13. Colorectal cancer Flashcards
What is the function of the colon?
- Extracts water from faeces (slightly involved in electrolyte balance)
- Faecal reservoir
- Bacterial digestion of vitamins
How fast do the bowel cells turnover and what eliminates genetically defective cells?
- 2-5 million cells die per minute
- Proliferation renders cells very vulnerable
Protective mechanisms to eliminate cells:
• Natural loss
• DNA monitors e.g. APC (adenomatous polyposis coli)
• Repair enzymes
What is a polyp?
- Any projection from a mucosal surface into a hollow viscus
* May be hyperplastic, neoplastic, inflammatory etc.
What is an adenoma?
Benign neoplasm of the mucosal epithelial cells
What are the colonic polyp types?
- Meta/hyperplastic - benign and common (mucosal damage)
- Adenomas - increase RISK of cancer
- Juvenile
- Peutz Jeghers
- Lipomas
- Others
Outline hyperplastic polyps?
- Very common and benign
- Not dysplastic
- 90% of all LI polyps
- No malignant potential
- 15% have k-ras mutation
What are the colonic adenoma types?
- Tubular - look like test tubes lined up (most common)
- Villous - look like sea anemone
- Tubulovillous - mixture of both
- Pedunculated - like a tree
- Sessile - like a rug on top of a carpet
Describe tubular adenomas
- Columnar cells with some elongation, nuclear enlargement, multi-layering and loss of polarity
- Increased proliferative activity
- Reduced differentiation
- Disorganised
- Hyperchromatic - look darker on slides (increased nucleus:cytoplasm)
Describe villous adenomas
- Mucinous cells with elongation, nuclear enlargement, multi-layering and loss of polarity
- Exophytic, frond-like extensions
- Rarely may have hyper-secretory function and result in excess mucus discharge and hypokalaemia
What is dysplasia?
- Abnormal growth of cells with some features of cancer
- Not yet cancer
- Disorganised
- Pseudostratification and granular hyper-chromatic dark nuclei
- Increased nucleo-cytoplasmic ratio
What is familial adenomatous polyposis?
- Disease in which there are thousands of polyps in the bowel
- Cancer is inevitable - prophylactic colectomy can stop this
- Mutation in 5q21 gene
- Associated with APC gene
- Site of mutation determines clinical variants
Does the size of a polyp change the risk of cancer?
Yes, large polyps have a higher risk of cancer
What is the incidence of cancer if a polyp is left?
5%
Mutations in what genes can increase the risk of getting polyps => adenoma carcinoma?
- APC
- k-RAS
- Smads
- p53
- Telomerase activation
What are microsatellites, what is microsatellite instability and how is this involved in adenoma carcinomas?
- Repeat sequences prone to misalignment
- Some microsatellites are in coding sequences of genes which inhibit growth or apoptosis
- Microsatellite instability results from impaired “mismatch repair genes”
- DNA can’t be repaired
- DNA damage accumulates and leads to cancer
- Recessive gene requiring 2 hits
- HNPCC - germ-line mutation in these genes
What 2 main genes pre-dispose someone to an adenoma carcinoma?
- FAP - inactivation of APC tumour suppressor genes
* HNPCC - microsatellite instability
When does an adenoma become a carcinoma?
When it invades the adjacent tissue
Can cooking food be dangerous?
- Yes, damaging and destroying it can release materials that may be carcinogenic
- Includes heterocyclic amines
What deficiencies are linked with colorectal cancer?
- Folate - it is a protector of cells and destroyed by over-cooking
- It is also a co-enzyme for nucleotide synthesis and DNA methylation
- MTHFR mutation affects the body’s ability to use folic acid -
- Decreased methionine synthesis leads to genomic hypomethylation and focal hypermethylation
List some anti-cancer food elements
- Vitamin C - ROS (reactive oxygen species) scavenger
- Vitamin E - ROS scavenger
- Isothiocyanates (cruciferous vegetables)
- Polyphenols - green tea (activate MAPK, EGCG-induced telomerase activity)
- Garlic - associated with apoptosis
Outline the clinical presentation of colorectal cancer
• Change in bowel habit
• Rectal bleeding
• Unexplained iron deficiency anaemia
(mucus, bloating, cramps, weight loss, fatigue etc.)
Why do people not present very often thinking they have colorectal cancer?
- People ignore the symptomatic presentation
* Patient’s (and doctors) rationalise these symptoms as ‘getting old’ etc.
Describe the distribution of colorectal cancer in the bowel?
- Caecum/ascending colon - 22%
- Transvers colon - 11%
- Descending colon - 6%
- Recto-sigmoid - 55%
Very similar to adenomas
What type are almost all cancers of the large bowel?
Adenocarcinomas (malignant tumours of glandular epithelium)
What are the subtypes of adenocarcinoma?
- Mucinous carcinoma
- Signet ring cell
- Neuroendocrine (carcinoid)
What proportion of adenocarcinomas are well, moderately or poorly differentiated?
- Well differentiated - 10%
- Moderately differentiated - 70%
- Poorly differentiated - 20%
Outline the Dukes classification in the staging of colorectal cancer
A) growth limited to wall (muscularis propria) - lymph nodes negative
B) growth beyond wall - lymph nodes negative
C1) nodes positive (but apical lymph nodes negative)
C2) apical lymph nodes positive - other nodes drain into apical lymph nodes
Is it prognosis worse when having cancer in the colon or rectum?
Rectum
How does a high serum CEA (carcinoembryonic antigen) level affect prognosis?
Diminished prognosis
Is the prognosis better or worse if rectal bleeding is a presenting symptom?
Improved prognosis
How does local inflammation and immunological reaction affect prognosis?
Improved prognosis
Who do you screen for high risk colorectal cancer?
(Family) History
• Previous adenoma
• 1st relative affected before the age of 45, or 2 affected 1st relatives
• Evidence of dominant familial cancer trait e.g. colorectal, uterine etc.
• UC and Crohn’s disease
Why does the natural history of the disease need to be known for colorectal screening?
To identify location of screening
What is the current NHS screening programme for colorectal cancer?
- Age 55 - faecal test to check for blood in faeces
* Positives are referred for colonoscopy (60-75 years) or sigmoidoscopy (55-60 years)
