Oncological Emergencies

Question 1

What is neutropenic sepsis as described by NICE?

Answer 1

A neutrophil count of 0.5 × 10^9 per litre or lower, plus one of the following:

• Temperature ≥ 38°C OR
• Other signs or symptoms consistent with significant sepsis
• Patient undergoing systemic anticancer treatment (SACT)

Question 2

What are some of the causes of neutropenia?

Answer 2

Recent chemotherapy

• Malignant bone marrow infiltration
• Extensive radiotherapy
• Bone marrow failure secondary to non-malignant disease (e.g. aplastic anaemia)
• Hypersplenism
• Megaloblastic anaemia
• Drug-induced (e.g. clozapine)

Question 3

What are some of the RFs for neutropenic sepsis?

Answer 3

• Patients over the age of 60
• Advanced malignancy
• Previous neutropenic sepsis
• Mucositis
• Poor performance status
• Significant co-morbidities (the risk increases further in the presence of multiple co-morbidities)
• Indwelling central venous catheters
• Corticosteroids (causes immunosuppression)
• Prolonged hospital admission
• Severe or prolonged neutropenia

Question 4

What are some of the clinical signs of neutropenic sepsis?

Answer 4

• Hypotension: URGENT ATTENTION – involve outreach and consider escalation above ward care
• Fever
• Reduced urine output
• Altered conscious level or confusion/ impaired MMSE
• Mottled/ashen appearance

Question 5

What investigations should be performed for neutropenic sepsis?

Answer 5

Bedside investigations

§Urinalysis: to look for urinary tract infection

§ECG: should be performed in all acutely unwell patients.

§Capillary blood glucose: to exclude hypoglycaemia.

Laboratory investigations

• Baseline blood tests (FBC, U&E, coagulation, CRP, LFTs): white cells may be low or raised and CRP may also be raised. Serum lactate, Group and save,
• Cultures (central and peripheral); urine
• ABG
• Microbiological cultures: wounds, urine, stool, sputum, and line tip (if indwelling line infection suspected).
• Viral respiratory swab: if viral respiratory infection suspected.

Imaging

§Chest X-ray: to look for evidence of pneumonia.

§High-resolution chest CT: if fungal pneumonia is suspected.

§Abdominal ultrasound or CT abdomen: if biliary or abdominal infection suspected.

Other investigations: Bronchoalveolar lavage: if an atypical chest source is suspected, such as Pneumocystis jirovecii.

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Question 6

How is neutropenic sepsis managed?

Answer 6

• The sepsis six care bundle should be completed.
• • Pharmacological
    
    • 1st line : IV piperacillin with tazobactam (tazocin). Some guidelines may also recommend the administration of gentamicin
    • 2nd line (e.g. penicillin allergy) may include IV meropenem (dependent on local guidelines)
• Other:
  
  • Additional anti-microbial cover (e.g. teicoplanin) for gram-positive organisms may be required for patients with indwelling central venous catheters.
  • Anti-fungal treatment may be considered when the fever persists beyond 4 – 6 days
  • Granulocyte-colony stimulating factor: Recombinant granulocyte-colony stimulating factor (G-CSF) may be used for both prophylaxis and treatment of neutropenia to reduce the risk of neutropenic sepsis.
    
    • Consider in patients who are profoundly septic/neutropenic
    • Mechanism: stimulates bone marrow to produce neutrophils and may form part of specific chemotherapy regimens. E.g. filgrastim

Question 7

What are some of the complications of neutropenic sepsis?

Answer 7

• Single or multi-organ failure (e.g. renal failure, heart failure and acute respiratory distress syndrome)
• VTE (e.g. PE), DIC, Opportunistic or hospital-acquired infections, Delirium, Psychological complications (e.g. anxiety regarding future infections and chemotherapy treatment)
• Delays in chemotherapy leading to worse cancer outcomes

Question 8

What cancers are most commonly associated with metastatic spinal cord compression?

Answer 8

• lung, prostate, breast, myeloma, melanoma.

Question 9

What is the incidence of MSCC?

Answer 9

• 3–5% of cancer patients have spinal metastases.
• ~15% of those with advanced cancers develop metastatic spinal cord compression
• 10% of patients with spinal mets develop MSCC
• Incidence may be as high as 19% in breast/prostate/lung cancer
• Breast, prostate and lung account for > 60% of cases

Question 10

How does MSCC arise?

Answer 10

• Collapse or compression of a vertebral body due to metastases (common), direct extension of a tumour into vertebral column (rare).
• 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 compression -> vascular injury, cord necrosis and permanent damage

Question 11

Where (location) does MSCC arise?

Answer 11

• 30-50% have > 1 area involved
• Below L2 vertebra =cauda equina compression of peripheral nerves and not spinal cord

Question 12

What are some of the signs and sx of MSCC?

