Lectures: Med D Flashcards
Define sensitivity
positivity in the presence of disease
Define specificity
negativity in the absence of disease
Give two prognostic indicators of testicular teratomas?
- HCG
- AFP
If a patient has HER2 positive breast cancer what can they be treated with?
Herceptin
- works to block receptors and stop signal responsible for cancer cell growth and division
What is Tumour Lysis Syndrome, and what are the biochemical features?
- massive necrosis of tumour cells
- during treatment with cytotoxic drugs
Features
1. Hyperkalaemia –> arrhythmias
2. Lactate
3. Hyperphosphatasaemia –> calcium, phosphate imbalance
What can be done to prevent tumour lysis syndrome?
- Maintain adequate hydration
-
Allopurinol
- (xanthine oxidase inhibitor) inhibits uric acid synthesis
- Monitor fluids and electrolytes
- Urinary alkalisation
- Renal dialysis
This is an immunological phenomenon:
- effectiveness of antibodies to form immune complexes can be impaired with concentrations of an antibody or antigen are too high
HOOK EFFECT
Key biochemical marker in ovarian cancer:
CA125
Key signs and symptoms of ovarian cancer
- abdominal distention
- early satiety
- pelvic / abdominal pain
- urinary urgency / frequency
What findings on examination would lead you to urgently refer a patient with suspected ovarian cancer
ascites or pelvic abdominal mass
A risk malignancy index of greater than what will lead to a patient being referred:
RMI = malignant features on US x menopausal status x Ca125 level
> 200 = high risk, staging ST and referral
What tumour marker is seen to be increased in patients with breast cancer with distant metastases?
CA15-3
Gene variations associated with increase risk of developing breast cancer:
- BRCA1
- BRCA2
Biochemical marker in pancreatic cancer
CA19-9
- low sensitivity
- main use is monitoring treatment
- may also be raised in gall bladder, bile duct and gastric cancers
Patients with what particular antigen will not produce the antigen for CA19-9 :
Patients who lack the LEWIS antigen will not express CA19.9
Marker for prostate cancer:
PSA
TOTAL VS FREE
- malignant prostate cells produce more bound PSA
- low level of free in relation to total PSA might indicate cancer
- high level of free indicate normal prostate, BPH or other conditions
Prolactinoma: symptoms
- Female: amenorrhoea, infertility, lactation, loss of libido
- Males: erectile dysfunction, libido, infertility
Pressure of prolactinoma on surrounding tissues:
- headaches
- vision loss
Treatment of prolactinoma
- Cabergoline (dopamine agonist, to shrink tumour)
- Bromocriptine
If suspecting growth hormone excess, what important test should be done:
Glucose tolerance test.
Notes
- glucose should suppress growth hormone levels.
- will help decide if there is excess GH production
- ACROMEGALY
Symptoms of primary aldosteronism:
- HTN resistance to medication
- Hypokalaemia
What test will be done to see where the excess aldosterone hormone is coming from:
- adrenal vein sampling to lateralise
- in unilateral disease
Pheochromocytoma
rare tumour, that forms in adrenal medulla
Paragangliomas
form outside the adrenal gland
Investigations for pheochromocytoma and paraganglioma
- plasma free metadrenalines
- total fractionated urine metadrenalines
PTHrP: What is this and where is it found?
- Found in pancreatic islet and ductal cells.
- PTHrP acts on PTH1P receptor
- regulate cell proliferation
- apoptosis
- differentiation
Role of PTHrP
- can stimulate calcium resorption from bone
- and reabsorption in the kidneys
- causing hypercalcaemia!
Tumours of pancreas summarised:
1. Insulinoma: Whipple’s triad
2. Glucagonoma –> 5Ds
- depression
- dermatitis
- diarrhoea
- diabetes
- deep vein thrombosis
3. Gastronioma –> Zollinger-Edison syndrome
4. VIPoma –> relaxes muscles in stomach and bowel
Zollinger-Ellison syndrome
multiple severe, recurrent peptic ulcers in part of small intestine
what occurs in carcinoid syndrome?
- tumour produces excessive amounts of serotonin that the liver can’t break down
What gene is implicated in MEN 1 and what possible biochemical tests would you want to do?
MEN 1 tumour suppressor gene
Pituitary adenoma
Parathyroid hyperplasia
Pancreatic tumours
Men 2A
RET PROTONCOGENE
Parathyroid hyperplasia
Medullary thyroid carcinoma
Pheochromocytoma
Men 2B
RET PROTONCOGENE
- mucosal neuroma
- marfanoid body habitus
- medullary thyroid carcinoma
- pheochromocytoma
What might be seen on blood film in acute myeloid leukaemia?
AUER ROD
Commonest childhood cancer:
acute lymphoblastic leukaemia
What additional test would you do in a patient with suspected chronic myeloid leukaemia?
FISH to look for Philadelphia chromosome
- translocation between chromosome 9 and chromosome 22.
- present in 95% of CML patients.
