Bowel cancer Flashcards
Risk factors for bowel cancer
1) environmental factors (eg migration from high risk to low risk, eating foods rich in red meat/fat, not consuming fruit/veg, physical inactivity/ high BMI)
2) longstanding ulcerative colitis
3) crohn’s disease
4) presence of adenoma in large bowel
5) prev history of bowel cancer surgery
6) fam Hx bowel cancer
7) old age
How does a high fibre diet reduce bowel cancer
by increasing formation of short chain fatty acids which promote healthy gut microbes which cause apoptosis. This reduces proliferation of potentially neoplastic cells
by increasing stool bulk thus decreasing tansit time> potential carcinogens in stool have shorter contact with bowel mucosa
by reducing secondary bile acid formation which are potentially carcinogenic
What is a polyp
a protrusion into a hollow viscus
What is the adenoma-carcinoma sequence
a stepwise progression to bowel cancer from normal mucosa to adenoma to cancer
what is the evidence for adenoma-carcinoma sequence
observational studies have shown that most sporadic cancers arise from adenomas:
a) populations that have high prevalence adenomas have high prevalence cancer
b) 60% of cancer arise in left colon and most adenomas arise in this region too
c) risk of cancer directly related to number of polyps
f) removal of adenomas reduces the incidence of bowel cancer
dysplasia
cells have morphological features of cancer without invasion
a polyp can be benign (hyperplastic), dysplastic (adenoma) or cancerous
what is familial adenomatous polyposis
> pts have minimum 100 polyps to make diagnosis
polyps are dysplastic = adenomas
100% risk of developing cancer by age 30
contributes to 1% of bowel cancer
> hereditary autosomal dominant condition, defective APC gene
pts acquire first abnormal gene in utero as germ cell mutation (first hit) and to develop polyps, a second genetic abnormality in somatic cells (second hit)
what is the two hit hypothesis. Apply to FAP and sporadic adenomas
in FAP the pt is born with a single genetic abnormality (first hit) and acquires the second genetic abnormality after birth (second hit)
in sporadic adenomas person acquires two hits in somatic cells only
what is loss of heteozygosity in cancer eg FAP
mutation in APC gene, one copy = heterozygous following ‘first hit’
‘second hit’: cells will acquire two identical copies of the abnormal genes ie become homozygous. these lose heterozygosity
after second hit cells progress with adenoma-carcinoma sequence
what genetic abnormalities are associated with bowel cancer
> Lynch syndrome
FAP
Serrated polyposis
What is lynch syndrome
> familial cancer affecting the caecum and right colon before age 50
associated with endometrial, ovarian, small bowel and cancer of urinary tract
accounts 2-3% of bowel cancer
no precursor polyps
genetic of lynch syndrome
how do we assess lynch syndrome
mismatch in DNA causes ‘microsatellite instability’ - a hallmark of defective mismatch repair
at least 4 genes are involved in pathogenesis
similar to FAP pts inheritive defective mismatch repair gene in utero (first hit) and acquire second copy after birth (second hit) & develop cancer
assessment: >one pt should be first degree relative
> 2 or more generations affected
> cancer in at least one relative before age 50
> FAP excluded
symptoms of bowel cancer
how do we diagnose bowel cancer
>can be asymptomatic > change in bowel habit: constipation alternating with diarrhoea due to an obstructive cancer > bleeding from rectum > anaemia esp with caners of caecum > abdominal pain due to obstruction
> Hx and clinical examination
patients who present with anaemia: upper GI and lower GI endoscopy
flexible sigmoidoscopy and colonoscopy and biopsy
CT colonography for pts who can’t tolerate colonoscopy
staging CT scan for distal metastasis
MRI for rectal cancer to asses local spread
how is adenocarcinoma graded
dukes staging
well, moderate or poorly differentiated
dukes staging:
>dukes A: cancer involves part of bowel wall; no lymph node metastasis
>dukes B: cancer involves full thickness of bowel wall; no LN metastasis
>dukes C: cancer involves any part of bowel wall with LN metastasis
>dukes D: denotes liver or other distant metastasis
TNM staging (Tumour node metastasis)
T1: cancer involves submucosa
T2: cancer involves inner layer of muscularis propria
T3: cancer involves full thickness of bowel wall
T4: perforated cancer or cancer cells on serosal surface
N1: <4 lymph nodes with metastasis
N2: 4 or more LN metastasis
M1: distant metastasis (liver)
