SA oncology

Question 1

How are solid tumours clinically staged?

Answer 1

TNR classification
T: primary tumour
- clinical exam
- location and palpable extent (well demarcated?)
- fixation to deep tissues, skin
- ulceration
- histological diagnosis (biopsy or FNA)
- diagnostic imaging
N: metastatic disease in local and regional lymph nodes
M: distant metastatic disease

Question 2

Difference between tumour stage and grade?

Answer 2

Stage: tumour burden and sites involved
Grade: histological features of tumour

Question 3

What is the gold standard for cancer diagnosis?

Answer 3

Histopathology

Question 4

Advantages and disadvantages of cytology for cancer diagnosis?

Answer 4

Relatively non-invasive
Often requires minimal restraint
Minimal tissue disruption
Rapidly performed
Rapid results
Cheaper
No architectural detail
Small numbers of cells examined- representative?
Limited assessment of tumour type/grade

Question 5

Advantages and disadvantages of histopathology for cancer diagnosis?

Answer 5

More invasive
GA (or sedation) required
Moderate tissue disruption
More time consuming
Delay in results
More expensive
Architecture apparent
Larger sample size - more representative
More accurate tumour type/grade

Question 6

Biopsy techniques for cancer diagnosis?

Answer 6

Needle core biopsy
Incisional biopsy
Surface and pinch biopsies
Punch biopsies
Excisional biopsy

Question 7

Risks of biopsy?

Answer 7

Haemmorrhage
Transplantation of tumour cells
Compromise of future surgery
Damage to adjacent structures

Question 8

Needle core biopsy - how?

Answer 8

Cylinder of tissue is removed from the lesion by a specialised needle
Ultrasound guidance very useful
Adequate restraint
Trucut needles - two handed operation, need assistance, can be cold sterilised
Cook’s/Arnolds biopsy needles - semi automated, can be cold sterilised
Clip, prepare site aseptically
Make small stab incision in skin (essential to not blunt needle)
Immobilise mass and introduce needle
Once embedded, advance central obturator, rotate through 90 degrees, briskly advance outer cannula over central obturator, remove from mass
Flush sample from notch with saline

Question 9

Advantages and disadvantages of needle core biopsies?

Answer 9

Advs:
- larger sample than aspirate
- comparatively inaccessible tissues can be accessed percutaneously
- multiple samples can easily be taken
- superficial lesions can be biopsied under sedation and local anaesthesia
Disadvs:
- small sample size compared to other biopsies (still might not be sufficient to view architectural change)
- greater risk of complications compared to FNA
- not good for lymph nodes (insensitive to metastatic disease, inadequate for architectural assessment in lymphoma)

Question 10

What is used for a bone core biopsy? What must be done/not done?

Answer 10

Jamshidi needle
Do not penetrate far cortex - risk of pathological fracture
Take multiple samples

Question 11

Advantages and disadvantages of incisional biopsies?

Answer 11

Advs:
- good evaluation of architecture
- histopathological grading
- surgical approach allows selection of biopsy site
- more tissue - can carry out special stains etc
Disadvs:
- GA normally required
- increased time
- both increase costs

Question 12

What is the most common technique used for incisional biopsies? Rules?

Answer 12

Inverted wedge - easy closure
Plan your site
Sample selection
Avoid major structures
Avoid necrotic, haemorrhagic or infected areas
Position incision and biopsy so that entire biopsy tract can be removed during subsequent surgery
Make the incision large enough to harvest the sample without excessive tissue manipulation
Minimise instrumental manipulation of biopsy
Avoid diathermy, cryosurgery etc
Include a portion of normal tissue only if easy to do so
Ensure adequate fixation - serially section large samples

Question 13

Surface pinch and grab biopsies - used for? how?

Answer 13

Accessible surfaces - resp tract, GIT, urogenital tract
Direct visualisation
Endoscopy
Blind
Laparoscopy/thoracoscopy
GA often required
Very small biopsies - always take multiple

Question 14

Punch biopsies - used for/not used for? How?

Answer 14

Cutaneous and other superficial lesions only
Not for lymph nodes
Sedation (+/- local)
Rotate punch continuously in same direction so don’t shear layers apart

Question 15

What is excision biopsy?

Answer 15

(Attempted) surgical extirpation of a lesion or mass, followed by removal of biopsies from it for histopathological evaluation or submission of whole sample if possible
Often results in inadequate excision
Only used when knowledge of tumour type will not affect surgical dose
Widely used in treatment of skin tumours
All excised tumours should be submitted for histopathology - assess margins

Question 16

Contraindications for excision biopsy for skin and s/c masses?

Answer 16

Rapidly growing masses
Ill defined or poorly demarcated lesion
Peritumoural oedema or erythema
Skin ulceration
Injection site masses in cats
FNA suspicious of MCT or STS
Non diagnostic FNA

Question 17

What percentage of bone mineral content must be lost for lysis to be apparent on radiographs?

Answer 17

> 60%

So lack of obvious lysis doesn’t mean no bony involvement

Question 18

Which lymph node enlargement may be seen on a lateral thorax radiograph?

Answer 18

Suprasternal
Cranial mediastinal
Tracheobronchial
Only moderate-marked enlargement detectable

Question 19

Which lymph node enlargement may be seen on an abdominal radiograph?

Answer 19

Medial iliac (sub lumbar) 
Very unlikely to detect enlargement of mesenteric nodes unless massively enlarged

Question 20

What is lymphangiography used for?

Answer 20

Detection of sentinel nodes
Inject contrast into the tumour to find out which nodes drain it
Doesn’t tell you if they are affected by metastases
Only tells you which are draining nodes

Question 21

FNA for lymph nodes?

Answer 21

More sensitive than palpation or needle core biopsy
Not infallible - can have negative aspirates from positive node
Use needle only technique

Question 22

Which lymph nodes do tumours metastasise to?

Answer 22

Most which spread by the lymphatic route go to the nearest node towards the centre of the body (ie towards the thoracic duct)
Cranial abdominal tumours can metastasise to the retropharyngeal lymph nodes
Metastases can skip a node
Lesions on the distal forelimb metastasise to the prescapular rather than the axillary lymph nodes
Lesions on the proximal forearm metastasise to the axillary node

Question 23

Common sites of distant metastasis?

Answer 23

Lung
Parenchymatous organs - liver, spleen, kidney
Bone
Skin
CNS
Distant nodes

Question 24

Detection of pulmonary metastases?

Answer 24

Very difficult to pick up on examination - adventitious sounds uncommon, may pick up if concurrent effusion, cough uncommon
Radiographs
- both lateral inflated views, ideally all 4 views
- do not confuse pleural plaques/pulmonary oesteomas with metastases
CT
- more sensitive but more expensive and less available

Question 25

Detection of metastases to parenchymatous organs?

Answer 25

Ultrasound generally superior to radiography NB old dog changes - nodular hyperplasia in the liver - nodular hyperplasia, lymphoid hyperplasia, haematomas in the spleen Confirm by FNA

Question 26

Are blood tests useful in cancer patients?

Answer 26

Haematology will only give a diagnosis if patient has leukaemia - lymphoma patients seldom have circulating tumour cells - required prior to chemo - paraneoplastic syndromes Biochemistry never diagnostic - poorly sensitive to organ infiltration - paraneoplastic syndromes - concurrent disease Infectious disease - vast majority of feline lymphoma patients are not FeLV positive

Question 27

What is involved in tumour metastasis?

Answer 27

Vascularisation of tumour - angiogenesis factors Invasion of tumour cells into vasculature - enzymes (collagenases, matrix metalloproteinases) - lack of adhesion - motility characteristics Dissemination - evasion host immunity Arrest - adhesion to normal cells Extravasation - enzymes Proliferation - angiogenesis

Question 28

Which tumours tend to have haematogenous metastases?

Answer 28

Sarcomas | Malignant melanomas

Question 29

Which tumours tend to have lymphatic metastases?

Answer 29

Local and regional lymph node spread Mast cell tumours Carcinomas Malignant melanomas

Question 30

Limitations of the TNM system?

Answer 30

Animals do not always present with the primary disease Metastatic disease Paraneoplastic syndromes Biological behaviour of the tumour must be born in mind

Question 31

Which tumours are highly metastatic?

Answer 31

Oral/mucosal malignant melanoma Visceral and some other soft tissue haemangiosarcomas Appendicular osteosarcoma High grade (Patniak grade III/Kiupel high grade or poorly differentiated) MCTs Subungual malignant melanoma (dogs) Poorly differentiated mammary tumours (dogs) Most mammary carcinomas in cats (Anal sac adenocarcinomas - often slow) (Prostatic carcinomas - often slow) (Digital squamous cell carcinomas - often slow)

Question 32

Which tumours are variably metastatic?

Answer 32

``` Oral/axial OSA Thyroid carcinomas (dog) Patnaik intermediate grade MCTs Injection site sarcoma Anaplastic sarcoma Insulinoma (most do) Mammary carcinoma (dog) Apocrine adenocarcinomas GIT carcinomas TCC of bladder Liposarcoma ```

Question 33

Which tumours have a lower metastatic potential?

Answer 33

Oral fibrosarcoma Non-tonsillar oral squamous cell carcinoma Most ST sarcomas Sebaceous adenocarcinoma Low grade MCTs Multilobular osteoma/osteosarcoma of bone Intranasal tumours

Question 34

Which tumours don't metastasise?

Answer 34

Oral acanthomatous ameloblastomas Haemangiopericytoma Schwannoma/neurofibroma Benign tumours!

Question 35

What are the aims of oncological surgery?

Answer 35

``` Prophylaxis Diagnosis and staging Definitive excision Cytoreduction of tumour mass Palliative treatment Treatment of metastatic disease ```

Question 36

Which cancers are castration and ovariohysterectomy prophylaxis for?

Answer 36

Castration: testicular neoplasia (not prostatic cancer) Ovariohysterectomy: ovarian/uterine neoplasia, reduces mammary cancer

Question 37

What is multimodality therapy for cancer?

Answer 37

Cytoreduction of tumour mass before, at time of or after radio- or chemotherapy

Question 38

When is palliative treatment for cancer used?

Answer 38

If hopeless prognosis (usually due to early metastasis) Pointless aggressively treating primary neoplasia if patient will die from diffuse disease Removal of tumour burden may restore or maintain quality of life until euthanasia is inevitable

Question 39

Pre-op considerations of oncological surgery?

Answer 39

``` Type, grade and stage Local and systemic effects of disease Is a cure possible? Is surgical intervention appropriate? Prognosis with/without surgery Anticipated complications Patient's quality of life Cost of (ongoing) treatment ```

Question 40

What to be careful of with oncological surgery?

Answer 40

Inappropriate surgery may seed tumour to tissue planes previously unaffected Most active/invasive parts of tumour are at edges If tumour recurs there is less normal tissue for closure

Question 41

Pre-operative nutritional support for oncological surgery?

Answer 41

Provide if: Anorexia for >5days >10% acute loss of lean body weight Disease or surgery will prevent feeding for >3-5 days post-op

Question 42

Methods to achieve surgical margins for cancers?

Answer 42

Local excision - easiest, often used inappropriately Wide excision Radical excision

Question 43

Preparation for oncological surgery?

Answer 43

Plan reconstruction before tumour excision Avoid vigorous palpation Clip and prepare wide area around proposed surgical site Gentle cleaning using effective skin preparation not vigorous scrubbing

Question 44

Why does oncological surgery have higher infection rates?

Answer 44

``` Old age Poor nutritional status Obesity Diabetes/concurrent disease Hypoxaemia Remote infection Corticosteroid therapy Immunocompromise Thrombocytopenia/poor blood supply ```

Question 45

When should antibiotic prophylaxis be used for oncological surgery?

Answer 45

If debilitated patient If clean-contaminated/contaminated/dirty surgery If surgical procedure >90 mins In general begin no more than 2h pre-op and continue no more than 24h post-op

Question 46

Are adhesions between a tumour and adjacent structures a problem?

Answer 46

Represent direct tumour invasion in >50% cases

Question 47

What to do after tumour excision during oncological surgery?

Answer 47

Saline lavage - allows removal of blood clots, foreign material, necrotic tissue and possibly any unattached tumour fragments Change gloves, drapes and instruments after tumour excision and lavage - tumours will adhere to inanimate objects and potentially seed to other tissues prior to closing

Question 48

Vascular occlusion techniques for oncological surgery?

