Alterations in Cell Alterations in Cell Function and Function and

DifferentiationDifferentiationManagement of Neoplastic Disruptions

I. Epidemiology of cancerI. Epidemiology of cancer

Uncontrolled and unregulated growth of cells Can occur in any age and ethnicity 2nd most common cause of death in US

1/5 deaths from cancer Over 50% under age 65

A. Cancer incidence and A. Cancer incidence and prevalence by site and sex prevalence by site and sex

Men Prostate Lung/Bronchus Colon/Rectum Urinary Tract Melanoma

Women Breast Lung /Bronchus Colon/Rectum Uterus Ovary

Leading Leading Cancer Site Cancer Site PercentagesPercentages

Estimated mortality Estimated mortality

Men Lung/Bronchus Prostate Colon/rectum Pancreas Non-Hodgkin’s

lymphoma

Women Lung/Bronchus Breast Colon/rectum Pancreas Ovary

II. Host defense mechanisms inII. Host defense mechanisms in control of cancer/neoplasia control of cancer/neoplasia

A. Tumor antigens

- Tumor-associated antigens (TAAs)

result of malignant transformations

- Oncofetal antigen: found on surface & inside of cells as well as fetal cells.

- CEA: carcinogen embryonic antigen

found in cancer cells of GI tract

- AFP: alpha-fetoprotein found in hepatocytes

B. Immunological defense B. Immunological defense against CAagainst CA

1. Immune surveillance mechanisms

Cytoxic T cells - kill tumor cells

Natural Killer cells - directly lyse tumor cells

Monocytes/Macrophages - important in detection of CA cells. Secret cytokines

B cells – produce antibodies that bind to and kill tumor cells

Macrophage functioning in response Macrophage functioning in response to malignant target cellsto malignant target cells

2. How cancerous cells evade2. How cancerous cells evade immune system immune system

Depends on ability of immune system to recognize cancer cells as being different from self cells

Closely resemble cells they originate from Process where cancer cells evade immune

system is called immunologic escape

Tumor associated antigens on Tumor associated antigens on surface of malignant cellssurface of malignant cells

Blocking Antibodies Preventing T-Blocking Antibodies Preventing T-Cell from Destroying Malignant CellCell from Destroying Malignant Cell

III. Normal vs. abnormal cellIII. Normal vs. abnormal cell growth and reproduction growth and reproduction

A. Review of normal cell cycle

Reproduction of both healthy and malignant cells follow cell cycle pattern

Time required for one tissue cell to divide and reproduce into 2 identical cells

Phases of normal cell cyclePhases of normal cell cycle

G1 phase – post mitotic phase. Relatively dormant - some RNA & protein synthesis

S phase - DNA synthesis occurs G 2 phase – pre mitotic phase. Some RNA &

protein synthesis M Phase - cell division occurs G o Phase - resting phase

Cell CycleCell Cycle

B. Cell proliferationB. Cell proliferation

Cells divide and reproduce Regulated so number of cells dividing = to

number dying or being shed Cell types fit into 3 large groups:

Well differentiated neurons, skeletal and cardiac muscle cells

Parent or progenitor cells Undifferentiated stem cells

C. Cell differentiationC. Cell differentiation

Cells transformed into different and more specialized cell types

Adult cell achieves specific set of structural, functional, and life expectancy characteristics

Orderly process

Normal Cellular DifferentiationNormal Cellular Differentiation

IV.IV. Characteristics of Benign andCharacteristics of Benign andMalignant NeoplasmsMalignant Neoplasms

A. Terminology

1. Tumor

2. Neoplasia

B. Benign NeoplasmsB. Benign Neoplasms

Well differentiated cells that cluster together in single mass

Resemble cells of tissue of origin Slow, progressive rate of growth Expands, but unable to metastasize Usually enclosed in fibrous capsule

C. Malignant NeoplasmsC. Malignant Neoplasms

Less well differentiated cells Able to break loose, enter circulation or lymph

system, and form secondary malignant tumors at other sites

Grow rapidly, spread widely Potential to kill regardless of original location

Benign vs. MalignantBenign vs. Malignant

1. Cancer cell characteristics1. Cancer cell characteristics

Cells fail to undergo normal cell proliferation and differentiation

Anaplasia – term used to describe lack of cell differentiation in cancerous tissue

Cancer cells do not function properly and do not die according to time frame of normal cells

2. Invasion and metastasis2. Invasion and metastasis

Cancer spreads by: Direct invasion and extension

Seeding of cancer cells in body cavities

Metastatic spread through blood or lymph pathways

MetastasisMetastasis

Process of metastasisProcess of metastasis

Sites of bloodborne metastasesSites of bloodborne metastases

Metastasis to the brainMetastasis to the brain

Metastasis to the boneMetastasis to the bone

3. Tumor growth3. Tumor growth

Rate of tissue growth in normal and cancerous cells depends on: Number of cells actively dividing or moving

through cell cycle Duration of cell cycle Number of cells being lost compared with number

of cells being produced

In blood cancers ex. leukemia, the cancer is rapidly dividing as it mimics normal life-cycle of surrounding cells EXCEPT scheduled death. The cancer cells persist.

