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Colorectal cancer: Pathophysiology, tumors, and stages

09 Aug, 2023

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In the vast landscape of global health challenges, colorectal cancer emerges as a significant concern, affecting countless individuals across demographics and borders. Its silent progression and potential severity underscore the importance of understanding, early detection, and proactive measures. As we navigate the complexities of this disease, it becomes evident that knowledge, awareness, and timely intervention can make a profound difference. This article seeks to shed light on the multifaceted aspects of colorectal cancer, offering insights and guidance for those seeking a comprehensive overview.


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Colorectal cancer


Colorectal cancer is a malignancy that originates in the cells lining the colon (the large intestine) and the rectum (the lower part of the colon that connects to the anus). It often begins as noncancerous polyps, which can over time develop into cancer if not detected and removed early.

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Understanding colorectal cancer is crucial for several reasons. Firstly, it is among the most common cancers globally, affecting both men and women. Early detection can significantly improve survival rates, making awareness and regular screenings vital. Additionally, understanding the risk factors and preventive measures can help reduce its incidence. Knowledge about colorectal cancer can empower individuals to make informed decisions about their health and seek timely medical intervention.


Anatomy & Physiology


Overview of the Colon and Rectum: The colon and rectum are parts of the large intestine, which is the final section of the digestive tract. The colon is divided into four parts: the ascending colon, the transverse colon, the descending colon, and the sigmoid colon. The rectum is the last 6 inches of the large intestine and ends with the anus, the opening where feces are expelled from the body.

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Function of the Colon and Rectum in Digestion: The primary function of the colon is to reabsorb water and electrolytes from the undigested food matter, converting it into feces. Beneficial bacteria in the colon further break down the food, releasing gases and short-chain fatty acids, which are absorbed by the colon's cells. The rectum serves as a temporary storage site for feces before they are eliminated from the body. Together, the colon and rectum play a crucial role in maintaining the body's fluid balance and waste elimination.


Colorectal cancer is one of the most commonly diagnosed cancers worldwide. According to the World Health Organization , colorectal cancer is the third most common cancer in men and the second in women, with over 1.8 million new cases diagnosed annually. The global prevalence indicates that millions are living with the disease at any given time, with higher rates observed in developed countries compared to developing ones. This disparity is often attributed to differences in dietary patterns, lifestyle, and access to screening and medical care.


How colorectal cancer develops:

Colorectal cancer typically originates from the inner lining of the colon or rectum. It often begins as a benign growth known as a polyp. Over time, due to genetic mutations and various environmental factors, some of these polyps can undergo malignant transformation, evolving from benign growths into cancerous tumors. The transition from a benign polyp to a malignant tumor is not instantaneous but is a gradual process influenced by a combination of genetic, environmental, and lifestyle factors.


Types of tumors:


1. Adenomas: These are benign polyps that have the potential to become cancerous. They are precursors to colorectal cancer. Not all adenomas become malignant, but nearly all colorectal cancers arise from adenomas.

2. Carcinomas: These are malignant tumors. The most common type of carcinoma in the colon and rectum is adenocarcinoma, which originates from the glandular cells that line the colon and rectum. Adenocarcinomas account for over 95% of colorectal cancer cases.


Stages of colorectal cancer:


Staging describes the extent of cancer's spread. The stages of colorectal cancer are:

  • Stage 0 (Carcinoma in Situ): The cancer is only in the innermost lining of the colon or rectum and has not spread.
  • Stage I: The cancer has spread to the inner wall of the colon or rectum but hasn't spread outside the wall.
  • Stage II: The cancer has spread outside the colon or rectum to nearby tissues but hasn't reached the nearby lymph nodes.
  • Stage III: The cancer has spread to nearby lymph nodes but hasn't spread to other parts of the body.
  • Stage IV: The cancer has spread to distant parts of the body, such as the liver, lungs, or bones.


Symptoms:


1. Changes in Bowel Habits: This can include diarrhea, constipation, or narrowing of the stool that lasts for more than a few days.

2. Blood in Stool: This can appear as bright red blood or as very dark stools. It's a common symptom but can also be indicative of other conditions like hemorrhoids.

3. Abdominal Pain: A persistent pain or discomfort in the abdomen, including gas, cramps, or bloating.

4. Unexplained Weight Loss: Losing weight without any changes in diet or physical activity can be a sign of colorectal cancer.

5. Fatigue: Constant tiredness or weakness, which can be due to anemia caused by the cancer.

6. Asymptomatic Presentation: In many cases, especially in the early stages, colorectal cancer might not cause any symptoms. This is why regular screening is crucial, especially for those at higher risk.

Early detection of colorectal cancer significantly improves the chances of successful treatment. Recognizing the symptoms and understanding the importance of regular screenings can save lives.


