Oncological Emergencies other than TLS

%%{init: {"themeVariables": { "lineWidth": "3px", "lineColor": "#000000" } }}%%
graph LR
    %% Root Node
    Root([Oncological Emergencies])
    style Root fill:#e1f5fe,stroke:#01579b,color:#01579b

    %% Main Categories
    MetHem[Metabolic & Hematologic]
    style MetHem fill:#e8f5e9,stroke:#2e7d32,color:#2e7d32

    Struct[Space-Occupying & Structural]
    style Struct fill:#ffebee,stroke:#c62828,color:#c62828

    Organ[Organ-Specific & GI]
    style Organ fill:#fff8e1,stroke:#f57f17,color:#f57f17

    SysTreat[Systemic & Treatment-Related]
    style SysTreat fill:#f3e5f5,stroke:#7b1fa2,color:#7b1fa2

    %% Sub-categories for Metabolic & Hematologic
    TLS[Tumor Lysis Syndrome]
    style TLS fill:#e8f5e9,stroke:#2e7d32,color:#2e7d32
    HyperL[Hyperleukocytosis]
    style HyperL fill:#e8f5e9,stroke:#2e7d32,color:#2e7d32
    HyperC[Hypercalcemia of Malignancy]
    style HyperC fill:#e8f5e9,stroke:#2e7d32,color:#2e7d32

    %% Sub-categories for Structural
    SVC[SVC / Superior Mediastinal Syndrome]
    style SVC fill:#ffebee,stroke:#c62828,color:#c62828
    Tamponade[Cardiac Tamponade]
    style Tamponade fill:#ffebee,stroke:#c62828,color:#c62828
    SCC[Spinal Cord Compression]
    style SCC fill:#ffebee,stroke:#c62828,color:#c62828
    ICP[Increased Intracranial Pressure]
    style ICP fill:#ffebee,stroke:#c62828,color:#c62828

    %% Sub-categories for Organ/GI
    Typh[Typhlitis - Neutropenic Enterocolitis]
    style Typh fill:#fff8e1,stroke:#f57f17,color:#f57f17
    SOS[Sinusoidal Obstructive Syndrome]
    style SOS fill:#fff8e1,stroke:#f57f17,color:#f57f17
    GI[Bowel Obstruction / GI Hemorrhage]
    style GI fill:#fff8e1,stroke:#f57f17,color:#f57f17

    %% Sub-categories for Systemic/Treatment
    FebNeu[Febrile Neutropenia]
    style FebNeu fill:#f3e5f5,stroke:#7b1fa2,color:#7b1fa2
    CRS[Cytokine Release Syndrome]
    style CRS fill:#f3e5f5,stroke:#7b1fa2,color:#7b1fa2
    DiffSyn[Differentiation Syndrome]
    style DiffSyn fill:#f3e5f5,stroke:#7b1fa2,color:#7b1fa2
    Endo[Endocrine: SIADH / Adrenal Insufficiency]
    style Endo fill:#f3e5f5,stroke:#7b1fa2,color:#7b1fa2

    %% Connections
    Root --> MetHem
    Root --> Struct
    Root --> Organ
    Root --> SysTreat

    MetHem --> TLS
    MetHem --> HyperL
    MetHem --> HyperC

    Struct --> SVC
    Struct --> Tamponade
    Struct --> SCC
    Struct --> ICP

    Organ --> Typh
    Organ --> SOS
    Organ --> GI

    SysTreat --> FebNeu
    SysTreat --> CRS
    SysTreat --> DiffSyn
    SysTreat --> Endo

Cardiothoracic Emergencies

Superior Vena Cava Syndrome And Superior Mediastinal Syndrome

• Results from compression of superior vena cava or trachea by anterior mediastinal masses.
• Commonly associated malignancies:
  • Non-Hodgkin lymphoma
  • T-cell acute lymphoblastic leukemia (ALL)
  • Hodgkin lymphoma
  • germ cell tumors
  • neuroblastoma
  • thymoma.
• Intrinsic etiologies: Intravascular tumor thrombosis (Wilms tumor, lymphoma), catheter-related thrombosis.

Cardiac Tamponade

• Results from massive pericardial effusion, intracardiac thrombus, tumors, or radiation-induced constrictive pericarditis.
• Presentation: Chest pain, cough, dyspnea, tachycardia, pulsus paradoxus.
• Intervention: Oxygenation, hydration, emergent percutaneous pericardial drainage, fluid cytology.

