Oncology Teaching Clinic - 2 Flashcards
Pathophysiology of oncological emergencies
- A space-occupying lesion causing obstruction
or pressure effect, ie. ductal obstruction, fluid accumulation, perforation, fistula, ulcers, hemorrhage and ischemia - Metabolic or hormonal problems: e.g. SIADH, PTHrP, hormone deficiency
-
Cytopenia because of disease involvement or
treatment side effects on bone marrow
Causes of sudden deterioration in cancer patient
- Disease progression
- Complications of disease
- Complications of treatment e.g. fibrosis from RT
- Co-morbid condition worsening
- Organ decompensation
- Infection
Presentation of mechanical oncological emergencies
Airway: Stridor, SOB, Hemoptysis
GI: Pain, distension, V/D, Hemorrhage
GU: Pain, low urine output, altered consciousness, hematuria
Neuro: focal neurological S/S, altered consciousness
General approach to oncological emergencies
History
—History of present illness
—Past history of disease and treatment
—Medical illness
—Drug history
Physical examination
—Local
—Regional
—Systemic
—Neurological
Investigation
—Simple and Quick
—Helps management of acute problem
—Long term management for disease control
later
—Assess fittness of patient for treatment
Treatment:
—Acute Management: life and death
—Long term Management: Disease control
Tumor lysis syndrome
- Clinical sequalae
- Diagnosis
Cause: Rapid lysis of tumor cells (e.g. by anti-cancer drugs) leads to release of excessive quantities of cellular contents into systemic circulation
Clinical sequalae:
- HyperK, hypoerPo4, hyperurate
- Metabolic acidosis (lactate)
- HypoCa
- ARF (uric acid nephropathy and acute nephrocalcinosis)
- Arrhythmia
Tumor lysis syndrome
Clinical and Lab diagnostic criteria
Lab diagnostic criteria: Within even days after initiation of therapy. Requires two or more of:
- Hyperuricaemia (uric acid > 8 mg/dl or 475μmol/L)
- Hyperphosphataemia (phosphate > 4.5mg/dl or 1.5 mmol/L)
- Hyperkalaemia (potassium > 6.0 mmol/L)
- Hypocalcaemia (corrected calcium < 7mg/dL or 1.75 mmol/L; or ionised Ca < 1.12)
Clinical TLS: requires criteria for laboratory TLS to be met + one of the following:
- Cardiac dysrhythmia or sudden death probably or definitely caused by hyperkalaemia
- Cardiac dysrhythmia, sudden death, seizure,
neuromuscular instability (such as tetany, paraesthesias, muscle twitching, Trousseau’s sign, Chvostek’s sign, laryngospasm or bronchospasm), hypotension or heart failure, probably or definitely due to hypocalcaemia.
- Increase in serum creatinine by 0.3 mg/dl (or a single value over 1.5 times upper limit of normal range if no baseline test available); or oliguria (urine output < 0.5 ml/kg/hr for six hours)
Risk factors of tumour lysis syndrome
High risk cancers to TLS
Prevention of TLS
Prevention:
* Recognition of patient at risk
* Before start of chemotherapy (48 hrs): aggressive hydration (UO > 100ml/h), use rasburicase or allopurinol as prophylaxis, urine alkalinisation, use furosemide/ mannitol as needed
* Continue for 3-5 days after chemotherapy
* Monitoring: BP, heart rate and rhythm, tumor mass measurement, blood electrolytes, renal function, urine output and urinalysis.
