Transcript Oncology Emergencies and Paraneoplastic disorders

Paraneoplastic Syndromes
and Oncology Emergencies
Jeffrey T. Reisert, DO
University of New England
Physician Assistant Program
4 MAR 2010
Contact Information
Jeffrey T. Reisert, DO
Tenney Mountain Internal Medicine, P.L.L.C.
16 Hospital Rd.
Plymouth, NH 03264
603-536-6355
603-536-6356 (fax)
[email protected]
Paraneoplastic syndromesRecognition
• Treatment of cancer involves treatment of
the disease and recognition/treatment of
complications
• A number of common syndromes can
develop in cancer patients that affect
course of disease
Mechanisms of syndromes
• May be related to cancer itself
– May be the presenting symptom of a malignancy
• May be due to treatment (and preventable in
some cases)
• Some mechanisms are direct such as tumor
invasion
• Some are mediated by other indirect
mechanisms (“humorally mediated”-through
body fluids)
Breakdown
• Some are general systemic problems
– General problems
– Infection related problems (most common)
– Hematologic
• Others are localized to an area
– Obstruction
– Many systems involved
• Some present as an oncologic emergency
General Syndromes in Cancer
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Seen in 30% of cancer pts
Weight loss
Anorexia
Cachexia
Fever
Generalized diminished immunity
– Typically results in specific infections
Treatment of Syndromes
• Difficult
• Treat disease?
• For weight loss
– Megestrol (Megace®) 400-800 mg of
suspension q daily
– Dronabinol (Marinol®) 2.5 mg q daily-bid
• Cannabinoid
– Prednisone
– Benzodiazepines (Lorazepam, others)
Infections
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Most common cause of death in CA
Need aggressive treatment
Broad spectrum antibiotics
Fungal coverage if indicated
– Fungal infections are rarely seen outside of
cancer therapy and HIV
• Guided by physical exam, etc.
Etiologies
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Skin breakdown (i.e.: Squamous cell)
Obstruction (i.e.: UTI in prostate CA)
Lymphedema (i.e.: Arm swelling in breast CA)
Splenectomy
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Used to treat some leukemias
“Encapsulated organisms”
Strep pneumonia
H. flu
Neisseria meningitidis
• Catheters (Urinary or venous)
Etiologies-cont.
• Immune system impairment
• Affects antigen presentation, cell killing,
humoral immunity (decreased immune
globulins)
• Neutropenia
• Exacerbated by corticosteroid use
• Specific examples-See next slide
Organisms
• Bacterial
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Staph
Strep
Pseudomonas
E. Coli
Clostridium deficil (“C. Diff”)-Antibiotic use, overgrowth
• Viral
– Herpes simplex virus (HSV)
– Zoster (shingles)-Varicella virus
• Fungal
– Oral thrush or esophageal candidiasis
– Pulmonary aspergillosis
– Hepatic candidiasis
• Others
– Typhlitis-Necrotizing colitis (RUQ pain)
Infection-Treatment
• Prevention-Hand washing, vaccines, etc.
• Vaccines
– Pneumococcal (Streptococcus pneumoniae)
– Haemophilus influenzae
– Meningococcal (Neisseria meningiditis)
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Dual drug/Broad spectrum
Institutionally based antibiotics
Later, culture based
Amphotericin B if fungus suspected
Pull catheter if necessary
Neutropenic fever
• An oncologic emergency
• Fever
• Absolute neutrophil count less than 500 (Multiply WBC
count by percent neutrophils)
• Culture and look for common causes
• Dual drug coverage usually recommended
• Granulocyte colony stimulating factor (GCSF)
– Filgrastim (Neupogen®)
– Pegfilgrastim (Neulasta®)
• Precautions (Gown and glove, avoid ill contacts, no fresh
fruits/vegetables)
• Exact etiology may or may not be identified
Superior vena cava (SVC)
syndrome
• Etiology
– Tumor obstructs venous return
– MC is lung CA (small cell). Others lymphoma,
non small cell lung, or metastatic cancer
• Diagnosis
– Neck, face, arm swollen/Increased collaterals
– CT scan
Superior vena cava (SVC)
syndrome-cont.
