bowel cancer

Question 1

what does bowel cancer apply to?

Answer 1

the large intestine

Question 2

describe the prevalence of bowel cancer? 4

Answer 2

• Third most common cancer in women after breast and lung cancer
• Third most common cancer in men after prostate and lung cancer
• High incidence of bowel cancer in the western world
• Effect’s men and women equally

Question 3

what are the risk factors for bowel cancer? 7

Answer 3

• environmental and preventable risks
• Longstanding ulcerative colitis
• Crohn’s disease
• Presence of adenoma in the large bowel
• Previous history of bowel cancer surgery
• Family history of bowel cancer
• Old age

Question 4

describe how bowel cancer is an environmental disease? 4

Answer 4

• Individuals who migrate from a low-risk area to a high-risk area increase their risk of developing bowel cancer
• Foods rich in red meat and fat increase the risk of bowel cancer
• Foods rich in vegetables, fruit and fibre reduce the risk of bowel cancer by increasing faecal bulk and reduces transit time
• Physical activity and low BMI are associated with low risk of bowel cancer

Question 5

how can a high fibre diet reduce bowel cancer? 3

Answer 5

• By increasing 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 a higher contact with the bowel mucosa
• High fibre diet reduces formation of secondary bile acids which are potentially carcinogenic

Question 6

what is a polyp? 6

Answer 6

• A polyp is a protruding growth into a hollow viscus, can be benign, adenoma or malignant
• Screening a polyp in bowel cancer is either ‘innocent’ or precancerous. If the cancer is polypoid, do not use the term polyp
• Most polyps in the large bowel are adenomas- pre-cancerous lesions and consist of dysplastic epithelium
  -Dysplasia= the cells have morphological features of cancer but without the invasion of the surrounding tissue
  Low grade dysplasia= early precancerous features
• High grade dysplasia= advances precancerous features with a high risk of invasion if not removed
• Whether a polyp is benign (hyper-plastic), dysplastic (adenoma) or cancerous, the diagnosis can only be confirmed on microscopic examination by the pathologist

Question 7

What are the pathological features of polyps? 5

Answer 7

• Hyperplastic consists of numerous goblet cells when compared to normal mucosa- has a lace like pattern
• Tubular adenoma has a test-tube like appearance
• Villous adenoma has a finger- tube appearance
• Tubulovillous adenoma has a mixture of tubular and villous features
• Pathology reporting= tubular adenoma with low or high grade dysplasia

Question 8

what is the adenoma-carcinoma sequence? 3

Answer 8

• stepwise progression from normal mucosa to adenoma or cancer
• morphological features- macroscopic and histological features are also mirrored at genetic level where there are stepwise genetic alterations
• carcinoma of the bowel is a classic example of a multistep carcinogenesis both phenotypically (morphologically) and genetically

Question 9

what is the evidence for the adenoma-carcinoma sequence? 7

Answer 9

• observational studies have shown that the most sporadic cancers which are not genetically determined arise from adenomas and this is supported by the following evidence:
• populations which have a high prevalence of adenomas have a high prevalence of cancer
• distribution of adenomas in the large bowel mirrors the distribution of bowel cancer
• peak incidence of polyps predates the development of cancer
• residual adenoma is found in most cases of early invasive cancer
• risk of cancer is directly related to the number of polyps
• programmes which follow up patents and remove adenomas reduce the incidence of bowel cancer

Question 10

what is familial adenomatous polyposis? FAP? 6

Answer 10

• patients with FAP have hundreds to thousands to polyps in the large bowel
• a minimum of 100 polyps are required to make the diagnosis
• the polyps are dysplastic and are therefore called adenomas
• FAP is associated with 100% risk of developing cancer by the age of 30
• patients undergo prophylactic colectomy around the age of 20
• contributes to 1% of bowel cancer

Question 11

describe genetics of FAP in bowel cancer? 6

Answer 11

• hereditary autosomal dominant condition
• the defective gene is on chromosome 5q21 known as the APC gene (adenomatous polyposis coli)
• patients acquire the first abdominal gene in utero 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 paves the way for the development of polyps from a young age throughout the teens
• patients have no polyps at birth and require the second hit to develop polyps

Question 12

describe the two hit hypothesis in hereditary and sporadic bowel cancer? 3

Answer 12

• in FAP the patient is born with a single genetic abnormality (first hit) and squires the second genetic abnormality (second hit) after birth to develop adenomas then cancer
• in sporadic bowel cancer the person acquires the two hits in the somatic cells to develop adenomas then cancer
• the two hit hypothesis was proposed by Knudson to explain hereditary retinoblastoma, cancer of the eye in children and is applicable to most cancers

