Paraneoplastic Syndromes Flashcards
What are Paraneoplastic Syndromes?
Systemic effects of cancer May involve hormones/other factors Usually unrelated to the tissue of origin May be more detrimental than the tumor May be the first symptom
What is Cancer Cachexia?
Profound state of malnutrition and weight loss despite adequate nutrition
A paraneoplastic syndrome
More common in cats
Clinical Significance of Cancer Cachexia
Decreased QOL
Decreased response to treatment
Decreased survival time
Cancer Cachexia Mechanism
Cancer stealing all energy!
Glucose is preferred substrate for cancer cells
Tumor cells incomplete glucose metabolism; molecules of ATP
Lactate is produced as an end product
Energy expended converting lactate back to glucose
Gluconeogenesis increases; net energy loss by host –> protein degradation (muscle wasting, decreased immune function, decreased wound healing)
Lipolysis occurs to provide energy for host
Cancer Cachexia
Treatment
Provide 30-50% of non-protein calories as fat vs. CHO
Provide adequate calories (1.5 to 3 times that of normal animals)
Cannot decrease intake because cancer will cause hypoglycemia
Best to stick to regular diet and give them more of the food
What is Hills N/d
Cancer diet
Actually caused diarrhea in dogs; malabsorption
Not shown to improve outcome or maintain weight
Only tested on dogs with lymphoma (stage III)
Not shown to starve cancer
What is a common labwork abnormality in both dogs and cats with cancer?
Hypercalcemia
Ectopic hormone production
Hypercalcemia
Tumor types
Lymphosarcoma
Anal sac Apocrine gland adenocarcinoma
Multiple myeloma Thymoma Parathyroid gland adenomas Mammary carcinomas SCC
Ectopic hormone production
Hypercalcemia
Mechanisms
Ectopic tumor produced parathomone like peptides (PTHrp)
True hyperparathyroidism (PTH)
Vitamin D like factors
Tumor production of osteoclast activating factor
Direct bone lysis (rare)
Ectopic hormone production
Hypercalcemia
Clinical Signs
Anorexia
Vomiting
PU/PD
Muscle weakness
Ectopic hormone production
Hypercalcemia
Diagnosis
Can be difficult if concurrent disease (renal)
Careful search for potential neoplasia
Assays for PTH, PTHrp
Avoid symptomatic therapy that may interfere with diagnosis (glucocorticoids)
Primary hyperparathyroidism
Serum Calcium
Serum Phos
Ca: slightly high
Ph: low
Vitamin D Toxicosis
Serum Calcium
Serum Phos
Ca: High to very high
Ph: High
Malignant humoral hypercalcemia
Serum Calcium
Serum Phos
Ca: High to very high
Ph: Normal or low
Bone lysis
Serum Calcium
Serum Phos
Ca: High
Ph: Normal or high
Ectopic hormone production
Hypercalcemia
Treatment Goals
Increase renal excretion of calcium (diuresis)
Inhibit bone reabsorption
Prevent calcium deposition in tissue
Promote external loss of Ca
Ectopic hormone production
Hypercalcemia
Treatment
Treat underlying disease!
