Emergencies in Oncologic

TUMORLYSISSYNDROME

Tumor Lysis SyndromeTLS: Metabolic derangements caused by the massive and abrupt release of cellular components into the blood after the rapid lysis of malignant cells. (phos , K , uric acid , Ca) Uric acid crystals and/or CaPO4 in renal tubules = impaired renal function, ARF, even deathphos leads to Ca : tetany, seizures, arrhythmiaK = life-threatening arrhythmia

WHO GETS IT?High tumor cell proliferation rate, large tumor burden, tumor chemosensitivityALL, AML, NHL, Burkitts Lymphoma (heme malignancies) Small cell >>> Hodgkins disease, Multiple Myeloma, Solid Tumors ( breast, GI, prostate etc.) Signs and Symptoms are non-specific: Can occur before chemo, but usually within 12 to 72hrs after starting chemo NauseaVomitingDiarrheaAnorexiaSyncopeLethargyEdemaFluid overloadCrampsSudden death

Usually develops after chemotherapy (paclitaxel, fludarabine, etoposide, thalidomide, bortezomib, and hydroxyurea )Can occur after radiation therapy, corticosteroids, chemoembolization, intrathecal chemotherapy, rarely from spontaneous necrosisLDH is considered by some a measure of tumor load and a marker of TLS risk

Prevention & ManagementThe best management is prevention.FLUIDS and HYDRATION:Aggressive hydration and diuresisImprove intravascular volume, renal blood flow, GFR (decrease [solute] in distal nephron/renal microcirculation)+/- diuretics (contraindicated in hypovolemia and obstructed uropathy)

ALKALINIZATION OF URINE:-Uric acid > 10xs more soluble in pH of 7.0 compared to pH of 5.0-Xanthine/hypoxanthine is also significantly more soluble in basic urine - Historically used, but not based on evidence based practice. NOT RECOMMENDED-Complications of alkalinization outweighs benefits (calcium phosphate precipitation, metabolic alkalosis)

ALLOPURINOL:-Competitive inhibitor of xanthine oxidase which decreases conversion of purine metabolites to uric acid. Used prophylactically for TLS -Prophylactic option for patients with a medium risk of TLS-Limitations: 1)ineffective in reducing uric acid levels before chemoTx2) Xanthine and hypoxanthine precipitateobstructive uropathy3)reduces clearance of some chemoTx (azothiopurine & 6-mercaptopurine)

RASBURICASE (recombinant urate oxidase) :-promotes catabolism of uric acid: Uric acid allantoin (10x more soluble than uric acid)-100 adult pt (w/ aggressive NHL) got 3 to 7 days of rasburicase beginning day 1 of chemo: 1)Uric acid levels decreased w/i 4 hrs of rasburicase2)Normalized uric acid levels maintained throughout chemo3)No increase in creatinine observed4)No patient required dialysis

NEUTROPENICFEVER

Neutropenic FeverBefore era of empiric antibiotics, infections accounted for 75% deaths related to chemotherapyFever is commonly the only symptom. Common infections present atypically (asymptomatic UTIs, PNA w/o infiltrates, meningitis w/o nuchal rigidity, bacteremia w/ only fatigue)Avoid digital rectal exams/manipulationsCareful oral exam and exam of catheter sites if anyPan Cx

BACTERIA:Until 1980s, GNR (P.aeruginosa) were the most commonly identified pathogens1995-2000, Gram + organisms = 62-76% of all bloodstream infectionsTrend toward Gram + due to introduction of long-term indwelling lines (Hickmans,Mediports)FUNGAL: - Risk increases w/ duration and severity of neutropenia, prolonged antibiotic use, and number of chemotherapy cycles-Candida (lines), aspergillus (immunocompromised, skin,sinus, PNA) >>>histo, blasto, coccidio, TB(prolonged steroids, other high risk patients)

