1. Oncological Emergencies
Özlem Sönmez, MD
Yeditepe University Hospital
Department of Medical Oncology

2. Oncological Emergency
Any acute potentially life threatening event which if not anticipated quickly and not treated effectively may rapidly result in permanent morbidity or the death of the patient.

3. Metabolic Emergencies
Tumor lysis syndrome
Hypercalcemia
Hyponatremia: Syndrome of inappropriate ADH (SIADH)
Mechanical Emergencies (Organ invasion, distant metastases related)
Superior vena kava syndrome
Spinal cord compression
Brain metastasis
Febrile neutropenia

4. TUMOR LYSIS SYNDROME

5. Tumor Lysis Syndrome DNA RNA
The rapid killing and lysis of neoplastic cells with the release of large quantities of intracellular products and ions may result in a life threatening metabolic derangements and acute renal failure.
Intracellular space Extracellular space
K+: 4 mEq/L
Phosphate : 4 mEq/L
K+: 140 mEq/L
Böbrek yetmezliği prezentasyon sırasında veya izlemde saptanır.
DNA
RNA
Phosphate: 75 mEq/L

7. Tumor Lysis Syndrome Hyperkalemia Hyperphosphotemia Hypocalcemia
Hyperuricemia
Purines  Hypoxanthine  Xanthine
Xanthine oxidase
Uric acid

8. Etiology
Mostly associated with cytotoxic chemotherapy and radiotherapy
Spontaneous tumor lysis syndrome on presentation : rare, reported particularly in patients with Burkitt’s lymphoma
After surgical manipulation of large tumor masses.
After hormonal therapy

9. Tumor Lysis Syndrome Risk factors:
High grade tumors: high growth fraction, high cell turn-over
Large tumor mass
Chemo- and radiosensitive tumors
Most frequently seen in acute leukemia and high grade lymphoma
Rarely;
Small cell lung cancer
Breast cancer
Head and neck cancer
Medulloblastoma

10. Clinical presentation
TLS usually occurs in bulky disease treated with cytotoxic agents.
Progressive oliguria
Uremia
Fluid overload
Hypertension
CHF
Seizure
Cardiac arrythmia: related to acute hyperkalemia and hypocalcemia
Syncope
Sudden death

11. Tumor Lysis Syndrome Hyperuricemia, Hyperphosphotemia  Renal failure
Hyperphosphotemia  Neuromuscular symytoms, arrhytmia, sudden death
Hypocalcemia Cramp, tetany, convulsion, arrhytmia

12. Prevention of TLS
Avoid using drugs that inhibit the tubular reabsorption of urate: Such as salicylates, radiographic contrast dye, ethambutol, probenecid and thiazide diuretic
Hydration: Individuals at risk should have pre-hydration hours before therapy (min 3000 cc).
Alkalinization of urine: Ph> 7
NaHCO3
Acetozolomide
Oral Allopurinol (Xanthine oxidase inhibitor) mg daily should be initiated 48 hours before therapy.
Vigilant metabolic monitoring: q 3-4 hours lab test after institution of therapy.

14. Potassium levels and ECG findings
Hyperkalemia
Fatique
Neuromuscular abnormalities
Arrythmia
ECG: tall tented T wave, flat P wave,increase P-R interval and widening of QRS complex, sine-wave patern, asystole or ventricular arrythmia
Potassium levels and ECG findings

15. An Electrocardiographic Sine Wave in Hyperkalemia
A 62-year old man with chronic renal insufficiency reported having reduced exercise tolerance for the previous week. The physical examination was unremarkable, but oxygen saturation was diminished. An electrocardiogram showed a regular rhythm, with a widened QRS complex in a sine-wave configuration, and there were no discernible P waves. The T waves were fused with the widened QRS complexes (Panel A) to form the sine-wave pattern (sinoventricular rhythm), raising suspicion of severe hyperkalemia. The patient's serum potassium level was 9.1 mmol per liter. His condition stabilized after the administration of calcium chloride, bicarbonate, glucose, and insulin therapy, which was followed by hemodialysis. Serial electrocardiograms showed progressive narrowing of the QRS complex. At 24 hours after presentation, electrocardiography revealed a left bundle-branch pattern (Panel B), and his condition remained stable. Hyperkalemia triggers a progression of electrocardiographic changes, beginning with peaked T waves and PR prolongation. More severe elevations in potassium level can result in QRS widening and loss of P waves, with eventual formation of the sine-wave pattern seen here. The rhythm can degenerate into ventricular fibrillation if the cardiac membrane is not stabilized.
Petrov DB. N Engl J Med 2012;366:

