Bowel cancer: pathology and the screening process Flashcards
Key facts about bowel cancer
Third most common cancer in women after breast cancer and lung cancer
Third most common cancer in men after prostate and lung cancer
High incidence of bowel cancer in western world; low incidence in Asia and Central Africa
Affects men and women equally
Risk factors for bowel cancer
- Environmental disease (low to high population migration, red meats and fatty foods)
- Longstanding ulcerative colitis
- Crohn’s disease
- Presence of adenoma in large bowel
- Previous history of bowel cancer surgery
- Family history
- Old age
High fibre diet reduces cancer
Increases formation of short chain fatty acids which promote healthy gut microbes which induces differentiation, arrest growth of cells and cause apoptosis
Increases stool bulk so reduces stool transit time so potential carcinogens have shorter contact with bowel mucosa
Reduces secondary bile acid formation which are potentially carcinogenic
Polyp
Protrusion into hollow viscus
Can be benign adenoma or malignant
Adenoma in GIT
Pre-cancerous lesions
Consist of dysplastic epithelium
Dysplasia
Cells have morphological features of cancer but without invasion
Low grade dysplasia
Early precancerous features
High grade dysplasia
Advanced precancerous features
High risk of invasion if not removed
Pathological features of polyps
Hyperplastic- more goblet cells than normal mucosa; has a lace like pattern
Tubular adenoma- has test tube appearance
Villous adenoma- has finger like appearance
Tubulovillous adenoma- a mixture of the above
Adenoma- cacrinoma sequence
Stepwise progression to bowel cancer from normal mucosa to adenoma to cancer
Evidence for adenoma- carcinoma sequence
Populations that have high prevalence of adenomas have high prevalence of cancer
Distributions of adenomas in large bowel mirrors distribution of bowel cancer
Peak incidence of polyp predates cancer
Residual adenoma is found in early invasive cancer
Risk of cancer directly related to number of polyps
Genetic basis of multistep carcinogenesis
To understant genetic and morphological features of bowel cancer
Best to understand how bowel cancer develops in familial adenomatous polyposis
Familial adenomatous polyposis
Hundred to thousands of polyps in large bowel
Minimum of 100
Polyps are dysplastic so called adenomas
100% risk of development of cancer by 30
Prophylactic colectomy around 20
FAP contributes to 1% bowel cancer
Genetics of FAP in carcinogensesis
Hereditary autosomal dominant condition
Defective gene in Chr 5q21 called APX gene
Aquire first abnormal gene in utero as germ cell mutation
Develop polyps they acquire second genetic abnormality in somatic cells
Second hit paves way for development of polyps from young age throughout teens
Two hit hypothesis
In FAP patient is born with single genetic abnormal and acquires second after birth
Sporadic adenomas person acquires two hits in somatic cells
Loss of heterozygosity
Mutation of APC gene important in initiation of bowel cancer
One copy of abnormal gene, cells are heterozygous
Loss of second set of normal genetic material during second hit termed loss of heterozygosity
Hereditary non-polyposis colorectal cancer
Familial cancer affecting predominantly caecum and right colon before the age of 50
Associated with endometrial, ovarian, small bowel and cancer of urinary tract
2-3% of bowel cancers
No precursor polyps
Genetics of HNPCC
Very different from FAP
During replication DNA base pairs can mismatch
Without repairs errors accumulate and create microsatellite instability
Microsatellites are tandem repeat of nucleotides in DNA of an individual and are fixed for life
Genetics of HNPCC
Errors due to mismatch in DNA causes expansion and contractions of repeat nucleotides causing microsatellite instability
Several mismatch repair genes
At least four genes involved in pathogenesis of HNPCC
MSH2 (2p16) and MLH1 (3p21) genes accound for 30% of HNPCC
PMS1 and PMS2 also involved
Inherit defective copy in utero and second copy during life and develop cancer
Amsterdam criteria to assess for HNPCC
Three or more relatives with HNPCC associated cancer plus all of the following:
- one affected patient should be first degree relative of the other two
- two or more successive generations should be affected
- cancer in one or more affected relatives should be diagnosed before 50
- familial adenomatous polyposis excluded in any cases of colorectal cancer
- tumours should be verified by pathological examination
Symptoms of bowel cancer
Detected during screening
Change in bowel habit, constipation alternating with diarrhoea due to obstructive cancer
Bleeding from rectum
Anaemia especially with cancers of the caecum
Abdominal pain due to obstruction
How to diagnose bowel cancer
History and clinical examination
Patients with anaemia- upper GI and lower GI endoscopy
Flexible sigmoidoscopy and colonoscopy and biopsy
Barium enema for patients who cannot tolerate colonoscopy
Histological examination of biopsy
Staging CT scan for distal metastasis
MRI for rectal cancer to assess local spread
Pathology of bowel cancer
Graded as well, moderate or poorly differentiated
Well differentiated resembles normal colonic mucosa
Moderately differentiated most common
Poorly differentiated minimal or no glandular differentiation
Dukes staging
A: cancer involves part of bowel wall; no lymph node metastasis (90-95% 5yr survival)
B: cancer involves full thickness of bowel wall; no lymph node metastasis (60-70%)
C: cancer involves any part of the bowel wall with lymph node metastasis; usually full thickness of bowel wall involved (20-25%)
D: was not in the original classification; denotes liver or other distant metastasis (15%)
TNM staging
T1- cancer involves submucosa
T2- cancer involves inner of muscularis propria
T3- cancer involves full thickness of the bowel wall
T4- perforated cancer or cancer cells on serosal surface
N1- less than four LN with metastasis
N2- four or more LN metastasis
M10 distal metastasis (liver)
Bowel cancer screening
Looking for early signs of disease in healthy people
Detect polyps before they turn into cancer
Detect at curable stage
Methods used for bowel cancer screening
Stool test or faecal occult blood test
Flexible sigmoidoscopy
Colonoscopy ideal but requires sedation, expertise
Colonoscopy used for screening in USA
In England: flexible sigmoidoscopy at 55 then faecal occult blood test from 60 every two years
Stool testing
Faecal occult blood testing
Testing for occult
Men and women 60-69 initially are invited to participate
Every two years
Positive test does not mean bowel cancer
Haemorrhoids and inflammation can cause positive test
Science behind stool test
Ulcerating cancer bleeds silently
Trauma to large polyps due to friction with stool also causes bleeding
Blood in stool reacts with chemical to show where there has been bleeding and sample turns blue
How to do the stool test
Privacy of your own home
Stool from three different days applied to screening carding using provided sticks
Card is posted or transported to Hub laboratory
After a positive stool test
Referred for colonoscopy to detect:
- polyps
- early cancer
- advanced cancer
Repeated every 2 years of negative test
Advantages of flexible sigmoidoscopy
Direct examination of mucosa bowel detects polyps and cancers better than stool test
2/3 cancers arise from left side of bowel
Majority arise from polyps
Removing polyps prevents progression to cancer
Studies shown up to 40% of lives saved by using FS as screening compared to 20% with FOBT
FS more acceptable to public than stool test
