Oncologic Emergencies

Authors

Judith Toski Welsh, MD, Emergency Services Institute, Cleveland Clinic, Cleveland, OH

Purva Grover, MD, FACEP, Emergency Services Institute, Cleveland Clinic, Cleveland, OH

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Pediatric Oncologic Emergencies

After trauma, cancer is the second most common cause of death in children older than 3 months. In 2014, about 16,000 new cases of cancer were diagnosed in children and adolescents.[1] In general, pediatric cancer has a favorable prognosis, but complications can occur from either the disease or the treatment regimen.

Disease Process	Location/Exam Findings	Peak Age of Incidence	High Risk Populations
Leukemia acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML)	Immature WBC proliferation in bone marrow. Most common pediatric cancer diagnosis	ALL: 3-5 years AML: constant throughout childhood, poorer prognosis than ALL	Trisomy 21
Non-Hodgkin Lymphoma	Group of malignancies of lymphatic tissue; present as adenopathy or masses, with symptoms correlating to site of tumor proliferation	No peak age; increasing numbers with age	HIV, HTLV-1, Epstein-Barr infectious mononucleosis Hepatitis B, C infection Organ transplant patients on immune suppression Wiskott-Aldrich Ataxia-Telangectasia
Hodgkin Disease	Lymph node malignancy, related to the Reed-Sternberg cell. Painless lymphadenopathy in neck	Peak incidence in adolescents and young adults	Epstein-Barr Virus HIV infection
Wilms Tumor (nephroblastoma)	Non-tender abdominal mass	Peak age 2-3 years, with almost all diagnosed by age 5	Trisomy 18
Neuroblastoma	Arises from neural crest cells, may present as an abdominal mass or less commonly as cervical or thoracic tumors	Almost all cases diagnosed before age 5	ALK gene mutation or overexpression (anaplastic lymphoma receptor tyrosine kinase)
CNS Tumors	Second most common pediatric cancer diagnosis	Supratentorial tumors: < 2 years Infratentorial tumors: > 2 years	Ataxia-telangectasia Trisomy 13 Tuberous sclerosis
Retinoblastoma	Most common intraocular tumor of childhood	Most cases diagnosed by age 4	Trisomy 21
Sarcomas	Musculoskeletal tissue – can be painful or painless depending on histology and location	Ewing Sarcoma: median age 13 Osteosarcoma: adolescents	Rhabdomyosarcoma in tuberous sclerosis complex

Evaluating Possible Malignancy in Children and Adolescents

Early diagnosis of childhood cancer is challenging, since the earliest symptoms are non-specific and often similar to those of common, benign ailments. Symptoms are related to tumor infiltration of organs by abnormal cells. Brain tumors can present as headaches that disturb sleep, nausea, or visual changes. Tumors in the abdomen can present as constipation. Unusual bruising patterns can occur as a consequence of bone marrow infiltration. [2]

High-Risk History, Signs, and Symptoms of Malignancy

Brain tumor	Headache that awakens patient from sleep Focal neurologic deficit or abnormality: ie head tilt Severe, incapacitating headaches Recurrent early morning headaches Cranial nerve palsy or papilledema on physical exam Increasing head circumference History of ALL with CNS irradiation Neurofibromatosis Loss of milestones
Lymphoma	Lymphadenopathy with constitutional symptoms Fixed lymph nodes Asymptomatic lymph node > 2.5 cm Intussusception in child older than 2 years Supraclavicular lymphadenopathy[3]
Ewing Sarcoma and Osteosarcoma	Bone pain related to strain Pain at night Refusal to walk Palpable mass[4]
Wilms Tumor and Neuroblastoma	Palpable abdominal mass
Leukemia	Excessive bleeding of relatively sudden onset Noticeable pallor Persistent unexplained fatigue

Initial evaluation of a patient with a suspected cancer should begin with a careful history and physical exam. Pain without injury, unexplained weight loss, headache present upon awakening, balance or gait problems, and prolonged fevers are among the most important symptoms suggestive of malignancy in children. On physical exam, findings of focal weakness, ataxia, palpable abdominal masses, diffuse lymphadenopathy (especially supraclavicular location), unexplained bruising, or testicular enlargement are all very concerning for possible tumor and mandate further evaluation.

