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Oncologic emergencies 2013
 

Oncologic emergencies 2013

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  • Review of patients at MSKCC – of 211 pt who present –firstsx in 94% was pain and very other few sxs; and once diagnosed, only 50% had autonomic, sensory loss but 97% had pain.
  • Of those patient ambulatory prior to treatment, percentage of pts that maintained ambulation was 80-97% vs. those paraplegic before, very few ambulated.
  • Etiology may be from increased direct bony invasion (lytic lesions most commonly) and increased local cytokines (Il-6, TNF, etc) with osteoclast activation and bone resorptionExamples = Multiple myeloma; breast cancerMany tumors are associated with PTH-RP
  • PTHrp stimulates normal osteoblast differentiation; also increases RANKL, which stimulates osteoclast precursors resulting in bone resorption
  • Only use after complete hydration
  • Need two or more of the above within 3 days before or 7 days after cytotoxic chemotherapy
  • Allopurinol inhibits Xanthine oxidase. Rasburicase is recombinant urate oxidase.
  • These charts aren’t for neutropenic fever

Oncologic emergencies 2013 Oncologic emergencies 2013 Presentation Transcript

  • Oncologic EmergenciesThe following material is intended for MSKCC internal medicine housestaff teaching purposes only.The slides were updated for the LibGuide in 2012-2013.
  • Topics• Cord compression• Hypercalcemia of malignancy• Tumor lysis syndrome• Neutropenic fever• SVC syndrome
  • MKSAP Case #1A 64-year-old woman is evaluated in the emergency department for a 4-day history ofprogressive leg weakness and numbness and a 1-day history of urinary incontinence. Shehas also had increasingly severe mid-back pain for the past 2 months. She has a history ofbreast cancer diagnosed 2 years ago, treated with surgery and local radiation therapy. Heronly current medication is tamoxifen.Physical examination shows normal mental status and cranial nerves. Strength in the armsis normal. Legs are diffusely weak, 3/5 proximally and 4/5 distally. Sensory examinationshows diminished pin sensation from the nipples downward; vibratory sense is severelydiminished in the feet. Reflexes are 2+ in the biceps and triceps and 3+ in the knees andankles. An extensor plantar response is present bilaterally. Anal sphincter tone isdiminished.Which of the following is the most appropriate diagnostic study at this time?A CT of the lumbar spineB Electromyography and nerve conduction studiesC MRI of the brainD MRI of the entire spineE Plain radiographs of the entire spine
  • MKSAP Case #1A 64-year-old woman is evaluated in the emergency department for a 4-day history ofprogressive leg weakness and numbness and a 1-day history of urinary incontinence. Shehas also had increasingly severe mid-back pain for the past 2 months. She has a history ofbreast cancer diagnosed 2 years ago, treated with surgery and local radiation therapy. Heronly current medication is tamoxifen.Physical examination shows normal mental status and cranial nerves. Strength in the armsis normal. Legs are diffusely weak, 3/5 proximally and 4/5 distally. Sensory examinationshows diminished pin sensation from the nipples downward; vibratory sense is severelydiminished in the feet. Reflexes are 2+ in the biceps and triceps and 3+ in the knees andankles. An extensor plantar response is present bilaterally. Anal sphincter tone isdiminished.Which of the following is the most appropriate diagnostic study at this time?A CT of the lumbar spineB Electromyography and nerve conduction studiesC MRI of the brainD MRI of the entire spineE Plain radiographs of the entire spine
  • Epidural Spinal Cord Compression• Incidence:– Varies depending on the type of malignancy• The most common causes are from:– Prostate (20%), Breast (20%), Lung (20%)– Lymphoma, MM• Occurs in 5-10% pts with cancer• 20 % of cord compression is a new diagnosis of malignancy– Localization in the spine• 60% in the T spine• 30% in the LS spine• 10 % in the C-spine• 20-30% may have multiple lesions
  • Epidural Spinal Cord Compression• Pathophysiology:– Often from vertebrae with extension into spinal canal– The tumor enlarges obstruction of epidural venous plexus production of inflammatory cytokines vasogenic edemacompression compromises blood flow  ischemia/infarction– Also can have direction extension ofa paravertebral lesion through theintervertebral foramen– Much less often: parenchymal spinalcord metastasis due to homogenousspread.
