Em - Oncologic Emergencies

Oncologic Emergencies

A 23 year old male presented with cough, facial swelling and neck vein engorgement. Examination of the chest showed prominence of venous collaterals and clear breath sounds. A lymph node was palpated in the right supraclavicular area. What syndrome does this patient present with? • Superior vena cava syndrome -

¶ venous return from head, neck, upper ext malignant tumors >90% of SCVS cases o lungs - approx 85% (small-cell, squam cell) o lymphoma – leading cause in young adults o metastatic (testes/breast) – small proportion o other: benign tumors, aortic aneurysm, thyroid enlargement, thrombosis, fibrosing mediastinitis (due to histoplasmosis, irrad)

Common Symptoms and Physical Findings of SVC Syndrome Symptoms Patients Physical Patients Affected (%) Findings Affected (%) Dyspnea 63 Venous 66 distension of neck Facial swell 50 Venous 54 and head distension of fullness chest wall Cough 24 Facial edema 46 Arm swelling 18 Cyanosis 20 Chest pain 15 Plethora of 19 face Dysphagia 9 Edema of 14 arms -

aggravated by bending forward or lying down cerebral and/or laryngeal edema – poor prognosis cardiorespiratory sx at rest (positional) – significant airway obstruction and vascular obstruction

Table 49.1-2: Primary Pathologic Diagnoses for Superior Vena Cava Syndrome

Histologic Diagnosis

Bell et al.,11 159 Patients

Schraufnagel et al.,4 107 Patients (%)

Parish et al.,10 86 Patients

Yellin et al.,12 63 Patients

Total, 415 Patient

129 (81)

67 (63)

45 (52)

30 (48)

271 (65)

Lymphoma

3 (2)

10 (9)

8 (9)

13 (21)

34 (8)

Other malignancies (primary or Nonneoplastic

4 (3)

14 (13)

14 (16)

8 (13)

40 (10)

2 (1)

16 (15)

19 (22)

11 (18)

50 (12)

Undiagnosed

21 (13)

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21 (5)

Lung cancer

How should this patient be managed? Immediate radiation therapy • Immediate chemotherapy • Work up including CT scan of the chest and lymph node • biopsy None • Management of SVC syndrome • SVCS has long been considered to be a potentially lifethreatening medical emergency • The safety of these invasive procedures in patients with SVCS has markedly improved • Therefore, modern treatment of SVCS has become disease specific from the outset Diagnostic procedures -

Diagnosis is based on clinical findings CXR: widening of superior mediastinum (right usually) o Pleural effusion on 25%

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CT: diminished or absent opacification of central venous structures with prominent venous circulation MRI = CT (most reliable view of mediastinal anatomy)

Bronchoscopy, percutaneous needle biopsy, mediastinoscopy, thoracotomy – performed w/out major risk of bleeding

Diagnostic procedures • Contrast venography - provides important information for determining if the vena cava is completely obstructed or remains patent and extrinsically compressed • Sputum cytology • Bronchoscopy • In the presence of pleural effusion, thoracocentesis • Biopsy of a supraclavicular node • Mediastinoscopy • Percutaneous transthoracic CT-guided fine-needle biopsy • Thoracotomy Biopsy of the cervical lymph node revealed diffuse large cell lymphoma. CT scans of the previously mentioned patient showed a bulky mediastinal mass with obstruction of the superior vena cava and large retroperitoneal lymph nodes and splenomegaly. Bone marrow biopsy did not show involvement. What is the definitive treatment for this patient? A. Chemotherapy B. Radiotherapy C. Monoclonal antibodies (rituximab) D. A & B E. All Management of SVCS Goals of treatment of SVCS are to relieve symptoms and to attempt the cure of the primary malignant process • Prognosis of patients strongly correlates with the prognosis of the underlying disease. • Medical adjuncts – Diuretics: symptomatic relief of edema, maybe immediate but transient • Furosemide: dose depends on state of hydration & renal function – Steroids: may improve obstruction by decreasing a possible inflammatory reaction associated with tumor or with irradiation • Dexamethasone: 6 – 10 mg IV q 6 hours •