Basic laboratory workup of possible malignancy includes a complete blood count (CBC) to evaluate for evidence of increased or decreased white blood cell count, platelet count, or hemoglobin levels. Serum electrolytes, including calcium, magnesium and phosphorus, liver function tests, serum creatinine, lactate dehydrogenase, and uric acid levels may also be helpful. Depending on the suspected diagnosis, plain radiography, CT, or ultrasound may be useful as initial imaging to determine the location and size of tumor. In the presence of bruising or petechiae, coagulation studies are helpful.

Workup of Suspected Malignancy

Complete blood count Electrolytes Liver function tests Renal function tests Lactate dehydrogenase Uric acid Coagulation studies CT or ultrasound

Leukemia

Acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML) are among the most common cancer diagnoses in children. ALL originates in the B- and T- lymphoblasts in the bone marrow. AML starts in the early forms of myeloid cells, those which become non-lymphocytic white blood cells, red blood cells, or platelets. ALL accounts for 1 in 4 diagnoses of cancer in children younger than 15 years of age, and sharply increases in incidence in children between the ages of 2 and 4 years. Cases of AML are more spread out across the childhood years, but this type of leukemia is slightly more common during the first 2 years of life and during the teenage years

Genetic abnormalities and environmental exposures to ionizing radiation are risk factors for developing ALL. Children with Trisomy 21 are also at a 20-fold increased risk of developing acute leukemia. ALL has an excellent overall prognosis, with 95% of children attaining remission and over 80% of children expected to be event-free survivors. The remission and survival rates are lower for AML than ALL, with a 5 year survival rate (in patients diagnosed between 2003 and 2009) of 64%.[5]

Initial symptoms may be nonspecific and consist of fevers and malaise. Later, unusual bleeding and bruising may be present. Enlargement of the liver and spleen may be felt on exam, and boys should be examined for painless testicular masses. CNS involvement in the form of nuchal rigidity, vomiting, and headaches can be present as well as palpable neck masses. In children with B-precursor ALL, bone pain and limping may be the only complaint 5% of the time[6].

Symptoms and Signs of Leukemia in Children

• Fever with or without source
• Anorexia
• Unexplained bleeding or bruising
• Hepatomegaly
• Splenomegaly
• Atraumatic limp or bone pain
• Headache, stiff neck, vomiting
• Palpable neck masses
• Painless testicular masses
• Respiratory symptoms, stridor
• Skin nodules or gingival involvement in children with AML

The differential diagnosis of acute leukemia in children includes:

• Idiopathic thrombocytopenia purpura (ITP)
• Osteomyelitis
• Mononucleosis and Epstein-Barr infection
• Lymphoma
• Aplastic anemia

Diagnostic Evaluation

When a new diagnosis of leukemia is suspected, early involvement of a pediatric oncologist can be helpful to guide further workup and to ensure appropriate disposition and treatment. Bone marrow examination and cytogenetic testing are the gold standard for establishing a diagnosis. CT scanning of the brain should be performed in children with severe headaches, focal neurologic deficit, or suspected CNS infiltration or mass. A chest radiograph may reveal a mediastinal mass, especially in children with respiratory distress or stridor.

Additional recommended workup includes:

• CBC with differential
• Electrolytes
• PT, PTT
• Uric acid
• Renal and liver function testing
• Viral titers: Epstein-Barr, Varicella zoster virus, HIV, Cytomegalovirus, Hepatitis B; patients undergoing treatment for leukemia may become infected even if previously immunized[7]

Packed red blood cell transfusion is frequently required in children with leukemia to increase the oxygen carrying capacity of the blood. A goal hemoglobin level of 7-8 mg/dL in the absence of other complicating conditions is usually sufficient. The presence of significant cardiovascular disease, need for mechanical ventilation, and plans for major surgery all require transfusion to a higher hemoglobin concentration.[8] Platelet transfusion may be required even in stable children if their platelet counts are < 10-20,000/mm³. Bone marrow infiltration and chemotherapy are the most common causes of anemia and thrombocytopenia requiring transfusion in leukemia patients.

