Oncology and Hematology Flashcards
What mutation is a concern in Collie-type breeds?
ABCB1 (mut/mut) phenotype
Name several alkalyating agents?
Chlorambucil (Leukran) Cyclophosphamide (Cytoxan) CCNU (Lomustine) Melphalan (Alkeran) Dacarbazine (DTIC) Ifosfamide (Ifexx) Nitrogen Mustard (Mustargen)
What is the MOA of alkylating agents?
They bind to DNA strands, insert alklyl group and inhibit protein synthesis
Chlorambucil
Cyclophosphamide
CCNU (Lomustine)
What drug can be substituted for cytoxan if hemorrhagic cystitis occurs?
Chlorambucil (Leukran)
Which alkylating agent can result in hemorrhagic cystitis?
Cyclophosphamide (Cytoxan)
Which alkylating agent can result in hepatotoxicity?
CNNU (Lomustine) = Give with Denamarin
What is the MOA of vinca alkaloids?
Plant alkaloids bind to microtubules to prevent normal formation and function of mitotic spindles, thus arresting cell division in metaphase (CELL cycle specific)
Name 3 plant alkaloids.
Vincristine
Vinblastine
Vinorelbine
What is the MOA of antimetabolite drugs?
Interfere with biosynthesis of nucleic acids by substituting them for normal metabolites and inhibiting normal enzymatic reactions
Name 5 antimetabolites.
Methotrexate Fluorouracil (5-FU) Gemcitabine Cytarabine (Cytosar) Hydroxyurea
What is the MOA of DNA cross-linker?
Binding within and between DNA strands and thus inhibiting protein synthesis in cell-cycle nonspecific manner
Name 2 DNA cross-linkers.
Carboplatin
Cisplatin
Why can cisplatin not be used in cats?
CISPLAT = SPLATS CATS
Causes severe pulmonary edema
What is the MOA of antitumor antibiotics?
Inhibition of toposiomerase II DNA synthesis (S phase specific) = Inhibitis DNA synthesis
Which medication can be given with doxorubicin to reduce cardiotoxicity?
Zinecard
Name several antitumor antibiotics?
Doxorubicin
Mitoxantrone
Acrinomycin D
Bleomycin
What is DIC?
Disseminated intravascular coagulation (DIC) → systemic microthrombosis can progress to life-threatening hemorrhage
What are the 4 steps in the pathogenesis of DIC?
- ↑ thrombin production
- Suppression of physiologic anticoagulant pathways
- Impaired fibrinolysis
- Activation of inflammatory pathways
When are tissue factor be expressed?
Monocytes and endothelial cells, circulating during inflammation and on cancer cells
What is the main stimulus for thrombin formation in DIC?
Tissue Fator: VIIa complex (extrinsic pathway)
When does bleeding and hypercaoguable occur during DIC?
Hypercoagulable condition occurs early in the course of DIC and bleeding associated with prolongation of coagulation times occurs later in the course § Consequence of coagulation activation, platelets, coagulation factors, and anticoagulants are consumed, degraded, and/or inhibited
§ Transition from accelerated coagulation to consumption of coagulants and anticoagulants corresponds with the clinical consequences of microthrombosis and vascular occlusion followed by uncontrolled hemorrhage
§ Combos of coagulation-anticoagulation-fibrinolytic-inflammatory derangements exist (depend on underlying cause and coexisting dzs)
What are the 5 general things that are associated with DIC and aid in diagnosis?
o Prolongation of coagulation times
o Reduction in platelet numbers
o Elevation of D-dimer or soluble fibrin
o Decrease in AT activity
o Clinical or postmortem evidence of thrombosis
What test in dogs can exclude DIC as diagnosis, with 95% confidence?
Negative D-dimer test
What are the 4 main goals in treating DIC?
Promoting capillary blood flow, eliminating underlying cause, supporting target organs, replacement therapy, and anticoagulants
What is the MOA of aspirin?
Nonreversible thromboxane-2 inhibitor that decrease platelet aggregation/adhesion
What is the MOA of heparin?
§ Glycosaminoglycan that exerts antithrombotic effect by binding to and potentiating the inhibitory actions of AT on thrombin and factors IXa, Xa, XIa, and TF:VIIa
What forms the hemostatic plug?
