Colorectal carcinoma, FAP, HNPCC, Peutz-Jeghers, GI polyps

Question 1

Epidemiology of colorectal carcinoma

Age? Sex? Geography?

Answer 1

Peak in 60s,
More in men
Western disease

Question 2

Role of adenomatous polyposis coli (APC) in colorectal cancer?

Answer 2

• APC is a protein that promotes degradation of β-catenin.

- mutations in APC lead to increased β-catenin, and increased cell proliferation

Question 3

Sequence of events from formation of adenomas to colorectal carcinomas caused by APC mutation?

Answer 3

1. First hit: mutation of one APC copy
2. Second hit: mutation of second copy of APC (leads to adenoma formation)
3. Further mutations (eg in KRAS and p53) in the adenoma –> malignant transformation

Question 4

Risk factors for colorectal cancer?

Answer 4

1. Diet: ↓ fibre + ↑ refined carbohydrate
2. Inflammatory bowel disease
3. Familial: FAP, HNPCC, Peut-Jeghers
4. Smoking
5. Genetic (one first degree relative makes it 50 times more likely)

NOTE:
NSAIDS/ Aspirin are protective

Question 5

What type of carcinoma are the majority of colorectal cancers?

Answer 5

• 95% adenocarcinoma

- others: lymphoma, GIST, carcinoid

Question 6

The 3 common sites for colorectal cancers?

Answer 6

Rectum: 35%
Sigmoid: 25%
Caecum and ascending colon: 20%

Question 7

Symptoms of colorectal cancer?

Answer 7

Left sided cancer: 
- Altered bowel habit
- PR mass
- Obstruction 
- bleeding/ mucus
Right sided cancer:
- Anaemia

Question 8

Examination findings of colorectal cancer?

Answer 8

Palpable mass
Perianal fistulae
Hepatomegaly 
Anaemia
Signs of obstruction

Question 9

Anal fistula

Answer 9

• a narrow tunnel with its internal opening in the anal canal and its external opening in the skin near the anus
• an abnormal communication bnormal communication between the epithelialised surface of the anal canal and (usually) the perianal skin

Question 10

Investigations for colorectal carcinoma?

Answer 10

1. Bloods:
   I. FBC: Hb
   II. LFTs: mets
   III. Tumour Marker: CEA (carcinoembryonic Ag)
2. Imaging
   I. CXR: mets
   II. Ultrasound liver: mets
   III. CT or MRI for staging (MRI best for rectal Ca and liver mets)
   IV. Endoanal ultrasound: staging rectal tumours
   V. Ba / gastrograffin enema: apple-core lesion
3. Endoscopy + biopsy:
   I. flexi sigmoid: 65% of tumours accessible
   II. colonoscopy

Question 11

DUKES staging of colorectal cancer?

Answer 11

A. confined to bowel wall
B. through bowel wall but not lymph nodes
C. regional lymph nodes
D. distant mets

Question 12

TNM staging of colorectal cancer?

Answer 12

TIS: carcinoma in situ
T1: submucosa
T2: muscularis propria
T3: subserosa
T4: through the serosa to adjacent organs
N1: 1-3 nodes
N2: >4 nodes

Question 13

Grading of colorectal cancer?

Answer 13

Grading from low to high

• Based on cell morphology
• Dysplasia, mitotic index, hyperchromatism

Question 14

Pre-operative preparation for colorectal cancer resection surgery?

Answer 14

I. Kleen Prep (Macrogol: osmotic laxative) the day before and phosphate enema in the morning of surgery.
II. discuss stomas (Stoma nurse consult for siting)

Question 15

Surgical options for rectal cancer management?

Answer 15

1. Anterior resection:
   - used for upper rectum (tumour 4-5cm from anal verge)
   - takes out rectum and anus
   - needs loop ileostomy
2. Abdominoperineal resection:
   - used for lower rectum ( tumour <4cm from anal verge)
   - leaves the anus untouched! but takes the rectum out
   +/- 3. Total mesorectal excision (TME)
   - removal of mesorectum
   - for tumours of the middle and lower third of rectum
   - it reduces the cancer recurrence
   - Side effect: ↑ risk of faecal incontinence

Question 16

Mesorectum?

Answer 16

is the perirectal fat separated by the rectal fascia

Question 17

Surgical options for tumours in the following:

1. sigmoid
2. Left sided
3. Transverse
4. caecal (right sided)

Answer 17

1/ Sigmoid: high anterior resection or sigmoid colectomy

2. Left: left hemicolectomy
3. Transverse: extended right hemicolectomy
4. Caecal / right: right hemicolectomy

Question 18

Screening programs for colorectal cancer?