Workup of acute anemia should include:

• Complete blood count
• Reticulocyte count and MCV
• Stool guaiac
• Evaluation for hemolysis, including Coombs panel, DIC panel, haptoglobin
• Nutritional studies, including ferritin, B12, folate
• Renal studies[9]

Children undergoing treatment for leukemia should receive irradiated blood components. RBC therapy should be initiated at 10-15 mL/kg of actual body weight infused over 3-4 hours. Each 10 mL/kg PRBC will raise the hemoglobin approximately 2 g/dL. Children with heart failure should be transfused more slowly, given diuretics before or during the procedure, and monitored closely in an intensive care setting to prevent fluid overload.[10]

Treatment

Pediatric leukemia is treated primarily with chemotherapy in three phases: induction, consolidation, and maintenance. The goal of induction is to bring about remission of disease, which occurs in 95% of patients within 1 month. Consolidation is then begun to eliminate residual disease, and lasts 1-2 months. The final phase is maintenance chemotherapy, which can begin if the disease remains in remission for the first two phases of treatment. The total length of chemotherapy is generally 2-3 years, but may be prolonged if relapses or if the leukemia fails to resolve. Stem cell transplant may be required for intractable or recurrent disease.[11]

ACADEMIC RESOURCES

Pediatric ALL

http://asheducationbook.hematologylibrary.org/content/2003/1/102.long

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Complications

Tumor Lysis Syndrome

Chemotherapy may cause massive tumor cell death and the release of large amounts of potassium, phosphates, and uric acid. This process is referred to as tumor lysis syndrome, and it occurs most commonly during the induction phase of lymphoma and leukemia chemotherapeutic treatment. Kidney injury or sudden death from hyperkalemia may develop.[12] Adequate hydration and administration of hypouricemic agents, such as rasburicase, may prevent tumor lysis syndrome. Urine alkalinization is no longer routinely recommended due to the efficacy of rasburicase in breaking down uric acid. The goal of hydration is to maintain adequate renal function and to increase excretion of uric acid and to prevent uric acid and calcium phosphate deposition in the renal tubules. The risk associated with aggressive IV hydration is fluid overload and edema. Children at risk of tumor lysis syndrome should receive 2-3 L/m³ or if < 10 kg, 200 mL/kg/day of isotonic fluid, with a goal of 80-100 mL/m²/hour (or 2 mL/kg/hour for children, 4-6 mL/kg/hour if < 10 kg) urine output. Intensive care monitoring is usually required. Five percent dextrose in one-quarter normal saline is the usual fluid of choice, but isotonic saline is recommended in children with hyponatremia or volume depletion.[13]

Lab Abnormalities in Tumor Lysis Syndrome

Elevated uric acid Hyperkalemia Hyperphosphatemia Hypocalcemia Abnormal renal function

Non-Hodgkin Lymphoma/Hodgkin Disease

Non-Hodgkin lymphoma (NHL) accounts for 7% of all childhood and adolescent cancers. NHL is very rare in infants, and unlike Hodgkin lymphoma, which has a bimodal distribution, NHL rates increase steadily with age. Clinical presentations of NHL are variable and depend on the histology of the tumor and site of disease. Generally, children with NHL appear ill on presentation, with an acute (< 1 month) onset of symptoms. Childhood NHL proliferates quickly and is often found outside of lymph node tissue at the time of presentation.

Symptoms and Signs of Non-Hodgkin Lymphoma

Firm, fixed cervical or supraclavicular lymphadenopathy Stridor or respiratory distress from mediastinal mass Neck vein distention in superior vena cava syndrome Pleural effusion resulting in rales or dyspnea Abdominal pain or palpable mass Atraumatic limb pain or limping CNS infiltration resulting in stiff neck, headache, altered mental status

Hodgkin disease is a cancer of the Reed-Sternberg cell of the lymph nodes. It accounts for 5% of all childhood malignancies, and reaches peak incidence in adolescents and young adults. Most patients present with painless, enlarged lymph nodes, frequently in the supraclavicular and cervical areas. About a third of patients will present also with “B” symptoms of fever, night sweats, and weight loss, and mediastinal masses are a common finding. The differential diagnosis of Hodgkin disease is similar to that of NHL.

