1. Diagnostics
1.1. Colonoscopy: can visualize small polyps that can be removed right then and there or at a later stage. A long tuber is used to screen the entire colon. Colonoscopies are also used as a follow-up test if anything unusual is found during one of the other screening tests. This is performed every 10 years. This exam is primarily used after showing symptoms of possible Colorectal Cancer.
1.2. Biopsy: evaluation of cancerous changes of tissue samples removed during test procedures.
1.3. Proctoscopy: procedure using a straight, hollow metal or plastic tube, sometimes with a tiny light at the end, that allows the gastroenterologist to examine the insides of the rectum and the anus. This instrument can take tissue samples for biopsy.
1.4. Tests
1.4.1. Digital Rectal Examination (DRE): a simple procedure to examine the prostate and other internal organs.
1.4.2. Blood and electrolyte exam will show anemia of iron deficiency, especially in right-side cancer.
1.4.2.1. Other blood exams that can help diagnose Colorectal Cancer include: Complete Blood Count (CBC), tumor markers, and liver enzymes.
1.4.3. Erythrocyte Sedimentation Rate (ESR) is a type of blood test that measures how quickly red blood cells settle at the bottom of a test tube.
1.4.4. Electrolyte disturbance may be evident as a result of diarrhea obstruction, vomiting, inadequate fluid intake, and/or increased urea due to dehydration.
1.4.5. Carcino-embryonic antigen (CEA): A blood test used to measure the amount of CEA in babies in the womb within the blood.
1.5. Imaging
1.5.1. CT-Scan (with or without contrast)
1.5.2. Endorectal MRI: Endorectal Coil probe is placed into the rectum while an MRI image is being taken.
1.5.3. PET (with or without CT): Both can be done at the same time allowing the physician to compare areas of higher radioactivity from PET, but with a clearer image from CT.
1.5.4. Angiography: X-Ray exam of the blood vessels where a dye is injected into an artery, outlining the vessels on an X-Ray image.
1.5.5. Ultrasound
1.5.5.1. Abdominal Ultrasound: transductor is placed alongside of the abdomen looking over the gallbladder, pancreas, and liver for tumors.
1.5.5.2. Endorectal Ultrasound: transductor is inserted into the rectum and is used to see how far through the rectal wall cancer has grown and whether it has reached nearby organs or lymph nodes.
1.5.5.3. Intraoperative Ultrasound: conducted during surgery and the transponder is placed directly over the liver to see of cancer has spread to the liver, allowing the surgeon to biopsy the tumor if found.
2. Treatment
2.1. Carcinoma in situ: surgery to remove any cancerous growths.
2.2. Chemotherapy is the current standard protocol for Colorectal Cancer treatment known to significantly reduce relapse and risks of dying from resected colon cancer by targeting tumor cells with toxic agents in a selective and specific manner, avoiding damage to normal tissues.
2.2.1. Chemotherapy treatments based on the drug fluorouracil (5-FU) combined with the vitamin Leucovorin have been shown to improve survival in patients with stage III or high-risk stage II disease.
2.2.1.1. This protocol significantly improves the 3- year disease- free survival rate. However, only 26% of patients respond. There are many types of chemotherapy drugs. Every cancer case is different, so a Oncology team will design a specific treatment plan for each case.
2.2.2. Gene therapy alongside chemotherapy reduces its systemic effects and involves gene transfer of an enzyme into tumor cells, which converts an inactive pro-drug into a toxic metabolite, leading to apoptosis.
2.2.3. Drug resistance is a major problem that limits the effectiveness of chemotherapy, and its toxic effects make it very difficult for some patients to tolerate.
2.2.3.1. Multidrug resistance is a phenomenon by which cancer cells evade the cytotoxic effects of chemotherapeutic agents. It can occur through different mechanisms, but more oftenly correlates with the overexpression of intracellular proteins, resulting in increased drug efflux, decreased drug influx, drug inactivation, alterations in drug targeting, processing of drug-induced damage, or evasion of apoptosis.
2.3. Immunotherapy is the second most common treatment and its goal is to boost the patient’s immune reaction to growing cancer cells to help them fight the disease more effectively.
2.3.1. Active Immunotherapy is intended to stimulate the immune system by using the patient’s antibodies to recognize any abnormal components in cancerous cells, selectively target, and kill the cell.
2.3.2. Passive Immunotherapy is very similar to active immunotherapy, but rather using the patient's antibodies, man-made antibodies are used in order to target the specific components on colorectal cancer cells and deliver cell-killing chemicals and/or radiation to the tumor itself.
