bowel cancer: pathology and screening process

Question 1

why use the term bowel cancer

Answer 1

public understanding
devised following survey following screening programme
only applies to large intestine

Question 2

how common is bowel cancer

Answer 2

1/3 most common cancer in women and men (breast/prostate and lung)
high incidence in west, low in Asia and central africa
affects men and women equally

Question 3

why does bowel cancer occur

Answer 3

environmental disease- preventable
migrating to high risk area inc risk eg Japan to USA study
red meat and fatinc
veg, fruit anf fibre dec by inc faecal bulk and reduce transit time
physical activity and low BMI - low risk

Question 4

risk factors for bowel cancer

Answer 4

inc
red meat and fat
UC, crohn’s (lesser), adenoma in LB, prev history of bowel cancer surgery, FH, old age

veg, fruit anf fibre dec by inc faecal bulk and reduce transit time
physical activity and low BMI - low risk

Question 5

how does a high fibre diet reduce bowel cancer

Answer 5

inc formation of short chain FAs promoting healthy gut micro-organism and reduce proliferation of neoplastic cells
inc stool bulk to reduce transit time so carcinogens have less contact with mucosa
high fibre diet stops secondary bile acids, potentially carcinogenic

Question 6

what is a polyp

Answer 6

protruding growth into a hollow viscus can be being, adenoma or malignant
in bowel cancer its either innocent or precancerous
if polypoid, not called polyp, just cancer

Question 7

what are most polyps in the LB

Answer 7

adenomas (precancerous lesions consisting of dysplastic epithelium)
diagnosis can only be confirmed on microscopic exam by pathologist

Question 8

what is dysplasia

Answer 8

cells have morphological features of cancer but without invading surrounding tissue
low grade - early precancerous features
high grade- advanced precancerous with high risk of invasion

Question 9

what are the pathological features of polyps

Answer 9

hyperplastic - numerous goblet cells, lace like patterns
tubular adenoma - test tube like appearance
villous adenoma - finger like
tubovillous adenoma - mix of tubular and villous features

Question 10

what is the adenoma-carcinoma sequence

Answer 10

stepwise progression from normal mucosa to adenoma to cancer
morphological features also mirrored at genetic level where there are stepwise alterations
carcinoma of bowel example

Question 11

what is the evidence of adenoma-carcinoma sequence

Answer 11

observation studies have shown sporadic cancer not genetically determined but arising from adenomas
shown by
pops high prevalence of adenoma - high prevalence of cancer
diet of adenomas in LB mirrors that of bowel cancer (eg 60% both arise from left colon and rectum)
peak incidence of polyps predates cancer dev
residual adenoma found
risk of cancer related to amount of polyps
remove adenomas ad reduce risk of cancer

Question 12

what is the genetic basis of the adenoma-carcinoma sequence

Answer 12

familial adenomatous polyposis (FAP)
min of 100 polyps in LB, usually have 500-2500
dysplastic so adenomas 
100% risk of cancer by 30
prophylactic colectomy at 20
cont to 1% bowel cancer

Question 13

genetics of FAP in bowel cancer

Answer 13

hereditary autosomal dominant
defective gene of Chronic 5q21 (APC gene)
get 1st abnormal gene in utero
2nd genetic abnormality in somatic cells
dev polyps young (need 2nd hit to dev)

Question 14

two hit hypothesis in hereditary and sporadic bowel cancer

Answer 14

FAP born with first hit and acquires 2nd hit after birth to develop adenomas then cancer
in sporadic cancer, two hits in somatic cells = a then c
Knudosn to explain hereditary retinoblastoma

Question 15

what does the 2nd hit result in

Answer 15

loss of heterozygosity (2 abnormal genes)
mutation of APC gene important to initiate BC
2nd hit - homozygous for cancer
acquire more genetic abnormalities to progress with AC seq

