Hemangiosarcoma

Question 1

Recent molecular data suggests that HSA arises from ___ rather than from malignant transformation of mature peripheral endothelial cells

Answer 1

bone marrow progenitor cells that undergo dysregulated maturation

Question 2

Mutations in ____ and ____ have been shown in the pathogenesis of angiosarcoma in mic and humans but are infrequent in canine HSA

Answer 2

p53 and Ras

Question 3

What key growth and apoptosis regulating proteins are overexpressed in HSA compared to hemangiomas or normal tissues

Answer 3

pRB, cyclin D1, Bcl2 and survivin

Question 4

Two large studies have shown _____ of dogs with splenic tumors have malignant disease and ______ of these are HSA

Answer 4

50%; 50-74%

Question 5

What IHC can be used to support diagnosis of HSA and rule out other sarcomas

Answer 5

CD31/platelet endothelial cell-adhesion molecule von Willebrand’s factor (factor VIII-related antigen)

Question 6

What RBC changes are common in dogs and cats with HSA

Answer 6

schistocytes, acanthocytes and nRBCs

Question 7

Thrombocytopenia is found in _____% of HSA

Answer 7

75-97%

Question 8

Alterations in secondary coag parameters (PT and PTT, fibrin degradation product, fibrinogen and d-dimers) are found in nearly _____% of patients with HSA

Answer 8

50%

Question 9

More than 50% of cats with HSA may have elevations in this chemistry value

Answer 9

AST

Question 10

What are the “T” classifications for HSA

Answer 10

0 = no evidence of tumor T1 = tumor <5cm diameter and confined to primary tissues T2 = tumor ≥5cm, or ruptured or invading into SQ tissues T3 = tumor invading adjacent structures including mm

Question 11

What are the TNM stages for HSA

Answer 11

I = T0 or T1, N0, M0 II = T1 or T2, N0 or N1, M0 III = T2 or T3, N0, N1 or N2, M1

Question 12

What is significantly elevated in dogs with cardiac HSA compared to HSA at other sites, dogs with other cancers, etc

Answer 12

cardiac troponin-1 also higher for HSA pericardial effusion vs. non-HSA pericardial effusion

Question 13

What is the MST for dogs with cardiac HSA treated with hypofractionated RT?

Answer 13

MST 2.5mo + decreased frequency of cardiac tamponade

Question 14

The original eBAT trial showed what?

Answer 14

MST 8.5mo, 6-mo survival of 70.6% (treatment before standard of care dox), six long term survivors All dogs were stage I or stage II

Question 15

What is the MST for dogs with stage I splenic HSA treated with surgery + chemo?

Answer 15

MST 239-355d

Question 16

What is the MST for dogs with stage II splenic HSA treated with surgery + chemo

Answer 16

MST 120-148d

Question 17

MST for dogs that were treated with surgery + thalidomide for splenic HSA? What was the 1yr survival rate? (Bray JSAP 2018)

Answer 17

MST 172d

33% of dogs alive >1 yr post-op (range 458-660d)

Question 18

For dogs with splenic HSA treated with thalidomide, what was prognostic for survival? (Bray JSAP 2018)

Answer 18

Stage II better than stage III (303d vs. 40d)

Question 19

What was the affect of yunnan baiyao and aminocaproic acid in dogs with right atrial masses for number of pericardiocenteses performed and the rate of recurrence of signs? (Murphy JVECC 2016)

Answer 19

No difference in treated dogs (YB alone or YB +AA) compared to pericariocentesis only dogs for number needed, recurrence of signs or MST

Question 20

What did yunnan biayo cause in HSA cell lines?

Answer 20

Dose and time dependent cell death through initiation of caspase-mediated apoptosis

No sig. changes in VEGF levels

Question 21

How was the HSA tumor vaccine made and what was the dosing schedule? (U’Ren JVIM 2007)

Answer 21

Lysates of allogeneic HSA cell lines mixed with adjuvant of liposome-DNA complexes

8 vaccines over 22wks

Question 22

What was the outcome in dogs treated with the HSA tumor vaccine? (U’Ren JVIM 2007)

Answer 22

Dogs mounted strong Ab responses

MST 182 days for stage II HSA treated with vaccine + doxo

Question 23

Yunnan Baiyao increases apoptosis in HSA cell lines by what mechanism (Wirth VCO 2014)

Answer 23

by caspase 3/7 and TUNEL

Question 24

What is L-MTP-PE and what cancer type was it investigated in? (Vail, Clin Can Research 1995)