Answer 12

• Back pain ~95%. – earliest and most common
• Nocturnal pain and pain with straining.
• Spinal or radicular pain (8/10)
• Red flag: cervical/thoracic pain.
• Other: limb weakness, difficulty walking, sensory loss, bowel/bladder dysfunction
• Sensory loss in the saddle area
• Neurological signs: depend on the level of the lesion.
  
  • Lesions above L1 – usually UMN signs in the legs and a sensory level.
  • Lesions below L1 - usually cause LMN signs in the legs and perianal numbness. Tendon reflexes tend to be increased below the level of the lesion and absent at the level of the lesion

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Question 13

What features can be seen of MSCC on clinical examination?

Answer 13

• Spasticity (increased tone, clonus and hyperreflexia in limbs below level of MSCC
• Plantar reflexes up going (not cauda equina)
• Sensory loss with well defined dermatonal level
• Palpable bladder (urinary retention)

Question 14

How is MSCC managed?

Answer 14

• Admit for bed rest with log rolling – lie pt flat
• Ix: Urgent (within 24h) MRI of whole spine.
• Pharmacological: Dexamethasone 16mg/24h PO + PPI (unless? lymphoma) for prophylatic gastroprotection and blood glucose monitoring.
• Thromboprophylaxis (compression stockings, LMWH: Consider if reduced mobility
• Urgent referral to clinical oncology/cancer MDT
• Radiotherapy is the commonest treatment and should be given within 24 hours of MRI diagnosis.
• Decompressive surgery (Balloon kyphoplasty) Treatment of choice if fit and good prognosis (>3/12)
  
  • Prognostic indicators: Multiple myeloma, lymphoma, or breast, prostate or renal cancers
    
    • Good motor function at presentation
    • Good performance status
    • Limited comorbidity
    • Single-level spinal disease
    • Absence of visceral metastasis
    • Long interval from primary diagnosis
    • Also for biopsy or stabilisation
• Urinary cathetarisation
• Supportive: Good nursing care; care re pressure areas; Analgesia; Laxatives; Bladder care; Monitor BMs; VTE prophylaxis; Physiotherapy; Occupational therapy

Question 15

In which cancers is metastatic hypercalcaemia most commonly seen?

Answer 15

• Most common in SCC (lung, H&N, kidney, cervix).
• Also seen in breast cancer and multiple myeloma

Question 16

How does hypercalcaemia arise?

Answer 16

• Tumour secretion parathyroid hormone-related peptide (PTHrP) (80%)
• Osteolytic metastases with local release of cytokines (20%)
• Tumour production of 1,25 dihydroxy vitamin D (lymphoma)

Question 17

What are some of the signs and sx of hypercalcaemia?

Answer 17

• Weight loss, anorexia, nausea, polydipsia, polyuria, constipation, abdominal pain, dehydration (thirstiness) , weakness, confusion, seizure, coma.
• Severe; N&V, ileus, delirium, coma and death

Question 18

How is hypercalaemia managed?

Answer 18

• Aggressive rehydration: IV 0.9% Normal Saline – several litres
• Bisphosphonates (if EGFT≥30 IV pamidronate 60-90mg or IV zolendronic acid 4mg
  
  • Can cause renal failure so must make sure properly rehydrated first
  • Takes 5-7 days to work
  • Denosumab for refractory hypercalcaemia
• Calcitonin produces a more rapid (2h) but short-term effect and tolerance can develop. Long-term treatment is by control of the underlying malignancy.

Question 19

What is SVCO?

Answer 19

• Reduced venous return from head, neck, and upper limbs.
• Due to extrinsic compression (most common), or venous thrombosis
• SVC Syndrome with airway compromise requires urgent treatment.

Question 20

What are some of the most common causes of SVCO?

Answer 20

• >90% of svc syndrome results from malignancy (extrinsic compression)

Most common cancers: lung cancer (80%) – Occurs in 10% SCLC cases and 2% of NSCLC cases, lymphoma (10%), metastatic (eg breast), thymoma, germ cell.

• Other malignancies: metastatic seminoma, Kaposi’s sarcoma, breast cancer
• Aortic aneurysm
• Mediastinal fibrosis
• Goitre
• SVC thrombosis

Question 21

What are some of the symptoms of SVCO?

Answer 21

• SOB (50%), Swelling of face and neck (40%) , Trunk and arm swelling (40%)
• Orthopnoea, stridor, plethora/cyanosis, oedema of face and arm, cough, headache, engorged neck veins (non-pulsatile ↑JVP), engorged chest wall veins.
• Headache and lethargy

Question 22

What are some of the key sign(s) of SVCO?

Answer 22

• Pemberton’s test: elevation of the arms to the side of the head causes facial plethora/cyanosis.
• Others:
  
  • Thoracic vein distension (65%)
  • Neck vein distension (55%)
  • Facial oedema (55%)
  • Increased RR (40%)
  • Plethora 15%, Cyanosis 15%, Arm oedema 10%, Advanced stages, Laryngeal stridor, Drowsy, Coma and death

Question 23

What investigations can be performed to work out the underlying cause with SVCO?

