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CES 2016 02 - Oncologic emergencies

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Clase de emergencias oncológicas para estudiantes de medicina, revisada y ampliada, 2016.

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CES 2016 02 - Oncologic emergencies

  1. 1. CES 2016.02: Oncologic emergencies Mauricio Lema Medina MD
  2. 2. Acknowledgments José Julián Acevedo MD Mateo Mejía MD
  3. 3. Pressure or obstruction caused by space-occupying lesion Metabolic or hormonal problems (paraneoplastic syndromes) Treatment related complications
  4. 4. Oncologic emergencies  SVCS  MSCC  Pericardial effusion  Visceral obstruction  Intracranial hypertension  Seizures  Hemoptysis Mechanical/Obstructive  Hypercalcemia  SIADH  Lactic acidosis  Hypoglycemia  Adrenal insuffiency Metabolic  Febril neutropenia  Tumor-lysis syndrome  Infusional reactions  Neutropenic colitis  Pulmonary infiltrates Treatment related
  5. 5. Obstruction of the superior vena cava (SVC): Severe reduction in venous return from the head, neck and upper extremieties Lung cancer, lymphoma (NHL), primary mediastinal germ-cell tumor metastatic disease (testicular cancer, breast cancer), intravascular devices, aortic aneurysm, thyromegaly, thrombosis, fibrosing mediastintis, histoplasmosis, Behcet’s disease http://www.aboutcancer.com/svco.htm
  6. 6. Superior vena cava syndrome Neck and facial swelling, dyspnea, cough. Other symptoms: hoarseness, tongue swellin, headache, nasal congestion, epistaxis, hemoptysis, dysphagia, pain, dizziness, syncope, and lethargy. Dilated neck veins, increased dilated collateral veins in the chest wall; cyanosis of the face, arms and chest; proptosis, glossal and pharyngeal edema, obtundation; cardiac arrest or respiratory failure. Esophageal varices may also occur. Enlarged mediastinum in CXR CT scan shows central mediastinal vein blockage + increased collateral vein circulation. Endobronchial or esophageal US guided biopsy may provide the diagnosis.Harrison’s 19th
  7. 7. CXR Mass, widening of the mediastinum, pleural effusion Main risk Tracheal obstuction Grades % 0 – Asymptomatic 10 Imaging 1 – Mild 25 Edema / cyanosis 2 – Moderate 50 Cough, dysphagia, visual disturbances 3 – Severe 10 Brain or laryngeal swelling, syncope on exertion 4 – Life-threatening 5 Brain or laryngeal swelling (obtundation, stridor), syncope or hypotension 5 - Fatal <1 Death Yu, JB, J Thoracic Oncol, 2008
  8. 8. Colaterales venosos del sindrome de vena cava superior Edema subcutáneo de la obstrucción de la vena cava Casi total oclusión de la vena cava superior por adenopatía mediastinal Superior vena cava syndrome SVC obstruction Collateral circulation Tumor
  9. 9. Superior vena cava syndrome Treatment Establish tissue diagnosis if unknown: Bronchoscopy, esophagoscopy, CT guided biopsy, thoracoscopy, etc. General measures Diuretics, low-salt diet, head elevation, oxygen. Glucocorticosteroids (only in lymphoma) Treat the underlying condition (Chemo)-RT for NSCLC RT for metastatic solid tumors Chemotherapy for SCLC, lymphoma and GCT Surgery for benign processes Anticoagulation / Device removal if due to thrombosis or fibrinolytic therapy SVCS relapses in 10% SVC stent Recommended in relapsed SVCS Severe SVCS Stent complications: heart failure, pulmonary edema, hematoma, SVC perforation, migration, fracture, pulmonary embolismHarrison’s 19th
