Management of Patients AB 18% Flashcards
(136 cards)
1
Q
Which interleukins send anorexigenic and orexigenic signals?
A
IL1 & IL6 - contribute to cancer cachexia
2
Q
Define cancer cachexia.
A
profound destructive process characterized by skeletal m wasting with or w/o loss of fat mass and harmful abnormalities in fat and CHO metabolism in spite of adequate intake
3
Q
Pathways involved in cancer cachexia
A
NF-kb –> ubiquitin proteasome pathway
TNFa up regulates myostatin (TGFb) that negatively regulates muscle mass
TNFa also interferes with anabolic effects of GH and IGF1
Cell autophagy/lysosomal and Ca2+-dependent protein degradation pathways, ER stress and mitochondrial dysfunction are involved in muscle protein degradation in cancer cachexia
4
Q
Most common cause of paraneoplastic GI ulceration?
A
MCT with histamine the main driver
5
Q
Tx for GI ulceration?
A
H2 blockers, PPIs, misoprostol, sucralfate, rehydration
prophylactically rec for advanced stage disease
6
Q
Tumors associated with hypercalcemia in dog? Cat? (in order of commonality)
A
Dog - LSA (35-55%), AGASACA (25%), MM, parathyroid, thymoma, melanoma, mammary tumors, multiple others
Cat- LSA, SCC, MM, others
7
Q
Tumors associated with hypoglycemia in order of commonality?
A
insulinoma, HCC, leiomyosarcoma/oma, HSA, LSA, lymphocytic leukemia, mammary carcinoma, melanoma, plasma cell, renal adenocarcinoma, salivary adenocarcinoma
8
Q
Tumors associated with hyperestrongenism in order of commonality?
A
Sertoli cell, seminoma, interstitial cell, granulosa cell
9
Q
Cause of acromegaly?
A
pituitary tumor (cat)
10
Q
Which tumor has been associated with paraneoplastic ectopic ACTH release?
A
primary lung tumors
11
Q
Most common cause of hyperglobulinemia?
A
MM
12
Q
What else can cause a monoclonal gammopathy?
other than cancer
A
Leishmania, Erhlichia
13
Q
Most common cause of hypercalcemia in cats (non-neoplastic v. LSA and myeloma)?
A
Options were: neoplasia 33%, idiopathic not listed
- Idiopathic 42%, CKD 35%, neoplasia 13% (LSA most common neoplasia, SCC second most)
- Confusing b/c Withrow – 1/3 (30%) cats w hypercalcemia was from malignancy
14
Q
Tumors associated with pareneoplastic anemia? Thrombocytopenia?
A
LSA, leukemias, HSA, others
same for PLT and hct
15
Q
Paraneoplastic erythrocytosis?
A
renal tumors, nasal fibrosarcoma, laeiomyosarcoma, schwannoma, tvt
16
Q
Paraneoplastic neutrophilic leukocytosis caused by wat cancers?
A
lung tumors, LSA
17
Q
Thrombocytopenia in tumor-bearing dogs typically secondary to?
A
- Chemotherapy
- As high as 36% in tumor-bearing dogs
- 58% in dogs w lymphoid neoplasia
- Also common in vascular splenic tumors
18
Q
% of cats with thrombocytopenia that is cancer related?
A
39% - LSA most common
19
Q
Mechanisms of cancer related thrombocytopenia?
A
- Platelet destruction
- Sequestration
- Consumption
- Decreased production
20
Q
Tumors associated with DIC?
A
- HSA
- inflammatory mammary carcinoma
- pulmonary carcinoma
21
Q
Nodular dermatofibrosis associated tumor?
A
renal cystadenoma/carcinoma
22
Q
Which tumor causes superficial necrolytic dermatitis?
A
glucagonoma
23
Q
Tumors associated with feline paraneoplastic alopecia?
A
pancreatic carcinoma, biliary carcinoma
24
Q
Which tumor can cause exfoliative dermatitis in a cat?
