Cancer 13: Colon Cancer Flashcards
colorectal cancer =
-4th most common cancer overall
2nd leading cause of death (after lungs)
-
what is the function of a colon?
- Extraction of water from faeces
(electrolyte balance) - Faecal reservoir (evolutionary advantage)
- Bacterial digestion for vitamins
(e. g. B and K)
describe the Organisation of the Colorectal crypt of Lieberkuhn
- crypt cells migrate up –> lost at tip
a) describe the turnover of colon mucosa
b) What are the 3 main protective mechanisms to eliminate genetically defective cells?
a) - highly turnover
- high proliferation –> higher chance of mutation occurrence
b) Normally we have protective mechanisms to eliminate genetically defective cells by;
- Natural loss
- DNA monitors
- Repair enzymes
what is the difference between polyps and adenomas?
polyp = any projection from a mucosal surface into a hollow viscus
may be:
- hyperplastic (common) <0.5cm , noplasti
- inflammatory
- hamartomatous, etc
adenoma is a benign neoplasm of the mucosal epithelial cells
types:
- tubular
- villous
- tubulovillous
What is meant by pendular and sessile adenoma?
- pedunculate adenoma
- -> (like a stalk)
- sessile adenoma
- -> (like a posh carpet - slightly raised)
what are microscopic structure of tubular adenoma?
- Columnar cells with nuclear enlargement, elongation, multilayering and loss of polarity
- Increased proliferative activity
- Reduced differentiation
- Complexity/disorganisation of architecture
what are microscopic structure of villous adenoma?
- Mucinous cells with nuclear enlargement, elongation, multilayering and loss of polarity
- Exophytic, frond-like extensions
- Rarely may have hypersecretory function and result in excess mucus discharge and hypokalemia
Dysplasia can be:
- indefinite
- low grade
- high grade –> means disorder = worse
- increased mitosis
- bigger nuclei
- darker nuclei
- pseudo stratified
- disordered growth
- increased cytoplasmic-nuclei ratio
adenomatous polyposis coli (APC)
- due to _____ gene mutation
- due to 5121 gene mutation
- thousands of polyps –> high risk of developing colorectal cancer
What is a potential surgical method of dealing with APC?
prophylactic colectomy
Describe the progression from adenoma to carcinoma
gradual increase in genetic mutation —> leads to cancer
note: Endoscopic removal of polyps decreases the incidence of subsequent CRC
What is the genetic pathway involved in development of
- adenoma carcinoma sequence
- -> APC, K ras, Smads, p53, telomerase activation
Microsatellite instability
–> comes in and repairs damaged DNA
but if DNA repairing genes is dysfunctional –> can lead to cancer
What are the 2 main genetic predisposition of colorectal cancer?
2 main pathways:
FAP - inactivation of APC tumour suppressor genes
HNPCC - microsatellite instability
what are dietary factors that contribute to colonic carcinoma?
- High Fat
- Low Fibre
- High Red meat
- Refined carbohydrates
NOTE: chemicals in food
–> antioxidants (good)
OR
–> Carcinogenic (can increase risk of mutagenesis)
-
folate deficiencies –> ca increase risk of colorectal cancer
how?
folate act as Co-enzyme for nucleotide synthesis and DNA methylation
folate deficiencies –> can increase risk of colorectal cancer
how?
folate act as Co-enzyme for nucleotide synthesis and DNA methylation
what are some healthy food?
- garlic
- green tea
- etc.
What clinical presentation would a patient with colorectal cancer show?
what are the 3 main TRIADS ?
TRIAD
- Change in bowel habit !!!
- Rectal Bleeding (usually if left sided)
- Unexplained iron deficiency anaemia (usually if right sided)
others: Mucus PR Bloating Cramps (‘colic’) Constitutional (weight loss, fatigue)
- rectosignmoid cancer = most common
55%
-
What types of colorectal cancer might you see?
- adenocarcinoma grade 1-3
others:
- mutinous carcinomas
- signet ring cell
- neuroendocrine
most cancers - in grading are
well differentiates
moderately differentiated (most common)
poorly differentiated
-
Dukes Classification - STAGING
Dukes A - growth limited to wall
- nodes negative
Dukes B - growth beyond musc propria
- nodes negative
Dukes C1 - nodes positive
- apical LN negative
Dukes C2 - apical LN positive
-
What clinical features affect the prognosis of the colorectal cancer?
IMPROVED PROGNONSIS:
- diagnosis in asymptomatic patients
- rectal bleeding
- tumour location ( colone is better than rectum, left better than right)
DIMINISHED PROGNOSIS
- bowel obstruction / perforation
- age <30
- preoperative serum CEA
- Distant metastases
- increased bowel wall penetration
- increase no. of lymph nodes involved
- decrease degree of differentiation
- any invasion
why is staging of tumors important?
alters the survival probability
What are treatment options of colorectal cancer?
stage 1 - surgery
stage 2 - surgery + 5FU
stage 3 - surgery + 5FU/Leucovorin
stage 4 - Metastatectomy + Chemo + Palliative RT
What are the conditions for high risk colon cancer category for screening?
-Previous adenoma
1st Degree relative affected by colorectal cancer before the age of 45
2 affected first degree relatives
evidence of dominant familial cancer trait including colorectal, uterine, and other cancers
UC and Crohn’s disease
Hereditable cancer families (include other sites)
Population screening = investigating apparently healthy individuals in a group with the object of detecting unrecognised disease
-
screening colon cancer = Faecal Occult Blood test
- given package through post
- sample taked from faces
- screened for blood
-
if FOB test comes out positive what might be the next procedure ?
Positives referred for:
60-75 years –> colonoscopy
55-60 years –> sigmoidoscopy
A 76 year old man presents with new onset rectal bleeding to the GP:
A) Haemorrhoids must be excluded in the first instance
B) Factor 5 leiden abnormalities are the likely cause
C) The GP should reassure and send the patient home
D) Colorectal malignancy must be excluded in the first instance
E) Crohn’s disease must be excluded in the first instance
D) Colorectal malignancy must be excluded in the first instance
With respect to the aetiology of colorectal adenocarcinoma:
A) Many carcinomas are derived from adenomas
B) Adenomas are invasive tumours
C) Ulcerative colitis is the underlying cause in many cases
D) Many carcinomas are derived from hyperplastic polyps
E) Angiodysplasia is the underlying cause in many cases
A) Many carcinomas are derived from adenomas
