Early adenomas lose APC; accumulate additional mutations over 10–15 years; progression to carcinoma. Explains why CRC risk rises with age and screening detects adenomas before malignancy.
LO 4 — Molecular
What is the serrated pathway and what genes distinguish it from the adenoma-carcinoma sequence?
Contrasts with CIN pathway. Sessile serrated polyps follow this route; can progress to CRC faster; higher risk of right-sided cancer and CIMP-high phenotype.
LO 4 — CRC
How do right-sided and left-sided colorectal cancers differ clinically?
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Answer
Right-sided: anemia (iron-deficiency), occult blood, palpable mass, may be asymptomatic Left-sided: apple-core strictures, obstruction, change in bowel habits, visible blood in stool
Right = larger lumen, proximal obstruction less likely. Left = narrower lumen, obstructive symptoms earlier.
LO 3 — Crohn vs UC
What is the "CHRISTMAS" mnemonic for Crohn disease complications?
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Answer
C = Cobblestone, H = fistulas (Holes), R = Rectal bleeding, I = Ileitis, S = Strictures, T = Transmural, M = skip lesions (patchiness), A = Abdominal pain, S = Sigma (sigmoid) spared
LO 1 — Signs & Symptoms
What is toxic megacolon and why is it a medical emergency?
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Answer
Dilation of colon (>6cm) during severe IBD flare, fulminant colitis, or C. difficile infection
Risk of perforation, sepsis, death. Presents with abdominal distension, pain, fever, altered mental status. Managed with NPO, IV fluids, antibiotics; surgery if perforation or no improvement in 48h.
LO 1 — IBD Surveillance
What are the surveillance recommendations for IBD-associated CRC?
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Answer
Colonoscopy every 1–2 years after 7 years of IBD (earlier if extensive disease or primary sclerosing cholangitis)
PSC + UC = annual surveillance. p53 mutations appear early in IBD-associated CRC. Dysplasia detection is key to preventing malignancy.
LO 4 — Hereditary Syndromes
What gene is mutated in FAP, and what is the cancer risk?
Hundreds to thousands of adenomas develop by age 20–30; nearly 100% CRC risk by age 50 if untreated. Screening begins age 10–12; prophylactic colectomy often performed by age 20–25.
LO 4 — Hereditary Syndromes
What is Lynch syndrome (HNPCC) and which genes are involved?
Causes microsatellite instability (MSI-high); ~70% lifetime CRC risk by age 70. Accounts for 2–4% of all CRCs. Colonoscopy every 1–2 years from age 20–25.
Question 1
In Crohn disease, the pattern of inflammation distinguishes it from UC, which is limited to the .
Hint: One disease goes deep; the other stays shallow.
Question 2
The histologic hallmark of Crohn disease is the presence of , while UC shows .
Granulomas in Crohn; neutrophil-filled crypts in UC.
Question 3
C. difficile produces two exotoxins: and . Both inactivate proteins, disrupting tight junctions.
Both toxins are named with letters; they damage the Rho family of GTPases.
Question 4
Diverticula are "false diverticula" because they herniate only the through the muscular layer, not the entire bowel wall.
False = not all layers; herniation occurs at weak points.
Question 5
The primary treatment of C. difficile colitis is or . For recurrent infection, is effective.
Oral antibiotics are first-line; FMT for refractory disease.
Question 6
Adenomatous polyps progress to carcinoma via the . The first mutation is usually in .
APC → KRAS → p53 over years to decades.
Question 7
Sessile serrated polyps follow a different molecular pathway called the , driven by mutations and resulting in .
BRAF → CIMP → MSI; very different from APC-KRAS-p53.
Question 8
IBD-associated CRC risk increases significantly after of disease. Patients with have even higher risk and require annual surveillance.
Each statement below may be true or false. Click TRUE or FALSE, then see the explanation.
Trap 1
Ulcerative colitis can involve the entire GI tract, including the small bowel and proximal colon, with skip lesions.
FALSE. UC is characterized by continuous mucosal involvement starting at the rectum and extending proximally—no skip lesions. The terminal ileum is typically spared. Transmural involvement and skip lesions are hallmarks of Crohn disease, not UC.
Trap 2
Pseudomembranous colitis is always caused by antibiotic use.
FALSE. While antibiotic-associated C. difficile is most common, C. difficile colitis can occur without recent antibiotics—especially in hospitalized or immunocompromised patients. Antibiotics are a major risk factor but not required.
Trap 3
True diverticula include only the mucosa herniated through the muscular wall.
FALSE.False diverticula (most common in colon) include only mucosa + submucosa. True diverticula (found in small bowel) include all layers. Colonic diverticula are false—herniation occurs at vasa recta weak points.
Trap 4
The adenoma-carcinoma sequence is driven primarily by BRAF mutations and microsatellite instability.
FALSE. The classic adenoma-carcinoma sequence is driven by APC → KRAS → p53 mutations (CIN pathway). BRAF mutations and MSI characterize the serrated pathway (sessile serrated polyps), which is a different route to CRC.
Trap 5
Right-sided colorectal cancers typically present with obstructive symptoms and "apple-core" appearance on imaging.
FALSE.Left-sided CRCs present with obstruction and apple-core strictures because the left colon has a narrower lumen. Right-sided CRCs have a larger lumen and typically present with anemia and occult blood, not obstruction.
Trap 6
Tubular adenomas have the highest malignant potential and require the most aggressive surveillance.
FALSE.Villous and tubulovillous adenomas have higher malignant potential. Tubular adenomas are the most common but have lowest risk. The "Big, Villous, Bad" rule captures high-risk features: large size, villous histology, and high-grade dysplasia.
Trap 7
Toxic megacolon is a specific complication of Crohn disease and does not occur in ulcerative colitis.
FALSE. Toxic megacolon can occur in both Crohn disease and UC during severe, fulminant flares. It also occurs with fulminant C. difficile colitis. It is not pathognomonic for Crohn disease.
Trap 8
MSI-high colorectal cancers are responsive to checkpoint inhibitors like pembrolizumab.
TRUE.MSI-high tumors have high mutational burden and are responsive to immune checkpoint inhibitors (pembrolizumab, nivolumab). This is a key insight: serrated pathway CRCs with MSI may respond better to immunotherapy than CIN-pathway CRCs.
Crohn Disease vs Ulcerative Colitis Comparison
Feature
Crohn Disease
Ulcerative Colitis
Pattern of inflammation
Skip lesions (patchy)
Continuous from rectum
Depth of involvement
Transmural (all layers)
Mucosa + submucosa only
Location
Terminal ileum > colon; can involve entire GI tract
Clinical pearl: Most diverticulosis is asymptomatic and discovered incidentally. Acute diverticulitis is infection/inflammation of a diverticulum; uncomplicated cases managed medically; complicated cases (perforation, peritonitis) require surgery.
Big, Villous, Bad rule: Adenomas >10mm, villous histology, or high-grade dysplasia have higher CRC risk and shorter surveillance intervals (3 years or sooner). Sessile serrated lesions require aggressive follow-up due to faster progression.