Hematologic And Metabolic Emergencies

Hyperleukocytosis

• Defined as total white blood cell (WBC) count >100,000/mm³.
• High blast burden causes microcirculatory sludging, tissue ischemia, local cytokine production.
• Adhesive reactions between blasts and endothelium worsen leukostasis, leading to thrombosis and secondary hemorrhage.

Management Interventions

• Intravenous (IV) hydration >2 times maintenance rate.
• Avoid packed red blood cell (RBC) transfusions (increases blood viscosity); transfuse only if hemodynamically unstable using small aliquots (5 cm³/kg).
• Transfuse platelets if count <20,000/mm³.
• Correct coagulopathy (vitamin K, fresh frozen plasma).
• Leukapheresis or exchange transfusion (contraindicated in acute promyelocytic leukemia).

Hypercalcemia Of Malignancy

• Pathophysiology: Osteolytic bone resorption (leukemia, lymphoma, rhabdomyosarcoma), paraneoplastic parathyroid-like hormone (PTHrP) production, immobilization, renal excretion defects.
• Presentation: Anorexia, nausea, polyuria, polydipsia, constipation, weakness, bradycardia, shortened QT interval, coma.
• Management:
  • Stop calcium-containing medications.
  • Aggressive IV hydration with normal saline (2-3 times maintenance).
  • Furosemide diuresis (1-2 mg/kg/dose every 6 hours).
  • Bisphosphonates (Pamidronate 0.5-1 mg/kg IV over 4-6 hours).
  • Corticosteroids (Prednisone 1.5-2.0 mg/kg daily) for lymphoproliferative disorders.
  • Calcitonin.

Neurologic Emergencies

Spinal Cord Compression

• Occurs in ~5% of pediatric oncology patients.
• Associated malignancies: Ewing sarcoma, neuroblastoma, lymphomas, epidural chloromas (leukemia), central nervous system (CNS) drop metastases.
• Pathogenesis: Direct tumor extension via vertebral foramina, vertebral metastasis, or subarachnoid spread.

Increased Intracranial Pressure (ICP)

• Etiology: Primary CNS tumors (medulloblastoma, glioma), brain metastasis, hydrocephalus, CNS leukemia, pseudotumor cerebri, hemorrhage.
• Presentation: Headache, morning emesis, hypertension, bradycardia, papilledema, cranial nerve III and VI palsies, altered mental status, seizures.
• Interventions: Dexamethasone, ventriculostomy, surgical excision, radiation, specific chemotherapy.

Gastrointestinal And Hepatic Emergencies

Typhlitis (Neutropenic Enterocolitis)

• Necrotizing colitis involving the cecum; progresses rapidly to bowel infarction and perforation.
• Associated heavily with severe myelosuppression, acute leukemia, and mucosal injury from cytotoxic chemotherapy.
• Manifestations: Acute abdomen, right lower quadrant pain, bloody diarrhea, hypotension, fever.
• Diagnosis: Abdominal radiograph or CT reveals thickened bowel wall, pneumatosis intestinalis, free air.
• Management: Strict bowel rest, nasogastric suction, surgical consultation, broad-spectrum antibiotics (covering Gram-negatives and anaerobes), antifungals.

Sinusoidal Obstructive Syndrome (Veno-Occlusive Disease)

• Pathophysiology: Fibrous obliteration of small hepatic vessels; necrosis of zone III hepatocytes.
• Triggers: Post-hematopoietic stem cell transplant, high-dose cyclophosphamide, total body irradiation, gemtuzumab ozogamicin, inotuzumab ozogamicin, thiopurines.
• Presentation: Jaundice, tender hepatomegaly, weight gain, ascites, edema.
• Intervention: Discontinue inciting agents, rigorous fluid management, defibrotide administration.

Bowel Obstruction And Gastrointestinal Hemorrhage

• Obstruction causes: Tumor masses (lymphoma, neuroblastoma), intussusception (Burkitt lymphoma), adhesions.
• Hemorrhage causes: Chemotherapy-induced thrombocytopenia, corticosteroid-induced ulcers, tumor masses, prolonged neutropenia.
• Interventions: Bowel rest, nasogastric suction, blood product transfusions, endoscopic evaluation, surgical consultation.

