Create
Learn
Share

Onco 1 - Intro

rename
sihirlifil's version from 2018-04-05 15:41

Intro

Question Answer
Normal cell proliferation?Multiple growth signal transduction pathways
Complex regulatory process (checks & balances)
Positive & negative signals
Cancer vs tumorAny swelling = tumor (abnormal mass of tissue that may be hyperplatic, metaplastic, or neoplastic), then find out if benign or malignant (loss of normal cell prloferation
Hyperplasia =Increase in cell numbers due to endogenous or exogenous stimulus- potentially reversible!
Metaplasia =Replacement of 1 mature cell type with another- reversible
Neoplasia =Increase in cell number due to uncontrolled proliferation-irreversible
Neoplasia vs HyperplasiaNeoplasia persist after removal of stimulus. Heritable genetic defect in affected cells
Hyperplasia = potentially reversible, elevated cell proliferation ceases after stimulus removed
What’s the current model for cancer development?Cells undergo a series of genetic mutations/alterations --> inability to respond normally to IC/EC signals that control proliferation, differentiation, untimely death
What kind of dz is cancer?Genetic dz, direct or indirect alterations
Factors: inherited gene mutations, chemical/radiation=induced DNA dmg, genetic instability, incorporation of viruses into cell, random errors during DNA synthesis
***Hallmarks of cancerSelf-sufficiency in growth signals
Insensitivity to anrigrowth signals
Ability to evade apoptosis
Limitless replicative potential
Sustained angiogenesis
Capacity to invade tissues & metastasize
Regulation of the cell cycle is crucial, errors can lead to cancer. What are the signal transduction pathways?Growth factors, GF receptors, activated kinases, message to nucleus, cell division
Goal of the cell cycleProduce 2 genetically identical cells from 1 precursor
If something goes wrong at a cell cycle checkpoint, cells can arrest to allow…Repair of cell dmg
Dissipation of exogenous cell stress signal
Availability of essential growth factors, hormones, or nutrients (or cell dies)
3 stages of tumor development?Initiation
Promotion
Progression
***(match) Types of carcinogenesisPassive
Heritable
Biological
Chemical
Physical
What is passive carcinogenesis?Random & spontaneous mutations
Accumulation of genetic material over time
Dz of old age
What is heritable carcinogenesis?Mutations may occur in germline of individual and be represented in every cell in the body
May occur in single somatic cell & be identified in a tumor following clonal proliferation
E.g. of heritable carcinogenesisBernese mtn dog get histiocytic sarcoma
(Germline p53 mutations)(Vax associated sarcoma in cats, OSA in dogs)
What is biological carcinogenesis?Viruses (implicated in 15% of all cancers)
2 groups of viral carginogensDNA tumor viruses: cause malignant transformation by inhibiting normal fxn of tumor suppressor genes
RNA tumor viruses: deregulate signal transduction pathways
What is chemical carcinogenesis?Repeated exposure w/ additive effects over time
Some may accumulate in body fat w/ slow systemic release (herbicides, TCC)
(Pyrrolizidine alkaloids, vinyl chloride, tobacco, nitrates/ites, pesticides, PCB, chemotherapy)
What is physical carcinogenesis?UV light e.g. SCC, cutaneous HSA (DNA point mutations), ionizing radiation e.g. chronic leukemia, thyroid tumors, FB/fibers (implant-induced sarcoma, vax-assoc mesothelioma from asbestos), parasites (S. lupi)
Angiongenesis: why important?(New blood vessels from existing ones) BV growth essential during normal development of embryo to supply organs & tissues w/ nutrients & O2, remove metabolic waste. Causes cancer to spread & disseminate throughout body (vasculogenesis = new BV from circulating mesodermal endothelial cell precursors. tumor angiogenesis = combo)
Characteristics of tumor angiogenesisDilated, leaky, tortuous, irregular shape, dead-ended, harbor tumor cells! Lack organizational patterns of capillaries, arteries, & venules. Slow & intermittent blood flow
Tumor metastasisTransfer of dz from 1 organ/site to another which is not in direct conact
Only characteristic unique to malignant cells, reason for most tx failures
3 routes of cancer metastasisPeritoneal seeding (spread along tissue planes, invade various tissue spaces & cavities
Lymphatic vessels (carcinoma)
Blood vessels (sarcoma)
memorize

