CES 2016 02 - Oncologic emergencies
-
Upload
mauricio-lema -
Category
Health & Medicine
-
view
336 -
download
1
Transcript of CES 2016 02 - Oncologic emergencies
CES 2016.02: Oncologic emergenciesMauricio Lema Medina MD
AcknowledgmentsJosé Julián Acevedo MD
Mateo Mejía MD
Pressure or obstruction caused by space-occupying lesion
Metabolic or hormonal problems (paraneoplastic syndromes)
Treatment related complications
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
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
Superior vena cava syndromeNeck 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 CXRCT scan shows central mediastinal vein blockage + increased collateral vein circulation.Endobronchial or esophageal US guided biopsy may provide the diagnosis.Harrison’s 19th
CXRMass, widening of the mediastinum, pleural effusion
Main riskTracheal 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
Colaterales venosos del sindrome de vena cava superiorEdema subcutáneo de la obstrucción de la vena cava
Casi total oclusión de la vena cava superior por adenopatía mediastinal
Superior vena cava syndrome
SVC obstructionCollateral circulationTumor
Superior vena cava syndrome Treatment
Establish tissue diagnosis if unknown:Bronchoscopy, esophagoscopy, CT guided biopsy, thoracoscopy, etc.
General measuresDiuretics, low-salt diet, head elevation, oxygen.Glucocorticosteroids (only in lymphoma)
Treat the underlying condition(Chemo)-RT for NSCLCRT for metastatic solid tumorsChemotherapy for SCLC, lymphoma and GCTSurgery for benign processesAnticoagulation / Device removal if due to thrombosis or fibrinolytic therapy
SVCS relapses in 10%
SVC stentRecommended in relapsed SVCSSevere SVCSStent complications: heart failure, pulmonary edema, hematoma, SVC perforation, migration, fracture, pulmonary embolismHarrison’s 19th
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
Malignant spinal cord compression (MSCC)Occurs in 5-10% of patients with cancerMSCC is the presenting feature in 10% of malignanciesLung cancer is the most common cause of MSCC
CausesLung, breast, prostate, multiple myeloma are the big ones. Lymphomas, melanomas, genitourinary tumors and RCC, neoplastic leptomeningitis cause MSCC too.
Non-oncologic differential diagnosisOsteoporotic vertebral collapse, disk disease, pyogenic abscess, vertebral tuberculosis, radiation myelopathy, benign tumors, epidural hematoma, and spinal lipomatosis.
SitesThoracic spine: 70%, Lumbosacral spine: 20%, Cervical spine: 10%.
MechanismVertebral 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
Malignant spinal cord compression (MSCC)Clinical presentationBack pain and tendernessIt is exacerbated by movement, cough or sneezing.Worsens in the supine position.Lhermitte’s sign may herald MSCCRadiculopathic pain may also be presentLoss of bladder or bowel control tend to occur late in the course of MSCC
Physical examinationPain 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 syndromeLow 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
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
T4
T12T10
Back pain
Neurologic exam
Suspicious of myelopathy
HD Dexamethasone
MRI of spine
Pain crescendo patternLhermitte’s signPain aggravated with cough, valsalva or recumbencyAbnormal spine x-ray
Normal
Spine x-ray
Symptomatic therapy Epidural metastases
Bone metastases, no epidural metastasesNormal
Surgery + RT or RT RTHarrison’s, 19th Ed
6 mg IV q6h
Whole spine, preferred
MSCC
http://www.bimjonline.com/Imageoftheweek/Imagewk17(28-05-2012).htm
MSCC
http://www.bimjonline.com/Imageoftheweek/Imagewk17(28-05-2012).htm
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.
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
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 23:2028-2037White BD et al. NICE Guidance. BMJ 2008; 337:a2538Harrison’s, 19th Ed
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%
Pericardial effusion/tamponadeFound in autopsy in 5-10% of cancer patients.
CausesLung cancer, breast cancer, leukemias and lymphomas
Non-tumoral differential diagnosisIrradiation, drug-induced pericarditis, hypothyroidism, idiopathic pericarditis, infection, autoimmun disease
Radiation pericarditisAcute inflammatory, self-limiting, within month of irradiation. Chronic effussive pericarditis up to 20 years post radiotherapy, with pericardial thickening.
SymptomsMost patients are asymptomatic.Dyspnea, cough, chest pain, orthopnea and weakness.
SignsPleural 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
Pericardial effusion/tamponadeTreatment optionsPericardiocentesis (with or withou sclerosing agents)Percardial windowComplete pericardial strippingCardiac irradiation orChemotherapy
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
Intestinal obstructionTreatment optionsPalliative (non-surgical) careSurgery (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 tubeCT abdomenSurgical consultationElectrolyte, fluid and drug evaluation
Surgery (Open) PalliationLaparoscopy GI stent
Aggressive nutrition Aggressive symptom control
Malignant biliary obstructionCausesCancer 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 causesFound in 25%: narcotics, vinca alcaloids, adhesions.
