Bowel Cancer Flashcards
Ten year survival rate for bowel cancer
53%
Polyp
is a projecting growth of tissue from a surface in the body usually a mucous membrane and can develop in the colon, rectum, ear canal, cervix, stomach, nose, uteruses, throat and bladder
Adenomatous polyps in the large bowel are cancerous.
True or False?
False
precancerous but only 5% progress into cancer can be 10 years
Colorectal cancer begins with the formation of a
small fixed adenoma
Pathogenesis of Bowel Cancer:
- small adenomas could progress into more advances,
more giant fixed adenomas - all adenomatous polyps have dysplasia, size is not
relevant, though larger polyps may be more likely to
have high grade dysplasia - some cancers will be seen in very small polyps and
many large polyps do not have cancer or even high
grade dysplasia
Adenoma-carcinoma sequence
- low grade dysplasia to high grade dysplasia, CRC
***APC inactivation
adenoma carcinoma sequence
Screening and prevention of bowel cancer (wilson’s criteria):
- identification of a pre-malignant phase (polyp)
- there is a good and acceptable test (colonoscopy)
- there is an agreed and acceptable treatment
(polypectomy)
serrated pathway in colorectal cancer
Genetics of colo-rectal cancer:
- 75% are sporadic
- 20% of CRC patients report a family history of the
disease - 3-5% are hereditary due to the highly penetrant
germline mutations
Two forms of hereditary colorectal cancer:
- polyposis
- lynch syndrome
Polyposis:
- familial adenomatous polyposis (FAP)are caused by
pathogenic varients in APC gene which is
chromosome 5q21 - MUTHY-associated polyposis: caused by pathogenic
variants in the MUYTH gene
What does the APC gene do?
- APC gene provides instructions for making the APC
protein, which is critical in several cellular processes - the apc protein acts as a tumour suppressor and
keeps cells from growing and dividing too fast or
uncontrolled
Lynch syndrome (hereditary nonpolyposis colorectal cancer):
- caused by germline pathogenic varients in DNA
mismatch repair genes (MMR genes and EPCAM)
Two Hit Hypothesis
- two genetic abnormalities are required (both copies
of the affected gene) to develop certain cancers - those with a hereditary susceptibility to cancer inherit
a damage chromosme , hence their first hit occurs at
conception, whereas others may receive their first hit
at a later stage
Two hit theory of cancer causation
Familial Adenomatous Polyposis (FAP):
- autosomal dominant
- 25% are new mutations; no family history
- > 100 polyps by late teens
- almost 100% risk of bowel cancer by 30
- surgery is reccomended by the 20s
- screening for cancers/polyps in stomach, small bowel
and thyroid
Lynch syndrome (hereditary nonpolyposis colorectal cancer):
-what % of cases are new mutations?
- does or doesnt follow two hit hypothesis?
- increases risk of what type of cancers?
- 20% are new mutations
- follows two hit hypothesis
- increases risk of endometrial and renal cell cancer,
sometimes breast, upper GI and prostate
Bowel Cancer Staging:
- TNM
- tumour: has the tumour grown into the wall of colon
or rectum? How many layers (serosa etc)? - nodes: has the tumour spread to the lymph nodes?
where and how many? - metastasis: has the cancer spread to other parts of
the body? Where and how much?
Distant metastasis sites of colorectal cancer?
- brain
- lungs
- liver (most)
- spleen
- mesentery (omentum)
- bone
Bowel Cancer: Risk factors:
- higher incidence in western world, and white
- roughly equal in both men and women
- 2/3 occur in those over 60
- genetics: polyposis like FAP
- longstanding inflammatory bowel disease like UC
What % of bowel cancer is preventable in the UK?
54%
(meat, alcohol, smoking)
High dietary fibre reduces the risk of bowel cancer:
- increases the formation of short chain fatty acids
- reduce stool transit time
- reduces secondary bile acid formation
High dietary fibre reduces the risk of bowel cancer: increases the formation of short chain fatty acids:
- promotes healthy gut bacteria, which can induce cell
differentiation, arrest cell growth and cause apoptosis - reduce proliferation of neoplastic cells
High dietary fibre reduces the risk of bowel cancer: reduce stool transit time:
- carcinogens are common in food, faster transit means
less time for these to act on the bowel mucosa
High dietary fibre reduces the risk of bowel cancer: reduces secondary bile acid formation:
- potentially carcinogenic
Clinical features of bowel cancer:
- changes in bowel movements
- gas/bloating
- abdo discomfort
- nausea/vomiting
- fatigue
- weight loss
- loss of appetite
- anaemia
- cramping
Clinical features of Rectal cancer:
- rectal bleeding
- change in bowel habits
- rectal pressure or fullness
- thin or ribbon like stools
- anaemia
- cramping
- weight loss
- loss of appetite
- fatigue
Clinical presentation of bowel cancer:
- > 60:
- iron deficiency anaemia
- change in bowel habit
- > 50:
- unexplained rectal bleeding
- <50:
- unexplained rectal bleeding
- abdominal pain
- change in bowel habits
- weight loss
- iron deficiency anaemia
- > 40:
- weight loss and abdo pain
- any age with abdo or rectal mass
Bowel Cancer Screening:
- 60-74
- every two years
- qFIT
- detects human goblin (amount of blood in stool)
- > 75 can request one every two years
Limitations of qFIT:
- 50% patients with documented colorectal cancers
have a negative faecal occult blood test, consistent
with the intermittent bleeding pattern of these
tumours
If qFIT is positive then definitely cancer/
True or False?
False
follow up tests required to determine the reason for the presence of blood in the stool
Further investigations for bowel cancer:
- qFIT
- physical exam
- colonoscopy “goldstandard”
- biopsy
- biomarker testing to identify specific genes, unique
factors of tumour - blood tests: anaemia (due to bleeding)
- ultrasound, CXR, CT, MRI
