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Tobias ECVS > Ch 25 - Introduction to oncologic surgery > Flashcards

Ch 25 - Introduction to oncologic surgery Flashcards

1
Q

Generally speaking, what alterations results in the formation of cancer?

A
  • Activation of tumour-promoting factors via oncogenes
    or
  • Loss of innate tumour inhibitory effects via tumour suppressor genes (e.g. p53 “guardian of the genome”)
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2
Q

What are the phenotypic characterisitics of cancer cells?

A
  • Self-sufficiency in growth signals
  • Insensitivity to anti-growth signals
  • Tissue invasion and metastasis
  • Limitless replicative potential
  • Sustained angiogenesis
  • Evasion of apoptosis
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3
Q

Which forms of neoplasia have confirmed, true genetic heritability in animals?

A
  • Osteosarcoma of Scottish Deerhounds
  • Renal cystadenocarcinoma in GSD
  • Nodular dermatofibrosis in GSD
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4
Q

List some biologic carcinogens in animals

A
  • FeLV and lymphoproliferative diseases
  • Feline sarcoma virus and FSA (must also be infected with FeLV)
  • Papillomavirus in puppies. Papilloma can klead to formation of SCC in rare cases
  • Spircocerca lupi and viral oesophageal sarcomas in dogs
  • Transmissible venereal tumour by direct cellular transmission
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5
Q

List some physical carcinogens

A
  • Asbestos and mesothelioma in humans
  • Injection-site sarcoma in cats
  • Post-trauma ocular sarcomas
  • Microchip-associated FSA
  • TPLO metallurgy and canine OSA
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6
Q

List the four possible mechanisms which can transform genes into oncogenes

A
  • Retrovirus-mediated transduction
  • Translocation mutation
  • Amplification
  • Proviral insertion
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7
Q

Translation of oncogenes leads to transcription of key proteins such as….

A
  • Growth factors
  • Growth factor receptors
  • Cytoplasmic kinases/Ras
  • Transcription factors
  • Antiapoptotic proteins
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8
Q

What are Ras oncogenes?

A

Lead to production of membrane-associated proteins that have a key role in cell signalling leading to activation of various cell-proliferative pathways

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9
Q

What are the two forms of tumour suppressor genes?

A
  • Gate keepers - Inhibit growth while promoting cell death (eg. p53)
  • Care takers - Ensure DNA repair while maintaining genomic stability

p53 is one of the most common mutations. It is crucial for normal cell cycle and serves as a checkpoint for entry into apoptosis

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10
Q

In general, how do carcinomas, round cell tumours and sarcomas metastasise?

A
  • Carcinomas and round cell tumours via lymphatics
  • Sarcomas via haematogenous routes
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11
Q

How do metastatic cells survive in their new environment?

A
  • Progressive hypoxia due to proliferation (need to be 100-200mcm from capillary bed for continued growth)
  • Hypoxia activates hypoxia-induced factor (HIF1alpha), an oxygen-dependant transcription factor
  • HIF-1a induced transcription of tumour-derived growth factos such as VEGF
  • Growth factors lead to endothelial recruitment and eventual organisation in capillaries
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12
Q

What factors need to be considered when choosing a biopsy?

A
  • Invasiveness of procedure
  • Potential for haemorrhage
  • Seeding of tumour cells
  • Will it change the treatment plan
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13
Q

How can nuclear scintigraphy be applied to dogs with OSA? What substance is used for this?

A

Technetium-99m hydromethylene diphosphate used for a whole body scan to detect aymphtomatic synchronous or asymptomatic lesions

In one study, 7.8% of 399 dogs with appendicular OSA were diagnosed with a second asymptomatic lesion. Not good candidates for amputation

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14
Q

List some uses of nuclear scintigraphy

A
  • Technetium-99m hydromethyl diphosphate for OSA to detect multiple lesions or to define margins for limb-sparing
  • Technetium-99m diethylenetriaminepentaacetic acid for GFR prior to nephrectomy
  • Technetium-99m for thyroid tumours to identify metastatic or ectopic disease
  • Indium-111 pentetreotide (somatostatin receptor scan) to identify primary and metastatic lesions in dogs with functional insulinomas
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15
Q

What is a PET-CT?
What are its limitations?

