Download UNIVERSITY OF PERPETUAL HELP LAGUNA

UNIVERSITY OF PERPETUAL HELP LAGUNA
COLLEGE OF NURSING
Sto. Niño, Biñan, Laguna
LECTURE HANDOUTS IN CELLULAR ABERRATIONS
CANCER
 A disease process whereby cells proliferate abnormally, ignoring growth-regulating signals in the
environment surrounding the cells.
 Comes from the Latin word cancri and the ancient Greek word cancere, which mean “crab”, based on the
old belief that cancerous tissues have the propensity to “scavenge” and eat up surrounding tissue, pretty
much the same way that crabs eat up anything on their path.
EPIDEMIOLOGY OF CANCER
 Most cases of cancer are seen in the elderly population for the following reasons:
o The aging process makes possible mutations of cells that lead to uncontrolled mitosis and
development of malignant properties.
o Cancer, for the most part, is a chronic process. Many symptoms and signs that lead to suspicion
and diagnosis of the condition are seen later on in life.
o Elderly people, by virtue of having lived longer, have cumulative exposures already to potential
carcinogens in the environment.
o The role of the immune system in recognizing and controlling the growth of abnormal cells
highlight the importance of an intact immune system in the prevention of cancer development.
Elderly people nay have already developed immune system alteration that make them
immunocompromised compared to their younger counterparts.
 There is a higher incidence of malignancy among men compared to their female counterparts.
 It is the second leading cause of mortality in the United States based on 2004 data.
 In terms of incidence, lung, prostate and colorectal cancers are the leading causes of cancer deaths among
men in the United States, while lung, breast and colorectal cancers are the leading causes of cancer deaths
among women for the same year (2004).
PATHOPHYSIOLOGY OF THE MALIGNANT PROCESS
Cancer is a disease process that begins when an abnormal cell is transformed by the genetic mutation of the cellular
DNA.
 Abnormal cells form clones and begin to proliferate abnormally, ignoring growth-regulating signals in the
environment surrounding the cell.
 The cells infiltrate normal tissues and gain access to lymph and blood vessels and carry the cancer cells to
other areas of the body (metastasis).
PROLIFERATIVE PATTERNS
Hyperplasia
This process refers to an increase in the size and number of cells in an organ or tissue, which may then have
increased volume. Possible causes include:
1. Physiologic
a. Hormonal causes like estrogen (endometrial thickening), thyroid (compensatory hyperplasia in
hypothyroid patients)
b. Compensatory mechanisms as seen in hypertrophic scar formation.
2. Pathologic
a. Excessive hormonal stimulation
b. Viral-induced
Metaplasia
Metaplasia is a reversible change in cellular appearance in which one adult cell type is replaced by another cell type.
This is often an excessive compensatory phenomenon in an attempt to restore volume in an otherwise abnormal
tissue. Common causes include:
1. Persistent irritation
a. Lichenification of skin constantly exposed to friction
b. Erythroplakia of the mucous membranes from ill-fitting dental gadgets or dentures
2. Infections
3. Malnutrition
Dysplasia
This is often considered a pre-malignant cellular transformation characterized by loss in the uniformity of the cells
in the affected tissue, as well as breakdown of their architectural orientation. Pleomorphism, or a variation in size
and shape, is the norm. Atypical cells develop and proliferate, changing the overall appearance of the tissue.
Dysplasia is often considered a maladaptive process and is seen as a turn towards the worse. It is never viewed as a
compensatory event.
Anaplasia
In anaplasia (from a- absence, and plasia “differentiation”), cells lack normal cellular characteristis, differing in
shape and organization with respect to their cellular origin. They often may not be classified into any typical
cellular type. Most anaplastic cells are malignant.
NEOPLASIA
 Literally means “new growth.”
 This refers to an abnormal mass of tissue wherein the growth is excessive and uncoordinated compared to
those of normal tissues.
 Growth of abnormal tissues persists even after cessation of the initial stimulus which evoked the change.
 Neoplastic lesions may either be benign or malignant (cancerous).
 Neoplasia is often cancerous if the cellular proliferation is uncontrolled, the cell growth and differentiation
are disorganized, and the effect on the organism is catastrophic.
DIVISION BEHAVIOR OF CELLS
Normal Cells
 Cells exhibit contact inhibition.
 Cells often form only monolayers.
 Division is up to 20 to 60 times only.
Cancer Cells
 Cells are insensitive to contact inhibition.
 They form a disorganized multi-layered architectural design.
 Division is limitless
CHARACTERISTICS OF BENIGN AND MALIGNANT NEOPLASMS
BENIGN
MALIGNANT
Well-differentiated and resemble normal cells of
Undifferentiated and bear little semblance to the
the tissue from which the tumor originated.
normal cells from which they arose.
Growth is by expansion; usually encapsulated.
Growth starts from the periphery and infiltrate
and destroy surrounding tissues.
Growth rate is usually slow.