  • Epidural Spinal Cord Compression• Presenting Symptoms:– WEAKNESS: Paresis & Plegia– PAIN– SENSORY LOSS– AUTONOMIC DYSFUNCTION:• Urinary retention• Bowel incontinence• Which is the most common FIRST presentingsymptom?
  • Epidural Spinal Cord Compression• PAIN!– If from thoracic roots, often BL and “band-like” and“tight”– Classically worse when supine, may awake from sleep,worse w coughing/sneezing– May precede sensory loss and weakness by days tomonths (average 7 weeks)– Red flag: back pain in cancer patient
  • Epidural Spinal Cord Compression
  • Epidural Spinal Cord Compression• Physical Exam:– +straight leg raise– Pain with vertebral percussion, neck flexion– +/- numbness, paresthesias, weakness, brisk DTRs– If autonomic dysfunction: decreased anal tone,distended bladder
  • Epidural Spinal Cord Compression• Cauda Equina syndrome:– Compression of nerve rootsas they leave spinal cord– Low back pain– Diminished sensation overbuttocks, posterior superiorthighs, perineal area insaddle distribution– Rectal/bladder dysfunction– Sexual impotence– LE weakness, absent reflexes
  • Epidural Spinal Cord Compression• Diagnosis:– MRI of total spine or CT Myelogram• Treatment:– Dexamethasone 10mg IV – 100mg IVthen 4mg IV q6h– Neurosurgery consult for emergentdecompression– Radiation Oncology consult for emergent XRT– Sometimes chemotherapy/hormonal tx play a role
  • Epidural Spinal Cord CompressionKristin G, Schiff D. Metastatic Spinal Cord Compression by SolidTumors. SEMINARS IN NEUROLOGY/VOLUME 24, NUMBER 4 2004Early treatment is essential!
  • MKSAP Case #2A 66-year-old woman is evaluated for malaise and confusion. She has smoked 1 packof cigarettes a day for the past 40 years. She takes hydrochlorothiazide forhypertension. Physical examination reveals distant breath sounds. Chest radiographshows a 1.5-cm mass in the proximal upper lobe of the left lung and infiltrates distalto the mass. A bone scan indicates no evidence of focal or metastatic disease.Laboratory StudiesCalcium 15.8 mg/dL (3.94 mmol/L)Phosphorus 4.0 mg/dL (1.29 mmol/L)Chloride 97 meq/L (97 mmol/L)Intact PTH <1.0 pg/mL (1.0 ng/L)Serum protein electrophoresis shows polyclonal gammopathy.Which of the following is the most likely cause of the patients hypercalcemia?A Thiazide-induced hypercalcemiaB Parathyroid adenomaC Parathyroid hyperplasiaD Humoral hypercalcemia of malignancyE Multiple myeloma
  • MKSAP Case #2A 66-year-old woman is evaluated for malaise and confusion. She has smoked 1 packof cigarettes a day for the past 40 years. She takes hydrochlorothiazide forhypertension. Physical examination reveals distant breath sounds. Chest radiographshows a 1.5-cm mass in the proximal upper lobe of the left lung and infiltrates distalto the mass. A bone scan indicates no evidence of focal or metastatic disease.Laboratory StudiesCalcium 15.8 mg/dL (3.94 mmol/L)Phosphorus 4.0 mg/dL (1.29 mmol/L)Chloride 97 meq/L (97 mmol/L)Intact PTH <1.0 pg/mL (1.0 ng/L)Serum protein electrophoresis shows polyclonal gammopathy.Which of the following is the most likely cause of the patients hypercalcemia?A Thiazide-induced hypercalcemiaB Parathyroid adenomaC Parathyroid hyperplasiaD Humoral hypercalcemia of malignancyE Multiple myeloma
  • Hypercalcemia of Malignancy• Occurs in 5-30 % of malignancy– Lung, breast and myeloma have the highestincidence– A poor prognostic factor– The level of hypercalcemia is typically much highercompared to hyperparathyroidism, hyperthyroid,hypervitaminosis D, thiazides