TREATMENTNumerous regimens studied: monotherapy demonstrated equivalent to two drug regimens (i.e.: piperacillin/tazobactam , cefepime, meropenem)In critically ill, add on aminoglycoside (better G - coverage)Addition of Gram (+) as initial empiric coverage in patients w/o port/catheter/line or mucositis has no proven clinical benefit (VRE) Vancomycin or Linezolid :

-Skin or catheter infection-Hx of MRSA colonization-recent quinolone proph-Clinical deterioration-Hypotension-Mucositis

Fungal coverage (candida or aspergillus ssp. ):Routinely added after 5-7 days of persistent neutropenic fever w/o clear sourcePost mortem of fatalities after prolonged febrile neutropenia (1966-1975) = 69% w/ evidence of systemic fungal diseaseTx with liposomal amphotericin B (most common), voriconazole(? failed noninferiority trial?), caspofungin (passed noninferiority trial, less nephrotoxic aspergillus failure?)No fluconazole = efficacy

Colony Stimulating Factors (CSF):NOT routinely used for neutropenic fever unless the patient had previous bout of neutropenic fever with prior chemo cycle. Not shown to decrease mortalityBeneficial effects are quite modestUsed in neutropenic septic shock/severe sepsis (hypotension, organ dysfunction, PNA)Used in patients whose bone marrow recovery is expected to be especially prolonged.

SPINAL CORDCOMPRESSION

Neoplastic epidural spinal cord compressionNeoplastic invasion of space between vertebrae and spinal cord (epidural invasion)Defined as ANY thecal sac indentation radiographically (spinal cord or cauda equina)

LOCATION:Thoracic spine: 60%Lumbosacral spine: 30%Cervical spine: 10%

Cord compression is a common complication in oncology patients (5-10% of all cancer patients: prostate, lung, breast) which is a cause of pain and irreversible loss of neurologic function. NOT immediately life threatening unless it involves C3 or aboveBack pain is the precursor to spinal cord injury in almost all (96%)patients w/ spinal mets. Pain similar to disc disease: except pain supine, upright

Besides back pain:Radicular painMotor weaknessGait disturbanceBowel bladder dysfunction

DiagnosisBack pain + known malignancy = SCC until proven otherwisePlain films NOT enoughExam has poor accuracy with localizing levelMRI without contrast is the best test for SCC when suspectedCan resort to CT (myelography) if pt cannot tolerate MRI, is not candidate for MRI, or not available.

TREATMENTSteroidsRadiation TherapySurgery

CorticosteroidsProvides pain relief and anti-inflammationDexamethasone: Loading dose of 10mg to 16mg; followed by 4mg q 4hrs. Higher doses (100mg) may be associated w/ slightly better outcome in exchange for higher incidence of adverse effects. Reserved for paraplegia/paraparesis generally. (low vs high dose studies = equivocal)Taper once definitive treatment is underway

Radiation TherapyThis alone can be used for patients who are ambulatory and for pretreatment before paresis occurs. Doses is variable and determined by the quantity of previous XRT, type of tumor, and the field of treatmentFor extensive disease; limited survival = meaningful palliation (short courses)Chemotherapy can be used but most tumor types not particularly chemosensitive (unless NHL, Hodgkins, germ cell, breast).

Surgery---evolving scienceTHEN: Previous studies: Laminectomy w/ or w/o RT vs RT alone = NO difference in outcomeDecompressive resection reserved for unstable spine, life threatening compression, unknown etiology, tumors that are not reliably radiosensitive or chemosensitive.NOW: Newer studies show surgical intervention + XRT show BETTER functional status than XRT alone (anterior approach, improvements in instrumentation)

Other Management issuesQuickly involve Rad/onc and NeuroSx / OrthoAnalgesia: opioids, steroidsBed rest: controversial- but generally unnecessaryAnticoagulation: DVT prophylaxisBowel regimen: autonomic dysfunction, opioids, limited mobility all contribute to constipationSpinal bracing: only in patients with refractory pain

Best predictor is pre-treatment functional/neurologic status Rapid onset and quick progression = poor Px75% of patients treated correctly while still ambulatory, will remain ambulatoryOnly 10% of patients presenting with paraplegia will regain ambulatory status