Clinical findingsJaundice, light colored stool, dark urine, priritus, and weight loss (due to malabsorption). Pain and infections are UNCOMMON.
Imaging modalitiesUS, CT scan, ERCP, percutaneous transhepatic cholangiography, MRI
TreatmentStentSurgical bypassRT (+/-) chemotherapy.
In the absence of pruritus, biliary obstruction may be a largely asymptomatic cause of death.
Harrison’s, 19th Ed
Increased intracraneial pressure25% of cancer patients die with CNS metastases.Brain metastases may be the first evidence of cancer.
CausesLung, breast, melanoma.
Non-oncologic causesTretinoin pseutumor cerebri with increased intracranial pressure.
Clinical findingsHeadache, 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 modalitiesCranial contrast-enhanced CT. If negative, Gadolinium-enhanced MRI.
TreatmentDexamethasone.SurgeryWhole brain radiotherapyGamma knifeShunt placement (if hydrocephaly an issue).
Harrison’s, 19th Ed
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 q6hNeurosurgical consultationRT consultation
*Surgery preferred if cancer diagnosis not histologically proven
WBRT: Whole brain radiotherapy
Surgery PalliationStereotactic radiosurgery Whole-brain irradiation
SeizuresApproximately 10% of CNS metastases patients develop seizures.
CausesTumor, 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)
SiteOccipital, 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.
TreatmentPhenytoin 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
HemoptysisUp to 20% of lung cancer patients have hemoptysis
CausesLung cancer, carcinoid tumors, breast cancer, colon cancer, kidney cancer and melanoma.
Massive hemoptysis: more than 200 mL/24hAll hemoptysis should be considered life-threatening.
TreatmentICU 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 patientSurgery 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
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.
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)
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 autólogoLinfomaMieloma múltipleLeucemia linfoide crónicaTerapia con análogos de purinaNeutropenia esperada de 7 a 10 días
Bacteriano: considerar fluoroquinolonas.Micótica: Considerar fluconazole durante la neutropenia y con la mucositis anticipadaViral: Durante la neutropenia y al menos 30 días después de trasplanta autólogo
Alta / ALTA Trasplante alogénicoInducción y consolidación de leucemia agudaTerapia con AlemtuzumabGVHD tratada con altas dosis de esteroidesDuración anticipada de la neutropenia >10 días
Bacteriana: Considere fluorquinolona.Micótica: considere fluconazol, amfotericina, voriconazol, posaconazolViral: Durante la neutropenia y al menos 30 días después de trasplanta autólogo
NCCN® Practice Guidelines in Oncology – v.2.2009, www.nccn.org
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
Score de Riesgo para Neutropenia Febril - MASCC
Síntomas leves (o no) de enfermedad 5Síntomas SEVEROS asociados a la enfermedad 3 No hipotensión 5 No EPOC 4 Tumor sólido / no infección micótica 4No 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.
Neutropenia febril
Infección identificada Sin Factor de Riesgo Con factor de riesgo
InestableEstable
Imipenem + VancomicinaCefepime*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 riesgoPara GNR: Hospitalización reciente; betalactámicos en los últimos 3 meses; historia de GNR
Para MRSA: Catéter; betalactámicos en los últimos 3 meses; historia de MRSAPara Pseudomona: Intubación >72 horas; úlceras crónicas; pneumopatía crónicamente infectada
Mi enfoque
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 periorbitarioAmfotericina si posible infección micótica
Dolor abdominal CT / Amilasa / AST / Bilirrubina Metronidazol (C. difficile)Terapia para anaerobios
Dolor perirrectal Inspección / CT Cubrimiento para anaerobiosCubrimiento para enterococoCuidado 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 MRSAConsiderar terapia antimicótica si hay alto riesgoConsiderar 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 + ampicilinaEncefalitis: Altas dosis de aciclovir
Neutropenia febril… Adicionar G-CSF
NCCN® Practice Guidelines in Oncology – v.2.2009, www.nccn.org
Sólo en las siguientes situaciones clínicas (categoría 2B):
PneumoníaInfección micótica invasiva
Infección progresiva
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
Neutropenia febril
NCCN® Practice Guidelines in Oncology – v.2.2009, www.nccn.org
Antibióticos
Evaluar respuesta 3-5 díasMejoría de la curva térmica
Signos y síntomas de infección estables o mejorandoPaciente 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
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
Tumor lysis syndrome (TLS)Hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia caused by the destruction of a large number of rapidly proliferating neoplastic cells.