Answer 48

Ligate vascular supply to tumour and venous and lymphatic drainage from it as early as possible Especially important for tumours of ectodermal origin (e.g. SCC, MCT) where probability of exfoliation is high)

Question 49

How to avoid wound complications (e.g. haematomas, serums, sepsis) in oncological surgery?

Answer 49

Meticulous haemostasis Effective closure of dead space Appropriate use of drains Appropriate use of perioperative antibiotics

Question 50

General recommendations for the management of local lymph nodes in oncological surgery?

Answer 50

Non destructive biopsy of grossly normal lymph node Lymph node removal if: - histologically proven to contain tumour cells - appears grossly abnormal at surgery - intimately associated with tissue being removed and surgical margins dictate its removal

Question 51

Indications for chemotherapy?

Answer 51

``` Systemic tumours Risk of metastatic disease Palliative treatment Delay/prevent local tumour recurrence Radiation sensitisation ```

Question 52

Types of chemotherapy?

Answer 52

Primary Adjunctive (used with another treatment) Neoadjunctive (used before a treatment to help its success)

Question 53

How does conventional chemotherapy work?

Answer 53

Cytotoxic drugs which are mainly active against highly proliferating cells So do not specifically target cancer cells Targets are DNA synthesis, RNA synthesis, protein synthesis and cell cycle progression

Question 54

Which part of the cell cycle is relatively resistant to the actions of cytotoxic chemotherapy drugs?

Answer 54

G0 - act as a reservoir to repopulate the tumour after therapy

Question 55

Define growth fraction, mitotic index and mass doubling time of tumours?

Answer 55

Growth fraction - fraction of cells actively dividing at any given time Mitotic index - % or number of mitoses per high power field on light microscopy Mass doubling time - time taken for tumour to double in size (affected by GF, cell cycle time, cell loss)

Question 56

What is Gompertzian growth of tumours? How does this affect chemotherapy sensitivity? Which tumours don't follow this growth pattern?

Answer 56

Decreasing growth rate with increasing number of cells Early stages (microscopic): - rapid growth, high GF, short MDT - more cells in chemotherapy sensitive phases of cell cycle Later stages (large bulky disease): - slower growth, lower GF, longer MDT - fewer cells in chemotherapy sensitive phases of cell cycle Not true of leukaemia and lymphoma

Question 57

Factors affecting chemotherapy success?

Answer 57

``` Growth fraction and mass doubling time Inherent tumour sensitivity Tumour cell heterogeneity Inherent tumour cell resistance/acquired drug resistance Drug dosage Interval between treatments Tumour blood supply/oxygenation ```

Question 58

Are lymphomas and melanomas chemo-sensitive?

Answer 58

Lymphoma: remains relatively sensitive even at large volumes Melanoma: poorly sensitive even with high GF

Question 59

What is Nowell's hypothesis?

Answer 59

Cancer is the result of genetic instability If a cell develops a genetic mutation this is transferred to further clones New clones may develop further genetic mutations

Question 60

Mechanisms of chemotherapy drug resistance of tumours?

Answer 60

``` Less drug entering cell Defective drug activation Increased drug inactivation Alteration in target molecules Enhanced DNA repair ```

Question 61

Intrinsic drug resistance of tumours?

Answer 61

Increased DNA repair Over expression of anti-apoptotic proteins Altered expression of oncogenes or tumour suppression genes P-glycoprotein

Question 62

Acquired drug resistance of tumours?

Answer 62

Single agent specific resistance Resistance to drugs which have similar modes of action Multidrug resistance

Question 63

How to minimise tumour drug resistance?

Answer 63

``` Treat as early as possible Use standard protocols Use correct doses Administer agents properly (e.g. don't pretreat lymphoma patients with steroids) At relapse, act sooner rather than later ```

Question 64

Drug dosage for chemotherapy?

Answer 64

Narrow therapeutic window Aim for maximum tolerated dose (MTD) to minimise tumour burden but without toxicity If no response to first dose, don't keep trying same dose as won't work Dose on the basis of body surface area (BSA) - correlates with blood supply to liver and kidneys (better than weight) For smaller patients sometimes mg/kg instead (dox, carbo)

Question 65

Tumour blood supply? Problems for chemotherapy?

Answer 65

Many tumours are poorly vascularised with disorganised sinusoidal blood vessels Larger tumours tend to outgrow their blood supply Poor blood supply results in: - inadequate drug delivery - inherently low growth fraction - areas of anoxia -> low pH, build up of toxic metabolites, interference with cytotoxicity

Question 66

What chemotherapy drugs are there?

Answer 66

Agents that affect DNA replication: - alkylating agents (cyclophosphamide, melphalan, chlorambucil, lomustine) - antitumour antibiotics (doxorubicin, epirubicin, mitoxantrone, Actinomycin D) - platinum compounds (cisplatin, carboplatin) Agents which affect purine and pyrimidine synthesis - antimetabolites (cytosine arabinoside, methotrexate, 5-fluorouracil) Agents which interfere with mitosis - vinca alkaloids (vincristine, vinblastine) Enzymes - e.g. L-asparaginase Miscellaneous agents - corticosteroids - NSAIDs

Question 67

Disadvantages of single agent chemotherapy? When used?

Answer 67

Tends to select rapidly for drug resistance Not capable of adequate antineoplastic activity Used for exquisitely sensitive tumours - transmissible venereal tumour Or where no other known effective agents: - platinum compounds in osteosarcoma - doxorubicin in high grade STS

Question 68

Polychemotherapy protocol?

Answer 68

``` Agents should: - have proven efficacy against the tumour - have different modes of action - affect different stages of the cell cycle - have non-overlapping DLT toxicities - not interfere with each others actions Combined or sequential Toxicity: combined > sequential ```

Question 69

Chemotherapy routes of administration?

Answer 69

``` Oral IV IM/SC Intracavitary Intratumoural Intrathecal ```

Question 70

Define chemotherapy drug dose intensity and dose density?

Answer 70

Dose intensity = the drug dose delivered per time unit, expressed as mg/m^2 per week Drug density = how often the drug is administered during the protocol - interval between doses needed to allow recovery of normal tissues - rapidly dividing tissue e.g. bone marrow and GIT have tremendous capacity to repair rapidly and tend to repair more rapidly than most tumours

Question 71

Which patients present chemotherapy drug dosing problems?

Answer 71

Obese patients - should we estimate lean weight? Collies and others with known drug sensitivity - can test for MDR1 (ABCB1) mutations Animals with hepatic functional compromise Animals with reduced renal function

Question 72

Immediate toxicity (<24hrs) reactions to chemotherapy?

Answer 72

``` Anaphylaxis/hypersensitivity: - L-asparaginase, antracyclines, cisplatin, cytosine - IVFT, dex IV, H1 blocker, adrenaline Cardiac arrhythmia - doxorubicin (epirubicin) Emesis - platinum compounds, antracyclines ```

Question 73

Possible toxicity reactions 1-5 days post chemotherapy treatment?

Answer 73

GI toxicity - most agents Perivascular reactions - antracyclines, platinums, vinka alkaloids Pancreatitis - corticosteroids, asparagina, azathioprine, platinum compounds

Question 74

Why can chemotherapy drugs cause GI toxicity 1-5 days post treatment? Signs? Treatment? Which drugs?

Answer 74

Direct damage to enterocytes Anorexia, nausea, vomiting, diarrhoea Syptomatic treatment: - treat more aggressively than non-chemo patients - anti-emetics, anti-diarrhoeals, antibiotics, IVFT, gastroprotectants, appetite stimulants GI toxicity seen before bone marrow toxicity Disrupted mucosal barrier with neutropenia increases risk of sepsis Mainly: doxorubicin/epi, vincristine, cyclophosphamide (cats), cytarabine infusion, platinum compounds

Question 75

Why may dogs/cats get myelosuppression 7-10 days post chemotherapy?

Answer 75

Damage to haematopoietic stem cells Neutropenia is generally the limiting toxicity (<3x10^9/L dog, <2.5x10^9/L cat) Thrombocytopenia less common

Question 76

What to do if pyrexic neutropenic patient 7-10 days post chemotherapy?

Answer 76

- medical emergency as may be septic - translocation of bacteria from patient's own GI flora - hospitalisation - stop all cytotoxic drugs - barrier nurse and aseptic technique - supportive therapy - bactericidal antibiotics

Question 77

``` What to do if asymtpmatic afebrile neutropenic patient: - <1x10^9/L - 1-1.5x10^9/L - 1.5-2x10^9/L 7-10 days post chemotherapy? ```

Answer 77

``` <1x10^9/L: - ABs if indicated - drug discontinuation and subsequent dose reduction - check temperature 1-1.5x10^9/L: - dose likely postponement - no Abs unless good reason 1.5-2x10^9/L: - dose may require postponement/modification ```

Question 78

Which chemotherapy drug can cause cumulative cardio toxicity (DCM) in dogs?

Answer 78

Doxorubicin

Question 79

What variable onset toxicities are there of chemotherapy?

Answer 79

Alopecia - rare Sterile haemorrhagic cystitis - cyclophosphamide Hepatotoxicity - Iomustine (dogs) Nephrotoxicity - cisplatin, doxorubicin (cats), Iomustine (dogs) Peripheral neuropathy - vincristine Fatal non cariogenic pulmonary oedema - cisplatin (cats) Fatal CNS signs - 5-FU (cats) Acute tumour lysis syndrome - large tumour burdens, rapid destruction of cancer cells, ARF

Question 80

Which chemotherapy drugs can cause extravasation? How to avoid it?

Answer 80

Vincristine and vinblastine are perivascular irritants (but stays local as non DNA binding) Doxorubicin, epirubicin and Actinomycin D are catastrophic perivascular irritants (DNA binding so will spread) Always use a cleanly placed first stick catheter Monitor for any swelling, discomfort, changes in resistance to injection or rate of infusion Never leave an animal unsupervised on an infusion Flush catheters appropriately before catheter removal

Question 81

Treatment for extravasation from chemotherapy?

Answer 81

Doxorubicin/epirubicin/actinomycin D: - cold packing - dexrazoxane (expensive) - topical DMSO (can't use at same time as dexrazoxane) - consider (immediate) surgical debridement Vincristine/vinblastine: - can try and aspirate drug back out - hot packing q4h - topical DMSO for a week - don't bandage - hyaluronidase (unknown efficacy, may mop up free radicals, not recommended)

Question 82

What is metronomic chemotherapy?

Answer 82

``` Continuous low dose chemotherapy (usually low dose cyclophosphamide with piroxicam or other NSAIDs) More recently: addition of thalidomide Dose dense chemotherapy strategy Main target is angiogenesis Also inhibition of CEPs Stimulation of immune response Direct action of tumour cells ```

Question 83

Tyrosine kinase inhibitors for chemotherapy?

Answer 83

Inhibit the activation of specific signalling pathways involved in specific types of cancer Two oral drugs targeting the RTK KIT (toceranib and masitinib) licensed for treatment of mast cell tumours in dogs - only in very specific situations Drugs affect non target tyrosine kinases: - have an effect on angiogenesis - other tumour targets - toxicity - need regular monitoring

Question 84

What is immunotherapy?

Answer 84

Patient's own immune system to target cancer cells Highly selective E.g. canine melanoma vaccine (produces anti-tyrosinase antibodies)

Question 85

Methods of radiotherapy?

Answer 85

Brachytherapy: - direct application (pleisiotherapy) - implantation (iridium wires to emit gamma rays) - systemic administration (iodine 131 in feline hyperthyroidism) Teletherapy: - external beam (orthovoltage source, linear accelerator, cobalt 60)

Question 86

Types of radiation used by teletherapy?