Diagnostic procedures


1. Colonoscopy:

  • A colonoscopy is a procedure that uses a long, flexible tube with a camera on the end (colonoscope) to examine the entire length of the colon and rectum.
  • Purpose: It can detect polyps, tumors, and other abnormalities. If polyps are found, they can often be removed during the procedure, preventing the development of cancer. Biopsies can also be taken during a colonoscopy.
  • Preparation: Patients typically undergo a bowel prep to clear the colon of stool. This often involves a special diet and laxatives.

2. Sigmoidoscopy:

  • Similar to a colonoscopy, a sigmoidoscopy uses a flexible tube to examine only the last third of the colon (the sigmoid colon) and the rectum.
  • Purpose: It's used to detect polyps and cancers in the lower part of the colon. It's less invasive than a colonoscopy but also covers a smaller area.
  • Preparation: A bowel prep is required, though it's typically less extensive than the prep for a colonoscopy.

3. Fecal Occult Blood Test (FOBT):

  • This test checks for hidden (occult) blood in the stool.
  • Purpose: It's used as a screening tool for colorectal cancer, as tumors and polyps may bleed, leading to trace amounts of blood in the stool.
  • Preparation: Patients might be asked to avoid certain foods or medications before the test to prevent false positives.

4. Fecal Immunochemical Test (FIT):

  • FIT also detects hidden blood in the stool but uses antibodies to detect human hemoglobin protein.
  • Purpose: Like FOBT, it's a screening tool for colorectal cancer. FIT is considered more specific than FOBT because it doesn't react to animal blood or to foods, reducing false positives.
  • Preparation: There are typically no dietary or medication restrictions for FIT.

5. CT Colonography:

  • Also known as a virtual colonoscopy, this test uses X-rays and computers to produce images of the entire colon, which are then assembled to create a detailed view.
  • Purpose: It can detect polyps and tumors. If abnormalities are found, a traditional colonoscopy might be needed afterward for biopsy or polyp removal.
  • Preparation: A bowel prep is required to clear the colon of stool.

6. Biopsy:

  • A biopsy involves taking a small sample of tissue for examination under a microscope.
  • Purpose: It's used to determine if a suspicious area is cancerous and, if so, the type and grade of the cancer.
  • Preparation: If done during a colonoscopy or sigmoidoscopy, the same bowel prep applies. If done separately, specific instructions will be provided based on the method used.

These diagnostic procedures are essential tools in detecting and diagnosing colorectal cancer. Regular screenings, especially for those at higher risk, can lead to early detection and improved outcomes.


Treatment options


Surgery: Surgery is the most common treatment for colorectal cancer, especially when it's localized. The type of surgery depends on the location and stage of the tumor.

1. Local Excision:

  • For cancers that are found at a very early stage and are located within the innermost lining of the colon or rectum, a local excision can be performed. This involves inserting a tube into the rectum and cutting out the cancerous tissue.
  • When Used: Typically for very early-stage cancers or precancerous polyps.

2. Colectomy:

  • This is the surgical removal of all or part of the colon. There are different types of colectomies, including partial (segmental), total, and hemicolectomy, depending on the extent and location of the cancer.
  • When Used: For more advanced cancers that have penetrated deeper into or through the walls of the colon.

3. Chemotherapy:

  • Chemotherapy uses drugs to kill cancer cells or stop them from growing. It can be given orally or injected into a vein.
  • Purpose: It can be used before surgery to shrink tumors (neoadjuvant therapy) or after surgery to kill any remaining cancer cells (adjuvant therapy). It's also used for advanced cancers that have spread to other parts of the body.

4. Radiation Therapy:

  • This therapy uses high-energy rays to kill or shrink cancer cells.
  • Purpose: Often used in conjunction with chemotherapy for rectal cancer, it can be used before surgery to shrink tumors or after surgery to kill any remaining cancer cells. It's also used to relieve symptoms of advanced cancer.

5. Targeted Therapies:

  • These are newer drugs that specifically target the changes in cells that cause cancer. They can work by stopping cancer from growing and spreading or by enhancing the immune system's ability to kill cancer cells.
  • Purpose: Used for advanced colorectal cancers, often in combination with chemotherapy. Examples include drugs that target vascular endothelial growth factor (VEGF) or epidermal growth factor receptor (EGFR).

6. Immunotherapy:

  • Immunotherapy boosts the body's natural defenses to fight cancer. It uses substances made by the body or in a lab to improve or restore immune system function.
  • Purpose: Some types of immunotherapy can be used to treat advanced colorectal cancers, especially those that have specific genetic changes or have stopped responding to other treatments.

The choice of treatment for colorectal cancer depends on several factors, including the stage and location of the cancer, the patient's overall health, and their preferences. Often, a combination of treatments is used to achieve the best outcomes. Regular follow-ups after treatment are crucial to monitor for any signs of cancer recurrence and to manage any potential side effects of treatment.


Risk factors:

1. Age: The risk of developing colorectal cancer increases with age. Most people diagnosed with this cancer are over the age of 50. However, it's worth noting that there's been a concerning rise in colorectal cancer rates among younger adults in recent years.

