Transcript ONCOLOGIC EMERGENCIES

ONCOLOGIC EMERGENCIES
종양혈액내과
정재헌
Oncologic Emergencies
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Superior Vena Cava Syndrome
Increased Intracranial Pressure
Spinal Cord Compression
Metabolic Emergencies
– Tumor lysis syndrome and Hyperuricemia
– Cancer and Hyponatremia
– Lactic Acidosis and Cancer
– Hypercalcemia and Cancer
– Cancer-Related Hemolytic Uremic Syndrome
Superior Vena Cava Syndrome (1)
• Clinical expression of obstruction of blood
flow through the superior vena cava
• Quickly or gradually
• Syphilitic aneurysm , tuberculosis
mediastinitis
• Malignancy most common
• Intravascular devices such as catheters and
pacemakers  more frequent thrombosis
• 15,000 people in the United States each year
Superior Vena Cava Syndrome (2)
Superior Vena Cava Syndrome (3)
• Anatomy and Pathophysiology
– Major low pressure vessel
– Drainage of venous blood from the head, neck,
upper extremities, and upper thorax
– Right mediastinum
– Surrounded by the sternum, trachea, right main
stem bronchus, aorta, pulmonary artery, and
perihilar and paratracheal LNs
– From the junction of the right and left
innominate veins to the right atrium
– Over a distance of 6cm to 8cm
Superior Vena Cava Syndrome (4)
• Clinical presentation and Etiology
Symptoms
Patients Affecteda
Physical Findings
(%)
Patients Affecteda
(%)
Dyspnea
63
Venous distention
of neck
66
Facial swelling
and head fullness
50
Venous distention
of chest wall
54
Cough
24
Facial edema
46
Arm swelling
18
Cyanosis
20
Chest pain
15
Plethora of face
19
Dysphagia
9
Edema of arms
14
a Analysis based on data from 370 pts
Superior Vena Cava Syndrome (5)
• Clinical presentation and Etiology
Bell et al.[7]
159 Patient
s (%)
Schraufnag
el et al.[10]
107 Patient
s (%)
Lung cancer
129 (81)
67 (63)
45 (52)
30 (48)
36 (46)
Lymphoma
3 (2)
10 (9)
8 (9)
13 (21)
6 (8)
Other maligna
ncies (primary
or metastatic)
4 (3)
14 (13)
14 (16)
8 (13)
5 (6)
Nonneoplastic
2 (1)
16 (15)
19 (22)
11 (18)
31 (40)
Undiagnosed
21 (13)
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Histologic
Diagnosis
Parish et al. Yellin et al.[
[9] 86 Patie 11] 63 Patie
nts (%)
nts (%)
Rice et al.[1
2] 78 Patien
ts (%)
Superior Vena Cava Syndrome (6)
• Clinical presentation and Etiology
– Non malignant condition thrombosis in the
presence of central vein catheter or pacemakers
– In pediatric age group
mainly iatrogenic secondary to cardiovascular
surgery for Congenital Heart Disease
ventriculoatrial shunt for hydrocephalus
SVC catheterization for parenteral nutrition
mediastinal fibrosis secondary to histoplasmo
sis
Superior Vena Cava Syndrome (7)
• Diagnostic Workup
• Clear diagnosis prior to initiation of emergency
treatment
• Complete staging workup prior to the initiation of
treatment
• CXR : Superior mediastinal widening
• CT and PET-CT : useful in lymphoma and lung cancer
• Pathologic confirmation : Endobronchial fine needle
aspiration, CT-guided needle biopsy, mediastinoscopy,
Percutaneous transthoracic CT-guided fine needle
biopsy, Thoracotomy
Superior Vena Cava Syndrome (8)
• Disease-Specific Management and Outcomes
• The cause and stage (in malignancies)
• Bed rest and Oxygen administration
• Diuretics and corticosteroid (after
pathologic confirmation)
• Prophylactic anticoagulation (no benefit)
• Endovascular stenting and angioplasty (venous
thrombosis)
Superior Vena Cava Syndrome (9)
• Small cell lung cancer – Chemotherapy alone or
in combination with thoracic irradiation
• Non small cell lung cancer – Radiotherapy
• Non-Hodgkin lymphoma – complete relief of
SVCS symptoms within 2 weeks of the onset of
any type of treatment (chemotherapy,
chemoradiation, radiotherapy)
• Non malignant causes – mediastinal granuloma
that was attributed histoplasmosis
• Catheter-Induced Obstruction – thrombosis
Recommendation
• Rare absolute emergency
• Efficient diagnostic effort (before oncologic
treatment)
• Mediastinoscopy or thoracotomy
• Cause  prompt treatment
• SCLC, NHL  Chemotherapy,
chemoradiotherapy, radiotherapy
• NSCLC  Radiotherapy
• Benign cause  indolent course and a
good prongosis
Increased Intracranial Pressure (1)
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Introduction
– ICP : common neurologic complication
– Large cerebral metastasis – Intracranial Hemorrhage
– Subependymal or leptomeningeal masses – obstructing
spinal fluid flow
– Hypercoagulable states – dural sinus thrombosis or
extracranial venous outflow obstruction, subdural bleeding
– Immunocompromised host infection
– Communicating hydrocephalus