Question 16

what is the stepwise progression from adenoma to cancer

Answer 16

inherited or acquired mutation 1st high
hyperproliferative epithelium - methylation abnormalities 2nd hit
early A - mutation K-RAS
int A and late A- lose TSGs
invasive cancer - telomerase activity for immortality

Question 17

genetic abnormalities associated with bowel cancer

Answer 17

Lynch syndrome/HNPCC
FAP
attenuated FAP (<100 adenomas)
familial colorectal cancer type X
MUTYH associated polyposis
serrated polyposis syndrome
hamartomatous polyposis syndrome

Question 18

what is Lynch syndrome

Answer 18

familial cancer affecting caecum and right colon before 50
ass with endometrial, SB, UT cancer
2-3% BC
no precursor polyps
BC young pts to advanced cancer tested for Lynch routinely

Question 19

what are the genetics of Lynch syndrome

Answer 19

different from FAP
during replication DNA BPs mismatch
no repairs - errors accumulate - microsatellites (tandem repeat of nucleotides in DNA, fixed for life)
expansion and contraction of repair nucleotides (=MS instability)
as FAP inherit 1st and acquire 2nd

Question 20

what genes are linked to LS and cancer

Answer 20

routinely test for MSH2, MLH1, PMSI and PMS2

Question 21

how is LS assessed

Answer 21

Amsterdam criteria
>3 relatives with LS related cancer (LB, SB, UT, endomet)
1 affected should be 1st deg relative of other 2
>2 successive gens
>1 diagnosed before 50
FAP excluded
tumour verified pathologically

Question 22

symptoms of bowel cancer

Answer 22

can be asymptomatic
change in bowel habit (constipation and diarrhoea from obstruction)
bleeding from rectum
anaemia (esp caecum due to slow occult blood loss)
abdo pain from obstruction

Question 23

how is bowel cancer diagnosed

Answer 23

history and examination
flexible sigmoidoscopy and colonoscopy with biopsy and histo exam 
CT colonography (if no colonoscopy)
staging CT
MRI for rectal cancer (local spread)

Question 24

what is the pathology of bowel cancer

Answer 24

graded as well, mod and poorly differentiated
well diff - normal mucosa
mod - most common
poor - minimal of no glandular differentiation

Question 25

how is bowel cancer staged

Answer 25

T- tumour, depth of invasion of bowel wall
N - lymph node metastasis
M - distant metastasis to liver or lung
bowel wall is mucosa to end of ext muscularis propria

Question 26

what are the types of T staging

Answer 26

T1 - invasion of submucosa, muscularis propria clear
T2 - muscularis propria but not full thickness invasion
T3 - full thickness bowel wall, nit serosa
T4 - present on serosa

Question 27

how is cancer N staged

Answer 27

Lymph node metastasis

eg Tn N1

Question 28

how is cancer T staged

Answer 28

liver metastasis M1

Tn Nn Mn

Question 29

what is bowel cancer screening

Answer 29

looking for early signs in healthy people
prevent cancer by detecting polyps precancer
curable stage

Question 30

methods for BCS

Answer 30

stool test or faecal immunochemical test (FIT)
Flex sigmoidoscopy (FS) (detects polyps and cancers in rectum and left colon)
Colonoscopy ideal but needs expert and sedation
in UK FS at 55, FIT from 60-74 yrs (2years)

Question 31

what is Stool Testing and FIT

Answer 31

test for occult blood
FIT Ab-antigen reaction to Ab in blood
+ve doesn’t = BC
haemorrhoids and inflammation can cause +ve

Question 32

what is the science behind the stool test

Answer 32

Ulcerating cancers bleed silently
trauma to large polyps due to friction with stool can bleed
get stool kit, do test in home, sent to lab and processed by machine

Question 33

what happens with a positive stool test

Answer 33

referred for colonoscopy to detect polyps, early cancer and advanced cancer
FIT doesn’t detect non-bleeding polyps or cancer, repeated every two years