  10. 10. SVCS Grade 1-3 Grade 4 SVC stent Tissue diagnosis (if applicable) Treat the underlying condition RT for other malignanciesChemo for SCLC, GCT, lymphomas Specific Rx for non-malignant Chemosensitive Non-malignantNon-chemosensitive Thrombosis Chemotherapy Anticoagulation/fibrinolytic(Chemo)-RT Surgery
  11. 11. Malignant spinal cord compression (MSCC) Occurs in 5-10% of patients with cancer MSCC is the presenting feature in 10% of malignancies Lung cancer is the most common cause of MSCC Causes Lung, breast, prostate, multiple myeloma are the big ones. Lymphomas, melanomas, genitourinary tumors and RCC, neoplastic leptomeningitis cause MSCC too. Non-oncologic differential diagnosis Osteoporotic vertebral collapse, disk disease, pyogenic abscess, vertebral tuberculosis, radiation myelopathy, benign tumors, epidural hematoma, and spinal lipomatosis. Sites Thoracic spine: 70%, Lumbosacral spine: 20%, Cervical spine: 10%. Mechanism Vertebral body metastases, extension of paravertebral tumors, intramedulary metastases (usually with CNS metastases and leptomeningeal disease). Tissue ischemia and cytokine release (VEGF) may accelerate tissue damage. Harrison’s, 19th Ed
  12. 12. Malignant spinal cord compression (MSCC) Clinical presentation Back pain and tenderness It is exacerbated by movement, cough or sneezing. Worsens in the supine position. Lhermitte’s sign may herald MSCC Radiculopathic pain may also be present Loss of bladder or bowel control tend to occur late in the course of MSCC Physical examination Pain induced by leg raising, neck flexion, or vertebral percussion; numbness or paresthesia; loss of pinprick or vibration of position. Weakness, spasticity and abnormal muscle stretching. Extensor plantar reflex. Deep tendon reflexes may be brisk. Decreased anal tonus, perineal sensibility, and a distended bladder. Absence of the anal wink and bulbocavernous reflexes. Cauda equina syndrome Low back pain, diminished sensation in a saddle distribution; rectal, bladder dysfunction, loss of bulbocavernous, patellar and Achilles relexes; lower extremity weakness. Causes: Primary tumors of the glia or nerve sheath Harrison’s, 19th Ed
  13. 13. Pérdida de las todas las modalidades sensoriales hasta el nivel de la lesión Fuerza y reflejos osteotendíneos disminuidos hasta el nivel de la lesión Miembros flácidos Vejiga dilatada – retención urinaria, Esfínter anal disfuncional - constipación
  14. 14. T4 T12 T10
  15. 15. Back pain Neurologic exam Suspicious of myelopathy HD Dexamethasone MRI of spine Pain crescendo pattern Lhermitte’s sign Pain aggravated with cough, valsalva or recumbency Abnormal spine x-ray Normal Spine x-ray Symptomatic therapy Epidural metastases Bone metastases, no epidural metastasesNormal Surgery + RT or RT RT Harrison’s, 19th Ed 6 mg IV q6h Whole spine, preferred
  16. 16. MSCC http://www.bimjonline.com/Imageoftheweek/Imagewk17(28-05-2012).htm
  17. 17. MSCC http://www.bimjonline.com/Imageoftheweek/Imagewk17(28-05-2012).htm
  18. 18. Loblaw A. J Clin Oncol 23:2028-2037 Esteroides en compresión medular Resultados Comentarios Dexametasona 96 mg IV x1, 24 mg VO q6h x3 día…(1) 81% ambulatorios @3m Toxicidad severa: 11% Nada(1) 61% ambulatorios @3m NS (n=57) Dexametasona 100 mg IV(2) Mejoría en la fuerza 25% NS Dexametasona 10 mg IV(2) Mejoría en la fuerza 8% NS (n=37) Dexametasona 100 mg(3) Efectos adversos serios: 14.2% Casos y controles Dexametasona 10 mg, seguido 4 mg IV q6h…(3) Efectos adversos serios: 0% Casos y controles No esteroides en ambulatorios(4) 20/20 ambulatorios @3m post RT (1) Sorensen et al, (2) Vecht et al, (3) Heimdal et al, (4) Maranzano et al.