Answer 18

I. FOB (faecal occult blood) Testing

• involves taking a sample from two separate bowel motions
• 60-75yrs
• Home FOB testing every 2yrs: ~1/50 have +ve FOB
• Colonoscopy if +ve: ~1/10 have Ca

II. Flexi Sigmoidoscopy

• 55-60yrs
• Once only

Question 19

Genetics of Familial adenomatous polyposis (FAP) ?

Answer 19

• Autosomal dominant

- Mutated APC gene

Question 20

Presentation features of Familial adenomatous polyposis (FAP) ?

Answer 20

• 100-1000s of adenomas by ~16yrs,
• mainly in large bowel (But also stomach and duodenum, near ampula)
• 100% develop colorectal cancer, often by ~40yrs

Question 21

Variants of Familial adenomatous polyposis (FAP) ?

Answer 21

1. attenuated FAP
2. Gardener’s syndrome
3. Turcot’s syndrome

Question 22

Attenuated FAP?

Answer 22

• <100 adenomas,

- leads to CRC at a later stage (>50yrs)

Question 23

Gardener’s syndrome 4 features?

Answer 23

A variant of FAP
TODE
- Thyroid tumours
- Osteomas of the mandible, skull and long bones
- Dental abnormalities: supernumerary teeth
- Epidermal cysts

Question 24

Turcot’s syndrome?

Answer 24

• A variant of Fap

- CNS tumours: medullo- and glio-blastomas

Question 25

Management of Familial adenomatous polyposis (FAP) ?

Answer 25

I. Prophylactic colectomy before 20yrs II. Total colectomy + ileorectal anastomosis (IRA) III. Proctocolectomy + ileal pouch anal anastomosis (IPAA) IV. Regular endoscopic screening as remain at risk of Cancer in stomach and duodenum

Question 26

Proctocolectomy + ileal pouch anal anastomosis (IPAA)?

Answer 26

- removal of rectum and large colon and then - surgical construction of internal reservoir; near where the rectum would be - folding loops of small intestine (the ileum) back on themselves and stitching them together. - The internal walls are removed - retains or restores functionality of the anus with stools passed under voluntary control of the patient

Question 27

Hereditary Non-Polyposis Colorectal Cancer (HNPCC) genetics?

Answer 27

- Autosomal dominant | - Mutation of mismatch repair enzymes (eg MSH2)

Question 28

Presentation of Hereditary Non-Polyposis Colorectal Cancer (HNPCC) ?

Answer 28

Lynch 1 syndrome: right sided colorectal carcinoma (CRC) Lynch 2 syndrome: CRC + gastric, endometrial, prostate, breast

Question 29

Diagnosis of Hereditary Non-Polyposis Colorectal Cancer (HNPCC)

Answer 29

“3, 2, 1, rule” ≥3 family members over 2 generations with one <50yrs

Question 30

Peutz-Jeghers Syndrome genetics?

Answer 30

- Autosomal dominant | - STK11 mutation

Question 31

Age of presentation of Peutz-Jeghers Syndrome?

Answer 31

at the age of ~ 10-15yrs

Question 32

Symptoms of Peutz-Jeghers Syndrome?

Answer 32

``` I. Mucocutaneous hyperpigmentation - Macules on palms, buccal mucosa II. Multiple GI hamartomatous polyps - Intussusception - Haemorrhage ```

Question 33

Risk associated with Peutz-Jeghers Syndrome?

Answer 33

↑ Cancer risk: - Colorectal - pancreas - breast - lung - ovaries - uterus

Question 34

Different types of GI polyps?

Answer 34

I. Inflammatory pseudopolyps II. Hyperplastic polyps III. Hamartomatous IV. neoplastic

Question 35

What are inflammatory pseudopolyps?

Answer 35

regenerating islands of mucosa in ulcerative colitis

Question 36

What are hyperplastic polyps?

Answer 36

- Piling up of goblet cells and absorptive cells | - No malignant potential

Question 37

What are Hamartomatous polyps

Answer 37

- Tumour-like growths composed of tissues present at site where they develop - Sporadic or part of familial syndromes

Question 38

Tenesmus?

Answer 38

- refers to cramping rectal pain | - Tenesmus makes patient feel like they need to have a bowel movement, even if they had one recently