High risk CA:
* Burkitt lymphoma
* Burkitt-type ALL
* Other ALL with WCC>=100
* AML with WCC>=50
TLS can precede chemotherapy
First-line investigation for TLS
Bloodtests
- Moderate risk patients – daily bloods
- High risk patients – every 8–12 hours
- Repeat tests over the period of highest risk for
TLS, seven days for haem. cancers
Biochemistry panel for Laboratory TLS:
- urea, creatinine, potassium, albumin and calcium
- Uric acid level
- Phosphate level
Treatment of TLS
- Discussion with a senior/consultant, or need
ICU support - Aggressive hydration (3 litres/m2 per day)
- Correction of hyperkalaemia
- ECG monitoring
- Rasburicase 0.2 mg/kg IV once daily (in 50 ml NS 0.9% over 30 minutes)** for 3– 7 days.**
- Stop allopurinol (allopurinol blocks conversion of xanthine to uric acid (affect Rasburiscase efficacy)
Rasburicase:
- Recombinant form of urate oxidase, Catalyzes the oxidation of uric acid to allantoin (soluble, excrete by kidney)
- C/I in G6PD deficiency
- Common S/E: rash and urticaria
Neutropenic fever
- Definition
- Risk
- Causes
- Pathogens
- Fever: defined as a single oral temperature
measurement of ≥38.3°C or a temperature
of ≥38.0°C sustained over a 1-hour period. - Neutropaenia: defined as an ANC of <500
cells/mm3, or an ANC expected to decrease
to <500 cells/mm3 during the next 48 hours
Risk: 10%–50% of patients with solid tumours
Causes:
* common sites of tissue-based infection include the intestinal tract, lung and skin
* Chemotherapy induced mucositis: esophagitis, enterocolitis, oral mucositis
* Catheter associated infections/ Air (pulmonary aspergillosis)
Pathogens:
* Fungi in haematological maligancy or
prolonged neutropenia
* Gram-positive microorganisms most common (2/3): coagulase-negative staphylococci in catheter-associated infection; viridans streptococci from oral mucositis
Neutropenic fever
S/S
Predisposing factors
Fever may be only symptom
Other S/S:
- abdominal pain, mucositis of the gastrointestinal tract, and perirectal pain.
- complications such as severe sepsis or septic shock
- Neurological or mental status changes of new onset
- Haemodynamic instability
- Evidence of hepatic insufficiency (defined as aminotransferase levels >5× normal values)
- renal insufficiency (defined as a creatinine clearance <30 ml/min)
Predisposing factors:
- severe active infections such as sepsis, hepatitis, or tuberculosis
- **bone marrow disorders **like aplastic anemia or myelofibrosis
- autoimmune diseases like systemic lupus erythematosus or rheumatoid arthritis
- cancer treatments such as chemotherapy, radiation therapy, and hematopoietic stem cell transplant (HSCT)
- Chemotherapy induced mucositis
- Indwelling vascular catheter
Neutropenic fever
First line investigations
Full Hx & P/E (daily): Focus on SKIN, GIT, RESPIRATORY tract
Skin, perianal skin (fungal cellulitis/ abscess: pain on defecation), surgical site infections S/S
Oral, abdomen exam (ask for mucositis, esophagitis, enterocolitis, bowel habits)
Lung, sinus (Respiratory S/S, Sinusitis S/S e.g. fungal sinusitis from inspiration)
Ix:
General (CBP, LFT, RFT)
Blood cultures from central venous catheter through 2 different ports
Abdomen:
Abdomen CT scan
stool culture: Add-on Clostridium difficile cytotoxin & culture
Lungs:
CXR (low risk); CT thorax (high risk)
BAL for sampling, culture
Others:
Urine, skin, sputum culture
Treatment of Neutropenic fever
Empirical broadspectrum antimicrobials with bactericidal activity (no WBC), minimal toxicity:
Oral out-patient treatment: Augmentin + Ciprofloxacin
– Amoxicillin-clavulanate (Augmentin) 40mg/kg/day
in 3 divided doses max. 500mg Q8H
– Ciprofloxacin 30mg/kg/day in 3 divided doses max. 750mg Q8H
IV monotherapy (standard in-patient tx)
– Piperacillin-tazobactam (Tazocin®)