  19. 19. Esteroides en compresión medular metastásica • Parecen eficaces (junto con RT) • Dosis demasiado altas, demasiado tóxicas • Dosis demasiado bajas, menos eficaces • En pacientes Ambulatorios, RT suficiente • Recomendación (Soft) • Dexametasona 6 mg IV q6h hasta que se defina el manejo definitivo White BD et al. NICE Guidance. BMJ 2008; 337:a2538
  20. 20. Cirugía para compresión medular oncológica • Indicaciones • Dislocación de fractura patológica • Falla de la radioterapia • Síntomas neurológicos rápidamente progresivos • Expectativa de vida >3 meses • Tumor radioresistente (melanoma, RCC) • No diagnóstico oncológico previo • Complementar con radioterapia (dentro de los primeros 14 días post-op). • Considerar bisfosfonatos / Denosumab • Limitaciones • Ineficaz si paraplejía o cuadriplejía >24 horas • No recomendada si expectativa de vida <3 meses • Mortalidad 0-13% • Complicación severa • Laminectomía: 0-10% • Resección de cuerpo vertebral: 10-54% Loblaw A. J Clin Oncol 23:2028-2037 White BD et al. NICE Guidance. BMJ 2008; 337:a2538 Harrison’s, 19th Ed
  21. 21. Loblaw A. J Clin Oncol 23:2028-2037 Estado a la presentación % ambulatorio después de radioterapia IC 95% Ambulatorio 92% 89% - 95% Ambulatoria con asistencia 65% 56% - 74% Paraparético 43% 38% - 48% Parapléjico 14% 10% - 17%
  22. 22. Pericardial effusion/tamponade Found in autopsy in 5-10% of cancer patients. Causes Lung cancer, breast cancer, leukemias and lymphomas Non-tumoral differential diagnosis Irradiation, drug-induced pericarditis, hypothyroidism, idiopathic pericarditis, infection, autoimmun disease Radiation pericarditis Acute inflammatory, self-limiting, within month of irradiation. Chronic effussive pericarditis up to 20 years post radiotherapy, with pericardial thickening. Symptoms Most patients are asymptomatic. Dyspnea, cough, chest pain, orthopnea and weakness. Signs Pleural effusions, sinus tachycardia, jugular venous distention, hepatomegaly, peripheral edema, and cyanosis. Typical pericardial signs are less frequent in malignant pericardial disease (pulsus alterans, paradoxical pulse, diminished heart sounds, and friction rub). Echocardiography is the test of choice. CT scan with irregular pericardial thickening and mediastinal lymph nodes is highly suspicious of malignant pericardial effusion Harrison’s, 19th Ed
  23. 23. Pericardial effusion/tamponade Treatment options Pericardiocentesis (with or withou sclerosing agents) Percardial window Complete pericardial stripping Cardiac irradiation or Chemotherapy Acute cardiac tamponade (malignant pericardial effusion with hemodynamic instability) requires IMMEDIATE drainage of fluid (ie, pericardiocentesis). Recurrence after pericardiocentesis occurs in 20% Sclerosing agents diminish the risk of recurrence. Bedside pericardiotomy should be reserved to TV shows. In about 10% of patients there is a paradoxical worsening of the hemodynamic status post pericardial fluid drainage (“low cardiac output syndrome”). Prognosis is dismal. Pericardial effusion with malignant cells carries a poor prognosis with a 7 week median survival in cancer patients. Harrison’s, 19th Ed
  24. 24. Intestinal obstruction Treatment options Palliative (non-surgical) care Surgery (high mortality rate: 10-20%). Laparoscopy (sometimes helps) Stents: may palliate patients without major surgery. Nasogastric decompression (mostly for advanced intra-abdominal malignancy). “Venting” gastrostomy (palliates nausea and vomiting). Medications: antiemetic agents, analgesics, antiespasmodic, steroides, octreotide Harrison’s, 19th Ed Intestinal obstruction Single-site, good PS Surgery/laparoscopy Single-site, poor PS Stent / medical Multiple sites Medical / palliative My algorithm… NG tube CT abdomen Surgical consultation Electrolyte, fluid and drug evaluation Surgery (Open) PalliationLaparoscopy GI stent Aggressive nutrition Aggressive symptom control
