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module 104 - theme 1 > bowel cancer > Flashcards

bowel cancer Flashcards

1
Q

what does bowel cancer refer to?

A

the large intestine

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2
Q

how common is bowel cancer?

A

3rd most common type of cancer in men and women

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3
Q

where in the world is bowel cancer most prevalent?

A

western world

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4
Q

what are the risk factors for bowel cancer?

A

1) individuals who migrate from low to high risk area
2) foods rich in red meat and fat
3) long standing ulcerative colitis
4) Crohn’s disease
5) previous history of bowel cancer surgery
6) family history of bowel cancer
7) old age

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5
Q

what factors decrease the risk of bowel cancer?

A

1) food rich in vegetables, fruit and fibre by increasing faecal bulk and reduces transit time
2) physical activity and low BMI

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6
Q

how does a high fibre diet reduce the risk of bowel cancer?

A
  • increases the formation of short chain fatty acids which promote healthy gut micro-organisms and reduces the proliferation of potentially neoplastic cells
  • increasing stool bulk reduces transit time and potential carcinogens in the stool have shorter contact with bowel mucosa
  • high fibre diet reduces formation of secondary bile acids which are potentially carcinogenic
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7
Q

what is a polyp?

A

a protruding growth into a hollow viscus; can be benign adenoma or malignant

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8
Q

what is dysplasia?

A

cells that have morphological features of cancer but without invasion of the surrounding tissue

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9
Q

what is low grade dysplasia?

A

early precancerous features

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10
Q

what is high grade dysplasia?

A

advanced precancerous features with high risk of invasion if not removed

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11
Q

what are the pathological features of a polyp?

A
  • hyperplastic consists of numerous goblet cells when compared to normal mucosa; has a lace like pattern
  • tubular adenine has test tube like appearance
  • villous adenoma has finger like appearance
  • tubulovillous adenoma has a mixture of tubular and villous features
  • pathology reporting: tubular adenocarcinoma with low or high grade dysplasia
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12
Q

what is the adenoma carcinoma sequence?

A
  • a stepwise progression from normal mucosa to adenoma to cancer
  • morphological features
  • carcinoma of the bowel is a classic example of multi step carcinogens both phenotypically and genetically
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13
Q

what is the evidence for adenoma carcinoma sequence?

A

1) populations which have high prevalence of adenomas have a high prevalence of cancer
2) distribution of adenomas in the large bowel mirrors the distribution of bowel cancer
3) peak incidence of polyps predicts the development of cancer
4) residual adenomas is found in most cases of early invasive cancer
5) risk of cancer is directly related to the number of polyps
6) programmes which follow-up patients and remove adenomas reduce the incidence of bowel cancer

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14
Q

what is familial adenomatous polyposis (FAP)?

A
  • patients with FAP have hundreds to thousands of polyps in large bowel (500-2500)
  • a minimum of 100 polyps is required to make the diagnosis of FAP
  • the polyps are dysplastic and therefore adenomas
  • FAP is associated with 100% risk of development of cancer by the age of 30
  • patients undergo prophylactic colectomy around the age of 20
  • FAP contributes to 1% of bowel cancer
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15
Q

what sort of condition is familial adenomatous polyposis (FAP)?

A

hereditary autosomal dominant condition

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16
Q

where is the defective gene in familial adenomatous polyposis (FAP)?

A

Chr 5q21 known as the APC gene

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17
Q

what happens with the genetics in familial adenomatous polyposis (FAP)?

A
  • patients acquire the first abdominal gene in uterus as a germ cell mutation known as the ‘first hit’
  • to develop polyps they acquire the second genetic abnormality in the somatic cells known as the ‘second hit’
  • the ‘second hit’ paved the way for the development of polyps fro a young age throughout the teens
  • patients have no polyps at brith and require ‘the second hit’ to develop polyps
18
Q

what is the 2 hit hypothesis in hereditary and sporadic bowel cancer?

A
  • in FAP the patient is born with a single genetic abnormality and acquires the second genetic abnormality after birth to develop adenomas and then cancer
  • in sporadic bowel cancer the person acquires the 2 hits in somatic cells to develop adenomas then cancer
19
Q

how does the second hit lead loss of heterozygosity?

A
  • the mutation of the APC gene is important in the initiation of bowel cancer
  • with one copy of abnormal gene the cells are heterozygous
  • the loss of the second set of normal genetic material during the second hit leads to loss heterozygosity and cells all acquire 2 identical copies of abnormal genes
  • after the second hit the cells acquire more genetic abnormalities to progress with adenoma-carcinoma sequence
20
Q

what is the order of the Fearson and Vogelstein model?

A

1) normal mucosa
2) hyper proliferative epithelium
3) early adenoma
4) intermediate adenoma
5) late adenoma
6) invasive cancer

21
Q

what are the genetic abnormalities associated with bowel cancer?