  • Hypercalcemia of Malignancy• Pathophysiology1) PTHrP (80%)2) excess production of 1,25 – dihydroxy vitamin D– Lymphomas produce an enzyme (1-a-hydroxylase) thatconverts 25 – hydroxy to the more active form  enhanced GIcalcium absorption3) tumor-mediated production of osteolyticcytokines and inflammatory mediators4) PTH secreting tumor
  • PTHrP• Binds to PTH receptor  distal tubular Ca2+reabsorption, bone absorption• No effect on vitamin D metabolism• Usually produced during development or cellrenewal• Increased production is stimulated by– Oncogene mutations– Altered expression of cellular transcription factors– Local growth factors
  • Hypercalcemia of MalignancyANTICANCER RESEARCH 29: 1551-1556 (2009)
  • Hypercalcemia of Malignancy• Signs & Symptoms– Fatigue– Altered mental status– Nausea, anorexia & constipation– Weakness– Polyuria & dehydration (nephrogenic DI),polydipsia– Depression & anxiety– EKG will show: Shortened QT
  • Hypercalcemia of Malignancy• Treatment:– Saline volume restoration: start with 200-300cc/hr andadjust to urine output ~150 cc’s q hour– Calcitonin: 4 IU/kg IM or SQ q12h x 4 doses• Good safety profile, works immediately– IV bisphosphonate: Zoledronic acid or pamidronate• Take 2-4 days to work, last for 2-4 weeks• Inhibit osteoclast-mediated bone resorption– Treat the underlying malignancy– Steroids ?– Lasix ?– Ultimately dialysis if all else fails
  • MKSAP Case #4A 20-year-old man is admitted to the hospital after a recent diagnosis of acute myeloidleukemia. He is scheduled to begin therapy with cytarabine and daunorubicin.Pre-treatment laboratory studies:Hemoglobin 6.0 g/dL (60 g/L) Leukocytes 80,000/µL (80 × 109/L)Platelet count 60,000/µL (60 × 109/L) Creatinine 1.5 mg/dL (114.5 µmol/L)Lactate dehydrogenase 250 U/L Calcium 9.1 mg/dL (2.3 mmol/L)Sodium 145 meq/L (145 mmol/L) Potassium 5.0 meq/L (5.0 mmol/L)Chloride 104 meq/L (104 mmol/L) Bicarbonate 24 meq/L (24 mmol/L)Phosphorus 5.6 mg/dL (1.8 mmol/L) Uric acid 8.8 mg/dL (0.5 mmol/L)Which of the following is the most appropriate next step before initiation of inductionchemotherapy?A Administration of granulocyte-macrophage colony-stimulating factorB Administration of vancomycinC Aggressive intravenous fluid hydration and allopurinol administrationD Alkalinization of the urine
  • MKSAP Case #4A 20-year-old man is admitted to the hospital after a recent diagnosis of acutemyeloid leukemia. He is scheduled to begin therapy with cytarabine anddaunorubicin.Pre-treatment laboratory studies:Hemoglobin 6.0 g/dL (60 g/L) Leukocytes 80,000/µL (80 × 109/L)Platelet count 60,000/µL (60 × 109/L) Creatinine 1.5 mg/dL (114.5 µmol/L)Lactate dehydrogenase 250 U/L Calcium 9.1 mg/dL (2.3 mmol/L)Sodium 145 meq/L (145 mmol/L) Potassium 5.0 meq/L (5.0 mmol/L)Chloride 104 meq/L (104 mmol/L) Bicarbonate 24 meq/L (24 mmol/L)Phosphorus 5.6 mg/dL (1.8 mmol/L) Uric acid 8.8 mg/dL (0.5 mmol/L)Which of the following is the most appropriate next step before initiation of inductionchemotherapy?A Administration of granulocyte-macrophage colony-stimulating factorB Administration of vancomycinC Aggressive intravenous fluid hydration and allopurinol administrationD Alkalinization of the urine
  • Tumor Lysis Syndrome• Metabolic abnormalities resulting from acute destruction of neoplasticcells and release of their contents into the circulation• Name the metabolic derangements:– Hyperkalemia– Hyperuricemia– Hyperphosphatemia– Hypocalcemia• May lead to Acute Renal Failure, Arrhythmias