Answer 86

``` Electromagnetic radiation: - X rays - high energy produced by linear accelerators or low energy produced by orthovoltage sources - Gamma rays - cobalt sources - Electrons Particle beam therapy - heavy particles ```

Question 87

What happens with low linear energy transfer of x rays or gamma rays for tele therapy radiation?

Answer 87

Loses energy slowly as passes through tissues Deep penetration Must consider effects on deep structures Indirectly ionising - absorption by the Compton effect, interaction of photons with water molecules important The maximum dose is not absorbed at the surface - build up effect

Question 88

What is the critical target for therapeutic radiation? What causes damage?

Answer 88

DNA Ionised water molecules around DNA -> free radicals generated -> damage DNA Damage is rapidly reversible unless fixed by oxygen Oxygen inhibits the repair of free radical induced damage - forms irreversible peroxides Requires 2/5-3 x more radiation to kill a hypoxic cell (larger tumours more difficult) Cell death occurs due to: - induction of apoptosis - permanent cell cycle arrest - mitotic catastrophe Damage often not expressed until cell tries to divide

Question 89

What is a dual modality Linac? How does it work?

Answer 89

Produces photons and electrons | Couch, collimator and gantry rotate around a fixed point

Question 90

How to target photons/electrons for radiotherapy?

Answer 90

Photons: - shape beam with the jaws - rectangle or tumour shaped - multiple beams can increase tumour dose while sparing surrounding tissue Electrons: - directly ionising - loses energy rapidly as passes through tissue so ionisation only occurs superficially - can treat superficial tumours

Question 91

What is fractionation?

Answer 91

= Giving multiple small doses instead of one big one Aim is to achieve better tumour cell kill Reduce repair and repopulation, achieve deoxygenation and redistribution Larger fraction sizes: greater normal tissue damage, especially late responding tissues Smaller fraction sizes: ideal for most tumours, more treatments required for the same anti-tumour effect Once weekly, M-W-F or daily Total dose of radiation required to kill cells is less if a few large doses are given rather than lots of smaller doses 2 doses of radiation given at separate times have less effect than the sum of the 2 doses given as a single treatment

Question 92

What happens in tissues after radiotherapy that affects the response?

Answer 92

Repair - between treatments cells can rapidly repair sublethal damage - tumour cells and normal cells have similar capacities Repopulation - seen in rapidly dividing tissues - cells are recruited from G0 - protects rapidly dividing normal tissues - rapidly dividing tumours also repopulate effectively Redistribution/reassortment - cells are more sensitive to radiation in late G2 and M - cells may become synchronised in post treatment period but soon lost Reoxygenation - changes in tumour vascularity

Question 93

Limitations of fractionation for animal radiotherapy?

Answer 93

Requirement of GA Cost Owner reluctance - inconvenience, frequent visits, long hospitalisation

Question 94

Tumour features which affect the response to radiotherapy?

Answer 94

Tumour growth characteristics - slowly dividing tissues may be more radio resistant as fewer cells in sensitive phases Tumour size - smaller tumours more sensitive, less likely to contain large numbers of hypoxic cells, easy to dose accurately and evenly Inherent sensitivity Tumour type Tumour site Patient species

Question 95

What tumour types are highly radiosensitive?

Answer 95

Lymphoma Transmissible venereal tumour Gingival basal cell carcinoma (acanthomatous epulid)

Question 96

What tumour types are moderately radiosensitive?

Answer 96

``` Oral SCC (dogs) Oral malignant melanoma (dogs) Nasal tumours Perianal adenocarcinoma MCTs Rhinarial SCC (cats) Thyroid carcinomas Brain tumours ```

Question 97

What tumour types are poorly radiosensitive?

Answer 97

``` Fibrosarcomas Haemangiopericytomas Oral SCC (cats) Osteosarcomas Rhinarial SCC (dogs) ```

Question 98

Side effects of radiotherapy? When seen? What?

Answer 98

Radiation damage not usually apparent until cells try to divide Acute side effects: - affect rapidly dividing tissues (skin, mm) - erythema, desquamation - develop during or soon after treatment (days-weeks) - resolve within a few weeks of cessation of therapy Late side effects: - affects slowly dividing tissues - develop many weeks, months or years after treatment - potentially very serious e.g. necrosis of brain or bone tissue - many inconsequential/less serious e.g. alopecia, skin fibrosis - reduced healing capacity

Question 99

Carcinogenesis of radiotherapy?

Answer 99

Radiation therapy is carcinogenic - DNA damage and mutagenesis Tends to be a long time period before development of malignancy - usually years in dogs Avoid irradiating young patients Avoid irradiation caused by inadequate surgery or poor surgical planning

Question 100

Radiotherapy post-operatively for tumours?

Answer 100

Commonly used After radical surgical debulking First treatment immediately post-op Remaining tumour has high growth fraction and should be well oxygenated

Question 101

Radiotherapy intra-operatively for tumours?

Answer 101

Application to unresectable, otherwise inaccessible tumours at the time of surgery Single large dose - side effects on normal tissues Prolonged surgical time so greater morbidity

Question 102

Radiotherapy pre-operatively or neo-adjunctive for tumours?

Answer 102

Reduces tumour burden Eliminates small numbers of tumour cells at the periphery of the lesion Can have negative impact on wound healing Used occasionally for OSA and ST sarcomas

Question 103

Radiotherapy outcomes?

Answer 103

The effects of radiation on tumour growth are not instantaneous Residual mass may be left esp mesenchymal tumours Analgesia may be achieved within hours - very valuable, powerful analgesic for the majority of patients

Question 104

Clinical signs of oral tumours?

Answer 104

``` Mass/facial swelling Oral bleeding Dysphagia/pain Loose teeth/proliferative lesions noted at dentals (always biopsy lesions) Halitosis Epistaxis Cervical lymphadenopathy ```

Question 105

Diagnosis and staging of oral tumours? Assessment of lymph nodes?

Answer 105

``` Assessment under GA usually required Diagnosis - FNA or biopsy Local staging: - many are locally invasive - visal assessment underestimates - advanced imaging Distant staging: - thoracic imaging adequate for some, CT greater se - abdominal imaging if melanoma Always assess local lymph nodes: - FNA submandibular lymph nodes - consider imaging retropharyngeal nodes ```

Question 106

Treatment for an oral tumour local disease?

Answer 106

Surgery preferred to RT where excision possible At least 2cm margin required Surgery well tolerated in dogs Cats take long time to adjust after mandibulectomy and may need a feeding tube for several months For FSA and SCC surgery, follow by adjuvant RT - better results than surgery alone RT alone is reasonable option for oral melanoma - 4 fractions

Question 107

Complications of surgery for oral tumours?

Answer 107

``` Bleeding Recurrence Infection Altered cosmetic appearance Difficulty pretending food Salivation Mandibular drift after semi-mandibulectomy ```

Question 108

Oral melanoma - which animals generally? Diagnosis? Invasiveness? Metastatic potential?

Answer 108

Generally smaller, older dogs GRT, cocker spaniel, miniature poodle, chow chow Diagnosis based upon melanin containing mesenchymal cells Some tumours don't contain melanin and IHC required to diagnose Locally invasive High metastatic rate (up to 80%) - check both submandibular lymph nodes

Question 109

Oral melanoma - treatment options

Answer 109

``` Surgery associated with quite high rates of local recurrence: - maxillectomy 48% - mandibulectomy 22% - higher risk of metastasis if >2cm - lower risk if more complete excision - 1 year survival 35% Radiotherapy: - 4 fractions -> RR >80% - median time to recurrence 5 months - 1 year survival 36% Chemotherapy can induce responses but does not appear to extend survival Plasmid vaccine immunotherapy: - used in stage II and III disease - targets melano-protein (tyrosinase) - injection leads to expression of human tyrosinase in dog cells - stimulates immune response - may help a minority of patients - no side effects ```

Question 110

Survival time with oral melanoma if distant metastasis?

Answer 110

<3 months

Question 111

Oral squamous cell carcinomas - metastatic rate? Treatment options?

Answer 111

``` Low metastatic rate - LN 10% - distant < 35% Local surgery: - mandible 10% recurrence - maxilla 30% recurrence - rostral mandible lesions have better outcome - MST 19-26 months Radiotherapy: - MST 15 months Surgery and radiotherapy - MST 34 months - good option for incomplete excision Medical therapy - metastatic disease - neoadjuvant - when other therapies not possible - Piroxicam RR 20% - Piroxicam + Carboplatin CR 57% - sustained responses with MST 18 months ```

Question 112

Clinical presentation of tonsillar squamous cell carcinoma? Metastatic rate? Treatment options? Prognosis (MST)?

Answer 112

Dysphagia, coughing Enlarged cervical lymph nodes -> abscessation (FNA yields necrotic debris and sometimes tumour cells) Oral exam - enlargement of one or both tonsils Metastatic rate >70% Local control of tonsillar enlargement - surgery or RT Surgery or RT for lymph node metastasis Carboplatin or mitoxantrone chemotherapy for be beneficial MST 7 months Patients who receive the most therapy survive longest

Question 113

Oral fibrosarcoma - Which animals? Invasiveness? Metastatic risk? Treatment options? MST?

Answer 113

``` Large breed dogs especially GRT and labrador Middle aged dogs (median 7.5years) Invasive Low/moderate metastatic risk - lung and occasionally lymph nodes Surgery single most important therapy: - but RR 40-60% - MST 1y after surgery Multimodal therapy often best outcomes: - surgery and RT: MST 18-26 months - RR 30% RT alone - MST 7 montjs Smaller tumours better outcomes - T1 tumours MST 31 months - T2 and T3 tumours (>2cm) MST 7 months Cats - similar to dogs, successful surgery has better outcome, mandibular more easily addressed, RT can be helpful ```

Question 114

Problem with low histological grade high biological grade sarcomas of the mouth? Treatment?

Answer 114

Aggressive, rapidly progressing oral tumour with benign histological appearance even after large biopsy Tumours reported as low grade, fibroma or even granulation tissue or epulis Very locally invasive so aggressive local management with surgery and RT required

Question 115

What are epulides? Types?

Answer 115

Benign lesions arising from gingiva Acanthomatous - aggressive local behaviour and bone invasion Peripheral odontogenic fibroma - slow growing firm masses usually not invasive

Question 116

Oral osteosarcoma - treatment options? MST?

Answer 116

``` Surgery most important treatment RT does not extend survival Mandibular 14-18 months Maxillary 5-10 months Complete excision vital Local RR >80% Significance of chemotherapy unknown ```

Question 117

What less common oral tumours are there? Treatment?

Answer 117

MCT and haemangiosarcoma Plasmacytoma Oral lymphoma - generally require multi-agent chemotherapy, some dogs with oral (only) epitheliotrophic lymphoma can do well with RT alone Undifferentiated tumour of young dogs - rare, grave prognosis

Question 118

Feline oral squamous cell carcinoma - what increases the risk? Signs? Invasiveness? Metastatic risk? Site?

Answer 118

Most common feline oral tumour Risk increased by: - use of flea collars - exposure to smoking - canned food including canned tuna Causes considerable oral discomfort -> anorexia Locally invasive Low metastatic risk - higher risk in caudally positioned lesions Predilection at base of tongue (but can be anywhere in mouth) Bone invasive

Question 119

Outcome of feline oral squamous cell carcinomas?

Answer 119

Cats with surgical resectable disease can have a good outcome but recurrence is common Best outcomes in rostral mandibular SCC - long term feeding tubes often needed for several months Soft tissue lesions affecting the tongue have a poor prognosis as resections are difficult RT occasionally helpful ECT is an emerging therapy

Question 120

Oral multilobular oesteochondrosarcoma in dogs - appearance?

Answer 120

Popcorn appearance | Usually local problem

Question 121

Oral viral papillomatosis in dogs - appearance? Prognosis?

Answer 121

Wart like lesions affecting oral soft tissues Usually resolve in 4-8 weeks Occasionally persist in immunosuppressed animals

Question 122

Oral eosinophilic granuloma - which animals? Treatment?

Answer 122

Dogs: - granuloma affecting ventral and lateral aspect of tongue - husky and CKCS - surgery and corticosteroids Cats: - typically erosive lesions affecting upper lip near midline - steroids/hypoallergenic diets, RT, surgery

Question 123

Transmissible venereal tumours in dogs - transmission? Prognosis?

Answer 123

Proliferative lesion affecting dogs who have been licking place they shoudn’t whilst on hols in southern europe Spontaneous regression and very responsive to vincristine

Question 124

Effect of neutering on risk of mammary tumours?

Answer 124

Neutering prior to first oestrus – 0.5 % risk Neutering prior to second oestrus – 8 % risk Neutering prior to third oestrus – 26 % risk No risk reduction if neutering after the second season Must balance early neutering against risk of urinary incontinence Progestin, oestrogen use increases risk of tumours

Question 125

Risk factors for mammary tumours?

