Colon

Question 1

What are risk factors for colorectal cancer?

Answer 1

Smoking
Age (70% of patients with CRC are over 65y)
Physical inactivity
High red meat consumption
Obesity
Heavy alcohol intake
Family history and inherited syndromes

Question 2

Clinical presentation of CRC?

Answer 2

Change in bowel habit, abdo pain, weight loss, anaemia iron deficiency, PR bleeding

Question 3

What are options for screening for CRC?

Answer 3

Flexible sigmoidoscopy
Colonoscopy
CT colongraphy
Faecal occult blood (shown to reduce CRC mortality by 32%)

Question 4

When to screen average population?

Answer 4

Start at age 50y

Continue until life expectancy

Question 5

When to screen for CRC in IBD?

Answer 5

if crohns colitis or ulcerative colitis - start colonscopic screening after 8 years of disease, then annually

Question 6

When to screen in patients with family history?

Answer 6

If family history of CRC

Question 7

When to screen Lynch syndrome?

Answer 7

Colonscopy every 1-2 years starting at age 20-25, or 5y before youngest case in family

Question 8

When to screen FAP?

Answer 8

Sigmoidoscopy every 2 years starting age 12-14, once adenomas detected then annual colonoscopy until colectomy

Question 9

How to diagnose CRC?

Answer 9

Colonoscopy - biopsy, removal of polyps

LFTs, CT abdo/pelvis, CXR

Question 10

What is value of CEA test?

Answer 10

Low diagnostic ability (sensitivity 46%, specificity 89%)
Prognostic value - if CEA >5 pre op = worse prognosis
Useful monitoring test post operatively

Question 11

What is the staging of CRC?

Answer 11

Need adequate sampling of at least 12 nodes
Stage 1: confined to muscularis
Stage 2: invasion through muscularis into pericolorectal tissues
Stage 3: spread to lymph nodes
Stage 4: distant metastases

Question 12

What are high risk features of Stage 2 CRC?

Answer 12

Presentation with perforation or obstruction

Inadequate lymph node sampling (

Question 13

What is the management strategy for Stage 1-2 CRC?

Answer 13

Wide surgical resection
No role for adjuvant chemotherapy

• if high risk stage 2 - can consider adjuvant chemotherapy

Question 14

What is the management strategy for Stage 3 CRC?

Answer 14

Wide surgical resection

Standard of care is adjuvant doublet chemotherapy with oxaliplatin and 5-FU derivative (capecitabine or 5-FU)

Question 15

How is advanced CRC stratified?

Answer 15

Resectable disease - resect with perioperative or post operative chemotherapy
Potentially resectable disease - neoadjuvant chemotherapy to down stage disease in attempt to become resectable
Unresectable disease - palliative chemotherapy

Question 16

What are the options for unresectable advanced CRC?

Answer 16

Backbone of treatment is 5-FU chemotherapy
Cycle combinations of 5-FU, oxaliplatin and irinotecan
Targeted therapies (bevacizumab and cetuximab) improve OS in first line

Question 17

When can cetuximab be used?

Answer 17

Only proven in KRAS wildtype (no RAS mutation)

Only in advanced disease

Question 18

What is recommended follow up after adjuvant treatment?

Answer 18

Colonosopy in first years, then every 3-5 years
History, physical examination and CEA monitoring everyr 3-6 months for 3 years, then every 6-12 months for next 2 years
CT CAP every 6-12 months for 3 years in high risk pt

Question 19

What is mutation in Lynch syndrome?

Answer 19

Mutations in mismatch repair genes (MMR)
Most common is MLH1 or MSH2 (account for 80%)
Also MSH6, PMS2
Mutations result in tumour DNA microsatellite instability

Question 20

What are patients with Lynch syndrome at risk of?

Answer 20

Colorectal cancer (30-70%)
Endometrial ca (30-60%))
Urinary tract ca
Small intestine ca
Ovary ca
Gastric ca
Pancreatic ca
Biliary tree ca
Skin ca
Brain ca

Question 21

What are Bethesda guidelines?

Answer 21

When to test patient with CRC for MSI (Lynch syndrome)

- age

Question 22

What is FAP, what are the manifestations and mutations involved?

Answer 22

Familial adenomatous polyposis
Autosomal dominance inheritance
APC mutations - correlate with number of polyps
Presence of multiple polyps in colon and rectum
Extraintestinal manifestations: gastric and duodenal polyps, desmoid tumours, thyroid and brain cancer, supernumerary teeth

Question 23

What are the two types of FAP?

Answer 23

Classical - more thatn 100 polyps, complete penetrance, will develop CRC by 40-50y
Attenuated - fewer polyps, later onset of disease, incomplete penetrance, develop CRC at 50-60y

Question 24

What is most important aspect of management of rectal cancer?

Answer 24

Excision of mesorectum (technically difficult)
Requires staging with MRI to adequately asses tumour penetration
If full thickness – standard of care is pre-operative chemoradiation with 5-FU, followed by surgery, followed by adjuvant chemotherapy

Question 25

What is the main association and risk factors for anal cancer?

Answer 25

Associated with Human Papilloma Virus (HPV) in 80-85%)

Increased risk in HIV positive, MSM, immunosuppresion

Question 26

What is treatment strategy for anal cancer?

Answer 26

Tends to relapse loco-regionally
First line treatment is radical chemoradiation with Mitomycin/5-FU and external beam radiation
If relapse - proceed to salvage surgery

Question 27

What is MSI and how does it occur?

Answer 27

Microsatellite instability
Occurs when abnormalities of the mismatch repair proteins mean that they are unable to correct errors occurring during DNA replication
This causes repeated sequences of DNA (called micro satellites)

Presence of MSI indicates that there is an abnormality of MMR (mismatch repair)

Question 28

What are the types of mutations causing MSI?

Answer 28

Sporadic - caused by hyper methylation of MLH 1 gene promotor
Germline - mutations of MLH1 or MSH2 (80%), MSH6 or PMS2 (20%)

Question 29

What are the clinical features of MSI- H colorectal cancer?

Answer 29

Proximal tumours
Poorly differentiated
Often mucinous or signet ring
Less likely to metastasize
Younger patients
Better prognosis than micro satellite stable CRC
Often chemo resistant
Respond better to surgery alone (esp stage 2)