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Life-threatening complication: tracheal obstruction • Diuretics w/ low salt diet, head elevation, oxygen Radiation – if due to non-small cell lung CA & metastatic CA Chemotherapy – if due to small cell CA of lung or lymphoma Recurrent 10-30% Æ palliated with self-expanding stents Surgery – immediate relief if benign cause

SCVS and Central Venous Catheters in Adults Risk of major vessel thrombosis

• Lecture + added notes from Harrison’s 16th ed

MML Batch 2009

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Remove catheter + anticoagulation Æ prevent embolization If early: fibrinolytic therapy Warfarin (1 mg/d) – ¶ thrombosis w/o altering coag tests

He was given saline hydration, allopurinol and sodium bicarbonate prior to institution of chemotherapy and rituximab. What metabolic complications are anticipated following treatment? A. Tumor lysis B. Hyperuricemia C. Hyponatremia D. Any of the above What are the components of tumor lysis syndrome? • Hyperuricemia • Hyperkalemia • hyperphosphatemia • hypocalcemia •

A 68 year old male who was recently diagnosed to have extensive Small cell lung cancer involving the bones of his thoracic and lumbar vertebrae developed low back pain, numbness and weakness of both lower extremities. He also complained of nausea, abdominal discomfort and constipation. Urine output was adequate. What syndromes should be strongly suspected in this patient? A. Spinal cord compression B. Hypercalcemia Spinal cord compression •

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Lactic acidosis

Tumor Lysis Syndrome • rapid release of intracellular contents into the bloodstream especially following chemotherapy • patients at risk: high grade lymphomas, leukemias with high leukocyte counts, Burkitt’s lymphoma, acute lymphblastic

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5-10% with cancer; lung cancer most common • Metastatic often involves vertebral column • Lung, breast, prostate cancer – most frequent • Multiply myeloma – high risk of spine involvement • Lymphomas, melanoma, renal cell CA, GU Most common: 70% thoracic, 20% lumbosacral, 10% cerv • Usually metastasis of breast and prostate cancer

Compressive indentation, displacement, or encasement of the spinal cord's thecal sac by metastatic or locally advanced cancer – posterior extension of a vertebral body mass: compression of the anterior aspect of the spinal cord – anterior or anterolateral extension of a mass arising from the dorsal elements or invading the vertebral foramen Intramedullary spinal cord metastases produce edema, distortion, and compression of the spinal cord parenchyma

leukemia, chronic leukemias, and rarely, with solid tumors •

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Prophylaxis for patients at risk – Adequate hydration – Alkalinize the urine – Allopurinol – Monitor Serum electrolytes, BUA, BUN, creatinine, phosphorus, Ca for 3–4 days after chemotx is initiated Established tumor lysis – Correct electrolyte abnormalities – Hydration – Hemodialysis – if with renal failure

Hyperuricemia Etiology – most often in hematologic malignancies: leukemias, high grade lymphomas, myeloproliferative disorders (polycythemia vera) – Drugs: • Cytotoxic agents: tiazofurin, aminothiadiazoles • Diuretics: thiazides, furosemide, ethacrynic acid • Antituberculous: pyrazinamide, ethambutol, nicotinic acid – Renal impairment • Renal complications and arthritis are the most important consequences of acute or chronic hyperuricemia • Diagnosis: – elevated serum uric acid levels – hyperuricosuria – increased serum creatinine, BUN

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SCC: Clinical presentation • majority of patients who present with spinal cord compression have a known diagnosis of cancer • 8% to 34%: initial manifestation of cancer • Early signs – Over 90%: pain localized to the spine or radicular – Pain exacerbated by movement, recumbency, coughing, sneezing, straining for days or months – Precede neurological symptoms by weeks or months – Radicular pain – tight, band-like constriction around thorax and abdomen – Lhermitte’s sign – tingling or electric sensation down the back, upper and lower limbs upon flexing and extending the neck Æ early sign of compression

– uric acid crystals in the urine •

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Prophylaxis prior to chemotherapy – Discontinue drugs that increase BUA – Alkalinization of urine: maintain urine pH >7.0 • May add acetazolamide to increase effects Allopurinol – Inhibits xanthine oxidase – Start 1 – 2 days prior to chemotherapy – Doses: 300 – 600 mg/day, continued for 1 – 2 wks Acute oliguria – Determine if ureteral obstruction by urate calculi is present, using ultrasound or CT – Do not use contrast agents Dialysis