A
thymoma
25
Tumors associated with glomerulonephritis?
primary erythrocytosis, lymphocytic leukemia
26
Which tumor is most likely to cause myasthenia gravis? Others?
thymoma
- OSA, biliary carcinoma, LSA, oral sarcoma
27
Tumors commonly associated with peripheral neuropathy?
insulinoma, lung tumors, mammary tumors
28
Most common cause of HO?
pulmonary metastasis from OSA > primary lung tumor
urinary tract tumors, esophageal tumors
29
Blood work for primary hyperparathyroidism? Most common cause?
- High iCa, normal or high PTH
- functional benign parathyroid adenoma or adenomatous hyperplasia
30
Case presented had increased TCa, increased Crea, N phos, N PTH, USG 1.011 =
inconclusive - either primary hyperparathyroidism or hypercalcemia of malignancy need more info
## Footnote
HARD IONS
31
Mechanism of hypercalcemia in osteolytic lesions (e.g. MM)?
TNF, IL-1, 6, calcitriol
32
Paracrine factors that increase osteoclast # and activity in bony metastasis?
IL1, 6, TNFa/b, RANKL
33
Most common CS of hyperCa in Dogs? Cats?
Dog - PU/PD d/t impaired action of ADH on renal tubular cells of collecting duct
Cat - anorexia, vomiting
34
Blood work for hypercalcemia of malignancy?
- low PTH, high OR normal PTHrp
- calcitriol is expected to be normal but can be high or low
35
When to tx hyperCa of malignancy?
- Always removal of cause or chemo induction if possible
- tCa > 16 mg/dL x phosphate (mg/dL) product > 60
- if p is ill or azotemia
- if p will not respond to sx or chemo
36
Fluid choice for hyperCa of malignancy? Why?
0.9% NaCl - competes with Ca for renal tubular absorption further enhancing calciuresis
37
TX mild hyperCa with minimal CS?
0.9% NaCl rehydration SQ or IV
38
Moderate to severe hyperCa tx?
- 0.9% NaCl over 4-6 hours rehydration then at 100-125 mg/kg/d (1.5-2x maintenance)
- Lasix 2-4 mg/kg q 8-12 IV, SC, PO **ONLY IF HYDRATED**
- Prednisone 1-2 mg/kg q12-24h PO **if diagnosis made**
- Pamidronate 1-2 mg/kg in 250 mL of NaCl IV over 2 hours
or
- Zoledronate 0.1-0.25 mg/kg diluted in 60 mL of NaCl IV over 15 mins
39
Which bisphosphanate is less nephrotoxic, zoledronate or pamidronate?
zoledronate though more (100x) more potent
40
Aminobisphosphonates bine strongly to hydroxyapatite at which site?
R1
- R2 determines amino-BP (ex.zol) vs nonamino-BP (ex. clodronate)
41
MOA of zoledronate?
- Mevalonate pathway --> inhibit farnesyl pyrophosphate
- **interfere with post translational prenylation of GTP-binding proteins (Ras, Rho, and Rac)**
- inhibit bone resorption w/o inhibiting mineralization
- induction of apoptosis net attenuation of pathologic bone resorption
- synthetic analogs of inorganic pyrophosphates with preferential absorption at sites of active remodeling
42
Most common mechanism of hypoglycemia in non-islet cell (insulin secreting) tumors?
IGF-2 secretion
- others: IGF-1 or somatomedins, hypermetabolism of glucose, production of substances stimulating insulin release, production of hepatic glucose inhibitor, insulin binding by monoclonal immunoglobulin, insulin receptor proliferation, ectopic insulin production
43
What is the MOA of hypoglycemia associated with plasma cell tumors?
insulin binding by monoclonal immunoglobulin
44
% of dogs with Sertoli cell tumors with hyperestrogenism?
25-50% - TX by removing tumor
45
TX for hypoglycemia?
