GIS Case 1: Colorectal Cancer

Question 1

Causes of lower GI bleeding

Answer 1

1. Diverticular disease
2. Colitis
3. Haemorrhoids
4. Inflammatory bowel disease
   - Crohn’s disease
   - Ulcerative colitis
5. Neoplasm

Question 2

Anatomy of colon and importance in cancer management

Answer 2

Anatomy: See lecture

Colonoscopy:

• Entire colon
• every 10 years
• sedation needed

Sigmoidoscopy:

• Only Rectum + Sigmoid colon
• every 5 years
• bowel prep less complicated
• sedation not needed

Question 3

Adenoma-carcinoma sequence in colorectal cancer development

Answer 3

Normal colon:
APC ***tumour suppressor gene (Inherited / Acquired mutation: 1st hit)

Mucosa at risk:
—> APC: Methylation abnormalities, Inactivation of normal alleles (2nd hit)

Adenoma:
—> K-RAS: **Protooncogene mutations
—> p53, LOH, SMAD 2 and 4: Homozygous loss of additional **tumour suppressor genes

Carcinoma:
—> Telomerase, many genes: Additional mutations, ***Gross chromosomal alterations

Question 4

Methods for colorectal cancer screening

Answer 4

Screening: examining people without symptoms

1. **Guaiac-based Faecal Occult Blood Test (gFOBT)
   - Guaiac causes stool sample to change colour
   - collect 3 stool samples
   - Detect **Heme —> oxidising activity —> colour change
   - False positive: Food / drugs
   - Detect Upper + Lower GI bleeding but cannot differentiate —> less specific
2. **Faecal Immunochemical test
   - Ab to detect hidden human blood
   - Detect **Haemoglobin instead of Heme
   - Specific for ***Lower GI bleeding (∵ Haemoglobin broken down in upper GI tract)
3. Sigmoidoscopy
4. Colonoscopy

Question 5

Diagnosis of Colorectal cancer

Answer 5

1. Colonoscopy
2. Biopsy
3. CT —> measure tumour size + contrast medium
4. MRI
5. Blood test
   - CBC —> Low Hb ∵ bleeding
   - ***Carcinoembryonic antigen (CEA) —> high level indicate spreading of cancer to other body parts

Question 6

Treatment principles of colorectal cancer

Answer 6

Stage 0:

• NOT grown beyond inner colon lining
• ***Surgical resection / Partial colectomy

Stage 1:

• Deeper into colon wall, NOT outside wall / nearby LN
• Polypoid cancers: ***Complete polyp removal via Colonoscopy
• Non-polypoid cancers: ***Partial colectomy

Stage 2:

• Through colon wall + nearby tissues, NOT to LN yet
• ***Partial colectomy

Stage 3:

• Spread to nearby LN
• **Partial colectomy + **LN resection + ***Adjuvant chemotherapy (e.g. 5-FU)
• Radiotherapy / Chemotherapy for people not eligible for surgery

Stage 4:

• Spread to distant tissues
  1. **Surgery to prolong life —> if obstruction use stent
  2. **Chemotherapy before + after surgery —> Hepatic artery infusion / Ablation / Embolisation if spread to liver
  3. **Radiotherapy —> relieve symptoms, shrink tumour temporarily
  3. **Immunotherapy for specific genetic mutations
  3. ***Targeted therapy

Question 7

Risk stratification in management of colorectal cancer

Answer 7

High risk group:

• HNPCC carriers
• FAP (APC mutation carriers)
• One 1st degree relative diagnosed with colorectal cancer <= 60 yo
• > = One 1st degree relative diagnosis with colorectal cancer regardless of age
• History of IBD

Question 8

Bowel preparation for colonoscopy

Answer 8

1. Diet
   - eat light 3-4 days before procedure
   - low fibre food
   - day of procedure —> cannot eat solid food
   - 2-4 hours before procedure —> no food / drink
2. Laxative
   - night before colonoscopy
   - clear bowel

Question 9

Epidemiology of colorectal cancer in HK

Answer 9

• Commonest cancer in HK
• Highest incidence
• 2nd leading cause of cancer deaths

Question 10

Principles of cancer screening

Answer 10

1. Disease should be an ***important public health problem
2. Have a ***window of opportunity for early detection
3. ***Effective treatment should be available
4. ***Suitable / Accurate screening test should be available —> easy to administer, safe, inexpensive

Question 11

Principles of genetic screening for cancer

Answer 11

Family with known cancer syndrome / Family with history of cancer / Early onset cancer
—> Pretest counselling
—> Identify possible cancer syndromes / candidate genes
—> Informed consent
—> Testing
—> Identification of disease-causing mutation
—> Screening of asymptomatic family members

Ethics:

1. Autonomy
   - Confidentiality
   - Informed consent
2. Beneficence
   - Benefits > Cost / harm
3. Non-maleficence
   - Do NO harm
4. Justice
   - Available to all people

Question 12

Implication of positive genetic test

Answer 12

1. Increased risk of developing a disease
   —> directs a person toward available prevention, monitoring, treatment options
   —> implication for direct relatives to undergo testing
2. Make decision regarding having children
3. Newborn screening to identify genetic disorders early in life
   —> start treatment as early as possible