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ONCOLOGIC EMERGENCIES 종양혈액내과 정재헌 Oncologic Emergencies • • • • 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) — — — — 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) • 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 • • • • • 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 – – early myelopathy » Impairment of venous drainage » Intramedullary vasogenic edema » Compromised cord perfusion » Necrosis Mechanical cord destruction » 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 • • • • 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 • • • • 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) – – – – – 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 • • • • 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 • • • • 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 • • • • 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 – – – – – 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