5. Diagnosis and treatment of colorectal cancer Flashcards
what is the survival rate for CRC?
53%
how many cases of CRC are preventable?
54%
why is prevention the best way to treat CRC?
over 50% of cases are driven by environmental factors that can be changed
how is the descriptive Epidemiology of CRC changing?
- CRC is reducing in older age groups but increasing in early onset cases
- age groups under 40 show higher rates of CRC
- CRC rates are not effected by gender
- younger people tend to have more advanced disease with lower survival after 5 years
- early onset CRC patients die from the cancer but late onset patients tend to die from other things so 5 year survival is not a good comparison
define the adenoma carcinoma sequence?
the multistep process leading to CRC
what is the adenoma carcinoma sequence?
- normal epithelium
- loss of APC and FAP
- Hyper proliferative epithelium
- DNA hypo methylation
- early adenoma
- K-Ras/BRAF mutation and inflammation
- intermediate adenoma
- loss of 18q/SMADs/CDC4
- late adenoma
- loss of 17q/TP53
- early carcinoma
- additional mutations
- late carcinoma
how long does adenocarcinoma take to develop?
around 10-15 years giving you time to detect it early
what determines how fast CRC will develop?
the type of mutations and the order it obtains them
what is the 2 week wait pathway?
a fast cancer diagnosis pathway
Political policy
have to be seen within 2 weeks
implemented because the UK have poor cancer outcome compared to the rest of Europe
the symptomatic diagnosis pathway
- large numbers of patients go to the gp with GI symptoms
- so use FIT test and persisting symptoms
- 10-30% of CRC patients present as an emergency
- develop a blockage/perforation
- if you reach this 2x more likely to be stage 3 or 4
what is the FIT test?
tests for human blood in the stool
invite to colonoscopy
for every 1200 people given this 1 will have CRC
why is the screening program good?
16% less at risk of dying when you have gone through the screening program
mostly picks up the early asymptomatic tumours which when removed prevent development of CRC
what is the polyp classification?
helps to determine which are at high risk of malignancy
haggit
kikuchi
paris
kudo
how many biopsies are taken from each tumour for diagnosis?
around 8 but they must be in the correct clinical context for diagnosis
ie important in metastatic disease to ensure CRC is the primary tumour
what kind of people are in a MDT?
- oncologist
- Pathologist
- radiologist
- nurses
- surgeon
- psychologist
when is surgical management of CRC appropriate?
when it has not spread anywhere and contained in the bowel and the lymph nodes
how much is removed also depends on the aorta so all the tumour must be one side of it
what happens to surgical specimens?
- histological analysis
- look for high risk features
- positive lymph nodes or complete removal
- immunohistochemical testing
- reflex MMR testing
what is DNA mismatch repair?
a highly conserved mechanism that maintains genomic stability
its primary function is to repair base-base mismatches or insertions/deletions mis pairs generated in replication and recombination
4 proteins do this and loss of 1 or more results in variant and frameshift mutations
MMR deficiency and CRC
around 10-15% of CRC have MMR deficiency
in one of the 4 genes leading to mutations called microsatellite repeats
leading to truncated proteins
what are the 4 genes involved in mismatch repair?
PMS2
MLH1
MSH2
MSH6
what are all CRC cases tested for?
lynch syndrome
why is lynch syndrome tested for?
surveillance has reduced CRC by 61%
and has increased the proportion of people diagnosed at an early stage (1/2)
enable testing for family members
how are PD1 monoclonal antibodies used in dMMR mCRC?
blocking receptors for immune defence to improve progression free survival for both metastatic and non metastatic cancer
what is a definitive factor in further CRC treatment?
pathology of the tumour
how is locally advanced rectal cancer managed?
neoadjuvant therapy
- this is short course radiotherapy or chemo and radiotherapy combined
- it is done before surgery to reduce risk of local recurrence
- the addition of chemo was stopping distant metastases
- long course chemo had better results
