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Bench to bedside and beyond > Colon cancer case study > Flashcards

Colon cancer case study Flashcards

1
Q

What is the bowel screening program in the UK?

A

done through the GP and available to over 50s
It is a FIT test every 2 years

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2
Q

what can put people at higher risk of CRC?

A
  1. inactive lifestyle
  2. low fibre diet
  3. diet high in processed meat
  4. obesity
  5. family history
  6. pre-existing conditions
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3
Q

what are some hereditary conditions that increase the risk of CRC?

A

lynch symdrome
familial adenomatous polyposis

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4
Q

what are some non-hereditary conditions that increase the risk of CRC?

A

IBD
serrated polyposis syndrome
polys

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5
Q

what does screening for CRC in IBD patients look like?

A

testing/risk depends on:
How long you’ve had the disease,
what part of the bowel it affects,
how serious the disease is
Family history of bowel cancer ​

Colonoscopy 8-10 years after first symptoms then every 1-5 years

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6
Q

what does screening for CRC in serrated polyposis syndrome patients look like?

A

colonoscopy every 1-3 years

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7
Q

what does screening for CRC in polys patients look like?

A

colonoscopy every 1-3 years

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8
Q

what does screening for CRC in Lynch syndrome patients look like?

A

Start screening at 25 (or 5 years before the age of diagnosis of your youngest affected relative) ​
Colonoscopy every 12-24 months

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9
Q

what does screening for CRC in familial adenomatous polyposis patients look like?

A

APC gene variant causing thousands of polyps. ​
Remove colon once disease appears and is confirmed

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10
Q

what does FIT stand for?

A

Faecal Immunochemical Testing

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11
Q

what is FIT testing?

A
  • testing for human blood in the stool
  • at home, non invasive dipstick
  • risks: false positives and negatives, treatment for harmless growths
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12
Q

what happens after a positive FIT test?

A

meet with a bowel nurse
arrange a colonoscopy for further investigation

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13
Q

what are the changes in bowel habits that indicate CRC?

A

sudden and noticeable

going more or less often
looser stools or constipated
blood in stool
bleeding

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14
Q

what is a colonoscopy?

A
  • a small camera passed through the colon
  • used to looks for polyps, IBD and CRC
  • cost = £370
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15
Q

what is the procedure for a colonoscopy?

A
  • Sedation, Gas and Air (not usually done under anaesthetic) ​
  • Look and take pictures of the colon lining ​
  • Take biopsies ​
  • Remove small polyps if present
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16
Q

how does CRC arise?

A

CRC arises from a multistep carcinogenesis due to genetic mutations and epigenetic modification of the human genome

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17
Q

what are the 3 pathways that lead to CRC?

A
  1. chromosomal instability (CIN)
  2. microsatellite instability (MSI)
  3. CpG island methylation phenotype pathway (CIMP)
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18
Q

what is chromosomal instability?

A

a persistently high rate of loss and gain of whole or large portions of chromosomes

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19
Q

what is microsatellite instability?

A

the accumulation of errors due to the mismatch repair deficiency in microsatellite regions

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20
Q

what does chromosomal instability and microsatellite instability lead to?

A

inactivation of tumour suppressor gene like APC, TP53 and MMR
the activation of proto-oncogenes like KRAS

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21
Q

what does the CpG island methylation phenotype pathway lead to?

A

DNA methylation in CpG rich sites in promoter regions of tumour supressor genes which can lead to loss of function of those genes
80% of CRC patients have a hyper methylated BRAF gene

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22
Q

what is the chromosomal instability pathway?

A
  1. APC inactivation leading to early adenoma
  2. KRAS mutation leading to intermediate adenoma
  3. 18q and SMAD2/4 loss leading to late adenoma
  4. TP53 mutation and loss finally leads to carcinoma formation
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23
Q

what is the microsatellite instability pathway?

A
  1. MMR mutation and MLH1 methylation leads to early adenoma
  2. BRAF mutation leads to intermediate adenoma
  3. TGFßR2, IGF2R, BAX mutation leads to carcinoma
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24
Q

what are common symptoms of bowel cancer?

A
  1. blood in stool
  2. change in bowel habits
  3. losing weight
  4. a lump on the right side of the abdomen or back passage
  5. tiredness
  6. breathlessness
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25
Q

what is the direct cause of weight loss in CRC?

A

as the cancer divides and proliferates they use energy from the body causing CRC patients to burn more calories at rest

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26
Q

what is the indirect cause of weight loss in CRC?

A

as the tumour grows in the colon it can interfere with digestion
for example it could mak the patient feel a false sense of fullness

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27
Q

what is histopathology?

