Colorectal Cancer

Epidemiology & Risk Factors - Cancer's Spread & Seeds

• Incidence: Globally common; rising in India. Peak age >50 yrs. M>F.
• Modifiable Risks:
  • Diet: ↓Fiber, ↑Red/processed meat.
  • Lifestyle: Obesity, smoking, alcohol, physical inactivity.
• Non-Modifiable Risks:
  • Family Hx: CRC/polyps (1st degree: ~2x risk).
  • Genetic: FAP, Lynch syndrome (HNPCC).
  • IBD: Ulcerative Colitis (UC) > Crohn's Disease (CD).
  • Personal Hx: Adenomatous polyps.

⭐ Most common inherited CRC: Lynch syndrome (HNPCC), due to mismatch repair (MMR) gene defects.

Pathology & Genetics - Malignant Makeover

• Histology: Adenocarcinoma (>90-95%).
  • Variants: Mucinous, Signet-ring cell (poor prognosis), Medullary (MSI-H, better prognosis).
• Key Genetic Pathways:
  • Chromosomal Instability (CIN) (~80-85%): APC (early) → KRAS → TP53 (late). FAP-associated. (📌 AK-53: APC, KRAS, p53)
  • Microsatellite Instability (MSI) (~15-20%): Defective DNA Mismatch Repair (dMMR) genes (MLH1, MSH2, MSH6, PMS2). MSI-H. Lynch Syndrome. Right-sided, mucinous, lymphocytic infiltrate.
  • Serrated Pathway: BRAF mutations, CIMP.

⭐ Lynch Syndrome (HNPCC) accounts for 2-5% of all CRCs and is due to germline mutations in MMR genes.

Clinical Features & Diagnosis - Symptoms & Sleuthing

• Common Symptoms: Altered bowel habits (constipation/diarrhea), rectal bleeding (hematochezia/melena), abdominal pain/mass, unexplained weight loss, iron-deficiency anemia.
  • Right-sided (ascending colon): Often insidious; anemia (occult blood loss), fatigue, vague abdominal pain. Mass palpable late.
  • Left-sided (descending/sigmoid): Change in bowel habit (pencil stools), colicky pain, overt bleeding, obstructive symptoms.
  • Rectal: Rectal bleeding (often bright red), tenesmus, urgency, feeling of incomplete evacuation.
• Diagnostic Approach (Sleuthing):
  • Digital Rectal Exam (DRE): Essential for low rectal lesions.
  • Fecal Occult Blood Test (FOBT) / Fecal Immunochemical Test (FIT).
  • Labs: CBC (for anemia), LFTs, Carcinoembryonic Antigen (CEA) - baseline for prognosis & recurrence monitoring.

  ⭐ Unexplained iron deficiency anemia in an adult (especially male or postmenopausal female) warrants investigation for colorectal cancer.

  • Colonoscopy: Gold standard for diagnosis; allows visualization & biopsy.

Staging & Management - Levels & Lifelines

• Staging (TNM):
  • T: T1-T4 tumor depth.
  • N: N0-N2 lymph nodes.
  • M: M0 (no metastasis), M1 (yes).
  • Workup: CT C/A/P, Pelvic MRI (rectal), CEA.
• Management:
  • Colon Cancer:
    • Non-metastatic: Surgery (e.g., hemicolectomy). Adjuvant chemo (FOLFOX) for Stage III/high-risk Stage II.
  • Rectal Cancer:
    • Early (T1-2N0 low risk): Surgery.
    • Locally Advanced (T3/4 or N+): Neoadjuvant Chemoradiotherapy (NCRT) → Total Mesorectal Excision (TME) surgery (APR/LAR) → Adjuvant chemo.

    ⭐ TME surgery post-NCRT for locally advanced rectal cancer is standard, ↓ local recurrence.

  • Metastatic (Stage IV): Palliative chemo ± targeted Rx (anti-EGFR/VEGF) ± surgery.

Screening & Prevention - Early Watch & Ward

• Average Risk (Age >45-50):
  • Annual FOBT/FIT.
  • Sigmoidoscopy q5 yrs.
  • Colonoscopy q10 yrs (Gold Standard).
• High-Risk (earlier/frequent):
  • Family Hx CRC/adenoma.
  • IBD (UC/Crohn's >8-10 yrs).
  • FAP (scope from 10-12 yrs), Lynch (scope from 20-25 yrs).
• Prevention:
  • Diet: ↑Fiber, ↓Red meat.
  • Lifestyle: Exercise, healthy weight, no smoking/alcohol.
  • Aspirin (select high-risk).

⭐ Lynch syndrome (HNPCC): most common inherited CRC, from mismatch repair gene defects.

High‑Yield Points - ⚡ Biggest Takeaways

• CEA is for prognosis and recurrence monitoring, not screening.
• Lynch syndrome (HNPCC): Most common hereditary CRC, due to DNA mismatch repair gene defects.
• Right-sided cancers often present with iron-deficiency anemia and occult bleeding.
• Left-sided cancers typically cause altered bowel habits, tenesmus, and obstruction.
• Liver is the most common site of distant metastasis from colorectal cancer.
• FAP (APC gene mutation): Near 100% cancer risk; prophylactic colectomy is standard.