Colorectal Cancer Overview

Colorectal Cancer (CRC)

• CRC is the third most common cancer in men and women.
• Early detection leads to an excellent prognosis.
• Screening average-risk individuals over 50 significantly reduces incidence and mortality.
• The presence of adenomatous polyps (precancerous) allows for precursor lesion removal, preventing cancer.
• Various screening tests are available, including stool-based tests, endoscopy, and radiologic tests; colonoscopy is often preferred.
• Hereditary syndromes increase CRC risk; genetic testing can identify these individuals.

CRC Epidemiology

• CRC is the third leading cause of cancer incidence and mortality in the US and WEurope, affecting both men and women.
• Estimated 2020 incidence: 142,820 cases (73,680 in men, 69,140 in women).
• Estimated 2020 mortality: 50,830 deaths (26,300 in men, 24,530 in women).
• Worldwide incidence (2008): 1,230,000 cases, 609,000 deaths.
• Worldwide (2008) European incidence: 450,000 cases, 230,000 deaths.

CRC Etiology

• Sporadic CRC etiology is unknown, likely a combination of environmental and genetic factors.
• Familial adenomatous polyposis (FAP) patients have a high CRC risk due to a mutated APC gene.
• Lynch syndrome patients inherit a mutated DNA mismatch repair gene, increasing CRC risk.

CRC Pathology/Pathogenesis

• Three main molecular pathways are involved:
  • Chromosomal instability (CIN): Accounts for ~70% of colon cancers.
  • Microsatellite instability (MSI): Seen in ~15% of sporadic CRC and all Lynch syndrome CRC.
  • CpG island methylator phenotype (CIMP): Present in at least 15% of CRCs.

CRC Risk Factors

• Highest risk: Age over 50, birth in "Westernized" countries, hereditary syndromes (FAP, Lynch), long-standing IBD (ulcerative colitis, Crohn's colitis).
• Moderate risk: Diet rich in red meat, previous adenoma/CRC, pelvic irradiation, diet rich in animal fat, obesity, smoking, alcohol, cholecystectomy.
• Protective factors: Colonoscopy/sigmoidoscopy, physical activity, aspirin/NSAID use, diet rich in fiber/fruits/vegetables, calcium/folate supplements, hormone replacement therapy.

CRC Clinical Diagnosis

• History should include details about symptoms like changes in bowel habits, blood in stool, abdominal pain, and weight loss.
• Medical history should consider family history of colon cancer, polyps, and other cancers (especially gynecologic).
• Patients with suspected FAP should have their extraintestinal manifestations detailed. Ask about red meat, fruits/vegetables, and fiber intake.
• Be aware that medications (e.g., aspirin, NSAIDs) can cause occult GI bleeding, potentially confounding diagnosis.

CRC Patient Examination

• Abdominal mass, signs of anemia, hepatomegaly
• Digital rectal examination

CRC Diagnostic Tests

• Colonoscopy with biopsy (preferred).
• Sigmoidoscopy with biopsy (if colonoscopy is unavailable).
• CT scan of abdomen/pelvis (to rule out metastasis).
• CT colonography (if colonoscopy is unavailable; no tissue diagnosis).
• MRI of abdomen/pelvis (if CT unavailable or to avoid radiation).
• Serum CEA (carcinoembryonic antigen) test (useful mainly for follow-up after treatment).
• CBC, LFTs (to assess for anemia, liver involvement).

CRC Screening Guidelines

• Average risk: Screening begins at 45 via stool tests or visual exams.
• High risk individuals: Screening before 45 and more frequent tests.

CRC Staging

• Staging is based on the TNM classification.
  • T (tumor): Primary tumor size and invasion.
  • N (nodes): Regional lymph node involvement.
  • M (metastasis): Distant metastasis presence.