A

the study of changes in tissue to diagnose and treat disease.
this is done by observing morphological changes under a microscope

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28
Q

how to histopathology samples come?

A

as small sections of tumour tissue called biopsies.
OR
as entire excision of tumour tissue called resections

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29
Q

What happens to tumour tissue when sent to histopathology?

A
  1. sample reception
  2. cut-up
  3. processing
  4. embedding
  5. sectioning
  6. staining
  7. quality control and pathologist signs off
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30
Q

what can additional procedures on sampled tissue determine?

A

factors that support the diagnosis
1. origin
2. type
3. severity
4. prognosis
5. clinical post-op outcomes

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31
Q

what does immunohistochemistry use?

A

specific labelled antibodies to target antigens present on the cells

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32
Q

what do the antibodies in IHC target?

A
  1. oncogene products to see if they are present in the tissue
  2. tumour suppressor gene products to see if they are absent in the tissue
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33
Q

how many lymph nodes should be examined to check for tumour presence?

A

at least 12

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34
Q

what are some risk factors for tumour metastasis?

A
  1. high number of tumour positive lymph nodes
  2. invasion of the tumour into the lmyphatics
  3. extracapsular extension in the lymph nodes which indicates an aggressive phenotype
  4. lymph node size - a large number of bulky tumour negative lymph nodes suggest an active immunological response and lower risk
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35
Q

what is metastasis?

A

the process of cancer cells spreading from the primary site of the tumour to secondary sites in the body

metastasis complicates treatment and determines malignancy

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36
Q

how can metastatic tumours spread?

A

local spread - through breach of the bowel wall
distant spread via the lymphatics or the blood stream

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37
Q

where does CRC usually spread to first?

A

the liver due to the connection to the bowel through the hepatic portal vein

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38
Q

what are the steps of metastatic tissue spreading?

A
  1. tissue invasion
  2. intravasation - enter the blood steam/lymph
  3. transport to secondary site
  4. extravasation - leave the blood/lymph
  5. metastatic colonisation
  6. angiogenesis - new blood vessel formation
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39
Q

what does the CEA test detect?

A

Carcinoembryonic antigen

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40
Q

what is Carcinoembryonic antigen?

A

a protein that is normally produced during fetal development.
in adults CEA is usually very low but it is often elevated in CRC so it is used as a tumour marker

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41
Q

what does the CEA blood test measure?

A

the level of Carcinoembryonic antigen released by cancer cells in the blood to monitor progression of cancer

42
Q

why is Carcinoembryonic antigen over expressed by cancer cells?

A

due to altered gene regulation, signalling pathways involved in cell growth, survival and differentiation may be dysregulated in cancer and the normal Carcinoembryonic antigen expression is altered

43
Q

what do increased CEA levels in the blood tell us?

A
  1. as the tumour grows or becomes more aggressive the amount of CEA released can increase
  2. tell us the level of inflammation that leads to tissue damage
  3. metastasis can cause an increase in CEA levels as there are more cancer cells in more locations that can produce CEA
44
Q

what other blood tests can be used to monitor CRC?

A
  1. CA19-9 and CA125 test
  2. liver function test
  3. complete blood count
45
Q

what does the CA19-9 and CA125 test
test for?

A

Cancer antigens and tumour markers which have higher production in cancer cells

46
Q

what does the liver function tests test for?

A

tests for alanine aminotransferase (ALT) and aspartate aminotransferase (AST)

these are used for assessing liver health and as CRC most commonly spreads to the liver it looks for abnormalities in the liver that could indicate metatasis

47
Q

what does the complete blood count test for?

A

the counts of different blood components
- RBC
- WBC
- platelets

commonly anemia is associated with CRC

48
Q

what are the limitations of CEA and other monitoring blood tests?

A
  1. CEA is not cancer specific and don’t exclusively indicate CRC
  2. other inflammatory conditions like IBD can raise CEA
  3. no single blood test is definitive on its own. a combination of tests are needed along with imaging and physical exams
49
Q

what is a haemangioma?

A

a common type of benign vascular tumour most often see in infants and are usually harmless

50
Q

what are the symptoms of haemangioma?

A

red/purple raised lesions on the skin that usually are asymptomatic and fade away over the years.

Complications: ulceration, bleeding, interfere with vision or breathing if in the right location

51
Q

what are the risk factors of haemangioma?

A

premature birth
family history of haemangioma

52
Q

what is the treatment for haemangioma?

A

not usually needed
but can use propranolol and laser therapy or surgery

53
Q

what is the TNM classification of cancer?