Hyperphosphatemia • Caused by release of intracellular phosphate pools Æ ¶ serum calcium Æ severe neuromuscular irritability & tetany • Renal failure, ventricular arrythmias, sudden death

Lecture + added notes from Harrison’s 16th ed

Intramedullary metastases: hematogenous Leptomeningeal metastases: intradural, extramedullary Epidural metastases arise from posterior aspect of vertebral body & produce compression of anterior spinal cord Epidural compression from paravertebral tumors that invade intervertebral foramina Epidural compression from masses within the epidural space

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Intermediate signs: – Weakness – Preceded or accompanied by sensory loss Late signs: – Autonomic dysfunction; urinary retention, constipation – Paralysis – Irreversible

SCC: Physical findings Tenderness of involved vertebral body Pain over involved vertebra or dist of involved nerve root

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Pain induced by SLR, neck flexion, vertebral percussion Numbness and paresthesia in extremities of trunk Loss of sensibility to pinprick

Muscle weakness Spasticity MML Batch 2009

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Abnormal muscle stretch reflexes & extensor plantar responses Sensory loss Autonomic dysfunction: palpable bladder, diminished rectal tone, decreased perineal sensibility

What is the most sensitive test to diagnose spinal cord compression? A. X ray B. CT scan C. MRI D. PET SCC: Diagnosis • Accurate history & neurologic examination • X-rays – Winking owl – erosion of pedicles; earliest CXR finding – µ intrapedicular distance, vertebral destruction, lytic or sclerotic lesions, scalloped vert bodies, vert collapse – More than 66% have bony abnormalities • erosion/loss of pedicles • partial/complete collapse of vertebral bodies • paraspinous soft tissue masses •

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Magnetic resonance imaging (MRI) – gold standard – neoplasms: ¶ signal intensity on T1-weighted images; µ signal intensity on T2-weighted images CT & myelography – diagnose & localize SCC if MRI not available If cord compression w/ unknown tumor: • CXR • Mammography • Measurement of prostate-specific antigen • Abdominal CT

MRI: sagittal view: intramedullary metastases

SCC: Etiology Frequent tumor types – Breast – Lung – Prostate – Lymphoma – Renal – Myeloma

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SCC: Goals of Treatment recovery & maintenance of normal neurological function local tumor control stabilization of the spine pain control

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SCC is an emergency! • treatment delays result in irreversible paralysis, loss of bladder & bowel function • with early diagnosis, treatment is effective in 90% of patients SCC: Treatment • Choice of treatment depends on – clinical presentation – availability of histologic diagnosis – rapidity of clinical course – type of malignancy – site of spinal involvement – stability of the spine – previous treatment • Radiation + glucocorticoids – standard initial treatment for a radiosensitive malignancy • Chemotherapy – selected patients with chemosensitive tumor • Steroids – as soon as the diagnosis is made – high dose IV (96 mg /day) dexamethasone for 3 days then tapering doses improved neurologic function – most common regimen 10 mg IV • • • •

MRI: sagittal view: anterior compression of cauda equina below conus medullaris from pathologic fracture of L2 vertebral body

29 % 17.2% 14 % 5% 4.2% 4%

Laminectomy – tissue diagnosis and removing posterior epidural deposits in absence of vertebral disease Resection of anterior vertebral body with tumor ff by spinal stabilization – good results and low mortality rate Percutaneous vertebroplasty – metastatic vertebral tumors o Inject acrylic cement into collapsed vertebra to stabilize Pain palliation – common

SCC: Indications for Surgery spinal instability retropulsion of bone fragments producing compression previous radiotherapy at the site of compression Æ resistant lack of tissue diagnosis in the setting of rapid neurologic deterioration

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unknown etiology radioresistant tumor type (e.g. melanoma or renal cell CA) pathologic fracture dislocation

SCC: Prognosis Maranzano & Latini, 1995 209 patients treated with RT & steroids – ambulatory 98% – nonambulatory 60% – paraplegic 11% able to ambulate following therapy – Outcome superior for radiosensitive malignancies: lymphoma, myeloma vs. renal, hepatoma The patient also complained of nausea, abdominal discomfort and constipation. What is the most probable cause of these symptoms? Hyperuricemia • Hypercalcemia • Hypocalcemia • GI involvement by cancer •