Clinical Oncology

Question Answer
Benign tumor =Clusters of abnormal cells that may compress but never invade surrounding tissues
Malignant tumor =Cells that can invade surrounding tissues & spread to distant sites
3 families of tumorsRound
Sarcoma (spindle, mesenchymal)
Epithelial
Describe mesenchymalSpindle cell. Fusiform w/ round-ovoid nucleus
Single cells
Poor exfoliation
Cytoplasmic tails (haphazard wispy)
Sarcoma
Tumor type?
Mesenchymal
Describe round cellDiscrete, excellent exfoliation
Types of round cell tumorsLymphoma
TVT
Plasmacytoma
MCT
Histiocytome
+/- malig melanoma, basal cell tumor (can have spindle cell characteristics)
Tumor type?
Round cell (MCT)
Describe epithelialRound to ovoid, round nucleus
Sheet-like groups & clusters
Good exfoliation
CARCINOMA
Tumor type?
Epithelial
Criteria for malignancyNUCLEAR more reliable than cytoplasmic, >3 = good indication of malignancy
Nuclear criteria for malignancyAnisokaryosis/anisonucleosis, angular nucleai
Increased nuclear:cytoplasmic ratio
Multinucleation
Coarse chromatin
Macrokaryosis/macronuclei
Increased or abnormal mitotic figures
Nuclear molding
General criteria for malignancyAnisocytosis & macrocytosis
Pleomorphism
Hypercellularity
‘Obvious’ tumor:
MCT (ddx histiocytoma)
‘Obvious’ tumor:
Vax-associated sarcoma
‘Obvious’ tumor:
Osteosarcoma
Hx/PE findings that point to cancerEvidence of pain
Changes in urinary/bowl habits
Lethargy, depression
Coughing, difficulty breathing
Change in appetite
Wt loss
Nonhealing wounds
Abnormal d/c
Abnormal odors
Lumps & bumps
How to describe tumor on PELocation, size, fixed/moveable, dermal/SQ, physical characteristics (raised, hairless, inflamed…)
Ddx for massCHANG: cyst, hyperplasia, abscess, neoplasia, granuloma
Then if neoplastic --> benign or malig
Ddx: Malignant neoplasmsMCT, SCC, FibroSA, OSA, HemangioSA, Hangiopericytoma, malignant melanoma
Ddx: Benign neoplasmsLipoma, histiocytoma, basal cell tumor
Which Dx tests?Complete PE
CBC, Chem, UA, RECTAL!
Thoracic rads (3 views)
Abdominal rads +/- US
FNA
+/- biopsy, advanced DI
Indications for FNA
Any mass, ddx inflammation vs neoplasia NOT benign vs malig
When is FNA contraindicated?Bleeding (deep in body cavity, cavitary mass)
Seeding (TCC)
If not going to change tx (e.g. splenic mass going to sx regardless)
Would you do FNA? why?
No! Cavitary mass = worry about bleeiding (recommend sx anyway, & sarcomas don’t exfoliate well so unlikely to get answer)
Would you do FNA? why?
(TCC) Actually yeah…? Patient usually succumb to disease before tumor can seed, but also low chance
FNA techniques?Syringe on/off (usu does off)
On: negative pressure, good for poor exfoliation (suspect arcoma)
Off: capillary method (good for energetic pt’s lol)
What can cytology tell you?
Benign vs malignant: depends on?PATHOLOGY!
Benign vs malignant (chart)
Diagnosis of neoplasia?Biopsy/histopath (vet preferred)
Save sample for 2nd opinion if possible
Ask for histopath grade!
Mark margins to assess completeness of excision
Biopsy: when to do incisionalPretreatment! Change treatment, or owner’s willingness to tx
Tumor in difficult area for reconstruction
Biopsy: when to do excisionalIf tx not altered by tumor type
Just as easy to remove en bloc as to do incisional
