Colorectal Cancer

Question 1

Describe the epidemiology of colorectal cancer

Answer 1

Second leading cause of cancer death in the western world.
17,000 deaths in UK per year
3rd commonest cancer diagnosis overall
95% are adenocarcinomas
2 thirds colonic. 1 Third rectal

Question 2

What are the risk factors for colorectal cancer?

Answer 2

Most (85%) are sporadic with no familial/genetic influence

10% have familial risk
Inheritable conditions: HNPCC (5%), FAP (

Question 3

What are the risk factors for sporadic colorectal cancer cases?

Answer 3

Age
Male gender
Previous adenoma/CRC
Environmental influences:
-Diet (Decreased fibre, fruit and veg and calcium. Increased red meat and alcohol)
-Obesity
-Lack of exercise
-Smoking
-Diabetes mellitus

Question 4

Why are colorectal polyps so important?

Answer 4

The majority of colorectal cancers arise from pre-existing polyps.

Protuberant Growths
Variety of histological types
epithelial or mesenchymal
benign or malignant

Question 5

Discuss adenomas

Answer 5

Benign, pre-malignant
Epithelial in origin

2 main histological types:

• Tubular (75%)
• Villous 10%
• Indeterminate Tubulovillus (15%)

Morpholigically: predunculated or sessile

High risk lesions = size, number, degree of dysplasia, Villous achitecture

Question 6

Describe the molecular aspects of the carcinoma sequence

Answer 6

Activation of oncogene: k-ras, c-myc
Loss of tumour suppressor gene- APC, p53, DCC
Defective DNA repair pathway genes- MSI

All these lead to cell growth, proliferation and apoptosis

Question 7

How does colorectal cancer present?

Answer 7

Rectal Bleeding
Altered bowel habit (diarrhoea)
(Each symptom on its own investigate >60yrs. Both symptoms, investigate >40yrs)

Iron deficiency anaemia (men and non-menstruating women)
(More likely right sided)
Palpable rectal or right lower abdominal mass
Acute colonic obstruction if stenosing tumour
Systemic symptoms of malignancy (weight loss, anorexia)

Question 8

What investigation do you carry out in suspected colorectal cancer

Answer 8

Colonoscopy (Gold standard)
Allows biopsies to be taken
Therapeutic as well as diagnostic (polypectomy)

Radiological imaging:

• Barium enema
• CT colonoscopy (3D Virtual colonoscopy)
• (CT abdo/pelvis)

Question 9

What are the advantages and disadvantages of colonoscopy vs Radiological imaging?

Answer 9

Sedation
Bowel preparation
Risks: Bleeding and perforation

Ionising radiation
Bowel preparation
No histology
No therapeutic intervention

Question 10

What investigations can you do to stage colorectal cancer?

Answer 10

CT of chest/abdomen/pelvis
MRI for rectal tumours
PET scan / Rectal endoscopic ultrasound in select cases

Question 11

Give a basic outline of TNM staging for colorectal cancer

Answer 11

T1-T4 = local disease progression
N0-N1 = lymph node involvement
M0-M1 = distant metastasis

Question 12

Give a basic outline for dukes staging in colorectal cancer

Answer 12

A = tumour confined to mucosa
B = Tumour extended through mucosa to muscle layer
C = Involvement of lymph nodes
D = Distant metastatic spread

Question 13

Describe the surgical treatment of colorectal cancer

Answer 13

Basis of therapy
About 80% of patients have surgery

Dukes A and cancer polyps = endoscopic or local resection
Operative procedure depends on site, size and stage of tumour
Laparotomy vs laparoscopic
Stoma formation - colostomy (temporary or permanent)
Removal of lymph nodes for histological analysis
Partial hepatectomy for metastasis

Question 14

Describe the use of chemotherapy in colorectal cancer treatment

Answer 14

Adjuvant
Dukes B (possibly C)
Positive lymph node histology
Mops up micro-metastases

Question 15

Describe the use of radiotherapy in colorectal cancer treatment

Answer 15

Rectal cancer only

Neoadjuvant +/- chemo to control primary tumour prior to surgery

Question 16

Describe the use of palliative care in colorectal cancer

Answer 16

For advanced disease
Chemotherapy
Colonic stenting to prevent colonic obstruction

Question 17

Describe the Scottish bowel screening program

Answer 17

Started 2007
Age 50-74 years
FOBT every 2 years
If positive then colonoscopy
About 15% reduction in the relative risk of CRC mortality

Question 18

What are some examples of high risk groups you may screen for CRC?

Answer 18

Heritable conditions:
-FAP (familial adenomatous polyposis)
-HNPCC (hereditary non-polyposis colorectal cancer)
IBD
Familial risk
Previous adenoma/CRC

Question 19

What is FAP?

Answer 19

Familial Adenomatous Polyposis

Autosomal Dominant Condition
Multiple (>100) adenomas throughout colon
(50% by 15. 95% by 35)
Mutation of APC gene on chromosome 5
(about 25% of all cases are due to new mutations)

High risk of early malignant change in early adulthood, in almost all cases by age 40 years if untreated

Question 20

How do you deal with patients with FAP?

Answer 20

Annual colonoscopy form age 10-12yrs

Prophylactic proctocolectomy usually age 16-25yrs

Question 21

What other non colonic problems does FAP cause?

Answer 21

Extracolonic manefestations:

• Benign gastric fundic cystic hyperplastic
• Duodenal adenomas in 90% with periampillary cancer

Desmoid tumours
CHRPE = congenital retinal hypertrophy of the pigment epithelia

Question 22

Describe NSAID chemoprevention

Answer 22

Used in FAP

Sulindac reduces polyp number and prevents recurrence of higher grade adenomas in the retained rectal segment

Question 23

Describe HNPCC

Answer 23

Autosomal dominant condition
Mutation in DNA MMR genes

TUMOURS TYPICALLY HAVE A MOLECULAR CHARACTERISTIC (MSI)
FREQUENT MUTATIONS IN SHORT REPEATED DNA SEQUENCES (MICROSATALITES)

Early onset of CRC (40 years right sided)
Associated with cancer at other sites: endometrial, genitourinary, stomach, pancreas

Question 24

What is the diagnosis procedure and screening in HNPCC?

Answer 24

Clinical criteria (Amsterdam / Bethesda)
Genetic testing

Screening from age 25 every (2 years colonoscopy)