cancer care Flashcards
things important
neutropenic sepsis abx
Tazocin
neutropenic sepsis time, presentation, differentials
10-14 days after chemo
diagnosis=
<0.5 x 10 ^9 + fever OR clinical sepsis
malignancy related fever
chemo related fever
Pulmonary embolism!
microbes neutro seps
usually line infection with commensals ent infection also common uti staph aureus epidermidis enterococcus streptococcus MRSA VRE
ix for neutr sepsis
FBC, CRP, blood culture, lactate, urine output - dipstick and mcs, u&es, LFTs,
swabs from lines
cxr/axr/mri
blood film, d-dimer and fibrinogen (to rule out DIC)
NEED TO CALL SpR and Consultant
Give Abx within one hour
fluids
O2 if desats
IF HYPOTENSIVE NEEDS URGENT ATTENTION
call itu outreach
consider escalation from ward care
prevention of neut sepsis
Patient information - hygiene, food be careful
Patient education: written and oral information, including how and when to contact 24-hour specialist oncology advice and seek emergency care
Antibiotic prophylaxis (versus increased antibiotic resistance)
Consider for future chemotherapy cycles Dose reduction (palliative chemo)
Prophylactic GCSF (curative/adjuvant)
?stop treatment
common ca that cause spinal chord compression
breast
prostate
lung
myeloma
when is spinal chord compression cauda equina
when below L2
what is the criteria for mri with suspected spinal chord compression
urgent mri within 24 hours if bone pain + abnormal neurology
otherwise within weekish
prevent scordc?
educate pts
spinal cord compression rx
admit + log roll
analgesia
steroids - dexamethasone 16mg STAT IV then 8mg BD, ppi for gastroprotection
neurosurgery review
if prog for cancer is >3months, consider surgery +/- radio +/- chemo
supportive therapy includes:
analgesia, managing pressure sores, laxatives, bladder (catheter), monitor BM, VTE prophylaxis, physiotherapy
common causes of hypercalcaemia
PTHrp Osteolytic mets - Breast, prostate, lung, kidney mets to bone multiple myeloma Lymphomas (can produce vit D) thiazide diuretics ca/vit d supplements misuse?? Addisons disease Acromegaly
why can lymphomas cause hypercalc
Lymphomas (can produce vit D)
which cancers metastasise to bone
Breast, prostate, lung, kidney mets to bone
rx hypercalcaemia
iv fluids iv zolendronic acid if refractory, rankal (which is needed by osteoclasts) inhibitor = Denosumab calcitonin steroids
tumour lysis parameters
3 up, 1 down
urea up
phosphate up
potassium up
calcium down
symptoms of tumour lysis syndrome
n+v dehydration AKI diarrhoea oliguria heart failure seizures
why can tumour lysis syndrome cause aki?
because capo4 crystals in kidney and also uric acid crystals
treatment for tumour lysis syndrome
allopurinol - xanthine oxidase inhibitor (reduces produc of uric acid)
Rasburicase (recomb uric oxidase enzyme), breaks down uric acid - also given prophylactically
manage other imbalances too
if bad, haemodialysis
when does tumour lysis present?
day 1-5 after chemo or radio
how to prevent tumour lysis syndrome?
Educate
Hydrate
monitor u&es
small bowel obstruction in cancer management
operate if operable
venting gastrostomy to decompress
switch oral meds to iv/subcut (NBM)
ppi
large bowel obstruction cancer rx
diverting stoma
chemo / radio
segmental resection
stent
Metoclopramide
moa
Acts on D2, 5HT4, 5HT3 both centrally in the chemoreceptor trigger zone (CTZ) and peripherally in the gut wall
metoclopramide indication
Indication
• Gastric stasis
• Ileus
• Chemotherapy related nausea/vomiting
metoclopramide adrs
Undesirable effects • Extra-pyramidal / antidopaminergic effects: o Tardive dyskinesia o Acute dystonic reaction (young women) o Akathesia o Parkinsonism o Neuroleptic malignant syndrome • Abdominal colic • Diarrhoea • Cardiac arrhythmias (when given intravenously (IV) in combination with HT3 antagonist (eg ondansetron)
Haloperidol moa
Haloperidol
Acts on D2 in the CTZ
Haloperidol indication for nv
- Opioid induced nausea and vomiting
- Metabolic disturbance (hypercalcaemia)
- Chemical – other drug causes
Haloperidol
adrs
- QT prolongation/Torsades de pointes
- Extra-pyramidal effects
- Neuroleptic malignant syndrome
- Sedation
Levomepromazine
moa and indication
Broad spectrum antiemetic. Acts on 5HT2 and H1 in the vomiting centre, and the D2 and alpha 1 adrenergic receptor in the CTZ and gut wall
- Nausea of unknown aetiology
- Bowel obstruction
Levomepromazine
adrs
- QT prolongation/Torsades de pointes
- Extrapyramidal effects
- Neuroleptic malignant syndrome
- Sedation
- Anticholinergic side effects
Ondansetron moa
indications
5HT3 in the CTZ and gut wall
• Used for chemotherapy induced nausea and vomiting
ondansetron adrs
- Constipation
- Headache
- Dizziness
- Nervousness
- Tremor
- Ataxia
Cyclizine
indication and moa
Acts on H1 in vomiting centre, vestibular area
- Raised intracranial pressure
- Vestibular causes
cyclizine adrs
Cyclizine Acts on H1 in vomiting centre, vestibular area • Raised intracranial pressure • Vestibular causes • Anticholinergic side effects: o Dry mouth o Confusion/delirium o Postural hypotension o Blurred vision o Constipation o Urinary retention o Arrhythmias • Drowsiness
colon cancer is now screened by what instead of faecal occult blood sampling?