  25. 25. Malignant biliary obstruction Causes Cancer arising in the pancreas, ampulla of Vater, bile duct, or liver or by metastatic disease to the periductal lymph nodes or liver parenchyma (gastric, colon, breast or lung). Non-oncologic causes Found in 25%: narcotics, vinca alcaloids, adhesions. Clinical findings Jaundice, light colored stool, dark urine, priritus, and weight loss (due to malabsorption). Pain and infections are UNCOMMON. Imaging modalities US, CT scan, ERCP, percutaneous transhepatic cholangiography, MRI Treatment Stent Surgical bypass RT (+/-) chemotherapy. In the absence of pruritus, biliary obstruction may be a largely asymptomatic cause of death. Harrison’s, 19th Ed
  26. 26. Increased intracraneial pressure 25% of cancer patients die with CNS metastases. Brain metastases may be the first evidence of cancer. Causes Lung, breast, melanoma. Non-oncologic causes Tretinoin pseutumor cerebri with increased intracranial pressure. Clinical findings Headache, nausea, vomiting, behavioral changes, seizures, and focal, progressive neurologic changes. Hemorrhagic metastases may mimick a hemorrhagic stroke (melanoma, GCT and RCC). Papilledema, neck stiffness, herniation syndromes. Imaging modalities Cranial contrast-enhanced CT. If negative, Gadolinium-enhanced MRI. Treatment Dexamethasone. Surgery Whole brain radiotherapy Gamma knife Shunt placement (if hydrocephaly an issue). Harrison’s, 19th Ed
  27. 27. Harrison’s, 19th Ed Brain mets Single-site, good PS, good prognosis Surgery* + Gamma knife Few small mets Gamma knife / WBRT Widespread CNS mets or poor prognosis WBRT/Palliation My algorithm… Dexamethasone 6 mg IV q6h Neurosurgical consultation RT consultation *Surgery preferred if cancer diagnosis not histologically proven WBRT: Whole brain radiotherapy Surgery PalliationStereotactic radiosurgery Whole-brain irradiation
  28. 28. Seizures Approximately 10% of CNS metastases patients develop seizures. Causes Tumor, metabolic, radiation injury, cerebral infarctions, chemotherapy-related, infections. Metastatic disease is the MOST frequent cause of seizures in cancer patients. Primary brain tumors cause seizure MORE often than metastatic tumors. Drug-related seizures are RARE but can occur (etoposide, busulfan, ifosfamide, chlorambucil) Site Occipital, posterior-fossa and sellar tumors are less likely to seize. Seizures are frequent in melanoma metastases, and LG brain tumors. Reversible posterior leukoencephalopathy syndrome(RPLS) Headache, altered consciousness, generalized seizures, visual disturbances, hypertension, and posterior cerebral white matter vasogenic edema on CT/MRI. RPLS is associated with: chemotherapy, antiangiogenic therapy, and transplantation. Treatment Phenytoin or Levetiracetam +/- valproic acid. Prefer levetiracetam (500 mg q12h, up to 3000 mg/day) or topiramate for long-term anticonvulsant therapy since they do not inducte cytochrome P450 as phenytoin/valproate do. Surgical or stereotactic radiosurgery may alleviate seizures in some patients. Harrison’s, 19th Ed
  29. 29. Hemoptysis Up to 20% of lung cancer patients have hemoptysis Causes Lung cancer, carcinoid tumors, breast cancer, colon cancer, kidney cancer and melanoma. Massive hemoptysis: more than 200 mL/24h All hemoptysis should be considered life-threatening. Treatment ICU is needed if respiratory distress. Lateral decubitus with the bleeding site down + oxygen. Consider ET-intubation if airway is/may-be compromised + emergency bronchoscopy. CT angiography with bronchial artery embolization may be an option for the stable patient Surgery may be effective as salvage therapy. Pulmonary hemorrhage may occur after Apergillus spp. Infection in hematologic malignancies with prolongued neutropenia. Bevacizumab may cause life-threatning bleeding in cavitated, vascular abutting or squamous-cell NSCLC patients. Harrison’s, 19th Ed
  30. 30. Neutropenia Febril • DEFINICIÓN – Fiebre mayor de 38 grados centígrados durante 1 hora o más o fiebre mayor de 38.3 grados centígrados en 1 ocasión. – Recuento absoluto de granulocitos menor de 500/mm3 o recuento de leucocitos < 1000/mm3 cuando se espera que el recuento de granulocitos es menor de 500/mm3.
