Flashcards in Oncological emergencies Deck (34):
What are the 3 most common malignancies associated with hypercalcaemia?
Breast, lung and multiple myeloma
What are some different mechanisms by which cancers cause hypercalcaemia?
Osteolytic bone metastasis
Ectopic (extra-renal) activation of Vitamin D
Ectopic PTH production (rare)
How do osteolytic bone metastases cause hypercalcaemia?
Small amount due to the immediate destructive effect on bone but most due to the release of local mediators of osteolysis. Breast cancer secretes PTHrP and other cytokines which increases RANK-ligand which binds to RANK and stimulates osteolytic activity
What is the most common mechanism of hypercalcaemia or malignancy?
PTHrP release - most common cause of hypercalcaemia in solid non metastatic tumours
What cancers cause PTHrP release?
What effect of PTH does PTHrP not mimic?
Does not stimulate activation of vitamin D, therefore does not increase calcium absorption at the gut
What are the main cancers to cause hypercalcaemia by ectopic activation of Vit D?
1/3 of NHL
Extra-renal activation by malignant lymphocytes and macrophages
Clinical features of hypercalcaemia?
Weakness, vomitting, constipation, confusion, seizures, arrythmias, polyuria, polydipsia, renal impairment, anorexia, pancreatitis, PUD, bone pain, shortened QT, bradycardia, hypertension
Treatment options for hypercalcaemia?
Initally IVF hydration
Bisphosphonates (Zoledronic acid has been shown to be better then pamidronate at effect and duration of effect)
Denosumab - in bisphosphonate refractory hypercalcaemia
Renal replacement therapy
Steroids can be used if ectopic activation of Vit D
Pathogenesis of tumour lysis syndrome?
Massive cell breakdown of tumour cells leads to release of large amounts of phosphate, pottassium and nucleic acids. Nucleic acids get catabolised to uric acid which causes crystalisation and vasconstriction of renal blood flow leading to renal impairment
Lab findings in TLS?
High potassium, high phosphate, high uric acid, low calcium (due to being taken up and made into calcium phosphate crystals in the kidneys)
Risk factors for TLS?
High tumour cell proliferation rate
Bulky disease - greater then 10cm, WCC greater then 50,000, LDH greater then 2x ULN
Pre-existing renal impairment or exposure to nephrotoxins
Oliguria/acidic urine (crystals precipitate in acidic environments)
Common causes of TLS?
Small cell lung cancer
Germ cell cancer
Prevention of TLS?
In high risk disease - rasburicase prophylaxis (one dose) and aggressive hydration
In medium risk disease - Allopurinol and IVF
Low risk - watch and wait
How does allopurinol prevent tumour lysis?
Xanthene oxidase inhibitor prevents formation of uric acid from hypoxanthene and xanthene
What are some problems with allopurinol in TLS?
Does not get rid of pre-formed uric acid, only stops further being formed.
Hypoxanthene and xanthene can accumulate and cause xanthene crystals in renal tubules
What is rasburicase?
Re-combinant urate oxidase (enzyme not usually found in humans) which metabolises uric acid to allantoin (a less nephrotoxic, more water soluble substance)
Who should rasburicase not be given to?
Patients with G6PD
Treatment of establised TLS?
Regular bloods 4-6 hourly
Repeated dosing of rasburicase
Renal replacement therapy if indicated - high K, low ca, anuria
What are some causes of SVCO?
Malignancy - most common 90%
Infection - histoplasma (fibrosing mediastinitis)
Device associated thrombus (becoming more common)
What are cancers that commonly cause SVCO?
Non small cell lung cancer (50%)
Small cell lung cancer (25%)
rare: thymoma, germ cell, mesothelioma
*10% of patients with SCLC get SVCO compared with only 2% of NSCLC
Pathogenesis of SVCO
invasion or external compression of SVC leads to development of collaterals over several weeks
Due to mass in right lung, mediastinum or lymph nodes
Symptoms of SVCO?
SOB, wheeze, stridor
Distended neck veins
Headache, reduced level of consiousness
Treatment of SVCO
Previously thought to be an emergency but now getting a histological diagnosis is most important to direct treatment (unless upper airway compromise or coma due to raised ICP = urgent stent placement and RT needed)
Nurse with head of bed elevated
Anticoagulate if clot present
Chemotherapy if chemosensitive
Endovascular stent insertion gives immediate relief followed by radiotherapy
Pathogenesis of spinal cord compression?
Cauda equina starts at L1
Tumour usually originates at bony metastasis in vertebral body then extends around thecal sac taking the path of least resistance
What is the most common site of spinal cord compression?
Thoracic spine (60%)
Clinical features of spinal cord compression?
Pain - predominant symptom
Weakness - typically pyramidal (upper limb extensor weakness and lower limb flexor weakness)
Hyper-reflexic (depending on level of compression, in cauda equina hypotonic reflexes)
Ascending numbness and parasthesia
Bowel and bladder disturbance - late sign
Best imaging study for spinal cord compression?
Gadolinium enhanced MRI scan
Treatment of spinal cord compression?
Steroids - for analgesia and reduce vasoactive odema
Surgical decompression and stabilisation is recommended first line for unstable fractures or radio-resistant tumours
External beam RT for those who are not surgery canidates
What are some poor prognostic factors for spinal cord compression?
Short time to development of motor deficits
Level of impairment of motor function pre-treatment (ie walking vs paralysis)
Short interval from cancer diagnosis to spinal cord compression
What are some common causes of brain mets causing raised ICP?
Where do metastases usually form in the brain?
The junction of white and grey matter where vessels get smaller and tumour emboli lodge
Most occur in cerebral hemispheres
Treatment of elevated ICP due to brain mets?
Drainage if hydrocephalus
Resection of a single metastasis