CRC

Question 1

List some DDx for a presentation of:

• fatigue, weight loss
• bright red PR bleed
• PR anterior firm, non-tender mass

Answer 1

PDx. CRC
DDx.
Neoplastic
- CRC
- large polyp
- carcinoid tumour (neuroendocrine)
- GI lymphoma 
- prostate ca
Vascular
- angiodysplasia
- ischaemic bowel (post shock or emboli)
Inflammatory
- UC 
- Diverticular disease
Infectious- gastro
Anal disease
- haemarrhoids
- anal fissure or fistula

Question 2

List some investigations you would do?

Answer 2

Bedside
- PR (blood character)
- abdo exam (masses, liver mets)
Labs
- FBC (iron deficiency anaemia)
- Iron studies (decreased ferritin, decreased transferrin sat)
- CRP/ESR
- EUC
- LFT- liver function, coag
- CMP- bony mets
- Tumour marker- CEA
Imaging
- colonoscopy and biopsy- ulcerating exophytic (externally proliferating) mucosal lesion, possible lumen narrowing 
- transrectal endoscopic US- staging (tumour infiltration)
- CT

Question 3

What are some risk factors for CRC?

Answer 3

Non-modifiable
- FMHx
- age (>70yo)
- male (equal if <50yo)
- bowel pathology (polyps, UC or CD)
- genetics: FAP, HNPCC/Lynch syndrome 
Modifiable
- diet (low fibre)
- obesity
- smoking
- ETOH
- sedentary lifestyle
- abdo radiation

Question 4

Describe the pathogenesis of CRC?

Answer 4

Path: dysplastic adenomatous polyps due to accumulation of genetic mutations -> unchecked growth
Normal cell -> hyperplasia -> metaplasia -> dysplasia -> neoplasia
2 pathways:
1) APC pathway (APC, KRAS, 18q21, p53)- 80%
2) DNA mismatch repair pathway (microsatellites)- 20%

Question 5

Describe the APC pathway of CRC pathogenesis?

Answer 5

Sporadic pedunculated colon tumours

1) APC pathway (80%)
- loss of APC tumour suppressor gene -> B-catenin accumulation -> activates genes for proliferation -> adenoma
- KRAS mutation (protoncogene) -> adenoma growth
- 18q21 deletion -> unrestrained cell growth
- p53 (tumour suppressant) deletion -> carcinoma

Question 6

Describe the DNA mismatch repair gene pathway of CRC pathogenesis?

Answer 6

Sessile serated right sided lesions (HNPCC)
(sessile worse than pedunculated)
2) DNA mismatch repair gene pathway (20% CRC)
- mutations in DNA mismatch repair genes (MSH2, MSH6)
- microsatellites (repetitive DNA sequences)
- if microsatellites in region of cell growth and apoptosis -> promote uncontrollable growth
- accumulation of gene mutations and loss of tumour suppressor genes -> CRC

Question 7

Describe the microscopic features of CRC?

Answer 7

• loss of organised glandular architecture
• malignant cells infiltrate muscle wall
• desmoplasia (increased collagen deposition)
• cells: high N:C ratio, hyperchromic nucleus, PMNs, mitotic figures

Proximal colon tumours: exophytic mass -> extends along one wall -> obstruction rare
Distal colon tumours: annular -> constriction -> luminal narrowing -> obstruction

Question 8

Compare right and left sided CRC?

Answer 8

Right sided CRC (25%):

• commonly ileocaecal junction
• polypoid -> along one wall -> obstruction rare
• clinical: occult bleeding (anaemia/ fatigue), RIF mass, nil bowel habit change, presents later

Left sided CRC (60%):

• commonly anorectal junction
• annular shape (central ulceration, raised edges)
• circumferential -> stricture > luminal narrowing -> obstruction
• clinical: change in bowel habit, tenesmus, bright red blood PR, LIF mass/pain, presents earlier

Question 9

Name some complications of CRC?

Answer 9

Local:
- bleed (iron deficiency)
- bowel obstruction -> perforation -> peritonitis
- electrolyte/fluid imbalance
- local invasion -> fistula or peritoneal seeding
Systemic- mets
- lymphatic: abdo LNs
- haematogenous: liver (most), lungs, bone, brain 
Paraneoplastic
- cachexia (bronchial pneumonia, sepsis)
- hypercoagulable (PE, DVT)
- sepsis

Question 10

How would you manage CRC?

Answer 10

Curative (stages 1-3)
Colon ca: surgery + adjuvant chemo (oxiplatin-based)
Rectal ca: surgery and neoadjuvant radio