CausesBurkitt’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
obstructionARF
High serum
P
Low serum
Ca
NM/Cardiac irritabilty/T
etany
High serum
K
Ventricular arrhythmias/sudden death
Kidney calcium phosphate deposition
Lactic acidosisAcidosisDehydration
Urinary uric acid crystalsUrinary uric acid higher than urinary creatinine
Sindrome de lisis tumoral
Coiffier B. J Clin Oncol 2008; 26:2767-2778
Cánceres asociados a SLT en adultosLinfoma 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%
Sindrome de lisis tumoral
Coiffier B. J Clin Oncol 2008; 26:2767-2778
Factores de riesgo para SLTTipo de tumor Linfoma de Burkitt
Linfoma linfoblásticoLinfoma difuso de células grandesLeucemia linfoide agudaTumores 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-existenteOliguria
Ácido úrico basal >7.5 mg/dL
Terapia eficaz citorreductiva Variable
Sindrome de lisis tumoral
Coiffier B. J Clin Oncol 2008; 26:2767-2778
Estratificación de riesgo de SLTTipo de tumor Alto riesgo Riesgo Intermedio Bajo RiesgoLinfoma 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/mm3Monoblástica
10-50k/mm3 <10k/mm3
Leucemia linfoide crónica
10-100k/mm3Fludarabina
Demás
Catabolismo de purinas
Hipoxantina
Xantina
Ácido úrico
Alantoína
Xantina oxidasa
Xantina oxidasa
Urato oxidasa
Alopurinol
Alopurinol
Rasburicasa
Sindrome de lisis tumoral
Coiffier B. J Clin Oncol 2008; 26:2767-2778
Definición de laboartorio de SLT – Cairo-BishopVariable 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
Definición y gradación clínica del SLT – Criterios de Cairo-BishopGrado
Complicación 1 2 3 4 5Creatinina <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 anticonvulsivante; 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
Harrison’s, 19th Ed
TLS
If high serum uric acid (8) and high creatinine (1.6)
IV hydration 3000 mL/m2/dayUrine pH above 7 with bicarbonate
Allopurinol 300 mg/m2/dayMonitor serum chemistry
Correct treatable renal conditionsRasburicase 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 oxidaseMay cause hypersensitivity: bronchospasm, hypoxemia, hypotensionDo not use in G6PD deficiency
Also discontinue bicarbonate if high Phosphate
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.
Hipercalcemia asociada a cáncerCa 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 cáncerTipo Frecuencia Metástasis
óseasAgente 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
Diagnóstico.
Calcio sérico normal: 8.5 – 10.5 mg/dl.Corregir con albúminaPseudohipercalcemia: deshidratación, mieloma múltipleCalcio 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
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
Bisphosphonates
RisedronateActonel
AledronateFosamax
PamidronateAredia, Aminomux
ZoledronateZometa
ClodronateBonefos, Loron, Ostac
EtidronateIbandronateBoniva, Bondronat
Potencia preclínica de bisfosfonatos selectosNombre genérico Marca original Potencia relativaEtidronato Didronel 1Clodronato Bonefos 10Pamidronato Aredia 100Ibandronato Bondronat 10000Zoledronato Zometa 10000
Major P, et al. J Clin Oncol 2001;19:558-567Stewart AF. N Engl J Med 2005;352:373-9
Hipercalcemia asociada a cáncerMedir 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 minPrednisolona: puede ser eficaz en linfoma y mieloma
Tratar la enfermedad de base
Human antibody infusion reactionsThe 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 abnormalitiesHigh LFTs, PT and thrombocytopenia.
MechanismCytokine release syndrome (CRS) with activation of immune effector processes (cells, complemente) mediated by TNFa, IFN gamma, IL6, IL10
PreventionAcetaminofen, defenhydramine and cortisone.
TreatmentStop the offending agentSymptomatic treatment (steroid, anti H1 and antipyretic)Reinitiate infusion at half the rate, when reaction subsides.
Hypersensitivity reactions to antineoplastic drugsMay 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
Hemorrhagic cystitisCaused 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 symptomsGross hematuria, frequency, disuria, burning, urgency, incontinence, nocturia.
PreventionHigh urine output with IV fluidsMESNA coadministration
TreatmentUrinary 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 findingsRLQ 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.
ImagesCT scan shows instetinal-wall thickening (1+ cm), pneumatosis intestinalis.
TreatmentWide-spectrum antibiotics (with C. difficile coverage), NG-tube, bowel rest. Avoid surgery unless an abdominal catastrophe is diagnosed.
Harrison’s, 19th Ed
Further reading
• Oncologic emergencies: Harrison’s chapter 331 (pages 1787-1798).• Infections in patients with cancer: Harrison’s chapter 104 (pages 490-
492)