Colorectal cancer Flashcards
What cause of cancer death is colorectal cancer?
2nd leading
What overall cause of cancer is colorectal cancer?
3rd
What is the most common histological classification of colorectal cancer?
Adenocarcinoma (95%)
What percentage of colorectal cancer is colonic and what is rectal?
2/3 is colonic
1/3 is rectal
What genes are associated with colorectal cancer?
HNPCC (5%)
FAP (<1%)
Other CRP syndromes
What are risk factors for sporadic cases of colorectal cancer?
Age
Male gender
Previous adenoma
Environmental influences (diet, obesity, lack of exercise, smoking, diabetes)
What kind of things in your diet are risk factors for colorectal cancer?
Low fibre
Low fruit and veg
Low calcium
High red meat
High alcohol
What percentage of colorectal cancers have no genetic influence?
85%
What do majority of colorectal cancers arise from?
Pre-existing polyps
What are polyps?
Protuberant growths
What are the different kinds of polyps?
Epithelial or mesenchymal
Benign or malignant
What is an adenoma?
Benign tumour of glandular tissue
What is an adenoma in origin?
Epithelial
What are the different histological types of adenoma?
Tubular (75%)
Indeterminate tubulovillous (15%)
Villous (10%)
Explain the adenoma-carcinoma sequence?
Activation of oncogene, loss of tumour suppresor gene and defective DNA repair pathway genes (microsatelite instability) cause adenoma to become carcinoma by causing cell growth proliferation apoptosis
What are examples of oncogenes?
K-ras
C-myc
What is an oncogene?
A gene that has the potential to cause cancer
What are examples of tumour suppressor genes?
APC
p53
DCC
What are tumour suppresor genes?
Ones that control cell growth
What is the presentation of colorectal cancer?
Rectal bleeding (especially if mixed in with stool)
Altered bowel opening to loose stools (longer than 4 weeks)
Palpable rectal or right lower abdominal mass
Acute chronic obstruction if stenosing tumour
Weight loss
Anorexia
What investigations are done for colorectal cancer?
Colonoscopy
Radiological imaging
is a colonoscopy therapeutic or diagnostic?
both
What can be done with a colonoscopy?
tissue biopsy
What does a colonoscopy require?
Sedation
Bowel preparation
What are risks of a colonoscopy?
Perforation
Bleeding
(particularly in patients with renal disease or bowel failure)
What radiological imaging is done for colorectal cancer?
CT colonography [3d virtual colonoscopy)
Barium enema (not gold standard)
what are issues with radiological imaging for colorectal cancer?
Ionising radiation
Bowel preparation
No histology
No therapeutic intervention
What investigations are done to stage colorectal cancer?
CT scan of chest/abdomen/pelvis
MRI scan for rectal tumours
PET scan/rectal endoscopic ultrasound in selected cases
what type of investigation is done for staging of rectal cancer?
MRI scan for rectal tumours
For Duke’s staging, what is T1 to T4?
T1 - confined to submucosa
T2 - confined to muscularis
T3 - confined to serosa
T4 - breached serosa, invading other structures
For Duke’s staging, what is N0 to N2?
N0 - no lymph node involvement
N1 - seen in 3 regional lymph nodes
N2 - seen in 4+ regional lymph nodes
For Duke’s staging, what is M0 to M1?
M0 - no metastases to distinct organs
M1 - metastasis to distinct organs
What is the treatment for colorectal cancer?
Surgery
Chemotherapy
Radiotherapy
What are the 2 surgical options for colorectal cancer?
Laparotomy vs laparosopic
how can dukes A and cancer polyps be treated?
endoscopic or local resection
what may have to be formed following surgery?
Stoma formation - colostomy (permanent/temporary)
Removal of lymph nodes for histological analysis
Partial hepatectomy for metastases
When is radiotherapy used?
rectal cancer only
or
‘neoadjuvant’ +/- chemotherapy to control primary tumour prior to surgery
when is chemotherapy used?
‘adjuvant’
Dukes C, ?Dukes B
positive lymph node histology
Mops up micrometastases
Agents - 5-FU (fluorouracil) +/- other agents
What is 5 year survival of Duke’s stage A?
83%
What is 5 year survival of Duke’s stage B?
64%
What is 5 year survival for Duke’s stage C?
38%
What is 5 year survival of Duke’s stage D?
3%
What can prognosis of colorectal cancer be improved by?
Prevention (changing lifestyle factors)
Screening (high risk groups and average risk population)
What is the aim of population screening?
Detect pre-malignant adenomas/early cancers in the general population
What are some modalities of screening?