– Imipenam-cilastatin (Tienam®)
– Meropenem (Meronam®)
– Cefepime (Maxipime®)
– Ceftazidime (Fortum®)
Reassess clinical status and myeloid recovery, daily examination and blood/site cultures, Consult Mibi
Modify IV antibiotics, add empirical anti-fungal therapy, re-image sites of infection if no recovery
Adjunct therapy:
- G-CSF (weak evidence)
- Vancomycin (if penicillin-resistant strep. infection/ severe mucositis)
Risk score for neutropenic fever
Multinational Association of Supportive Care in Cancer (MASCC) score
Clinical condition: Temp > 38.5 + ANC < 0.5 x 10^9/L
+ Low MASCC risk score = outpatient discharge with oral anti-bacterial therapy (Augmentin and ciprofloxacin)
+ High MASCC risk score = hospital admission with IV anti-biotics
High risk: : MASCC score is less than 21, with Profound neutropaenia (ANC≤100 cells/mm3) expected to last >7 days
Examples of multidrug resistant pathogens
- MRSA,
- VRE,
- ESBL-producing gram-negative bacteria
- Carbapenemase-producing enterobacteriaceae
Adrenal crisis
- Cause
- Presenting S/S
- First line investigations
Cause:
- Primary adrenal insufficiency: Sepsis, acute metabolic stress, abrupt glucocorticoid withrawal, bilateral adrenal metastasis
- Bilateral adrenal infarct/ hemorrhage
- Pituitary or hypothalamic adrenal insufficiency (rare)
S/S:
- Hyperpigmentation of skin
- Hypoglycaemia and HyperK: Lethargy and fatigue, confusion
- Fever, rigour
- Diffuse bone pain, abdominal pain
- Shock
- Dehydration: Postural Hypotension +/- reflex tachycardia, Cold peripheries
- Renal failure: HypoNa, HyperK
Ix:
- Electrolytes and renal function test
- ACTH deficiency: Low 9am serum cortisol, Short synacthen test, Insulin tolerance test, serum ACTH
- Check RAAS function: Basal aldosterone, Basal plasma renin activity
- Ddx: CT abdomen, Cranial MRI, Septic workup, Autoimmune diseases
Approach to HypoNa (e.g. due to adrenal crisis)
Adrenal crisis
Treatment
Treat hypotension: IV fluid resuscitation, monitor CVP via central line, monitor fluid status and UO
Treat cortisol deficiency:
- Dexamethasone 4mg stat then 4-8 mg over 24 hours (divded dose) if continuously measuring serum cortisol level
- Hydrocortisone 100mg stat then 100-200mg
over 24 hours (divided dose) if no repeating biochemical tests frequently
- Fludocortisone for chronic adrenal deficiency
- Correct low Na (12mmol/day change max), glucose level and hyperkalemia
Anaphylaxis and hypersensitivity
- Presenting S/S
- Ix
- High risk drugs
S/S: Mild symptoms (no respiratory distress) or Severe shock
- Atopy: periorbital edema, bronchospasm/ laryngeal edema/ SOB/ wheezing, uritcaria/ angioedema, allergic conjuntivitis, facial flushing
- Anaphylatic shock: distributive shock, warm peripheries with tachycardia, chest pain…etc
Ix: Plasma mast cell tryptase, CBC with WBC differential count, pulse oximetry, BP/P, ABG ± UO, CVP if severe hypotension
High risk drugs:
- Platinum based chemo (e.g. cisplatin, carboplatin, oxaliplatin)
- Taxane chemo (e.g. paclitaxel, docetaxel)
- Monoclonal Ab (e.g. rituximab)
- Analgesics: morphine, NSAIDs
- Contrasts, vaccines
- Skin prep (e.g. alcohol, chlorhexidine), latex
Anaphylaxis and hypersensitivity
- Treatment
Stop inciting drug, call for help
0.5mg (0.01mg/kg) IM epinephrine every 5 minutes, IV epinephrine ( 50 mcg, 0.5 ml, 1:10,000 dilution in boluses) if refractory
Airway: Immeidate intubation vs angioedema/ bronchospasm
Breathing: 100% O2, 15L/ min via non-rebreathing mask
Circulation:
- Place pt in recumbent position and elevate the feet to restore intravascular volume
- Secure IV access and give rapid fluid challenge (1-2L IV NS)
Drug therapy:
→ Antihistamines: chlorphenamine 10-20mg slowly IV or IM
→ Steroids: hydrocortisone 200mg slowly IV or IM
