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Oncologic emergencies

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Oncologic emergencies Powered By Docstoc
					Oncologic emergencies
        Orna Kristal, DVM
   Diplomate ACVIM (oncology)
                  Topics
Chemotherapy induced myelosuppression
Hemangiosarcoma
–   Hemoabdomen
–   Cardiac tamponade
Hypercalcemia
Hypoglycemia
Complications of Mast Cell Tumors
       Myelosuppression/sepsis
Mildly           Moderately         Highly
myelosuppressive myelosuppressive   myelosuppressive
Actinomycin D Melphalan             carboplatin
chlorambucil     Vinblastine        CCNU
cisplatin        doxorubicin        mitoxantrone
L-asparaginase vincristine          L-asp+vinc
vincristine      cyclophosphamide vinc+CTX
                                    dacarbazine
   Myelosuppression/sepsis
Signs
– 5-8 d post-tx, exceptions (doxo, cis, carbo)
– Neutropenia
– thrombocytopenia
– Acute onset
– Lethargy, fever, inappetance


Mechanism
– Marrow progenitor cell cytotoxicity
   Myelosuppression/sepsis
Nadir = lowest point   Recovery in 2-3 days
Usually around day 7




                       N           N



                 C          C
     Myelosuppression/sepsis
 Neutrophil count and NOT total WBC is
 most important

Definitions of neutropenia
  – Mild       2,000 – 2,999 cells/µL
  – Moderate   1,000 – 1,999 cells/µL
  – Severe     < 1,000 cells/µL

 Severe neutropenia – high risk for sepsis
        Febrile neutropenia
Most cases have systemic infection
Source is absorption of enteric bacteria
– urogenital, respiratory, skin – less common
Rarely localized infection
– Septic arthritis
In people blood cultures rarely positive
Take culture only if source is identified
Myelosuppression/sepsis - prevention

 Use appropriate doses of chemo drugs
*** Lower doses for small dogs and cats***
                 (certain drugs)
Check CBC at expected nadir of drug
Do not treat if < 3,000 neutrophils
Prophylactic antibiotics
– Controversial in dogs
– Not used in cats
rhG-CSF (Neupogen) – if overdose
Neutropenia/sepsis - treatment
Afebrile, healthy, > 1,000 neutrophils:
 – Delay chemo (2-5 d rebound), No Tx needed

Afebrile, healthy, < 1,000 neutrophils (cats <
500 neutrophils):
 – Delay chemo, give oral prophylactic antibiotics

Febrile, systemic signs
 – Hospitalize, IV antibiotics, supportive care

< 1,000 neutrophils – reduce dose by 25% in
the future
     Prophylactic antibiotics
Oral, broad spectrum, good gram neg &
anaerobe coverage for GI flora
Treat for one week
Trimethoprim sulfa (Resprim)
– 15 mg/kg q12 hours
   NOT IN DOBERMAN
   KCS, IMMUNE MEDIATED DISEASES

Sinulox/Augmentin
– 20 mg/kg q 12 hrs
          Febrile neutropenia
Never send a patient on chemotherapy
          with a fever home

Patient must be hospitalized on IV fluids and broad
               spectrum IV antibiotics

  Septic, neutropenic cancer patients that do not
    receive appropriate therapy within 24 hrs of
     presentation have a 50-75% mortality rate
        Febrile neutropenia
Hospitalize, IV fluids, broad spectrum antibiotics

Get CBC + manual differential if not recently
done, don’t wait for results to start Tx

Treat aseptically
– Surgical scrub of IV cath site, use gloves, avoid SQ
  injections

Do not give Optalgin or other NSAIDs to reduce
fever
        Febrile neutropenia
IV antibiotics – always use high end of the dose
Ampicillin 20 mg/kg IV q8 hours (gm+ and
anaerobes) or cefazolin and enrofloxacin (gm-) 5
mg/kg IV diluted in saline and given slowly over
10 minutes, q12 hours in dogs, q24 hours in cats
Continue IV Tx until ≥ 24 hrs with no fever and
pet is eating and drinking
Send home on same antibiotics PO for 1 week
Fever persisting for > 2 days warrants additional
workup and/or changing antibiotics
Hemoabdomen – clinical presentation