Platelet aggregates stabilized by generation of thrombin-mediated platelet fibrin meshwork, trapping PLT and RBCs
Which platelet receptor is important for fibrinogen, fibronectin, and vWF to bind?
GPIIb/IIIa
What 3 things does a BMBT allow you to assess?
Thrombocytopenia, platelet dysfunction, vWD
Which breeds get Glanzmann thrombasthenia?
Otter hound and Great Pyrenees
Abnormal adhesion and clot retraction, aggregation failure, reduced or absent GPIIb/IIIa
What is Chediak Higashi syndrome and which breed gets it?
Persian cats. Lack of dense granules, secretion failure, abnormal platelet aggregation
Name 3 blood products that can supply ACTIVE platelets?
Fresh whole blood, platelet rich plasma, platelet concentrate
What is posttransfusion purpura?
Immune thrombocytopenia in a recipient due to development of high titer alloantibodies that cross-react with the recipients’ platelet antigens
What is a Phase I clinical trial?
Toxicity dose finding
What is a Phase II clinical trial?
Efficacy and responding histologies
What is a Phase III clinical trial?
Comparison to standard of care
What is the suggested percentages of dogs undergoing chemo that will need dose reduction, get life-threatening toxicity, and will die?
Less than 20% need dose reduction (due to hospitalization or severe neutropenia), less than 5% have life-threatening toxicity, less than 1% reis of treatment-related mortality
What is the traditional dosing for chemotherapy?
Based on metabolic body size, body surface area, m2 (smaller animals have high metabolic rate = higher dose)
Which chemo can have cumulative thrombocytopenia?
CCNU
Which chemo can have cumulative cardiotoxicity effects leading to irreversible DCM and CHF and what is the cumulative dose?
Doxorubicin
Cumulative dose above 180 mg/m2
What results in cyclophosphamide resulting in hemorrhagic cystitis?
Metabolite acrolein
Thus give with lasix
Which chemo has irrversible hepatotoxicity?
CCNU
What is a benefit and drawback of pegylated liposomal doxorubicin?
Less cardiotoxicity and myleosuppression, BUT cutaneous toxocity = Palmar and plantar erythrodysesthesia syndrome (mild crusting to severe ulceration)
Which vinca alkaloid is thought to concentrate in lung tissue?
Vinorelbine
Which antimetabolite has been used as a radio-sensitizer?
Gemcitabine
What are the 2 types of radiation therapy that can be used?
· Particulate: has mass and include electrons, protons, neutrons
· Electromagnetic: no mass, made of photons including X-rays and γ-rays
How does radiation work for neoplasia?
· Direct action occurs when photon strikes electron knocking it off creating positive ion. Electron then causes DNA damage. (1/3 of the time)
· Indirect action occurs when electron interacts with water near DNA creating free radicals, which then damage DNA. (2/3 of the time). Oxygen must be present.
· Damage is single- and double-strand breaks of DNA. Single-strand breaks are common, but can be repaired. Double-strand breaks occur more rarely, but usually result in cell death.
How many hours are required for normal tissue to repair single-strand breaks?
About 6 hours
What is fractionation with radiation therapy?
§ Fractionation, delivery of multiple doses of radiation at intervals that allow normal tissues time to repair DNA damage. Each single dose kills the same percent of cells each time, therefore unlikely one large dose is sufficient to kill all tumor cells.
What is a gray?
1 J of energy deposited into 1 kg of mass
What are the acute side effects of radiation?
due to death of stem cell population. Inflammation, ulceration, mucositis, desquamation. These usually resolve in 2 to 3 weeks following treatment. Must provide hydration and nutrition if oral cavity involved.
What are the late side effects of radiation?
slowly proliferating tissues. Endothelial and parenchymal cells die later, these effects permanent. Examples: bowel stricture, cataracts, demyelinating myelopathy, osteonecrosis, KCS, skin fibrosis. Larger doses result in more late effects.
What is the route that soft tissue sarcomas like to met?
Hematogenously
Which tumor can Spirocerca lupi be associated with?
