other conditions. Other systems are also closely examined to note signs of possible metastasis. Following a systemic examination, a digital rectal examination is done. The doctor will, after application of a lubricant jelly, examine the anal opening and rectum with their gloved fingers. To visualise the colon further, special tools are used.

Following investigations may be required to diagnose colon cancer:

• Stool tests: In order to detect blood in the stool that may not be visible to the naked eye, fecal occult blood tests (FOBT) are done. Two types of tests can be commonly conducted and the patient will have to submit a sample of their stool for both of them.
  • Guaiac-based fecal occult blood test (gFOBT): The stool sample is applied on a card containing a substance called guaiac. The colour of the card changes if occult blood is present in the stool. Red meat and NSAIDs should be avoided before this test to reduce interference.
  • Fecal immunochemical testing (FIT): This test is considered a more precise one as it detects hemoglobin, the main protein of blood, in the stool. The test results are not affected by food or drugs.
• Blood tests:
  • Complete blood count: Hemoglobin levels can be low due to anemia caused by bleeding from the colon.
  • Blood glucose levels: Diabetes mellitus can be detected.
  • Liver function test: Metastasis can cause liver enzyme derangements and jaundice.
  • ESR and CRP: These markers of inflammation can hint at underlying inflammatory bowel disease.
• Colon-specific visualisation investigations:
  • Sigmoidoscopy: A flexible tube is inserted through the rectum and into the sigmoid colon (the last portion of the large intestine before the rectum begins). It can help visualise any growths or polyps better.
  • Colonoscopy: The patient prepares a day in advance by taking prescribed purgative medications that forcefully and completely evacuate the bowels to help with a better visualisation. A tube is inserted through the rectum, after application of lubricant and local anaesthetic, and it helps visualise the entire length of the colon. Biopsies, or tissue samples, from suspicious growths, can also be taken.
• Radiological imaging investigations: 
  • X-ray with a barium enema. A contrast dye called barium is infused through the rectum and X-rays are taken. This helps visualise any abnormal growths inside the lumen of the colon.
  • CT scan: It helps visualise the colon anatomy with more precision.
  • Chest X-ray: Liver metastasis can appear as “cannon balls” on film.

For people with an average risk for colon cancer, regular screening is advised with stool and visual examination (like colonoscopy) after the age of 45. For people with added risk factors, more frequent screening with more specific tests should be started before the age of 45.

The treatment of colon cancer can include surgery, chemotherapy, radiation and immunotherapy.

Surgical: In the case of a cancerous polyp that has not tracked to the opposite colon wall, the outcome of surgical removal is excellent. In cases where the cancer has spread through the large intestines, the cancerous part is sectioned out and removed. If enough length of the healthy bowel is available, it will be reattached. If not, then a colostomy, or an external opening of the colon stub through the abdominal wall, is made to remove the fecal waste.

Chemotherapy: Certain drugs can kill and inhibit the regrowth of cancer cells in colon cancer. These drugs are usually started after surgical management. Additional side effects can arise from these drugs and may need further medication to be brought under control. Chemotherapy drugs used for colon cancer include:

• Capecitabine (Xeloda)
• Fluorouracil
• Oxaliplatin (Eloxatin)
• Irinotecan (Camptosar)

Radiation: Radiation therapy can be used alongside chemotherapy to improve the clinical outcome. High-energy radiation is inflicted on cancer cells to kill them. 

Immunotherapy: Late-stage and more advanced colorectal cancer that does not respond to other treatment modalities can be subjected to immunotherapy. Some immunotherapy drugs used for colon cancer treatment are:

• Bevacizumab (Avastin)
• Cetuximab (Erbitux)
• Pembrolizumab (Keytruda)

While it can be worrying to be diagnosed with colorectal cancer, the prognosis is generally fair. If caught early and treated, the five-year survival rate for colon cancer is nearly 65%. This means that 65% of people who get diagnosed with colon cancer survive for at least 5 years after that. Although the rate of colorectal cancer is declining in older patients, it is found to be on the rise in younger ones, possibly due to lifestyle habits.