Lecture + added notes from Harrison’s 16th ed

MML Batch 2009

Hypercalcemia • Most common metabolic emergency • Etiology: – Myeloma – Lung cancer (epidermoid more often than SCLC) – Renal • Incidence varies with the underlying disorder – highest with myeloma & breast : 40% – intermediate with non small cell lung cancer – uncommon in colon, prostate, SCLC Mechanisms underlying osteolysis & subsequent hypercalcemia: PTHrP

– once euvolemia is achieved, may be useful in preventing •

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Hypercalcemia: Signs and Symptoms General CNS Cardiac GI

Renal

Dehydration Weakness Bradycardia Nausea & Polyuria vomiting Anorexia Hypotonia Short QT Constipation Nephrocalci interval nosis Pruritus Proximal Prolonged Ileus myopathy PR interval Weight loss Mental Wide T Pancreatitis changes wave Fatigue Seizure Atrial or Dyspepsia Coma ventricular arrhythmias Hypercalcemia: Diagnosis • Accurate history & physical examination • Identify the underlying malignancy • Determine presence or absence of bone metastases • In humoral hypercalcemia of malignancy: – serum iPTH: low or undetectable – inorganic phosphorus: low or normal – 1,25-hydroxyvitamin D: low or normal

Hypercalcemia:Acute management Volume expansion with saline 250 – 500 ml/h Maintain CVP – 10 cm H20 Furosemide 20 – 40 mg IV q 2 – 4h Maintain urine output at 150 – 200 ml/h Monitor electrolytes, creatinine, BUN Calcium, ionized calcium

Pamidronate 90 mg IV ( in saline) piggyback over 4 hours or Zolendronic acid 4 mg ( in saline) over 15 min Hydrocortisone 250 – 500 mg IV q 8h Followed by maintenance prednisone 10 – 100 mg po OD If no response to the above treatment strategies, consider Mithramycin

Calcitonin

Gallium nitrate

Hypercalcemia: Treatment Volume expansion & natriuresis – increase renal blood flow – enhance calcium excretion sec to ionic exchange of calcium for sodium in the distal tubule • Loop diuretics – in theory, enhance calcium excretion •

Lecture + added notes from Harrison’s 16th ed

hypervolemia Bisphosphonates – bind avidly to hydroyapatite crystals & inhibit bone resorption – may be mediated by inhibition of osteoclasts and activation of cytokines – inhibit recruitment & differentiation of osteoclast precursors Corticosteroids – of use in lymphoid malignancies bec antitumor effect Calcitonin – inhibits bone degradation by binding directly to receptors on the osteoclast – onset of action: 2 – 4 h – short duration of action – little response to continued treatment – dose: 2 – 8 U/kg sq or im q 6 – 12h Mithramycin – directly inhibits osteoclasts – onset of action : 24 – 48 h – re- treatment necessary in 72 – 96 h – dose: 25 mcg/kg Gallium nitrate – directly inhibits osteoclasts, increases bone calcium without cytotoxic effects on bone cells – onset of action: 24 –48h – dose: 100 – 200 mg/m2 IV infusion for 5 days

A 55 year old female presented with headache, vomiting and dizziness. Past history revealed nonproductive cough of 3 months duration and upper back pain made worse during coughing. Chest CT scan should a peripheral left mid lung mass which on biopsy revealed adenocarcinoma. Increase in intracranial pressure (ICP)

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25% of cancer patients most often cause brain metastasis: lung, breast, melanoma

common neurologic complication of patients with cancer involving the nervous system mechanisms – large cerebral metastases • can give rise to intracranial hemorrhage – coagulopathies predispose to subdural hemorrhage – infections of the nervous system, such as fungal or bacterial meningitis or a bacterial abscess

Clinical Presentation headache - most common complaint nausea and vomiting cognitive complaints such as slowness to respond and inattentiveness – reflect frontal lobe dysfunction • increasingly somnolent and ultimately falls into a coma • • •

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fundoscopic examination with papilledema: half of patients focal neurologic deficits can help localize the mass – gaze paresis to the side opposite the lesion: involvement of the frontal center for horizontal gaze. – posterior frontal masses: contralateral hemiparesis. Hyponatremia: result of inappropriate secretion of antidiuretic hormone

