Lecture 24 Colorectal Cancer Flashcards
Risk factors for CRC
Sporadic
Familial
HNPCC, FAP
IBD
Risk factors for sporadic cases
• Age • Male gender • Previous adenoma/CRC • Environmental influences: – Diet (fibre, fruit & veg, calcium, red meat, alcohol,) – Obesity – Lack of exercise – Smoking – Diabetes Mellitus • Colorectal Polyps:
What are the 3 main histological types of adenomas
Tubular
Villous
Intermediate tubulovillous
Morphologically how can adenomas present
Pedunculated
Sessile
What changes lead to the transition of normal epithelium to small sdenoma
APC mutation MCC mutation 5q deletion c-myc activation bel-2 mutation
What changes lead to the transition from small adenoma to are adenoma
KRAS mutation
c-yes mutation
What causes the transition from large adenoma to invasive adenocarcinoma
Chromosome 17p, 18q deletions
p53 mutation
What causes the change from invasive adenocarcinoma to metastases
nm23 deletion
Presentation of CRC
- Rectal bleeding (especially if mixed in with stool)
- Altered bowel opening to loose stools >4 weeks
- Iron Deficiency Anaemia men of any age and non-menstruating women (more likely to have right sided colonic malignancy)
- Palpable rectal or right lower abdominal mass
- Acute colonic obstruction if stenosing tumour
- Systemic symptoms of malignancy: Weight loss, Anorexia
Investigation for CRC
Colonoscopy
Tissue bx
Radiological imaging for CRC
• Barium enema
• CT colonography
o 3D virtual colonoscopy
Dukes A
Confined to mucosa
Dukes B
Invasion through muscularis without LN involvement
Dukes C
Invasion through muscularis with regional LN involvement (1-4)
Dukes D
Presence of distant metastases
T1
T2
T3
T4
Confined to submucosa
Confined to muscularis
Confined to serosa
Branched serosa, invading other structures
N0
N1
N2
No tumour involvement in regional LN
Tumour seen in up to 3 regional L
Tumour seen in 4+ regional LN
M0
M1
No metastases to distant organs
Metastases to distant organ
What type of surgery would Dukes A and cancer polyps require
Endoscopic or local resection
Screening methods for CRC
FOBT
FIT
Flexible sigmoidoscopy
CT colonography
Describe the Scottish Bowel Screening Programme
Age 50-74 years
FOBT every 2 years
If FOBT positive colonoscopy
FOBT has low positivity is what gender
Women
Describe the Faecal Immunochemical test
– Specific for human haemoglobin
– Automated
– Quantitative
– User friendly format that increases uptake
What type of disease is– FAP (familial adenomatous polyposis)
Autosomal dominant condition
What is the cause of FAB
Mutation of the APC gene on chromosome 5
How is FAP prevented from becoming malignant
Screening – annual colonoscopy from age 10-12 yrs
Prophylactic proctocolectomy (surgical removal of the rectum and all or part of the colon) usually age 16 - 25 yrs
• NSAIDs chemoprevention
Sulindac reduces polyp number and prevents recurrence of higher-grade adenomas in the retained rectal segment
What type of disease is HNPCC (hereditary non-polyposis colorectal cancer)
Autosomal dominant
What mutation causes HNPCC
Mutation in DNA mismatch repair (MMR) genes
- e.g MLH1 and MSH2
Diagnosis of HNPCC
Tumours typically have a molecular characteristic called microsatellite instability (MSI) - frequent mutations in short repeated DNA sequences (microsatellites).
Diagnosis – clinical criteria (Amsterdam / Bethesda), genetic testing
2 yearly colonoscopy
Other high risk groups of CRC
Family history
IBD
Previous CRC
Previous adenomas
