Wk 16: GI cancers Flashcards
What is familial adenomatous polyposis (FAP)?
- Inherited mutation in APC gene
- Diagnosed: colonoscopy + genetic testing
- Develop age 40
- Colectomy in early life when detected
What are the variants in FAP?
Tumour supressor gene:
- Attenuated FAP: specific APC mutants, fewer polyps
- MUTYH: base excision repair
What are the risk factors of CRC?
- Inc red/processed meat
- Lack physical activity
- Obesity
- Alcohol + smoking
- Genetic predisposition
What could decrease the likelihood of CRC?
Fibre, chicken + fish
Where is sporadic CRC most commonly found?
- Descending colon
- Sigmoid colon (KRAS)
- Rectum (KRAS)
Where is IBD related CRC most commonly found?
Ascending colon (BRAF)
What is the CRC histology?
- Loss of normal architecture
- Hyperchromatic
- Invasion through submucosa
- Nucleus takes up greater proportion of cell
What are the 2 main sites for CRC metastases?
- Liver (most common): venous drainage from colon to liver
- Lungs: rare to see lungs alone
What is used to screen CRC?
- Faecal occult blood stool test
Endoscopy:
- Colonoscopy (gold standard)
- Flexible sigmoidoscopy
What is faecal occult blood stool test?
- Measure blood in stool
- Card coated w/ guaic resin
- Sample of stool applied to card
- Hydrogen peroxide developer sol applied
- Detects pseudoperoxidase activity of Hb
- +ve = sigmoidoscopy
What are the limitations of faecal occult blood stool test?
- +ve: red meat, cauliflower, uncooked veg + haemorrhoids
- -ve: vit C
What happens when a patient undergoes colonoscopy?
- Diet 3 days advance (low fibre + clear liquid)
- Bowel prep (laxatives)
- Every 5-10 yrs
- Detects: polyps, adenomas + tumours
- Usually for colitis associated CRC
What happens during sigmoidoscopy?
- Removal of polyps + takes biopsies
- Covers descending colon
- No sedation
- Red cost + shorter duration
What is the first treatment for CRC?
- Surgery to remove tumour + adjuvant chemo red metastases
- Adjuvant begins 6 wks after surgery
- Radio not usually used
When would you usually use radiotherapy?
- Not clear if tumour completely removed
- Unable to have surgery
- Rectal cancer to prevent recurrence
What are the agents used to target CRC?
- EGFR inhibitors
- VEGFR inhibitors: VEGF promotes neovasculature growth
- Immunotherapy: targets PD-1, inc immune response - usually when not responding to chemo
What can wild type patients receive + what renders this therapy ineffective?
- Cetuximab/panitumumab - EGFR MAb
- Ras mutant
What is the VEGF pathway in CRC?
- Tumour secretes VEGF
- VEGF inc blood vessel expression + movement to tumour
- Tumour inc blood supply
What are examples of VEGF MAb?
- Bevacizumab
- Aflibercept
- Ramucirumab
- Regorafenib
What are the key pathways in CRC?
- Mismatch repair deficiency
- High microsatellite instability
Mutations = abnormal antigens, targeted by immune cells
What agent is used as immunotherapy to target PD-1?
Pembrolizumab
What is the adjuvant treatment for Duke B + C colorectal cancer?
5-FU + folinic acid weekly
What is the adjuvant treatment for Duke C?
- FOLFOX (Oxaliplatin + 5 FU)
- CAPOX (Capecitabine & Oxaliplatin)
- Capecitabine
What is the treatment for advanced disease?
- FOLFIRI (Irinotecan + 5 FU)
- CAPIRI (Irinotecan & Capecitabine)
What is PD-L1?
Immune checkpoint that distinguishes self from nonself cells triggering an immune response against the tumour
What does the vogelstein model describe in CRC?
How accumulation of DNA mutation leads to CRC progression
What is the classification used in CRC?
Dukes