16. Treatment of hyperkalemia
Avoid drugs that cause hyperkalemia, NSAIDS, Beta blocker, ACE inhibitor, K+ sparing diuretic
IV 10 ml calcium gluconate 10% over 2 minutes (This provides cardioprotection)
IV 20 units soluble Insulin + 50ml of glucose 50% ( Insulin moves K+ into the cell)
Nebulized Salbutamol 2.5mg also moves K+ into the cell.
Dialysis

17. Hyperphosphatemia (>4.5 mg/dl)
Treatment
Hydration: 2-4 lt/day
IV 20 units soluble Insulin + 50 ml of glucose 50% ( Insulin moves K+ into the cell)
Aliminium hydroxate 4x ml
Dialysis

18. Hyperuricemia Precipitation in renal medulla, distal tubules Treatment
Hydration
Alkalinization of urine pH 7-7,5
NaHCO3
Acetozolamide mg
Dialysis

19. Hypocalcemia Treat only if tetany develops Treatment
Ca gluconate or Ca chloride

20. HYPERCALCEMİA

21. Hypercalcemia
Cancer is the 2nd most common cause of hypercalcemia after primary hyperparathyroidism.
Cancer associated hypercalcemia is due to an imbalance between bone resorption and calcium excretion.
Most common malignancy associated hypercalcemia include:
Non small cell lung cancer (squmous cell )
Breast cancer
Renal cell cancer
Multiple myeloma and lymphoma
Head and Neck cancers

22. Pathogenesis Direct bone destruction Humoral factors PTH
PTH-related protein - squamous cell ca, renal cell ca
Prostoglandins(PGE)
Vit D (1-25 DHKK)-lymphoma
Cytokines IL-1, IL-6, EGF,
TNF-B, TGF-, PDGF

23. Tumors not associated with hypercalcemia
Small cell lung cancer
Prostate ca
Colorectal ca

24. Clinical Presentation
General: Dehydration, weakness, fatigue.
CNS: Hyporeflexia, mental status changes,
seizure, proximal neuropathy, coma.
GIS: Weight loss, nausea, vomiting, constipation, ileus, dyspepsia, pancreatitis.
Genitourinary: Polyuria
Cardiac: Bradycardia, short QT interval, wide T wave, Prolong PR interval, arrythmia, arrest.

25. Laboratory Findings Serum Ca, P, albumin
Serum alkalen phosphatase (HyperPTH, metas)
Electrolytes, BUN, Creatinine
ECG
Radiology
PTH, PTH-RP
Corrected Ca (mg/dl): 0.8x [(4-Albumin)+Measured Ca]

26. Treatment
All patients with hypercalcemia of malignancy should be actively treated.
Hydration with normal saline and diuretic:
ml/hr hours with adequate K+
Furosemide: Forceful diuresis increase calcium excretion.
Biphosphonates:
IV Pamidronate or zolendronate is effective in 70-90%.
Maximum effect achieved within 72 hours after treatment.

27. Treatment 3. Calcitonin and Corticosteroids:
Are used in combination, effective in lowering the serum calcium. They have rapid mode of action and no toxicity when used in short term.
Salmon calcitonin is given SC or IM at 4 units/kg 12 hourly
Oral prednisolone: 40mg/day.

28. Treatment Mithramycin, 25 gr/kg Gallium nitrate, 100-200 mg/m2
PG inhibitors
Steroids
Dialysis

29. Hyponatremia: Syndrome of inappropriate ADH (SIADH)

31. ADH secretion Increased osmolality
Plasma osmolality: 2xNa+K+BUN/2.8+Glukoz/18
Normal: mOsm/kg
Decreased plasma volume

32. Inappropriate ADH secretion
Hypotonic plasma
Hyponatremia
Urine not maximally diluted

33. Etiology Tumor CNS disease (mass, bleeding, infection)
Lung cancer (esp. Small cell)
Mesothelioma
CNS disease (mass, bleeding, infection)
Pulmonary infection (pnemonia, tbc, abcess)
Hyponatremic agents
Vincristine, cyclophosphamide
Chlorpropamide (sulfonylurea)
Carbamazepine
IV narcotics
Psychotropic agents: Amitriptilin, Thioridazine