→ Bronchodilators: salbutamol 2.5-5.0mg nebulized or 0.25mg IV
→ IV glucagon for those on β-blocker
→ Atropine for bradycardia
SVCO
- Presenting S/S
- Ix
- Most common causes
Common causes: Lung cancer (SCC or SCLC usu), Lymphoma, metastatic breast cancer, germ-cell tumours, thymoma and mesothelioma
Presenting S/S:
Symptoms
* Dyspnoea, cough
* Facial swelling, dysphagia
* Head ‘fullness’
* Symptoms exacerbated by bending forwards / lying down
Signs
* Facial swelling and plethora, cyanosis
* Distended neck and chest wall veins
* Upper limb oedema
* Cognitive dysfunction, coma
* Pemberton sign
Ix:
- CXR, CT thorax, Venogram
- Cancer: Sputum/ pleural/ FNAC LN cytology; CT guided biopsy, Bronchoscopy and Mediastinoscopy
SVCO
Management
Acute Management:
- Dexamethasone 16mg daily divided dose (4mg Qid) with Pantoloc (PPI)
- Endovascular stenting + LMWH coverage +/- systemic thrombolysis: relief in 2-3 days, subject to availability
- Surgical resection of obstruction
Treating underlying cancer:
- Chemotherapy: for chemo-sensitive CA such as SCLC and lymphoma
- Radiotherapy: for non severe symptoms (e.g. established collaterals), slow effect onset
Malignant spinal cord compression
- Presenting S/S
- Ix
- Red flag signs
S/S:
- Chronic back pain
- Sensory symptoms (negative or positive), Motor symptoms (weakness, reflexes, incoordination…), Autonomic symptoms (sympathetic, urinary, bowel, sexual)
Ix:
- Clinical exam: Straight leg raise test for herniated disc/ sciatica, Full neurological exam, Pelvic and abdominal exams for autonomic function, Log-roll test for spinal stability
- Spine imaging: X-ray, MRI, CT myelogram, PET-CT (met.)
- Blood tests: tumour markers, electrolytes (Calcium, phosphate esp.), PTHrP, Vitamin D
Red flag signs:
- Pain in C or T or L spine, severe and unremitting, affects sleep
- Spinal pain exacerbated by straining (e.g. cough, sneeze)
- Local bony tenderness
Malignant spinal cord compression
Treatment
Scoring systems for choice of surgery
Acute management:
- Dexamethasone 16mg in divided dose with PPI cover
- Analgesia: Weak opioids or higher for neurological pain
- Consult orthopaedics for surgical decompression ad stabilisation, Vertobroplasty or Kphoplasty for vertebral body collapse
- Radiotherapy: alone or post-op
- Prophylactic LWMH
Long-term management:
- Rehabilitation
- Systemic treatment for CA
Scoring systems: Tokuhashi scoring system/ SINS score (Spinal Instability Neoplastic Score)
Hypercalcemia of malignancy
- Presenting S/S
- Causes
- ## Ix
Causes:
- PTHrP/ Ectopic PTH production
- Bone metastasis and osteolysis
- Lymphokine production that activate osteoclasts (e.g. MM)
- Extra-renal production of dihydroxy-VitD (e.g. T-cell lymphoma)
S/S:
- Typical hyperCa S/S: “moans, groans, thrones, stones, psychiatric overtones…”
Ix:
- Corrected total serum calcium/ Ionized Ca
- Phosphate, hydroxy-Vit D and dihydroxy Vit D level
- PTH level, PTHrP assay
- CBC with WBC differential, SPEP/ UPEP, Serum free light chain assay, urinalysis, serum albumin/globulin ratio
- Imaging: as indicated by localizing signs of different CA
Hypercalcemia of malignancy
Treatment
Acute treatment:
- Aggressive Hydration to increase Ca excretion: NS 200 500ml/hour (unless cardiac/renal disease), with potassium maintenance
- Forced diuresis once euvolaemic: use Furosemide, NOT thiazide (increase distal tubular reabsorption of calcium, causes hypocalcuiric hypercalcaemia)
- Calcitonin: inhibit bone resorption and increase renal excretion, rapid onset, short duration
Second-line:
- Denosumab: Anti-RANKL mAb
- Bisphosphonate: slow onset
- Corticosteroids
Last line:
- Mithramycin: highly toxic
- Dialysis
Seizure
causes of seizure / altered
conscious state in cancer patients?
