Colorectal Cancer and Screening Flashcards
What is the epidemiology of CRC?
- 2nd leading cause of cancer death in the Western world
- 17,000 UK deaths per year
- 3rd commonest cancer diagnosis overall
- 2/3rds colonic cancer
- 1/3 rectal cancer
What are 95% of CRCs?
Adenocarcinomas
What are the risk factors for CRC?
- Sporadic cancers
- Familial risk
- Inheritable conditions : HNPCC, FAP
- IBD
What are the risk factors for sporadic CRC?
- Age
- Male
- Previous adenoma/CRC
- Diet
- Obesity
- Lack of exercise
- Smoking
- Diabetes mellitus
What diet choices can increase your risk of CRC?
- Decreased fire
- Decreased fruit and veg
- Decreased calcium
- Increased red meat
- Increased alcohol
What do the majority of CRCs arise from?
Pre-existing polyps
what are colorectal polyps?
- Protuberant growths that vary in histological types.
- They can be epithelial or mesenchymal and benign or malignant
What is the origin of adenomas?
Epithelial
What stage are adenomas?
- Benign
- Pre-malignant
What are the 2 main histological types of adenomas?
- Tubular
- Villous
What is the other histological type of adenoma?
Indeterminate tubulovillous
How can adenomas present morphologically?
- Pedunculated
- Sessile
What can affect the severity of an adenoma?
- Size
- Number
- Degree of dysplasia
- Villous architecture
What are the 3 stages involved in the carcinoma sequence?
- Activation of oncogenes
- Loss of tumour suppressor gene
- Defective DNA repair pathway genes (microsatellite instability)
What oncogenes are associated with CRC?
- KRAS
- CMYC
What tumour suppressor genes are associated with CRC?
- APC
- p53
- DCC
How does CRC present?
- Rectal bleeding
- Altered bowel opening
- Iron deficiency anaemia
- Palpable rectal or right lower abdominal mass
- Acute colonic obstruction if stenosing tumour
- Systemic symptoms of malignancy (weight loss, anorexia)
What does presenting with iron deficiency anaemia suggest?
Right sided colonic malignancy
When should rectal bleeding and altered bowel opening be investigated?
- Each symptom on its own >60years
- Combined >40 years
What is the investigation of choice in CRC?
Colonoscopy
What can also be carried out during colonoscopy?
- Tissue biopsies
- Therapeutic measures (polypectomy)
What is preparation is required for a colonoscopy?
- Sedation
- Bowel preparation
What are the risks when carrying out therapeutic interventions during colonoscopy?
- Perforation
- Bleeding
What radiological imaging can be carried out when investigating CRC?
- Barium enema
- CT colonography (3D virtual colonoscopy)
- CT abdo/pelvis
What are the disadvantages of radiological imaging in CRC investigation?
- Ionising radiation
- Bowel preparation
- No histology
- No therapeutic intervention
What can malignant cell invade?
Local tissues, metastasise to lymph odes or via blood to other solid organs
What investigations are carried out in the staging process?
- CT scan chest/abdomen/pelvis
- MRI scan for rectal tumours
- PET scan / rectal endoscopic ultrasound in selected cases
What are the 2 classifications for staging?
- TNM
- Dukes classification
What are the stages in the Duke’s classification
- A: tumour confined to mucosa
- B: tumour extended through mucosa to muscle layer
- C: involvement of lymph nodes
- D: distant metastatic spread
What is the basis of therapy in CRC?
Surgery
What does the operative procedure performed depend on?
- Site
- Size
- Stage of tumour
What are the 2 ways in which surgery can be carried out?
- Laparotomy
- Laparoscopic
How are Dukes A and “cancer polyps” treated?
Endoscopic or local resection
What other procedures can be carried out during surgery for CRC?
- Stoma formation
- Removal of lymph nodes for histological analysis
- Partial hepatectomy for metastases
When is chemotherapy given as a treatment?
- Adjuvant
- Dukes C, Dukes B
- +ve LN histology
- Mops up metastases
What chemotherapy agents are used?
5FU (flurouracil) and other agents
When is radiotherapy given as a treatment for CRC?
- Rectal cancer only
- Neo-adjuvant +/- chemotherapy to control primary tumour prior to surgery
What palliative care can be given for advanced disease?
- Chemotherapy
- Colonic stenting to prevent colonic obstruction
How can the outlooks be improved?
- Prevention
- Screening
What is the aim of CRC population screening?
Detect pre-malignant adenomas and early cancers in the general population
What are the modalities of screening?
-Faecal occult blood test (FOBT)
-Faecal immunochemical test (FIT)
-Flexible sigmoidoscopy
-Colonoscopy
CT colongraphy
Describe the Scottish bowel screening programme.
- Rolled out in 2007
- Age 50-74 years
- FOBT every 2 years
- If FOBT positive then colonoscopy
What has the Scottish bowel screening programme resulted in?
- Stage shift in detected cancers
- Reduction in the relative risk of CRC mortality
What high risk groups are screened for CRC?
- Heritable conditions (FAP, HNPCC)
- IBD
- Familial risk
- Previous adenomas/CRC
FAP
Familial adenomatous polyposis
HNPCC
Hereditary non-polyposis colorectal cancer
What type of condition is FAP?
Autosomal dominant
What occurs in FAP?
Multiple adenomas throughout colon
What causes FAP?
Mutation of the APC gene on chromosome 5
What is the risk of malignancy with FAP?
High risk of malignancy in early adulthood, in almost all cases by age 40 if untreated
What is the screening provided to those with FAP?
Annual colonoscopy from age 10-12 years
What prophylaxis is offered to those with FAP?
Proctocolectomy usually age 16-25
What are the extracolonic manifestations of FAP?
- Benign gastric fundic cystic hyperplastic
- Duodenal adenomas with periampullary cancer
- Desmoid tumours
- Congenital retinal hypertrophy of the pigment epithelia (CHRPE)
What NSAID chemoprevention is there for FAP?
Sulindac reduces polyp number and prevents recurrence of higher grade adenomas in the retained rectal segment
What type of condition is HNPCC?
Autosomal dominant
What causes HNPCC?
Mutation in DNA mismatch repair genes
What do tumours as a result of HNPCC typically have?
A characteristic called microsatellite instability- frequent mutations in short repeated DNA sequences
What can HNPCC predispose you to?
- Early onset CRC (40s) right sided
- Associated with cancers at other sites : endometrial, genitourinary, stomach, pancrease
How is HNPCC diagnosed?
- Clinical criteria (Amsterdam/Bethesda)
- Genetic testing
What is the screening provided to those with HNPCC?
- Screening from age 25
- 2 yearly colonoscopy
What screening is provided for those with IBD?
Index surveillance colonoscopy 10 years post diagnosis then dependent on duration, extent and activity of inflammation and presence of dysplasia
What is the screening provided for previous CRC patients?
5 yearly colonoscopy
What is the screening dependent on for those with previous adenomas?
- Number of polyps
- Size
- Degree of dysplasia
What is the screening provided for those with familial history of CRC in the high moderate risk group?
- CRC in 3 FDR none <50 years
- CRC in 2 FDR mean age <60 years
- 5 yearly colonoscopy from age 50
What is the screening provided to those with familial history of CRC in the low moderate risk group?
- CRC in 2FDR >60 years
- CRC in 1 FDR <50 years
- Once only colonoscopy at age 55 years