Answer 24

Liposome-encapsulated muramyl tripeptide phosphatidylethanolamine adjuvant immunotherapy - synthetic derivative of bacterial cell wall - increases monocyte tumoricidal activity and increases TNF alpha and IL6

HSA

Question 25

What is e-bat? \*\*Borgatti VCO 2020

Answer 25

EGF bispecific angiotoxin

Question 26

What was the outcome for dogs treated with eBAT 1-wk post splenectomy and 1wk prior to dox 1, 2, 5th chemo? \*\*Borgatti\*\* VCO 2020

Answer 26

No survival benefit for eBAT treated dogs compared to contemporary comparison of dogs with stage 1-3 HSA treated with surgery + dox

Question 27

What was the MST for dogs with stage 1 or 2 splenic HSA treated with anthracycline chemo and/or metronomic chemo after splenectomy? (Treggiari VCO 2019)

Answer 27

Antracycline: 154d Anthrcycline followed by metronomic 338d Metronomic alone 225d Not statistically different

Question 28

What was the MST for stage III HSA treated with maximal tolerated chemo vs. metronomic vs. splenectomy alone? (Marconato VCO 2019)

Answer 28

MTD ST 140d MC 58d sx alone 40d

Question 29

What was the mst for dogs with HSA (any stage) with maximally tolerated chemo (doxorubicin or ctx) vs. MTD chemo followed by metronomic cytoxan (Alexander JSAP 2018)

Answer 29

No stat difference MST for MTD chemo = 180d MST for MTD chemo + metronomic = 212d

Question 30

In the Finotello VCO 2016 study, dogs treated with doxo followed by metronomic chemo had a significantly longer MST (not reached) than dogs with doxo alone (168d). What was different about this metronomic protocol compared to other studies?

Answer 30

70% of dogs also on thalidomide for metronomic - Bray study suggests thalidomide after surgery have a better MST

Question 31

Doxorubicin combined with what other chemotherapy improved MST for dogs with HSA compared to doxo/cytoxan (Finotello VCO 2015)

Answer 31

DTIC (dacarbazine) MST 550d Dox/Cytoxan = 100-150d

Question 32

What was the MST for dogs treated with surgery alone for splenic HSA? What was prognostic? (Wendelburg JAVMA 2015)

Answer 32

1.6mo Stage prognostic

Question 33

What was the MST for dogs treated with splenectomy + dox followed by continuous Palladia for stage I or II HSA? (Gardner BMC 2015)

Answer 33

MST 172d - no improvement compared to sx+dox alone

Question 34

Was doxorubicin or doxil (liposome encaspulated dox) more effective for adjuvant therapy for splenic HSA in dogs? (Teske VCO 2011)

Answer 34

trick question - no difference b/w treatment groups

Question 35

What were the unique AEs associated for doxil in dogs with HSA compared to those treated with doxo? (Teske VCO 2011)

Answer 35

desquamating dermatitis like palmar-plantar erythrodysesthesia (PPES) was seen in two dogs, while three other dogs showed anaphylactic reactions.

Question 36

What was the MST for dogs treated with splenectomy + epirubicin for HSA? Why might this not be better than dox? (Kim JAVMA 2007)

Answer 36

MST 144d, but 7/18 dogs hospitalized for GI AEs (higher than rate for doxo)

Question 37

What was the result in dogs treated with ifosfamide alternating with dox for HSA? (VCO 2003)

Answer 37

No imporvement in MST (149d.)

Question 38

What is the DAV protocol for HSA? (Dervisis JAAHA 2011)

Answer 38

Doxo + DTIC day 1 Vinc d. 8 and 15 repeat

Question 39

What was the ORR and MST for dogs with stage II and II HSA treated with DAV? (Dervisis JAAHA 2011)

Answer 39

RR 47.4% (CR in 5) MST 125 days

Question 40

What was associated for a better outcome in dogs with stage II or III HSA treated with DAV? (Dervisis JAAHA 2011)

Answer 40

Needing a dose reduction in dacarbazine

Question 41

What is the VAC protocol for HSA? (Alvarez JAAHA 2013)

Answer 41

Day 1 doxorubicin day 8 vinc day 10 ctx day 15 vinc dogs on TMS at all times

Question 42

What was the ORR response and MST for dogs treated for HSA with VAC?

Answer 42

ORR 86% - no difference in survival between stage I/II (189d) vs. stage III (195d) - may be better for advanced stage HSA?