What examinations are indicated to document ICP and its possible cause? Skull X-ray • Lumbar puncture • CT scan of the brain • MRI – more sensitive; meningeal & small lesions • Imaging Studies Unenhanced computed tomography – adequate to determine the presence of intraventricular and subarachnoid CSF flow obstruction , as well as uncal, transfalcian, and transtentorial herniation

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MML Batch 2009

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– presence of intracranial hemorrhage or a neoplastic or •

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infectious mass lesion can be identified MRI and magnetic spectroscopy – more detailed neuroanatomic imaging and the distinction between a neoplastic, infectious, inflammatory, or ischemic process Lumbar puncture – bears the risk of initiating or aggravating cerebral herniation. The risk is considerable in mass lesions of the posterior fossa

Treatment Best position: head and upper trunk slightly elevated Body temperature elevation: treated with antipyretics Serum osmolality is kept in the high normal range Isotonic saline solutions for intravenous hydration. Corticosteroids: effective for the initial management of increased ICP caused by vasogenic edema – should be avoided if CNS lymphoma is considered , no tissue diagnosis yet • Osmotic diuresis through infusion of hyperosmolar agents such as mannitol or glycerol • Monitoring in the neurologic intensive care unit is required in patients with depressed mental status secondary to ICP elevation – most rapid method is intubation with mechanical hyperventilation • Obstructive hydrocephalus constitutes a neurosurgical emergency • Disease-specific treatment • • • • •

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If brain herniation: • Intubated & hyperventilated: PCO2 25-30 mm Hg • Mannitol (1-1.5 g/kg) every 6 hours Dexamethasone – initial tx for all symp brain metastases If multiple lesions – whole-brain radiation therapy If 1 brain metastasis – surgical excision + whole-braid rad If radioresistant tumors – resected, if possible If recurrent or inaccessible – sterotactic radiosurgery If with hydrocephalus – shunt replacement If irrev neuro sx w/ med tx – ventriculotomy (to remove CSF) or craniotomy (to remove tumors/hematomas)

Pericardial Infusion ƒ 5-10% with cancer patients o most freq in lung, breast, leukemia, lymphomas ƒ Cardiac tamponade – initial sx of extrathoracic malignancy o Irradiation, drug-induced pericarditis, hypothyroidism, idiopathic pericarditis, infection, autoimmune ƒ Two types of radiation pericarditis: o Acute – w/in mos of irradiation; spontaneous resol’n o Chronic – up to 20 yrs after; has thick pericardium ƒ Most are asymptomatic, but most common: o Dyspnea, cough, chest pain, orthopnea, weakness o Pleural effusion, sinus tachycardia, jugular venous distension, hepatomegaly, peripheral edema, cyanosis o Specific dx findings: paradoxical pulse, diminished heart sounds, pulsus alterans, friction rub ƒ Dx: Echocardiography – most useful ƒ Dx: Cytologic exam of pericardiac fluid o False negative: lymphoma, mesothelioma ƒ Tx: o Pericardiocentesis o Creation of pericardial window o Complete pericardial stripping o Cardiac irradiation o Systemic chemotherapy ƒ Emergency Acute: drain fluid by pericardiocentesis o Subxiphoid pericardiotomy in 45 min under local anes ƒ Tx for benign cause: thoracoscopic pericardial fenestration Intestinal Obstruction ƒ common in colorectal or ovarian cancer ƒ other can metastasize in abd: lung, breast, melanoma ƒ occurs at multiple sites o melanoma – small bowel ƒ causes of pseudoobstruction: o infiltration of mesentery or bowel muscle by tumor o involvement of celiac plexus o paraneoplastic neuropathy (small cell lung CA) IgG antibodies reactive to neurons of myenteric and submucosal plexuses of jejunum & stomach ƒ Pain – most common; colicky in nature

