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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 • • • • • • 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 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 • • • • • 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 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 • • • • 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 • • • • • • 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