Question 43

What was the ORR and MST for dogs with presumed cardiac HSA treated with doxorubicin (Mullin VCO 2014)

Answer 43

ORR 41% MST 116d

Question 44

What was the MST for dogs with cutaneous HSA (Nobrega J Comp Path 2019)

Answer 44

12mo - study didn't mention differences for stages (ie. cutaneous vs. sq vs. mm)

Question 45

What IHC labeling was associated with OS in dogs with cutaneous HSA (Nobrega J Comp Path 2019)

Answer 45

trick question - none of the ones looked at had an impact on OS (FVIII, COX2, VEGF, PCNA and Casp-3)

Question 46

What was the MST for dogs with dermal HSA treated with surgical excision (Szivek VCO 2011)

Answer 46

MST 987d Dogs with predisposition (whippets, pitties, it greyhound, etc) better (1570d) than non-predisposed breeds (593D)

Question 47

What were positive prognostic factors for survival in dogs with dermal HSA? (Szivek VCO 2011)

Answer 47

Predispose breed, solar induced, ventral abdomen

Question 48

What was the ORR for dogs with nonresectable HSA treated with doxorubicin? What improved this? (Wiley VCO 2010)

Answer 48

ORR 38.8% Dogs that had complete sx excision after neoadjuvant chemo did better (207d vs. 83d)

Question 49

What were prognostic factors for OST in dogs with SQ or IM HSA? (Shiu JAVMA 2011)

Answer 49

adequate local control \<4cm size mets at dx gross disease

Question 50

**What other than cardiac neoplasia, what is a dx for nontraumatic hemothorax? (Rutherford JAAHA 2016)**

Answer 50

**Intrathoracic, extracardiac HSA** **Surgery can be palliative - 1 dog alive 1mo post-op, 1 alive 5mo, 1 euthanized on table because not resectable**

Question 51

What was the MST for dogs with right atrial masses + pericardial effusion treated with doxorubicin alone? (Ghaffari JSAP 2014)

Answer 51

MST 139.5d.

Question 52

What was the MST for dogs treated with nephrectomy +/- adjuvant chemo for renal HSA? (Locke JVIM 2006)

Answer 52

MST 278d, maybe better location for HSA

Question 53

What is the MST for lingual HSA? What was prognostic?

Answer 53

MST 533d - all low or intermed grade positive prog = small size, absence of clinical signs

Question 54

What 4 predictors were used to calculate the risk score for HSA for dogs presenting with hemoabdomen? (Schick JVECC 2019) \*\*Committee member\*\*

Answer 54

weight plasma protein platelet counts CXR findings

Question 55

What was the incidence in low, medium or high risk groups based on the HELP score for dogs presenting with hemoabdomen? (Schick JVECC 2019) \*\*committee member\*\*

Answer 55

Low: 36% medium 76% high 96%

Question 56

What PET CT better at staging/monitoring dogs with HSA? (Borgatti PLoS one )

Answer 56

9 dogs - also getting eBAT pet CT found two lesions that weren't found on routine imaging + they were larger with higher metabolic activity on second scan

Question 57

What characteristic on CT may be different for nonparenchymal HSA compared to other STS? (Fukuda VRU 2014)

Answer 57

Presence of intense foci of contrast enhancement (13/17 dogs with HSA) - not typical for other STS

Question 58

What is the rate of cardiac masses in dogs presenting with splenic HSA? (Boston JAAHA 2011)

Answer 58

8.7%

Question 59

What was the rate of a concurrent splenic HSA in dogs with cardiac HSA? (Boston JAAHA 2011)

Answer 59

29% 42% had mets to other site as well

Question 60

What marker was higher in dogs with HSA than normal dogs, but was not different in dogs with a hemoabdomen for HSA vs. benign causes of hemoabdomen? (Thamm VCO 2011)

Answer 60

Serum Thymidine Kinase 1

Question 61

**What ultrasonographic feature of the spleen is suggestive of malignancy in cats? (Bertal JFMS 2017)**

Answer 61

**The presence of a splenic mass \>1cm on AUS**

Question 62

**What appearance on AUS of the spleen was NOT correlated with the presence of malignancy in cats? (Bertal JFMS 2017)**

Answer 62

**Moth-eaten appearance**

Question 63

What was the MST for cats with cutaneous HSA? (McAbee JAAHA 2005)

Answer 63

Majority SQ MST \>1460 days with surgery (only 60d w/o)