Answer 125

``` Obesity: - reduced sex hormone-binding globulin -> oestrogen levels - underweight at puberty reduces risk Age: - mean age with benign tumours 7-9yo - mean age with malignant tumours 9-11yo - mean age of cats 10-12yo Breed: - poodles, chihuahua, dachshund, maltese, cocker spaniels and yorkshire terriers - siamese cats ```

Question 126

Diagnosis and staging of canine and mammary tumours?

Answer 126

>70% have more than one tumour 30-50% are malignant Incidence increases after 6yo Majority of malignant tumours are carcinomas FNA can be useful to exclude other ddx e.g. mastitis, lipoma, MCT Excisional biopsy by single or segmental mastectomy reasonable for single lesions without negative prognostic indicators Staging prior to treatment of suspicious lesions Tumours >3cm have poorer outcome Local staging: - assessment of local lymph nodes - cranial two glands drain to axillary lymph node - caudal two glands drain to inguinal lymph node - middle gland drains either way Distant staging - thoracic radiographs - abdominal ultrasound - consider bone pain as mammary tumours metastasise to bone

Question 127

Surgery for canine mammary tumours?

Answer 127

Single mastectomy adequate for low risk lesions Consider regional mastectomy in higher risk tumours or intact bitches - cranial 3 or caudal 3 glands 55% of intact bitches develop a new tumour on the ipsilateral side so consider unilateral chain mastectomy Likely hormone field effect so consider bilateral resection in young intact bitches with multiple tumours Mobile lesions - whole gland removal enough Fixed lesions - need 2cm margins and removal of affected abdominal fascia/wall - if neutering do not penetrate tumour before Ovariohysterectomy at time of mastectomy in dogs with benign mammary tumours halves the chance of a new mammary tumour (to 35%) Benefit of OHE less clear for carcinoma but unlikely to be detrimental Benefit of OHE at time of mastectomy has not been evaluated in cats

Question 128

Post surgical prognostic factors for mammary tumours

Answer 128

``` Tumour type - Benign versus malignant - Less tissue heterogeneity associated with a poorer outcome - Osteosarcoma - poorer Inflammatory carcinoma - very poor Possible prognostic factors - Ki-67 - Grade - Hormone receptor expression - lack of expression correlate with poorer outcome ```

Question 129

Canine inflammatory carcinomas (mammary) - Presentation? Behaviour? FNA results? Treatment? Prognosis?

Answer 129

Extremely painful, oedema, inflammation, often ulcerated, rash like appearance Rapid growth, invade cutaneous lymphatics Difficult to differentiate from mastitis on clinical exam and cytology FNA yields inflammatory cells and tumour cells Excision not typically feasible - recurrence very common Treatment is palliative Medical therapy might prolong survival for few months Generally very poor prognosis

Question 130

Clinical presentation of feline mammary tumours? What type are most? Ddx?

Answer 130

Often poorly defined, grow rapidly, metastasise to lymph nodes and lungs early Mainly occur in intact females >60% have more than one tumour at diagnosis 95% are malignant Most are adenocarcinomas Poor prognosis A significant dddx is fibroepithelial hyperplasia - usually all glands enlarged

Question 131

Clinical prognostic indicators for feline mammary tumours?

Answer 131

Tumour size (>2 cm MST 6 months, <2 cm MST >3 years) Lymph node metastasis - lymphatic drainage less predictable than dog, assess inguinal and axillary nodes bilaterally Distant metastasis Breed - DSH have better outcome

Question 132

Surgery for feline mammary tumours?

Answer 132

Chain mastectomy better than single or regional mastectomy Unilateral when lesions on one side Stage bilateral when lesions bilateral Surgical resection of inguinal and /or axillary lymph nodes for high risk tumours recommended by some

Question 133

Chemotherapy for mammary tumours?

Answer 133

Poss benefit of 5-FU and cyclophosphamide in dogs Doxorubicin often used in dogs >50% of cats showed a gross response to doxorubicin Doxorubicin and cyclophosphamide associated with prolonged survival in one study in cats

Question 134

What is a sarcoma?

Answer 134

A malignant cancer that arises from transformed cells of mesenchymal origin

Question 135

Sarcoma subtypes (by cell of origin)?

Answer 135

Connective tissue - soft tissue sarcoma, fibrosarcoma, myxosarcoma Peripheral nerves - peripheral nerve sheath tumour Bone - osteosarcoma Blood vessels - haemangiosarcoma Muscle – rhabdomyosarcoma (striated muscle rare), leiomyosarcoma (smooth muscle - uncommon) Fat – infiltrative lipoma, liposarcoma Cartilage - chondrosarcoma, synovial cell sarcoma (Lymphatic and haematopoetic cells – many of these tumours are considered separately – based on behaviour)

Question 136

Behaviour of sarcomas?

Answer 136

Locally invasive Metastatic risk varies by type: - lower risk <40%: peripheral nerve sheath tumour, fibrosarcoma/soft tissue sarcoma, histiocytic sarcoma around joint, chondrosarcoma, feline injection site sarcoma - higher risk >90%: osteosarcoma, haemangiosarcoma, histiocytic sarcoma not around joint - PNST, FSA and STS: low grade 10%, intermediate grade 20%, high grade 40%

Question 137

Where to image for sarcomas?

Answer 137

All have predilection for lung metastasis - inflated 3 view thoracic radiographs CT more sensitive if availble Abdomen, areas of bone pain, echocardiography depending on tumour type

Question 138

Osteosarcomas - which animals generally? Which limbs?

Answer 138

``` Middle age and older dogs Typically large breeds - front limbs 2:1 hind limbs - appendicular skeleton: metaphysis of long bones - 'near the knee, away from the elbow' Small breeds <15kg only 5% of cases - 60% in axial skeleton ```

Question 139

Clinical signs and diagnosis of osteosarcomas?

Answer 139

Pain and lameness - sudden and progressive onset - localisation to a single bone or joint Radiographic changes: - bone lysis - soft tissue swelling - new bone - palisades perpendicular ro bone - periosteal elevation - Codman's triangle - zone of transition Cytology or histology needed to confirm diagnosis

Question 140

Treatment for osteosarcomas?

Answer 140

Aims are to prevent/reduce pain and slow development of metastatic disease Amputation: - most tolerate well - even large with mild-moderate orthopaedic problems - pain free around 1 week after amputation - complete ambulatory adaptation takes around 1 month Analgesia - multimodal, opioids, NSAIDs, paracetamol, amantadine Slow bone destruction - biphosphanates e.g. pamidronate Reduce sensation - radiation therapy (1 fraction yields pain relied in 60-90% cases for 1-3 months) Ongoing and increasing risk of pathological fracture Bone stabilisation and fixation - spares surgery, aims to retain limb function, selected cases for lower limb lesions, high rate of infection and implant failure, patient never pain free

Question 141

Metastasis and chemotherapy of osteosarcomas?

Answer 141

95% have metastasis at diagnosis - mostly micrometastasis Chemotherapy extends survival in patients without gross metastasis at diagnosis - carboplatin or anthracyclines - MST 9-11 months, compared to 5-6 months with surgery alone Toceranib may be helpful in presence of gross metastasis Conventional chemotherapy does not extend survival with gross metastasis

Question 142

Osteosarcoma prognostic factors in dogs?

Answer 142

Location: - humerus poorer prognosis - skull has lower metastatic rate - local invasion still problem - rib, vertebral and pelvis all poorer Presence of metastatic disease Total alkaline phosphatase - indirect measure of bone isoenzyme ALKP

Question 143

Cats with primary bone tumours - treatment?

Answer 143

Usually cured by surgery alone

Question 144

Treatment for soft tissue sarcoma?

Answer 144

Wide surgical resection If histologically incomplete margins, wide surgical resection of scar or adjuvant radiotherapy Histologically complete margins -> grade tumour, consider follow up adjuvant chemotherapy with doxorubicin

Question 145

Surgical margins for soft tissue sarcomas?

Answer 145

Ideal surgical margins: 3cm lateral and 1 fascial plane beyond the extent of tumour 'Tumour' includes FNA tracts and biopsy scars Not always possible

Question 146

Assessment of margins of excision? How are they assessed?

Answer 146

``` Assessed histologically Aim is complete excision Can be incomplete excision Excision with narrow margins - rule of thumb 1-3mm between tumour and small edges Most common method of assessment: - 3 sections - relies on mass being spheroid - not always true - some tumours invade along tissue planes ```

Question 147

Treatment options form microscopic disease remaining or narrow margins excisions of soft tissue sarcomas?

Answer 147

Further wide surgical excision Adjuvant radiation therapy Metronomic chemotherapy (usually cyclophosphamide and an NSAID, risk of sterile haemorrhagic cystitis, stop if haematuria and no UTI) Active monitoring - only when chance of recurrence considered low: - lower grade tumours - when no gross disease left in animal - margins are incomplete in a small area not for whole sample - monitor monthly for at least a year

Question 148

Response rate of soft tissue sarcomas to chemotherapy as anti-metastatic treatment?

Answer 148

<40%

Question 149

Outcome of soft tissue sarcoma treatment in patients without metastatic disease?

Answer 149

Successful surgery +/- RT associated with very good survival MST>4 years

Question 150

Prognostic factors for soft tissue sarcoma treatment?

Answer 150

Tumour grade and mitotic rate Tumour size Tumour location Achieving local control of the tumour

Question 151

Feline injection site sarcomas - histology?

Answer 151

Malignant fibroblasts Inflammation - often high lymphocyte component Macrophages taking up foreign material thought to be adjuvant/carrier

Question 152

FISS - diagnosis and staging?

Answer 152

3-2-1 rule: be suspicious of any mass that: - Persists longer than 3 months after an injection - Is > 2cm - Increases in size after 1 month after an injection Cytology not always helpful - reported as inflammation 50% of time - biopsy better Advanced imaging - local staging: assess size and margins as highly invasive - distant staging (metastatic rate around 20%)

Question 153

FISS treatment?

Answer 153

Surgery: - 3-5 cm surgical margins required to give a chance of surgical cure - can involve removal of spinous processes of vertebrae - first surgery is best chance of a good outcome - outcomes are better if surgery is performed by a specialist Adjuvant treatments: - pre-op radiation therapy and/or chemotherapy can be useful for non resectable tumours - RT for incomplete resections or marginal resections - doxorubicin based chemotherapy - prolongs survival in cats treated with surgery, radiation therapy and then chemotherapy

Question 154

FISS prevention?

Answer 154

Injections to be given in sites amenable to wide surgical excision e.g. limb or tail Reduce inflammatory reactions at injection sites - avoid irritating substances where possible Don't over-vaccinate

Question 155

Clinical signs and diagnosis of haemangiosarcomas?

Answer 155

Clinical signs usually associated with bleeding - shock, collapse, haemoabdomen or pericardial effusion - intramuscular bruising in the dependent part of the limb - pericardial effusion if right auricular appendage Clinical pathology changes reflect bleeding and altered coagulation - anaemia and sometimes schistocytosis - in early stages of bleeding: effusion and reduced TP precede measurable anaemia - low platelet count - prolonged coagulation tests and DIC Diagnosis usually requires histological confirmation

Question 156

Staging of haemangiosarcomas? Poor prognostic factors?

Answer 156

Should be performed prior to any splenectomy - thoracic and abdominal +/- cardiac imaging - in older dogs hyperplastic liver nodules cannot be differentiated from metastasis on appearance alone - requires cytology/histology Poor prognostic factors: - invasive tumours - tumour rupture and bleeding into the abdomen (but diagnosis often not known at this point, other types of splenic tumour will also rupture)

Question 157

Treatment of primary splenic haemangiosarcoma?

Answer 157

For splenic tumours surgery is important as a diagnostic tool 50 – 50 rule for splenic tumours Surgical excision of spleen or masses where possible Beware of ventricular arrythmias after splenectomy Tumours are responsive to radiation - useful for muscular or dermal tumours

Question 158

Treatment of haemangiosarcoma metastatic disease? Survival?

