How common is CRC?
3rd commonest cancer and 2nd biggest cancer killer in the west?
What are the types of CRC? (cell type, location and hereditariness)
95% are adenocarcinomas
2/3rds colonic and 1/3rd rectal
10% familial risk
5% heritable conditions
1% IBD related
What are the risk factors for sporadic CRC?
> 50 yrs
Environmental Influences e.g. diet, obesity, smoking, diabetes, sedentary
What are the most common heritable conditions leading to CRC?
- Hereditary Non-Polyposis Colorectal Cancer
- Familial Adenomatous Polyposis
Both are autosomal Dominant
Most colorectal cancers develop from pre-existing polyps, what do we call them and what histological types do they come in?
Benign pre-malignant Adenomas
- Tubular 75%
- Villous 10%
- Intermediate Tubulovillous 15%
What are the morphological types of benign pre-malignant adenomas?
Pedunculated - on a stalk
Sessile - No peduncle (much harder to spot)
How do we describe the level of dysplasia in an adenoma?
High grade - Crowded, irregular, carcinoma in situ
Low grade - Increased nuclear size/number and less mucin
How does an adenoma develop into a carcinoma?
By a number of gene changes:
- Oncogene activation (K-ras)
- Loss of Tumor Suppressor Genes (APC, p53)
- Defective DNA repair pathway genes
Together these processes lead to increased cell growth, proliferation and a drop in apoptosis
How does CRC present?
Usually with rectal bleeding and altered bowel opening (most often diarrhoea).
If theres just one of the both then investigates >60s and if both investigate >40s
- Iron deficiency anaemia
- Palpable rectal or right lower mass
- Acute colonic obstruction
- Systemic Symptoms e.g. weight loss & anorexia
What is the gold standard investigation for CRC?
What are the pros and cons of colonoscopy?
Allows looking, biopsy and therapeutic options.
Requires sedation & bowel prep
Also has risks such as perforation and bleeding
What radiology investigations are there for CRC?
- Best imaging technique essentially a 3D virtual colonography
CT Adbodmen and pelvis
What are the cons of radiology investigations for CRC?
Involves ionising radiation
Doesnt allow biopsies for histology or therapeutic intervention
How do we stage CRC?
MRI for rectal tumours
PET scan or rectal endoscopic US in select cases
TNM staging and DUkes classification
What is the duke classification?
A = Tumour in mucosa B = Tumour extended to muscle layer C = Involves lymph nodes D = Distant metastatic spread
What methods of treatment are there for CRC?
Surgery is the mainstay with 80% of patients getting it.
Can aso use chemo/radiotherapy/colonic stenting
What surgical ops are there for CRC patients?
- Resection of the diseased section of bowel
- Protectomy (rectum removal)
- Lymph node removal
- Partial Hepactectomy for metastases are also quite common
- Dukes A cancers can also be removed endoscopically or by local resection
How is chemo used for CRC?
Adjuvantly for Dukes C & B when they’ve been surgically removed
Also to mop up micro metastases & lymph nodes
How is radiotherapy used for CRC?
- For Rectal Cancer
- Can also be used neoadjuvantly +/- chemo to control a primary tumour
How do we treat CRC palliatively?
Chemo and colonic stenting
Whats the prognosis for CRC?
Very good for Duke’s A (83% 5 yr survival rate)
Gets progressively worse with each stage, hits 3% for Dukes D
What advice to we give to prevent CRC?
Exercise Maintain a healthy BMI Eat 5 veg/fruit a day Not Smoking Get Gender reassignment surgery Get Basil Hallward to paint your picture
How do we screen the general population for CRC?
Every 2 yrs from 50-74 you get a faecal occult blood test.
If its +ve go for a colonoscopy.
Resulted in a rise in Duke A cancers from 11->48% and a 15% reduction in CRC mortality
What does FAP cause?
Growth of 100+ adenoms in the colon. 50% by age 15, 95% by mid 30s
Due to a mutation of the APC gene on chromosome 5
How we screen for CRC in people with a family history of FAP?
Annual colonoscopy from age 10
Prophylactic proctocolectomy around 16-25 yrs
Whats the relation of NSAIDs to FAP?
Some NSAIDS work as chemoprevention.
E.g. Sulindac reduces polyp number and prevents recurrence of high grade adenomas in the retained segment after a proctectomy.
What causes HNPCC?
A mutation in the DNA mismatch repair genes (MMR) causing early onset CRC on the right side (40s).
Its associated with cancers at other sites e.g. endometrial, genitourinary, stomach and pancreas
How do we diagnose HNPCC?
A mixture of clinical criteria (the amsterdam or bethesda criteria) and genetic tests
How do we screen for CRC in people with HNPCC?
a 2 yrly colonoscopy from age 25
How do we screen for CRC in people with a non-heritable familial risk of CRC?
CRC in 3 FDRs with mean age <60
- -> High moderate risk
- -> 5 yrly colonoscopy from age 50
CRC in 2 FDRs over 60 or in 1 FDR <50
- -> Low Moderate Risk
- -> One Colonoscopy at age 55
IBD is associated with about 1% of CRC cases, how do we screen for it in such people?
A surveillance colonoscopy 10yrs post diagnosis
Then further investigations dependant on duration, extent, dysplasia and activity of the IBD
How do we screen for CRC in people with previous CRC?
Screen with a 5 yrly colonoscopy