Soft Tissue Sarcomas
For soft tissue sarcomas with incomplete margins what is the recurrence rate in 1 year?
60%
10X more likely to recur with incomplete excision
What factors are associated with survival for soft tissue sarcomas?
Mitotic rate (>20 MF/HPF = 2.6 x more likely to die) Tumor necrosis (>10% necrosis = 2.8X more likely to die) Size, completeness of excision, degree of differentiation, grade, local control
What is the classic signalment for hemangiosarcoma?
Median age of 10 yrs
GSD, Goldens, Labs
What has been changed in animals with hemangiosacromas?
STAT3
Mutation in p53 and PTEN
VEGF
Endostatin (elevated)
What is the most common sarcoma to met to CNS?
Hemangiosarcoma
What is metachronous disease with hemangiosarcoma?
Although no considered metastatic dissemination, 25% of dogs with HSA in one site will have another primary site in second location, called metachronous disease.
What percentage of dogs with splenic nodules have benign nodules?
33-50%
What percentage of dogs with nontraumatic hemoabdomen have neoplasia?
80% neoplasia = Hemangiosarcoma in 70% of these
What are other common sites for hemangiosarcoma?
Spleen, right atrium/auricle, skin, SQ, liver
What is the recommended chemo for hemangiosarcomas?
Doxorubicin +/- cyclophosphamide or vinc
MST 140-202 days
What 2 vaccines have been associated with feline vaccine-associated sarcomas?
Aluminum-adjuvanted - Rabies and FeLV
What has been shown to increased frequency of feline vaccine associated sarcomas?
Increased # of vaccines given at any one time
What is the remission rate and MST for lymphoma?
Remission rate 80-90% NOT curable!
MST 12-14 months
What is the CHOP protocol?
Vincristine, Cyclophosphamide, doxorubicin, and pred for 25 wks
Why is L-asparaginase not always used in CHOP?
§ One study with 115 dogs did not show difference in first remission duration, ORR, OST or toxicity with L-asparaginase. This may be saved for rescue protocols.
What has been shown to have long term remission rates for LSA?
Bone Marrow Transplantation
What factors are associated with prognoses in LSA?
Phenotype (B cell is better than T cell (terrible))
Clinical stage
If a cat has an abdominal mass and we are concerned about LSA, which type should we be most concerned about?
HIGH grade lymphoma
What is the prognosis for high grade and low grade (small cell) gastrointestinal lymphoma in cats?
§ Response to therapy for High Grade GI Lymphoma is poor (CHOP, Doxorubicin, COP)
§ Clinical Response to therapy for Low Grade GI lymphoma is good (Chlorambucil at high and low doses, Prednisone)
What is a prognostic factor for feline gastrointestinal lymphoma?
Grade: Low (small cell) does better than high grade
But most significant prognostic indicator is response to tx
What are the 4 tumors that are implicated in hypercalcemia of malignancy?
§ Lymphoma: 15% of all forms; 40% of mediastinal
§ Apocrine Gland Adenocarcinomas of the Anal Sac
§ Multiple Myeloma
§ Feline Head and Neck SCC
Which type of lymphoma results in hypercalcemia in 40% of patients?
Mediastinal LSA
What are the most common etiologies of paraneoplastic hypercalcemia?
PTHrp (most common)
Vitamin D analog (directly from tumor cells or by renal parenchyma secondary to PTHrp elevation)
If you have hypercalcemia and low phosphorus, this makes what diseases likely?
Primary hyperPTH and HCM
If you have hypercalcemia and high phosphorus, this makes what diseases likely?
Vit D toxicosis
What is recommended to manage paraneoplastic hypercalemia?
Treat the cancer, aggressive fluid therapy (replacement and diuresis), after rehydrated can give Furosemide to promote Na and Ca exchange, glucocorticoids, calcitonin, bisphosphonates, mithramycin and gallium nitrate
In which dog breed are multiple histiocytomas common?
Shar Pei - Spontaneously regress
What is canine Langerhans Cell histiocytosis?
rare, characterized by extensive regional infiltration of histiocytes. Can resemble histiocytoma although rapid systemic metastasis is observed.
What is systemic histiocytosis?