V. Carcinogenesis and majorV. Carcinogenesis and major risk factors risk factors

A. Carcinogenesis

1. Terms important in carcinogenesis Two mutational routes that result in

uncontrolled cell proliferation are characteristic of cancer:

stimulation of gene causing hyperactivity inhibition of gene causing inactivity

a. Oncogenea. Oncogene

Cancer causing gene – altered gene Gene that promotes autonomous cell growth in

cancer cells Mutations of normal growth-regulating genes

Oncogenesis: mechanism by which normal cells mutate into cancer cellsOnly one single altered gene copy can cause an overgrowth

b. Proto-oncogeneb. Proto-oncogene

Normal growth-promoting gene thought to be active when appropriate growth-promoting signals reach cell

“On switch” for cellular growth

If there’s a mutation in the proto-oncogene, then the cell is released from…?

c. Anti-oncogene/Suppressor genec. Anti-oncogene/Suppressor gene

Gene that inhibits proliferation of cells Genetic signal that normally inhibits

proliferation is removed – causes unregulated growth

“Turns off” or regulates unneeded cellular proliferation

Stages in Development of a Malignant NeoplasmStages in Development of a Malignant Neoplasm

2. Cancer cell transformation2. Cancer cell transformation

a. Initiation – 1st Step Exposure of cells to appropriate doses of

carcinogenic agent - makes them susceptible to malignant transformation

Irreversible alteration in cell’s genetic structure Not usually significant to cells until 2nd step of

carcinogenesis

Physical/chemical/biological agents, ex. virus, can cause cancer

b. Promotion – 2nd stepUnregulated accelerated growth in already initiated cells by various chemical and growth factorsCharacterized by reversible proliferation of altered cell if promoter substance removed

2. Cancer cell transformation2. Cancer cell transformation

c. Progression – 3rd stepCellular changes formed during initiation and promotion assume increased malignant behaviorCells divide in uncoordinated fashion, invade and destroy neighboring tissue

2. Cancer cell transformation2. Cancer cell transformation

Process of Cancer DevelopmentProcess of Cancer Development

Initiation, Promotion and ProgressionInitiation, Promotion and Progression

B. Risk factors B. Risk factors

1. Heredity Predisposition to approx. 50 types of cancer

has been observed in families 10% of cancers have strong genetic link

2. Hormones2. Hormones

Thought to drive cell division Women – breast, ovary, endometrium Men – prostate, testis

3. Immunologic mechanisms3. Immunologic mechanisms

Cancer associated with impairment or decline in immune system. See increase in: People with immunodeficiency disease Organ transplant pts taking immunosuppressant

drugs Elderly

4. Chemical carcinogens4. Chemical carcinogens

Cigarette smoke Workplace carcinogens Air pollution Diet Alcohol

5. Radiation5. Radiation

Ultraviolet exposure

Ionizing radiation exposure

Electromagnetic field exposure

6. Oncogenic viruses6. Oncogenic viruses

Incorporate themselves into genetic structure of cell

Alter future generations of cell Human papillomavirus (HPV) Epstein-Barr virus (EBV)

VI. Prevention and early VI. Prevention and early detection of cancer detection of cancer

Primary Prevention

Secondary Prevention

Tertiary Prevention

A. Preventive measuresA. Preventive measures

Important role for RN Must have knowledge and skills to educate

community about: health-related behaviors risk factors screening and detection methods

1. Patient education1. Patient education

Numerous factors influence degree of knowledge people have about CA risk factors and health promoting behaviors:

race cultural influences level of education income age

Seven Warning Signs of CancerSeven Warning Signs of Cancer

C A U T I O N – nagging cough/hoarseness See Lewis Table 16-8

B. Screening procedures forB. Screening procedures for different types of cancer sites different types of cancer sites

SBE for breast cancer Rectal exams for prostate cancer Sigmoidoscopy/colonoscopy Occult blood for colon cancer

VII. Ways of classifying cancerVII. Ways of classifying cancer

Tumors are classified on basis of: cell type tissue of origin benign or malignant degree of differentiation anatomic site function

A. By anatomic siteA. By anatomic site

Epithelial tissue - carcinomas

Connective tissue - sarcomas

Lymphatic tissue - lymphomas

Glial cells of the CNS - gliomas

Blood forming organs (mainly bone marrow)- leukemias

B. Histological Analysis B. Histological Analysis ( (““GradingGrading””))

Grade I: cells differ slightly from normal cells and are well differentiated

Grade II: cells are more abnormal and moderately differentiated

Grade III: cells are very abnormal (severe hyperplasia) and poorly differentiated

Grade IV: cells are immature and primitive and undifferentiated, no resemblance to tissue of origin

Mutation of a Cell LineMutation of a Cell Line

C. Extent of disease (C. Extent of disease (““StagingStaging””))

Describes location and pattern of spread of tumor TNM most common:

Tumor (primary) Node Metastasis

Clinical StagingClinical Staging

0 - CA in situ I - tumor limited to tissue or organ II - limited local spread III - extensive local and regional spread IV - metastasis