Weakness
Collapse and shock
Pale mucous membranes
Tachycardia
Cardiac arrhythmias
Enlarged and/or painful
abdomen
Vomiting/diarrhea
Hemoabdomen – clinical presentation

Cardiac arrhythmias
 –   In 38% of splenic HSA
Ventricular
Etiology
 –   Myocardial ischemia & hypoxia
 –   Compression of caudal vena cava by splenic
     mass
 –   Myocardial depressant factors (MDF) from
     ischemic pancreas
    Hemoabdomen - diagnosis
Abdominocentesis
–   PCV ≥ 5% = hemorrhage
Decreased T.S/PCV
Differential diagnosis (no Hx of trauma)
–   HSA – spleen, liver, kidney, prostate,
    peritoneum
–   Hematoma
–   Other neoplasia
Hemoabdomen – diagnosis and staging
CBC, chemistry, U/A
–   Anemia

–   Thrombocytopenia (75%)

–   Abnormal RBCs
      NRBCs, acanthocytes, schistocyes
      (50%) → common in HSA

–   Etiology: Microangiopathic
    hemolytic anemia (MAHA) and
    DIC

–   Leukocytosis
Hemoabdomen – diagnosis and staging
 Coagulation profile
 –   DIC present in 50% of dogs with HSA
 –   ↓ plts.,↑ APTT & PT, ↓ fibrinogen, ↑ FDPs
 –   Up to 80% of dogs with DIC die
 Abdominal U/S
 –   Splenic mass – often cavitated
 –   Metastases (liver, ommentum)
 Chest radiographs – 3 views
 EKG
 Echocardiogram
 – essential in only 5%
Diagnosis and staging - CT
Hemoabdomen – diagnosis and staging

 Cytology
 –   Fluid – usually just blood
 –   FNA of primary – avoid!
        Can seed tumor cells
        Iatrogenic rupture of mass
        nondiagnostic
 Histopathology
 –   Only after surgical removal
 There is no pre-operative method to obtain a
 definitive diagnosis
Prevalence of HSA in dogs with a
          splenic mass
Histologic studies
–   2/3 or 50:50 rules
–   25-43% of all splenic masses were HSA

Clinical study (Hammond. JAVMA 2008;232:553-558)
–   Dogs with anemia, splenic mass, hemoperitoneum
    that required transfusion (n=71)
–   76% had neoplasia and 92% were HSA
–   Overall prevalence of HSA – 70%
–   Dogs with T.S < 5.8 mg/dL and plt. Count < 90,000
    were more likely to have HSA

Tell owners to help their decision on Sx
    Hemoabdomen & splenic mass –
         treatment - initial
Start resuscitation ASAP
IV fluids (LRS)
Oxygen if severe hypovolemic shock
Transfusion
–   pRBCs or fresh whole blood
–   Goal to get PCV > 25%
Treat DIC
–   Fresh whole blood or fresh frozen plasma
–   +/- low dose heparin (ATIII co-factor)
Treat ventricular arrhythmias
–   If rate > 160 bpm after resuscitation & clinical
    Hemoabdomen & splenic mass –
         treatment - surgery
If dog is stabilized can
postpone until Dx complete