– Dural venous sinus stenosis
Increased Intracranial Pressure (2)
• Pathophysiologic Consideration
– Average volume of brain : 1,400ml, spinal fluid :
52 to 160 ml, and blood 150 ml
– Increase in the volume of one compartment 
the expense of the other two (Monro-Kellie
hypothesis)
Increased Intracranial Pressure (3)
• Clinical Presentation
– Headache
– Papilledema
– Focal Neurologic Deficits
– Aggravated by vasogenic edema
Hyponatremia  SIADH
– Slow progressive static ICP change  little or no
symptoms
– The syndrome of raised ICP
Increased Intracranial Pressure (4)
• Diagnosis
– History and clinical examination increased ICP
– Computed tomography  the most readily
available imaging study
– Magnetic Resonance Imaging  more detailed
neuroanatomic imaging
Increased Intracranial Pressure (5)
• Treatment
– Increased ICP  Symptomatic measure 
Diagnostic procedure  Definitive treatment
– Normovolemic patient with increased ICP and
suspected decreased intracranial compliance
head and upper trunk elevation (-30 degree)
use of antipyretics (acetaminophen)
Increased Intracranial Pressure (6)
• Treatment
– Corticosteroids effective agents
• Dexamethasone 6-10mg every 6 hours
• Should be avoided if CNS lymphoma is suspected
– Osmotic diuresis
– Monitoring of ICP is necessary
Increased Intracranial Pressure (7)
• Treatment
– Intubation : The most rapid method to decrease
ICP
– Obstructive hydrocephalus  Neurosurgical
Emergency,
– Available Filter System  VP shunt is avoided in
order to prevent peritoneal seeding
Increased Intracranial Pressure (8)
• Disease specific treatment
– Infectious complication  antimicrobial therapy
– Brain abscess  Surgical Drainage and IV
antibiotics
– Subdural hematoma or empyema  immediate
surgical decompression
– Leukostasis in leukemic disease  hydration,
leukapheresis, systemic chemotherapy, low-dose
whole-brain irradiation
Increased Intracranial Pressure (9)
• Disease specific treatment
– Dural sinus thrombosis  anticoagulation
– Leptomeningeal carcinomatosis  irradiation and
intrathecal chemotherapy
– CSF flow obstruction prohibits intraventricular
injection of cytotoxic agents as it can give rise to a
severe, irreversible toxic encephalopathy
Spinal Cord Compression (1)
• Affecting 5% - 10% of patients who have
cancer
• Pain is the most common initial clinical
manifestation
• Description : clinical syndrome, diagnosis,
and treatment of epidural cancer
metastases, isolated radiculopathies or a
cauda equina syndrome
Spinal Cord Compression (2)
• Epidemiology
– 20,000 patients diagnosed with MSCC per year (U.S.A)
– Lifetime incidence in cancer patients (1 -6%)
(Autopsy 5-10%)
– Cumulative incidence decreases with age
4.4% in 40-50, 3.8% in 50-60, 2.9% 60-70, 1.7% in 7080, and 0.54% older than 80 years
Spinal Cord Compression (3)
• Epidemiology
– breast cancer, prostate cancer, lung cancer, and lymphoma
– Cumulative incidence
multiple myeloma (8%), prostate cancer (7%),
nasopharyngeal cancer (6.5%), and breast cancer
(5.5%)
– Median interval from Dx to manifestation of MSCC 6 to 12.5
mon
– Two-thirds thoracic spine, 20% lumbar spine, and cervical
and sacral spine (<10% for each site)
– Colon and prostate cancer  lumbosacral spine
– Lung and breast cancer  thoracic spine
– Multiple epidural metastases: initial presentation in up to
one-third of patients in whom the whole axial skeleton is
investigated
Spinal Cord Compression (4)
• Pathophysiology
– Bone (axial skeleton) one of the most common
organ systems
– One-third : spine metastasis (dying of cancer)
– Venous blood from intra-abdominal and
intrathoracic organ: drained through the vena
cava also through the vertebral and epidural
venous plexus (Batson plexus)
– Low pressure circulation, frequent flow reversal:
ideal transportation system for cancer cells
Cord injury by a bone fragment or spine instability
Spinal Cord Compression (6)
• Pathophysiology
– Mechanism of spinal cord compression
• Hematogenous metastasis to vertebral body
• Pathologic fracture of a vertebral body
• Involvement of posterior spine elements
(less common)
• Transforaminal progression of
paravertebral tumor –lymphoma and
neuroblastoma
Spinal Cord Compression (7)
• Pathophysiology
– Mechanism of spinal cord compression
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Primary hematogenous seeding to the epidural space (rare)
Intradural mass lesion – meningioma, nerve sheath tumors, large
leptomeningeal metastasis
Intraneural spread of neurogenic tumors
Non metastatic causes – epidural hematoma in pts with coagulopathy
