Colorectal Cancer

Question 1

What cancer is the major cancer of the developed world?

Answer 1

Colorectal cancer

- Environmental (diet) and genetic factors in aetiology

Question 2

3 main functions of the colon

Answer 2

• Extraction of water from faeces
  (electrolyte balance)
• Faecal reservoir
• Bacterial digestion for vitamins (e.g. B and K)

Question 3

What type of carcinoma are most colon cancers?

Answer 3

Adenocarcinoma

Question 4

What is the rate of turnover of cells in the colon?

Answer 4

2-5 million cells per minute

Question 5

What is a polyp?

Answer 5

Any projection from a mucosal surface into a hollow viscus, and may be hyperplastic, neoplastic, inflammatory, hamartomatous, etc.

Question 6

What is an adenoma (of the colon)?

Answer 6

An adenoma is a benign neoplasm of the mucosal epithelial cells

Question 7

What are the different types of colonic polyp?

Answer 7

Metaplastic/hyperplastic

Adenoma

Question 8

State some characteristics of hyperplastic polyps.

Answer 8

• VERY COMMON (90% of all colonic polyps)
• They have NO malignant potential
• 15% have K-ras mutations

Question 9

What are the different types of colonic adenoma?

Answer 9

• Tubular
• Tubulovillous
• Villous
  NOTE: the more villous it is the worse it is

Question 10

What are the different shapes of colonic adenomas?

Answer 10

Pedunculated – Adenomas on a stalk (looks like a tree)

Sessile – Flat and raised adenoma (looks like a hedge)

Question 11

Describe the microscopic structure of tubular adenomas

Answer 11

• Columnar cells with nuclear enlargement, elongation, multilayering and loss of polarity
• Increased proliferative activity
• Reduced differentiation
• Complexity/disorganisation of architecture

Question 12

Describe the microscopic structure of villous adenomas

Answer 12

• Mucinous cells with nuclear enlargement, elongation, multilayering and loss of polarity
• Exophytic
• Rarely may have hypersecretory function and result in excess mucus discharge

Question 13

Where is the gene mutation that causes familial adenomaous polyposis (FAP aka APC) caused by?
Many patients with the mutation have what?

Answer 13

5q21 (Site of mutation determines clinical variants)

Many patients have prophylactic colectomy

Question 14

25% of adults have adenomas at age 50. What does the adenoma usually progress into? How do decrease the incidence of this progression?

Answer 14

Most carcinomas arise from adenomas

Endoscopic removal of polyps decreases the incidence.

Question 15

What are the two genetic pathways in colorectal cancer?

Answer 15

Adenoma-carcinoma sequence

Microsatellite instability

Question 16

What are microsatellites?

Answer 16

Repeat sequences of DNA that are prone to misalignment

Some microsatellites are found in coding sequences of genes which inhibit growth or are involved in apoptosis

Question 17

State two genetic diseases that predispose to colorectal cancer.

Answer 17

Familial adenomatous polyposis – inactivation of the APC tumour suppressor gene
HNPCC – microsatellite instability (affects mismatch repair genes)

Question 18

State some dietary factors that can increase the risk of colorectal cancer.

Answer 18

High fat
Low fibre
High red meat
Refined carbohydrates

Question 19

State two dietary deficiencies that can increase the risk of colorectal cancer.

Answer 19

Folates:
Folates are co-enzymes needed for nucleotide synthesis and DNA methylation.

MTHFR – Methylenetetrahydrofolate Reductase:

• Deficiency leads to disruption in DNA synthesis causing DNA instability and mutation.
• Decreased methionine synthesis leads to genomic hypomethylation and focal hypermethylation à gene activating and silencing effects.

Question 20

What is the clinical presentation of colorectal cancer?

Answer 20

Change in bowel habit
Pre-Rectal bleeding
Unexplained iron deficiency anaemia

Question 21

Describe the distribution of colorectal cancer.

Answer 21

Half of all cancers will occur in the rectosigmoid area, the remainder are distributed throughout the colon

Question 22

Describe the Dukes classification of colorectal cancers.

Answer 22

Dukes A
-Growth is limited to the mucosa/submucosa
- Nodes negative
Dukes B
- Growth beyond the muscularis propria (into serosa)
- Nodes negative
Dukes C1
- Nodes positive
- Apical nodes negative
Dukes C2
- Apical nodes positive

Question 23

How do tumours occurring in the caecum and right colon present typically, and why?

Answer 23

Tumours occurring in the caecum and right colon often present later and with vaguer symptoms, partly due to the capacity of the caecum to expand before getting blocked

Question 24

Diagnosis of colon cancer?

Answer 24

Diagnosis is usually by a combination of radiology, but particularly endoscopy.
As yet, there are no reliable markers of colorectal cancer than can be measured in the blood.

Question 25

State some clinical features that affect the prognosis of colorectal cancer.

Answer 25

Bowel obstruction (diminished prognosis)
Age < 30 (diminished prognosis)
Distant metastases (diminished prognosis)

Question 26

State some pathological features that affect the prognosis of colorectal cancer.

Answer 26

Depth of bowel wall penetration
Number of regional lymph nodes involved
Venous invasion
Lymphatic invasion
Degree of differentiation

Question 27

What are the criteria for a screening programme?

Answer 27

Condition should be important with respect to the seriousness and/or frequency
The natural history of the disease must be known in order to:
- Identify where screening can take place
- To enable the effects of any intervention to be assessed

Question 28

What are the characteristics of a screening test?

Answer 28

Simple and acceptable to the patient
Sensitive and selective
Cost effective
Screening population should have equal access to the screening procedure

Question 29

What does the NHS colorectal cancer screening look for?

Answer 29

Faecal occult blood (FOB)
If positive and 55-60 years = sigmoidoscopy
If positive and over 60 years = full colonoscopy

Question 30

State some patient prerequisites for admission to screening for colon cancer

Answer 30

• Previous adenoma
• 1st Degree relative affected by colorectal cancer before the age of 45
• 2 affected first degree relatives
• Evidence of dominant familial cancer trait