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

1. CES 2016.02: Oncologic emergencies
Mauricio Lema Medina MD

2. Acknowledgments
José Julián Acevedo MD
Mateo Mejía MD

3. Pressure or obstruction caused
by space-occupying lesion
Metabolic or hormonal problems
(paraneoplastic syndromes)
Treatment related complications

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. T4
T12
T10

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

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

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Catabolismo de purinas
Hipoxantina
Xantina
Ácido úrico
Alantoína
Xantina oxidasa
Xantina oxidasa
Urato oxidasa
Alopurinol
Alopurinol
Rasburicasa

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Further reading
• Oncologic emergencies: Harrison’s chapter 331 (pages 1787-1798).
• Infections in patients with cancer: Harrison’s chapter 104 (pages 490-
492)