34. Diagnosis Symptoms and Signs : Laboratorary findings:
Lethargy, nausea, anorexia, fatigue, confusion, convulsion, coma
Laboratorary findings:
Serum electrolite, creatinin, BUN, Ca, P, glukoz, T. protein, TG
Urine Na
Chest X-ray
Urine and serum osmalality
If signs of Endocrine hypofunction:
TFT, Adrenal function tests, hypophysis function tests

35. Diagnostic Criteria
Hyponatremia + inappropriately low BUN (<10 mg/dl)
No intravascular volume deficit
Urine Na > 30 mEq/L
Absence of abnormal fluid retention
Normal renal function
Serum hypotonicity along with urine that is not maximally diluted
Serum osmo: <260 mOsm/kg
Urine osmo: > mOsm/kg (Urine SG >1003)

36. Treatment Severe hyponatremi (Na <110 mEq/L)
Lower plasma volume  prox. tubule Na absorp
IV %3 NaCl, 1 lt every 6-8 hours
Furosemide mg, every 6-8 hr
Na correction must be <12 mEq/L/d (<2 mEq/4 hours)
Moderately severe hyponatremi (Na >110 mEq/L)
Fluid restriction
If Na <125: cc/d
If Na >125: 1000 cc/d
Demeclocycline: 4x mg PO
Induces renal resistance to ADH
Major toxicity: Azotemia
Lithium

37. SUPERIOR VENA CAVA OBSTRUCTION (SVCO)

38. SVCO Superior vena cava: Obstruction of SVC may be due to:
Drain head, neck, upper extremities and upper thorax
The superior vena cava is located in the middle mediastinum surrounded by trachea, (R) bronchus, aorta, pulmonary artery and perihilar and paratracheal lymph nodes.
Obstruction of SVC may be due to:
Extrinsic compression
Direct invasion by disease process
Thrombosis.
>90% SVCO: Due to malignant process.

39. Etiology Malignancy Benign Causes
Lung cancer: 67-82% (small cell cancers)
Lymphomas: 5-15%
Thymomas
Germ cell tumor
Metastatic disease: 3-20% ( Breast cancer most common)
Benign Causes
Fibrous mediastinitis from granulomatous disease include histoplasmosis, tuberculosis, syphilis.
Thrombosis due to central line catheter
Behçet’s diseases

40. Clinical presentation
Usually incidious in onset.
Dyspnea
Facial swelling
Neck, chest and upper extremity edema
Facial and head fullness
Dizziness, Fatigue
Visual disturbance
Cough
Hoarseness of voice
Chest pain
Dysphagia
Neurological findings: (2-22%)
Due to increase intracranial pressure
Agitation, Confusion, Seizure

42. Physical Findings Venous distention in the neck and chest.
Facial edema, Plethora
Cyanosis
Arm and hand edema
Telangiectasis of chest and upper back
Tachypnea
Stridor
Papilloedema

44. Diagnosis
The diagnosis is usually obvious clinically but at the time of presentation less than 50% of patients have a known diagnosis of cancer.
The diagnostic approach should begin with least invasive procedure.

45. Imaging study Chest Radiograph: CT Scan thorax: MRI
Usually abnormal in majority of cases.
Show mediastinal mass or widening.
Some have right hilar mass or pleural effusion.
CT Scan thorax:
Further define the anatomy of intrathoracic structures and pathologic lesions.
Level of SVC obstruction.
Superimposed SVC thrombosis.
Collateral circulation.
Mediastinal adenopathy or masses.
MRI

47. Histological diagnosis
Sputum cytology
FNAC
Bronchoscopy
Thoracocentesis
Lymph node biopsy
Bone marrow biopsy
Mediastinoscopy

48. Treatment The aim of treatment is to relieve the symptom and to cure.
Emergency measures:
Life threatening cerebral or laryngeal edema require immediate radiation therapy without a firm tissue diagnosis.

49. General measures: Bed rest with head elevated Diuresis
Reduce sodium intake
Corticosteroid
Anticoagulant

50. Specific measures: Radiation therapy is the primary treatment.
Chemotherapy alone may be beneficial for chemosensitive tumors i.e,
SCLC (small cell lung cancer)
NHL
Germ cell tumors
Relief from signs and symptoms usually occurs within 7-10 days.
Evidence of benefit within 24 hours in some cases.

