Principles of Surgical Oncology Tranx

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    THE ROLE OF SURGERY INCANCER MANAGEMENT

    Cancer Statistics - according to theInternational Agency for Research onCancer, WHO (2008)

    Most Frequent Cancers in theworld:Female:

    Incidence Mortality

    1. Breast2. Colorectum3. Cervix Uteri4. Lung5. Stomach6. Corpus Uteri7. Liver8. Ovary9. Thyroid

    10. Others

    1. Breast2. Colorectum3. Cervix Uteri4. Lung5. Stomach6. Liver7. Ovary8. Corpus

    Uteri

    9. Thyroid10. Others

    Male:Incidence Mortality

    1. Lung2. Prostate3. Colorectum4. Stomach5. Liver6. Esophagus7. Bladder8. Non-Hodgkin

    Lymphoma9. Leukemia10. Others

    1. Lung2. Prostate3. Colorectum4. Stomach5. Liver6. Esophagus7. Leukemia8. Bladder9. Non-

    HodgkinLymphoma

    10. Others

    Both sexes:Incidence: Mortality

    1. Breast

    2. Prostate3. Lung4. Colorectum5. Cervix Uteri6. Stomach7. Liver8. Corpus Uteri9. Esophagus10. Ovary

    1. Lung

    2. Breast3. Stomach4. Liver5. Colorectum6. Cervix Uteri7. Prostate8. Esophagus9. Ovary10. Leuke

    mia

    Most Frequent Cancers in thePhilippines:Female:

    Incidence Mortality

    1. Breast2. Cervix Uteri3. Lung

    4. Colorectum5. Ovary6. Liver7. Corpus Uteri8. Thyroid9. Leukemia10. Stomach

    1. Breast2. Lung3. Cervix Uteri

    4. Liver5. Colorectum6. Ovary7. Leukemia8. Stomach9. Corpus Uteri10. Thyroid

    Male:Incidence Mortality

    1. Lung2. Liver3. Prostate4. Colorectum5. Stomach6. Leukemia7. Pharynx,

    Others8. Brain9. Non-Hodgkin

    Lymphoma

    10. Lip/Oral Cavity

    1. Lung2. Liver3. Colorectum4. Prostate5. Stomach6. Leukemia7. Brain8. Pharynx,

    Others9. Non-Hodgkin

    Lymphoma

    10. Lip/OralCavity

    Both sexes:Incidence: Mortality

    11. Breast12. Lung13. Cervix

    Uteri14. Liver15. Prosta

    te16. Colore

    ctum17. Ovary18. Stoma

    ch

    11. Lung12. Breast13. Liver

    14. CervixUteri

    15. Prostate

    16. Colorectum

    17. Stomach

    18. Leuke

    Subject: SurgeryTopic: Principles of Surgical OncologyLecturer: Dr. Malen M. GellidoDate of Lecture: 22 July 2011Transcriptionist: GluttonoidsPages: 13

    SY

    2011-2

    012

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    19. Corpus Uteri

    20. Leukemia

    mia19. Ovary20. Brain

    Incidence Rate of NeoplasmsMalignant Neoplasms ranked

    number 3 in the over-all cause ofmorbidity in 2005

    -Causes of death in the Philippinesas of 2005 (DOH):

    1st and 2nd =Cardiovasculardisease 3rd = MalignantNeoplasms

    CARCINOGENESIS

    The Cell Cycle

    During the synthetic or Sphase, the cell generates a singlecopy of its genetic material,.

    Mitotic or M phase, the

    cellular components arepartitioned between two daughtercells.

    The G1 and G2 phasesrepresent gap phases duringwhich the cells preparethemselves for completion of theS and M phases, respectively.

    When cells ceaseproliferation, they exit the cellcycle and enter the quiescentstate referred to as G0.

    In human tumor cell-cycle

    regulators like INK4A, INK4B, andKIP1 are frequently mutated oraltered in expression.

    These alterationsunderscore the importance of

    cell-cycle regulation in theprevention of human cancers.

    Six Essential Alteration in CellPhysiology that Dictate MalignantGrowth

    1. Self- sufficiency in growth signals2. Insensetivity to antigrowth signals3. Tissue invasion and metastasis4. Limited replicative potential5. Sustained angiogenesis6. Evading apoptosis

    **RememberSALISE in patho.Self sufficiency in growth signalsAbility to invade and metastasizeLimitless replicative potentialInsensitivity to growth-inhibitorysignalsSustained angiogenesisEvasion of APOPTOSIS

    Angiogenesis is theestablishment of new bloodvessels from a pre-existingvascular bed which is essentialfor tumor growth and metastasis.

    Tumors develop an angiogenic

    phenotype as a result of accumulated genetic alterationsand in response to local selectionpressures such as hypoxia.

    Apoptosis is a geneticallyregulated program to dispose ofcells.

    o Cancer cells must avoidapoptosis if tumors are toarise.

    o The growth of a tumor

    mass is dependent not onlyon an increase inproliferation of tumor cellsbut also on a decrease intheir apoptotic rate.