The differential diagnosis of NHL/Hodgkin disease is broad and includes other cancers as well as common childhood diseases, including:

• Acute leukemia
• Intussusception – increased probability of cancer if occurring in children over age 2
• Appendicitis
• Lymphadenitis
• Wilms tumor
• Mononucleosis
• Rhabdomyosarcoma

Superior Vena Cava Syndrome

Chest masses in children can cause external compression of the superior vena cava and decreased venous return to the right atrium, referred to as superior vena cava syndrome. Thrombosis from indwelling catheters can also cause similar symptoms. Superior vena cava syndrome can manifest as:

• Swelling and vascular congestion of the head, neck, and upper extremities
• Cough and shortness of breath
• Trouble swallowing
• Headache or mental status changes from increased intracranial pressure

Diagnostic Evaluation

Definitive diagnosis of lymphoma is by excisional biopsy and tissue examination. Chest radiography should be performed in any child presenting with respiratory distress. Most mediastinal masses will be seen with plain films. CT of the neck, chest, abdomen, and pelvis is usually performed to evaluate for extranodal disease. A PET scan may also be performed due to its higher sensitivity than bone marrow biopsy to determine presence of bone marrow involvement.[14]

Emergency Treatment Considerations

In children, the most common etiology of pleural or pericardial effusions is a rapidly dividing cancer (like lymphoma or leukemia) associated with a mediastinal mass. Large pleural effusions can cause respiratory distress, while pericardial effusions can cause cardiac tamponade. Tamponade is the result of compression of the heart chambers by fluid and resulting in reduction in cardiac output. Cardiomegaly may be present on chest radiography but echocardiography is more sensitive for smaller effusions.

The acutely ill child with respiratory symptoms from lymphoma should be kept in an upright position and provided with supplemental oxygen; urgent transfer to an ICU setting at a pediatric oncology center is appropriate. Children with stridor from a mediastinal mass are at risk of respiratory failure. Strong consideration should be given to airway protection prior to transport of children with significant respiratory symptoms related to tumor infiltration.[15]

Wilms Tumor (Nephroblastoma)

Wilms tumor arises from embryonal renal cells and is the most common pediatric intra-abdominal tumor. The median age of diagnosis is 3.5 years of age, and it accounts for 6-7% of all pediatric cancers. A predisposition to Wilms tumor is seen in children with aniridia (congenital absence of the iris) due to a genetic abnormality. The differential diagnosis includes other renal cancers (most of which are very rare in young children) and other diseases presenting with an abdominal mass.

Physical exam demonstrates an asymptomatic abdominal mass in 80% of children at presentation. Hematuria, abdominal pain, and symptoms from metastatic disease are rare. When hematuria does occur, it is usually microscopic. CT or ultrasound imaging demonstrates a large encapsulated mass arising from the kidney. CT scanning may show a large tumor with a “claw sign” of normal tissue surrounding the tumor. Plain films are not diagnostic but may show a soft-tissue mass and displaced bowel loops.[16] Wilms tumor is bilateral in 5-10% of cases. Treatment is primarily surgical. Nephrectomy is usually followed by chemotherapy, with or without postoperative radiation.

Wilms tumor follows the “Rule of 10s”:

• 10% unfavorable histology
• 10% bilateral
• 10% with vascular invasion
• 10% calcifications on CT
• 10% pulmonary metastases on presentation[17]

Neuroblastoma

Neuroblastoma is the most common cancer in infancy, and often presents with nonspecific symptoms of abdominal pain, vomiting, fatigue, or bone pain. The median age at diagnosis is 19 months, and most cases are diagnosed before age 5.[18] Neuroblastoma is a neuroendocrine tumor, meaning that it arises from immature nerve cells. It is most commonly found in and around the adrenal glands and along the paraspinal sympathetic nerves. It can be found in the neck, chest, abdomen, and pelvis. Most cases are sporadic, but neuroblastoma is found with increased prevalence in children with neurofibromatosis type I and Beckwith-Wiedemann Syndrome.