- Oral karosyrup–0.5-1.0ml/kg
- 50%dextrose–1ml/kgIV; Maintain with 2.5-5.0% dextrose CRI
- Small frequent meals
- Treat underlying disease
- Low dose glucocorticoids (0.5mg/kg SID)
- Diazoxide, octreotide
46
MOA of steroids for hypoglycemia?
- Increases gluconeogenesis
- Decreases peripheral tissue glucose utilization
47
MOA diazoxide?
- Inhibits insulin secretion
- Increases epinephrine release –-> inhibits glucose uptake by cells
48
MOA octreotide?
Somatostatin analogue that inhibits release of insulin
49
TX for ectopic ACTH secreting lung tumor?
- remove if possible
- Trilostane
50
In MM the M component is most likely to cause monoclonal gammopathy. How does the M component interfere with coagulation?
- coats PLT inhibiting aggregation to damaged endothelial surfaces
- release of PLT factor 3
51
Affects of Bence Jones proteinuria?
light chain tubular casts--> interstitial nephritis and renal failure
52
Causes of hyper viscosity syndrome?
monoclonal gammopathy, polycythemia vera, paraneoplastic erythrocytosis
53
Why is IgM macroglobulinemia most likely to cause hyper viscosity?
high molecular weight pentamer
- in MM the M component is more commonly IgA (dimer) than IgG (monomer); IgA will polymerize
54
TX for hyper viscosity syndrome?
- plasmapheresis if d/t serum proteins
- phlebotomy and IV fluids if d/t erythrocytosis
55
Feline MCT paraneoplastic?
anemia, erythrocytosis
56
What are paraneoplastic syndromes with leiomyosarcoma?
Hypoglycemia, Nephrogenic diabetes insipidus, 2nd erythrocytosis
57
What is paraneoplastic syndrome for TVT?
Erythrocytosis
58
What testicular tumor has a paraneoplastic syndrome and is it reversible?
Sertoli-hyperestrogenism, reverses 1-3months post-op unless mets
59
MOA of paraneoplastic severe leukocytosis?
producing of granulocyte stimulating factor G-CSF and/or granulocyte-macrophage colony stimulating factor GM-CSF
60
Tumors associated with eosinophilia?
- MCT, T-cell LSA via IL-5
61
MOA of heparin release causing clotting issues?
heparin acts as a cofactor for anti-thrombin III to inactivate clotting factors XII, XI, X, and IX
62
Gene associated with nodular dermatofibrosis?
- German Sheperds
- Birt-Hogg- Dube (BHD) gene on chromosome 5
63
TX for nodular dermatofibrosis and renal cystadenocaricnoma?
- none; sx usually not possible as bilateral renal tumors, can consider for ulcerative/painful nodules
- MST 2.5 yr from CS
64
TX for superficial necrolytic dermatitis in dogs with glucagonomas?
- typically limited since most metastatic
- octreotide and AA infusions have been reported
65
MOA acquired paraneoplastic myasthenia gravis?
Ab formed against nicotinic acetylcholine receptors on the postsynaptic sarcolemmal surface within the neuromuscular jxn
66
How to dx myasthenia gravis?
- definitive circulating Ab against AcH receptors
- + edrophonium chloride challange test is helpful in dogs with generalized to support
67
TX for myasthenia gravis?
pyridostigmine bromide - rec. prior to SX and/or RT especially if megaesophagus d/t risk of aspiration
- in recent studies neither MG or megaesophagus affected prognosis in dogs or cats with thymoma but aspiration is a common perioperative morbidity and mortality
68
Most common cause of HO?
Pulmonary mets (OSA), primary lung tumor
if no lung pathology then tumors of urinary system (renal UC, nephroblastoam, botryoid rhabdo, etc)
Cat - renal adrenocortical carcinoma and renal adenoma
69
Non-neoplastic causes of HO?
dirofilaria immitis, bacterial endocarditis, PDA with L to R shunt, spirocerca lupi esophageal granulomas, esophageal FB, congenital megaesophagus
70
CS HO?
swelling and edema of peripheral limbs, lameness, painful/warm to touch, symmetric, serous to mucupurulent bilateral ocular and nasal d/c, respiratory changes
71
TX for HO?