2. Family history: Individuals with a first-degree relative (parent, sibling, or child) who has had colorectal cancer are at a higher risk. The risk is even greater if that relative was diagnosed before the age of 45 or if more than one first-degree relative is affected.

3. Genetic mutations: Certain inherited gene mutations can increase the risk of colorectal cancer. Examples include familial adenomatous polyposis (FAP) and Lynch syndrome (hereditary non-polyposis colorectal cancer or HNPCC). These syndromes can lead to a much higher risk of colorectal cancer and often at a younger age.

4. Lifestyle factors:

  • Diet: A diet high in red and processed meats can increase the risk of colorectal cancer. Conversely, diets rich in fruits, vegetables, and whole grains have been linked to a reduced risk.
  • Smoking: Long-term smokers are more likely than non-smokers to develop and die from colorectal cancer.
  • Alcohol: Heavy alcohol consumption can increase the risk of colorectal cancer. It's advised to limit alcohol intake to moderate levels.

5. Previous history of polyps or colorectal cancer: Individuals who have previously had colorectal cancer or adenomatous polyps are at a higher risk of developing colorectal cancer in the future.

6. Inflammatory Bowel Diseases: Chronic inflammatory diseases of the colon, such as Crohn's disease and ulcerative colitis, can increase the risk of colorectal cancer. The risk is proportional to the duration and extent of the disease.


Prognosis

Factors affecting prognosis:

  1. Stage of the Cancer: The extent to which the cancer has spread is a primary determinant. Early-stage cancers generally have a better prognosis than advanced-stage cancers.
  2. Tumor Grade: This refers to how abnormal the cancer cells look under a microscope. High-grade tumors tend to grow and spread more rapidly than low-grade tumors.
  3. Location of the Tumor: Tumors in certain locations may be more challenging to treat and may have a different prognosis.
  4. Patient's Overall Health: Individuals with good overall health often have better outcomes.
  5. Response to Treatment: How the cancer responds to initial treatments can influence prognosis.
  6. Presence of Specific Genetic Changes: Some genetic mutations can influence how aggressive the cancer is and how it responds to treatment.

Survival Rates by Stage: Survival rates provide an estimate of the percentage of people with the same type and stage of cancer who survive a specific amount of time after their diagnosis. As of my last update in 2021:

  • Stage I: The 5-year survival rate is about 90%.
  • Stage II: The 5-year survival rate ranges from 70% to 85%, depending on the depth of tumor invasion and other factors.
  • Stage III: The 5-year survival rate ranges from 40% to 70%, depending on the number of lymph nodes affected.
  • Stage IV: The 5-year survival rate is about 10-15%.

It's essential to note that these are averages, and individual prognosis can vary based on a multitude of factors.

Prevention

1. Screening recommendations:

  1. Age: Begin regular screenings at age 45 for those at average risk, according to the American Cancer Society. However, those with increased risk factors may need to start earlier.
  2. Frequency: Depending on the type of test (e.g., colonoscopy every 10 years, FIT annually), the frequency can vary.
  3. High-risk Individuals: More frequent screenings or starting at an earlier age may be recommended.

2. Lifestyle Modifications:

  • Diet:
    • Consume a diet rich in fruits, vegetables, and whole grains.
    • Limit intake of red meats (like beef, pork, and lamb) and processed meats (like hot dogs and some luncheon meats).
  • Physical Activity: Engage in regular physical activity. Aim for at least 150 minutes of moderate-intensity or 75 minutes of high-intensity exercise each week.
  • Limiting Alcohol and Tobacco Use:
    • Limit alcohol consumption to moderate levels (up to one drink a day for women and up to two drinks a day for men).
    • Avoid smoking. If you smoke, seek help to quit.

Genetic Counseling for High-risk Individuals: For those with a strong family history of colorectal cancer or known genetic mutations (like Lynch syndrome), genetic counseling can provide information about the risk of developing cancer. It can also guide decisions about screening and prevention strategies.

Prevention and early detection are crucial in managing colorectal cancer. By understanding risk factors and making lifestyle modifications, individuals can significantly reduce their risk. Regular screenings can detect precancerous polyps and early-stage cancers, leading to better outcomes.

Colorectal cancer, one of the most common cancers globally, underscores the critical importance of early detection and prevention. Regular screenings can identify precancerous conditions, making treatment more effective and improving survival rates. By prioritizing and promoting these screenings, combined with informed lifestyle choices, individuals can significantly reduce their risk and combat the disease's progression. Encouraging regular check-ups and fostering awareness are essential steps in safeguarding public health against this prevalent threat.

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FAQs

Early signs can include changes in bowel habits (diarrhea, constipation, or narrowing of the stool), blood in the stool, persistent abdominal discomfort (cramps, gas, or pain), unexplained weight loss, and fatigue. However, many people with early-stage colorectal cancer don't experience any symptoms, which underscores the importance of regular screenings