An abdominal mass is the most common finding on exam, and may be painful due to mass effect and abdominal distention. Neuroblastoma can spread along the sympathetic nerve roots through the spinal foramina, compressing the spinal cord and causing paralysis. Horner syndrome can also be the consequence of sympathetic nerve compression in the neck from tumor burden, and presents with miosis, ptosis, and anhydrosis.

Paraneoplastic processes occur more commonly in adults with cancer, but are also described as rare findings in neuroblastoma. Paraneoplastic phenomena occurs when hormones or cytokines are excreted by the tumor or as a result of an immune response to the tumor. Intractable diarrhea can be the result of a paraneoplastic syndrome in children with neuroblastoma. One of the more dramatic findings of neuroblastoma is opsoclonus-myoclonus, which occurs in 2% of patients. It is characterized by random eye movements and jerking.

ED evaluation of a suspected neuroblastoma should include CT scanning of chest, abdomen, and pelvis to evaluate the area of interest and to determine presence of metastatic disease. The brain and spine are best evaluated by contrast-enhanced MRI.[19] Catecholamines are present in urinalysis in over 90% of patients. Plain films are not usually helpful for diagnosis.

Central Nervous System Tumors

Brain Tumor

Ninety percent of central nervous system (CNS) tumors are in the brain, with the rest present in the spinal cord and cranial nerves. Primary CNS tumors are more common in children than in adults, in whom metastatic lesions are more common.[20] Exposure to ionizing radiation and genetic syndromes such as neurofibromatosis, tuberous sclerosis complex, and von Hippel-Landau syndrome are associated with CNS neoplasms.

Symptoms are variable depending on the age of the patient and location of the lesion. The most common complaint in children older than 4 years of age is headache, but this is present only in about a third of patients. Most children complaining of headaches do not have brain tumors. Other symptoms include: nausea and vomiting, abnormal gait and coordination, or seizures. Children younger than 4 years of age most frequently present with macrocephaly, nausea and vomiting, lethargy, and abnormal gait and coordination.

CT imaging of the brain is a quick, relatively easy option for initial evaluation of a child with a suspected brain tumor, but MRI is more sensitive and provides more detail of the posterior fossa, where about half of childhood brain masses are located.

ED treatment

Intracranial complications can occur as a result of primary tumor or treatment and include hemorrhagic or thrombotic stroke or abscess. Mass effect of a tumor can cause increased intracranial pressure or cerebral hemorrhage. Certain chemotherapeutic agents can cause neurotoxicity resulting in altered mental status or coma. CT scanning rapidly assesses for these complications, but can miss problems in the posterior fossa where many childhood cancers arise. Oncology and neurosurgical staff should be made aware of the patient early in their ED course.

Symptoms of Increased Intracranial Pressure
Infants	Drowsiness Separated sutures of skull Bulging fontanelle Vomiting
Older Children	Change in behavior Lethargy Headache Vomiting Seizures Focal weakness Cranial nerve abnormalities Diplopia

ED treatment of an acutely decompensated child with a brain tumor should initially focus on stabilization of airway, breathing and circulation, and aborting any seizure activity. Corticosteroid therapy can be administered to patients with increased intracranial pressure related to edema around a tumor. Long-term administration may cause psychological effects, weight gain, cataracts, an increased risk of cardiovascular disease, and adrenal suppression.[21] Dexamethasone (0.25-0.5 mg/kg/dose every 6 hours to max of 16 mg) is the treatment of choice.

ACADEMIC RESOURCES

Pediatric brain tumors: current treatment strategies and future therapeutic approaches

http://www.ncbi.nlm.nih.gov/pubmed/19560746

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Syndrome of Inappropriate Antidiuretic Hormone Secretion

The syndrome of inappropriate antidiuretic hormone secretion is caused by some chemotherapeutic agents or injury to the brain from surgery or radiation and results in results in hyponatremia. The initial symptoms are nausea and weakness, which can progress to confusion and altered mental status when the sodium level drops below 120 mg/dL. Seizures and coma can be the result of unchecked hyponatremia. Fluid restriction is the mainstay of treatment.