Lecture + added notes from Harrison’s 16th ed

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Due to distention, tumor mass, or hepatomegaly Vomiting – intermittent or continuous Constipation – if complete obstruction PE: distention w/ tympany, ascites, visible peristalsis, high-pitched bowel sounds, tumor masses CXR: multiple air-fluid levels, dilation of bowel o Acute cecal dilation > 12-14 cm – surgical emergency o High likelihood of rupture CT – useful in differentiating benign from malignant o Malignant Mass at site of obstruction or prior surgery, adenopathy, or abrupt transition zone Irregular bowel thickening at obstruction site o Benign Mesenteric vascular changes Large volume of ascites Smooth transition zone and smooth bowel thickening at obstruction site Poor prognosis; median survival is 3-4 months Other causes: o adhesions from prev operations o ileus induced by vincristine Tx – depends on extent and fxnal status of major organs o Initial mgt: surgical evaluation o Self-expanding metal stents o If advance malignancy: prolonged conservative mgt (e.g. nasogastric decompression) o Antiemetics, antispasmodics, analgesics – OPD o Octreotide – relieve by inh GI secretion

Urinary Obstruction ƒ May occur in px w/ prostatic, cervical, metastatic (breast, stomach, lung, colon, pancreas, lymphomas) CA ƒ Radiation tx Æ fibrosis & ureteral obstruction Æ hydronephrosis and renal failure ƒ Most common symptom: Flank pain o Persistent UTI, proteinuria, hematuria o Anuria w/ polyuria may occur o Slow, continuous rise in serum creatinine ƒ Dx: o Renal UTZ – safest and cheapest o nuclear scan – assess function of obstructed kidney o CT – retroperitoneal mass or adenopathy ƒ Tx: Urinary diversion – flank pain, sepsis, fistula o Internal ureteral stents under local anes o Percutaneous nephrostomy – alternative for drainage o Suprapubic cystostomy – bladder outlet obstruction Malignant Biliary Obstruction ƒ Primary carcinoma in pancreas, ampulla of Vater, bile duct liver or metastasis to periductal LN or liver parenchyma (gastric, colon, breast, lung) ƒ Sx: o Jaundice o Acholic stools o Dark urine o Pruritus o Weight loss – due to malabsorption ƒ Pain and secondary infxn – uncommon ƒ Dx: UTZ, CT, percutaneous transhepatic or ERCP ƒ Tx: o Palliative – if disabling pruritus, resistant to medical tx, severe malabsorption, or infection o Stenting under radiographic control o Surgical bypass o Radiation therapy ± chemotherapy o Depends on site of obstruction (prox VS distal), type of tumor, general medical condition of patient o If no pruritus – biliary obstruction may be largely asymptomatic cause of death Neoplastic Meningitis ƒ Involves leptomeninges ƒ Complication of primary and secondary CNS tumors ƒ 3-8% of cancer patients o melanoma, breast, lung, lymphoma, acute leukemia ƒ Sx: o Multifocal neurologic: headache, gait abn, mental, N&V, seizures, back/radicular pain, limb weakness o CN palsies, extremity weakness, paresthesia, ¶ deep tendon reflexes ƒ Dx: malignant cells in CSF, µ CSF CHON o Repeat spinal tap at least three times ƒ Dx: MRI o Leptomeningeal, subependymal, dural, enhanced CN, superficial cerebral lesions, comm. hydrocephalus MML Batch 2009

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o Cauda equina – common, but may be seen anywhere Dx: Radiolabeled CSF flow – 70% abnormal Ventricular outlet obstruction, abn flow in spinal canal, impaired flow over cerebral convexities may affect distribution or intrathecal chemotx Æ ¶ efficacy or µ toxic o Tx: radiation therapy Tx: Intrathecal chemotherapy o Methotrexate, cytarabine, or thiotepa o By lumbar puncture or intraventricular reservoir o Breast CA – responds best o Acute leukemia/lymphoma – eliminate systemic dse

