Colorectal Cancer Flashcards
What is the definition of colorectal cancer?
a cancer (malignant neoplasm) developing in the large bowel
it has the potential to spread elsewhere in the body
the cancer can occur anywhere from the beginning of the large bowel (caecum) to the end (rectum)
bowel cancers tend to be more common in the left side of the bowel (in the sigmoid colon and rectum)
In terms of cell invasion, how is a cancer defined?
Why is it defined in this way?
neoplastic cells must have invaded through the muscularis mucosae into the submucosa
the mucularis mucosae separates the mucosa from the submucosa
this is because once the cancer is in the submucosa, it can access lymphatics and blood vessels and spread around the body
What is the most common site for bowel cancer to spread to?
the liver
What is the epidemiology of colorectal cancer like?
In which groups is it more common?
- 41,000 new cases in the UK every year
- linked to aging (average age of presentation is 65)
- more common in men
- more common in western populations
What is the aetiology of bowel cancer like?
- predominantly linked to environmental factors
- poor diet (red meat, high fat, low fibre)
- obesity / inactivity
- alcohol, smoking & radiation
- factors of lesser importance
- inherited factors (defined syndrome or non-specific association)
- inflammatory bowel disease
- especially long term ulcerative colitis
What is involved in the pathogenesis of colorectal cancer?
the vast majority of bowel cancers develop along the adenoma-carcinoma sequence
What are the stages in the adenoma carcinoma sequence?
normal epithelium
5q mutation or loss FAP
hyper-proliferative epithelium
DNA hypomethylation
early adenoma
12p mutation K RAS
intermediate adenoma
18q loss DCC ?
late adenoma
17p loss p53
carcinoma
other alterations
metastasis
What is the concept behind the adenoma carcinoma sequence?
movement from normal mucosa through to metastasis
at each stage there are genomic events that happen within the cell that cause further progression along the pathway
with each genetic hit, the cancer progresses further down the pathway
What % of bowel cancers follow the adenoma-carcinoma sequence?
What other factors are involved in the pathogenesis?
- around 85% of colorectal cancer is thought to follow the adenoma-carcinoma sequence
- around 15% are due to microsatellite instability
What is involved in microsatellite instability?
Who is more likely to have colorectal cancer resulting from this?
- loss of function of the DNA mismatch repair genes
- these are the genes that repair any mutational damage that occurs sporadically throughout the genome
- tend to be female and cancer tends to be right-sided
- may show typical morphology
- certain features are associated with microsatellite instability
- more likely to be mucinous, poor differentiation, infiltration by high levels of immune cells
What are the key clinical features of colorectal cancer?
- many tumours ulcerate leading to bleeding
- can be occult in the right colon and patients often fail to notice it
- patients may present with signs of anaemia due to chronic bleeding, without noticing the blood
- if the tumour is in the left side of the colon / rectum then the blood passed is bright red and the patient often notices it
- can be stenotic leading to pain
- if the tumour completely obstructs the bowel, patients present acutely as a surgical emergency
- weight loss and altered bowel habit are common
What is the treatment offered for bowel cancer?
removal of the cancer with a bit of normal bowel either side
then the two sides of the bowel are rejoined to maintain intestinal continuity
if the cancer is in the rectum, the anal sphincters may need to be removed and the patient will have a permanent colostomy
additional treatment involves radiotherapy and chemotherapy (after surgery)
How does bowel cancer screening work?
it detects faecal occult blood
if blood is detected above a certain level, then patients are invited for colonoscopy to try and identify the source of the bleeding
this allows more cancers to be picked up at an early stage, where they are far more treatable