Spinal Cord Compression

Spinal cord compression in children is most commonly the result of spread of tumor from outside the spinal cord; neuroblastoma and soft tissue sarcomas are the most common causes. Back pain is the most common complaint in these children. Any child with cancer who has new-onset or worsening back pain should be considered to have cord compression until proven otherwise. Plain films are not sensitive enough to rule out the diagnosis, but may occasionally show findings and are a reasonable first step. MRI is more sensitive and specific, but may be more challenging to obtain in a pediatric patient. Steroids may be used to reduce neurologic damage, but local radiation may be a more appropriate treatment. Early consultation with pediatric oncology should be obtained to appropriately treat and disposition these patients.

Retinoblastoma

Retinoblastoma is the most common malignancy of the eye in childhood. It presents frequently (but not always) with leukocoria, i.e., a white pupillary reflex. Strabismus is the second most common sign. The disease is most frequently unilateral, but can be bilateral in about 25% of patients. Bilateral involvement is always related to a genetic abnormality, and is usually diagnosed earlier than in children with unilateral involvement, whose disease is more likely to be sporadic. The differential diagnosis of retinoblastoma includes other diseases that cause leukocoria, including retinopathy of prematurity, cataract, uveitis, and vitreous hemorrhage.

Diagnostic Evaluation

Urgent consultation with ophthalmology should be obtained for a child with suspected retinoblastoma. Ocular ultrasound or MRI may be performed to confirm the diagnosis, determine tumor size, and to delineate intracranial extension. Metastatic disease is rarely present at the time of initial presentation, so extensive metastatic screening tests are low-yield unless there is obvious evidence of tumor outside the eye, constitutional symptoms, or evidence of increased intracranial pressure.[22]

Treatment

Treatment of retinoblastoma is commonly surgical. Vision-sparing treatment is possible for smaller tumors, while enucleation is performed for larger tumors, for recurrent disease following vision-sparing surgery, or if complications such as total retinal detachment, total hyphema, or complete vitreous opacity are present. Enucleation results in a cure rate of 95%. Chemotherapy is rarely curative but may be considered in children with bilateral involvement. [23]

Sarcomas

Sarcomas are tumors that arise from embryonal mesenchymal cells and account for 12% of pediatric cancers. Rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma are the more common forms in children and adolescents. Rhabdomyosarcoma is the most common pediatric tumor of soft-tissue origin and occurs most commonly in children younger than six years old. Ewing Sarcoma is primarily a disease of long and flat bones, and presents with bony pain that intensifies with exercise and is worse overnight. Radiographs may show an “onion-peel” appearance to bone. Pathologic fractures are diagnosed at presentation about 10-15% of the time.[24] Osteosarcoma is the most common sarcoma of bone in pediatric patients. The peak incidence of osteosarcoma is during the adolescent growth spurt. Most patients with osteosarcoma complain of waxing and waning pain over months, and constitutional symptoms are rare. Palpable masses overlying the tumor are common. The distal femur and proximal tibia are most commonly involved.

Complications Associated with Cancer Treatment

Indwelling catheters. Implanted vascular access devices are a necessity for most kinds of pediatric chemotherapy and may be left in place for years in a child undergoing cancer treatment.[25]

Complications of placement and long-term use are:

• Thrombosis: intraluminal occlusion, right atrial thrombosis, superior vena cava syndrome, pulmonary embolism
• Subclavian vein stenosis: often related to infection
• Sepsis: especially in immune-suppressed patient
• Primary infection of catheter site
• Mechanical failure of the device
• Hematoma: generally with placement, high risk of infection if occurs
• Skin necrosis due to vesicant extravasation[26]

Thrombosis-related disease is relatively common in children with implanted vascular access devices, and children may be at risk for years even after treatment has ended and their catheter has been removed. Younger age at diagnosis, longer duration of treatment, and left-sided placement all increase risk of thrombosis.[27]

Gastrointestinal Bleeding

GI bleeding in pediatric cancer patients is most commonly seen in rapidly growing lymphoma and is the result of perforation of a mass into a vessel. It can be exacerbated by coagulation abnormalities from the cancer or its treatment. The use of steroids in cancer treatment can also cause GI bleeding due to ulcer formation.