FIT
faecal immunochemical testing?
colon ca screening programme
60-74 years
every 2 years send poop
if + colonoscopy
SE of bleomycin
pulmonary fibrosis
SE of cisplatin
othotoxicity, nephrotoxicity
SE of cyclophosphamide
haemorrhagic cystitis, nephrotox, SiADH
SE of doxorubicin
Cardiotoxicity
SE of vinchristine
Christ my nerves
nerve damage
SE of vinblastin
Blast my bones - myelosuppresion
SE of mtx
myelosuppor
nephrotoxic
Tamoxefen hormone therapy SEs
menopausal symptoms
DVt
Endo ca
vaginal discharge
osteoporosis in pre-meno, no added risk in post menop
teratogenecity hence need barrier contraceptives
cytotoxic chemo SEs
myelosuppresion nv mucositis oral ulcers diarrhoea weight loss infertility
immunotherapy SEs
may not occur straight away
organs inflamed
radio SEs
burns, desquamation, erythema, radiation fibrosis
further ca risk
rectal proctitis
WHO status
0-5
0 = fit and well
1 = can do work, but not strenous activity
2 = can do ADLs, but not work. Up and about >50% of the day.
3 = limited self-care, up and about <50% of the day.
4 = bed bound, disabled, unable to ADLs
5 = dead
what is different about haem chemo in neutropaenia
the nadir (low point) is usually deeper and prolonged
what should chemo pts have?
All patients should be issued with an alert card with
24 hour contact numbers.
Chemo units should rehearse situations with patients to ensure that they understand when and who they should contact if they have a proble
spin chord compres pathophysic
Usually caused by the collapse or compression of a vertebral body that contains metastatic disease (arterial seeding)
10% by direct tumour (paraspinal mass) extension into the vertebral column
Compression of cord initially causes oedema, venous congestion and demyelination which are reversible
Prolonged compressionvascular injury, cord necrosis and permanent damage
features of spin chord compre
>90% have back pain
Frequently first symptom and prolonged
Spinal or radicular pain (8/10)
Exacerbated by straight leg raising, coughing, sneezing or straining
> 75% have Limb weakness
>50% have sensory level (not cauda equina)
> 40% have bladder and anal sphincter dysfunction
Diminishing performance status/generally unwell
hcg as tumour marker
testicular
placental choriocarcinomas
hydatidiform moles
alpha foetoprotein in cancer
foetus - albumin
in ca pancreatic biliary/hcc gastric bronchial
ca19-9
mucin in epithelium of foetal git
used to monitor response to rx in pancreatc, gastric, mucinous ovarian
lead bias
detected earlier via screening
false illusion improved survival
lag bias
slower growing tumour detected
false illusion
demeclcycline is used for…
siadh
pembrolizumab
Nsclc targeted therapy:
Selective, humanized monoclonal anti-PD-1 antibody agaonst programmed death (PD) inhibitor
Blocks the interaction of PD-1 on T-cells with its
ligands, PD-L1 and PD-L2, to reactivate anti-tumor
immunity
Dual ligand blockade of PD-1 pathway
aml definition
characteristic blood film finding
accumulation of immature myeloblasts in blood and bone marrow
auer rods
gingival hyperplasia which blood ca