Answer 158

Survival with metastasis typically 4-6 weeks Chemotherapy more useful if no gross metastasis Systemic chemotherapy with anthracycline based protocol - 4-6 treatments at 3 weekly intervals - for splenic HSA if no metastasis on staging sx alone MST 2-4 mths; sx + Doxorubicin MST 4-6 mths Metronomic chemotherapy another option

Question 159

Outcomes of haemangiosarcomas (MST)?

Answer 159

Splenic, intramuscular/subcutaneous and right atrial appendage HSA have a poor px - MST not past 6 months in most studies Intramuscular HSA in cats can be less aggressive Dermal HSA can have an excellent outcome - MST of around 1000 days

Question 160

Histiocytic sarcomas?

Answer 160

Highly metastatic sarcoma Arising from histiocytes – professional antigen presenting cells of the immune system Can affect lung, spleen, liver, bone, brain and joint Best outcomes are achieved with multi-modal therapy - Surgery, radiation and lomustine / anthracycline chemotherapy - Dogs wt gross metastasis have quite short survival: MST circa 4 – 5 months - Dogs with complete response to therapy or no metastasis at diagnosis who have chemotherapy live much longer: MST circa 500 days Dogs with periarticular histiocytic sarcoma have much better survival if no metastasis at staging: MST around 950 days

Question 161

Clinical presentation of mast cell tumours (MCT)?

Answer 161

Any age and no sex predilection Breed predilections e.g. Boxer, Boston Terrier Usually solitary 44% develop new mass post treatment Local effects - erythema, oedema, pruritus, haemorrhage Systemic signs - vomiting, melaena, rarely collapse

Question 162

What are mast cell tumours made up of?

Answer 162

Intracytoplasmic granules containing histamine, heparin and proteases -> degranulation

Question 163

Diagnosis of MCTs?

Answer 163

FNA - usually diagnostic, round cells, characteristic purple granules, Diff Quick usually fine For some poorly differentiated, biopsy +/- IHC required

Question 164

Staging of MCTs?

Answer 164

Haematology/biochemsitry/urine analysis usually unremarkable, rule out any other problems FNA of local LN - always FNA regional LN regardless of size Abdominal ultrasound - assess liver, spleen , LNs, FNA of spleen (routine - controversial), FNA of liver if abnormal) Thoracic radiography - lung metastasis uncommon but to evaluate sternal LN and Buffy coat - non specific and greater in inflammatory disease Bone marrow aspirates - rare unless extensive disease Biopsy - FNA inconclusive, pre-surgical to determine grade

Question 165

Factors affecting prognosis of MCTs?

Answer 165

``` Location Breed Appearance Systemic illness Recurrence Clinical staging - ie presence of metastatic disease Tumour histological grade - most important prognostic indicator Ki67 AGNORs C-kit mutation ```

Question 166

Patnaik grading system for MCTs?

Answer 166

``` Grades I (low) - III (high) Grade I: well differentiated tumours: - benign (<10% metastasis) - low recurrence rate - unlikely to cause death (up to 7-12%) Grade II: intermediate tumours: - variably metastatic (5-22%) - cause of death in 17-56% of patients - nodal metastases associated with poorer prognosis in some studies Grade III: poorly differentiated tumours: - highly metastatic (>80%) - likely to be cause of death ```

Question 167

Kiupel grading system for MCTs?

Answer 167

Low grade and high grade Low grade: MST > 2 years High grade: MST < 4 months

Question 168

Surgery for MCTs?

Answer 168

3cm margins and 1 fascial plane deep 1-2cm lateral margins may be adequate for grade I and II tumours Histopathology of all excised masses - grade and assess margins Potential to be curative for grade I and II

Question 169

MCT recurrence?

Answer 169

23% of incompletely excised grade II | 5-11% completely excised

Question 170

Indications for radiotherapy for MCTs?

Answer 170

Post op of incompletely excised MCTs Local nodal metastasis Gross disease - degranulation

Question 171

Indications for chemotherapy for MCTs? Which drugs?

Answer 171

High grade and/or confirmed metastasis Neoadjunctively prior to surgery Residual microscopic disease Commonly used: - vinblastine and prednisolone, approx 50% response rate with gross disease - lomustine - TKIs (toceranib/mastinib, have to test for KIT mutation on histopath, only 30% will respond if haven't got mutation)

Question 172

Clinical presentation, diagnosis and treatment of feline cutaneous MCT?

Answer 172

Cutaneous raised hairless masses Easily diagnosed by cytology and rarely metastatic Multiple tumours Surgical excision is usually curative

Question 173

Treatment of feline visceral MCTs?

Answer 173

Splenic: splenectomy, unclear role of chemotherapy Intestinal: metastasis common, poor prognosis, chemotherapy/TKI?

Question 174

TCCs - location? metastasis? Signs?

Answer 174

Most commonly -> bladder trigone but urethra and prostate High metastatic rate to medial iliac lymph nodes and other organs Metastatic rate 14% (local) and 16% (distant) at diagnosis but up to 50% at necropsy Breed predisposition - Scottish Terriers LUT signs - haematuria, stranguria, pollakyuria Occasionally signs related to bone metastasis (lameness_ or renal dysfunction Signs can be present for months as dog gets treated for 'complicated UTIs' Signs may improve with antibiotics

Question 175

Diagnosis of TCCs?

Answer 175

Histopathology Risk of seeding with FNA Traumatic cathetarisation Prostatic wash

Question 176

Staging of TCCs?

Answer 176

Haematology/Biochemistry/Urine analysis (including culture): - may show neutrophilia, renal dysfunction, presence of UTI - rule out any other problems Abdominal ultrasound - assess bladder wall, urethra, prostate and kidneys +/- metastasis in other organs - FNA T&A radiography - lung metastasis uncommon - bone metastasis

Question 177

Treatment of TCCs?

Answer 177

Surgery rarely possible due to location External beam radiotherapy - high rate of complications Medical treatment: - NSAIDs alone: MST 181 days - Mitoxantrone and NSAIDs: MST 291 days - Other chemotherapy drugs (Vinblastine, chlorambucil, carboplatin) Palliative care - regular urine cultures and antibiotic courses as appropriate cystotomy tubes/ Urethral stents

Question 178

Prognosis of TCCs?

Answer 178

Poor long term prognosis but quality of life can be maintained for several months. Local disease most likely cause of death/euthanasia (MST 6-8 months). Rapid deterioration due to renal failure or clinical signs associated with bone metastasis (pain) also possible Owner counselling and regular monitoring of quality of life.

Question 179

What is lymphoma? Aetiology?

Answer 179

A group of neoplasms that arise from the lymphoreticular cells (T or B cells) Normally arise from lymphoid tissue but can arise from virtually any tissue Aetiology: multifactorial and largely unknown - genetic and molecular factors - infectious diseases (retroviruses/Epstain-Barr virus/Helicobacter) - toxins - immunological factors

Question 180

Clinical presentation of lymphoma?

Answer 180

Can affect virtually any dog Middle age to old dogs Breed predispositions - boxer, bullmastiff, english bulldogs Intact females have reduced risk

Question 181

Anatomical classification of lymphoma?

Answer 181

``` Multicentric Craniomediastinal Gastro-intestinal Cutaneous Extra-nodal forms (CNS, renal, heart, bladder) ```

Question 182

Clinical signs of multi centric lymphoma?

Answer 182

Generalised peripheral lymphadenopathy +/- other signs: - moderate to marked lymph node enlargement - some dogs clinically well - rapid deterioration - non specific signs (weight loss, inappetance/anorexia, lethargy, pyrexia) - more specific signs (diarrhoea, vomiting, cough, ocular signs) - regional oedema if lymph drainage impaired

Question 183

Clinical signs of cranial mediastinal lymphoma?

Answer 183

Can be solitary lesion or part of multi centric form Tachypnoea, dyspnoea Signs of hypercalcaemia (PU/PD, vomiting/diarrhoea, muscle tremors, anorexia, weight loss) Occasionally pre-caval syndrome Altered position of PMI for cardiac auscultation, displacement of apex beat

Question 184

Clinical signs of GI (alimentary) lymphoma?

Answer 184

``` Weight loss, anorexia Pan-hypoproteinaemia (hypoalbuminemia), Evidence of malabsorption Abdominal masses or diffuse Occasionally multicentric lymphadenopathy Tends to be aggressive in dogs ```

Question 185

Forms of cutaneous lymphoma? Appearance?

Answer 185

Epitheliotrophic: T cell, solitary or generalised Non-epitheliotrophic: more frequently B cell, more likely to have lesions elsewhere Progression to raised, erythematous plaques/nodules Variable pruritus In general poorly responsive to chemotherapy

Question 186

Features of hepatosplenic and CNS lymphoma?

Answer 186

Hepatosplenic: aggressive, no peripheral lymphadenopathy, T cell CNS: mass lesion or diffuse, commonly ocular involvement, generally T cell

Question 187

Define paraneoplastic syndromes?

Answer 187

A syndrome (set of signs) that is a consequence of the tumour but it is not due to the presence of tumour cells in that location

Question 188

Paraneoplastic syndromes seen with lymphoma?

Answer 188

Hypercalcaemia (PTHrp): T cell (35%), mediastinal and GI forms Immune mediated diseases: IMHA, IMTP, pemphigus foliaceous Monoclonal gammopathies: B cell Neuropathies Cachexia

Question 189

Diagnosis of lymphoma?

Answer 189

Always cytological or histopathological Ancillary tests: - PARR (PCR): clonality and phenotype (B or T cell) - Flow cytometry: cell size, phenotype and expression of aberrant markers, requires living cells - Immunohistochemistry - Multiple biomarker test (canine lymphoma blood test, cLBT)

Question 190

Staging of lymphoma?

Answer 190

Stage I: single lymph node or lymphoid tissue in a single organ Stage II: multiple lymph nodes in one region +/- tonsils Stage III: generalised lymph node involvement Stage IV: hepatic and/or splenic involvement Grade V: manifestations in the blood and involvement of bone marrow and/or other organ systems (extra nodal forms always stage V, poorer prognosis) ``` Haematology - thrombocytopenia - neutrophilia - lymphocytosis - abnormal cells on smear Biochemistry - hypercalcaemia Aspirate or biopsy of other lymph nodes/organs Thoracic radiographs, abdominal ultrasound Bone marrow biopsy ```

Question 191

Treatment of lymphoma?

Answer 191

No treatment - MST 4-6 weeks for asymptomatic dogs - consider euthanasia for symptomatic dogs Prednisolone alone - ORR 30% median response duration 1-2 months Gold standard is multidrug chemotherapy - survival time varies - lower doses and prolonged intervals between doses compared to humans -> less side effects - rarely curative and very prolonged survivals in 20% of cases - high dose COP - discontinuous CHOP/CEOP Local treatments: Radiation may be useful for stage I disease, palliative therapy of local disease and mass lesions on CNS Surgery could be considered for rare Hodgkin's lymphoma and possibly extra nodal and early stage I disease Local treatments generally adjuvant of chemotherapy, not substitute

Question 192

High dose COP for lymphoma?

Answer 192

Preferred to low dose COP = cyclophosphamide, vincristine, prednisolone Well tolerated protocol Easily and safely administered in general practice setting Haematology performed prior to each treatment Urine sample prior to each cyclophosphamide Overall response rate 60-80% Median survival around 6-9 months

Question 193

Discontinuous CHOP/CEOP for lymphoma?

Answer 193

= cyclophosphamide, doxorubicin/epirubicin, vincristine, prednisolone Response rate 90-95% Median survival time 1--12 months No advantage to continuous treatment

Question 194

Specific chemotherapy toxicities of cyclophosphamide, doxirubicin/epirubicin and lomustine? How to avoid?

Answer 194

Cyclophosphamide: sterile haemorrhagic cystitis - furosemide, encourage urination Doxorubicin/epirubicin: cardiotoxicity - echocardiographic monitoring Lomustine: hepatotoxicity - monitor ALT and liver protectors

Question 195

What must be considered when treating CNS lymphoma?

Answer 195

Many drugs do not penetrate blood brain barrier - cytarabine, lomustine, steroids, L-asparaginase

Question 196

Treatment for epitheliotrophic lymphoma?

Answer 196

Typical protocols are COP or CCNU + Prednisolone: - no proven extension of life span (6-8 months) - may improve quality of life - response to treatment can be hard to gauge due to natural behaviour of disease Retinoids have also been used with moderate success for controlling clinical signs (pruritus) Radiation therapy is very useful for localized mucocutaneous disease

Question 197

Assessing response of lymphoma patient to treatment?