Hypercalcemia

Hypercalcemia in children with cancer is usually the result of bony destruction by marrow infiltration or metastases of solid tumors with release of calcium into the central circulation. Levels > 12 mg/dL cause the following symptoms:

• Muscular weakness and pain
• Abdominal pain, vomiting, constipation
• Depression or altered mental status
• Polyuria
• Biliary or renal stones

Infectious Emergencies

Fever is very common in neutropenic patients undergoing chemotherapy, and neutropenia and immunosuppression result in an increased risk of infection in children with cancer. Common pediatric pathogens, opportunistic organisms, normal flora, and dormant viral infections may all cause fevers. Febrile neutropenia, defined as a fever > 38^o C associated with an absolute neutrophil count > 500 cells/microL, should be addressed aggressively. Cultures of blood, urine, stool, CSF should be obtained, and early broad-spectrum antibiotic treatment should be initiated with guidance from the patient’s oncologist. If an indwelling catheter is present, a blood culture should be obtained through the line.[28]

Typhlitis (neutropenic enterocolitis) is the result of bacterial and fungal invasion of the bowel wall during periods of neutropenia. In children with cancer, it is observed with induction therapy for ALL and AML, and during aggressive chemotherapy for solid tumors. Typhlitis should be suspected in any neutropenic patient (ANC < 500 cells/microL) who presents with abdominal pain and fever. CT is the preferred diagnostic test; barium enema should be avoided due to risk of perforation. Broad-spectrum antibiotics and bowel rest are first-line treatment options.

Pain Management for Oncology Patients

Effective management of pain in children with cancer starts with assessment. Different assessment methods are implemented in pediatric EDs depending on whether a child is capable of self-report. Infants and children younger than 3 years of age generally cannot self-report pain, but there are observational scales geared toward this age range that are validated for use in the ED such as the FLACC (Face, Legs, Activity, Cry, Consolability) Ssale.[29]

Both pharmacologic and non-pharmacologic interventions are appropriate for pediatric cancer patients and should be tailored to the child’s specific needs and the situation. The World Health Organization recommends a two-step approach to pharmacologic management of pain, scaled to a child’s needs. Opiate analgesia, such as morphine or oxycodone, is suggested for treatment of moderate to severe pain. For cancer pain, regular dosing intervals are advised with a second medication for breakthrough pain as needed.[30] Non-pharmacologic interventions can be:

• Physical: massage, acupuncture
• Behavioral: relaxation, art and play therapy
• Cognitive: distraction, imagery, hypnosis

ACADEMIC RESOURCES

WHO guidelines on the Pharmacological treatment of persisting pain in children with medical illness

http://whqlibdoc.who.int/publications/2012/9789241548120_Guidelines.pdf

[1] Ward, E et al. Childhood and adolescent cancer statistics, 2014. CA CANCER J CLIN 2014;00:00-00. Accessed on 12/19/2014 at: https://www.acco.org/LinkClick.aspx?fileticket=gAi0ji8IFPU%3d&tabid=670.

[2] Dang-Tan T, Franco EL. Diagnosis delays in childhood cancer: a review. Cancer. 2007;110:703-713.

[3] Soldes OS, Younger JG, Hirschl RB. Predictors of malignancy in childhood peripheral lymphadenopathy. J Pediatr Surg. 1999;34(10):1447.

[4] Widhe B, Widhe T. Initial symptoms and clinical features in osteosarcoma and Ewing sarcoma. J Bone Joint Surg Am. 2000;82(5):667.

[5] Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014.

[6] Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet. Mar 22 2008;371(9617):1030-43.

[7] NCCN Guidelines: Acute lymphoblastic leukemia. http://williams.medicine.wisc.edu/all.pdf Accessed 6/24/15.

