L4 Diagnostics and Treatment (CRC) Flashcards
(30 cards)
Where is colorectal cancer sited?
Adenocarcinoma of the lower GI tract.
Ileocecal valve onwards = large bowel
Of what origin is CRC usually?
Epithelial
How many new cases of bowel cancer are there in the UK each year? (2016-18 average)
~42,000
How many deaths from bowel cancer were there in the UK from 2017-19?
~17,000
What percentage of bowel cancer cases are preventable cases?
54%
What percentage of people survive bowel cancer for 10 or more years?
53%
Worldwide incidence of bowel cancer is increasing, what are the numbers from 2012 and the predicted 2030 value?
2012 - 1.4 million
2030 - 2.2 million
What is causing an increasing incidence of bowel cancer in low income countries?
epidemiological transition away from infectious disease and towards non-communicable diseases.
westernised diets/ lifestyle?
EORC is increasing across the world. What are some countries with the highest EOCRC rates?
Korea - 12.9 / 100,000
Australia - 11.2 / 100,000
USA - 10.0 / 100,000
After what decade was there a large increase in incidence of colorectal cancer, indicating a changing epidemiology in the UK?
1980’s
In the 20-29 age group, what is the increase of EOCRC per 100,000?
1-2 per 100,000
no differences in incidence between sexes.
However, even in these age groups it demonstrates that there is a higher incidence as you age.
EOCRC presents with more advanced disease. Why, and what are the implications?
Younger ages not involved in screening programmes - less likely to be caught early.
Higher chance these patients will develop metastatic disease over the course of treatment.
what are the difference in % of metastatic disease between age groups <40 and >40?
<40 = 56%
>40 = 23%
What does developing metastatic CRC correlate with in regard to survival rates?
Lower survival rates.
If there is no development of recurrent disease where the tumour is situated, the survival rate is 94%.
What is the multistep process of CRC development known as?
adeno carcinoma sequence
What is the adenocarcinoma sequence?
Multistep process over 1-15 years.
Involves a series of genetic ‘hits’ :
1. APC mutation (gatekeeper)
- tumour suppressor gene (increased Wnt signalling and conversion of normal epithelium to early adenoma)
2. KRAS (promoter of growth)
- oncogene - cells grow from small to larger adenoma.
3. TP53 mutation (genome guardian)
- tumour suppressor involved in DNA repair, apoptosis, and cell cycle arrest. Loss of p53 = cells survive and replicale.
malignant transformation –> carcinoma.
Name some of the CRC diagnostic pathways.
Faecal Immunochemical Test (FIT)
Colonoscopy
2 week wait pathway (2WW)
What is a FIT test?
- detects human haemoglobin in stools
- postal fit test was 60-74 years now 50
What is involved in a routine colonoscopy?
- high risk individuals i.e. Lynch syndrome or FAP.
- direct visual examination of the bowel
- can also remove polyps (or biopsies)
- flexible tube with cameras, instrument channel
- con: can cause perforation and bleeding
What is the 2WW pathway?
- NHS initiative to increase early diagnosis.
- symptom criteria to refer patients for urgent investigation within 2 weeks
Criteria:
>40 unexpected weight loss + abdominal pain
>50 unexplained rectal bleeding
>60 iron deficiency anaemia or change in bowel habits
any positive FIT
What stains are the gold-standard for diagnosis?
Haematoxylin and eosin (H&E stains)
looking for evidence that there is distortion of the crypts.
Why do we test mismatch repair in CRC?
MMR is a reflex test in CRC.
Looks for hereditary cancer syndromes such as Lynch Syndrome (3-5% all CRC).
MMR genes = MLH1, MSH2, MSH6, PMS2
What MMR gene is Lynch syndrome associated with?
MSH6
What do mutations in MMR genes lead to?
Truncated proteins.
Mutations in genes with simple repeat sections of DNA, such as poly-A repeats (BAX, TGFBR2), known as microsatellite repeats.