  31. 31. Fisiopatología. • Barreras mucosas. • Defectos inmunes. Día 1 Día 8 Día 15 Día 22 Inicio de ciclo de quimioterapia Inicio de ciclo de quimioterapia ANC<500/mm3 Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011;52(4)
  32. 32. Riesgo de infección en pacientes con cáncer Riesgo de infección / CATEGORÍA DE RIESGO PARA NEUTROPENIA FEBRIL Ejemplos de enfermedad y terapia Profilaxis antimicrobiana Baja / BAJA Quimioterapia estándar para la mayoría de tumores sólidos. Neutropenia esperada <7 días Ninguna (excepto profilaxis viral en pacientes con historia de episodio por HSV) Intermedia / Usualmente, ALTA Trasplante autólogo Linfoma Mieloma múltiple Leucemia linfoide crónica Terapia con análogos de purina Neutropenia esperada de 7 a 10 días Bacteriano: considerar fluoroquinolonas. Micótica: Considerar fluconazole durante la neutropenia y con la mucositis anticipada Viral: Durante la neutropenia y al menos 30 días después de trasplanta autólogo Alta / ALTA Trasplante alogénico Inducción y consolidación de leucemia aguda Terapia con Alemtuzumab GVHD tratada con altas dosis de esteroides Duración anticipada de la neutropenia >10 días Bacteriana: Considere fluorquinolona. Micótica: considere fluconazol, amfotericina, voriconazol, posaconazol Viral: Durante la neutropenia y al menos 30 días después de trasplanta autólogo NCCN® Practice Guidelines in Oncology – v.2.2009, www.nccn.org
  33. 33. Common infectiuous agents Gram Positive Cocci and Bacilli Gram Negative Cocci and Bacilli Anaerobic Cocci and Bacilli Staphylococcus epidermidis Escherichia coli Bacteroides spp Staphylococcus aureus. Klebsiella spp Clostridium spp Streptococcus spp Pseudomonas aeruginosa Fusobacterium spp Streptococcus viridans Enterobacter spp Peptococcus Streptococcus pneumoniae Acinetobacter spp Peptostreptococcus spp Streptococcus pyogenes Enterobacter spp E. faecalis/faecium Proteus spp Listeria monocytogenes Stenotrophomonas maltophilia
  34. 34. Score de Riesgo para Neutropenia Febril - MASCC Síntomas leves (o no) de enfermedad 5 Síntomas SEVEROS asociados a la enfermedad 3 No hipotensión 5 No EPOC 4 Tumor sólido / no infección micótica 4 No deshidratación 3 Inicio de la fiebre FUERA del hospital 3 Edad entre 16 y 60 años 2 Con un puntaje igual o mayor a 21 se considera que es de bajo riesgo con un valor predictivo positivo de 91%, especificidad de 68% y sensibilidad de 71%. Klastersky J, Paesmans M, Rubenstein EJ et al. The Multinational Association for Supportive Care in Cancer Risk Index: A Multinational Scoring System for Identifying Low-Risk Febrile Neutropenic Cancer Patients. J Clin Oncol 2000;18(16):3038-51.
  35. 35. Neutropenia febrilNeutropenia febril Infección identificada Sin Factor de Riesgo Con factor de riesgo InestableEstable Imipenem + Vancomicina Cefepime* Piperacilina/Tazobactam o Ceftriaxona* Rx apropiado GNR: Gram Negativos resistentes / MRSA: Staphylococcus aureus resistentes a meticilina * + Vancomicina si factor de riesgo para MRSA Factores de riesgo Para GNR: Hospitalización reciente; betalactámicos en los últimos 3 meses; historia de GNR Para MRSA: Catéter; betalactámicos en los últimos 3 meses; historia de MRSA Para Pseudomona: Intubación >72 horas; úlceras crónicas; pneumopatía crónicamente infectada Mi enfoque
