CES 2016 02 - Oncologic emergencies

57
CES 2016.02: Oncologic emergencies Mauricio Lema Medina MD

Transcript of CES 2016 02 - Oncologic emergencies

Page 1: CES 2016 02 - Oncologic emergencies

CES 2016.02: Oncologic emergenciesMauricio Lema Medina MD

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AcknowledgmentsJosé Julián Acevedo MD

Mateo Mejía MD

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Pressure or obstruction caused by space-occupying lesion

Metabolic or hormonal problems (paraneoplastic syndromes)

Treatment related complications

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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T4

T12T10

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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

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MSCC

http://www.bimjonline.com/Imageoftheweek/Imagewk17(28-05-2012).htm

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MSCC

http://www.bimjonline.com/Imageoftheweek/Imagewk17(28-05-2012).htm

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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.

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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

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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

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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%

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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

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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

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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

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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

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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

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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

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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

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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

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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.

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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)

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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

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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

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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.

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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

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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

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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

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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

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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

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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

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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

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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%

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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

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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

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Catabolismo de purinas

Hipoxantina

Xantina

Ácido úrico

Alantoína

Xantina oxidasa

Xantina oxidasa

Urato oxidasa

Alopurinol

Alopurinol

Rasburicasa

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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

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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

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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

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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.

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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

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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

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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

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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

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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

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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

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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

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Further reading

• Oncologic emergencies: Harrison’s chapter 331 (pages 1787-1798).• Infections in patients with cancer: Harrison’s chapter 104 (pages 490-

492)