Rate of growth is variable; the more anaplastic the
cell, the faster is its growth.
Does not metastasize.
Metastasizes throughout the body.
Localized; does not cause generalized effects
Often causes generalized effects, such as anemia,
unless its location interferes with vital function.
weakness and weight loss.
Does not usually cause tissue damage, unless the
Often causes extensive tissue damage; may also
location interferes with blood flow.
produce substances that cause cell damage.
Does not usually cause death unless, its location
Usually causes death, unless growth can be
interferes with vital functions.
controlled.
CHARACTERISTICS OF MALIGNANT CELLS
1. Cell membranes of malignant cells contain proteins called tumor-specific antigens which develop as they
become less differentiated over time.
2. Malignant cells contain less fibronectin, a cellular cement. They are therefore less cohesive and do not
adhere to adjacent cells readily.
3. The nuclei are large and exhibit pleomorphism.
4. There are a lot of chromosomal abnormalities like translocations, deletions and additions.
5. Mitosis occurs more frequently.
METASTASIS
Sequence of Events in Invasion and Metastasis:
1. Invasion of intracellular matrix
a. Detachment of tumor cells
b. Attachment to matrix components
c. Degradation of extracellular matrix
d. Migration of tumor cells
2. Vascular dissemination / Homing
a. Vascular / lymphatic drainage
b. Microenvironment formation
Mechanisms of Metastasis
1. Lymphatic spread
2. Hematogenous spread
3. Angiogenesis
CARCINOGENESIS
PATHOGENESIS OF CANCER
1. Cellular transformation and derangement theory – conceptualizes that normal cells may be transformed into
malignant cells due to exposure to some etiologic agents.
2. Failure of the immune response theory – advocates that all individuals possess cancer cells. However, the
cancer cells are recognized by the immune response system, so they can undergo destruction. Failure of the
immune response system leads to inability to destroy the cancer cells.
CELLULAR TRANSFORMATION AND DERANGEMENT THEORY
THREE-STEP CELLULAR PROCESS
Initiation
 Initiators (carcinogens) such as chemicals, physical factors and biologic agents escape normal enzymatic
mechanisms and alter the genetic structure of the cellular DNA.
 Normally these alterations are reversed by DNA repair mechanisms, or the affected cells undergo
apoptosis.
 If cells escape protective mechanisms, the event will lead to permanent mutations.
Promotion
 Repeated exposures to carcinogens cause expression of abnormal or mutant genetic information even after
long latency periods.
 PROTO-ONCOGENES act as an “on switch” for cellular growth.
 Cellular ONCOGENES are DNA sequences within eukaryotic cells that seem to be involved in the
development and maintenance of tumors. These genes direct he synthesis of proteins that, under some
conditions, transform a benign host cell into a cancer cell.
 The conversion of proto-oncogenes to oncogenes is mediated by exposure to carcinogens.
 If proto-oncogenes are turned on, cancer suppressor genes are turned off.
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Tumor-suppressor genes keep cells benign, even when the oncogenes are activated. The p53 gene product
is a sequence-specific binder to DNA that prevents mitosis during times of cell injury, so that there will be
more time for DNA repair.
Progression
 The cellular changes formed during initiation and promotion exhibit increased malignant behavior.
 These cells now have a propensity to invade adjacent tissues and to metastasize.
ETIOLOGIC FACTORS
1. Viruses and bacteria
 Integrate genetic material into the host DNA
 Human papilloma virus (cervical squamous cell CA, genital warts, herpes simplex type II,
cytomegalovirus, Kaposi’s sarcoma
 Epstein-Barr virus (Burkitt’s lymphoma, nasopharyngeal CA, lymphoma in AIDS)
 Hepatitis B virus (hepatocellular carcinoma)
 Helicobacter pylori (peptic ulcer disease, gastric and duodenal CA)
2. Physical agents
 Exposure to sunlight or radiation
 Chronic irritation or inflammation
 Use of tobacco
3. Chemical agents
 They alter DNA structure in body sites distant to chemical exposure.
 Liver, lungs and kidneys are the organs often affected.
 75% of cancers are thought to be related to the environment
 Industrial compounds (vinyl chloride, polycyclic aromatic hydrocarbons, fertilizers and weed killers,
dyes and drugs)
 Foods and preservatives (nitrites, talc, food sweeteners, nitrosamines, aflatoxins, polycyclic
hydrocarbons)
4. Genetic and familial factors
 This may be due to genetics, shared environments, cultural or lifestyle factors, or chance alone.
 Approximately 5% of cancers of adults display a familial predisposition.
 May include cancer in two or more relatives, cancers in family members younger that 50 years of age,
the same type of cancer in several family members, family members with more than one type of
cancer, and a rare cancer in one or more family members
5. Dietary factors
 High fat diet
 Alcohol abuse
 Salt-cured food
 Smoked meats
 Nitrate and nitrite-containing foods
 High caloric diet (obesity is a risk factor for the development of breast, endometrial and colorectal
cancer)
 Note: a high-fiber diet decreases risk for cancer
6. Hormonal agents
 Hormonal imbalance may promote tumor growth whether by endogenous or exogenous hormones
 Diethylstilbestrol (DES) has been shown to cause vaginal or vulvar carcinoma.