Saline diuresis
Furosemide (inhibits reabsorption at loop of Henle)
Glucocorticoids
Bisphosphonates
Bisphosphonates
Example
What they do
Pyrophosphate analogues (Pamidronate)
Keeps Ca in the bone
Helps patient when hypercalcemia is making them clinically ill
Ectopic hormone production
Hypoglycemia
Causes
Insulinoma Hepatic tumors (not making glucose) Leiomyoma/Leiomyosarcoma Oral melenoma Lymphosarcoma
Hypoglycemia
Clinical Signs
Weakness
Tremors
Seizures
Ectopic hormone production
Hypoglycemia
Treatment
Feed frequently; high protein better than high CHO but avoid giving too much sugar (hepatic overload)
Glucose IV or orally (careful with insulinoma)
Glucocorticoids; increase hepatic gluconeogenesis (okay to do this prior to diagnosis)
Eventually need to address tumor; stabilize first
Ectopic hormone production
Treatment of Insulinoma
Causes hypoglycemia
Remove the underlying problem/tumor (prognosis; 14 months)
Streptozotocin; antineoplastic agent with affinity for pancreatic islet cells (nephrotoxic, must administer with fluids); could induce diabetes mellitus
+/-Tocernib (Palladia)
Ectopic Hormone Production
Erythropoietin
Tumor examples
Causes polycythemia
Renal cell tumors
Lymphosarcoma
Hepatic tumors
Nasal fibrosarcoma
Ectopic Hormone Production
Erythropoietin
Clinical Signs
Polycythemia
Neurologic; motor or sensory depression, dullness, lethargy, seizures
Hemorrhage (epitaxis, hyphema)
Ectopic Hormone Production
Erythropoietin
Treatment
Polycythemia
Phelbotomy (bleed them)
Remove or treat primary tumor
Hydroxyurea (suppresses bone marrow; decreases RBC production)
Hypertrophic Osteopathy
What is it?
Pain, reluctance to move, “swollen legs or swollen joints” – very painful
Periosteal proliferation of new bone along the shafts of long bones
Hypertrophic Osteopathy
Radiographic findings
Thickening of long bones; proliferative bone
Associated with large thoracic or abdominal cavity mass (unknown mechanism)
Hypertrophic Osteopathy
Treatment
Treat or remove primary tumor
Corticosteroids
NSAIDs; has been proven to help
Bisphosphonates
Fever and Neoplasia
Cancer is always a DfDx for fever of unknown origin
Possible cytokine release by tumor or macrophages responding to tumor (IL-1, IL-2, IL-6, TNF-alpha)
Cancer Hematologic Abnormalities (broad)
Failure of production
Loss
Sequestration (tumor or spleen)
Destruction
Cancer Hematologic Abnormalities
Anemia
Chronic inflammation Blood loss Microangiopathic hemolytic anemia (HSA0 IMHA Chemotherapeutic drugs Bone marrow infiltration with tumor Hyperestrogenism (sertoli cell tumor)
Cancer Hematologic Abnormalities
WBC
Leukocytosis
Common
Granulopoietic factors
Inflammation
Chronic inflammation
Note: rebound after chemotherapy leukopenia or anemia
Cancer Hematologic Abnormalities
Platelets
Thrombocytopenia
35% of dogs with tumors
Mechanism: decreased production, sequestration, increased consumption, increased destruction
Thrombocytosis
Chronic inflammation
Cancer Hematologic Abnormalities
Globulins
Hypergammaglobulinemia:
PU/PD, neurologic signs, bleeding, more signs secondary to tumor
Monoclonal gammopathy
Single clone of Ig-producing cells
Cancer Hematologic Abnormalities
Globulins
Tumor types
Plasma cell tumors (sky high globulins)
Lymphoma
Leukemia
Cancer: Neurologic Syndromes (3)
Myasthenia gravis
Peripheral neuropathies
Chemo related neurologic toxicity
What causes Myasthenia gravis (cancer wise)
Thymoma
Anti-Ach receptor antibody
Drug that should be avoided in cats
5 Flurouracil
Seizures and death
Cancer Dermatologic Syndromes (3 main)
Cutaneous flushing
Nodular dermatofibrosis in German Shepherds
Alopeica
Cancer Dermatologic Syndromes
What causes cutaneous flushing
Pheochromocytoma
Mast cell tumors (degranulation)
Cancer Dermatologic Syndromes
Nodular dermatofibrosis
Rare
German Shepherds! Autosomal dominant inheritance
Lumps and bumps everywhere
Linked to renal cysts or cystadenocarcinomas
Cancer Dermatologic Syndromes
What causes alopecia
Pancreatic carcinomas in cats – pathopneumonic
