Introduction
Breed associated tumours in dogs
a) Flat-coated retrievers and Bernese Mountain
b) German shepherd and Golden retrievers
c) Boxers, pugs, golden retrievers
d) Giant breeds
a) Disseminated histiocytic sarcomas
b) Haemangiosarcoma
c) Mast cell tumour
d) Osteosarcoma of appendicular skeleton
Introduction
Features of neoplasia (4)
- Uncontrolled cell proliferation
- Impaired cellular differentiation
- Chromosomal instability, mutations, altered gene expression
- Invasion and metastasis
Introduction
Cytological features of malignancy
a) Cell number
b) Cytoplasmic features
c) Nuclear features
a) Numerous cells
b)
- Large/giant cells (anisocytosis)
- Poorly differentiated
- High nuclear : cytoplasmic ratio
c)
- Large nuclear size
- Multiple prominent nucleoli
- Hyperchromatic
Introduction
Histological features of malignancy
a) Tumour architecture
b) Other features
a)
- Densely cellular mass
- Lack of structural organisation
- Cytological features
b)
- Invasion of cells into adjacent tissues
- Tumour necrosis
- Evidence of vascular or lymphatic invasion by tumour cells
Introduction
Common sites of metastasis (2)
- Drainage lymph nodes
- Viscera (lungs, kidney, liver, spleen)
Clincal approach to cancer
Histology biopsy techniques (5)
- Needle - eg Tru cut
- Skin Punch
- Grab biopsy
- Incisional biopsy
- Excisional biopsy
Clinical approach to cancer
Cytology techniques (3)
- Impression smears
- Fine needle aspiration
- Cytospins of body fluids / effusions
Clinical approach to cancer
Cytology vs Histology (advantages and disadvantages)
Cytology
- Quick
- Cheap
- Gives valuable info on cell type and malignancy
- Cannot grade tumours
Histology
- Should provide definite diagnosis
- Histological features provide Grade
- Takes time to process tissue
- Biopsy procedure and processing costs
Clinical approach to cancer
Primary tumours
a) physical signs of local invasion (3)
b) Other diagnostic techniques to be considered to aid evaluation (4)
a)
- diffuse, indistinct boundaries between normal tissue and tumour
- fixation of tumour mass in one or more planes
- thickening of adjacent tissues
b)
- radiography: tumours near bone, especially oral cavity and nasal chambers, contrast used for body cavities
- ultrasound: soft tissues and abdominal organs
- endoscopy: hollow organs
- CT/MRI: tumours otherwise inaccessible (brain)
Cancer complications
Direct effect of tumours on haematopoesis
- neoplastic invasion of bone marrow (myelophthisis) in lymphoproliferative and myeloproliferative conditions
- reduction in normal cell numbers (non-regenerative anaemia, thrombocytopenia, neutropenia)
Cancer complications
a) Indirect effect on haematopoesis
b) How tumours can cause blood loss
a)
- oestrogen producing tumours
- myelofibrosis (non-regenerative anemia, thrombocytopenia, neutropenia)
b)
- haemorrhage from tumour
- gastroduodenal ulceration due to hyperhistaminaemia or hypergastinaemia
- secondary to bleeding disorder
Cancer complications
Paraneoplastic syndromes
a) Topic vs ectopic
b) Examples of topic paraneoplastic syndromes (5)
c) Examples of ectopic paraneoplastic syndromes (3)
a)
- Topic: resulting from functional tumour of endocrine origin
- Ectopic: non-endocrine tumours
b)
- Hyperadrenocorticism (cushings)
- Hyperthyroidism
- Primary hyperparathyroidism
- Hypoglycaemia
- Hypergastrinaemia
c)
- Hypercalcaemia
- Hypoglycaemia
- Hyperhistaminaemia
Cancer complications
Hypercalcaemia
a) Common malignancies causing (2)
b) Effects (4)
c) How to manage hypercalcaemia
a)
- Lymphoid tumours
- Anal gland adenocarcinoma
b)
- Renal effects: renal failure
- Gastrointestinal effects: anorexia, vomiting
- Neuromuscular effects: lethargy, weakness
- Cardiovascular effects: bradycardia, arrhythmias
c)
- restore circulating volume (IV fluids)
- reduce plasma calcium concentration
- identify and treat cause
Cancer complications
Mast cell tumours
a) Commonly affected species
b) What is it associated with and local effects of this (5)