• Treatment
– Protect airway
– RT.-especially in NSC Lung CA
– Surgery occasionally
Pericardial effusion
• Etiology
– Fluid collection around heart
– 5-10% of CA pts on autopsy
– May be due to malignancy
• Primary (pericardial seeding of tumor)
• Metastasis
• Or by other mechanisms
– Lung, breast, leukemia, lymphoma
Pericardial effusion-cont.
• Diagnosis
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Dyspnea (MC)
Cough
Chest pain
Jugular venous distension (JVD)
Kussmaul’s sign (Increased JVD with inspiration)
Echocardiogram to confirm
CT also (not as good)
• Shortness of breath out of proportion to
pulmonary edema on CXR
Pericardial effusion-Treatment
• Pericardiocentesis
– May help diagnosis
• Pericardial window
• Sclerosing agent
– Eliminates effective space to prevent
reoccurrence
– Tetracycline
Pleural effusion
• Intrathoracic fluid collection
• Dyspnea
• May be easy means for cell
sampling/cancer diagnosis
• Thoracentesis
– Diagnostic
– Palliative
• Sclerosis-To prevent reoccurrence
Pleural effusion-Treatment
• Pleural space between visceral (lung) and
parietal pleura (chest wall)
• Insert chest tube
– Drain out any fluid
• Instill talc or other agent
– Clamp chest tube
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Painful
Leads to scarring, thus eliminating the space
Prevent recurrence of fluid collections
Sort of a last resort treatment
Obstruction
• Etiology
– Intestine, urinary, biliary
• Diagnosis
– Colicky pain, vomiting, infection
• Treatment
– Typically, surgery
– Treat CA
Spinal cord compression/
Increased ICP
• Etiology
– 5-10% CA pts
– Lung, breast, prostate, lymphoma, myeloma,
metastatic CA, metastatic CA of unknown primary
• Diagnosis
– 90% have back pain
• Thoracic>Lumbar>Cervical
• Pain worse when supine (unlike disk disease)
– X ray (for completeness, but not that great)
– CT, or myelogram
– MRI best
Spinal cord compression/
Increased ICP-Treatment
• Treatment
– Corticosteroids such as dexamethasone
– Dilantin if seizure
– Pain Rx, RT., Rarely surgery
Hypercalcemia
• Definition
– Most common paraneoplastic syndrome
– Ca++ leeches from the bone resulting in high serum
calcium levels
– Recall majority of Ca++ is stored in bones
– High levels in serum result in illness
– Seen in lung, breast, head/neck, kidney, multiple
myeloma
• Another oncologic emergency
• Remember to correct calcium levels for albumen
(Measured Ca ++ + O.8 x (4-albumen)
Hypercalcemia-Four Mechanisms
• 1) Lytic bone lesions
– Usually metastasis of solid tumors
• 2) Humorally mediated
– Ectopic parathyroid hormone
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Squamous cell tumors
Renal cell tumors
Transitional cell tumors
Ovarian CA
– Parathyroid related protein (PTHrP)
– Others (Interleukin1, tumor necrosis factor,
prostaglandins)
Hypercalcemia-Mechanisms-cont.
• 3) Osteoclastic activating factor
– Plasma cell dyscrasias (multiple myeloma)
• 4) Vitamin D metabolites
– Increase Ca++ absorption
– Lymphomas
Hypercalcemia-Symptoms
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Fatigue
Anorexia
Constipation
Nausea and vomiting
Thirst
Look for in common malignancies that
cause (i.e.: Squamous cell cancers)
Hypercalcemia-Treatment
• Treatment
– Treat hypercalcemia AND cancer
– Normal saline
– IV resorptive agents
• Push Ca++ back into bone Bisphosphonates
• i.e.: Pamidronate (Aredia®), Zoledronic acid
(Zometa®)
Syndrome of inappropriate antidiuretic hormone (SIADH)
• Results in water retention greater than
sodium excretion
– Increase urine osmolality
– Urinary sodium normal or increased
– Decrease in serum osmolality
– Hyponatremia (Key feature)
– Low BUN. Normal creatinine
– No edema
SIADH-Mechanisms
• Due to tumor produced arginine
vasopressin or atrial natriuretic factor
– Small cell lung cancer
– Some chemo also causes (vincristine,
cyclophosphamide, cisplatin, others)
SIADH-Diagnosis
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Anorexia
Lethargy
Confusion
Low serum sodium
If severe-convulsions
– Na+ less than 110
SIADH-Treatment
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Treat CA
Restrict water
If seizures, 3% saline solution
Demeclocycline 150-300 mg po qid
– Inhibits AVP
• Lithium 200mg po qid
– Interferes with AVP as well
Ectopic Cushing syndromes
• Small cell lung CA and metastatic disease
• ACTH secreting tumors
– Hypokalemia/electrolyte abnormalities
– Usually no change in body habitus
• Pituitary adenomas
– Often Cushingoid
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Moon facies
Central fat deposition
Buffalo hump
Etc.