  • Tumor Lysis SyndromeAmerican Journal of Kidney Diseases, Vol 55, No 5, Suppl 3(May), 2010: pp S1-S13
  • Tumor Lysis SyndromeAmerican Journal of Kidney Diseases, Vol 55, No 5, Suppl 3(May), 2010: pp S1-S13
  • Tumor Lysis Syndrome• Risk of Tumor lysis depends on the following–Tumor Burden and Tumor Type–Proliferation Rate–Chemosensitivity of the diseaseAmerican Journal of Kidney Diseases, Vol 55, No 5, Suppl 3(May), 2010: pp S1-S13
  • Tumor Lysis SyndromeAmerican Journal of Kidney Diseases, Vol 55, No 5, Suppl 3(May), 2010: pp S1-S13Depends on:Tumor burdenProliferation rateChemosensitivity of the disease
  • Tumor Lysis Syndrome• Prophylaxis– Vigorous hydration with normal saline• goal urine output of 80 - 100 cc’s/M2– Diuretics can be used to maintain UOP andmanage edema– Allopurinol (100mg/M2 q 8) dose reduced in renalfailure  many drug-drug interactions
  • Tumor Lysis Syndrome• How does Allopurinol work?Howard SC et al. N Engl J Med 2011;364:1844-1854
  • Tumor Lysis Syndrome• How does Rasburicase work?• Rasburicase  recombinanturate oxidase– Risks: anaphylaxis,hemolysis, hemoglobinuria,methemoglobinemia– Used as PPX in extremelyhigh risk pts (i.e. kids wBurkitts) and for treatmentin refractory cases– Expensive!! $5000 per doseHoward SC et al. N Engl J Med 2011;364:1844-1854
  • Tumor Lysis Syndrome• Treatment– Increase IV Fluids– Continue allopurinol– Treatment of specific electrolyte abnormalities• Diuretics/kayexalate for hyperkalemia• Phosphate binders for hyperphosphatemia• Tolerate mild hypocalcemia, so as not to precipitateCalcium phosphate– Rasburicase– Dialysis, if needed
  • Tumor Lysis Syndrome• Indications for dialysis:– Oliguria– Persistent hyperphosphatemia/hyperkalemia– Persistent hyperuricemia– Persistently low calcium levels
  • MSKAP Case #545 year-old male with AML is hospitalized with fever afterreceiving chemotherapy. Physical exam is nonrevealing. Vitals arestable. Bloodwork reveals a total WBC count of 0.4. UA, CXRunremarkable. BCx pending. He has no central venous line.He has no allergies, and no known history of resistant organismsor colonizations.The next step in management is:A Start empiric Zosyn monotherapyB Start empiric Vancomycin monotherapyC Start empiric Vancomycin & ZosynD Admit for observation, start antibiotics if infectious sourceidentified
  • MSKAP Question45 year-old male with AML is hospitalized with fever afterreceiving chemotherapy. Physical exam is nonrevealing. Vitals arestable. Bloodwork reveals a total WBC count of 0.4. UA, CXRunremarkable. BCx pending. He has no central venous line.He has no allergies, and no known history of resistant organismsor colonizations.The next step in management is:A Start empiric Zosyn monotherapyB Start empiric Vancomycin monotherapyC Start empiric Vancomycin & ZosynD Admit for observation, start antibiotics if infectious sourceidentified
  • Neutropenic Fever• ANC < 500– Or ANC < 1000 with anticipated drop < 500• Fever: T>38.3oC once or T>38.0oC x 2 one hourapart– NB: at MSKCC, start work up for patients withT>38.0oC• An emergency
  • Neutropenic Fever• Panculture, examine. Only visual inspection of anorectalregion, not manual.• EMPIRIC COVERAGEAGAINST:– Gram negatives• Pseudomonas– Gram positives
  • Bacterial isolates in cancer patients
  • Neutropenic FeverAdapted from: CID 2011:52 (Freifeld et al)