A

A radiopharmaceutical (F-fluorodeoxyglucose FDG) is used and is transported into and trapped inside tumour cells because it is not utlised in the glycolic pathway. Signal is higher in tumour cells as they have a higher uptake of glucose

Limitations
- Not all tumours will have increased uptake
- Non-specific (inflammation reacts similarly)
- Not readily available

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16
Q

What size metastatic lesions can be seen on thoracic radiographs and CT?

A
  • 6mm on radiographs
  • 1mm on CT
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17
Q

What are the major potential side effects of doxorubicine and cisplatin?

A
  • Doxorubicine can cause cardiotoxicity
  • Cisplatin can cause nephrotoxicity
18
Q

What are the 4 categories of tumour excision?

A
  • Debulking
  • Marginal
  • Wide
  • Radical
19
Q

What are the general rules for lateral margins of soft tissue sarcomas, MCT and carcinomas

A
  • Sarcomas and MCT - 2-3cm lateral margins
  • Carcinomas - 1cm usually sufficient
20
Q

A study by Simpson et al revealed what regarding lateral margins for MCT excision?

A
  • All grade 1 MCT were completely excised with 1cm margins
  • Only 75% of grade 2 MCT were completely excised with 1cm margins, increasing to 100% with 2cm margins

2cm margins recommended for grade 1 and 2, not enough data to make recommendations for grade 3 so should aim for 3cm if possible

21
Q

What are the 4 options when incomplete excision is achieved?

A
  • No treatment
  • Staged resection of the scar
  • Wide scar revision
  • Combination with radiation or chemo

78% of STS reported as incompletely excised do not have any evidence of residual tumour following further resection

22
Q

Is LN size a predictor of mets? Give an example from the literature

A

No
A study of 100 dogs with oral malignant melanoma, 40% of dogs with normal-sized LN had metastasis and 49% of dogs with enlarged LN did not have metastasis

23
Q

List some methods of identifying the sentinel lymph node

A
  • Lymphoscintigraphy
  • Peritumoural injection of blue dye
  • Intra-op cytology or histo
24
Q

What are some considerations regarding surgical technique for oncologic surgeries?

A
  • Early haemostasis to prevent release of tumour emboli
  • Careful handling to prevent exfoliation
  • Structures adhered to the tumour should be resected en bloc if possible (57% rate of invasion in humans)
  • Multifilament suture associated with an increased risk of recurrence
  • Ideally avoiding drains as can extend margins if resection is incomplete
  • Reconstructive surgery is ideally done as a second procedure once histology results have confirmed clean margins
  • Gloves and instruments changes prior to closure or between mass removals
25
Q

What IHC markers are used for carcinomas and sarcomas?

A
  • Cytokeratin (found in epithelial cells) stain for carcinomas
  • Vimentin (found in mesenchymal cells) stain for sarcomas (and melanoma)
26
Q

What proliferation markers can be used to help predict recurrence of incompletely excised grade 2 MCT?

A
  • Ki67 (low vs high have signifcantly prognosis)
  • Proliferating cell nuclear antigen (PCNA) combined with Ki67 is prognostic for recurrence
27
Q

What are the advantages of neoadjuvant radiation therapy vs adjuvant radiation therapy

A
  • Neoadjuvant (prior to surgery) is theoretically more effective due to unimpaired vascular supply (better oxygenated, less hypoxic and therefore more radiosensitive)
  • Irradiated skin is more likely to develop incisional complications
  • Adjuvant radiation can also increase incisional complications, especially if started before 7 days post-op
  • Radiation is much more effective against microscopic disease and there is no delay in surgery with adjuvant radiation
28
Q

Define “maximally tolerated dose” chemotherapy

A

Chemotherapy where toxicity, dosage and interval of treatment are base on phase I clinical trials . This data is not often available for vet patients and is extrapolated from human date. Drug doses delivered in vet med are typically half that in humans