Treatment of chronic lymphocytic leukaemia:
IMATINIB (tyrosine kinase inhibitors)
What is a blast crisis:
progression of CML to acute blast phase —> acute leukaemia
Myelodysplastic syndromes
- group of cancers
- immature blood cells in bone marrow do not mature or become healthy blood cells
- bone marrow doesn’t make normal blood cells
Myeloma is associated with what abnormal proteins produced by the immune system:
Paraproteins
- IgG
- IgA
- free light chain
Paraproteins in blood may lead to abnormal blood flow
- hyper viscosity
Vertebral collapse in myeloma may lead to what condition:
Spinal cord compression
What type of cell is classically seen in Hodgkin Lymphoma
-
REED STERNBERG CELL
- abnormal lymphocytes containing more than one nucleus
Name the most rapidly growing type of non-Hodgkin lymphoma:
BURKITT lymphoma
Staging for lymphoma
Ann Arbor staging - done with CT
- Localised
- Two or more on same side of diaphragm
- two or more above and below diaphragm
- widespread disease, multiple organs and nodal involvement
Microcytic anaemia causes:
TAILS
T- thalassemia
A- anaemia of chronic disease
I- iron deficiency
L- lead poisoning
S- sideroblastic anaemia
Macrocytic anaemia causes:
Megaloblast
- b12 deficiency (e.g. pernicious anaemia)
- folate deficiency
Non-megaloblast
- alcohol
- reticulocytosis
- liver disease
- hypothyroid
LDH is a marker of:
cell turnover so can show cell and tissue damage in the body
What test might you do to help determine the potential cause of haemolysis
DAT (direct antiglobulin test)
Direct coombs test
What genetic mutation has been shown to be associated with myeloproliferative neoplasm in a patient?
JAK 2 mutation
When would a patient with thrombocythemia be referred to haematology?
- Platelet count > 1000 (unexplained)
- Platelets 600-1000 in association with thrombotic event
What intervention may be used to help control the blood cell count without allowing blood cell count to do down:
cytoreductive therapy: hydroxycarbamide
Important side effect of bisphosphonate use:
jaw necrosis
DRAW OUT THE CHEMOTHERAPY TOXICITY BEAR
D- doxorubicin (cardiomyopathy)
A- asparagine (alopecia)
C- cisplatin (nephrotoxic)
What is the ALARA principle:
- avoiding exposure to radiation that does not have direct benefit to you
- keep dose as low as reasonably possible
What method may be used to help define quality of life:
EQD5 questionnaire
Looks at:
- mobility
- self-care
- usual activities
- pain / discomfort
- anxiety/ depression
What sign is seen in superior vena cava obstruction:
Pemberton sign
Management of superior vena cava obstruction:
EMERGENCY
- ABCDE
a. nurse upright
b. oxygen
c. dexamethasone 8-16mg daily with PPI
d. if thrombus then LMWH
Definitive treatment of superior vena cava obstruction:
vascular stenting
Case 1: 65 yo male, 4/52 hx of dyspnoea
- Cough productive of thick yellow sputum with streaks of blood
- Weight Loss ~ 1 stone
- Noticed his face is puffy at the end of the day last 2/52
- PMHx:
- T2DM
- SHx
- Smoker, 30 pack year hx. Retired factory supervisor.
Indicative of:
Superior vena cava obstruction
Case 2: 58 Female, generally unwell
- known breast cancer
- received her second cycle of adjuvant chemotherapy 10 days ago
- 2/7 hx of dysuria and frequency of micturition
- feeling hot and cold
- uncontrollable shaking this afternoon
Observations:
- HR 110bpm , BP 92/60mmHg
- RR 18, oxygen sats 99% on RA
- Temp 38.8
Indicative of:
Neutropenic sepsis
Definition of febrile neutropenia
- temperature > 38 degrees
- neutrophils < 0.5
What scoring system is used to identify low risk febrile neutropenic patients:
MASCC score - > 21 considered low risk
Antibiotic protocol for low vs high risk patients of neutropenic sepsis
Low risk
No allergies: PO co-amoxiclav & Ciprofloxacin
Pen allergic: PO doxy & Cipro
High risk
No allergies: IV TAZ & IV Gent
Pen allergic: IV meropenem & IV gentamicin
Severe allergic: IV Teicoplanin & IV cipro & IV gent
Case 3: 70 Male not his usual self
PC: attended for radical radiotherapy for known Lung Ca.
Complaining of feeling muddled over last 24 hours, disorientation. Tiredness, nauseated, increasingly thirsty, vague abdominal pain and constipation.