  • Neutropenic Fever• High-risk options:– Zosyn monotherapy(gets good GP & GN coverage, including Pseudomonas)– Cefepime monotherapy(gets good GP & GN coverage, including Pseudomonas)– Carbapenem monotherapy(gets good GP & GN coverage, including Pseudomonas & beta-lactamase-resistant organisms)
  • Neutropenic Fever• Add vancomycin if:– Suspicion for soft tissue infection– Suspicion for line infection– Hx MRSA infection or colonization– Pt has hardware– Hemodynamically unstable– Can discontinue after 48 hours ifcultures negative and no suspicionfor MRSACan consider linezolidif patient has a hx ofVRE infection orcolonization
  • Neutropenic Fever• Other antibiotics:– Consider amikacin if the patient is unstable or if yoususpect MDR gram-negative infection– Avoid fluoroquinolones if the patient was on FQprophylaxis– If persistently febrile > 5 days, add fungal coverage• Duration:– If source found, complete standard course– If no source found, treat until no longer febrile x 48hours and no longer neutropenic
  • MSKAP Question (part 2)• 45 year-old male with AML is hospitalized with fever after receivingchemotherapy. Physical exam is nonrevealing. Vitals are stable.Bloodwork reveals a total WBC count of 0.4. UA, CXRunremarkable. BCx pending. He has no central venous line.He has a hx of anaphylaxis with penicillin.The next step in management is:A Start empiric Cefepime monotherapyB Start empiric Aztreonam monotherapyC Start empiric Vancomycin monotherapyD Start empiric Vancomycin & CefepimeE Start empiric Vancomycin & AztreonamF Admit for observation, start antibiotics if infectious sourceidentified
  • MSKAP Question (part 3)• 45 year-old male with AML is hospitalized with fever after receivingchemotherapy. Physical exam is nonrevealing. Vitals are stable.Bloodwork reveals a total WBC count of 0.4. UA, CXRunremarkable. BCx pending. He has no central venous line.He has a hx of anaphylaxis with penicillin.The next step in management is:A Start empiric Cefepime monotherapyB Start empiric Aztreonam monotherapyC Start empiric Vancomycin monotherapyD Start empiric Vancomycin & CefepimeE Start empiric Vancomycin & AztreonamF Admit for observation, start antibiotics if infectious sourceidentified
  • A 39-year-old man with pancreatic cancer is evaluated for profound neutropenia occurringwith each of several rounds of chemotherapy. His absolute neutrophil count has been lessthan 100/µL (0.10 × 109/L) for the past 15 days. He also has a cough productive of blood-tinged brown sputum and has had temperatures to 40.1 °C (104.1 °F) for 3 days. Empirictreatment with piperacillin/tazobactam is started. Chest radiographs reveal several cavitarylesions in both lungs.On physical examination, temperature is 39.1 °C (102.3 °F), blood pressure is 98/62 mmHg, pulse rate is 118/min, and respiration rate is 24/min. Pulmonary examination disclosesbilateral crackles and occasional wheezes.Nasopharyngeal swab and expectorated sputum cultures both grow Aspergillus fumigatus.Which of the following is the most appropriate addition to his treatment?A Amphotericin B deoxycholateB FluconazoleC KetoconazoleD Liposomal amphotericin BE Voriconazole
