Alterations in Cell Function and Differentiation

Management of Neoplastic Disruptions

I. 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 prevalence by site and
sex
Men
Prostate
Lung/Bronchus
Colon/Rectum
Urinary Tract
Melanoma
Women
Breast
Lung /Bronchus
Colon/Rectum
Uterus
Ovary
Leading Cancer Site Percentages
Estimated mortality
Men
Lung/Bronchus
Prostate
Colon/rectum
Pancreas
Non-Hodgkins lymphoma
Women
Lung/Bronchus
Breast
Colon/rectum
Pancreas
Ovary
II. Host defense mechanisms in
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 against 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 to malignant
target cells
2. How cancerous cells evade
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 surface of
malignant cells
Blocking Antibodies Preventing T-Cell from
Destroying Malignant Cell
III. Normal vs. abnormal cell
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 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 Cycle
B. 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 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 Differentiation
IV.
Characteristics of Benign and
Malignant Neoplasms
A. Terminology
1. Tumor
2. Neoplasia
B. 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 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. Malignant
1. 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 metastasis
Cancer spreads by:
Direct invasion and extension
Seeding of cancer cells in body
cavities
Metastatic spread through blood
or lymph pathways
Metastasis
Process of metastasis
Sites of bloodborne metastases
Metastasis to the liver
Metastasis to the lungs
Metastasis to the brain
Metastasis to the bone
3. 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
V. Carcinogenesis and major
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. Oncogene
Cancer causing gene altered gene

Gene that promotes autonomous cell growth in

cancer cells
Mutations of normal growth-regulating genes
b. Proto-oncogene
Normal growth-promoting gene thought to be
active when appropriate growth-promoting
signals reach cell
On switch for cellular growth
c. 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 Neoplasm
2. 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 cells genetic structure
Not usually significant to cells until 2nd step of
carcinogenesis
2. Cancer cell transformation
b. Promotion 2nd step
Unregulated accelerated growth in already
initiated cells by various chemical and growth
factors
Characterized by reversible proliferation of
altered cell if promoter substance removed
2. Cancer cell transformation
c. Progression 3rd step
Cellular changes formed during initiation and
promotion assume increased malignant behavior
Cells divide in uncoordinated fashion, invade and
destroy neighboring tissue
Process of Cancer Development
Initiation, Promotion and Progression
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. Hormones
Thought to drive cell division
Women breast, ovary, endometrium
Men prostate, testis
3. 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 carcinogens
Cigarette smoke

 Workplace carcinogens
Air pollution
Diet
Alcohol
5. Radiation
Ultraviolet exposure
Ionizing radiation exposure
Electromagnetic field exposure
6. 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
detection of cancer
Primary Prevention
Secondary Prevention
Tertiary Prevention
A. 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 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 Cancer
C
A
U
T
I
O
N nagging cough/hoarseness
See Lewis Table 16-8
B. Screening procedures for
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 cancer
Tumors are classified on basis of:
cell type
tissue of origin
benign or malignant

degree of differentiation
anatomic site
function
A. 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
(Grading)
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 Line
C. Extent of disease (Staging)
Describes location and pattern of spread
of tumor
TNM most common:
Tumor (primary)
Node
Metastasis
Clinical 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
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 treatment
A. 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 surgery
B. 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 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 head and neck
cancer
Wet desquamation from RT
Dry desquamation from RT
C. 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 chemotherapy
1. 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] Drugs

Action Sites of NonCell CycleSpecific
Antineoplastic Agents
2. Examples
See Table 16-9 Classifications of Chemotherapy
Drugs in Lewis
Chemotherapy/survival relationship
3. 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 placement
Tunneled Central Line
Huber needle access of implanted port
4. 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 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.)
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
function
Some choose to bank their
gametes.
6. Nursing consideration for
patients 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 therapy
Used for cancers that are responsive to or
dependent on hormones for growth:
breast
prostate
adrenal glands
endometrium
E. 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 Modifiers
Changes persons biologic response to cancer
Cytokines: IFNs, ILs that bind
Monoclonal antibodies: produced by B-cells
Hematopoietic growth factors: epogen?

F. Targeted therapy
Drugs that target processes of cancer cells
specifically
Leave normal cells unharmed
G. Bone marrow and peripheral
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 transplant