PMH: HTN and IHD
High creatinine, high calcium
Differential diagnosis
HYPERCALCAEMIA
- Painful bones
- renal stones
- abdominal groans
- psychiatric moans
Management of hypercalcaemia
-
Vigorous rehydration
- 4L of IV fluid in 24 hours
-
Monitor for fluid overload
- repeat serum Ca before giving bisphosphonate
- commence bisphosphonates 24hrs post rehydration
- repeat serum Ca before giving bisphosphonate
- RANK-ligand inhibitors such as denosumab
Case 4:
PC: progressive lower thoracic back pain, radiates bilaterally around umbilicus, worse on coughing
PMH: metastatic prostate cancer
DH: 3 monthly zoladex (goserelin)
OE:
- normal tone, power, reflexes
- sensation normal
- spinal bony tenderness palpable at T10
Differential diagnoses:
metastatic spinal cord compression
Management of MSCC
URGENT MRI WHOLE SPINE (within 24hrs)
- lie flat (log roll)
STEROIDS —> dexamethasone 8mg BD PO with PPI
- WHO analgesia ladder
- Consider: catheterisation, laxatives
Definitive treatment - surgery vs radiotherapy
- MSCC pathway
Case 6: 49 Male, diarrhoea and dizziness
PC: diarrhoea watery, non bloody, no vomiting and patient is afebrile.
Obs: T36.7, 114bpm, BP 98/56
PMH: advanced kidney Ca.
DH: new cancer drug about 7 weeks ago
OE: abdomen SNT, no masses
Likely diagnosis:
Immunotherapy mediated colitis
Management of immunotherapy induced colitis
GRADE 1
—> fluids, loperamide
–> up to 3 extra stools, no blood or pain
Grade 2
–> admit under gastro
–> oral pred w/ PPI cover
–> omit next dose immunotherapy
–> regular obs/ NEWS/ Stool
Grade 3-4
–> more than 7 stools than baseline
–> severe abdo pain
–> methyl pred
–> stop immunotherapy
What is brachytherapy?
- Radioactive sources implanted into tumour or surrounding tissue
- Like 125 I, 103Pd, 192Ir, 137Cs
- Delivers high dose of radiation to desired target while minimizing the dose to surrounding normal tissues
Chemotherapy: How to antimetabolites work ?
prevent DNA synthesis
Cell cycle specific (S-phase)
- folate antagonist (methotrexate)
Chemotherapy: How do alkylating agents work?
prevent uncoiling of DNA for replication
- Topoisomerase inhibitors –> prevent uncoiling of DNA but breaking down enzymes used for uncoiling
- Non-classical alkylating agents –> lock cross links preventing them from uncoiling
How do Vinca alkaloids work?
cell cycle arrest
by preventing microtubule formation
How do antimitotic antibiotics work?
e.g. BLEOMYCIN
prevent mitosis from occuring
How do Taxanes work?
spindle cell inhibition
examples: paclitaxel, docetaxel
Give some examples of anti-metabolite drugs?
- methotrexate
- 5-FU
- Capecitabine
Give some examples of alkylating drugs (classical)?
- etoposide
- ifosphamide
Give examples of alkylating drugs (non-classical)
- cisplatin
- carboplatin
- oxaliplatin
Give examples of Vinca Alkaloids:
- Vincristine
- Vinblastine
Give examples of antimitotic antibodies
Anthracycline
- doxorubicin
- Epirubicin
Non-anthracycline
- bleomycin
Terminology used to determine response to chemotherapy
Complete response –> disappearance of all measurable disease
Partial response –> 30% decrease from baseline
Minimal response –> decrease in measurable lesions, no new lesions observed
Stable response –> neither partial response or progressive disease criteria have been met
Progressive disease –> 20% increase in one or more lesions
One dose of an oncology therapy is known as:
cycle
Course = number of cycles given in one block
What criteria may be used to determine response to treatment?
RECIST criteria
Grading system used to determine severity of chemotherapy:
CTCAE - common terminology criteria for adverse events
Intrathecal method of administration is:
given into CSF
What is given alongside treatments which suppress bone growth?
growth factor
What does it mean by maximum cumulative doses?
- the max dose of drug a patient can be given in their lifetime
- e.g. bleomycin can cause significant pneumonitis and interstitial lung disease! used in patients with testicular cancer
Majority of chemotherapy is dosed based on what calculation
** body surface area (Duboi and Dubois) **
Obesity may affect the way drugs are handled / metabolised
- increase blood volume (decreased steady state concentration)
- increase in lean body mass
- increase in organ size
- increase phase 2 metabolism in liver
- increase GFR
Specific side effects of bleomycin
pulmonary fibrosis
Specific side effects of gemcitabine
pneumonitis
Specific side effects of anthracyclines
cardiac toxicity
Specific side effects of cisplatin:
hearing loss
Peripheral neuropathy quite common with what class of chemotherapy :
Taxanes
What genetic deficiency in 5-FU toxicity can lead to significant mucositis, diarrhoea, extreme fatigue and dehydration
DPD deficiency
What mutation results in loss of drug function of cetuximab in the treatment of colorectal cancer:
KRAS mutation
- people with colorectal cancer with a RAS mutation will not respond to treatment even if treated with it
- cetuximab cannot bind !
Patients with BRCA mutation tend to respond well to what drug?
carboplatin
How do PARP inhibitors work?
- prevent cell DNA from repairing itself
- e.g. Olaraparib
What kind of receptors are quite active in melanoma and can be targeted with immunotherapy:
BRAF
Name the type of cancer which develops in the glands that line your organs:
adenocarcinoma
- produce mucin
- mucin is a protein produced by epithelial cells
Molecular tests in routine use for breast cancer
- ER
- PR
- HER-2