  36. 36. Neutropenia febril … Adicionar NCCN® Practice Guidelines in Oncology – v.2.2009, www.nccn.org Sitio o presentación Comentario Considerar (adición) Senos paranasales CT / RM / ORL Vancomicina si edema periorbitario Amfotericina si posible infección micótica Dolor abdominal CT / Amilasa / AST / Bilirrubina Metronidazol (C. difficile) Terapia para anaerobios Dolor perirrectal Inspección / CT Cubrimiento para anaerobios Cubrimiento para enterococo Cuidado local Diarrea C. Difficile Metronidazol oral o IV si se sospecha C. difficile Catéter vascular Cultivo de cada puerto y del sitio de inserción Vancomicina inicial (o a las 48 horas si no hay mejoría con el antibiótico empírico) Considerar retirar el catheter Infiltrados pulmonares Evaluación según riesgo Adicionar Azitromicina o Fluorquinolonas para cubrir bacterias atípicas. Vancomicina o Linezolid si sospecha de MRSA Considerar terapia antimicótica si hay alto riesgo Considerar TMP-SMX si Pneumocystis jiroveci posible Síntomas urinarios Citoquímico de orina, urocultivo Según patógeno aislado Sistema nervioso central LCR / CT o RM Antipseudomona que atraviese la BHE + vancomicina + ampicilina Encefalitis: Altas dosis de aciclovir
  37. 37. Neutropenia febril … Adicionar G-CSF NCCN® Practice Guidelines in Oncology – v.2.2009, www.nccn.org Sólo en las siguientes situaciones clínicas (categoría 2B): Pneumonía Infección micótica invasiva Infección progresiva
  38. 38. Neutropenia febril NCCN® Practice Guidelines in Oncology – v.2.2009, www.nccn.org Así haya una infección establecida, el cubrimiento antibiótico de amplio espectro se debe conservar en el paciente neutropénico febril
  39. 39. Neutropenia febril NCCN® Practice Guidelines in Oncology – v.2.2009, www.nccn.org Antibióticos Evaluar respuesta 3-5 días Mejoría de la curva térmica Signos y síntomas de infección estables o mejorando Paciente estable hemodinámicamente No beneficio en el cambio de antibiótico por “fiebre” dentro de los primeros 3-5 días Continuar hasta El esquema antibiótico inicial debe continuarse mínimo hasta ANC >500/mcl Otras variables deben ser tenidas en cuenta: Velocidad de defervescencia Sitio específico de infección (si lo hay) Patógeno aislado Enfermedad de base
  40. 40. NCCN® Practice Guidelines in Oncology – v.2.2009, www.nccn.org Duración sugerida de la terapia antibiótica para infección documentada Infección Duración sugerida (Días) Comentario Piel / tejido blando 7-14 Bacteremia gram negativa 10-14 Bacteremia gram positiva 7-14 S. Aureus 14 Contados a partir del primer cultivo negativo y ecocardiografía negativa Candida spp. 14 Contados a partir del primer cultivo negativo Sinusitis 10-21 Pneumonía bacteriana 10-21 Aspergillus spp. 90 HSV/VZV 7-10 Influenza 5 Considerar retirar el catéter de acceso venoso cuando hay infecciones en la corriente sanguínea de: Cancida, S. aureus, Pseudomona aeruginosa, Corynebacterium jeikeium, Acinetobacter, Bacillus, micobacterias atípicas, levaduras, hongos, enterococos resistentes a vancomicna y Stenotrophomonas maltophilla, flebitis séptica, infecciónes tuneladas o infección del bolsillo del puerto
  41. 41. Tumor lysis syndrome (TLS) Hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia caused by the destruction of a large number of rapidly proliferating neoplastic cells. Causes Burkitt’s lymphoma, ALL, High-grade Lymphomas, chronic leukemias, and, rarely, solid tumors. Fludarabine-treated CLL. TLS has been described with the administration of glucocorticoids, letrozol, tamoxifen, rituximab, or spontaneously. TLS occurs during or shortly (1-5 days) after chemotherapy. Harrison’s, 19th Ed Rapid cell killing High serum uric acid Urinary urate obstruction ARF High serum P Low serum Ca NM/Cardiac irritabilty/T etany High serum K Ventricular arrhythmias/s udden death Kidney calcium phosphate deposition Lactic acidosis Acidosis Dehydration Urinary uric acid crystals Urinary uric acid higher than urinary creatinine