A

T = tumour size
N = node
M = metastasis

54
Q

T in TNM classification

A

range from Tis in very early cancer to T1-4 which described the development and intrusiveness of the tumout

55
Q

N in TNM classification

A

describes whether the tumour has spread to the lymph nodes
N0 = no regional lymph node metastasis
N1(a/b/c), = 1-3 regional lymph nodes
N2 (a/b) = 4 or more regional lymph nodes

56
Q

M in TNM classification

A

describes whether the cancer has spread to different parts of the body
M0 = no distant metastases
M1(a/b/c) = distant metastases

57
Q

what is the Bethesda classification in CRC?

A

categorises tumours into different groups based on their likelihood of being associated with hereditary nonpolyposis colorectal cancer (HNPCC)

58
Q

what are the criteria for the Bethesda classification?

A
  1. The patient is under 50
  2. synchronous CRCs or multiple CRCs or other related cancers
  3. CRC with high microsatellite instability histology
  4. CRC in one or more 1st degree relatives with a HNPCC related tumour under 50 years old
  5. CRC in 2 or more 1st or 2nd degree relatives with HNPCC related tumours
59
Q

what does HNPCC stand for?

A

hereditary nonpolyposis colorectal cancer

60
Q

what is the most common CRC subtype?

A

adenocarcinoma
- originates in the lining of the inner surface of the colon and rectum

61
Q

what are other CRC subtypes?

A

Mucinous adenocarcinoma - presence of mucin in the cancer
signet ring cell carcinoma - cells with a distinctive appearance
medullary carcinoma- poorly differentiated cells
serrated adenocarcinoma - from serrated polyps

62
Q

what is a CT scan?

A

computed tomography scan

works by using Xrays to make a detailed cross sectional image to make a 3D computer generated image

initial CRC screening and assesses the extent of local invasion and detect lymph node metastasis

63
Q

what is a MRI scan?

A

Magnetic resonance imaging

uses strong magnets and radio waves to make detailed images of the body.

used to assess soft tissue of rectum and nearby structures and to identify local tumour invasion

64
Q

what is a PET scan?

A

positron emission tomography

works by injecting a radioactive substance into the body as cancer cells absorb more then the healthy cells and a camera detects the emitted positrons

used for detecting distant metastasis and metabolic activity of tumours

65
Q

what is aortic nodal disease?

A

a lymph node tumour
this is a prognostic factor
detected by PET-CT scan
the number of lymph nodes effected can influence treatment plans

66
Q

how is next generation sequencing used to planning treatment of CRC?

A

NGS is faster and cheaper to allow for individual treatment.
check for genes predisposing to malignancy
check for genes preventing treatment with chemo therapy drugs
aid with hereditary cancers

67
Q

why does NGS look for B-RAF, KRas, NRas and MMR mutations?

A

they are genes involved in a signalling pathway that drives proliferation, differentiation and migration of cancer cells

68
Q

what is the MMR gene?

A

Mismatch repair gene

69
Q

what is KRas associated with?

A

a very common mutation
associated with aggressive cancers

70
Q

what is BRaf associated with?

A

invasion into the lymphovascular system

71
Q

why might a patient not be suitable for cetuximab treatment?

A

KRas mutation is associated with activation of MAPK and causes resistance to anti-epidermal growth factor drugs like cetuximab

72
Q

what is chemotherapy?

A

a treatment approach for cancer that involves the use of drugs to kill or slow the growth of rapidly dividing cells like cancer cells.
It is a systemic treatment as it circulated through the body via the blood stream

73
Q

what cells does chemotherapy kill?

A

cells that are in the process of splitting into 2 daughter cells via mitosis by damaging the DNA
they can also target cells during transcription

74
Q

what cells won’t chemotherapy target?

A

cells at rest

75
Q

what are some types of chemotherapy?

A
  1. alkylating agents
  2. anti metabolites
  3. anti tumour antibiotics
  4. topoisomerase inhibitors
  5. hormone therapies
76
Q

how do topoisomerase inhibitors work?

A

they interfere with enzymes involved in DNA replication, leading to DNA strand breaks and preventing cancer cell division

77
Q

what kind of things determine the type of chemotherapy a patient will receive?

A
  1. cancer type and stage
  2. medical history
  3. current health
  4. genetic factors
  5. treatment goals
  6. patient preferences
  7. response to previous treatment
  8. clinical trial availability
78
Q

what is FOLFOX?

