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)