Seizures ƒ Caused by: o Tumor itself o Metabolic disturbances o Radiation injury o Cerebral infarctions o Chemotx-related encephalopathies o CNS infections o Metastatic disease – most common cause ƒ But occur more freq in primary brain tumors than metastatic brain lesions ƒ 6-29% of patients with CNS metastasis ƒ Frontal lesions – early seizures ƒ Hemispheric symptoms – µ risk for late seizures ƒ Posterior fossa lesions – early and late seizures ƒ Common in patients with CNS metastases from melanoma ƒ Cytotoxic drugs – etoposide, busulfan, chlorambucin ƒ Tx: o Anticonvulsants – diphenylhydantoin o Phenytoin – drug reaction with dexamethasone o Most anti-seizure drugs alter metab of antitumor agts PULMONARY AND INTRACEREBRAL LEUKOCYTOSTASIS ƒ Hyperleukocytosis and leukostasis syndrome – fatal complication of acute leukemia (esp myeloid leukemia) ƒ Peripheral blast cell count > 100,000/mL ƒ Occurs 5–13% in AML and 10–30% in ALL ƒ Rare in lymphoid leukaemia ƒ µ bld viscosity Æ bld flow is slowed by aggregates of tumor cells Æ primitive myeloid leukemic cells may invade endothelium Æ hemorrhage ƒ Brain and lung - most commonly affected o Brain leukostasis: stupor, headache, dizzy, tinnitus, visual dist, ataxia, confusion, coma, or sudden death o Tx: 600 cGy whole-brain irradiation + antileukemic tx o Pulmo leukostasis: resp distress, hypoxemia, resp fail o CXR: normal but w/ interstitial or alveolar infiltrates o Leukapheresis - helpful in ¶ circulating blast counts o Lysis of blasts in the lung Æ pulmo hemorrhage Æ “leukemic cell lysis pneumopathy” o Worsened by vol depletion & blood transfusions ƒ Leukostasis – not assoc w/ CLL or CML ƒ Acute promyelocytic leukemia + tx w/ tretinoin and arsenic trioxide Æ possible cerebral or pulmo leukostasis o Prevent by cytotoxic chemotx + differentiating agents

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After granulocytopenia resolves Æ lung infiltrates cavitate Æ massive hemoptysis Correct thrombocytopenia and coagulation defects Surgery - aspergillosis-related cavitary lesions

AIRWAY OBSTRUCTION ƒ Blockage at the level of the mainstem bronchi or above ƒ From intraluminal tumor growth/ext airway compression ƒ Most common cause of malignant upper airway obstruct: o Invasion from adj primary tumor o Lung cancer o FF by esophageal, thyroid, mediastinal malignancies ƒ Extrathoracic primary tumors (renal cell, colon, or breast) o Obstruction by endobronchial and/or mediastinal lymph node metastases ƒ Clinical Manifestations: o Dyspnea o Hemoptysis o Stridor o Wheezing o Intractable cough o Post-obstructive pneumonia o Hoarseness ƒ Diagnosis: o CXR: obstructing lesions o CT: more detailed information about tumor extent ƒ Treatment: o Cool humidified oxygen, glucocorticoids, and Helium + oxygen (Heliox) ventilation o If prox to larynx: tracheostomy may be life-saving o If more distal, inc obstruct: bronchoscopy with laser treatment photodynamic therapy stenting – symptomatic extrinsic compression o Ext-beam irradiation or brachytherapy + glucocortic o Surgery – primary airway tumors SCC Carcinoid tumor Adenocystic carcinoma Non-small cell lung cancer

HEMOPTYSIS ƒ May have nonmalignant causes but lung cancer accounts for a large proportion of cases o 20% with lung cancer have hemoptysis ƒ Endobronchial metastases from carcinoid tumors, breast, colon, kidney cancer, and melanoma ƒ Volume of bleeding is often difficult to gauge ƒ Massive hemoptysis > 600 mL of blood in 48 h o When resp difficulty occurs Æ treated emergently ƒ Often patients can tell where the bleeding is occurring o Placed bleeding side down o Given supplemental oxygen o Emergency bronchoscopy ƒ If the site of the lesion is detected: o Undergoes a definitive surgical procedure or neodymium:yttrium-aluminum-garnet (Nd:YAG) laser o Bronchial artery embolization - control brisk bleeding in 75 to 90% Æ surgery to be safer o Embolization w/ surgery - rebleeding in 20-50% cases o Recurrent hemoptysis – responds to 2nd embolization o Post-embolization – pleuritic pain, fever, dysphagia, and leukocytosis for 5–7 days; resolves w/ sx tx o Rare complications: Bronchial oresophageal wall necrosis Myocardial infarction Spinal cord infarction ƒ Pulmonary hemorrhage ± hemoptysis + hema CA Æ fungal infxn (Aspergillus sp)

Lecture + added notes from Harrison’s 16th ed

MML Batch 2009