VIII. Major treatment options in VIII. Major treatment options in

cancer treatment cancer treatment Goals - Cure, Control, Palliation Used to be considered cured if no cancer

recurrence for 5 years after treatment Widespread invasions associated with poor

prognosis Choice of Rx depends on staging - more

metastasis = more aggressive approach

Goals of cancer treatmentGoals of cancer treatment

A. SurgeryA. Surgery

Approx 90% treated surgically Main benefit - removal of tumor with minimal

damage to other body cells Surgery involves risk Usually followed by radiation or

chemotherapy

Goals of surgeryGoals of surgery

B. RadiationB. Radiation

Used to interrupt cellular growth. Can: immediately kill cells delay or halt cell cycle progression cause damage in nucleus that causes cell death

after replication

Types of RadiationTypes of Radiation

1. External radiation - source placed outside the body

“Lethal tumor dose”: will eradicate 95% of tumor while preserving normal tissue

2. Internal radiation/Brachytherapy - source placed close to or directly in the tumor site

Seeds, beads, needle, catheter, etc.

Brachytherapy: limits radiation to duration of treatment?

Time, Distance, Shielding

Linear accelerator treatment for Linear accelerator treatment for head and neck cancerhead and neck cancer

Wet desquamation from RT

Dry desquamation from RT

C. ChemotherapyC. Chemotherapy

Systemic administration of anticancer chemicals

Most agents are cytotoxic - interfere with some aspect of cell division

More rapidly dividing cells more susceptible Normal cells die too

Goals of chemotherapyGoals of chemotherapy

1. Classifications1. Classifications

a. Cell cycle specific Destroys cells in specific phases of cell cycle

b. Cell cycle non-specific Act independently of cell cycle phases Often combine with cell-cycle specific to

increase number of cells killed

Action Sites of CCS [Antineoplastic] DrugsAction Sites of CCS [Antineoplastic] Drugs

Action Sites of Non–Cell Cycle–Specific Action Sites of Non–Cell Cycle–Specific Antineoplastic Agents Antineoplastic Agents

2. Examples2. Examples

See Table 16-9 “Classifications of Chemotherapy Drugs” in Lewis

Chemotherapy/survival relationshipChemotherapy/survival relationship

3. Routes of administration3. Routes of administration

Topical, Oral, IM, IV, SQ, Arterial, Intercavity, Intrathecal routes

Depends on type of drug, required dose, and type, location, and extent of tumor

Patients frequently have central lines placed for chemotherapy due to the frequency of treatment and vesicant (caustic) nature of the medications

PICC Line placementPICC Line placement

Tunneled Central LineTunneled Central Line

Huber needle access of implanted portHuber needle access of implanted port

4. Extravasations4. Extravasations

“Escape of fluids into the surrounding tissue” Such as in IV infiltration. Apply ice to slow

circulation. Can cause tissue necrosis and damage to

underlying tendons, nerves, and blood vessels Treatment - stop drug immediately and apply

ice. Notify MD

5. Toxicity and side effects5. Toxicity and side effects

Can be acute or chronic Cells with rapid growth rates are very

susceptible to damage Various body systems may be affected

5. Toxicity and side effects (cont.)5. Toxicity and side effects (cont.)GI system - N & V most common; stomatitis

Hematopoietic system - depressed bone marrow function

anemia, thrombocytopenia, etc.

Renal system - damage by direct effects during excretion or accumulation of end products after cell lysis

Hair loss (alopecia) - hair cells are rapidly dividing

Cardiopulmonary system - can cause cumulative cardiac toxicities. Toxic effects on lung function.

Sometimes necessitates transplant.

Reproductive system - affects testicular & ovarian functionSome choose to bank their gametes.

6. Nursing consideration for6. Nursing consideration forpatients on chemotherapypatients on chemotherapy

Fluid and electrolytes Infection and bleeding

thrombocytopenia, leukopenia

Skin Problems Hair Loss Nutritional Concerns

d/t stomatitis, anorexia, N/V

Chemotherapy administration Self protection

D. Hormonal therapyD. Hormonal therapy

Used for cancers that are responsive to or dependent on hormones for growth: breast prostate adrenal glands endometrium

E. BiotherapyE. Biotherapy

Active Immunotherapy – acts as nonspecific stimulant of immune system

Passive Immunotherapy – transfer of cultured immune cells into person with cancer Sensitized NK cell T lymphocytes Cytokines

Biologic Response ModifiersBiologic Response Modifiers

Changes person’s biologic response to cancer Cytokines: IFNs, ILs that bind Monoclonal antibodies: produced by B-cells Hematopoietic growth factors: epogen?

F. Targeted therapyF. Targeted therapy

Drugs that target processes of cancer cells specifically

Leave normal cells unharmed

G. Bone marrow and peripheralG. Bone marrow and peripheral blood stem cell transplantation blood stem cell transplantation

High dose chemo and radiation therapy used to ablate or suppress bone marrow

Self or donor stem cells transplanted

Stem cell transplantStem cell transplant