Exploratory laparotomy +
splenectomy
–   Biopsy lesions in other
    organs

Lavage before closing

Monitor PCV, EKG, BP
               Splenectomy
             post-op treatment
Need to hospitalize
10-30% peri-operative mortality
IV fluids
Analgesia (narcotics)
Monitor EKG
–   ∼40% develop V tach
–   Most develop post-op, resolve within 5d
–   Lidocaine if heart rate > 160 bpm and clinical
Submit multiple sections or entire spleen
Hemangiosarcoma - treatment
∼ 40% have liver metastasis at Sx
Majority will die of metastases in abdomen
Splenectomy alone
–   MST – 86d, 1 yr survival – 6%
Splenectomy + doxorubicin (stage 1+2)
–   MST – 172d, 1 yr survival – 20%, P <0.05
Stage 3 (metastasis)
–   MST 1-2m
–   Some will respond to doxo and live 3-4m
Cardiac tamponade - presentation
Weakness, collapse
Pale mucous membranes
Tachycardia
Tachypnea
Muffled heart sounds
Pulsus paradoxus
Jugular vein distention
Chronic - ascites
          Cardiac tamponade
Third most common site of HSA
Right atrium is most common location
HSA accounts for 33-40% of pericardial effusion
Differentials
–   Neoplastic: mesothelioma, lymphoma, aortic body
    tumor, ectopic thyroid tumor, metastatic neoplasia
–   Non neoplastic (10%): coagulopathies, infection,
    CHF, hypoalbuminemia, left atrial tear, F.B, idiopathic
Cardiac tamponade - Radiographs
Large, globoid heart
Pleural effusion possible
Look for metastasis
Cardiac tamponade - diagnostics
 EKG
 – Tachycardia – sinus, SVT, V tach
 – Low voltage QRS
 – Electrical alternans
                    Diagnostics
Echocardiography + Abd US
  –   Pericardial effusion
  –   Cardiac mass (low sensitivity)
        Seen better when effusion present
Cardiac tamponade - treatment
Pericardiocentesis (can guide with echo)
  –   Sternal recumbency
  –   Right side
  –   EKG monitor
  –   5th intercostal space below CC junction, local block
  –   18g long IV catheter
  –   Check if fluid clots and Ht to differentiate pericardial
      from intracardiac fluid
  –   Remove as much fluid as possible, watch EKG
  –   Ventricular arrhythmias are common after procedure
  –   Effusion may resolve – depending on 1° cause
                Surgery

Removal of right atrial HSA has been
done Weisse (JAVMA 2005;226:575-579)
–   MST:
    Sx alone – 42d
    Sx + chemo – 175d
    P < 0.001
            Pericardiectomy
Thoracotomy or thoracoscopy
Not recommended for HSA
Always biopsy pericardium
– Idiopathic – rec after 3rd recurrence - LT control
– Aortic body tumor
    MST 730d compared w 42d for untreated
– Mesthelioma
    Biopsy allows Dx
    Adding intracavitary cisplatin ST > 1 yr reported
           Hypercalcemia
Most common PNS
Cancer is most common cause of ↑Ca
True frequency is unknown
–   Humans – up to 30%
–   Dogs – 25-40%
–   Cats - uncommon
Etiology in humans – multiple myeloma,
breast cancer, primary lung tumors
                 Etiology
Dogs                  Cats
 Lymphoma (T-cell)     Lymphoma
 Anal sac carcinoma    Squamous Cell
 Multiple myeloma      Carcinoma
 Leukemias
 Thymoma
 Carcinomas
 Melanoma
 Parathyroid tumors
             Pathophysiology
Normal calcium homeostasis maintained
by
–   PTH, Vitamin D - ↑
–   Calcitonin - ↓
Humoral hypercalcemia – most common
–   PTH-rp
Hematopoietic bone marrow malignancies
–   Example: Multiple myeloma
Metastasis of solid tumors into bones
          Clinical Symptoms
Severity depends on magnitude, rate of
onset and duration of hypercalcemia
–   Mild: Ca > 12 mg/dL, slow onset
–   Moderate: Ca > 14 mg/dL
–   Life threatening: Ca > 18 mg/dL, rapid onset
Non-specific
Reflect damage to kidneys, GIT,
neuromuscular and cardiac
           Clinical Symptoms
PU/PD                Bradycardia
Lethargy, muscle     Arrhythmias
weakness, tremors    Urolithiasis +/- UTI
Inappetance          – LUT signs

Vomiting             Cats
Diarrhea or          – Anorexia

constipation         – Lethargy
      Differential diagnoses
Hypercalcemia of malignancy
Renal failure
Vitamin D toxicosis (rodenticides, iatrogenic)
Hypoadrenocorticism
Primary hyperparathyroidism
Granulomatous disease
Idiopathic hypercalcemia of cats
Young dog (< 6 months)
Hyperalbuminemia
Lab error – lipemia, hemolysis
             Diagnostics
Hypercalcemia: > 12 mg/dL - dogs
                 > 11 mg/dL - cats
Interpret results in relation to serum
albumin
– Correction formula:
  Adjusted Ca (mg/dL) = 3.5 – albumin (g/dL)
  + Ca (mg/dL)
              Workup
History and physical examination
CBC, biochemistry panel and urinalysis
Chest and abdominal radiographs
Abdominal ultrasound
Cytology/Histopathology
Bone marrow aspirates
PTH/PTH-rp/iCa levels
Cervical ultrasound
                                 Hypercalcemia