Answer 197

Palpation of lymph nodes/other lesions prior to every treatment Resolution of clinical signs Repeating imaging (restaging) for internal lesions Monitoring blood parameters (Ca, ALT etc.) Achieving a complete response (CR) is vital: - increases time to relapse - increases survival time - being in CR at the end of a discontinuous protocol leads to a very high chance of regaining remission later using the same protocol If CR not achieved, suggests resistant population of tumour cells - will rapidly become the dominant population

Question 198

Rescue protocols for lymphoma if complete response of lymphoma not achieved/initial treatment not worked?

Answer 198

DMAC (Dexamethasone, Melphalan, Actinomycin-D, Citarabine) CCNU, L-asparaginase and prednisolone Single agent anthracyclines (doxorubicin/ epirubicin) if not already used In general short lived responses but occasional long term survivors

Question 199

Follow up of lymphoma complete response patients following treatment? When is restating needed?

Answer 199

Monthly at least for the first 6 months and every 2-3 months thereafter Average time to relapse 4 months but very variable Restaging: - when there are no sentinel lymph nodes to follow - when patient not doing as well as expected or all clinical signs do not resolve - at the end of the induction phase - at the end of a discontinuous protocol

Question 200

What is an appropriate reticulocyte count?

Answer 200

In mild anaemia: >60 | Get from cases

Question 201

What are schistocytes?

Answer 201

Abnormally shaped RBCs | Indicates shearing through narrow vessels

Question 202

Types of lymphoma seen in cats?

Answer 202

Pre FeLV: mediastinal/multicentric lymphoma in young/adult cats Post FeLV: gastrointestinal lymphoma in geriatric cats (most common intestinal tumour in cats)

Question 203

How does FIV cause lymphoma?

Answer 203

Oncogenesis through immune suppression B cell lymphomas GIT more often affected

Question 204

Risk of developing lymphoma in cats with FIV and FeLV?

Answer 204

FeLV +ve: 62 x risk FIV +ve: 5-6 x risk FeLV and FIV +ve: 80 x risk

Question 205

Aetiological factors for lymphoma in cats?

Answer 205

``` FeLV FIV Genetic predisposition Altered expression of oncogenes, tumour expression genes Epigenetic modifications Tobacco smoke Chronic inflammatory conditions ie IBD ```

Question 206

Types of lymphoma in cats?

Answer 206

``` Nodal lymphoma (multicentric) Alimentary lymphoma Mediastinal lymphoma Extranodal lymphoma - nasal/retrobulbar - laryngeal - renal - CNS - ocular - cutaneous ```

Question 207

Features of nodal-multicentric lymphoma in cats? Clinical signs?

Answer 207

``` True multi centric lymphoma with symmetrical generalised lymphadenopathy is rare in cats (most common form in dogs) Regional lymphadenopathy more common Middle aged cats Clinical signs: - non painful lymph node enlargement - anorexia - depression - non specific malaise - pyrexia - (PUPD) ```

Question 208

Clinical signs of mediastinal lymphoma in cats? Examination findings?

Answer 208

``` Younger cats? Siamese? Respiratory distress Regurgitation/dysphagia Weight loss Lethargy, exercise intolerance Cough (rare) Palpable reduction in compressibility of cranial thorax Decreased lung sounds ```

Question 209

Differentials for mediastinal lymphoma in cats?

Answer 209

Thymoma Other cranial mediastinal lymphadenopathy Other causes of pleural effusions - CHF, pyothorax, FIP, haemothorax

Question 210

Differentials for nodal-multicentric lymphoma in cats?

Answer 210

Retroviral, viral, bacterial, fungal, mycobacterial and (protozoal) infections Immune mediated disease Idiopathic forms Metastatic disease (regional)

Question 211

Clinical signs of alimentary lymphoma in cats?

Answer 211

Older cats Insidious weight loss Anorexia - more common and severe in cats than dogs Diarrhoea (may not be observed) Malabsorption/PLE Occasionally vomiting - gastric involvement

Question 212

Differentials of alimentary lymphoma in cats?

Answer 212

``` Many other causes of GI signs FIP IBD Metastatic neoplasia Pancreatitis Mycobacterial infection ```

Question 213

Extranodal lymphoma in cats? Clinical signs?

Answer 213

CNS Nasal/retrobulbar - nasal discharge, epistaxis, obstruction, exopthalmos Renal - malaise, anorexia, renomegaly (bilateral), azotaemia

Question 214

Renal lymphoma in cats?

Answer 214

Degree of azotaemia not prognostic of outcome Overall low response rate and poor survival time High incidence of CNS involvement in cats with renal lymphoma - few agents cross blood brain barrier, add cytosine arabinoside in induction?

Question 215

Cutaneous lymphoma in cats?

Answer 215

Generally non epitheliotropic in cats Generally not very responsive to chemotherapy - clinical response is not as rapid as skin must repair Role of retinoids - in amelioration of clinical signs of epitheliotropic lymphoma Other agents e.g. interferon

Question 216

FNA for lymphoma in cats?

Answer 216

Cats often have low grade small cell or mixed lymphomas, especially multicentric lymphomas - difficult to differentiate from reactive hyperplasia on cytology, FNAs much less likely to be diagnostic than in dogs Cranial mediastinal and extra nodal lymphomas may be higher grade - easier to diagnose on FNA Renal lymphoma often requires biopsy GI lymphomas often high grade (can be low) - LN FNA in GI lymphoma rarely diagnostic

Question 217

Biopsy for diagnosis of lymphoma in cats?

Answer 217

Excisions biopsy of node Avoid Trucut needle biopsies - except renal lymphoma (check co-ag times) Wedge biopsy from extra nodal lesion or enormous node - impression smears If chance of mycobacterial disease (or fungal) keep some fresh tissue

Question 218

PARR for diagnosis of lymphoma in cats?

Answer 218

= PCR for antigen receptor rearrangements Clonality detection - identifies a clonal population in a background of normal lymphocytes High specificity Clonality not only feature of neoplasia Can get negative results if not enough cells Identifies 65-70% of lymphomas in cats

Question 219

Clinical staging, grading and typing of lymphoma in cats?

Answer 219

Don't fit in standard staging used for dogs No simple useful staging system adopted WHO grading for canine lymphoma recently applied to cats Immunophenotype not prognostic

Question 220

Positive and negative prognostic indicators for lymphoma in cats?

Answer 220

``` Positive: - Achieving CR - Small volume extra nodal disease - nasal lymphoma - T cell immunophenotype in indolent lymphomas? Negative: - Failure to achieve CR - FeLV +ve status - previous therapy with corticosteroids? ```

Question 221

Treatment of lymphoma?

Answer 221

Corticosteroids Multi drug regimes - COP, CHOP, COAP Non continuous regimes - poorly evaluated for cats High dose COP (cyclophosphamide, vincristine, prednisolone) is excellent protocol for cats - 75% CR, 1 year survival 49%, 2 year survival 40% Use of doxorubicin controversial - poor response rates was single agent Survival times for multi drug regimes disappointing: MW 5-6 months

Question 222

Median survival of cat with lymphoma without therapy?

Answer 222

4 weeks

Question 223

Patient monitoring for side effects of cat with lymphoma treated with chemotherapy

Answer 223

Myelosuprpessive agents - check haemorrhage prior to every bolus dose, on low dose COP check at appropriate intervals Intermittently check urine Hair loss (whiskers) GI signs

Question 224

Treatment for alimentary lymphoma?

Answer 224

Surgical excision of solitary mass lesion - must biopsy nodes Follow up chemotherapy? Extensive infiltration - staggered induction to reduce risk of perforation? Supportive therapy - appetite stimulants, O-tube?, vitamin B12 Gastric lymphoma very difficult to treat LGL lymphoma has poor response to chemotherapy Low grade 'epitheliotrophic' tend to respond to chlorambucil and prednisolone only - extended survival times can be achieved (2 years)

Question 225

What is the outcome of lymphoma in cats following chemotherapy?

Answer 225

Most cats will develop drug resistance and will relapse Rescue therapy - single agent doxorubicin or lumustine (RR 40%) Could consider radiation if local disease Small % of cats will be cured

Question 226

Features of acute lymphoid leukaemia (ALL) and acute myeloid leukaemia (AML) in cats?

Answer 226

High WBC counts Concurrent pancytopenias Poor prognosis (weeks-months) even with chemotherapy Myelodysplastic syndrome (MDS) recognised as precursor to acute leukaemia in FeLV positive cats - characterised by cytopenias without circulating neoplastic cells

Question 227

Acute leukaemia treatment in cats?

Answer 227

``` Supportive therapy - very sick patients: - blood transfusion - antibiotics - barrier nursing - CSF? Multi-agent chemotherapy protocols: - COP vs CHOP - addition of cytarabine infusions may improve response MST of all treated with chemotherapy is 120 days in dogs ```

Question 228

Features of chronic lymphoid leukaemia in cats? Treatment?

Answer 228

Proliferation of mature lymphocytes in bone marrow Rare (T cell > B cell) Lymphocyte counts >30x10^9/L Decision to treat based on the individual (presence of CS, degree of lymphocytosis) Treat with prednisolone/chlorambucil - survival times of 1-3 years reported

Question 229

Features of chronic myeloid leukaemia?

Answer 229

Proliferation of mature myeloid cells (normally neutrophils) in bone marrow Rarer than chronic lymphoid leukaemia Have to exclude other causes of extreme neutrophilia: infection, immune mediated disease, paraneoplastic disease

Question 230

Leukaemia diagnosis in cats?

Answer 230

Haematology with manual differential and smear evaluation Flow cytometry of peripheral blood Staging to evaluate extent of disease - thoracic radiographs, abdominal ultrasound, cytology of liver/spleen Bone marrow biopsy (cytology + histology)

Question 231

Features of myeloma related disorders in cats?

Answer 231

AKA multiple myeloma Rare <1% of malignant tumours in animals Systemic neoplastic proliferation of plasma cells results in overproduction of antibody (IgA or IgG) Can get local disease - extramedullary plasmacytoma which can progress to multiple myeloma Hyperproteinemia can lead to hyperviscosity syndrome - neurological symptoms, retinal detachment, CHF (cats > dogs), hypertension, coagulopathy Bone marrow involvement can lead to cytopenias - secondary infections Renal disease present in 33-50% of dogs (multifactorial due to proteinuria, hypercalcaemia, renal infiltration, urinary infection)

Question 232

Multiple myeloma diagnosis?

Answer 232

Haematology, biochemistry, urinalysis: - non specific, may see circulating plasma cells - proteinuria - hypercalcaemia - hyperglobinaemia Serum protein electrophoresis - monoclonal gammopathy Diagnostic imaging: - hepatosplenomegaly - osteolytic bone lesions Cytology - liver, spleen and bone marrow In dogs, have to fulfil 2 of following criteria: - monoclonal gammopathy - radiographic evidence of osteolytic bone lesions - >5% neoplastic plasma cells or >10-20% plasmacytosis in the bone marrow - Bence-Jones proteinuria In feline myeloma related disorder there is rarely bone marrow involvement so should demonstrate plasma cell infiltration of visceral organs

Question 233

Multiple myeloma treatment?

Answer 233

``` Supportive treatment: - blood transfusions - plasmaphoeresis - antibiotics if secondary infection - therapy for hypercalcaemia Prednisolone Chemotherapy - prednisolone, melphalan - cumulative myelosuppression is seen (perform haematology every 2 weeks, then monthly) Median survival 540 days (dogs) Local extra medullary plasma cell disease may be treated surgically if no systemic involvement ```

Question 234

What gastrointestinal paraneoplastic syndromes are there?

Answer 234

Cancer cachexia/sarcopenia complex Cancer anorexia Gastro-duodenal ulceration Protein losing enteropathy

Question 235

What causes cancer cachexia/sarcopenia and anorexia?