- remove primary tumor if solitary or few mets
- chemotherapy if sensitive tumor
- bisphosphonates
- vagotomy has been described
72
Fever is primarily mediated by?
TNF-a, IL-1, IL-6 on the hypothalamus --> activate arachidonic acid cascade --> prostaglandin E production --> thermoregulatory center
73
DX of paraneoplastic fever?
must r/o other causes (sepsis, infection, etc)
74
TX for fever?
- tx underlying cancer
- NSAIDs and steroids if not cancer directed therapy
75
VCOG LSA response
CR: disappearance of all target lesions (LN)
PR: >30% decrease mean sum
PD : >20% increase in mean sum or relevant new lesion
SD: neither PR or PD
76
Minimum size for consistently measurable LN?
1 cm
77
Minimum single LN increase to warrant PD?
5 mm
78
What is the minimum size of a target single LN pre-treatment to be used to monitor response?
2 cm
- can use sum if using individual LN should not be included for response if <2cm
- minimum of 1 and max of 5 target lesions
79
Direction to measure LN with LSA?
longest diameter
80
What are considered non-measurable lesions?
LN <1cm, bone marrow, hypercalcemia or other lab parameter, effusions, CXR lesions
81
When LN are normal in size/non-palpable which value should be assigned to them?
5 mm
82
What size must a new PLN be to be considered a new lesion representing PD?
1.5 cm
- otherwise likely represents an overlooked lesion
83
Does VCOG recommend bone more assessment at baseline for LSA?
No
- only if significant infiltration e.g. concern for leukemia and going to change TX recommendations
- additional can only be used as a Yes/No in monitoring response to tx (e.g. to confirm a CR)
- only used for PD if new cytopenias developed and then performed otherwise infiltration considered equivocal
84
VCOG follow up recommendations LSA?
monthly monitoring q1 mo for 1.5 years then q2 mo thereafter
85
VCOG solid tumor minimum size recommendations for monitoring?
- tumor 1 cm via caliper long axis with photo documentation
- CT/MRI: 1 cm with maximum slice thickness 5 mm
- CXR: 2 cm
- LN > 1.5 cm **SHORT AXIS**
- U/S: 2 cm (not a preferred modality)
86
Can bone scan be used to measure lesions according to VCOG solid tumor response?
No - only yes/no for lesions
- same for PET-CT
87
Which imaging modality is preferred for response monitoring?
CT > MRI or CXR
88
How to monitor multiple target lesions solid tumors?
create baseline sum of the longest diameter of all lesions and compare
89
Short axis size for a LN to be considered non-pathological?
1 cm
90
VCOG solid tumors response
91
RECIST grade 1-5 general
1: Mild; asymptomatic or mild symptoms; clinical signs or diagnostic observations only; intervention not indicated.
2: Moderate; outpatient or non-invasive intervention indicated; moderate limitation of Activities of Daily Living (ADL).
3: Severe or medically significant but not immediately life threatening; hospitalization or prolongation of
hospitalization indicated; disabling; significantly limiting Activities of Daily Living (ADL).
4: Life-threatening consequences; urgent interventions indicated
5: Death related to AE Death can be defined as either euthanasia or natural death, according to the investigators' discretion.
92
Neutropenia grading
1: lower limits of normal - 1,500
2: 1,000-1,499
3: 500-999
4: <500
5: dead
93
GI tox grading generalities
1: self limiting with outpatient care
2: >24h
3: requires hospitalization
4: life threatening
5: dead
94
Published neutrophil cut off for ABX?
750
95
Prednisone cardiovascular effects?
- reduce capillary permeability and enhance vasoconstriction
96
Prednisone cellular effects?
- inhibit fibroblast proliferation, macrophage response to migration inhibiting factor, sensitization of lymphocytes, and the cellular response to mediators of inflammation
- stabilize lysosomal membranes.
