Colorectal Cancer Flashcards
Describe the epidemiology of colorectal cancer
Second leading cause of cancer death in the western world. 17,000 deaths in UK per year 3rd commonest cancer diagnosis overall 95% are adenocarcinomas 2 thirds colonic. 1 Third rectal
What are the risk factors for colorectal cancer?
Most (85%) are sporadic with no familial/genetic influence
10% have familial risk
Inheritable conditions: HNPCC (5%), FAP (
What are the risk factors for sporadic colorectal cancer cases?
Age Male gender Previous adenoma/CRC Environmental influences: -Diet (Decreased fibre, fruit and veg and calcium. Increased red meat and alcohol) -Obesity -Lack of exercise -Smoking -Diabetes mellitus
Why are colorectal polyps so important?
The majority of colorectal cancers arise from pre-existing polyps.
Protuberant Growths
Variety of histological types
epithelial or mesenchymal
benign or malignant
Discuss adenomas
Benign, pre-malignant
Epithelial in origin
2 main histological types:
- Tubular (75%)
- Villous 10%
- Indeterminate Tubulovillus (15%)
Morpholigically: predunculated or sessile
High risk lesions = size, number, degree of dysplasia, Villous achitecture
Describe the molecular aspects of the carcinoma sequence
Activation of oncogene: k-ras, c-myc
Loss of tumour suppressor gene- APC, p53, DCC
Defective DNA repair pathway genes- MSI
All these lead to cell growth, proliferation and apoptosis
How does colorectal cancer present?
Rectal Bleeding
Altered bowel habit (diarrhoea)
(Each symptom on its own investigate >60yrs. Both symptoms, investigate >40yrs)
Iron deficiency anaemia (men and non-menstruating women)
(More likely right sided)
Palpable rectal or right lower abdominal mass
Acute colonic obstruction if stenosing tumour
Systemic symptoms of malignancy (weight loss, anorexia)
What investigation do you carry out in suspected colorectal cancer
Colonoscopy (Gold standard)
Allows biopsies to be taken
Therapeutic as well as diagnostic (polypectomy)
Radiological imaging:
- Barium enema
- CT colonoscopy (3D Virtual colonoscopy)
- (CT abdo/pelvis)
What are the advantages and disadvantages of colonoscopy vs Radiological imaging?
Sedation
Bowel preparation
Risks: Bleeding and perforation
Ionising radiation
Bowel preparation
No histology
No therapeutic intervention
What investigations can you do to stage colorectal cancer?
CT of chest/abdomen/pelvis
MRI for rectal tumours
PET scan / Rectal endoscopic ultrasound in select cases
Give a basic outline of TNM staging for colorectal cancer
T1-T4 = local disease progression N0-N1 = lymph node involvement M0-M1 = distant metastasis
Give a basic outline for dukes staging in colorectal cancer
A = tumour confined to mucosa B = Tumour extended through mucosa to muscle layer C = Involvement of lymph nodes D = Distant metastatic spread
Describe the surgical treatment of colorectal cancer
Basis of therapy
About 80% of patients have surgery
Dukes A and cancer polyps = endoscopic or local resection
Operative procedure depends on site, size and stage of tumour
Laparotomy vs laparoscopic
Stoma formation - colostomy (temporary or permanent)
Removal of lymph nodes for histological analysis
Partial hepatectomy for metastasis
Describe the use of chemotherapy in colorectal cancer treatment
Adjuvant
Dukes B (possibly C)
Positive lymph node histology
Mops up micro-metastases
Describe the use of radiotherapy in colorectal cancer treatment
Rectal cancer only
Neoadjuvant +/- chemo to control primary tumour prior to surgery
Describe the use of palliative care in colorectal cancer
For advanced disease
Chemotherapy
Colonic stenting to prevent colonic obstruction
Describe the Scottish bowel screening program
Started 2007 Age 50-74 years FOBT every 2 years If positive then colonoscopy About 15% reduction in the relative risk of CRC mortality
What are some examples of high risk groups you may screen for CRC?
Heritable conditions: -FAP (familial adenomatous polyposis) -HNPCC (hereditary non-polyposis colorectal cancer) IBD Familial risk Previous adenoma/CRC
What is FAP?
Familial Adenomatous Polyposis
Autosomal Dominant Condition
Multiple (>100) adenomas throughout colon
(50% by 15. 95% by 35)
Mutation of APC gene on chromosome 5
(about 25% of all cases are due to new mutations)
High risk of early malignant change in early adulthood, in almost all cases by age 40 years if untreated
How do you deal with patients with FAP?
Annual colonoscopy form age 10-12yrs
Prophylactic proctocolectomy usually age 16-25yrs
What other non colonic problems does FAP cause?
Extracolonic manefestations:
- Benign gastric fundic cystic hyperplastic
- Duodenal adenomas in 90% with periampillary cancer
Desmoid tumours
CHRPE = congenital retinal hypertrophy of the pigment epithelia
Describe NSAID chemoprevention
Used in FAP
Sulindac reduces polyp number and prevents recurrence of higher grade adenomas in the retained rectal segment
Describe HNPCC
Autosomal dominant condition
Mutation in DNA MMR genes
TUMOURS TYPICALLY HAVE A MOLECULAR CHARACTERISTIC (MSI)
FREQUENT MUTATIONS IN SHORT REPEATED DNA SEQUENCES (MICROSATALITES)
Early onset of CRC (40 years right sided)
Associated with cancer at other sites: endometrial, genitourinary, stomach, pancreas
What is the diagnosis procedure and screening in HNPCC?
Clinical criteria (Amsterdam / Bethesda) Genetic testing
Screening from age 25 every (2 years colonoscopy)