Answer 235

1. Cancer cells preferentially use glucose for energy and poor tumour blood flow leads to anaerobic respiration -> increased lactate production and altered insulin sensitivity 2. Cancer related cytokine production and inflammation can also alter metabolism 3. Some patients suffer poor appetite but can see changes even with normal appetite Anorexia common - cytokine release (IL-6, IL-1) 'anorexigen' - abdominal pain with GI neoplasia - use of chemotherapy: taste alteration? GI side effects Cachexia uncommon in dogs, more common in cats: - cytokine release (IL-1B, TGFB, IL-6) - insulin resistance, extensive lipolysis, proteolysis

Question 236

Clinical signs of cancer cachexia/sarcopenia and anorexia? Treatment? Quality of life?

Answer 236

Weight loss, reduced fat mass, lean muscle loss, poor tolerance of treatment Treatment: - maintain caloric intake with low carbohydrate high fat diet - omega 3 PUFA may be beneficial in reducing inflammation related changes Uncommon problem in animals but might indicate poor quality of life

Question 237

Why can cancers cause gastro-duodenal ulceration? Problems?

Answer 237

GI tumours often have associated gastric or duodenal ulceration at their location due to poor blood supply and altered wall structure - often bleed -> anaemia - can sometimes rupture Some tumours produce hormones/metabolites -> gastric acid -> ulceration - dogs with MCT have elevated blood histamine -> GI signs, ulceration and bleeding - gastrinomas produce gastrin -> GI signs, ulceration and bleeding - some neuroendocrine tumours can cause GI bleeding (hormone/cytokine production)

Question 238

Which types of tumours can cause protein losing enteropathy? Problems?

Answer 238

Diffuse GI lesions can allow protein loss - seen particularly with GI lymphoma Typically low TP, globulin and albumin, often accompanied by diarrhoea Low albumin can lead to ascites Other effects due to loss of proteins binding hormones, clotting factors etc

Question 239

How can tumours cause acute blood loss anaemia? Clinical signs? Type of anaemia?

Answer 239

Due to haemorrhage from a tumour - spleen, GI Clinical signs of hypovolaemia and shock TP drops before PCV Anaemia initially nonregenerative, then becomes regenerative Platelet count normal then low

Question 240

How can tumours cause chronic blood loss anaemia? Clinical signs? Type of anaemia?

Answer 240

Low grade haemorrhage from GI tumour or PNS: excess histamine (MCT) or gastrin (gastrinoma) causing ulceration Main differentials are other GI or oral lesions Clinical signs of lethargy, pallor Poorly regenerative microcytic hypo chromic anaemia due to iron deficiency Normal or elevated platelet count

Question 241

How can tumours cause myelophthisis?

Answer 241

Crowding out of stem cells in the bone marrow by tumour cells Tumours might produce suppressive cytokines (tumour types include lymphoma, leukaemia, multiple myeloma, occasionally histiocytic sarcoma and mast cell tumour) One or several cytopenias Neutropenia then thrombocytopenia before anaemia Non regenerative normochromic normocytic anaemia Diagnosis by bone marrow aspirate

Question 242

What reduced production cytopenias can cancers cause?

Answer 242

Myelophthisis Anaemia of chronic inflammatory disease Hyperoestrogenism

Question 243

Which tumour can cause hyperoestrogenism? Problems? Signs? Treatment?

Answer 243

Testicular tumours - 50% of dogs with Sertoli cell tumours Initially neutrophilia then progression to bone marrow hypoplasia Neutropenia, thrombocytopenia and non-regenerative anaemia Other signs are feminisation signs and include symmetrical alopecia, pendulous prepuce, hyperpigmentation, penile atrophy, gynecomastia, prostatic metaplasia Castration can reverse many signs but bone marrow changes can be slow to recover or irreversible

Question 244

Which tumours can cause immune mediated anaemia and thrombocytopenia?

Answer 244

Secondary to lymphoproliferative tumours (must exclude before treating IMHA or IMTP)

Question 245

Why can tumours cause microangiopathic anaemia? Indicator?

Answer 245

Fragmentation and shearing of RBCs leads to anaemia Caused by fibrin networks Causes include HSA and DIC Schistocytosis is a key indicator

Question 246

Which tumours can cause erythrocytosis? Signs? Treatment?

Answer 246

Renal tumours via increased EPO, lymphoma, nasal fibrosarcoma, TVT, hepatic tumours Clinically significant erythrocytoses include PUPD, neurological signs and seizures Treatment - phlebotomy, removal of inciting cause, hydroxyurea

Question 247

What paraneoplastic cytoses are there?

Answer 247

Erythrocytosis Neutrophilia Eusinophilia

Question 248

Why do many tumours cause neutrophilia?

Answer 248

Tumour indeed or an immune response to the tumour

Question 249

Which tumours most commonly cause eosinophilia? Why?

Answer 249

T cell lymphoma and MCT | Due to IL-5 production

Question 250

Which tumours produce mono-clonal gammopathies? Signs? Diagnosis? Treatment?

Answer 250

Multiple myeloma - a tumour of plasma cells, lymphoma, leukaemia Elevated serum globulins on biochemistry Clinical signs due to hyperviscosity (neurological including seizures, coma, cardiac signs), reduced immune function, renal failure, coagulopathies and ocular disorders Gammopathies detected by electrophoresis of serum and urine (Bence-Jones proteins) Treatment by plasmapheresis and tumour directed therapy?

Question 251

What coagulation problems can tumours cause?

Answer 251

``` Altered coagulation - Altered platelet function - Infarcts/thromboembolism can result DIC - mainly in association with carcinoma and HSA ```

Question 252

What is DIC? Diagnosis?

Answer 252

Syndrome of altered consumptive coagulation Thromboembolism in small vessels and bleeding due to consumption of platelets and clotting factors Multi-organ failure and death Elevated APTT, PT, FDPs/D dimers, low fibrinogen, low platelet count, schistocytes

Question 253

What endocrine paraneoplastic syndromes are there?

Answer 253

Hypercalcaemia Hypoglycaemia Ectopic ACTH syndrome Hyperoestrogenism

Question 254

How often is hypercalcaemia due to PNS? Other differentials?

Answer 254

Cause of 2/3 canine hypercalcaemia and 1/3 feline hypercalcaemia Other ddx: lab error, renal failure, hypervitaminosis D, hypoadrenocorticism, granulomatous disease

Question 255

Which tumours most commonly cause hypercalcaemia? Less common ones? Mechanisms?

Answer 255

Lymphoma, anal sac adenocarcinoma (25%), hyperparathyroidism | Others - multiple myeloma, thymoma

Question 256

Clinical signs of hypercalcaemia?

Answer 256

* PU/PD * Dehydration * GI signs - inappetence and vomiting * Weakness * Muscle fasciculation * Calcification of soft tissues (especially kidneys) * Arrhythmias * Death

Question 257

Management of severe hypercalcaemia in an emergency? Long term treatment?

Answer 257

Initially: - rehydrate with NaCl 0.9% 3-4 x maintenance - also enhances calciuresis The: - continue fluids - consider furosemide - increases calciuresis by increased Na loss - consider bisphosphonates - toxic to osteoclasts so slows Ca release from bone - consider salmon calcitonin - short acting (a few days) but often effective - consider prednisolone - only when lymphoproliferative disease diagnosed or excluded - removal of inciting lesion - only effective long term treatment

Question 258

Work up for hypercalcaemia?

Answer 258

* Assess tCa and if elevated assess iCa, also consider phosphate * Ensure rectal exam negative for anal gland tumours * Assess and aspirate lymph node * Check history for diet and toxin exposure * Imaging of thorax and abdomen and ultrasound neck esp. if iCa ↑ and Phos ↓ * PTH / PTHrp / vitamin D if appropriate history of exposure * Bone marrow biopsy * Consider ACTH stim if other signs are consistent with hypoadrenocorticism

Question 259

Which tumours can cause hypoglycaemia? Clinical signs? Management?

Answer 259

Most commonly insulinoma IGF-II-omas Hepatocellular carcinoma, smooth muscle tumours - caused by IGF-II Weakness, disorientation, seizures, coma and death Emergency - IV glucose and CRI glucose if necessary Medical management - prednisolone, diazoxide, octreotide Removal of inciting tumour

Question 260

Non neoplastic ddx for hypoglycaemia?

Answer 260

``` Sepsis Starvation Liver dysfunction Hypoadrenocorticism Lab error Some toxicities ```

Question 261

What cutaneous paraneoplastic syndromes are there?

Answer 261

* Alopecia and Malassezzia associated dermatitis * Pancreatic associated panniculitis * Superficial necrolytic dermatitis (SND) * Paraneoplastic immune mediated disease – Pemphigus and Erythema multiforme * Feline Thymoma-Associated Exfoliative Dermatitis (FTAED) * Cutaneous flushing * Nodular dermatofibrosis

Question 262

Feline Paraneoplastic Alopecia (FPA) - signs?

Answer 262

Acute-onset, non pruritic, progressive symmetrical alopecia Initially affects ventral abdomen and limbs then generalises hair easily epilated Glistening skin: alopecia skin elastic and thin - smooth shiny appearance Footpad lesions: concentric scale, crusting and painful fissures affecting footpads Malassezia dermatitis: brown greasy accumulations around eyes, nose and claw beds, may be pruritic Older cats (7-16 years) No sex or breed predilection

Question 263

Ddx for feline paraneoplastic alopecia (FPA)?

Answer 263

``` Dermatophytosis Demodicosis SIA (pruritis, psychogenic) Telogen defluxion Endocrinopathies Superficial necrolytic dermatitis (SND) ```

Question 264

What is superficial necrolytic dermatitis (SND)? Signs?

Answer 264

Dogs and cats Hepatic disease and pancreatic neoplasia Associated amino acid deficiency Distinctive histo and U/S Footpad hyperkeratosis - erythema, crusting, hyperkeratosis Crusting dermatitis - alopecia, erosions, ulceration, adherent crusts Other signs - none in early stages, lethargy, inappetence, systemic signs associated with hepatic/pancreatic disease, some cases develop DM in association with hepatic disease

Question 265

Paraneoplastic pemphigus (PNP) - signs? Aetiopathogenesis?

Answer 265

Very rare cutaneous PNS Autoimmune-induced ulceration of the mucosae and mucocutaneous junctions Lymphoma, thymoma, splenic sarcoma, metastatic thymic mass Primary immune mediated pemphigus also seen Exact pathomechanism unknown Antibodies against tumour antigens cross-react with self-antigens

Question 266

Cutaneous markers for paraneoplastic pemphigus (PNP)?

Answer 266

Oral and much-cutaneous ulceration: - vesicles (rapidly rupture) - severe ulceration of oral cavity and mucocutaneous junctions - lesions often bilaterally symmetrical - claw beds and pressure points may be affected

Question 267

Feline Thymoma-Associated Exfoliative Dermatitis (FTAED) - which cats? Cutaneous markers?

Answer 267

Older cats, no sex or breed predilection Exfoliative dermatitis - non pruritic, diffuse erythema and skin exfoliation/scaling, alopecia, head and pinnae and then generalied Keratosebaceous accumulations - brown, keratosebaceous debris interdigital skin, claw beds and ear canals, some cases associated with Malassezia dermatitis Crusting and ulceration

Question 268

What is cutaneous flushing? Which tumours can cause it? Ddx?

Answer 268

Periodic release of vasoactive substances by tumours leads skin colour changes Rarely reported but reported with pheochromocytoma, lung tumours and MCT Ddx: Demodicosis, drug reactions and systemic lupus erythematosus

Question 269

Nodular dermatofibrosis - signs? Which animals? Cause?

Answer 269

Nodules of well differentiated collagenous nevi mainly on limbs but also heads and trunk Middle aged GSDs with bilateral renal cysts or cyst adenocarcinoma Inherited in autosomal dominant fashion Due to mutated Birt-Hogge-Dube gene

Question 270

Hypertrophic osteopathy - what is it? Which tumours can cause it? Why? Clinical signs? Diagnosis? Treatment?

Answer 270

Palisading periosteal proliferation along shafts of long bones Pulmonary (or occasionally abdominal) tumours Cause unknown - poss increased blood flow to limbs due to afferent neurological stimulation In humans vagotomy can lead to resolution Shifting lameness Swelling/oedema Limbs feel warm and are uncomfortable to touch Diagnosis - clinical signs and radiography of long bones and pelvis Treatment: • Remove inciting cause • Prednisolone • Pain relief • Bisphosponates

Question 271

Why can tumours cause paraneoplastic pyrexia? Which tumours? Problems? Treatment?

Answer 271

Due to expression of inflammatory cytokines by or in response to the tumour Especially lymphoma, renal cancers and hepatic tumours Can lead to anorexia and malaise. Need to exclude other causes especially infection before assuming pyrexia is neoplasia associated Treatment by removal of the tumour, NSAIDS/paracetamol

Question 272

What is palliative care?

Answer 272

Relieving pain without dealing with the cause of the condition Improves quality of life

Question 273

What is quality of life?

Answer 273

An individual satisfaction with: - physical and psychological health (physical state e.g. pain, mentation e.g. active) - physical and social environment (daily activities e.g. food intake and walks, behaviour) - ability to interact with that environment (interaction with owners e.g. playful

Question 274

What are primary concerns for health related quality of life in animals?

Answer 274

Appetite Mobility Pain Behaviour

Question 275

How to improve quality of life with palliative care for cancer?

Answer 275

``` Pain management Treatment of side effects Nutrition Treatment of cancer-specific signs Owner's expectations Alternative medicine ```

Question 276

Types of pain in cancer patients?