Question 64

**What are the most common clinical signs for cats with visceral HSA? (Culp JVIM 2008)**

Answer 64

**Lethargy, anorexia, respiratory difficulty, collapse**

Question 65

**The majority of cats (82%) had what abnormality on CBC? (Culp JVIM 2008)**

Answer 65

**Anemia**

Question 66

**What was the rate of lung metastasis in cats with visceral HSA (Culp JVIM 2008)**

Answer 66

**33% lung mets**

Question 67

**What was the rate of multifocal disease (and where was it) in cats with visceral HSA? (Culp JVIM 2008)**

Answer 67

**Overall 77%** **Liver 35%** **SI 31%** **LI 31%** **Abd LN, mesentery, spleen 23%** **brain 8%**

Question 68

**What was the MST for cats with visceral HSA (Culp JVIM 2008)**

Answer 68

**Most euthanized w/in 1 day of dx** **For those that weren't, MST 77d**

Question 69

What has been associated with shorter survival times in cats with HSA (Visceral or cutaneous) (Johannes JAVMA 2007)

Answer 69

MI \>3/10hpf

Question 70

**What factors were associated with survival time (on univariate) analysis in dogs with stage II splenic HSA treated with sx + chemo? Also, what chemo was used? (Moore JAVMA 2017)**

Answer 70

**Chemo was combination of CCNU + either doxo (25), mito (4) or epirubicin (1) +/- metronomic CTX (5)** **Factors on univariate: MI, Tumor differentiation, histo grade CCNU dose, metronomic chemo**

Question 71

**What factors were associated with survival time (on multivariate) analysis in dogs with stage II splenic HSA treated with sx + chemo? (Moore JAVMA 2017)**

Answer 71

**MI only signficant factor - score 0 or 1 better than ≥2** **Score 0 = \<11 MI (MST 292d, 1yr survival 42%** **Score 1 = 11-20 MI, MST 212d** **2 = 21-30, MST 118d** **3 = \>30, MST 116d**

Question 72

**What was the overall MST and 1yr survival rate for stage II HSA treated with splenectomy + CCNU based chemo in dogs? (Moore JAVMA 2017)**

Answer 72

**MST 158d, 1yr survival 16%**

Question 73

What is the problem with CD31 IHC for differentiating HSA from other nonendothelial tumors? (Ramos-Vara, Vet Path 2018)

Answer 73

Has cross-reactivity with other tumor types (plasmacytoma, AGASACA, carcinoma) and normal tissues

Question 74

What were the IHC characteristic of canine angiosarcoma? (Bertazzolo Vet Clin Path 2005)

Answer 74

IHC majority positive for both CD31 and FVIII-related Ag

Question 75

What are the growth patterns of HSA and what is their influence on survival in dogs? (Goritz J Comp Path 2013)

Answer 75

Cavernous, capillary or solid NOT PROGNOSTIC

Question 76

What was the incidence of metastatic HSA in dogs with grossly abnormal appearing livers at time of splenectomy? (Clendaniel JAAHA 2014)

Answer 76

50% If grossly normal, no dogs had mets

Question 77

What gross liver apperance was highly associated with metastatic HSA in dogs undergoing splenectomy for HSA? (Clendaniel JAAHA 2014)

Answer 77

Multiple nodules, dark colored nodules, bleeding nodules

Question 78

What was the response to HSA cell lines treated with TRAIL? (Goto VCO 2019)

Answer 78

TRAIL = tumor necrosis factor-related apoptosis-inducing ligand 2 recombinant human TRAILS decreased cell viability some increased caspase 3 and 8 leading to ADP ribose polymerase degredation and apoptosis

Question 79

What pathway dos resveratrol activate in canine HSA cell lines and what was the result? (Carlson VCO 2018)

Answer 79

Activated p38 MAPK pathway --\> inhibited growth, induced apoptosis, augmented doxo effects \*\*did not impact AMPK or ERK1/2 pathways\*\* Resveratrol is a stilbenoid, a type of natural phenol, just btdubs.

Question 80

What cancer cells were found to express procoagulant tissue factor (TF) (Witter AJVR 2017)

Answer 80

Canine HSA cell lines

Question 81

What is tetrathiomolybdate (TM) and what does it do to canine HSA cells? (Sloan AJVR 2017)

Answer 81

TM = copper chelator Dox + TM --\> greater decrease in proliferation and survival rates than each drug alone; also increased ROS formation and apoptosis

Question 82

Suppressing what with small interfacing RNA promoted apoptosis in HSA cell lines suggesting it may paly an important cytoprotective role (Anwar J Comp Path 2016)

Answer 82

Peroxiredoxin 6 (PRDX6)

Question 83

Big endothelin-1 has 100% sensitivity and 95% specificity for ____ (Fukumoto Vet J 2015)

