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

Lecture 24 Colorectal Cancer Flashcards by Jessica Eze

Risk factors for CRC

Sporadic
Familial
HNPCC, FAP
IBD

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Risk factors for sporadic cases

•	Age 
•	Male gender
•	Previous adenoma/CRC
•	Environmental influences:
–	Diet (fibre, fruit &amp; veg,
 calcium, red meat, alcohol,)
–	Obesity
–	Lack of exercise
–	Smoking
–	Diabetes Mellitus
•	Colorectal Polyps:

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What are the 3 main histological types of adenomas

Tubular
Villous
Intermediate tubulovillous

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Morphologically how can adenomas present

Pedunculated

Sessile

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What changes lead to the transition of normal epithelium to small sdenoma

APC mutation
MCC mutation
5q deletion
c-myc activation
bel-2 mutation

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What changes lead to the transition from small adenoma to are adenoma

KRAS mutation

c-yes mutation

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What causes the transition from large adenoma to invasive adenocarcinoma

Chromosome 17p, 18q deletions

p53 mutation

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What causes the change from invasive adenocarcinoma to metastases

nm23 deletion

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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

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Investigation for CRC

Colonoscopy

Tissue bx

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Radiological imaging for CRC

• Barium enema
• CT colonography
o 3D virtual colonoscopy

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Dukes A

Confined to mucosa

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Dukes B

Invasion through muscularis without LN involvement

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Dukes C

Invasion through muscularis with regional LN involvement (1-4)

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Dukes D

Presence of distant metastases

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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

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