Lecture 12 Flashcards
(18 cards)
What are the risk factors for bowel cancer
Bowel cancer is believed to be an environmental disease and
potentially preventable, thus:
1a) Migration from a low-risk population to a high-risk population increases the risk in the migrant
b) Foods rich in red meat and fat increase the risk of bowel
cancer
c) Food rich in vegetables, fruit & fibre reduces the risk of bowel
cancer by ↑ faecal bulk & reduces transit time
d) Physical activity and low BMI are associated with low risk of cancer
2. Longstanding ulcerative colitis
3. Crohn’s disease – to a lesser extend than UC
4. Presence of adenoma in the large bowel
5. Previous history of bowel cancer surgery
6. Family history of bowel cancer
7. Old age
How does high fibre diet reduce bowel cancer?
By increasing the formation of short chain fatty acids which promote healthy gut microbes which induce differentiation, arrest the growth of cells and cause apoptosis i.e. reduces the proliferation of potentially neoplastic cells
By increasing stool bulk thereby reducing stool transit time →potential carcinogens in the stool have a shorter contact with the bowel mucosa
By reducing secondary bile acid formation which is potentially carcinogenic
Define polyp
Polyp is a protrusion into a hollow viscus; can be benign adenoma or malignant
Define dysplasia
the cells have morphological features of cancer but without invasion
What are the 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 a finger-like appearance
Tubulovillous adenoma – a mixture of the
above
What is the Adenoma-Carcinoma Sequence?
This is a stepwise progression to bowel cancer from normal mucosa to adenoma to cancer
Morphological features i.e. 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 multistep carcinogenesis both phenotypically (morphologically) and genetically
What is the two hit hypothesis
In FAP the patient is born with a single genetic abnormal (first hit) and acquires the second genetic abnormality (second hit) after birth
In sporadic adenomas the person acquires the two hits in somatic cells
The two hit hypothesis was proposed by Knudson to explain hereditary retinoblastoma, cancer of the eye in children and is applicable to most cancers
Describe Hereditary non-Polyposis Colorectal Cancer (HNPCC)/Lynch Syndrome
Familial cancer affecting predominantly the caecum and right colon, before the age of 50
Associated with endometrial, ovarian, small bowel and cancer of the urinary tract.
No precursor polyps
What are the genetics of HNPCC
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 microsatellite instability
Errors due to mismatch in the DNA causes expansion and contractions of these repeat nucleotides causing what is termed as microsatellite instability – a hallmark of defective mismatch repair
At least four genes are involved in the pathogenesis
MSH2 (2p16) and MLH1 (3p21) genes account for 30% of the HNPCC
PMS1 and PMS2 are the other genes involved in HNPCC
Two hit hypothesis involved
What are the symptoms of bowel cancer
Change in bowel habit, constipation alternating with diarrhoea due to an obstructive cancer
Bleeding from rectum
Anaemia especially with cancers of the caecum
Abdominal pain due to obstruction
How do we diagnose bowel cancer?
History and clinical examination
Patients who present with anaemia – upper GI and lower GI endoscopy
Flexible sigmoidoscopy, 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
Describe dukes staging
Dukes A: cancer involves part of the bowel wall; no lymph node (LN) metastasis (90 – 95% 5yr survival)
Dukes B: cancer involves the full thickness of the bowel wall; no LN metastasis ( 60-70%)
Dukes C: cancer involves any part of the bowel wall with LN metastasis; usually full thickness of bowel wall involved (20-25%)
Dukes D: was not in the original classification - denotes liver or other distant metastasis (~15%)
Describe the Tumour node metastasis TNM staging
T1 – cancer involves the submucosa
T2 – cancer involves inner of muscularis propria
T3 – cancer involves full thickness of the bowel wall i.e. inner and outer layers of muscularis propria
T4 – perforated cancer or cancer cells on serosal surface
N1 – less than four LN with metastasis
N2 – four or more LN metastasis
M1 – distal metastasis (liver)
What is Bowel Cancer Screening (BCS)?
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 a curable stage
What are the methods used for BCS
Stool test or faecal occult blood test (FOBT) Flexible sigmoidoscopy (FS)
Colonoscopy is ideal, but requires sedation, expertise; associated with 1-2% risk of perforation;
Colonoscopy used for screening in the USA
England: FS @ 55 years then FOBT from 60 every two years
To change to Faecal Immunochemical Test (FIT) which is more specific for human blood
Discuss Faecal Occult Blood Testing (FOBT)
Testing for occult i.e. hidden blood in the stool, not visible to the naked eye
Men and women 60 – 69yrs initially ( extended to 75 yrs in 2007 ) are invited to participate
Test performed every two years
A positive test does not mean one has bowel cancer
Haemorrhoids & inflammation can cause a positive test
What is the science behind the stool test?
Ulcerating cancer bleeds silently
Trauma to large polyps due to friction with stool also causes bleeding
The blood in the stool reacts with a chemical to show there has been bleeding and the sample turns blue
What are the advantages of flexible sigmoidoscopy (FS)?
Direct examination of mucosa bowel detects polyps and cancers better than the stool test
2/3 of cancers arise from the left side of the bowel
Majority of cancers arise from polyps
Removing the polyps will prevent progression to cancer
FS is more acceptable to the public than the stool test