or abscess in an immunocompromised host
Mechanism of cord injury
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early myelopathy
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Impairment of venous drainage
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Intramedullary vasogenic edema
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Compromised cord perfusion
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Necrosis
Mechanical cord destruction
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Fracture of vertebral body and posterior displacement of bone fragment
Spinal Cord Compression (8)
• Pathophysiology
– Complex syndrome of back pain
• Local – Infiltrating periostium
• Radicular – compression or infiltration of a nerve
root
• Referred components – irritation of long tracts of the
spinal cord (funicular pain) or paravertebral muscle
– Micturition
• Frequently impaired in patients with MSCC
Spinal Cord Compression (9)
• Clinical presentation
– Pain
– Neurologic symptoms
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Evolution of paraplegia
Motor dysfunction (weakness, spasticity)
Quadriparesis
Conus medullaris syndrome : distal lower extremity
weakness, saddle paresthesia, and overflow leakage
from bladder and bowel
• Diminished sensation below the level of compression
at initial presentation :only few
Spinal Cord Compression (10)
• Clinical presentation
– Neurogenic bladder dysfunction
• less common at symptom onset
• Alraming symptom: hesitancy and urinary retension
• At diagnosis, almost half of patients with MSCC
: incontinent or require catheterization
– Horner syndrome (miosis, ptosis, and
enophthalmos) : transforaminal progression
cervicothoracic junction and infiltration of the
stellate ganglion
Spinal Cord Compression (11)
• Differential Diagnosis
– Infiltration of the lumbosacral plexus or peripheral
nerves
– Cauda equina syndrome
– Intraparenchymal spinal cord metastasis (small cell
lung cancer and breast cancer)
– Primary cord tumors
– Infectious (herpes simplex, human T-lymphotropic
virus) and autoimmune myelitis
– Spinal cord hemisyndrome (intrinsic spinal cord
disease, leptomeningeal spread  spinal cord
infiltration)
Spinal Cord Compression (12)
• Diagnosis
– Average time between onset of symptoms
and definitive diagnosis : 3 months
– Magnetic resonance imaging
– X-ray
Spinal Cord Compression (13)
• Treatment
– Corticosteroid
– Radiotherapy
– Surgery
– Systemic chemotherapy: non-Hodgkin
lymphoma, germ cell tumor
– Bisphosphonates or Denosumab
Spinal Cord Compression (14)
• Prognosis
– The type and extent of the underlying
malignancy
– Median survival 3 to 16 months
– Most patients die of systemic tumor
progression
– Remain ambulatory or regain the ability to walk
after treatment
• 80% significant neurologic deficit is absent
• 50% those with mild transverse myelopathy
• 5% paraplegic
Metabolic Emergency (1)
• Introduction
– Increased awareness and improved
prophylaxis  preempt metabolic
emergencies
– Their occurrence  present challenges to
the practicing oncologist
– Successful outcome  prompt recognition
and the rapid institution of adequate
therapy
Metabolic Emergency (2)
• Tumor Lysis Syndrome and Hyperuricemia
• Tumor cell death with release of intracellular contents
• Occur spontaneously in rapidly proliferating tumors
• Following administration of cytotoxic chemotherapy to
patients with hematologic malignancies with a large
percentage of proliferating, drug-sensitive cells
• A few hours to a few days after the initiation of therapy
• Cell death  release of potassium, phosphate, uric acid,
and other purine metabolites  hyperkalemia,
hyperphosphatemia, secondary hypocalcemia, and
hyperuricemia acute renal failure and metabolic
acidosis
Metabolic Emergency (3)
• Tumor Lysis Syndrome and Hyperuricemia
– Pathogenesis
Metabolic Emergency (4)
• Tumor Lysis Syndrome and Hyperuricemia
– Treatment
• Preventive measure
– Foremost hydration, allopurinol, and oral phosphate binders beginning
preferably 24 hours before chemotherapy administration
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Aggressive hydration
Hyperkalemia
Hyperphosphatemia
Hyperuricemia
Metabolic Emergency (5)
• Cancer and Hyponatremia
– Water and sodium homeostasis frequently disordered in
cancer patients
– None to impaired consciousness progressing to coma and
generalized hypotonia, or seizure activity all secondary to
cerebral edema
– Anorexia, nausea, and asthenia
– Differential of hyponatremia
• Inappropriate secretion of arginine vasopressin