  42. 42. Sindrome de lisis tumoral Coiffier B. J Clin Oncol 2008; 26:2767-2778 Cánceres asociados a SLT en adultos Linfoma no Hodgkin 28% Leucemia mieloide aguda 27% Leucemia linfoide aguda 19% Leucemia linfoide crónica 10% Mieloma múltiple 3.9% Enfermedad de Hodgkin 1.6% Tumores sólidos 1%
  43. 43. Sindrome de lisis tumoral Coiffier B. J Clin Oncol 2008; 26:2767-2778 Factores de riesgo para SLT Tipo de tumor Linfoma de Burkitt Linfoma linfoblástico Linfoma difuso de células grandes Leucemia linfoide aguda Tumores sólidos (alta proliferación y respuesta rápida a tratamiento) Masa tumoral Enfermedad voluminosa (>10 cm) Incremento LDH (> 2 x LSN) Leucocitos > 25000/uL Función renal Falla renal pre-existente Oliguria Ácido úrico basal >7.5 mg/dL Terapia eficaz citorreductiva Variable
  44. 44. Sindrome de lisis tumoral Coiffier B. J Clin Oncol 2008; 26:2767-2778 Estratificación de riesgo de SLT Tipo de tumor Alto riesgo Riesgo Intermedio Bajo Riesgo Linfoma No Hodgkin Burkitt, linfoblástico, Leucemia linfoide aguda Linfoma difuso de células grandes Linfoma indolente Leucemia linfoide aguda >100k/mm3 50-100k/mm3 <50k/mm3 Leucemia linfoide aguda >50k/mm3 Monoblástica 10-50k/mm3 <10k/mm3 Leucemia linfoide crónica 10-100k/mm3 Fludarabina Demás
  45. 45. Catabolismo de purinas Hipoxantina Xantina Ácido úrico Alantoína Xantina oxidasa Xantina oxidasa Urato oxidasa Alopurinol Alopurinol Rasburicasa
  46. 46. Sindrome de lisis tumoral Coiffier B. J Clin Oncol 2008; 26:2767-2778 Definición de laboartorio de SLT – Cairo-Bishop Variable Valor Δ del basal Ácido úrico > 8 mg/dL ↑ 25% Potasio > 6 mg/L ↑ 25% Fósforo > 1.45 mMol/L ↑ 25% Calcio < 1.75 mMol/L ↓ 25% NOTA: 2 o más cambios de laboratorio que dentro de 3 días antes o 7 días después de quimioterapia citotóxica
  47. 47. Definición y gradación clínica del SLT – Criterios de Cairo-Bishop Grado Complicación 1 2 3 4 5 Creatinina <1.5 x LSN 1.5-3 x LSN 3-6 x LSN >6 x LSN Muerte Arritmias No requiere tratamiento Tratamiento no urgente Sintomática o requiere de dispositivo Con peligro para la vida Muerte Convulsiones Ninguna Una generalizada, controlada con anticonvulsivan te; hasta varias focales, infrecuentes, que no afecten las actividades diarias Convulsiones con alteración de la consciencia. Convulsiones pobremente controladas. Convulsiones con pobre respuesta al tratamiento Status epilepticus, convulsiones de difícil control - prolongadas Muerte LSN: Límite superior de lo normal Coiffier B. J Clin Oncol 2008; 26:2767-2778
  48. 48. Harrison’s, 19th Ed TLS If high serum uric acid (8) and high creatinine (1.6) IV hydration 3000 mL/m2/day Urine pH above 7 with bicarbonate Allopurinol 300 mg/m2/day Monitor serum chemistry Correct treatable renal conditions Rasburicase 0.2 mg/kg/day If high serum uric acid (8) and high creatinine (1.6) Delay chemo or chemo + hemodialysis If not high-serum uric acid (8) and not- high creatinine (1.6), high urine pH (7) Discontinue bicarbonate, start chemotherapy Begin hemodialysis if high serum potassium (6), serum uric acid (10), high cratinine (10), high phosphate (10), sympotomatic hypocalcemia Recombinant urate oxidase May cause hypersensitivity: bronchospasm, hypoxemia, hypotension Do not use in G6PD deficiency Also discontinue bicarbonate if high Phosphate
  49. 49. Hipercalcemia asociada a malignidad • Incidencia: 20 – 30% • Más comunes • Ca de mama • Ca de pulmón. • Mieloma múltiple. • Mecanismos - Metástasis líticas (20%). - MM / Ca de mama. - PTHrp (80%) - No metastásicos / LNH / SCC. - Calcitriol (1-25 diOHvitD) - Linfoma Hodgkin. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005;352(4):373.
