Colorectal cancer

Question 1

five symptoms of colorectal

Answer 1

occult or overt rectal bleeding 
change in bowel habits 
pain and discomfort in bowel
weakness/fatigue 
weight loss

Question 2

inside to outside of colonic histology (and what it’s made of)

Answer 2

mucosa (epithelial goblet cells making crypts and lamina propria)
muscularis mucosa (thin muscle layer aids peristalsis)
submucosa (dense irregular connective tissue, vasculature and nerves)
MUSCULARIS EXTERNA made up of:
- inner circle
- outer longitudinal
Serosa (intraperitoneal lining)

Question 3

TNM staging pT (extent of local invasion)

Answer 3

pT0 - no evidence of primary tumour 
pT1 - tumour invades submucosa 
pT2 - tumour invades muscularis propria 
pT3 - invades into subserosa 
pT4 - tumour perforates visceral peritoneum (4a) and/or directly invades other organs

Question 4

What is grade

Answer 4

differentation - architecture and specifically gland formation (how close does it resemble a normal gland)

Question 5

Other prognostic factors than grade/staging

Answer 5

tumour deposits
venous invasion
lymphatic invasion
perineural invasion

Question 6

colorectal cancer usually arises from what

Answer 6

a polyp (10-15y) 
origin cell: stem cell in base of crypt

Question 7

what are the two major pathways to neoplastic disease

Answer 7

1. adenoma to carcinoma (chromosomal instability)

2. serrated neoplasia sequence (microsatellite stable/instable)

Question 8

specific risk factors for CRC (4)

Answer 8

age >50
polyps in colon (tubulovillous adenoma)
family history <10% (FAP, HNPCC)
ulcerative colitis

Question 9

red flags for CRC

Answer 9

change in bowel habits 
per rectal bleed 
iron deficiency anaemia 
weight loss/appetite 
family history

Question 10

investigations

Answer 10

colonscopy
CT colonogram
bowel screening programme

Question 11

who is offered bowel screening

Answer 11

every 2 years to M/W aged 60-74

Question 12

25 y/o woman with persistent diarrhoea and rectal bleed. which investigation would you do?

Answer 12

flexible sigmoidoscopy

Question 13

55 y/o with Hx of painless jaundice for 4 weeks. which investigation?

Answer 13

abdo USS

Question 14

two main types of genetic colorectal cancer

Answer 14

familial adenomatous polypopsis

hereditary nonolyposis colon cancer (HNPCC or Lynch)

Question 15

FAP
hereditary
features

Answer 15

autosomal dominant

large number of polyps 100+ developing from adolescence. 90% have pigmented lesions in retina (CHRPE)

Question 16

what’s the gene defect in FAP?

Answer 16

adenomatous polyposis coli (APC) gene on chrom 5.

nonsense or frameshift mutation

Question 17

how to test for gene defect in FAP

Answer 17

protein truncation test

direct sequencing

Question 18

APC is a tumour suppressor gene. what does it normally do

Answer 18

bind beta catenin

bind microtubules

Question 19

what is beta catenin

Answer 19

a transcription factor usually present at low levels. when a cell wants to prolif, it synthesises lots of it. stimulates genes that promote cell division

when not needed - degraded by APC

APC keeps levels of beta-cat low.

Question 20

why do apc defects affect the colon

Answer 20

normally Wnt pignalling is inactive halfway up the villus

when defect - activated all the way up - cells don’t know where they are. disordered signalling

Question 21

extra-intestinal involvement of FAP CRC

Answer 21

masses of benign tumours 
jaw cysts 
sebaceous cysts 
osteomata 
pigmented lesions of the retina (CHRPE)

Question 22

Features of HPNCC/lynch syndrome

Answer 22

low number of polyps

can be underlying cause of other tumours (endometrium, ovarian, small intes, stomach)

Question 23

what do the defective genes in HNPCC mutations have in common

Answer 23

they all recognise when DNA bases haven’t been matched up properly (mismatch repair genes)

either involved in recognising the mismatch or cutting away section for repair

Question 24

what regions are more susceptible to errors in DNA base matching

Answer 24

repetitive regions (microsatellite instability)

Question 25

how to test for HPNCC defect

Answer 25

look at repeat legnths
(will be normal microsatellite stable in FAP)

look at IHC (matrix)

Question 26

does FAP or HNPCC have higher mutation rate?

Answer 26

HNPCC

Question 27

is penetrance higher for FAP or HNPCC

Answer 27

FAP

Question 28

if known FAP/HNPCC - what screening

Answer 28

biannual colonoscopy from 25 years

Question 29

Cetuximab drug for what

Answer 29

inhibits the proliferation that happens as result of eGFR signalling (used if wildtype Kras)

Question 30

why do people predisposed take aspirin?

Answer 30

inhibit COX-2 which is inc in early stages of CRC
increased prostaglandin synthesis
stimulates proliferation and angiogeneisis