paraneoplastic syndromes and oncology emergencies jeffrey t. reisert, do university of new england...
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Paraneoplastic Syndromes and Oncology Emergencies
Jeffrey T. Reisert, DOUniversity of New England
Physician Assistant Program4 MAR 2010
Contact Information
Jeffrey T. Reisert, DOTenney Mountain Internal Medicine, P.L.L.C.
16 Hospital Rd.Plymouth, NH 03264
603-536-6355603-536-6356 (fax)
Paraneoplastic syndromes-Recognition
• 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
• 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
• 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
• Skin breakdown (i.e.: Squamous cell)• Obstruction (i.e.: UTI in prostate CA)• Lymphedema (i.e.: Arm swelling in breast CA)• Splenectomy
– 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
– 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)
• 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– 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
• 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
• 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
• 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 anti-diuretic 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
• Anorexia
• Lethargy
• Confusion
• Low serum sodium
• If severe-convulsions– Na+ less than 110
SIADH-Treatment
• 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
• 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
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
• 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
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?
Paraneoplastic syndromes
• Numerous
• Interesting
• Stay alert
• Prevent complications
• Treat early
• Oncology is a multisystem disease