29
Q

Define metronomic chemotherapy

A

Frequent, even daily, administration of chemotherapeutics at doses significantly below maximally tolerated dose, with no prolonged drug-free breaks

Aims to control or minimise angiogenesis and invasion rather than cytotoxicity

30
Q

Alkylating agents

A
  • Non cell cycle specific, interfere with DNA replication and translation
  • Loumustine (Histiocytic sarcoma, MCT). Severe hepatotoxicity 6%
  • Cyclophosphamide (lymphoma). Furosemide can reduce occurence of sterile haemorrhagic cystitis
31
Q

Microtubule inhibitors

A
  • Cell cycle specific, affect spindle apparatus during mitosis
  • Vincristine (lymphoma)
  • Vinblastine (MCT)
  • Vinorelbine (lymphoma, MCT, lung tumour)

Minimally myelosuppresive and well tolerative. Can cause paralytic ileus and extravasation phlebitis

32
Q

Doxorubicin

A
  • non cell cycle specific with multiple mechanisms of action
  • Lymphoma, HSA, high grade STS, high grade carcinoma, OSA
  • Can cause DCM like damage in dogs, renal insufficiency in cats
  • Significant myelosuppression and GI toxicity
33
Q

Platinum agents

A
  • Non cell cycle specific - caused binding of DNA, restricting replication and protein systhesis
  • Carboplatin and cisplatin - OSA, rescue for other sarcoma and carcinomas
  • Cisplatin fatal to cats! Fatal pulmonary oedema
  • Nephrotoxicity
34
Q

Bisphosphonates

A
  • Inhibits osteoclast activity - palliative Tx for osteolytic disease from OSA, multiple myeloma and metastatic bone disease
  • IV is preferred (low oral bioavailability, cause reflux)
  • Pamidronate most common - approx 30% successful palliation
  • Zoledronate - shorter infusion time, improved inhibition or resorption (100x potency), potential for less frequent treatment
35
Q

What are the reported morbidity and mortality rates of chemotherapy patients as a whole?

A
  • 15% require nonhospitalised medical attention
  • 5% hospitalised
  • 1% mortality rate
36
Q

When is the bone marrow nadir with chemotherapeutics?
At what level is chemo delayed?

A

Typically approx 7 days with the exception of carboplatin which is approx 10-14 days

Chemo is delayed by 5-7 days if neutrophils are less than 1500-2000/mcL and platelets less than 50,000/mcL

If neuts under 1000, prophylactic ABx initiated and future doses reduced by 20%

37
Q

What is the most available form of immunotherapy?

A

Melanoma vaccine

DNA vaccine utilising human tyrodinase DNA which shows an unregulation of antibodies in dogs against human tyrosinase. Clinical studies show mixed efficacy…

38
Q

Tyrosine Kinase inhibitors

A
  • Target the ATP binding sites of membrane and cytoplasmic tyrosine kinases which are responsible for phosphorylation causing cell proliferation
  • Imatinib (vaccine assoc FSA in cats) Used for chronic myelogenous leukaemia and GIST in humasns
  • Toceranib (Palladia) for MCT in dogs - targets c-kit. Indicated for high grade or metastatic disease and work best on microscopic disease
39
Q

What is the most common mechanism of acquired chemotherapeutic resistance?

A

Mutation in the canine MDR-1 gene (Collies, Shelties, Australian Cattle Dogs may already have this mutation)

40
Q

What proliferation markers can be used to help predict recurrence of incompletely excised grade 2 MCT?

A
  • Ki67 (low vs high have signifcantly prognosis)
  • Proliferating cell nuclear antigen (PCNA) combined with Ki67 is prognostic for recurrence
41
Q

How do metastatic cells survive in their new environment?

A
  • Progressive hypoxia due to proliferation (need to be 100-200mcm from capillary bed for continued growth)
  • Hypoxia activates hypoxia-induced factor (HIF1alpha), an oxygen-dependant transcription factor
  • HIF-1a induced transcription of tumour-derived growth factos such as VEGF
  • Growth factors lead to endothelial recruitment and eventual organisation in capillaries

Tobias ECVS (110 decks)

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