Causes of CancerCauses of Cancer Defective cellular growthDefective cellular growth
– Stem cellsStem cells– Generation timeGeneration time– Contact InhibitorContact Inhibitor
Defective cellular differentiationDefective cellular differentiation– Exposure to carcinogensExposure to carcinogens– Moves to less mature formMoves to less mature form– Leads to invasion and metastasisLeads to invasion and metastasis
Characteristics of Characteristics of Normal CellsNormal Cells
Limited Cell DivisionLimited Cell Division Specific MorphologySpecific Morphology SmallSmall Nuclear-Cytoplasmic Ratio Nuclear-Cytoplasmic Ratio Perform Specific Differentiated FunctionsPerform Specific Differentiated Functions Adhere tightly together…Adhere tightly together… Are nonmigratoryAre nonmigratory Grow in an Grow in an orderly and well orderly and well
differentiateddifferentiated manner manner Are contact inhibitedAre contact inhibited
Characteristics of Early Characteristics of Early Embryonic CellsEmbryonic Cells
Demonstrate rapid and continuous cell Demonstrate rapid and continuous cell divisiondivision
Show anaplastic morphologyShow anaplastic morphology Have a Have a largelarge nuclear-cytoplasmic ratio nuclear-cytoplasmic ratio Perform no differentiated functions Perform no differentiated functions Adhere loosely togetherAdhere loosely together Are able to migrateAre able to migrate Are not contact inhibited. Are not contact inhibited.
Characteristics of Characteristics of Benign CellsBenign Cells Demonstrate continuous or Demonstrate continuous or
inappropriateinappropriate cell growth. cell growth. Show specific morphologyShow specific morphology Have a Have a smallsmall nuclear-cytoplasmic rationuclear-cytoplasmic ratio Perform differentiated functionsPerform differentiated functions Adhere tightly togetherAdhere tightly together Are nonmigratoryAre nonmigratory Grow in an orderly and well regulated Grow in an orderly and well regulated
fashion.fashion.
Characteristics of Characteristics of Malignant CellsMalignant Cells Demonstrate rapid or continuous Demonstrate rapid or continuous
cellular division. cellular division. Show Show anaplastic morphologyanaplastic morphology Have aHave a largelarge nuclear-cytoplasmic rationuclear-cytoplasmic ratio Lose some or all differentiated functionsLose some or all differentiated functions Adhere loosely togetherAdhere loosely together Are able to migrateAre able to migrate Grow by invasionGrow by invasion Are Are not contact-inhibitednot contact-inhibited
DefinitionsDefinitionsDefinitionsDefinitions
AnaplasiaAnaplasia
AnaplasticAnaplastic
CarcinogenCarcinogen
CarcinomaCarcinoma
HyperplasiaHyperplasia
HypertrophyHypertrophy
MetastasisMetastasis
NeoplasiaNeoplasia
NeoplasmNeoplasm
Stages of Stages of CarcinogenesisCarcinogenesis(Oncogenesis)(Oncogenesis)
InitiationInitiation
PromotionPromotion
ProgressionProgression
MetastasisMetastasis
Common Steps in Common Steps in MetastasisMetastasis
Extension into Surrounding Tissues Extension into Surrounding Tissues Penetration into Blood VesselsPenetration into Blood Vessels Release of Tumor CellsRelease of Tumor Cells Invasion of Tissue at the Site of ArrestInvasion of Tissue at the Site of Arrest
Immune ResponseImmune Response Attempts to destroy abnormal cellsAttempts to destroy abnormal cells Surface AntigensSurface Antigens
– Used as tracers to indicate success of Used as tracers to indicate success of treatmenttreatment
– CEA (carcinoembrionic antigen) - GI CEA (carcinoembrionic antigen) - GI tracttract
– AFP (alphafetoprotein) - liverAFP (alphafetoprotein) - liver– CA 125 - ovarianCA 125 - ovarian– PSA – prostatePSA – prostate
Cancer Grade and Cancer Grade and StageStage
Grading;Grading; Classifies Classifies cellular cellular aspectsaspects of a cancer. of a cancer.
Staging;Staging; Classifies Classifies clinical clinical aspectsaspects of the cancer. of the cancer.
