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Theme 1: The Alimentary System > Bowel cancer: pathology and the screening process > Flashcards

Bowel cancer: pathology and the screening process Flashcards

1
Q

Key facts about bowel cancer

A

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

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2
Q

Risk factors for bowel cancer

A
  1. Environmental disease (low to high population migration, red meats and fatty foods)
  2. Longstanding ulcerative colitis
  3. Crohn’s disease
  4. Presence of adenoma in large bowel
  5. Previous history of bowel cancer surgery
  6. Family history
  7. Old age
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3
Q

High fibre diet reduces cancer

A

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

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4
Q

Polyp

A

Protrusion into hollow viscus

Can be benign adenoma or malignant

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5
Q

Adenoma in GIT

A

Pre-cancerous lesions

Consist of dysplastic epithelium

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6
Q

Dysplasia

A

Cells have morphological features of cancer but without invasion

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7
Q

Low grade dysplasia

A

Early precancerous features

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8
Q

High grade dysplasia

A

Advanced precancerous features

High risk of invasion if not removed

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9
Q

Pathological features of polyps

A

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

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10
Q

Adenoma- cacrinoma sequence

A

Stepwise progression to bowel cancer from normal mucosa to adenoma to cancer

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11
Q

Evidence for adenoma- carcinoma sequence

A

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

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12
Q

Genetic basis of multistep carcinogenesis

A

To understant genetic and morphological features of bowel cancer

Best to understand how bowel cancer develops in familial adenomatous polyposis

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13
Q

Familial adenomatous polyposis

A

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

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14
Q

Genetics of FAP in carcinogensesis

A

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

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15
Q

Two hit hypothesis

A

In FAP patient is born with single genetic abnormal and acquires second after birth

Sporadic adenomas person acquires two hits in somatic cells

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16
Q

Loss of heterozygosity

A

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

17
Q

Hereditary non-polyposis colorectal cancer

A

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

18
Q

Genetics of HNPCC

A

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

19
Q

Genetics of HNPCC

A

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

20
Q

Amsterdam criteria to assess for HNPCC

A

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
21
Q

Symptoms of bowel cancer

A

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

22
Q

How to diagnose bowel cancer

A

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

23
Q

Pathology of bowel cancer

A

Graded as well, moderate or poorly differentiated

Well differentiated resembles normal colonic mucosa

Moderately differentiated most common

Poorly differentiated minimal or no glandular differentiation

24
Q

Dukes staging

A

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%)

25
Q

TNM staging

A

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)

26
Q

Bowel cancer screening

A

Looking for early signs of disease in healthy people

Detect polyps before they turn into cancer

Detect at curable stage

27
Q

Methods used for bowel cancer screening

A

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

28
Q

Stool testing

Faecal occult blood testing

A

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

29
Q

Science behind stool test

A

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

30
Q

How to do the stool test

A

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

31
Q

After a positive stool test

A

Referred for colonoscopy to detect:

  • polyps
  • early cancer
  • advanced cancer

Repeated every 2 years of negative test

32
Q

Advantages of flexible sigmoidoscopy

A

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

Theme 1: The Alimentary System (16 decks)

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