CRC Treatment

• Surgery is the cornerstone of treatment for stages I and II.
• Adjuvant chemotherapy is given for stage III.
• Advanced disease chemotherapy regimens are used for stage IV.
• Neoadjuvant therapy (chemo/radiation) followed by postoperative therapy is common for rectal cancers.
• Polyp removal (polypectomy) might be curative, depending on the characteristics, for certain colorectal tumors.

CRC Distant Metastasis

• Common sites: Liver, lung, brain, bone.

CRC Follow-up

• Includes history and physical every few months or years.
• CEA monitoring may be included at intervals.
• Imaging/endoscopy to assess for recurrent disease, with specific intervals based on risk factors.

CRC Prevention

• Limit red meat intake (500 g/week or 70 g/day recommended for healthy adults, with limiting processed meats).
• Eat high fiber foods (wheat bran, vegetables).
• Avoid exposure of meat to high heat.

Colorectal Polyps

• GI polyp is a discrete tissue mass protruding into the bowel lumen.
• Classification based on appearance (flat, sessile, pedunculated).
• Histologic characteristics are crucial for classification.
• Hyperplastic polyps, hamartomas, inflammatory polyps, and neoplastic polyps (tubular, tubulovillous, villous, serrated) have differing malignant potentials.
• Advanced adenomas (large size, villous histology, high-grade dysplasia) have a higher cancer risk.
• Sessile serrated polyps have a cancer development propensity similar to adenomas.

Colorectal Polyp Detection

• Polyps are often silent.
• Detected in asymptomatic screened individuals or incidentally during other investigations (e.g., iron deficiency anemia).
• Symptoms can include bleeding or obstruction.

Colorectal Polyp Diagnosis

• Fecal occult blood tests (FOBT/FIT).
• Fecal DNA screening tests.
• Colonography (CT or MRI) cannot detect small polyps accurately.
• Colonoscopy is effective for screening, diagnoses, and polypectomy .
• Sigmoidoscopy is useful for screening when combined with FOBT.
• NICE classification can help with assessing the risk of cancerous lesions.

Hereditary Colorectal Cancer Syndromes

• These account for a significant percentage of all large-bowel malignancies (~15%).
• Several well-defined syndromes are known.
• Patients with gene mutations may have elevated risks of cancers outside the colon.

Familial Adenomatous Polyposis (FAP)

• Genetic mutation in the APC gene causes the development of polyps in the colon.
• Typically, all polyps in FAP become cancerous.
• Colon cancer development begins in the teens/20s and progresses to total cases by 40s without treatment.
• Detection involves genetic testing and regular colonoscopies.
• Treatment generally involves total proctocolectomy (removal of colon and rectum).
• Upper endoscopy (EGD) is needed for stomach and duodenum surveillance from age 20 onwards.

Lynch Syndrome

• Also known as hereditary nonpolyposis colorectal cancer (HNPCC).
• Genetic predisposition to diverse cancers, primarily colorectal, due to malfunctioning DNA mismatch repair genes.
• Bethesda Criteria are used for diagnosis based on patient history and/or genetic testing.

Bethesda Criteria

• Criteria for diagnosing Lynch syndrome, based on family history and testing of cancerous tissue (MSI or MMR deficiency).

Molecular Genetic Evidence (Further Details)

• Several genetic alterations in oncogenes and tumor suppressor genes (like APC, KRAS, DCC, and p53) drive the development and progression of colon cancer.
• The progression from polyps to malignant cancer takes ~10-20 years with progression through stages from initiation to metastasis).

Molecular Genetic Testing (Used in Lynch Syndrome)

• MLH1, MSH2, MSH6, and PMS2 are important genes involved in Lynch syndrome; certain genetic variations in these genes affect risk.

This quiz explores key facts about colorectal cancer (CRC), including its prevalence, screening methods, and the importance of early detection. It highlights how screening for at-risk individuals can dramatically decrease incidence and mortality rates. Understand the epidemiology and risk factors associated with this common cancer.