clinical oncology 2: colorectal cancer

Question 1

epidemiology of colorectal cancer:

Answer 1

• 4th most common cancer overall
• 2nd most common cancer cause of death (behind lung cancer)
• 25% adults have adenomas by 50 -> 5% become colorectal cancer

Question 2

what are the functions of the colon?

Answer 2

extract water from faeces

• faecal resevoir
• bacterial digestion eg for vitamin B & K

Question 3

what is the microanatomy of the colon?

Answer 3

IMAGE 1 crypts of Lieberkuhn

Question 4

why is the colon particuarly susceptible to cancer?

Answer 4

very high turnover of cells -> proliferation renders cells vulnerable

Question 5

what is a polyp?

Answer 5

any projection from a mucosal surface into a hollow viscus
- may be hyperplastic, neoplastic, inflammatory, hamartomatous etc

Question 6

what is an adenoma?

Answer 6

benign neoplasm of mucosal epithelial cells

Question 7

what are the types of colonic polyps?

Answer 7

• metaplastic/hyperplastic
• adenomas
• juvenile
• peutz jeghers
• lipomas

Question 8

what are hyperplastic polyps?

Answer 8

very common benign polyps

• 90% of all polyps
• <5mm
• cells well ordered
• multiple polyps often present IMAGE 2

Question 9

what are the types of colonic adenomas?

Answer 9

cell type: tubular / villous
protrusion: pedunculated / sessile
IMAGE 3

Question 10

what are tubular adenomas?

Answer 10

columnar cells with signs of dysplasia
(nuclear enlargement, multilayering, loss of polarity, increased proliferation, decreased differentiation, architectural disorganisation)

Question 11

what are villous adenomas?

Answer 11

mucinous cells with signs of dysplasia
(same as tubular + exophytic, frond-like extensions)
- rarely may be hypersecretory -> hypokalaemia

Question 12

what is dysplasia?

Answer 12

‘bad growth’ - abnormal growth of cells with some features of cancer

Question 13

how does ulcerative colitis affect the risk of colorectal cancer and why?

Answer 13

increases risk
- UC causes increased proliferation of cells in attempt to repair damage & inflammation damages basement membrane -> invasion is easier

Question 14

outline the adeno-carcinoma sequence:

Answer 14

IMAGE 4

Question 15

what mutation causes APC?

Answer 15

• 5q21 mutation
• site of mutation determines clinical variants
• many patients have prophylactic colectomy <30

Question 16

what genetic conditions predispose to colorectal cancer?

Answer 16

FAP (familial adenomatous polyposis): inactivation of APC tumour suppressor genes
HNPCC (hereditary non-polyposis colorectal cancer): due to microsatellite instability
(microsatellites are repeat sequences prone to misalignment, often mismatch repair genes)

Question 17

how does colorectal cancer present clinically?

Answer 17

• change in bowel habit
• bleeding PR
• iron deficient anaemia
• mucus PR
• bloating
• cramps
• weight loss, fatigue etc

Question 18

where do colorectal cancers usually occur?

Answer 18

signmoid colon or rectum

- others distributed fairly evenly

Question 19

what is the Duke’s classification?

Answer 19

first staging system that proved staging a cancer can improve its management
- TNM classification used nowadays

Question 20

how does the Duke’s classification work?

Answer 20

Duke’s A: growth limited to wall (muscularis propria), nodes negative
Duke’s B: growth beyond muscularis propria, nodes negative
Duke’s C1: nodes positive, apical lymph node negative
Duke’s C2: apical lymph node positive

Question 21

when are patients screened for colorectal cancer?

Answer 21

if deemed high-risk ie if they have:

• had a previous adenoma
• a close relative affected by colorectal cancer <45
• 2 close relatives ever affected by colorectal cancer
• evidence of a dominant familial cancer trait
• UC/Crohn’s
• heritable cancer within the family (including other sites)

Question 22

what is population screening?

Answer 22

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