  • A 39-year-old man with pancreatic cancer is evaluated for profound neutropenia occurring witheach of several rounds of chemotherapy. His absolute neutrophil count has been less than100/µL (0.10 × 109/L) for the past 15 days. He also has a cough productive of blood-tingedbrown sputum and has had temperatures to 40.1 °C (104.1 °F) for 3 days. Empiric treatmentwith piperacillin/tazobactam is started. Chest radiographs reveal several cavitary lesions in bothlungs.On physical examination, temperature is 39.1 °C (102.3 °F), blood pressure is 98/62 mm Hg,pulse rate is 118/min, and respiration rate is 24/min. Pulmonary examination discloses bilateralcrackles and occasional wheezes.Nasopharyngeal swab and expectorated sputum cultures both grow Aspergillus fumigatus.Which of the following is the most appropriate addition to his treatment?A Amphotericin B deoxycholateB FluconazoleC KetoconazoleD Liposomal amphotericin BE Voriconazole
  • MKSAP Case #660M is evaluated in ED for weight loss, progressive cough, dyspnea, head fullness, anddifficulty swallowing X 3 months. Over past 2 days he has also noted progressive facialswelling. Denies fever, chills, or sputum production. The pt has 45-pack-year smoking hx.On PE, temp is 37.1 °C (98.8 °F), BP 100/50 mm Hg, pulse is 120/min, and RR is 20/min.The patient’s face is edematous, and there is venous distention noted on the neck andchest wall. Cardiac examination reveals normal heart sounds without evidence of extraheart sounds, murmurs, or rubs. Faint expiratory wheezes but no crackles are heard onpulmonary auscultation. There is no hepatomegaly or peripheral edema.A chest radiograph shows mediastinal widening and small, bilateral pleural effusions.Which of the following is the most likely diagnosis?A. Heart FailureB. PneumoniaC. Pulmonary EmbolismD. Superior Vena Cava Syndrome
  • MKSAP Case #660M is evaluated in ED for weight loss, progressive cough, dyspnea, head fullness, anddifficulty swallowing X 3 months. Over past 2 days he has also noted progressive facialswelling. Denies fever, chills, or sputum production. The pt has 45-pack-year smoking hx.On PE, temp is 37.1 °C (98.8 °F), BP 100/50 mm Hg, pulse is 120/min, and RR is 20/min.The patient’s face is edematous, and there is venous distention noted on the neck andchest wall. Cardiac examination reveals normal heart sounds without evidence of extraheart sounds, murmurs, or rubs. Faint expiratory wheezes but no crackles are heard onpulmonary auscultation. There is no hepatomegaly or peripheral edema.A chest radiograph shows mediastinal widening and small, bilateral pleural effusions.Which of the following is the most likely diagnosis?A. Heart FailureB. PneumoniaC. Pulmonary EmbolismD. Superior Vena Cava Syndrome
  • SVC syndrome (oncologic urgency)• SVC obstruction severe reduction in venousreturn from head, neck, and upper extremities• Clinical Presentation:– Dilated neck veins, anterior chestwall collateral veins– Cyanosis, edema face, neck, UE– Cerebral and laryngeal edema: poorprognosis so evaluate urgently!• 75% from lung cancer (NSCLC 50% and 25% SCLC)
  • SVC syndrome• Diagnosis: clinically + CT Chest with contrast– diminished opacification of central venous structures withprominent collateral venous circulation• Management– Elevate head of bed, low salt diet, diuretics– Treat underlying malignancy• SCLC, NHL are chemosensitive• NSCLC often requires endovascular stent 2/2 obstruction• Glucocorticoids - lymphoma– If presenting condition, first obtain histologic diagnosis• Unless airway compromise or cerebral edema emergent RT and/orstent
  • Topics Covered• Cord compression• Hypercalcemia of malignancy• Tumor lysis syndrome• Neutropenic fever• SVC Syndrome