Colorectal Cancer

Question 1

How common is CRC?

Answer 1

3rd commonest cancer and 2nd biggest cancer killer in the west?

Question 2

What are the types of CRC? (cell type, location and hereditariness)

Answer 2

95% are adenocarcinomas

2/3rds colonic and 1/3rd rectal

85% sporadic
10% familial risk
5% heritable conditions
1% IBD related

Question 3

What are the risk factors for sporadic CRC?

Answer 3

> 50 yrs
Male Gender
Previous Adenoma/CRC
Environmental Influences e.g. diet, obesity, smoking, diabetes, sedentary

Question 4

What are the most common heritable conditions leading to CRC?

Answer 4

• Hereditary Non-Polyposis Colorectal Cancer
• Familial Adenomatous Polyposis

Both are autosomal Dominant

Question 5

Most colorectal cancers develop from pre-existing polyps, what do we call them and what histological types do they come in?

Answer 5

Benign pre-malignant Adenomas

Comes in:

• Tubular 75%
• Villous 10%
• Intermediate Tubulovillous 15%

Question 6

What are the morphological types of benign pre-malignant adenomas?

Answer 6

Pedunculated - on a stalk

Sessile - No peduncle (much harder to spot)

Question 7

How do we describe the level of dysplasia in an adenoma?

Answer 7

High grade - Crowded, irregular, carcinoma in situ

Low grade - Increased nuclear size/number and less mucin

Question 8

How does an adenoma develop into a carcinoma?

Answer 8

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

Question 9

How does CRC present?

Answer 9

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

Also:

• Iron deficiency anaemia
• Palpable rectal or right lower mass
• Acute colonic obstruction
• Systemic Symptoms e.g. weight loss & anorexia

Question 10

What is the gold standard investigation for CRC?

Answer 10

Colonoscopy

Question 11

What are the pros and cons of colonoscopy?

Answer 11

Allows looking, biopsy and therapeutic options.

Requires sedation & bowel prep
Also has risks such as perforation and bleeding

Question 12

What radiology investigations are there for CRC?

Answer 12

CT Colonography
- Best imaging technique essentially a 3D virtual colonography

CT Adbodmen and pelvis

Barium enema

Question 13

What are the cons of radiology investigations for CRC?

Answer 13

Involves ionising radiation
Bowel Prep
Doesnt allow biopsies for histology or therapeutic intervention

Question 14

How do we stage CRC?

Answer 14

CT chest/abdomen/pelvis
MRI for rectal tumours
PET scan or rectal endoscopic US in select cases

TNM staging and DUkes classification

Question 15

What is the duke classification?

Answer 15

A = Tumour in mucosa
B = Tumour extended to muscle layer
C = Involves lymph nodes
D = Distant metastatic spread

Question 16

What methods of treatment are there for CRC?

Answer 16

Surgery is the mainstay with 80% of patients getting it.

Can aso use chemo/radiotherapy/colonic stenting

Question 17

What surgical ops are there for CRC patients?

Answer 17

• 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

Question 18

How is chemo used for CRC?

Answer 18

Adjuvantly for Dukes C & B when they’ve been surgically removed
Also to mop up micro metastases & lymph nodes

5-FU (Fluorouracil)

Question 19

How is radiotherapy used for CRC?

Answer 19

• For Rectal Cancer

- Can also be used neoadjuvantly +/- chemo to control a primary tumour

Question 20

How do we treat CRC palliatively?

Answer 20

Chemo and colonic stenting

Question 21

Whats the prognosis for CRC?

Answer 21

Very good for Duke’s A (83% 5 yr survival rate)

Gets progressively worse with each stage, hits 3% for Dukes D

Question 22

What advice to we give to prevent CRC?

Answer 22

Exercise
Maintain a healthy BMI
Eat 5 veg/fruit a day
Not Smoking
Get Gender reassignment surgery
Get Basil Hallward to paint your picture

Question 23

How do we screen the general population for CRC?

Answer 23

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

Question 24

What does FAP cause?

Answer 24

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

Question 25

How we screen for CRC in people with a family history of FAP?

Answer 25

Annual colonoscopy from age 10

Prophylactic proctocolectomy around 16-25 yrs

Question 26

Whats the relation of NSAIDs to FAP?

Answer 26

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.

Question 27

What causes HNPCC?

Answer 27

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

Question 28

How do we diagnose HNPCC?

Answer 28

A mixture of clinical criteria (the amsterdam or bethesda criteria) and genetic tests

Question 29

How do we screen for CRC in people with HNPCC?

Answer 29

a 2 yrly colonoscopy from age 25

Question 30

How do we screen for CRC in people with a non-heritable familial risk of CRC?

Answer 30

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

Question 31

IBD is associated with about 1% of CRC cases, how do we screen for it in such people?

Answer 31

A surveillance colonoscopy 10yrs post diagnosis

Then further investigations dependant on duration, extent, dysplasia and activity of the IBD

Question 32

How do we screen for CRC in people with previous CRC?

Answer 32

Screen with a 5 yrly colonoscopy