Answer 83

canine HSA

Question 84

Serum VEGF is significantly higher or lower in dogs with spelnic masses compared to those without. Also, what is the difference between serum VEGF b/w hematoma and HSA? (Frenz Res Vet Sci 2014)

Answer 84

VEGF higher in dogs with splenic masses, but NO difference between hematoma and HSA

Question 85

Concentration of _____ is 9.5x higher in dogs with metastatic HSA compared to heatlhy dogs. It is also elevated in dogs with OSA, LSA, carcinoma and inflammatory disease, but to a lower amount than HSA (Kirby JVIM 2011)

Answer 85

liopcalin region of collagen 27alpha1 in serum

Question 86

What PTEN mutations have been detected in canine HSA? (Dickerson Vet Path 2005)

Answer 86

point mutations or deletions in c-terminal domain of PTEN

Question 87

What were the affects of masitinib on canine HSA cell lines? (Lyles VCO 2012)

Answer 87

Dose and time dependent decrease in cell proliferation Induced apoptosis by activating caspase 3/7

Question 88

What markers can differentiate HSA and lymphangiosarcoma? (Halsey VCO 2014)

Answer 88

LYVE-1 and PROX-1 (specific for lymphatic endothelial cells)

Question 89

What chromosomal abberations have been identified in HSA? (Thomas and Modiano Csome res 2014)

Answer 89

CDKN2A, VEGFA and SKI

Question 90

In small-breed dogs with nodular splenic lesions, what was the incidence of HSA? Fernandez JAAHA 2019

Answer 90

27%

Question 91

In small breed dogs with splenic nodules, presence of what was associated with malignancy? Fernandez JAAHA 2019

Answer 91

Hemoabdomen - present in 31% of dogs, 66% of which had malignant lesions

Question 92

Of small breed dogs with splenic nodules, what breeds were most common and positively assoc with malignancy? Fernandez JAAHA 2019

Answer 92

Mini schanuzers, dachshunds beagles most common, beagles assoc' with malignancy

Question 93

What factors were associated with a higher likelihood of HSA in dogs regardless of their size? (Sherwood, JAAHA 2016) \*\*committee member\*\*

Answer 93

pre-op anemia, hemoabdomen, thrombocytopenia, blood transfusions

Question 94

What was the difference in odds of having a malignant splenic lesion or HSA in small dogs vs. large dogs undergoing splenectomy? (Sherwood JAAHA 2016) \*\*committee\*\*

Answer 94

No difference in overall odds of malignancy but large dogs significantly more likely to have HSA compared to small dogs

Question 95

What was the rate of HSA vs hematoma for nontraumatic hemoab in dogs? (Aronsohn JAAHA 2009)

Answer 95

63.3% HSA, 26.6% hematoma (others = splenic torsion, HCC and carcinomatosis)

Question 96

**Small dogs with spontaneous hemoabdomen are more likely to have bleeding from _____ compared to large dogs (Fleming Vet Surg 2018)**

Answer 96

**Liver and other sites - retroperitoneal mass, kidney, adrenal (vs majority spleen in large dogs)**

Question 97

**HSA associated with splenic bleeding occurs more commonly in small/large dogs (Fleming Vet Surg)? What are the other size more likely to have hemoab from?**

Answer 97

**Large** **HCC, LSA, adrenal tumors, OSA, renal carcinoma - ie. not spleen**

Question 98

**What was the difference in DFI for dogs with HSA treated with surgery that received a blood transfusion vs. those that did not? (Ciepluch Vet Surg 2018)**

Answer 98

**Dogs w/blood transfusion 76d (1-836) vs. w/o 120d (38-916) but confounding factors present**

Question 99

What risk factors were identified for dogs undergoing splenectomy? (Wendelburg JAVMA 2014)

Answer 99

Each decrease of 10,000 plt = odss of death increase by 6% PCV \< 30% odds of death 2x higher than if \>30 Intraoperative arrhythmias increase risk of death 2x

Question 100

What was the response to HSA cell lines treated with TRAIL? (Goto VCO 2019)

Answer 100

TRAIL = tumor necrosis factor-related apoptosis-inducing ligand 2 recombinant human TRAILS decreased cell viability some increased caspase 3 and 8 leading to ADP ribose polymerase degredation and apoptosis

Question 101

What gross liver apperance was highly associated with metastatic HSA in dogs undergoing splenectomy for HSA? (Clendaniel JAAHA 2014)

Answer 101

Multiple nodules, dark colored nodules, bleeding nodules