TOPIC
MECHANISM · DETAILS
FEATURES
CLUE
Age, adenomatous polyps, IBD, FAP, Lynch, family history, red/processed meat, low fiber, obesity, smoking, alcohol
Aspirin/NSAIDs reduce risk (COX-2)
S gallolyticus (bovis) endocarditis, C septicum → look for CRC
Chromosomal instability pathway
~80%
APC loss (normal mucosa → polyp) → KRAS (adenoma grows) → TP53 (carcinoma); COX-2 ↑
Classic adenoma-carcinoma sequence; mostly left-sided
"AK-53"
Microsatellite instability pathway
Mismatch-repair loss: germline (Lynch) or sporadic MLH1 promoter methylation; serrated lesions (BRAF, CIMP)
Right-sided, mucinous or signet ring, tumor-infiltrating lymphocytes
Better prognosis; responds to checkpoint inhibitors
Cecum, ascending colon; wide lumen, liquid stool
Exophytic mass; occult bleeding → iron-deficiency anemia, fatigue, weight loss
Older adult with iron deficiency = colonoscopy
Descending, sigmoid, rectum; narrower lumen, formed stool
Napkin ring growth → obstruction, change in bowel habits, "pencil" stools, hematochezia
Apple core lesion on barium enema
AD germline MLH1, MSH2, MSH6, PMS2 (or EPCAM) mutation
Few polyps; CRC often right-sided, < 50; endometrial (most common extracolonic), ovarian, gastric, small bowel, urothelial
3-2-1 rule: 3 relatives, 2 generations, 1 before 50 · sebaceous tumors = Muir-Torre
Lymphatic, then portal blood → liver (most common metastatic site); distal rectum → systemic (lungs)
Stage (TNM) is the strongest prognostic factor
Depth of invasion + nodes
Glycoprotein tumor marker
Elevated in many CRCs; also smokers, other cancers
Monitor recurrence — not for screening
Average risk from 45: colonoscopy every 10 years, annual FIT, stool DNA, CT colonography
Family history: start at 40 or 10 years before relative's diagnosis
Positive stool test → colonoscopy
Surgery ± chemo: 5-FU + leucovorin, oxaliplatin, irinotecan; cetuximab/panitumumab (EGFR); bevacizumab (VEGF)
Anti-EGFR antibodies work only if KRAS wild-type
Irinotecan → diarrhea · oxaliplatin → neuropathy