A
  • Lynch syndrome
  • familial adenomatous polyposis
  • attenuated FAP
  • familial colorectal cancer type x
  • MUTYH associated polyposis
  • serrated polyposis syndrome
  • hamartomatous polyposis syndrome
22
Q

what is Lynch syndrome (LS) hereditary non-polyposis colorectal cancer (HNPCC)?

A
  • familial cancer affecting mainly the ace and right colon before the age of 50
  • associated with endometrial, small bowel and cancer of the urinary tract
  • there are no precursor polyps
23
Q

what percentage of bowel cancer does Lynch syndrome count for?

A

2-3%

24
Q

what are the genetics of Lynch syndrome?

A
  • during replication the DNA base pairs can mismatch
  • the are mismatch repairs genes which act as ‘spell checkers’ and correct these mismatches
  • without the repairs the errors accumulate and create micro satellites
  • micro satellites are tandem repeat of nucleotides in the DNA of an individual and are fixed for life
  • errors due to mismatch in the DNA leads to expansion and contractions of these repeat nucleotides causing what is termed as micro satellites instability
  • there are several mismatch repair genes
  • at least 4 genes are involved in LS and these are routinely tested for in bowel cancer
  • individuals inherit the defective copy of the mismatch repair gene in utero and acquire the second copy during life and develop cancer
25
Q

what genes account for 30% of Lynch syndrome?

A

MSH2 and MLH1

26
Q

what are the other genes involved in Lynch syndrome?

A

PMS1 and PMS1

27
Q

how is Lynch syndrome assessed by the Amsterdam criteria?

A

3 or more relatives with LS associated cancer plus all 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 are affected relatives should be diagnosed before the age of 50
  • familial adenomatous polyposis should be excluded in any cases of colorectal cancer
  • tumours should be verified by pathological examinations
28
Q

what are the symptoms of bowel cancer?

A
  • can be asymptomatic and detected during screening
  • change in bowel habit: constipation alternating with diarrhoea due to an obstructive cancer
  • bleeding from the rectum
  • anaemia especially with cancers of the caecum due to slow occult blood loss
  • abdominal pain due to obstruction
29
Q

how do you diagnose bowel cancer?

A
  • history and clinical examination
  • flexible sigmoidoscopy and colonoscopy with biopsy and histological examination
  • CT colonography for patients who cannot tolerate a colonoscopy
  • staging CT scan for distal metastasis
  • MRI for rectal cancer to assess local spread
30
Q

what is the pathology of bowel cancer?

A
  • histologically adenocarcinoma

- graded as well, moderate and poorly differentiated

31
Q

what does T, N, M stand for in the staging of bowel cancer?

A 
T = tumour; assesses depth of invasion of the bowel wall
N = lymph node metastasis
M = distant metastasis to liver of lung
32
Q

what does T1 mean in staging of bowel cancer?

A

invasion of the submucosa, the muscular propria is clear

33
Q

what does T2 mean in staging of bowel cancer?

A

involves the muscularis proprietary without full thickness invasion

34
Q

what does T3 mean in staging of bowel cancer?

A

invasion of the full thickness of the bowel wall but not the serosa

35
Q

what does T4 mean in staging of bowel cancer?

A

the cancer has gone through the bowel wall and is present on the serosa

36
Q

what is bowel cancer screening?

A
  • looking for early signs of disease in ‘healthy people’
  • bowel screening can prevent cancer by detecting polyps before they turn into cancer
  • will detect early cancers at a curable stage
37
Q

what methods are used for bowel cancer screening?

A
  • stool test or faecal immunochemical test (FIT)
  • flexible sigmoidoscopy
  • colonoscopy is ideal but requires sedation and expertise
  • colonoscopy is used for screening in the USA
  • in the UK: flexible sigmoidoscopy at 55 years then FIT from 60-74 years every 2 years
  • sigmoidoscopy detects polyps and cancers in the rectum and left colon
38
Q

how does stool testing FIT work?

A
  • testing for occult blood
  • FIT is an antibody-antigen reaction; the reagent contains an antibody specific to human blood
  • positive test doesn’t mean one has bowel cancer
  • haemorrhoids and inflammation can cause a positive test
39
Q

what is the science behind the stool test?

A
  • ulcerative cancers bleed silently
  • trauma to large polyps due to friction with stool also causes bleeding
  • the participants receive a stool kit
  • the test is done in the privacy of their own home
  • the stool kit is sent the lab
  • the resultant an antigen-antibody is read by machine
40
Q

what happens after a positive stool test?

A
  • if positive: the patients will be referred for a colonoscopy
  • colonoscopy will detect: polyps, early cancers, advanced cancers
  • FIT does not detect non-bleeding polyps or non-bleeding cancers and the test is repeated every 2 years in people with negative tests

module 104 - theme 1 (17 decks)

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