c) Systemic effects of (b)
d) Treatment
a) Dogs (occasionall cats and horses)
b) Hyperhistaminaemia
- oedema
- erythema
- pruritis
- bleeding tendency
- delayed wound healing
c)
- anaphylaxis
- gastroduodenal ulceration
d) H2 antagonists
Chemotherapy
a) Types of tumour that have high chemosensitivity (3)
b) Types of tumour that have low chemosensitivity (3)
c) Define growth fraction
a)
- lymphoma
- myeloma
- some forms of leukaemia
b)
- slow growing sarcomas
- carcinomas
- melanoma
c) Determines whether chemotherapy will be effective. Drugs are only active against dividing cells, so the most proliferative cancers will respond
Chemotherapy
a) Induction therapy
b) Maintenance therapy
c) Rescue therapy
a)
- reduce tumour burden to a minimal level below limits of detection (remission)
- involves intensive course of treatment over a defined time period
b)
- when clinical remission achieved by induction treatment, a less intensive treatment can be adopted to maintain remission
c)
- establish further remission of the tumour, usually with a more aggressive therapy with agents that the tumour hasn’t been exposed to
Chemotherapy
Myelosuppression
a) Exceptions of cytotoxic drugs that aren’t myelosuppressive (2)
b) Clinically significant effects of myelosuppression (2)
a)
- vincristine
- L-asparaginase
b)
- neutropenia: significant risk of overwhelming infection/sepsis
- thrombocytopenia
Chemotherapy
Common complications of chemotherapy (4)
- myelosuppression
- anorexia, vomiting, GI toxicity (provide anti-emetics, antacids, appetite stimulants)
- hypersensitivity/anaphylaxis (L-asparaginase, doxorubicin)
- phlebitis and tissue necrosis (at injection site)
Chemotherapy
Specific drug associated toxicity
Cyclophosphamide
- Alkylating agent
- Associated with haemorrhagic cystitis
- metabolites are excreted in the urine, which irritates bladder mucosa
- To prevent: administer early in the morning, ensure good fluid intake, encourage regular bladder emptying
Chemotherapy
Specific drug asociated toxicity
Doxorubicin
- Anti-tumour antibiotic
- Associated with cardiotoxicity (acute or chronic changes)
- Acute: tachycardia and arrhythmia on administration/immediately after
- Chronic: due to cumulative, dose-related damage to myocardium
- Drug should be infused over at least 15 minutes
- All patients should have thoracic radiographs, ECG and ultrasound assesment prior to treatment
Chemotherapy
Specific drug associated toxicity
Cisplatin (carboplatin)
- Associated with nephrotoxicity
- Platimum compounds accumulate in renal tubular epithelial cells, leading to proximal tubular necrosis
- Must be administered with fluid diuresis and monitor renal parameters
Chemotherapy
Breed predisposition to toxicity
- MDR-1 gene mutation can lead to an increased risk of toxicity
- Encodes P-gp drug transport protein, and when mutation is present, substrates are not excreted, leading to increased drug exposure and toxicity
- Involved vinca alkaloids, doxorubicin, actinomycin D and taxanes
- Common in herding breeds, german shepherds and mixed breed dogs
Radiotherapy
What determines radiosensitivity of living cells (3)
- Growth fraction: dividing cells more sensitive (eg bone marrow, GI epithelium, tumours with high turnover)
- Cell cycle: cells in M phase are most radiosensitve, cells in S phase or G0 are more radioresistant
- Oxygenation: tumour cells in low oxygen tension (hypoxic cells) are less sensitive
Radiotherapy
Application of radiation
a) Teletherapy
b) Brachytherapy
c) Advantages/disadvantages of each
a) Radiation applied as an external beam of X-rays, γ-rays or electrons directed to the tumour
b) Radioactive substances that emit γ or β rays are applied to the tumour surface, implanted in the tumour, or administered systemically
c)
- Teletherapy: safe for operator, but expensive and multiple treatments needed
- Brachytherapy: single treatment and better localisation, but does result in a radioactive patient