Infectious Emergencies

Febrile Neutropenia

• Definition: Absolute neutrophil count (ANC) <500/mm³ (or <1000/mm³ with expected decline) accompanied by fever >38.3°C orally or sustained >38.0°C.
• Carries immediate risk of life-threatening sepsis, shock, disseminated intravascular coagulation.
• Pathogens: Gram-negative bacteria, Gram-positive bacteria, fungi (Candida, Aspergillus), opportunistic organisms (Pneumocystis jiroveci).
• Management Protocol:
  • Mandatory hospitalization.
  • Immediate empiric broad-spectrum IV antimicrobial therapy (e.g., Cefepime, Vancomycin).
  • Add empiric antifungals if fever persists beyond 3-5 days of broad-spectrum antibiotics.
  • Granulocyte colony-stimulating factor (G-CSF) if appropriate.

Endocrine Emergencies

Syndrome Of Inappropriate Antidiuretic Hormone Secretion (SIADH)

• Pathophysiology: Continuous, unregulated pituitary release of antidiuretic hormone irrespective of plasma osmolality.
• Triggers: Vincristine, cyclophosphamide, ifosfamide, cisplatin, CNS/pulmonary lesions, severe physiologic stress.
• Presentation: Oliguria, weight gain, fatigue, nausea. Progression to lethargy, seizures, coma.
• Laboratory Profile: Hyponatremia (<130 mEq/L), low serum osmolality (<280 mOsm/L), high urine osmolality (>500 mOsm/L), increased urine specific gravity.
• Management:
  • Strict fluid restriction.
  • Furosemide (1 mg/kg/dose) diuresis.
  • Severe neurologic symptoms: 3% hypertonic saline. Correct cautiously (maximum 2 mEq/L/hour initially) to prevent permanent neurologic sequelae.

Adrenal Insufficiency

• Triggers: Prior profound corticosteroid exposure, abrupt withdrawal, critical illness, sepsis, tumor infiltration, radiation injury to adrenal glands.
• Presentation: Fatigue, dizziness, nausea, severe hypotension, profound shock, hyponatremia, hyperkalemia, normal anion gap metabolic acidosis.
• Management: Immediate glucocorticoid replacement (Hydrocortisone 100 mg/m² loading dose, followed by 25 mg/m² every 6 hours for 7 days without taper). Fludrocortisone. Monitor for hyperglycemia.

Treatment-Associated Emergencies

Cytokine Release Syndrome (CRS)

• Pathophysiology: Acute systemic inflammation linked to T-cell expansion, macrophage activation, and massive cytokine production (IL-6, IL-10, interferon-gamma).
• Triggers: Chimeric antigen receptor (CAR) T-cell therapy (tisagenlecleucel), bispecific T-cell engagers (blinatumomab), monoclonal antibodies.
• Manifestations: Required fever, hypotension, hypoxemia, end-organ dysfunction, capillary leak.
• Associated Laboratory Findings: Markedly elevated C-reactive protein and ferritin.
• Interventions:
  • Antipyretics, judicious fluid resuscitation (avoid exacerbating vascular leak), vasoactive agents.
  • Interrupt immunotherapy infusion.
  • Targeted modulation: Tocilizumab (IL-6 receptor antibody) is first-line for CAR T-cell associated severe CRS. Corticosteroids for neurotoxicity or refractory CRS.

Differentiation Syndrome

• Pathophysiology: Complication of all-trans-retinoic acid (ATRA) and/or arsenic trioxide therapy for acute promyelocytic leukemia. Maturation of leukemic cells produces inflammatory cytokines causing endothelial damage, capillary leak, and microcirculation occlusion.
• Bimodal Onset: Occurs within 1 week or 3-4 weeks of initiating therapy.
• Presentation: Respiratory distress, pulmonary infiltrates, peripheral edema, weight gain, hypotension, pleuropericardial effusions, acute renal failure, fever.
• Interventions: Immediate Dexamethasone (0.5-1 mg/kg every 12 hours). Temporarily halt ATRA/arsenic therapy if symptoms are life-threatening.

Anaphylaxis And Hypersensitivity

• Implicated Agents: Asparaginase, platinum agents, etoposide, bleomycin, monoclonal antibodies (dinutuximab, rituximab).
• Presentation: Bronchospasm, laryngospasm, wheezing, hypotension, angioedema, urticaria, flushing.
• Management: Immediate cessation of infusion. Epinephrine administration. Supportive fluids, oxygen, parenteral corticosteroids (methylprednisolone/hydrocortisone), H1/H2 antagonists. Switch to alternative preparations if available (e.g., Erwinia asparaginase for pegaspargase allergy).