Question 13

describe what the second hit leads to? 5

Answer 13

• the loss of heterozygosity
• the mutation of the APC gene is important in the imitation of bowel cancer
• with one copy of the abnormal gene, the cells are heterozygous
• the loss of the second set of the normal genetic material during the second hit leads to the loss of heterozygosity of the cell wall will acquire two identical copies of abnormal genes (become homozygous for the cancer gene)
• after the second hit the cells acquire more genetic abnormalities to progress with adenoma-carcinoma sequence

Question 14

what are the genetic abnormalities associated with bowel? 7

Answer 14

• Lynch syndrome (previously hereditary non-polyposis colorectal cancer (HNPCC))
• Familial adenomatous polyposis (FAP)
• Attenuated FAP- less than 100 adenomas
• Familial colorectal cancer type X (FCCX)
• MUTYH associated polyposis (MAP)
• Serrated polyposis syndrome
• Hamartomatous polyposis syndrome

Question 15

what is Lynch syndrome? 6

Answer 15

• Familial cancer affecting predominantly the caecum and right colon before the age of 50
• Associated with endometrial, small bowel and cancer of the urinary tract
• It is important when asking about FH of cancer, not to just concentrate on the large bowel
• LS accounts for 2-3% of bowel cancer
• Important to understand the genetics of LS because of this practical value
• Bowel cancer from young patients and advanced cancers are routinely checked for LS genetic mutations whether they have a FH of cancer or not

Question 16

describe the genetics of Lynch syndrome? 10

Answer 16

• Very different from FAP
• During replication the DNA base pairs can mismatch
• There are mismatch repair genes which act as spell checkers and correct these mismatches
• Without the repairs the errors accumulate and create microsatellites
• Microsatellites 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 microsatellite instability- a hallmark of defective mismatch repair
• There are several mismatch repair genes
• At least 4 genes are involved in LS and these are routinely tested for cancer
• MSH2 (2p16) and MLH1 (3p21) genes account for 30% of the LS
  PMS1 and PMS2 are other genes involved in LS
• Similar to FAP individuals, inherit the defective copy of the mismatch repair gene in utero (first hit) and acquire the second copy during life (second hit) and develop cancer

Question 17

how is Lynch syndrome assessed? 7

Answer 17

• the Amsterdam criteria
• Three or more relatives with LS-associated cancer (bowel cancer or cancer of the endometrium, small bowel, ureter or renal pelvis) plus the following:
• One affected patient should be a first degree relative of the other 2
• Two or more successive generations should be affected
• Cancer in one or more affected relatives should be diagnosed before 50
• Familial adenomatous polyposis should be excluded in any cases of colorectal cancer
• Tumours should be verified by pathological examination

Question 18

what are the symptoms of bowel cancer? 5

Answer 18

• 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 the cancer of the caecum due to slow occult blood loss
• Abdominal pain due to obstruction

Question 19

how do we diagnose bowel cancer? 5

Answer 19

• History and clinical examination
• Flexible sigmoidoscopy and colonoscopy with biopsy and histological examination
• CT colonography for patients who cannot tolerate colonoscopy
• Staging CT scan for distal metastasis
• MRI for rectal cancer to assess local spread

Question 20

what is the pathology of bowel cancer? 5

Answer 20

• Histologically adenocarcinoma
• Graded as well, moderate and poorly differentiated A
• Well differentiated, resemble colonic mucosa B
• Moderately differentiated is most common C
• Poorly differentiated- minimal or no glandular differentiation D

Question 21

describe the grading scale? 3

Answer 21

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

Question 22

what is bowel cancer screening? 3

Answer 22

Screening means 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 curable stage

Question 23

what are the methods used for bowel cancer screening? 5

Answer 23

• Stool test or faecal immunochemical test. (FIT)
• Flexible sigmoidoscopy (FS)- detects polyps and cancers in the rectum and left colon
• Colonoscopy is ideal but requires sedation, expertise, associated with 1-2% risk of perforation
• Colonoscopy used for screening in the USA
• In the UK= flexible sigmoidoscopy at 55 years then FIT from 60-74 years every 2 years

Question 24

what is stool testing? 4

Answer 24

• Testing for occult blood- hidden blood in the stool, not visible to the naked eye
• FIT is an antibody-antigen reaction; the reagent contains antibody specific to human blood
• Positive tests do not mean one bowel has cancer
• Haemorrhoids and inflammation can cause a positive test

Question 25

describe the science between the stool test? 6

Answer 25

• Ulcerating cancers bleed silently
• Trauma to large polyps due to friction with stool also causes bleeding
• The precipitants receive a stool kit
• The test is done at home in private
• The stool kit is sent to the lab
• The resultant antigen-antibody reaction is reads by a machine

Question 26

what happens after a positive stool test? 3

Answer 26

• If positive= the patient will be referred for a colonoscopy
• This will detect polyps (benign and precancerous), early cancers and 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