Chapter 25: Intro to Oncologic Surgery Flashcards
Generally speaking, what alterations results in the formation of cancer?
- Activation of tumor-promoting factors via oncogenes
or - Loss of innate tumor inhibitory effects via tumor suppressor genes (e.g. p53 “guardian of the genome”)
What are the (6) phenotypic characteristics of cancer cells?
- Self-sufficiency in growth signals
- Insensitivity to anti-growth signals
- Tissue invasion and metastasis
- Limitless replicative potential
- Sustained angiogenesis
- Evasion of apoptosis
Which forms of neoplasia have confirmed, true genetic heritability in animals?
- Osteosarcoma of Scottish Deerhounds
- Renal cystadenocarcinoma in GSD
- Nodular dermatofibrosis in GSD
List (5) biologic carcinogens in animals:
- FeLV and lymphoproliferative diseases
- Feline sarcoma virus and FSA (must also be infected with FeLV)
- Papillomavirus in puppies. Papilloma can lead to formation of SCC in rare cases
- Spircocerca lupi and esophageal sarcomas in dogs
- Transmissible venereal tumor by direct cellular transmission
List (5) physical carcinogens:
- Asbestos and mesothelioma in humans
- Injection-site sarcoma in cats
- Post-trauma ocular sarcomas
- Microchip-associated FSA
- TPLO metallurgy and canine OSA
List the four possible mechanisms which can transform genes into oncogenes:
- Retrovirus-mediated transduction
- Translocation mutation
- Amplification
- Proviral insertion
Translation of oncogenes leads to transcription of key proteins such as….
- Growth factors
- Growth factor receptors
- Cytoplasmic kinases/Ras
- Transcription factors
- Antiapoptotic proteins
What are Ras oncogenes?
Lead to production of membrane-associated proteins that have a key role in cell signalling leading to activation of various cell-proliferative pathways
What are the two forms of tumor suppressor genes?
- 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
In general, how do carcinomas, round cell tumors and sarcomas metastasize?
- Carcinomas and round cell tumors via lymphatics
- Sarcomas via hematogenous routes
How do metastatic cells survive in their new environment?
- Progressive hypoxia due to proliferation (need to be 100-200mcm from capillary bed for continued growth)
- Hypoxia activates hypoxia-induced factor (HIF1alpha), an oxygen-dependent transcription factor
- HIF-1a induced transcription of tumor-derived growth factors such as VEGF
- Growth factors lead to endothelial recruitment and eventual organization in capillaries
What factors need to be considered when choosing a biopsy?
- Invasiveness of procedure
- Potential for hemorrhage
- Seeding of tumor cells
- Will it change the treatment plan
How can nuclear scintigraphy be applied to dogs with OSA? What substance is used for this?
Technetium-99m hydromethylene diphosphate used for a whole body scan to detect asymptomatic 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
List some uses of nuclear scintigraphy:
- 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 tumors to identify metastatic or ectopic disease
- Indium-111 pentetreotide (somatostatin receptor scan) to identify primary and metastatic lesions in dogs with functional insulinomas
What is a PET-CT?
What are its limitations?
A radiopharmaceutical (F-fluorodeoxyglucose; FDG) is transported into and trapped inside tumor cells because it is not utilized in the glycolic pathway. Signal is higher in tumor cells as they have a higher uptake of glucose.
Limitations
- Not all tumors will have increased uptake
- Non-specific (inflammation reacts similarly)
- Not readily available
What size metastatic lesions can be seen on thoracic radiographs and CT?
- 6mm on radiographs
- 1mm on CT
What are the major potential side effects of doxorubicine and cisplatin?
- Doxorubicine can cause cardiotoxicity
- Cisplatin can cause nephrotoxicity
What are the 4 categories of tumor excision?
- Debulking
- Marginal
- Wide
- Radical
What are the general rules for lateral margins of soft tissue sarcomas, MCT and carcinomas?
- Sarcomas and MCT - 2-3cm lateral margins
- Carcinomas - 1cm usually sufficient
A study by Simpson et al revealed what regarding lateral margins for MCT excision?
- 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
What are the 4 options when incomplete excision of an STS is achieved?
- 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 tumor following further resection
Is lymph node size a predictor of metastasis?
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
List 3 methods of identifying the sentinel lymph node:
- Lymphoscintigraphy
- Peritumoral injection of blue dye
- Intra-op cytology or histopath
What are some considerations regarding surgical technique for oncologic surgeries?
- Early hemostasis to prevent release of tumor emboli
- Careful handling to prevent exfoliation
- Structures adhered to the tumor should be resected en bloc if possible (57% rate of invasion in humans)
- Multifilament suture is associated with an increased risk of recurrence
- Ideally avoiding drains as can extend margins if resection if 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
