Colorectal Cancer

Question 1

Describe the epidemiology of Colorectal cancer

Answer 1

Major Cancer in ‘developed’ countries
4th most common cancer overall
2 leading cause of cancer death overall, behind lung cancer

Question 2

What is the function of the colon

Answer 2

Extraction of water from faeces (electrolyte balance)

Faecal reservoir (evolutionary advantage)

Bacterial digestion for vitamins (e.g. B and K)

Question 3

Describe the micro anatomy of the colon

Answer 3

Crypts of Lieberkuhn

Made up of columnar, goblet and endocrine cells + STEM cells. Surrounded by ECM and mesenchymal cells

Question 4

Describe the turnover of the colon

Answer 4

2-5 million cells die every minute in the colon and these are replaced
Proliferation renders cells vulnerable (e.g. APC mutation prevents cell loss mutation)

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

Answer 6

benign neoplasm of the mucosal epithelial cells

Question 7

What are the types of polyp

Answer 7

Hyperplastic / metaplastic
Adenomas
Juvenile
Peutz Jeghers
Lipomas

Question 8

Describe the hyperplastic polyp

Answer 8

Benign
90% of all colonic polyps
<0.5cm
Cells well ordered (see right) 
Multiple polyps often present 
No malignant potential

Question 9

What type of cell can a colonic adenoma contain

Answer 9

tubular or villous (or tubulovillous if mixed)

Question 10

Describe the protrusion of colonic adenomas

Answer 10

pedunculated or sessile

Question 11

Which types of cell are sessile adenomas usually made up of

Answer 11

sessile ones tend to be more villous

Question 12

Describe tubular ademonas

Answer 12

Tubular adenomas are the most common type

Comprise columnar cells showing signs of dysplasia

Question 13

What are the signs of dysplasia

Answer 13

Nuclear enlargement
Multilayering
Loss of polarity
Increased proliferation
Decreased differentiation
Architectural disorganisation

Question 14

Describe villous adenomas

Answer 14

Comprise mucinous cells also showing the signs of dysplasia, with exophytic, frond-like extensions.
In rare cases they can be hypersecretory and lead to hypokalaemia.

Question 15

Explain how ulcerative colitis affects colorectal cancer risk

Answer 15

Causes increased proliferation in an attempt to repair damage, and the inflammation also damages the basement membrane, making invasion easier. Thus, UC causes a higher risk of colorectal cancer.

Question 16

What can be done to reduce risk of cancer

Answer 16

Remove any polyps

Question 17

Describe the adenoma-carcinoma sequence

Answer 17

1. Germline or somatic mutations of cancer suppressor genes (first hit)
2. Methylation abnormalities, inactivation of normal alleles (second hit)
3. Protooncogene mutation
4. Homozygous loss of additional cancer suppressor genes
5. Additional mutations
6. Gross chromosome alterations

Question 18

What are the 2 main ways in which genetic predisposition to colon cancer can occur

Answer 18

familial adenomatous polyposis (FAP)

hereditary non-polyposis colorectal cancer (HNPCC)

Question 19

How does familial adenomatous polyposis lead to genetic disposition to colon cancer

Answer 19

inactivation of APC tumour suppressor genes.

Question 20

How does hereditary non-polyposis colorectal cancer lead to genetic disposition to colon cancer

Answer 20

Due to microsatellite instability

Microsatellites are repeat sequences prone to misalignment, often mismatch repair genes.

Question 21

Describe the major clinical presentation of colorectal cancer

Answer 21

Change in bowel habit (more/less constipated, going more frequently, anything) 
Bleeding PR (per rectum)
Iron deficient anaemia otherwise unexplained

Question 22

What are the potential clinical presentations of colorectal cancer

Answer 22

Mucus PR
Bloating
Cramps (‘colic’)
Weight loss, fatigue, etc.

Question 23

Describe the distribution of colon cancer

Answer 23

Most colorectal cancers occur in the sigmoid colon or rectum, the rest distributed fairly evenly.

Since malignancy often develops from dysplasia, you can find small carcinomas
present within larger polyps.

Question 24

What proportion of colorectal cancers are moderately differentiated

Answer 24

70%
10% well
20% poorly

Question 25

Describe Dukes A

Answer 25

growth limited to wall (muscularis propria); nodes negative

Question 26

Describe Dukes B

Answer 26

growth beyond muscularis propria; nodes negative

Question 27

Describe Dukes C1

Answer 27

nodes positive; apical lymph node negative

Question 28

Describe Dukes C2

Answer 28

apical lymph node positive

Question 29

What features suggest that patients are at high-risk for colorectal cancer (and are screened)

Answer 29

Had a previous adenoma
A close relative affected by colorectal cancer <45yo
2 close relatives affected by colorectal cancer at all
Evidence of a dominant familial cancer trait
Ulcerative colitis or Crohn’s disease

Question 30

Define population screening

Answer 30

the practice of investigating apparently healthy individuals with the object of detecting unrecognised disease or a high risk of developing disease, and of intervening in ways that will prevent the occurrence of disease or improve the prognosis when it develops