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    Metastases arise from thespread of cancer cells from theprimary site and the formation ofnew tumors in distant sites.

    A feature of malignant cells istheir ability to invade thesurrounding normal tissue. Theability to invade involves

    o changes in adhesion,o initiation of motility, ando proteolysis of the

    extracellular matrix (ECM).

    Oncogenes counterpart: Proto-oncogenes

    they are originally proto-oncogenesthat become abnormal throughmutation, chromosomal transfer, oramplification

    These are:

    o PGFR (growth

    factor)

    o HER 2 neu

    (growth factor receptor)

    o c-myc

    (nuclear transcription factor)

    o ras

    (intracellular signaltransduction molecules)

    Tumor supressor genes (mutationsin these genes leads to cancer):

    o RB1o p53o APCo BRCA 1 and 2-breast cancer genes

    FACTORS AFFECTINGCARCINOGENESIS

    A. Genetic Factors(See Last Page for table)

    General Features of HereditaryCancer Syndromes

    Same or linked forms of cancer intwo or more close relatives

    Earlier than usual cancer onset in

    one or more relatives

    Bilateral cancer in paired organs Multiple primary tumors in the

    same individual

    Specific constellation of tumorsare part of known cancersyndrome

    Evidence of autosomal dominant

    transmission of cancersusceptibility

    B. Chemical Factorso even chemotherapicagents can cause malignancies.

    o chemical carcinogensusually affect specific organs,targeting the epithelial cells (orother susceptible cells within anorgan) and causing geneticdamage (genotoxic)

    o the most commonlyassociated exposures that increasecancer risk are:

    tobacco,alcohol,

    diet, and

    reproductivefactors (e.g., sexual behaviorand hormones).

    o Chemically relatedDNA damage and consequentsomatic mutations relevant tohuman cancer can occur:

    Directy fromexogenous exposures

    Indirectly activation of endogenousmutagenic pathways (e.g.,nitric oxide and oxyradicals)

    Chemotherapeutic Agents

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    C. Viral Factors

    May cause or increase the risk ofmalignancy through:

    o direct transformation,

    expression of oncogenes thatinterfere with cell-cycle

    checkpoints or DNA repairo expression of cytokines or other growthfactorso alteration of theimmune system.

    Oncogenic viruses may beRNA or DNA types

    1. RNA Viruses

    Retroviruses that containreverse transcriptase.

    After infection, the single-stranded RNA viral genome istranscribed into a double-

    stranded DNA copy, which isthen integrated into thechromosomal DNA of the cell.

    Retroviral infection of thecell is permanent; thusintegrated DNA sequencesremain in the host chromosome

    2. DNA Viruses

    Unlike the oncogenes of the RNAviruses, those of the DNA tumorviruses are viral, not cellular, inorigin.

    These genes are required for viralreplication using the host cellmachinery.

    In permissive hosts, infection withan oncogenic DNA virus mayresult in a productive lyticinfection, which leads to celldeath and the release of newlyformed viruses.

    In nonpermissive cells, the viralDNA can be integrated into thecellular chromosomal DNA, andsome of the early viral genes canbe synthesized persistently,which leads to transformation ofcells to a neoplastic state.

    The binding of viral oncoproteinsto cellular tumor-suppressorproteins p53 and Rb isfundamental to thecarcinogenesis induced by mostDNA viruses, although sometarget different cellular proteins.

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    Biological Agents that CauseCarcinogenesis

    D. Physical Factors1. Radiation

    Damage nucleotides,cross linkage, DNA single anddouble stranded breaks,inactivates tumor suppressorgene, induces genomic instabilityin cells that persist at least 30generations

    Induces DNA lesions that

    damage nucleotide bases andcross-linking, and DNA single-and double-strand breaks(DSBs).

    Misrepaired DSBs are theprincipal lesions of importance inthe induction of chromosomalabnormalities and gene

    mutations.

    DSBs in irradiated cellsare repaired primarily by anonhomologous end-joiningprocess, which is error prone;thus DSBs facilitate theproduction of chromosomal

    rearrangements and other large-scale changes such aschromosomal deletions.

    It is thought that radiationmay initiate cancer byinactivating tumor-suppressorgenes.

    Radiation inducesgenomic instability in cells thatpersists for at least 30generations after irradiation.

    Therefore, even if cells donot acquire mutations at initialirradiation, they remain at riskfor developing new mutations forseveral generations.

    ** how radiation produce cancer allthe things are on the molecular level

    2. UV Rays

    UV light creates UV-specificdipyrimidine photoproducts in theDNA of the target cells.

    When these are not sufficientlyrepaired, errors in replication canresult in characteristic mutations

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    in critical genes.

    3. Asbestos

    Asbestos is a naturally occurringmineral silicone that results from

    fibrous crystallization

    Induce D