Answer 276

Adaptive nociceptive = direct tissue injury - somatic = cancer cell invasion of skeleton, soft tissue, tendons/ligaments (focal, stabbing) - visceral = cancer cell infiltration, compression or distortion of internal organs (diffuse, squeezing) Maladaptive neuropathic = infiltration of nerves and spinal cord (burning, shooting, numbness)

Question 277

Which tumours cause somatic adaptive nociceptive pain?

Answer 277

Bone and joint sarcoma Oral, nasal tumour Inflammatory mammary carcinoma ASAC

Question 278

Which tumours cause visceral adaptive nociceptive pain?

Answer 278

TCC Pancreatic carcinoma Hemangiosarcoma Carcinomatosis

Question 279

Signs of pain in cancer patients?

Answer 279

Reduced activity Appetite change Increased respiration/heart rate Attitude change (aggressiveness, dullness, shyness) Facial expression (head hung low, squinted eye, sad expression) Appearance of the coat (failure to groom) Response to palpation Self trauma (licking, scratching) Posture and ambulation Vocalisation Sleep disturbance

Question 280

Pain management for cancer patients?

Answer 280

Non opioid +/- adjuvant - NSAIDs, paracetamol Opioid for mild to moderate pain +/- non opioid +/- adjuvant - codeine, tramadol Opioid for moderate to severe pain +/- non opioid +/- adjuvant - morphine, methadone, fentanyl

Question 281

What are NSAIDs good for in cancer patients? Contra-indications?

Answer 281

Very good painkiller May have some anti-cancer action (carcinoma) Contra-indicated with corticosteroids GI/kidney issues

Question 282

What is tramadol? Side effects?

Answer 282

Opoidergic/monoaminergic drug Main action: weak u-agonist (inhibition of serotonin reuptake) Can cause dysphoria, sedation, nausea Doubt on its efficacy in dogs

Question 283

Adjuvants for pain management of cancer patients?

Answer 283

``` Gabapentin: - good for neuropathic pain - can cause mild sedation and ataxia Amantadine: - minimal evidence of action - minimal side effects (lethargy, dizziness) - NMDA agonist Oral buprenorphine Tricyclic antidepressants (amitriptyline, clomipramine, fluoxetine) ```

Question 284

Mechanisms of pain from osteosarcomas? Pain management?

Answer 284

Tumour associated inflammation due to neoplastic osteoblasts Bone destruction due to osteoclasts Multimodal approach: - e.g. NSAID, paracetamol, gabapentin/amantadine +/- tramadol Radiation therapy - aim for pain management = cell death of both neoplastic osteoblasts and resorbing osteoclasts - palliative setting: 1-4 treatments, minimal side effects - 75-95% of pain alleviation for 2-4 months Biphosphonates - aim = induction of osteoclasts apoptosis -> limit bone resorption - can be used for multiple cancers with associated osteolysis - IV or oral - moderate efficacy 50%

Question 285

What cancer specific palliative treatments can be used?

Answer 285

Stenting - urethra, trachea, minimally invasive but technically challenging Cystotomy tubes - urethral obstructions (TCC), not long term solution, risk of abdominal metastasis Amputation Surgical excision of ulcerated/painful mass

Question 286

Nutritional management of cancer patients?

Answer 286

Low carbohydrate diet - theoretical benefit to limit glucose intake, benefit in mouse model, no proof in clinic, danger with cancer cachexia/anorexia Well balanced diet - adapt to BCS/MCS Supplements? - Omega 3, vitamins, anti-oxidants (no clear evidence of benefit) Feeding techniques - change diet slowly (more appellant), change consistency, small frequent meals, warm up Medications - maropitant to manage vomiting/nausea, mirtazapine, cyproheptatide Assisted feeding techniques - oesophagostomy tubes, PEG tubes Steroids?

Question 287

Difference between anorexia and cachexia?

Answer 287

Anorexia - decreased fat | Cachexia - decrease lean body mass +/- fat

Question 288

Nutrition assessment of cancer patients?

Answer 288

BCS Muscle condition score Poor hair coat, seborrhoea

Question 289

Pros and cons of steroids for palliative cancer treatment?

Answer 289

``` Pros: - can stimulate appetite - useful for round cell tumours - reduces inflammation (brain tumours, radiation therapy side effects) Cons: - weak analgesia effect - precludes use of NSAIDs - muscle wastage - no effects on carcinoma and sarcoma - can prevent diagnosis - can create resistance (lymphoma) ```

Question 290

What alternative medicines are there for palliative cancer care?

Answer 290

``` Acupuncture - neuromodulation - pain control, poss anti-emetic Herbs - theoretical benefit - limited evidence - possible harmful effect (coagulation, increases toxicity to chemo/RT) - lack of regulation Cannabinoids - analgesia, anti-emetic, anti-tumour effects - can produce neurological signs - lack of proof in small animals ```

Question 291

What should neutrophils be before chemotherapy? What if less?

Answer 291

>3 (delay if <3) Some clinicians may go ahead if 2-3 with reduce dose If <1 but clinically well, send home with oral antibiotics If <1 and clinically unwell, admit

Question 292

What should platelets be before chemotherapy?

Answer 292

>100

Question 293

Usual protocol used for lymphoma in dogs and cats?

Answer 293

CHOP in dogs | COP in cats

Question 294

When is cyclophosphamide contraindicated?

Answer 294

If UTI - check dipstick before treatment If haematuria: - Cysto and culture to check if UTI - Substitute for chlorambucil for that treatment while treating UTI/waiting for results - Can use cyclo for next treatment if UTI cleared but if second case of haematuria, don't use cyclo again

Question 295

What to do before/while infusing epirubicin/doxorubicin as part of CHOP protocol? What to check before treatment?

Answer 295

Can give maropitant 1-2h before as causes nausea and inappetence Infuse slowly over 20 mins as risk of cardiac arrhythmias and anaphylaxis Watch for restlessness, discomfort, femoral pulse/HR Echo before treatment if DCM/breeds predisposed to DCM Check urea and creatinine of cats before treatment Can cure hepatic damage - careful if pre-existing liver problem

Question 296

Cutaneous squamous cell carcinoma: Signs?Treatment options? Prognosis?

Answer 296

``` Signs: - common in white cats: face, pinna - scabs - reddened, thickened skin - ulceration, plaques Options: - excise when small ASAP - RT unknown effectiveness - chemo - photodynamic therapy - laser ablation - imiquiod on small lesions caused by papillomavirus Prognosis: - excellent following sx - poor if large and invasive ```

Question 297

Treatment of hypercalcaemia?

Answer 297

IVFT Bisphosphonate (reduces osteoclast activity) Avoid steroids before diagnosed lymphoma (as can reduce the lymphoma)

Question 298

Why do you get paraneoplastic hypercalcaemiua?

Answer 298

Cytokine release | PTH related hormone released

Question 299

What makes up a normal lymph node on cytology? What is abnormal?

Answer 299

``` Normal: - 80% small lymphocytes (mature) - 15% intermediate lymphocytes - 5% large lymphocytes (immature) Abnormal: - >50% large lymphocytes - anisocytosis/anisokaryosis - mitotic index - can get small cell lymphomas - impossible to dx on cytology (need PARR) ```

Question 300

Main side effects of CHOP protocol for lymphoma?

Answer 300

``` Anaemia, thrombocytopenia, myelosuppression Sterile haemorrhagic cystitis Cardiotixicity GI toxicity Occurs in 20-30% of patients ```

Question 301

Are B or T cell lymphomas better?

Answer 301

B cell better | T cell lymphomas respond less to chemo

Question 302

Rescue protocols for lymphoma?

Answer 302

Lomustine LPP = lomustine, procarbazine, prednisolone DMAC = dexamathasone, metphalan, actinomycin, cytosine arabinoside Actinomycin D

Question 303

What to do before surgery to remove MCT?

Answer 303

Steroids for couple of weeks before to shrink tumour - helps get appropriate margins

Question 304

What is Darier's sign?

Answer 304

Degranulation of MCT after FNA (can use chlorphenamine prior to FNA to prevent this) Looks like a bullseye

Question 305

What locations have a worse prognosis for MCTs?

Answer 305

Mucocutaneous Muzzle Inguinal

Question 306

Where do anal sac adenocarcinomas often metastasis to?

Answer 306

Via lymphatics to medial iliac LNs - so FNA

Question 307

Ddx for anal sac issue?

Answer 307

Anal gland abscess Impaction Anal sac adenocarcinoma Skin - MCT, STS, lipoma, cutaneous lymphoma, SCC

Question 308

Signs of anal sac adenocarcinoma?

Answer 308

Tenesmus, straining (usually due to metastasis to medial iliac lymph nodes) Scooting Flat faeces Hypercalcaemia: PUPD, restless, anorexic, lethargic, V+, D, facial paresis, cardiac arrhythmias

Question 309

Treatment for anal sac carcinomas?

Answer 309

Surgery - care not to damage anal sphincter, risk of incontinence Chemo - need oral successive treatment, tokeranib Steroids for hypercalcaemia Stool softener NSAIDs if no hypercalcaemia

Question 310

Ddx for nasal discharge and how would they present?

Answer 310

``` Allergic rhinitis - May be seasonal - Marked snotty nasal discharge - Bilateral Fungal rhinitis (Aspergillosis) - Nasal depigmentation - Painful around muzzle: owner may note not wanting to put head in deep bowls, head shy, not wanting to push doors with nose etc Foreign body - Acute - Paroxysmal dramatic sneezing Neoplasia - Sneezing - Unilateral - May be progressive - Often serosanguinous nasal discharge - Exopthalmos - Check airflow: would have obstructed airway down one nostril - Stertorous breathing: owner may say snoring ```

Question 311

Diagnostic investigation of nasal discharge? Findings for different ddx?

Answer 311

DV intraoral radiograph: - FB: mucosal inflammation may increase ST opacity but generally often don’t see much (need scope) - Neoplasia: loss of turbinates, usually start at the back, bone lysis, cribriform plate damage, septum may be deviated, tumour may expand into oropharynx, increased ST opacity - Fungal rhinitis: punctate lucency of turbinates, destructive rhinitis, uncommon to cause other bony lysis - Allergic rhinitis: increased ST from mucosal inflammation so turbinates look coarser, no lysis Endoscopy - If no endoscope available, can use otoscope to see first part, or laryngoscope to look under soft palate Pinch biopsy: - Risks: undiagnostic sample, going through into brain, haemorrhage - Avoid going into brain by measuring length need to go in - Urinary catheter for cats may work - If think neoplasia, whilst under GA: FNA submandibular, retropharyngeal, prescapular LNs

Question 312

What is nasal neoplasia likely to be in dogs?

Answer 312

``` Adenocarcinoma usually (unlikely to have metastasised) <10% are lymphomas - important to diagnose as more likely to have metastasised at diagnosis ```

Question 313

Treatment of choice for nasal carcinoma?

Answer 313

Radiotherapy | Eye and nose side effects

Question 314

What to assume if cat with mass between shoulders?

Answer 314

Treat as feline injection site sarcoma (FISS) until proven otherwise

Question 315

Where do prostate TCCs like to metastasise to?

Answer 315

LNs Lungs Bone - so can see lameness