—Tumor manifestation
—Drug overdose
—Infection
—Metabolic disturbance
—Cerebral vascular accidents
—Treatment complications
—Major organ failure
Immune related Adverse Events associated with immunotherapies
Treatment of immune-related adverse events
Endocrine: Thyroiditis, hypophysitis
Lung: Pneumonitis, Lung fibrosis
Kidney: Nephritis
Neuro: Meningitis, MG
Opthal: Anterior uveitis
Skin: Dermatitis, Lichen planus, Psoriasis, SJS/TEN, Vitiligo
GI: Colitis, Hepatitis
Treatment:
* Cease checkpoint inhibitor, consult sub-specialty and
consider hospitalisation
Immunosuppression:
* Systemic corticosteroids
* Infliximab (anti-TNFα)
* Mycophenolate mofetil
* Tacrolimus
Other: plasmapheresis, anti-thymocyte globulin, IVIG
Patient developed shock, loss of
consciousness and diffuse rash 15 min after
starting carboplatin infusion. You decided to
give adrenaline. Best dosage is?
0.5mg (0.01mg/kg) IM epinephrine every 5 minutes, IV epinephrine ( 50 mcg, 0.5 ml, 1:10,000 dilution in boluses) if refractory
Which of the following drug has highest risk of causing allergy/anaphylaxis?
* 1, Rituximab
* 2, Panitumumab
* 3, cyclophosphamide
* 4, Trustuzumab (herceptin)
* 5, 5-fluorouridine
Rituximab
High risk drugs:
- Platinum based chemo (e.g. cisplatin, carboplatin, oxaliplatin)
- Taxane chemo (e.g. paclitaxel, docetaxel)
- Monoclonal Ab (e.g. rituximab)
55/M good past health, heavy smoker with newly diagnosed small cell lung CA developed SVCO. He presented with severe SOB and facial swelling. CT
scan shows right paratracheal LN compressing on SVC. Best drug to give to relieve symptoms
1. Furosemide
2. Mannitol
3. Hydrocortisone
4. Prednisolone
5. dexamethasone
Ans: dexamethasone
SVCO acute Management:
- Dexamethasone 16mg daily divided dose (4mg Qid) with Pantoloc (PPI)
- Endovascular stenting + LMWH coverage +/- systemic thrombolysis: relief in 2-3 days, subject to availability
- Surgical resection of obstruction
- RT: slow onset, not for symptomatic case
SVCO symptoms are only partially relieved after medication. You decided to give more definite treatment to this patient. Unfortunately SVC stent is not available at your hospital. What will you do next?
1. Radiotherapy
2. Surgical resection
3. IV Pulse dose steroid
4. Chemotherapy
5. Best Supportive Care
Ans: Surgical resection
SVCO acute Management:
- Dexamethasone 16mg daily divided dose (4mg Qid) with Pantoloc (PPI)
- Endovascular stenting + LMWH coverage +/- systemic thrombolysis: relief in 2-3 days, subject to availability
- Surgical resection of obstruction
- RT: slow onset, not for symptomatic case
70/M with metatstatic prostatic cancer
developed sudden onset of LL weakness, constipation and urinary incontinence. You highly suspect spinal cord compression (SCC). What is the most common presentation at initial diagnosis of SCC
- Back pain
- Limb weakness
- Sensory deficit
- Dermatomal level
5.Bladder or bowel dysfunction
Ans: Back Pain
back pain is present at 95% in cord compression and can precede other symptoms by two months!
A 25 years gentleman had newly diagnosed stage IV lymphoblastic lymphoma with bulky abdominal lymph nodes. He was started on chemotherapy. He tolerated chemotherapy well but 3 days after start of chemotherapy, he developed oligouria and become confused
You ordered some blood tests. Which of following parameter is most likely to be low?
1. Urate
2. Calcium
3. Potassium
4. Phosphate
5. Haemoglobin
Ans: Hypocalcemia
TLS Lab diagnosis:
- Hyperuricaemia (uric acid > 8 mg/dl or 475μmol/L)
- Hyperphosphataemia (phosphate > 4.5mg/dl or 1.5 mmol/L)
- Hyperkalaemia (potassium > 6.0 mmol/L)
- Hypocalcaemia (corrected calcium < 7mg/dL or 1.75 mmol/L; or ionised Ca < 1.12)
cause of deranged RFT in myeloma patient?
—Infection
—Hypercalcemia
—Hyperuricemia
—Myeloma kidney: cast nephropathy, tubulointerstitial nephritis, glomerular deposition diseases/ glomerulonephritis
