Exam 7 L. 7

Question 1

Paraneoplastic syndromes

Answer 1

1) CANCER ASSOCIATED ALTERATIONS OCCURRING DISTANT TO TUMOR

2) typically result from tumor production of small molecules
- hormones, cytokines, peptides, enzymes
3) other causes = immune -related
- antibody cross-reactivity, immune complex development, autoimmune component

Question 2

Clinical importance of Paraneoplastic Syndromes (PNS)

Answer 2

1) PNS often are the 1st sign of cancer!!*
- They may be a hallmark of certain types of tumor
2) PNS frequently parallel underlying malignancy
- treatment of tumor often resolves PNS

3)PNS MAY CAUSE GREATER MORBIDITY THAN PRIMARY TUMOR

Question 3

Gastrointestinal manifestations of cancer

Answer 3

1) cachexia -wasting syndrome and weight loss
2) inappetence
3) protein losing enteropathy
4) Gastroduodenal ulceration

Question 4

Cerenia (Maropitant): acts on..

Answer 4

1) Acts on the chemoreceptor trigger zone
- NK1 receptor
2) Emetic Center
- NK1 receptor

Question 5

Metoclopramide acts on..

Answer 5

1) Chemoreceptor trigger zone
- D2 antagonist
2) Afferent neurons
- 5-HT3 receptors

NOTE: sedation +/-, behavioral changes

Question 6

Ondansetron

Answer 6

Acts on chemoreceptor trigger zone

- 5-HT3 receptor

Question 7

Control of food intake is complicated

Answer 7

1) increases feeding: Ghrelin
2) decreases feeding: stretch receptors, cholecystokinin, insulin, leptin
* ***a lot of negative input to the brain saying “not hungry” ===> many of these are upregulated in oncology patients

Question 8

Capromorelin

Answer 8

1) the 1st FDA approved veterinary product for inappetence!
2) mimics the action of ghrelin*
- effect at appetite center to increase food intake
3) potent and selective growth hormone secretagogue receptor agonist = increases growth hormone secretion!!!!
- NOTE: because negative feedback loop is in place, these animals WON’T have abnormal growth

Question 9

Gastroduodenal ulceration: mast cell tumors

Answer 9

1) mast cell tumors ==> hyperhistaminemia
- elevated plasma histamine = negative prognostic factor
2) histamine binds gastric H2 receptors ==> increased HCl***
- predisposes dog to gastric and duodenal ulcers
3) treatment: PPI, H2 blocker, misoprostol, sucralfate

NOTE: gastrinoma (gastrin secreting non-islet pancreatic tumor) can also cause G.I. ulceration

Question 10

Endocrine manifestations of cancer

Answer 10

1) hypercalcemia

2) hypoglycemia

Question 11

Causes of hypercalcemia

Answer 11

H-hyperparathyroidism
A-Addison's disease (hypoadrenocortiscism)
R-renal disease
D-hypervitaminosis D
I-idiopathic (cats)
O-osteolysis (not common)
N-neoplasia**(very common!)
S-Systemic granulomatous disease

NOTE: most significant levels of hypercalcemia are seen with:

• malignancy/neoplasia
• primary hyperparathyroidism
• vitamin D toxicity

Question 12

What is the number 1 cause of hypercalcemia in dogs?

Answer 12

CANCER!!

1) neoplasia is diagnosed in approximately 2/3 of dogs with hypercalcemia
- lymphoma: 10-35%
- apocrine gland anal sac adenocarcinoma (AGASACA)
- multiple myeloma
- ANY tumor can potentially cause hypercalcemia!

CATS: ~10-30% have hypercalcemia with neoplasia

• lymphoma
• squamous cell carcinoma (usually oral)

Question 13

How do tumors cause hypercalcemia of malignancy?

-Most common cause of pathologic hypercalcemia in dogs and cats**

Answer 13

1) Ectopic production of parathyroid hormone (PTH) or PTH-related peptide (PTH-rp)

Question 14

Clinical signs of hypercalcemia

Answer 14

1) PU/PD*
2) listlessness
3) urinary incontinence (secondary to PU/PD)
4) weakness
5) exercise intolerance
6) inappetence

NOTE: if you can’t find cause for hypercalcemia, remember to do a rectal exam! (AGASACA)

Question 15

Therapy for hypercalcemia

Answer 15

1) IV fluid therapy (0.9% NaCl)
- Saline diuresis (2-3x maintenance): it will increase calcium excretion in kidneys
2) diuretic therapy (furosemide)
- IF and ONLY IF fluid deficits have been replaced
3) glucocorticoid therapy (prednisone)
- IF and ONLY IF diagnosis has been made (prednisone will kill lymphoma cells => makes it hard to get diagnosis!)
4) bisphosphonates: decrease osteoclast resorption

*determine/treat underlying cause of hypercalcemia!

Question 16

Causes of cancer induced hypoglycemia

Answer 16

1) insulinoma (beta-islet cell tumor)
- produce excessive circulating insulin levels
2) non-islet cell tumors associated with PNS hypoglycemia
- hepatocellular carcinoma**(most common)
- hepatoma
- leiomyoma/leiomyosacoma
* most common = liver and small bowel*

Note: rule out other causes - lab error, liver failure, sepsis, hypoadrenocortiscism

Question 17

Hypergammaglobulinemia PNS

Answer 17

1) excessive production of immunoglobulin proteins from MONOCLONAL line of plasma cells or lymphocytes
2) most commonly seen plasma cell tumor (i.e. multiple myeloma), lymphoma
3) non-neoplastic differentials:
- Rickettsial diseases
- chronic granulomatous diseases (systemic fungal infections)

Question 18

Hypergammaglobulinenemia PNS

Answer 18

1) clinical signs:
- hyperviscosity: ataxia, depression, cardiac signs, seizures, coma
- tissue hypoxia
- bleeding (often from mucous areas) due to platelet coating with immunoglobulins
- ocular changes: retinal hemorrhage/detachment

Question 19

DIC

Answer 19

1) ~10% in dogs with malignant tumors

2) especially associated with hemangiosarcoma

Question 20

Cutaneous manifestations of cancer

Answer 20

1) alopecia

2) nodular dermatofibrosis

Question 21

Alopecia as PNS-cats

Answer 21

1) Pancreatic carcinoma*

2) acute, bilaterally symmetric alopecia (ventral, limbs),glistening

Question 22

Neurologic manifestations of cancer

Answer 22

Myasthenia gravis

peripheral neuropathy

Question 23

Myasthenia gravis

Answer 23

1) associated with THYMOMA

2) causes: antibody to acetylcholine receptor/calcium channel

Question 24

Hypertrophic osteopathy

Answer 24

1) associated with primary or metastatic lung tumors**
2) clinical appearance: periosteal proliferation of new bone along the shafts of long bones
- shifting leg lameness, can be quite painful (all 4 limbs affected)