  50. 50. Hipercalcemia asociada a cáncer Ca corregido(mg/dL) = Ca medido(mg/dL) + 0.8 (4 - Albúmina(gr/dL) ) Ca (mMol/L) = Ca sangre (mg/dL) * 0.25 Stewart AF. N Engl J Med 2005;352:373-9 Tipos de hipercalcemia asociada a cáncer Tipo Frecuencia Metástasis óseas Agente causal Tipo de tumor Hipercalcemia humoral asociada a malignidad 80% Rara PTHrP Escamocelulares, renales, ovario, endometrio, mama Osteolítica 20% Universal Citokinas Mama, mieloma, linfoma Vitamina D <1% Rara Vitamina D Linfoma Hiperparatiroidismo ectópico <1% Variable PTH Variable
  51. 51. Diagnóstico. Calcio sérico normal: 8.5 – 10.5 mg/dl. Corregir con albúmina Pseudohipercalcemia: deshidratación, mieloma múltiple Calcio ionizado: Más específico. EKG: Prolongación PR, QRS ancho, QT corto Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005;352(4):373. 300 ms
  52. 52. Hipercalcemia asociada a malignidad • Calcio Corregido – Leve: Calcio Corregido 3.1 – 3.2 mMol/L • Anorexia, náuseas, pérdida de peso, debilidad, constipación y alteraciones en el estado mental – Moderada: Calcio Corregido 3.2-3.3 mMol/L • Similar a la hipercalcemia leve con disfunción renal asociada y depósito de calcio en los órganos y tejidos – Severa: Calcio Corregido 3.3-3.4 mMol/L • Náuseas y vómito severos, deshidratación, disfunción renal, estado confusional severo con pérdida de la conciencia – Potencialmente fatal: Calcio corregido > 3.4 mMol/L • Coma, paro cardíaco
  53. 53. Bisphosphonates Risedronate Actonel Aledronate Fosamax Pamidronate Aredia, Aminomux Zoledronate Zometa Clodronate Bonefos, Loron, Ostac EtidronateIbandronate Boniva, Bondronat Potencia preclínica de bisfosfonatos selectos Nombre genérico Marca original Potencia relativa Etidronato Didronel 1 Clodronato Bonefos 10 Pamidronato Aredia 100 Ibandronato Bondronat 10000 Zoledronato Zometa 10000
  54. 54. Major P, et al. J Clin Oncol 2001;19:558-567 Stewart AF. N Engl J Med 2005;352:373-9 Hipercalcemia asociada a cáncer Medir calcio, albúmina, fósforo y creatinina Establecer severidad > 12 mg/dL (3 mMol/L)< 12 mg/dL + síntomas SSN @ 100-150 mL/hora Considerar furosemida Corregir fosfato (si <3 mg/dL) Ácido zoledrónico 4 mg IV – 15 min Prednisolona: puede ser eficaz en linfoma y mieloma Tratar la enfermedad de base
  55. 55. Human antibody infusion reactions The initial infusion of Monoclonal Antibodies is associated with fever, chills, nausea, asthenia and headache in up to half the patients. Hypotension and bronchospasm occur in 1%, or less. Severe AEs like ARDS, pulmonary infiltrates or cardiogenic shock are very rare. Laboratory abnormalities High LFTs, PT and thrombocytopenia. Mechanism Cytokine release syndrome (CRS) with activation of immune effector processes (cells, complemente) mediated by TNFa, IFN gamma, IL6, IL10 Prevention Acetaminofen, defenhydramine and cortisone. Treatment Stop the offending agent Symptomatic treatment (steroid, anti H1 and antipyretic) Reinitiate infusion at half the rate, when reaction subsides. Hypersensitivity reactions to antineoplastic drugs May occur with several antineoplastic agents, most notably, taxanes and platinum compounds. Prevention of infusional reaction is the cornerstone of pacltaxel-induced hypersensitivity reaction. It is accomplished with antiH1, antiH2 and glucocorticosteroids administered BEFORE paclitaxel infusion. Paclitaxel must be infused with a filter. Desensitization should be considered in hypersensitivity type I with high IgE (ie, Carboplatin). Harrison’s, 19th Ed
  56. 56. Hemorrhagic cystitis Caused by Cyclophosphamide or Ifosfamide (both are metabolized to acrolein, an irritant). Late allogeneic BMT hemorrhagic cystitis may be related to polyoma virus BKV or adenovirus type-11. Clinical symptoms Gross hematuria, frequency, disuria, burning, urgency, incontinence, nocturia. Prevention High urine output with IV fluids MESNA coadministration Treatment Urinary irrigation with formalin solution (0.37-0.74%) for 10 mins (N-Acetyl cysteine may also be used). Neutropenic enterocolitis (Typhlitis) Inflammation and necrosis of the cecum and surrounding tissues that may complicate therapy of acute leukemia (or any setting with prolongued neutropenia). Clinical findings RLQ abdominal pain, rebound tenderness, and a tense, distended abdomen in the setting of fever and neutropenia. Watery diarrhea with mucosal sloughing and bacteremia are common. Images CT scan shows instetinal-wall thickening (1+ cm), pneumatosis intestinalis. Treatment Wide-spectrum antibiotics (with C. difficile coverage), NG-tube, bowel rest. Avoid surgery unless an abdominal catastrophe is diagnosed. Harrison’s, 19th Ed
  57. 57. Further reading • Oncologic emergencies: Harrison’s chapter 331 (pages 1787-1798). • Infections in patients with cancer: Harrison’s chapter 104 (pages 490- 492)

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