Colorectal cancer Flashcards
(12 cards)
Risk factors for developing colorectal cancer
Non-modifiable
1. Age > 50 years old
2. Family history
3. Inflammatory bowel disease
4. Sex - men > women
5. Genetics / hereditary
Modifiable
1. Diet - low fibre, high red meat, processed food
2. Diabetes mellitus
3. Alcohol
4. Smoking
5. Obesity
Histological classification of colorectal cancer
- Adenocarcinoma
- Adenosquamous carcinoma
- Spindle cell carcinoma
- Squamous cell carcinoma
- Undifferentiated carcinoma
Molecular pathogenesis of colorectal carcinoma
Stepwise accumulation of mutations
1. Loss of APC suppressor gene – adenoma formation
2. B-catenin accumulation – promotes cell proliferation
3. K-RAS mutation – continuous mitotic signals, ↓ apoptosis
4. Loss of SMAD tumour suppressor genes
5. Loss of P53 tumour suppressor gene – unrestrained growth
Clinical presentation of patients with colorectal carcinoma
- Asymptomatic - incidentally on routine colonoscopy
- Suspicious signs and symptoms
- Change in bowel habit
- PR bleeding
- Perianal symptoms
- Constitutional symptoms
- Abdominal or rectal pain
- Anaemia symptoms - Emergency conditions
- Intestinal obstruction
- Peritonitis
- Massive GI bleeding
Investigations for colorectal cancer
- FBC, iron panel, B12/folate
- Liver panel - albumin, mets
- Tumour markers - CEA
- Fecal occult blood (screening)
- OGD and colonoscopy
- CT TAP - assess site and mets
- Genetic and family screening (if applicable)
Management of colorectal cancer
- MDT- dietitian, general surgery
- Family screening
- Surgical resection
- Chemo-radiotherapy - FOLFOX, monoclonals (bevacizumab)
Complications of colorectal carcinoma
- Intestinal obstruction
- Malnutrition
- GI bleeding
- Bowel perforation
- Metastasis - liver, lungs
What inherited conditions predispose to colorectal cancer?
- Hereditary non-polyposis colorectal cancer (HNPCC) (Lynch syndrome) - autosomal dominant
- Familial adenomatous polyposis (FAP) - autosomal dominant
- Peutz-Jeghers syndrome - associated with pigmented lesions in the buccal mucosa and lips, autosomal dominant
Hereditary non-polyposis colorectal cancer (HNPCC) is also known as Lynch syndrome.
- Autosomal dominant, high penetrance
- Mutations in DNA mismatch repair genes
Incidence: 1-3% of all colonic adenocarcinoma
Extracolonic tumours:
1. Endometrium
2. Ovary
3. Stomach
4. Small intestine
5. Hepatobiliary
6. Urogenital
Diagnosis:
1. Amsterdam Criteria
2. Molecular testing
Amsterdam Criteria for HNPCC
(Rule of 3-2-1-exclude-confirm)
3 relatives with colorectal cancer (with one being 1st degree relative)
2 generations of colorectal cancer
1 colorectal cancer before age 50
Additional criterias:
- FAP excluded
- Confirmed by histopathology
Familial adenomatous polyposis (FAP) is due to adenomatous polyposis coli (APC) gene mutation. Almost all patients develop colorectal carcinoma by age 45.
It can be inherited autosomal dominant or arise de-novo (1/3 patients)
Extracolonic tumour:
1. Duodenal ampullary cancer
2. Gastric cancer
3. Papillary thyroid cancer
4. Follicular thyroid cancer
5. CNS tumours
Variants of FAP:
1. Gardner’s syndrome - colorectal ca + skin lesions (desmoid tumour, sebaceous cyst, lipoma, osteoma, supernumerary teeth) or thyroid cancer
2. Turcot’s syndrome - colorectal ca + medulloblastoma (cerebellar tumour)
Peutz-Jeghers syndrome is an autosomal dominant condition with multiple hamartomatous polyps in small intestines, colon and stomach. Cancer risk if 9-fold increased.
Patient may also have numerous pigmented lesions on lips and buccal mucosa.
Polyps frequency: jejunum > ileum > duodenum > large intestine > stomach
Extracolonic tumours:
1. Breast
2. Lungs
3. Uterus
4. Ovary
5. Testicular
6. Pancreatic