aml - monocytic infiltration into gums
where does aml infiltrate
lung bladder skin sinus
serious complication of aml presentation
leukostasis
Leukostasis management
too many blasts in blood impairment of microvasc perfusion hypoxia mi stroke bowl inschaemia renal failure priapism
treat with hydroxyurea, chemo, leukopheresis
what is a particularly aggressive type of aml in young people
acute promyelocytic leukemia
but
responds to all trans retinoic acid (ATRA)
age of aml
> 40yo
rarely <4
features of aml
paradoxical bleeding and thrombosis
b marrow failure
b symptoms
bone pains
ix for ?AML
FBC - pancytopaenia with blasts deranged LFTs CXr infection coag - dic (ddimer) bone marrow ex
Myelofibrosis aetiology
abnormal proliferation of all myeloid cells megakaryocytes start to release PDGF this over time leads to fibrosis of BM may even lead to failure results in EXTRAMEDULLARY HAEMATOPOESIS
Symptoms of myelofibrosis
MASSIVE hepatosplenomegaly (+ assoc symp) fever fatiguability sob hyperuricaemia bm failure
signs of myelofibrosis
pallor plethora petechiae/ecchymoses febrile/b symptoms cachexia
ix for ?myelofibrosis
fbc blood film TEAR DROP RBC pathognomonic bizarre platelets PCR/FISH for Bcr-abl Serum urate/ldh
key treatment of myelofibrosis
patient education support rx anaemia management manage thrombocytopaenia splenectomy hydroxyurea RUXOLITINIB - Jak1/2 inhibitor
causes of massive splenomegaly
CML/CLL Myelofibrosis Hairy cell leukemia Marginal zone lymphoma Sarcoidosis Gaucher disease Kala-azar
if kidney normal, what is an increased beta microbulin a sign of?
lymphoma
Physiological polycythaemia causes
smoking high altitude kidney issues that cause ^EPO e.g. ca or polycystic kidney disease sleep apnoea congenital heart disease ida
polycythaemia rubra vera define and symptoms
too many RBC, platelets, basophils, mast cells (hence aquagenic pruritis)
symptoms of hyperviscosity - cns(lethargy confusion headaches), visual disturbances, gout, arterial/venous thrombosis AND haemorrhage, burning fingers/toes, splenomegaly
poly rubra vera key mutation and rx
JAK2 - activates EPO and thromboEPO receptors
rx: clots reduce, venesection, aspirin,
if needed, chemo - hydroxycarbamide (decreases DNA synthesis)
Essential thrombocythaemia ix findings
fbc - thrombocythaemia
jak2/calr/mpl
BM - large megakaryocytes
Essential thrombocythaemia rx
aspirin
hydroxycarbamide
interferon alpha
myelodysplastic syndrom is FABULOUS
FAB classification
RA - refractory anaemia
RAS - “ with sideroblasts in BM
RAEB - refractory anaemia with >5% blasts but not enough to become a leukemia <20%
ix to do when ?MDS
FBC, bm t and a with cytogenetics and immunophenotyping to exclude AML
LDH/urate
rule out other causes:
B12/folate, UEs, LFTs, infections - HIV, Hep, EBV
what is a ring sideroblast a sign of?
x-linked sideroblastic anaemia
low grade mds
could also be alcohol abuse and lead poisoning
aplastic anaemia aetiology
immune response to initial bone marrow insult that causes damage to HPC
= pancytopaenia
= ATG, ALG and supportive rx + transfusions
prog <6 months without rx!