                   Na, Cl: ↓ / K: ↑


          Addison’s
           Disease


           Phosphorus: ↑                          Phosphorus:N-↓


   iCa: N-↓              iCa: ↑              iCa: ↑           iCa: ↑
                      PTH:↓/PTHrp:↓       PTH:↓/PTHrp:↑    PTH:↑/PTHrp:↓


                                                              Primary
1˚ Renal failure      Vit. D toxicity      Malignancy
                                                              Hyper PT
                  Treatment
Tx underlying disease
Symptomatic
– DO NOT USE STEROIDS until you have a diagnosis!
– 0.9% saline diuresis – 2-4 x maintenance + KCl
     Monitor for volume overload, electrolytes and BUN/creat
     Improvement is usually minimal and of short duration
– Furosemide – I never use it
– Calcitonin – 4-8 IU/kg q8-12 hrs
– Bisphosphonates (pamidronate)
               Pamidronate
2nd generation aminobisphosphonate
1.3-2 mg/kg, diluted in 150 ml saline, IV CRI
over 2 hrs
Rapid onset of action, effective, duration?
Humans
– Maintenance: q3-4 weeks
– Efficacy correlated with levels of PTH-rp
S.E: renal, electrolyte imbalance, acute-phase
Rxn, cytopenias.
Indications: life threatening, maintenance for
refractory hypercalcemia
          Case example 1
8 yr old, mix breed, intact male
Presented with anorexia, V/D, lethargy
PE: oral ulcers, hind limb edema, no masses or
lymphadenopathy
Blood work showed normal CBC, hypercalcemia,
mild renal azotemia
Chest x-rays, AUS – NED
Sent iCa/PTH/PTH-rp to the U.S.
Tx with IV saline and sent home on furosemide
          Case example 1
What would you have done differently?
– Diagnostically?
– Treatment?
          Case example 1
Dog returned 3 days later
Hind limb edema and hypercalcemia resolved
Dehydrated, lethargic
Electrolyte imbalance
Azotemia worse
Tx with IV fluids, HL edema recurred
Referred for further workup
Died over the weekend
         Case example 2
8 yr old SF, mix breed
Presented for anal sac
mass → carcinoma
Had sublumbar lymph node
metastasis
Mild hypercalcemia – not
symptomatic
Treated with surgery,
radiation & chemotherapy
          Case example 2
Good PR to Tx and hypercalcemia resolved
Hypercalcemia recurred 2m from end of Tx,
lymph node was stable
Tx with pamidronate x 2 – minimal response
Switched to prednisone (1 mg/kg/d) – good
response for a few months
Then developed symptoms – on/off anorexia + D
IV saline diuresis, repeated x 3 – helped for 1m
Altogether received symptomatic Ca Tx for 8m
           Case example 3
10 yr old, SF Dachshund
AGACA completely excised
No metastasis
6 m later presented with lethargy, anorexia,
vomiting, difficulty defecating
PE: severe obstructive sublumbar
lymphadenopathy, inguinal lymphadenopathy,
dehydrated
          Case example 3
Calcium was 24 mg/dL!
Supportive Tx: IV saline diuresis,
prednisone, calcitonin
Palliative radiation therapy in 3 fractions
Initially C.S worse, but then resolved
Hypercalcemia resolved following rapid
response to RT
Lost to follow up after 6 months
   Hypoglycemia - Etiology

Insulinoma
Hepatoma/hepatic cell carcinoma
GI leiomyoma/leiomyosarcoma
Lymphoma
Plasma cell tumors
Hemangiosarcoma
Oral melanoma
          Pathophysiology
Islet cell tumors
– Excess production of insulin