Answer 23

• CXR Is there a mass?
• CT with contrast
  
  • Extensive collateralization
  • Intraluminal thrombus of SVC
  • Evidence of extrinsic compression

Question 24

How is SVCO managed?

Answer 24

• Prop up. Assess for hypoxia (pulse oximetry, blood gas): Give 02 if needed.
• Pharmacological: Dexamethasone 16mg/24h. CT is used to define the anatomy of the obstruction.
• Surgical: Balloon venoplasty and SVC stenting provide the most rapid relief of symptoms
  
  • Stenting: can be use if not radio or chemotherapy sensitive. 95% response rate. Symptomatic relief only
• Oncological management: Treat with radiotherapy or chemotherapy depending on the sensitivity of the underlying cancer.
  
  • Small cell: chemotherapy + radiotherapy
  • Non-small cell: radiotherapy
  • Chemotherapy: Used for SCLC, lymphoma and teratoma response rate >70%.

Question 25

What is tumour lysis syndrome?

Answer 25

* Oncological emergency due to turnover of high cell mass malignancies resulting in severe metabolic derangement * Occurs when the rapid destruction of malignant cells releases intracellular contents * Chemotherapy for rapidly - proliferating tumours (leukaemia, lymphoma, myeloma) leads to cell death and **↑urate, ↑K+, ↑phosphate, ↓ calcium, AKI (uric acid and/or calcium phosphate crystals in the renal tubules)**

Question 26

What metabolic derangements can be seen with tumour lysis syndrome?

Answer 26

**HIGH: ↑urate ↑K+, ↑phosphate** **LOW:↓ calcium** **AKI (uric acid and/or calcium phosphate crystals in the renal tubules)**

Question 27

How does tumour lysis syndrome present?

Answer 27

* Lymphoproliferative malignancy + chemotherapy, radiotherapy or corticosteroids * Can occur spontaneously * Normally **12-72h** hours post chemo * GI upset, oedema, fluid overload, haematuria, symptoms of metabolic derangements

Question 28

What are some of the RFs for tumour lysis syndrome?

Answer 28

* Large tumour burden * **LDH \> 1500 IU** * Extensive marrow involvement * High tumour sensitivity to chemotherapeutic agents * ALL, Burkitt lymphoma * Chemotherapy – cisplatin, etoposide, fludarabine, intrathecal methotrexate, paclitaxel, ritiuximab, radiation, interferon, corticosteroids, tamoxifen

Question 29

What are some of the tumours that cause **TLS?**

Answer 29

* **Poorly differentiated lymphomas,** e.g. Burkitt lymphoma and high-grade non-Hodgkin lymphomas * **Haematological malignancies: Leukemia**, e.g. acute myeloid leukemia (AML), transformed chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) * **Some fast-growing solid tumours** such as hepatocellular carcinoma, hepatoblastoma, testicular cancer, small cell lung cancer, breast cancer and neuroblastoma

Question 30

What clinical signs may be seen on examination in a patient with tumour lysis syndrome?

Answer 30

* **Clinical features**: including nausea, diarrhoea, muscle weakness, tetany, arrhythmias, seizures and sudden death *(Requires appropriate prophylaxis and early recognition and treatment)* * **Haematuria** -\> oliguria -\> anuric * **Heart failure** * Cardiac arrhythmia/arrest * Peaked T waves, QTc derangement * Primary presentation of malignancy * ‘Spontaneous tumor lysis’ ####

Question 31

How is tumour lysis syndrome managed?

Answer 31

* Prevent with **hydration** and **uricolytics**, eg: * **Rasburicase (**Synthetic uricase -\> degrades uric acid to allantoin (water soluble) * **Allopurinol (**Xanthine oxidase inhibitor -\> less hyperuricemia) * Increasing renal clearance -\> **dialysis** **Management of complications** * **Hyperkalaemia**: (1) membrane stabilisation -\> **calcium gluconate**; (2) shift of K+ intracellularly -\> **insulin, 50% dextrose, salbutamol** (3) reduction of K+ load -\> resonium, diuretics, dialysis * **Hyperphosphataemia**. Mx: **phosphate binders,** dialysis, low phosphate diet * **Hypocalcaemia**. Mx: **calcium gluconate**

Question 32

How does raised ICP present?

Answer 32

* Headache (worse in the morning, when coughing or bending over) * N+V * Papilloedema * Fits * Focal neurological signs

Question 33

How is raised ICP managed (Ix and mx)?

Answer 33

* **Ix:** urgent **CT/ MRI** (for diagnosis of expanding mass, cystic degeneration, haemorrhage within a tumour, cerebral oedema, hydrocephalus due to a tumour or blocked shunt * **Mx**: **dexamethasone**, **mannitol** (for relief of cerebral oedema)