Paraneoplastic Syndromes and Oncology Emergencies Jeffrey T. Reisert,

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