Faecal occult blood test (FOBT)
Faecal immunochemical (FIT)
Flexible sigmoidoscopy
Colonoscopy
CT colonography
When does the Scottish population start getting an FOBT every 2 years?
Between age 50 to 74
What happens if a FOBT is positive?
Colonoscopy
What does FOBT stand for?
Faecal occult blood test
Does FOBT have a greater positivity in men or woman?
men
What does faecal immunochemical testing check?
Specific for human haemoglobin
What are examples of high risk groups for colorectal cancer that require screening?
Heritable conditions (FAP and HNPCC)
Inflammatory bowel disease
Familial risk
Previous adenomas/colorectal cancer
What does FAP stand for?
Familial adenomatous polyposis
what are disadvantages of screening?
high interval cancer rate
FOBT has lower positivity in women
what is a more recent method of screening?
Faecal Immunochemical Testing (FIT) introduced in Scotland in Nov 2017
Specific for human haemoglobin
Automated
Quantitative
User friendly format that increases uptake
Provides flexibility to alter the cut-off to accommodate risk factors including age
and gender which could reduce the interval cancer rate
What does HNPCC stand for?
Hereditary non-polyposis colorectal cancer
What kind of genetic condition if FAP?
Autosomal dominant
What gene is FAP a mutation of?
ACP gene on chromosome 5
What do people with FAP have a high risk of?
Malignant change in early adulthood, in almost all cases by age 40 years if left untreated
What screening is done for people with FAP?
Annual colonoscopy from age 10-12
Other than screening, what else is often done for people with FAP to reduce the risk of colorectal cancer?
Prophylactic proctocolectomy usually age 16 to 25
What is proctocolectomy?
Surgical removal of all of the rectum and part of the colon
Prophylactic proctocolectomy usually age 16 - 25 yrs
What are extracolonic manifestations of FAP?
Benign gastric fundic cystic hyperplastic
Duodenal adenomas with periampullary cancer
What kind of chemoprevention is often given to people with FAP?
NSAIDs chemoprevention
What does NSAIDs chemoprevention do?
Reduces the number of polyps and prevent recurrence of higher grade adenomas in the retained rectal segment
what type of genetic mutation is MAP?
Autosomal recessive
what gene is responsible for the genetic mutation in MAP?
pathogenic variants in the MUTYH base-excision repair gene
what is CRC in MAP more likely to be?
right sided and synchronous
Cumulative CRC risk of 63% at 60 years
Polyposis predisposition syndrome with significant phenotypic overlap with FAP; polyps develop in early adult life.
Annual colorectal surveillance commencing age 18–20 years
Duodenal adenomas have been reported in 17–34%; upper GI surveillance starting at the age of 35 years
What kind of genetic condition is HNPCC?
Autosomal dominant condition
What gene causes HNPCC?
Mutation in DNA mismatch repair (MMR) genes
What are examples of DNA mismatch repair genes (MMR) that cause HNPCC?
MLH1
MSH2
What characteristics do tumours caused by HNPCC usually have?
Microsatellite instability (MSI) which are frequent mutations in short repeated DNA sequences (microsatellites)
Where in the colon does HNPCC usually cause cancer?
Right sided
Other than the colon, what other sites can HNPCC cause cancer?
Endometrial
Genitourinary
Stomach
Pancreas
How is HNPCC diagnosed?
Clinical criteria (Amsterdam/Bethesda)
Genetic testing
What is done for people with HNPCC to reduce the change of them developing colorectal cancer?
Screening is given every 2 years as a colonoscopy
In terms of a family history of colorectal cancer, who is considered a high moderate risk?
Colorectal cancer in 3 first degree relatives where none <50
or
Colorectal cancer in 2 first degree relatives mean age <60
What is done for people who are considered a high moderate risk with a family history of colorectal cancer?
5 yearly colonoscopy from age 50 years
In terms of a family history of colorectal cancer, who is considered to be low moderate risk?
Colorectal cancer in 2 first degree relatives >60
or
Colorectal cancer in 1 first degree relative <50 years
What is done for people with a family history of colorectal cancer who are considered low moderate risk?
Once only colonoscopy at 55 years
What are people with IBD given to reduce change of getting colorectal cancer?
Index surveillance colonoscopy 10 years post diagnosis, then dependent on duration, extent and activity of inflammation and presence of dysplasia
What are people with previous colorectal cancer given to reduce the chance of getting it again?
5 yearly colonoscopy
What are people with previous adenomas given to reduce the chances of developing colorectal cancer?
Colonoscopy dependent on number of polyps, size and degree of dysplasia
FIT occult blood for Symptomatic Patients?
FIT (at 100 µg Hb/g cut-off) more accurate than standard alarm symptoms NICE or SIGN referral criteria for detection of CRC