Tumor lysis syndrome
• Release of intracellular contents into
serum (next slide)
• May occur hours to days after treatment
• Usually associated with chemotherapy and
tumors with high nucleic acid turnover
• Acute leukemias, Lymphomas (such as
Burkitt’s), occasionally solid tumors (such
as small cell lung)
Tumor lysis syndrome-Diagnosis
• High K+, uric acid, phosphate, lactate
• Low Ca++ (tetany)
• Renal failure
Tumor lysis syndrome
• Treatment
– Prevention, hydration
– Allopurinol, sodium bicarbonate
– Dialysis
Other renal disorders
• Nephrotic syndrome
• Glomerulonephritis
Neuromuscular complications of
cancer
• Myopathy, polymyositis
• Myasthenic syndrome (Eaton-Lambert
syndrome)
– May have optic sequelae
• Neuropathy
– Most common is distal sensorimotor
polyneuropathy
• Myelopathy
Neuromuscular complications of
cancer-cont.
• Meningitis
– S. pneumoniae
– Other encapsulated organisms if splenectomy
• Sub acute cerebellar degeneration
• Encephalopathy
• Encephalitis
– Varicella zoster virus
– Creutzfeldt-Jakob
• Brain abscess
– Cryptococcus (Lymphoma, steroid associated)
Cerebral metastasis
• 50% get headaches
– Worse in morning
– Better as day progresses
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Nausea/vomiting
Focal neurological deficits
Treatment-Steroids and RT
May go to surgery if single metastasis
Musculoskeletal processes
• Clubbing (Drum sticking of distal finger,
with flattening of nail angle)
– Non small cell lung CA
• Hypertrophic pulmonary osteoarthropathy
(skeletal connective tissue syndrome)
– Joint pain
– Positive bone scan
– Non small cell lung CA
Hematologic problems
• Anemias
• Neutropenia (covered above)
• Clotting/bleeding disorders
Anemias
• Largely covered in other lectures
• May be due to blood loss
– NSAIDS
– Low platelet counts such as DIC
– Hemolysis
• May be bone marrow related
– Myelophthesis-Tumor filled marrow
– Chemo/Radiation effect
• May be a paraneoplastic disorder
– Pancreas CA
– Prostate CA
• Transfusion may be necessary
• May respond to erythropoeitin
Clotting disorders
• Migratory venous thrombophlebitis
(Trousseau’s syndrome)
• DIC
• Marantic endocarditis (next slide)
Clotting disorders-cont.
• Non-bacterial thrombotic endocarditis
(Marantic endocarditis)
– Arterial thrombosis/Embolic events
– Peripheral or cerebral
– Often hard to elicit (can be found in some only
on autopsy)
– Treat with anti-coagulants and anti-platelets
– Seen in lung, stomach, ovarian CA, others
Bleeding disorders
• Disseminated intravascular coagulation
(DIC)-Covered previously
• Hemolytic uremic syndrome (HUS)
• May result in anemia
Hemolytic uremic syndrome (HUS)/Thrombotic
thrombocytopenic purpura (TTP)
• Diagnosis
– Hemolytic anemia, thrombocytopenia, renal
failure
– Dyspnea, weak, low urine output,
hypertension, pulmonary edema
– Anemia, high LDH, low haptoglobin,
COOMBS negative
– Hematuria, proteinuria, and casts
HUS/TTP-Mechanisms
• Mitomycin, cisplatin, bleomycin
• Gastric, colorectal, breast CA
• Fibrin deposits in capillary walls?
Hemolytic uremic syndrome
(HUS)/TTP-II
• Treatment
– Plasmapheresis, immunoperfusion
Paraneoplastic syndromes
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Numerous
Interesting
Stay alert
Prevent complications
Treat early
Oncology is a multisystem disease
Resources
• Washington Manual
– Great coverage of treatments of these
disorders
– Now in handheld version