• Sodium depletion secondary to reduced intake and gastrointestinal
or renal losses
• Ectopic atrial natriuretic peptide (ANP) production
• Hyponatremia associated with third spacing of fluids (ascites)
• Pseudohyponatremia (multiple myeloma and hyperproteinemia)
Metabolic Emergency (6)
• Cancer and hyponatremia
– Pathogenesis
– Criteria for Diagnosing SIADH
• Decreased effective osmolality of the extracellular fluid (<275
mOsm/kg of water)
• Inappropriate urinary concentration: Urine osmolality >100
mOsm/kg H2O with normal renal function
• Clinical euvolemia as defined by the absence of signs of
hypovolemia (orthostasis, tachycardia, decreased skin turgor,
dry mucous membranes) or hypervolemia (subcutaneous
edema, ascites)
• Urine sodium >20–30 mmol/L in the face of normal salt and
water intake
• Normal thyroid and adrenal function
• Normal renal function and no recent diuretic use
Metabolic Emergency (7)
• Cancer and hyponatremia
– Treatment
• High Risk of ODS (osmotic demyelination
syndrome)
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Serum Na+ concentration ≤105 mmol/L
Alcoholisma
Advanced liver diseasea
Hypokalemiaa
Malnutritiona
Metabolic Emergency (8)
• Cancer and hyponatremia
– Treatment
– Asymptomatic or serum sodium <=125 mmol/L and
developed over weeks
• Chronic hyponatremia: Neurologic sequelae more likely if
correction too rapid
• Increase serum Na a maximum of 0.5-2 mmol/L/hr
• High risk of ODS: Correct serum Na by 4-6 mmol/L/d not >8
mmol/L/24 h
• Normal risk of ODS: correct serum Na 4-8/L/d, not>10-12
mmol/L/24h
• Intravenous normal saline 20 to 40mg furosemide when
patient is euvolemic
Metabolic Emergency (9)
• Cancer and hyponatremia
– Treatment
– Symptomatic or serum sodium <=115 mmol/L and
developed acutely
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Increase serum sodium 2 mmol/L/hr; 4-6 mmol/L increase
in serum Na sufficient to reverse most serious
manifestation
Severe symptoms: 100mL of 3% NaCl over 10 minutes
times three as needed
Mild to moderate symptoms with low risk of herniation: 1
to 2 mL/Kg/hour 3% NaCl then 100 to 250 mL/hour
normal saline
20 – 40mg oral or intravenous furosemide when patient is
euvolemic
Metabolic Emergency (10)
• Lactic Acidosis and Cancer
– pH≤7.35, with plasma lactate concentration ≥5 meq
– Spontaneous lactic acidosis hematologic and
lymphoid malignancies as well as solid tumors such as
breast, colon, ovarian, and smll-cell lung cancer
– TLS combined by lactic acidosis
– Latic acid metabolism 90% liver 10% kidney
– Cancer cell large quantities of lactate  severe in
patents with compromised liver function
– Mortality 60% - 90%
– Aggressive therapeutic approach
Metabolic Emergency (11)
• Lactic Acidosis and Cancer
– Aggressive therapeutic approach
• Aggressively support blood pressure with fluids and
vasopressors  decreasing further lactic acid accumulation
• Use of sodium bicarbonate
• Hemodialysis and hemofiltration with a bicarbonate-based
replacement fluids
• Correction of the underlying causes is essential, but often very
difficult
Metabolic Emergency (12)
• Hypercalcemia and Cancer
– Most common paraneoplastic syndrome
– 10 – 30% of patients with advanced cancer (carcinomas of
the breast, lung, kidney, and head and neck)
– Nausae, vomitting, constipation, polyuria, and disorientation
– Bone destruction (osteolytic) or PTHrP (parathyroid
hormone-related protein)
– Treatment
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Hydration
Bisphosphonates
Osteoprotegerin (inhibition of osteoclast differentiation)
Denosumab (fully human monoclonal antibody with a high affinity
and specificity for RANKL)
Metabolic Emergency (13)
• Cancer-Related Hemolytic Uremic Syndrome
– HUS : microvascular disorder characterizaed
histopathologically by disseminated microthrombi
occluding the microvasculature
– Thrombotic thrombocytopenic purpura : spectrum with
considerable overlap invariable renal insufficiency vs
predominant neurologic symptoms
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Manifestation of the cancer itself
As a cocmplication of chemotherapy
In the setting of bone marrow transplantation
More recently as a problem in patients receiving antibodies and
immunotoxins
Metabolic Emergency (14)
• Therapy
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Blood pressure control
Steroid – uncertain
Hemodialysis –in patients with renal failure
Therapeutic plasma exchange
Therapy more efficacious in HUS (manifestation of the underlying cancer
than as a complication of therapy)
• The End