Active euthanasia
Witholding rx
Assisted suicide
difference
Active euthanasia = the doctor intention to end a patients life
WWT = intention is not to shorten life
Assisted suicide = a doctor helps a patient to
bring about their own death
Aprepitant
Aprepitant
NK1 antagonist; acts mainly centrally Used for more emetogenic chemo; augments
5HT3 and dex
S/E; constipation, headache
Metoclopramide
Metoclopramide Prokinetic D2 blocker (CTZ- some central activity) Can help gastric stasis 10mg TDS orally or 30mg/24 hrs SCSD Avoid long term use S/E; extra-pyramidal (may include muscle spasms and tardive dyskinesia Parkinsonian
Haloperidol
Haloperidol
D2 blocker
Acts at CTZ
Good for metabolic and drug causes of N&V 0.5-5mg in 24 hrs orally or SC
S/E; extra-pyramidal , restlessness, sedation
Parkinsonian
Cyclizine
Cyclizine
Anti-cholinergic and H1 antagonist
Blocks conduction in vestibular-cerebellar pathway and acts at VC
Good for ICP, motion sickness, pharyngeal stim, BO
50mg TDS orally or 150mg/24hrs via SCSD
Avoid in cardiac failure
S/E; hypotension, urinary retention, dry mouth, constipation, restlessness
Ondansetron
Ondansetron
5HT3 antagonist; peripheral (vagal N) and central (CTZ) action
Serotonin release triggered by bowel injury, chemo, RT
Primarily used for acute CINV
Can help in BO and renal failure
S/E; constipation, headache
4-8mg BD-TDS orally or 8-16mg/24hr SCSD Reduce dose in hepatic failure
levomepromazine
May consider levomepromazine „Domestos‟ of anti-emetics
A phenothiazine
Acts at vomiting centre and CTZ Drowsiness main dose limiting S/E 6.25mg – 12.5mg SC/orally
how to treat chemotherapy induced nausea and vomitign
CINV
N&V frequently cited as the most distressing side-effects of chemotherapy
Up to 75% of all cancer patients will experience chemotherapy-related emesis
Increased risk associated with specific chemo agents, female gender, age <50 years, past Hx of N&V (pregnancy, prior chemotherapy use, motion sickness)
Acute, delayed, anticipatory 5HT3, NK1, dexamethasone
Factor V Leiden
Factor V Leiden
Factor V Leiden (activated protein C resistance) is the most common inherited thrombophilia, being present in around 5% of the UK population.
It is due to a gain of function mutation in the Factor V Leiden protein. The result of the mis-sense mutation is that activated factor V (a clotting factor) is inactivated 10 times more slowly by activated protein C than normal. This explains the alternative name for factor V Leiden of activated protein C resistance,
random fact about cholangiocarcinoma
as w primary sclerosing cholangitis - a rare complication of ulcerative colitis
what is percutaneous transhepatic cholangiography? PTC
Needle passed through skin into dilated extrahepatic bile duct under uss
contrast injected into biliary tree
cholangiogram obtained
Lynch syndrome
autosomal dom
DNA mismatch repair gene mutation
Hereditary non-polyposis colon cancer
HNPCC
FAP
rare autosomal dom
APC tumour suppressor gene mutation
affected individuals develop multiple polyps, inevitably one will transform into cancer (accumulation of mutations)
prophylactic surgical excision of colon and rectum is advised in young adults
Peutz-jeghers syndrome
v similar to FAP
STK11 tumour suppressor gene
multiple bowel hamartomas
cancer
Duke Staging for colorectal cancer
a - within bowel lumen 90% survival
b - breached in to bowel wall 70%
c - lymph nodes 40%
d - distant mets
Bowel cancer screening
60-75
every 2 years
faecal immunochemical test (FIT)
EGFR monoclonal ab
colorectal ca
TTP
Pentad of Features: Haemolytic anaemia Thrombocytopenia Renal impairment Fever Neurology: Hallucinations, behavioural change, headaches
Path: Antibody against a metalloprotease
Reduces function of Von Willebrand’s factor
Mx: Plasmapheresis (removes antibody) and FFP
Cx: Fatal without treatment, 20% mortality with treatment
Modified hartmans explain
Operation for L sided pathology
when making anastamosis is unsafe
excise lesion, cross-staple the rectal stump, bring out the proximal part into a colostomy.
can reverse at later date.
Prostate ca
Local t1-2
Radical prostatectomy
Robotic if under 70 and thin
Or radio - brachy or external beam
Hormones via watchful waiting or active surveillance
Palliative with hormones
Locally advanced t3-4 gone through capsule
Radical radiotherapy plus hormones
Or watchful waiting
Metastatic
If fit, neoadjuvant docetaxil
Hormones
4 weeks of anti androgen + LHRH long term
Last resort steroids
Taxanes and vinca alkaloids moa
spindle poisons
doxorubicin, daunorubicin moa
dna intercalating agents
prevents transcription and replication
bleomycin moa
scission of DNA strands
Cisplatin moa
covalently binds DNA
Forms DNA-DNA adducts + cross-linking
physical disruption of DNA therefore no replication
Give two examples of antimetabolites
Purine analoge - 6-mercaptopurine
Pyrimidine analogue - 5FU, inhibits thymidilate synthase
moa of methotrexate in chemo
binds to DHFR
interferes with folate metabolism which is key to DNA synthesis
SEs of chemo
Mucositis, alopecia, Diarrhoea, NV, pulmonary fibrosis, cardiotoxicity, renal failure, myelosuppresion, phlebitis, myalgia, sterility, DIC