[8] American Red Cross. Practice Guidelines for Blood Transfusion: A compilation from peer-reviewed literature, second edition. 2007; accessed at http://www.sld.cu/galerias/pdf/sitios/anestesiologia/practical_guidelines_blood_transfusion.pdf on 6/24/15.

[9] Rodgers GM, Becker PS, Blinder M et al. Cancer and chemotherapy-induced anemia: Clinical guidelines in oncology. Journal of the National Comprehensive Cancer Network May 2012; 10 (5): 628-653.

[10] Shah N, Andrews J, Goodnough LT. Transfusions for adult and pediatric patients with malignancies. Blood Reviews 2015; in press. Accessed at http://www.sciencedirect.com/science/article/pii/S0268960X15000168 on 6/24/15.

[11] Oliansky DM, Camitta B, Gaynon P et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of pediatric acute lymphoblastic leukemia: update of the 2005 evidence-based review. ASBMT position statement Biol Blood Bone Marrow Transplant 2012; 18:979-981.

[12] Coiffier B, Altman A, Pui CH, et al. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol 2008; 26:2767.

[13] Cairo MS, Coiffier B, Reiter A et al. Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus. British Journal of Hematology 2010; 149(4): 578-586.

[14] Sioka C. The utility of FDG PET in diagnosis and follow-up of lymphoma in childhood.

[15] Prusakowski MK, Cannone C. Pediatric oncologic emergencies. Emergency Medicine Clinics of North America 2014 Aug; 32(3):527-548.

[16] Dumba et al.

[17] Dahnert W. Urogenital tract. In: Radiology Review Manual 7^th Edition, Lippincott Williams and Wilkins, (2011), p.895-1012.

[18] London WB, Castleberry RP, Matthay KK, et al.: Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children's Oncology Group. J Clin Oncol 23 (27): 6459-65, 2005.

[19] Dumba M, Jawad N, McHugh K. Neuroblastoma and Nephroblastoma: a radiological review. Cancer Imaging 2015; 15(1): 5-14.

[20] CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. Ostrom QT, Gittleman H, Liao P, Rouse C, Chen Y, Dowling J, Wolinsky Y, Kruchko C, Barnholtz-Sloan J. Neuro Oncol. 2014; 16 Suppl 4:iv1.

[21] Roth P, Happold C, Weller M. Corticosteroid use in neuro-oncology: an update. Neurooncology Practice 2015; 2(1):6-12.

[22] Mohney BG, Robertson DM. Ancillary testing for metastasis in patients with newly diagnosed retinoblastoma. American Journal of Opthalmology 1994; 118(6): 707-711.

[23] Canadian Opthalmological Society. National Retinoblastoma Strategy Canadian Guidelines for Care Canadian Journal of Opthalmology 2009; 44 Supp. 2 S7-S88.

[24] Widhe B, Widhe T. J Bone Joint Surg Am. 2000; 82(5):667.

[25] Wiegering V, Schmid S, Andres O et al. Thrombosis as a complication of central venous access in pediatric paitents with malignancies: a 5-year single center experience. BMC Hematology 2014; 14(18) 1-10. http:// www.biomedcentral.com/2051-1839/14/18 accessed on 6/25/15.

[26] Shafir M. Chapter 33: Vascular access in cancer patients in Holland-Frei Cancer Medicine, 5^th Edition. Hamilton ON: BC Decker; 2000.

[27] Albisetti M, Kellenberger CJ, Bergstrasser E et al. Port-a-cath-related thrombosis and ostthrombotic syndrome in pediatric oncology patients Journal of Pediatrics 2013; 163(5):1340-6.

[28] Freifeld, A. et al. 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): e56-e93.doi: 10.1093/cid/cir073.

[29] Voepel-Lewis T, Zanotti , Dammeyer JA, Merkel S. Reliability and validity of the face, legs, activity, cry, consolability behavioral tool in assessing pain in critically ill patients. American Journal of Critical Care 2010; 19(1):55-61.

[30] McGrath PA. Development of the World Health Organization guidelines on cancer pain relief and palliative care in children. J Pain Symptom Management 1996; 12(2) 87.

Oncologic emergencies