97
Prednisone CNS effects?
- lower the seizure threshold, alter mood and behavior, diminish response to pyrogens, stimulate appetite, and maintain alpha-rhythm
- COMMONLY USED FOR CNS tumors
98
Prednisone endocrine effects?
- suppress the release of ACTH from the anterior pituitary, which reduces or prevents the release of endogenous corticosteroids.
- suppress TSH release
- inhibit osteoblast function
- release ADH
- inhibit insulin
99
Prednisone effect on fluids and electrolytes?
-increase renal potassium and calcium excretion
- sodium and chloride reabsorption
- diuresis
100
Prednisone effect on GI/hepatic system?
- increase the secretion of gastric acid, pepsin, and trypsin
- alter the structure of mucin and decrease mucosal cell proliferation
- Iron salts and calcium absorption are decreased, whereas fat absorption is increased
- increased fat and glycogen deposits in hepatocytes and increased serum levels of ALT, GGT, ALP
101
Prednisone hematopoetic effects?
- increase the number of circulating platelets, neutrophils, and RBCs
- Inhibit PLT aggregation
- Decreased amounts of lymphocytes (peripheral), monocytes, and eosinophils are seen because glucocorticoids can sequester these cells into the lungs and spleen and can prompt decreased release from bone marrow
- Glucocorticoids can cause involution of lymphoid tissue
102
Prednisone immune effect?
- decrease circulating levels of T-lymphocytes
- inhibit lymphokines
- inhibit neutrophil, macrophage, and monocyte migration
- reduce production of interferon
- inhibit phagocytosis, chemotaxis, antigen processing, and intracellular killing
- antagonize the complement cascade
103
Prednisone metabolic effects?
- stimulate gluconeogenesis. - Lipogenesis in abd
- Fatty acid mobilization and oxidation
- Plasma levels of triglycerides, cholesterol, and glycerol are increased
- Protein is mobilized from most areas of the body (not the liver).
104
Prednisone musculoskeletal effects?
- muscular weakness, atrophy, and osteoporosis
- Bone growth inhibited via growth hormone and somatomedin inhibition
- increased calcium excretion, and inhibition of vitamin D activation
- enhanced reabsorption of bone
- Fibrocartilage growth inhibition
105
Prednisone respiratory effects?
- increase the number of beta-adrenergic receptors as well as their binding affinity
- inhibit beta-adrenergic receptor down-regulation, preventing tachyphylaxis and potentiating beta-adrenergic agonist effects on bronchial smooth muscle
106
When should prednisone be avoided?
with NSAID, without diagnosis, if liver disease, DM, acute infection
107
Alternative to prednisone in the event of significant liver disease?
Prednisolone
108
Prednisone uses in oncology?
- Direct cell killing in LSA
- anti-inflammatory
- CNS/nerve tumors
109
Which factor helps optimize APC presentation?
GM-CSF
110
What are hematopoietic GF?
cytokines that regulate the growth, development, and function of hematopoietic lineages
111
Hematopoietic GF to stimulate erythroid lineage development?
EPO, SCF (stem cell factor), IL-3, and GM- CSF
112
Hematopoietic GF to stimulate monocytes lineage development?
IL-3, GM-CSF, G-CSF, and M-CSF
113
Hematopoietic GF to stimulate eosinophil lineage?
IL-3, GM-CSF, and IL-5
114
Which GF stimulate uncommitted progenitor cells such as stem cells and multipotent progenitors?
SCF, IL-3, and GM- CSF
115
GF with growth-promoting and possibly differentiative cytokine with effects on pre-B cells and immature thymocytes?
IL-7
116
Functions of hematopoietic GF?
Direct:
- changes in membrane structure and function
- modulation of receptor expression
- inhibition of migration of the cells being stimulated or affected
Indirect:
- enhanced chemotaxis
- enhanced phagocytosis
- enhanced oxidative metabolism
- enhanced cytotoxicity
- increased arachidonic acid release
- increased leukotriene B4 synthesis
- change in calcium flux and pH within and around the cell
- potentiation of antigen processing
117
EPO uses?