51. Surgical measure
Surgery to remove thrombi or to bypass obstruction of SVC:
is not widely applied unless all conservative therapy (radiation therapy and chemotherapy) fails.
Expansile stent in the lumen of the compressed vessel

52. SPINAL CORD COMPRESSION

53. Spinal cord compression
Incidence: Occurs in approx. 5% of cancer patients, need rapid assessment and immediate treatment.
Etiology: Metastatic tumor from;
Breast
Lung
Prostate
Lymphoma
Multiple Myeloma
Renal
GIS
Unknown primary
Site:
Thoracic 70%
Lumbar 20%
Cervical 10%

54. Mechanism of compression
Extradural compression (most common)
Collapse of vertebral body caused by destructive lesion.
Nodal mass or primary tumor.
Intradural compression
Primary spinal cord tumor.
Secondary deposits.

56. Clinical findings
Pain 90%, usually localized to involved spinal segment.
Weakness.
Sensory changes.
Bladder and bowel dysfunction.
Paraplegia ( may develop in hours to days ).
Approx 2/3 of the patients will have sensory loss or weakness by the time of diagnosis of compression is made.

58. Diagnosis Physical examination:
Evaluation for motor or sensory weakness.
Passive neck flexion.
Straight leg raising.
Rectal examination to evaluate sphincter tone.
Pin prick testing from toe to head to establish sensory level if present.

59. Imaging study
Plain Radiograph of spine: 80-90% positive (abnormalities include erosion of pedicle, vertebral collapse and a paravertebral mass).
MRI: is the standard for diagnosis, highly sensitive and specific to detect spinal cord compression.
Other imaging study include,
CT scan of spine (computed tomography)

61. Management Treatment must be instituted immediately Corticosteroid:
A delay of several hours may lead to failure of neurological recovery.
Corticosteroid:
IV Dexamethasone 16-40mg/day in divided dose
Relieve cord compression by decreasing cord edema  improve neurological function.

62. Decompressive Surgery
If medically fit for surgery (Age, general condition)
Well localized site of compression
Life expectancy is good
Radio-resistant tumor

63. Radiotherapy Not fit for surgery Multiple sites of compression
Advanced malignancy
Life expectancy poor
Radio-sensitive tumor

64. Outcome
Overall less than 20% patients achieve significant neurological improvement
Full recovery can only be expected if the lesion is of less than 24 hour duration and neurological loss is not complete at the time of treatment.

65. BRAIN METASTASES

66. Brain metastases
25% of patients who die of cancer have brain metastases
Clinical presentation
Headache, mental changes,
Increased intracranial pressure: Papilledema, nausea, vomitting
Focal signs and symptoms: Hemiparesis
Seizure

68. Etiology
Lung cancer
Breast cancer
Renal cell cancer
Melanoma

69. Management Dexamethasone Anticonvulsant therapy: If needed
Radiation therapy
Radiosurgery
Chemotherapy

70. Febrile Neutropenia

71. Febrile Neutropenia The most common predisposing factor for infection
in cancer patients.
Definition: Currently accepted standard definition;
An absolute neutrophil count (ANC) of 500 cells/m2 or less.
Three oral temperature greater than 38 C in 24 hours period or a single oral temperature of 38.3 C.

72. Patient Evaluation History Physical Examination focus on potential
site of infection.
Most common site of infection include respiratory tract, sinuses, oropharynx, blood, urinary tract, GIT, skin, soft tissue, venous catheter sites.

73. General measures:
Isolation unit: Protect the patient against nosocomial contamination.
Good nutrition with well cooked foods to maintain immunity.

74. Lab Evaluation: Septic workup
Full blood picture to check degree of neutropenia.
Hepatic and renal function.
Blood culture x 2 times ( Aerobes, Anaerobes).
Throat swab for culture.
Sputum culture.
Urine analysis and culture.
Stool analysis and culture if diarrhea.
Chest Radiograph

75. Pathogens
60% - 70% of fevers during neutropenia have no identifiable etiology i.e fever of unknown origin.
Bacteremia seen in 10%- 20% of patients with fever and neutropenia,
Gram positive bacteremia 70%
Gram negative bacteremia 30%

76. Common pathogen in neutropenia
Bacteria:
Gram positive organisms
Staphylococcus aureus
Coagulase-negative staphylococcus
Alpha and beta hemolytic streptococcus
Gram negative organisms
Escherichia coli
Klebsiella pneumoniae
Pseudomonas aeruginosa
Fungi:
Candida
Aspergillus

77. Empiric antibiotic therapy
Broad spectrum empiric antibiotic therapy must be started properly prior to organism identification.
Survival is greater than 90% when patients are treated with appropriate empiric therapy.
Combination therapy
Antipseudomonal penicillins plus an aminoglycosides.