Originally recognized in BMD. It is a generalized histiocytic proliferative disease with marked tendency to involve skin, ocular, and nasal mucosae along with LN.
Name 2 dog breeds that get systemic histiocytosis.
Irish Wolfhound
Basset Hounds
What is the recommended treatment for canine reactive histiocytoses and systemic histiocytosis?
Cyclopsorine (Leflunomide)
What neoplasia develops commonly in Bermese Mountain Dogs?
Histiocytic Sarcoma Complex - Solitary lesions in spleen, LN, lung, BM, skin, subcutis, brain and periarticular tissue. Can start focally and become systemic
What is recommended for treatment of histiocytic sarcoma complex?
Localized - Raditiaton or amputation
If disseminated = CCNU (but response is brief)
What is the most common form of feline histocytic disease?
Feline Progressive Histiocytosis
§ Adult cats: present with skin lesions (solitary or multiple nonpruritic, firm papules, nodules and plaques). Seen on feet, legs and face. Histiocytic infiltrations is noted. Has progressive clinical course limited to skin for extended time (~13 months). Eventually extends beyond the skin.
§ Treatment not successful: Vinc, Vinb, CCNU, L-asparaginase, Steroids, Cyclosporine, Leflunomide, Interferonγ, retenoids, antibiotics. Surgery not successful.
What is the most common nasal tumor?
60% carcinoma and 30% sarcomas (adenocarcinoma, SCC, FSA, CSA, OCA)
What type of dog is at increased risk of developing a nasal tumor?
Dolichocephalic breed
What is the most common feline nasal tumor?
Lymphoma (then carcinoma, followed by sarcoma)
Name 5 prognostic indicators for pulmonary tumors?
- CS at diagnosis
- Solitary nodule
- Peripheral location
- < or > 5 cm
- LN involvement
What is a neoplasia of the pleural space?
Mesothelioma
What is the most common pulmonary neoplasia?
Pulmonary adenocarcinomas
What is the prognosis of pulmonary tumor with surgical removal?
MST 10-13 months
What is the prognosis of mesothelioma?
Poor, with intracavitary chem MST 129-400 days
What disease is associated with mediastinal lymphoma in cats?
FeLV
Which tumor can be associated with myasthenia gravis?
Thymoma
What is the treatment of choice for thymomas?
Surgical excision = can also use radiation (ORR 75%; MST dogs 248 days, MST cats 720)
What is the treatment of choice for mediastinal LSA?
chemotherapy with RT to palliate signs (MST for dogs 6 to 12 months, MST cats 6 to 9 months)
What is a chemodectoma?
Tumor that arises from carotid or aortic body
What type of neoplasia is found concurrently with chemodectomas - up to 50%?
Endocrine neoplasia
What is the most common primary bone tumor?
Osteosarcoma - 75-80% Arise from osteoblasts within metaphysis of long bones
What are the ages that you should consider osteosarcoma?
Older dogs and spike at 2 yrs
What are the main locations of osteosarcoma?
Distal radius, proximal humerus, proximal tibia
What is the biologic behavior of osteosarcoma?
Locally invasive and highly metastatic (lungs)
What is the curative intent for osteosarcoma?
Amputation, limb spare sx with chemo
What are the 2 mainstays for chem with osteosarcoma?
Doxorubicin and Carboplatin
What are the current recommendations for OHE to prevent mammary cancer in dogs and cats?
Before 2.5 yr dog and 1 yr in cat
What 3 dog breeds are over-represented for mammary tumors?
Springers, Spaniels, and Poodles
If a mammary mass is found on a dog what are the chances that it is malignant?
50% and of these 50% will have mets (sarcoma and inflammatory carcinomas = WORST)
What are the 4 factors that can affect prognosis in canine mammary tumors?
< or > 3 cm, nodal metastasis, complete excision, histologic grade
If a mammary mass is found on a cat what are the changes that it is malignant?
80-96%!!! Met to LNS (25-100%) - Adenocarcinomas
What is the most reliable prognostic indicator for feline mammary tumors?
SIZE, if > 3 cm = 12 months, and if < 3 cm = 21 months
Which breed is at risk of TCC?
Scottish Terriers
What adjuant to chemo is suggested for TCC?