A

a type of chemotherapy involving:

  • 5-Fluorouracil = interferes with DNA and RNA synthesis by inhibiting thymidylate synthase
  • Oxaliplatin = forms platinum-DNA adducts that induce DNA damage leading to apoptosis
  • Leucovorin = a folic acid that enhances 5-FU activity by stabilising the binding between 5-FU and thymidylate synthase
79
Q

What is FOLFIRI?

A

a type of chemotherapy involving:

  • 5-Fluorouracil = interferes with DNA and RNA synthesis by inhibiting thymidylate synthase
  • Leucovorin = a folic acid that enhances 5-FU activity by stabilising the binding between 5-FU and thymidylate synthase
  • Irinotecan = a topoisomerase 1 inhibitor with interferes with DNA replication and transcription by preventing re-ligation of DNA strands ad triggers apoptosis pathways
80
Q

how can chemotherapy be administered?

A
  • an injection
  • an IV
  • tablets/capsules
  • central lines/PICC lines
  • ports and cannulas
81
Q

what other healthy fast dividing tissues does chemotherapy kill?

A
  1. hair
  2. bone marrow
  3. skin
  4. lining of the mouth, throat, and GI tract
    can also causes neuropathy
    most side effect only occuring during treatment
82
Q

what is DPYD?

A

Dihydropyrimidine dehydrogenase

83
Q

what does Dihydropyrimidine dehydrogenase do?

A

it is essential in the breakdown of uracil and thymidine.
if you have a DPYD deficiency you are at increased risk of toxicity in cancer patients receiving 5FU

84
Q

what can happen with a DPYD deficiency in chemotherapy?

A

Without enough DPD enzyme, these chemotherapy drugs build up in the body and can cause:
a drop in the level of blood cells (increasing risk of infections, breathlessness, and bleeding), diarrhoea,
a sore mouth,
nausea and vomiting which can cause dehydration,
soreness, redness and peeling on palms and soles of feet

85
Q

why might a patient have chemotherapy after surgery?

A

to lower the risk of the cancer returning

86
Q

why might a patient be offered chemotherapy even if a cure is unlikely?

A

to:
shrink the cancer
relieve symptoms
potentially extend lifespan

87
Q

what is surgery mostly used for?

A
  1. local control
  2. tumour debulking
  3. staging
  4. diagnostic conformation
  5. prevention and risk reduction
88
Q

what is chemotherapy mostly used for?

A
  1. systemic treatment
  2. adjuvant therapy
  3. shrinking tumours
  4. Metastatic disease treatment
  5. combination therapy with radiotherapy
  6. palliative care
  7. targeted therapy
89
Q

what is the follow up for adenomas?

A

they take 7-10 years to evolve into cancer so regular screening is used to remove adenomas before they become malignant
3 year follow up colonoscopy due to high risk of neoplasia

90
Q

what is anastomosis?

A

a surgical connection created between tubular structures like blood vessels or loops of intestines

91
Q

why are regular follow ups on anastomosis important?

A

to ensure integrity and function
early detection of any leak is essential

leaks could lead to severe sepsis, multi organ failure and death

92
Q

what is the add aspirin trial?

A

a 5 year randomised controlled trial to look at the effects of taking aspirin to prevent reoccurance of CRC or reduce metastasis

93
Q

what are the aims of the add aspirin trial?

A

Investigating the effect of taking aspirin after having been treated for cancer of the breast, stomach, oesophagus (food pipe), prostate or bowel – for non-metastatic cancer

94
Q

what are the possible side effects of the add aspirin trial?

A

indigestion, nausea, stomach pain
minor bleeding from the bowel
anaemia
vomiting blood
kidney and liver impairments

95
Q

what groups are in the add aspiring trial?

A
  1. Placebo
  2. high dose aspirin
  3. low dose aspirin
96
Q

what is a colectomy?

A

the removal of the colon

97
Q

what is a righ hemicolectomy?

A

the surgical removal of the right side of the colon
done through traditional open surgery or laparoscopic surgery

98
Q

what is removed in a right hemicolectomy?

A
  1. removes the last part of the small bowel
  2. removes the right side of the colon including the appendix
  3. the 2 remaining ends are then stitched together
99
Q

when is surgery not an option for CRC?

A
  1. presence of unhealthy bowel ends
  2. risk of anastomosis not healing usually due to poor nutrition
  3. Emergency situations
  4. overall health and cancer stage
  5. nutritional status
100
Q

what is the post operative care for a hemicolectomy?

A
  1. monitoring on a surgical ward recieving oxygen, IV fluids, urinary catheter and pain management
  2. ICU only for specific complications
  3. reintroduce diet and early mobilisation
  4. discharge when: solid food, pain managed without IV meds, normal bowel functions
  5. usual hospital stay 3-7 days

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