- myelodysplasia
- CKD
- HCT <25% dog, <20% cat
118
EPO risks?
- transform myelodysplasia to overt neoplasia
-can cause anti-EPO Ab resulting in transfusion dependency (less with Darbepoietin)
- pure red blood cell aplasia
119
What is darbepoietin?
hyperglycosylated synthetic human recombinant erythropoietin analogue
- less immunogenic
- issue with all hemoatpotic GF is species specific
120
G-CSF is produced by?
monocyte macrophage cells and by fibroblasts and endo- thelial cells in response to IL-l, tumor necrosis factor, and bacteria
121
What is Neupogen?
- cytokine that primarily increases the proliferation, differentiation, and activation of progenitor cells in the neutrophil-granulocyte line in BM
- human product
122
Neupogen uses?
- severe infection
- BM transplant
- should not be given within 24 hours of chemo
- increase dose intensity by counteracting neutropenia with chemo/RT
- same for GM-CSF but not clinically available as far as I can tell
123
Neupogen risks?
- hypersensitivity
- severe neutropenia from Ag development (less if species specific)
- irritation at injection site
- Bone or musculoskeletal pain, splenomegaly (including splenic rupture), glomerulonephritis, capillary leak syndrome, and hypotension have been reported in human
124
Steroids MOA in pain modulation?
- inhibition of collagenase and pro inflammatory cytokines
- trigger lipocortin and block production of eicosanoids (e.g. prostaglandin)
125
What is the ideal first line treatment for cancer pain?
NSAIDs
126
Differences in toxicity COX 1 vs COX2 inhibitors?
- GI more common with COX 1
- similar with renal & liver
127
MOA grapiprant?
selective EP4 prostaglandin PGE2 receptor antagonist
128
COX 1 selective inhibitors?
Aspirin
129
COX 2 preferential (non-selective) inhibitors? Selective?
- Piroxicam, meloxicam, carprofen
- deracoxib, firocoxib, robenacoxib
130
When is multimodal pain therapy PROVEN to be effective?
Only in immediate operative period however extrapolated to be beneficial for chronic pain
131
Drugs that can result in hypersensitivity?
Doxorubicin, Taxol, Etoposide, L-asparaginase during or shortly after tx
132
TX for hypersensitivity?
- Discontinue infusion
- Ensure patent airway
- Establish vascular access – initial fluids at shock dose if necessary
- Dex-SP at 0.5-2.0 mg/kg IV
- Diphenhydramine at 2 mg/kg IM
- Epineprhine (0.1 to 0.3ml of a 1:1,000 solution) can be given IV or IM if severe
- If reaction was hypersensitivity alone – may be possible to resume infusion once clinical signs subside – give at slower rate
133
What are electrolyte abnormalities with acute tumor lysis?
Hyperphosphatemia, hyperkalemia, hypocalcemia, acidosis, hyperuricemia
134
TX/monitoring for tumor lysis syndrome?
- IV fluid diuresis
- EKG monitoring
- VBG: (K+, Ca2+, PO4-)
- phosphate binder
- hypertonic dextrose/insulin to drive K/P intracellular
- anti-emetics
- may need blood products if DIC
- my need Bicarb supplemenation
135
What is used in humans for acute tumor lysis treatment?
- Allopurinol (xanthine oxidase inhibitor; purine analog)
- Blocks conversion of xanthine/hypoxanthine to uric acid
- ↓ risk of hyperuricemia-induced ARF
136
Who is at increased risk for acute tumor lysis
- Advanced disease / large tumor burden
- High proliferative fraction (hematopoietic tumors)
- Abdominal involvement
- Pre-existing renal insufficiency
- dehydration
- Dalmatians/English Bulldogs (lack uricase)
- Renal clearance is primary mechanism for excretion of P / K /uric acid