Piroxicam (MST 109 days) with carboplatin (MST 291days)
Which tyrosine kinase is found on MCT?
cKit - Dogs with mutation have higher rates of mets and recurrence
What 3 canine breeds are over-represented for MCT?
Boxer, Boston Terrier, English bulldog (benign) Shar Peis (more aggressive tumors)
What is a Darier’s sign associated with a MCT?
waxing and waning due to degranulation.
What is the grading scheme used for MCT?
Patnaik grading scheme
· Grade I: benign, excision usually curative.
· Grade II: many cured with wide surgical excision, can follow with RT (cure for 80% of patients).
· Grade III: biologically aggressive. MST 18 weeks. Oral cavity, nail bed, inguinal, preputial, perneal regions may be more malignant. Disseminated form carries grave prognosis. Ki-67 staining maybe marker for behavior. Mitotic index greater than 5 carries poorer prognosis
Dogs that have gross MC disease should be on which 2 drugs?
Diphenhydramine and H2 antagonist or PPI
What is the most common oral tumor?
Malignant melanoma
What types of melanomas behave malignantly?
Oral and digital
What are negative prognostic factors for oral malignant melanoma?
Narrow, incomplete sx margins, location (caudal), mitotic index > 3, bony invasion/lysis
What 2 stains have been sued to predict the behavior of cutenaous melanoma?
Ki-67 and AgNOR
What are treatment options for malignant melanoma?
Local control = Sx and RT
Systemic = Chemo (Carboplatin) and vaccine??
What are potential treatment options for anal sac tumors?
§ Surgery: best option. Will always come with narrow margins. Lymph node extirpation should also be included if noted to metastatic. Complications can include infection and fecal incontinence. Surgery alone: recurrence rate of 50%. MDFI 10 months. Dogs that have surgery have significantly longer survival times.
§ Surgery + Radiation Therapy: Significant acute side effects, late can also be severe (rectal strictures). MST 31 months
§ Surgery + Chemotherapy: Melphalan MST 20 months
§ Chemotherapy alone: MST 7months (actinomycinD, cisplatin, carboplatin, doxorubicin)
§ Palliative Treatments: Pamidronate for the treatment of hypercalcemia, lactulose, psyllium.
Why are feline RBCs more sensitive to oxidative damage?
High number of thiol (SH) groups = Prime target for oxidative damage
Less glutathione
What is different about the feline spleen that allows for free passage of Heinz Bodies?
Nonsinusoidal spleen
What are causes of Heniz body anemia in cats?
- Drug induced - Acetaminophen, profopol (repeated dosing)
- Diet-induced: Onions, propylene glycol (food additive), garlic
- Disease induced: DKA, hyperT4, neoplasia (LSA)
What should be considered for Heniz body anemia in cats?
Antioxidant therapy - Restore depleted glutathione (esp with acetaminophen) = N-acetylcysteine (Mucomyst)
In what disease do over 50% of cats develop poikilocytosis?
Hepatic dz = Acanthocytes
What drug can induce poikilocytosis in cats?
Doxorubicin
What should you consider if a cat has a high MCV and with no polychromasia?
FeLV infection
What is the Pelger-Huet anomaly?
Granulocyte nuclear hyposegmentation in presence of mature nuclear chromatin - Degenerative left shit appearance only affected neutrophil function in one foxhound
Akita RBCs are….
Microcytosis
Miniature Poodle RBCs are…..
Macrocytosis
What is the life span of a dog and cat RBCs?
Dog = 100-120 days Cat = 70-75 days
Which breed has “leaky” in vitro RBCs resulting in pseudohyperkalemia?
Akitas
What dog breed and 2 cat breed have increased osmotic fragility to their RBCs?
English Springer Spaniel
Abyssinian and Somali cats
What dog breed gets pyruvate kinase (PK) def?
Basenjis, WHWT, Beagles
What dog breed gets phosphofructokinase (PFK)?
English Springer Spaniel and Cocker Spaniel
What happens in dogs with PFK deficient RBCs?
Hemolytic crises and exertional myopathy
Which breed gets Pelger-Huet?
Australian Shep - Failure of PMN nucleus segmentation (but normal function)