2.4. Radiation Therapy uses high-energy rays to destroy cancer cells, often used alongside chemotherapy.
2.4.1. External Beam Radiation Therapy (EBRT): focuses on cancer cells outside the body via machine giving off intense radiation therapeutically. Treatments might be given over the course of a few days to several weeks.
2.4.2. Internal Radiation Therapy (Brachytherapy) uses a radioactive source that is put inside your rectum directly next to or into the tumor.
2.4.2.1. Endocavitary Radiation Therapy uses a small balloon-like device and placed into the rectum to deliver high-intensity radiation for a few minutes.
2.4.2.2. Interstitial Brachytherapy uses a tube that is placed right into the tumor and small pellets of radioactive material are then put into the tube for several minutes.
2.5. Angiogenesis Inhibiting therapy, also known as targeting therapy, is a drug therapy used alongside chemotherapy that stops tumors from growing their own blood vessels, leading to malnutrition of the tumor which will either slow the growth or shrink it as a result.
2.5.1. Some cancer cells make a protein known as vascular endothelial growth factor (VEGF) which attaches to the cell receptors that line tumor's endothelial cells which triggers the blood vessels to grow so that the cancer can grow as well.
2.5.1.1. Bevacizumab (Avastin) is an example of an Anti-angiogenesis drug specifically designed for advanced stage Colorectal Cancer.
3. Colorectal Cancer Staging
3.1. Stage 0: Polyps found on the mucosa known as carcinoma in situ because the cells are confined to their place of origin. Cells in this stage can either be cancerous or precancerous.
3.2. Stage I: Cancer has grown into the intestinal wall through the mucosa and into the submucosa. There is a possibility that the cancer may have entered the muscle as well. (Survival Rate: 80-95%).
3.3. Stage II (Survival Rate: 55-80%)
3.3.1. IIA: The cancer has grown into the serosa, but has not grown through it.
3.3.2. IIB: Cancer has gone through all layers of the Colon or Rectum.
3.3.3. IIC: The cancer has grown through all layers of the intestine and in nearby organs or tissues.
3.4. Stage III (Survival Rate: ~40%)
3.4.1. IIIA: The cancer has grown into the intestinal wall through the mucosa, into the submucosa, and may have entered the muscle. The cancer has also spread up to 3 lymph nodes near the site of the primary tumor.
3.4.2. IIIB: The cancer has grown into or through the outermost layer of the colon or rectum and may have spread into nearby organs or tissues. Up to 3 lymph nodes are affected.
3.4.3. IIIC: Cancer has grown into or through the outermost layer of the colon or rectum and may have spread to 4+ lymph nodes. Cancer has also spread to nearby organs.
3.5. Stage IV: This is the most advanced stage of Colorectal Cancer and has metastasized to distant organ(s). The cancer may or may not have grown through the wall of the colon or rectum, lymph nodes may or many not have been affected (Survival Rate: 10%).
3.5.1. IVA: Metastasis to one organ.
3.5.2. IVB: Metastasis to more than one organ.
4. Statistics
4.1. The overall likelihood of developing Colorectal Cancer is about 1 in 23 for men, and 1 in 25 for women, the majority diagnosed at age 50 and over.
4.2. In the US, Colorectal Cancer is the second leading cause of cancer-related deaths with men and women combined (~862,000 deaths); just behind Lung Cancer (WHO).
4.3. Westernized countries are most at risk for developing Colorectal Cancer.
4.3.1. For Colon Cancer: Southern & Northern Europe, Australia and New Zealand have the highest incidence.
4.3.2. For Rectal Cancer, regions with the highest incidence include Eastern Europe, Australia, New Zealand, and East Asia.
4.3.3. North America is featured in the highest incidence for both cancers.
4.4. Five-year relative survival rate for Colon and Rectal Cancer in the US is 63.8%.
4.5. Survival within the US are race and ethnicity-dependent. African & Native Americans have a higher incidence and lower survival rate, while Hispanics and Caucasians display the same rates.