Histologic ClassHistologic Class
I - Well differentiatedI - Well differentiated II - Moderate differentiationII - Moderate differentiation III - Poor differentiationIII - Poor differentiation IV - Immature & UndifferentiatedIV - Immature & Undifferentiated
Clinical StagingClinical Staging
O - Ca in situO - Ca in situ I (A) - Localized growthI (A) - Localized growth II (B) - Limited local growthII (B) - Limited local growth III (C) - Extensive local and III (C) - Extensive local and
regional growthregional growth IV (D) - MetastasisIV (D) - Metastasis
TNM ClassificationTNM Classification
T - Primary tumorT - Primary tumor N - Regional lymph nodesN - Regional lymph nodes M - Distant metastasisM - Distant metastasis
– TTisis N No o MMoo
– TT44 NN33 MM11
GoalGoal Education and early detectionEducation and early detection CC AA UU TT II OO NN
Surgical InterventionsSurgical Interventions
BiopsyBiopsy CureCure Control - DebulkingControl - Debulking PalliativePalliative StagingStaging ReconstructiveReconstructive ProphylaxisProphylaxis
RadiationRadiation Destroys cells, causes inflammatory Destroys cells, causes inflammatory
responseresponse Side EffectsSide Effects Goals:Goals:
– CureCure– ControlControl– PalliativePalliative
Radiation RecallRadiation Recall ExternalExternal ImplantsImplants IsotopesIsotopes
ChemotherapyChemotherapy Cell Cycle Non-specificCell Cycle Non-specific
– Alkylating –Cytoxan, Leukeran, N.MustardAlkylating –Cytoxan, Leukeran, N.Mustard– Antitumor antibiotics - AdriamycinAntitumor antibiotics - Adriamycin– Nitrosoureas –Carmustine, HydroureaNitrosoureas –Carmustine, Hydrourea– Corticosteroids –Prednisone, DecadronCorticosteroids –Prednisone, Decadron– Hormones –Estrogen, Provera, AndrogenHormones –Estrogen, Provera, Androgen
Cell Cycle SpecificCell Cycle Specific– Antimetabolities –Methotrexate, 5-FUAntimetabolities –Methotrexate, 5-FU– Plant Alkaloids (Miotic Inhibitors) –Vinblastine, Plant Alkaloids (Miotic Inhibitors) –Vinblastine,
VincristineVincristine CisplatinCisplatin TamoxifenTamoxifen
Synergistic EffectSynergistic Effect
The total is greater than the The total is greater than the individual partsindividual parts
Each agent has:Each agent has:– action against canceraction against cancer– different site of actiondifferent site of action– different organ toxicity or time of different organ toxicity or time of
toxicitytoxicity
MOPP ProtocolMOPP Protocol
Complete response
Agent Action Toxicity
20% Mustargen DNA Marrow – 10 days
10% Oncovin Mitosis Neurotoxic
10% Procarbazine RNA Synthesis
Marrow – 21 days
5% Prednisone Cell membrane
Immune suppression
80% Synergistic Effect
Side EffectsSide Effects
Cluster the common onesCluster the common ones::bone marrow suppressionbone marrow suppression
alopeciaalopecia
nausea and vomitingnausea and vomiting
AdriamycinAdriamycin - Cardiac - Cardiac
CisplatinCisplatin – Renal – Renal
ComplicationsComplications Pain ControlPain Control Bone Marrow SuppressionBone Marrow Suppression
– Infection - NeutropeniaInfection - Neutropenia– HemorrhageHemorrhage– AnemiaAnemia
InfarctionInfarction Superior Vena Cava SyndromeSuperior Vena Cava Syndrome Spinal Cord CompressionSpinal Cord Compression Tumor Lysis SyndromeTumor Lysis Syndrome
Common Common Problems/Complications Problems/Complications Associated With CancerAssociated With Cancer
Tumor Lysis Syndrome (TLS);Tumor Lysis Syndrome (TLS);
Destruction of cells (lysis)Destruction of cells (lysis)
Release of Purine and Potassium (K+) into BloodstreamRelease of Purine and Potassium (K+) into Bloodstream
Purines converted to uric acid (in liver) K+ into BloodstreamPurines converted to uric acid (in liver) K+ into Bloodstream
HyperuricemiaHyperuricemia HyperkalemiaHyperkalemia
Obstruction of Kidney TubulesObstruction of Kidney Tubules
ARFARF
Paraneoplastic Paraneoplastic SyndromesSyndromes
Secretion of InsulinSecretion of Insulin Secretion of ACTHSecretion of ACTH HypercalcemiaHypercalcemia SIADHSIADH
SIADH - Syndrome of SIADH - Syndrome of Inappropriate ADHInappropriate ADH ADH releaseADH release
Water Reabsorption into circulation -Water Reabsorption into circulation -
Renal TubulesRenal Tubules
Extravascular FluidExtravascular Fluid
Plasma OsmolalityPlasma Osmolality
Glomerular Filtration RateGlomerular Filtration Rate
Serum Sodium Levels Serum Sodium Levels
CEREBRAL EDEMACEREBRAL EDEMA
LeukemiaLeukemia AML - Acute MyelogenousAML - Acute Myelogenous
– Age of Onset (15-39 yrs), usually affects adultsAge of Onset (15-39 yrs), usually affects adults– Prognosis is generally poor, best with bone Prognosis is generally poor, best with bone
marrow transplantmarrow transplant– Most common type of leukemiaMost common type of leukemia– Equal incidence in males and femalesEqual incidence in males and females
ALL - Acute LymphocyticALL - Acute Lymphocytic – Age of Onset (<15 yrs), usually affects Age of Onset (<15 yrs), usually affects
children, accounts for approx 10% of adult children, accounts for approx 10% of adult leukemia'sleukemia's
– Prognosis is poorer for adults than for childrenPrognosis is poorer for adults than for children– Fever & BleedingFever & Bleeding– Increased incidence in malesIncreased incidence in males
LeukemiaLeukemia
CML - Chronic MyelogenousCML - Chronic Myelogenous– Age of Onset (>50 yrs)Age of Onset (>50 yrs)– Involves liver & spleenInvolves liver & spleen– Blastic CrisisBlastic Crisis
CLL - Chronic LymphocyticCLL - Chronic Lymphocytic– Older patients – over 50Older patients – over 50– Lymph node involvement Lymph node involvement
LymphomaLymphoma
Lymph systemLymph system Lymphocytes & histiocytes Lymphocytes & histiocytes
(macrophages)(macrophages) HodgkinsHodgkins
– 15-35 and over 50 yrs.15-35 and over 50 yrs. Non-Hodgkins Non-Hodgkins
– Outside of lymph nodesOutside of lymph nodes– Wide spread before DxWide spread before Dx
Multiple MyelomaMultiple Myeloma– Infiltrates marrow Infiltrates marrow – destroys bonedestroys bone
BreastBreast
Early detection - EducationEarly detection - Education
Treatment optionsTreatment options
Mastectomy careMastectomy care
ReferralsReferrals
GynecologicalGynecological
CervicalCervical
EndometrialEndometrial
OvarianOvarian
Genetics and CancerGenetics and Cancer
BRCABRCA
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