Techniques for incisional biopsyWedge biopsy: ulcerated/necrotic tissues, longitudinal on legs, biopsy area that will be removed w/ sx
Punch biopsy
(DO NOT open normal tissue, place drains, laser/electrocautery (deforms architecture), grab w/ rat-tooth forceps)
Considerations w/ sample submissionALWAYS submit!
Large samples better. 1:10 tissue:formalin, submit entire mass, ink margins for excisional
DON’T freeze, submit 1/2 of mass, throw sample away
Factors associated w risk of cancer dev’pNutrition (cats: canned food SCC)
OVH/orchiectomy (decr mammary gland tumor devp’t, testicular tumors)
Genetics (GSD = HSA, scotish terriers = TCC, Bernese mtn dog = malig histiocytosis)
Environmental (coal, kerosene, tobacco, asbestos)
Staging tumorsClinical & pathological inflammation
TNM system: size of 1ry Tumor, assessment of regional LN, Metastasis
Staging: what does it tell you about biological behavior?Potential for metastasis (HAS check ALL body cavities, oral SCC check regional LN & lungs)
Route of metastasis
Staging: possible routes of metastasisLymphatics (round cell, carcinomas): regional LN; liver spleen, mesenteric LN; thoracic cavity LN
Hematogenous (sarcomas): lungs. thoracic rads
Staging: how to assess T?Measurements
Imaging: Rads, US, endoscopy (scintigraphy, CT, MRI)
Staging: how to assess N?Palpate LN, measure, aspirate (+/- biopsy)
Staging: how to assess M?Thoracic rads (need to be at least 6mm to be able to see)
*** STAGING VS GRADING
Grading: Histopath characteristics?Differentiation
Mitotic index (# per 10 HPFs) (# cells dividing in tumor)
Necrosis (outgrew blood supply)
Nuclear pleomorphism (same family)
Grading: schemes1, 2, 3
Low, intermediate, high
Grading: tumor typesMCT
Soft-tissue sarcoma
Others
Options for tx (general 3)Curative vs palliative
Local vs systemic
rDVM vs referral
Treatment considerationsType of therapy available
Most effective therapy?
Potential SEffx
Can be treated by local vet or referral?
Most cost-effective
Localized therapy: sx?Best when possible! plan appropriately (margins, nutritional)
Careful of pseudocapsules (tumor shells right out, malig cells left behind)
Localized therapy: radiation?Incomplete margins/unresectable
Palliation
(want to shrink before sx)
Systemic therapy: Types of chemotherapy1ry, adjuvant, neoadjuvant (before 1ry tx), induction (induce remission), maintenance (maintain remission), rescue (back into remission), metronomic (continuous low dose)
Systemic therapy: what can you do with immunotherapy?Target the tumor! usually adjuvant (Acemannan & Merial Melanoma vax only 2 approved by USDA)
Systemic therapy: what else besides chemo/immuno?Pain management, nutritional support, antiangiogenic, complementary
SEffx of tx?Bone marrow suppression (7-10)
Alopecia
GI upset (3-5d)
Complications of chemoGI 3-5d later
Myelosuppression 7-10d later
Complications of radiationAcute: skin, muc mb
Late: BM, nerve, lens
Complications of sxDehiscence/seroma/he
SCC
OSA
Splenic HSA
Lymphoma
Commandments of cancer careDon’t let them hurt
Don’t let them V+ or D+
Don’t let them starve
Steps for delivering cancer careDon’t prejudge client desires & capabilities
Review team philosophy
Define importance of preventing tox/illness
Contingency plans for problems
Inform clients
Listen & respond to needs, goals, concerns, desires… QOL
memorize