Non-islet cell tumors
– ↑ tumor utilization of glucose
– ↓ hepatic glycogenolysis and gluconeogenesis
– Secretion of insulin-like growth factors
  (IGFI and IGFII)
            Pathophysiology
Insulin - ↑ glucose uptake, ↓ glucose
output by liver
Insulinoma
–   Autonomous insulin secretion
–   Signs seen after fasting, or exercise
–   Signs also seen after feeding
CNS uses glucose exclusively → 1st organ
to be affected
           Clinical Signs
Neuroglycopenic       Adrenergic
– Lethargy            – Muscle tremor
– Weakness            – Nervousness
– Ataxia              – Hunger
– Abnormal behavior
– Seizures            Polyneuropathy
– Coma
                      Onset
                      – degree and rate of
                        hypoglycemia
              Diagnostics
CBC, biochemistry panel and urinalysis
– R/O lab error and other DD’s
– May need fasting BG
Chest radiographs
Abdominal ultrasound
– low sensitivity for insulinoma
Basal insulin and glucose determination
Exploratory laparotomy
      Treatment - emergency
Goal is to control C.S not to restore euglycemia
Dextrose 2.5-5% added to fluids (LRS)
Dextrose bolus: 0.5 g/kg (20% sol) slow IV if
critical (Seizures)
Corticosteroids (after R/O Addison’s)
Tx cerbral edema + diazepam
Glucagon IV CRI: 5-13 ng/kg/min if all else fail
–   1 mg/1 liter 0.9% saline = 1µg/ml
–   Use syringe pump
–   Onset of effect within minutes
      Surgery - insulinoma
50% are metastatic @ diagnosis
– Regional lymph nodes and liver most common
Goal: remove primary tumor and debulk
metastatic disease
Complications
– pancreatitis, ↑ or ↓ BG
Intensive peri-op Tx
– 5% dextrose, steroids
– IV fluids
             Medical therapy
Exercise restriction
Diet
–   Multiple small meals
–   Complex carbohydrates,
    high protein, high fat
Prednisone 0.5 mg/kg/d, ↑ dose to effect
Diazoxide (Proglycem) 5-30 mg/kg q 12 hrs
Octreotide (Sandostatin) – effective?
Chemotherapy - Streptozotocin
        Complications of MCT
MC granules contain pro-inflammatory mediators
including histamine
Mediators cause
–   Increased vascular permeability   - Vasodilation
–   Pruritus                          - Mucous secretion
–   anticoagulation
Histamine level sig higher in neoplastic MC
Plasma histamine level increase with disease
progression
      Complications of MCT
More likely to occur
with:
– larger tumors
– Systemic disease




                       – Tx of large tumors
        Complications of MCT
Gastric ulceration
– Mechanism: histamine → stimulates H2 blockers on
  BM of parietal cells → ↑ acid secretion
– Symptoms: anorexia → V/D, melena
Delayed wound healing (Sx site)
– Mediated through H1+H2 receptors on macrophages
Lethargy
– Increased levels of circulating infamm mediators
Hypotensive shock
–   Massive degranulation
–   Advanced disease
–   Following Tx of large tumors
              Treatment
Indications
– Large tumor burden
– Before and after Tx (Sx, radiation, chemo)
– Symptomatic (GI ulcers, lethargy, shock)


Injectable for active GI ulcers and shock

PO for minimal signs or prophylactic
               H1 Blockers
Diphenhydramine 2–4 mg/kg q8-12 hrs PO/IM
– Also has an anti emetic effect

Chlorpheniramine (Ahiston) 4-8 mg q 8-12 hrs PO
max 0.5 mg/kg (Plumb)

Loratadine - 2nd generation
– Inhibits histamine release from normal MC in vitro
– May be good choice but no data for MCT
– Dose for dogs (VIN): > 20 kg – 10 mg q 12 hrs;
  7-20 kg – 10 mg q24 hrs; < 7 kg – 5 mg q 24 hrs, PO
              Other drugs
H2 blockers
– Ranitidine 2 mg/kg q 12 hrs PO,SQ,IV
– Famotidine 0.5 mg/kg q 12-24 hrs

Omeprazole – proton pump inhibitor
– For cases refractory to H2 blockers
– 0.5-1 mg/kg q 24 hrs

Sucralfate – for active ulcers

				
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