5. Clinical Manifestations
5.1. Early Warning Signs
5.1.1. Rectal bleeding, wither bright or dark red in color
5.1.2. Narrow stools or blood in stools
5.1.3. Tenesmus
5.1.4. Anemia caused by an iron deficiency
5.1.5. Persistant abdominal pain
5.1.6. Unexplained weight loss
5.2. Local Symptoms
5.2.1. Constipation and/or Diarrhea
5.2.2. Alternating constipation/diarrhea, or other changes in bowl habits
5.2.3. Rectal bleeding/ bloody stools, thinner than normal stools
5.2.4. Bloating, cramps, or discomfort in the abdomen region
5.2.5. Feeling as if the bowel is not completely emptying
5.3. Systematic Symptoms
5.3.1. Unexplained loss of appetite
5.3.2. Unexplained weight loss
5.3.3. Nausea/Vomiting
5.3.4. Jaundice
5.3.5. Weakness/Fatigue
5.3.6. Anemia
5.4. Colon-Specific Cancer Symptoms
5.4.1. Frequent change in bowel movements
5.4.2. Constipation
5.4.3. Inconsistant stools (loose or watery)
5.4.4. Blood either as bright red spots or dark and tar-like in stools
5.4.5. Rectal Bleeding
5.4.6. Abdominal pain, bloating, or cramps
5.4.7. Persistant feeling that one cannot completely empty the bowel
5.5. Rectal-Specific Cancer Symptoms
5.5.1. Diarrhea/Constipation
5.5.2. Change in shape/size of stools and presence of blood
5.5.3. Inability to fully empty the bowel
6. Pathogenesis
6.1. Colorectal Cancer tends to develop slowly, starting with polyps occurring on the epithelial lining of the colon or rectum.
6.2. Polyps are a small clump of cells that form on the lining of the colon or rectum. Most are harmles, but some can develop into cancer.
6.3. Polyps can either be benign, pre-malignant, or malignant.
6.3.1. Bengin polyps: hyperplastic polyps, inflammatory polyps, and hamartomatous polyps.
6.3.2. Pre-malignant polyps: tubular adenoma, sessile serrated adenomas, dysplasia polyp, and villous adenomas.
6.3.3. Malignant Polyps: colorectal adenocarcinoma, and invasive adenocarcinomas.
7. Risk Factors
7.1. Modifiable risk factors for Colorectal Cancer include heavy alcohol consumption, obesity, excess red meat, raw meat and processed food consumption, smoking, low fiber/high fat diet, high calorie intake, and very low vitamin C, calcium, salt and selenium content.
7.2. Hereditary factors can can also increase one's risk of developing Colorectal Cancer. Pre-existing health conditions including family history of Colorectal Cancer, Adenoma, Inflammatory bowl disease, Cystic Fibrosis, Type II Diabetes, and a rare inherited cancer predisposition syndrome known as Familial adenomatous polyposis (FAP).
7.3. Childhood malignancy survivors who were exposed to radiation in the abdomen are significantly at increased risk for developing gastrointestinal neoplasm as an adult.
7.3.1. The dose-response effect on Colorectal cancer had a 70% increase in risk for every 10Gy increase in the radiation dose.
8. Prevention
8.1. Primary Prevention
8.1.1. Diets low in fat, high in fiber with adequate fruit and vegetable intake.
8.1.2. Vitamins/Supplements including vitamin A, C and E along with folate, selenium, and calcium supplements.
8.1.3. Lifestyle Habits including exercise, normal body weight, moderate to no alcohol intake, and avoiding smoking can significantly reduce cancer risk regardless of the type.
8.1.4. Medications such as Asprin and other NSAID's, postmenopausal hormonal replacement drugs, and HMG-CoA inhibiting drugs have links to reduce the risk of cancer formation.
8.2. Secondary Prevention
8.2.1. A Cohort Study might be conducted on the patient along with their illness journey for medical research.
8.2.2. A Prospective Study is a type of cohort study but involves many patients and their medical journey used for research and publications.
8.2.3. Screening
8.2.3.1. Flexible Sigmoidoscopy: This procedures requires a doctor's visit and a short, thin, flexible, lighted tube is put into the rectum which checks for polyps or cancer in the rectum and lower third of the colon. This is done every 5-10 years with a FIT test.
8.2.3.2. Barium Enema X-Ray (usually with double contrast): X-Ray of the colon and rectum in which barium is given as an enema. Air is blown into the rectum in order to expand the colon to produce an outline of the colon on the X-Ray image.
8.2.3.3. CT Colonography (with Barium contrast): Just like a regular CT Abdomen/Pelvis exam, but a liquid Barium contrast dye is ingested and air is inflated into the rectum.
8.2.3.4. Stool Tests
8.2.3.4.1. Guaiac-Based Fecal Occult Blood Test (gFOBT): This once a year at-home test kit given by your healthcare provider uses the chemical Guaiac to detect blood in the stool by using a stick or bush to obtain a small amount of stool. After the stool is obtained, return to your doctor or a lab where the sample can be tested (Conducted once a year).
8.2.3.4.2. Fecal Immunochemical Test (FIT): This exam uses antibodies to detect blood in the stool, just like a gFOBT and also conducted once a year.
8.2.3.4.3. Multitargeted DNA (Cologuard): this exam combines a FIT exam that detects altered DNA in the stool. This exam requires an entire bowel movement which is then sent to a lab where it is checked for cancer cells. This can be done once to three times per year.