 Oral contraceptives promote hepatocellular, endometrial, breast carcinoma, but lowers the risk for
ovarian carcinoma.
 A combination of estrogen and progesterone in oral contraceptive pills has been found to be safer than
pure estrogen pills.
 Increased numbers of pregnancies decrease the incidence of breast, endometrial and ovarian cancer.
FAILURE OF THE IMMUNE RESPONSE THEORY
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If the body fails to recognize the malignant cell as different from “self”, the immune response may not be
stimulated.
When tumors do not possess tumor-associated antigens that label them as foreign, the immune response is
not alerted.
Failure of the immune system to respond promptly to the malignant cells allows the tumor to grow too
large to be managed by normal immune mechanisms
Tumor antigens may combine with antibodies produced by the immune system and hide or disguise
themselves from normal immune defense mechanisms. These tumor antigen-antibody complexes can
suppress further production of antibodies.
The presence of host suppressor T cells or T lymphocytes in abnormal concentration may play a role in
cancer development.
Tumors are also capable of changing their appearance, or producing substances that impair usual immune
responses. These substances increase the patient’s susceptibility to infection, and prolonged contact may
deplete specific lymphocytes.
PATHOPHYSIOLOGIC BASIS OF MALIGNANT NEOPLASIS
Predisposing Factors / Etiologic Factors
CELLULAR ABERRATIONS
CA Cell Proliferation
Pressure
Obsruction
Pain
Effusion
Ulceration
Vascular thrombosis
embolism and
thrombophlebitis
Malignant cells produce
enzymes, hormones and
other substances
(Paraneoplastic Syndrome)
Anemia
Hypercalcemia
Edema
Disseminated intravascular
coagulation
Anorexia / Cachexia
Syndrome
Tissue wasting
Severe weight loss
Severe debilitation
Proliferation of Cancer Cells
 Pressure due to increase in size of neoplastic growth.
 Obstruction – as tumor continues to grow, hollow organs and vessels become compressed and obstructed.
 Pain due to:
o Pressure on nerve endings
o Distention of organs and vessels
o Lack of oxygen to tissues and organs
o Release of pain mediators by the tumor
 Effusion due to obstruction of lymphatic flow
 Ulceration result as the tumor erodes blood vessels, and pressure on tissue causes ischemia with tissue
damage, bleeding and infection.
 Vascular thrombosis, embolism and thrombophlebitis develop as tumors produce coagulate factors that
cause increased clotting.
Paraneoplastic Syndrome
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Anemia
o Cancer cells produce chemicals that interfere with RBC production.
o Iron uptake is greater in the tumor than that deposited in the liver.
o Blood loss from tumor expansion and erosion of blood vessels and normal tissues.
Hypercalcemia
o Tumors of the bone, squamous cell lung CA, and breast cancer produce a PTH-like hormone that
increases or accelerates bone breakdown and release of calcium.
o May also result from bone metastasis.
o Further enhanced by immobilization and dehydration.
Disseminated intravascular coagulation
o More likely to occur in carcinoma of the lungs, pancreas, stomach and prostate gland.
o Precipitated by the release of tissue thromboplastin, or by endothelial injury
Anorexia – Cachexia Syndrome
 The final outcome of unrestrained cancer cell growth
 Malignant neoplasms deprive normal cells of nutrition.
 Tumors produce alteration in enzyme systems necessary for normal metabolism.
 Tumors revert to anaerobic metabolism.
 Protein depletion, serum albumin levels decrease.
 Tumors take up sodium, water retention masks malnutrition and is not immediately reflected as weight loss.
 Cancer cells produce anorexigenic substances that act in the satiety center of the hypothalamus, causing
anorexia.
 Taste sensation diminishes or becomes altered, and the individual may have aversion to eating, particularly
meat.
DETECTION AND PREVENTION OF CANCER
PRIMARY PREVENTION
 Includes reducing the risks of cancer in otherwise healthy people.
 Patient education on cancer risk is crucial in primary prevention.
 Instruct patient to avoid known carcinogens.
 Encourage patients to make dietary and various lifestyle changes.
 Estrogen antagonists (tamoxifen) has been shown to effectively reduce the incidence of breast cancer by
49% in postmenopausal women.
SECONDARY PREVENTION
 Early screening for patients with a strong family history of cancer.
 Implementation of programs for early detection of cancer.
 Breast self-examination
 Testicular self-examination
 Papanicolaou (Pap) smear examination
Breast Self Examination
 This should be done monthly starting age 20 years.
 Best performed around 7 to 10 days from the first day of menstrual flow.
 If menstrual cycle is irregular, or if the patient is not menstruating (pregnant or postmenopausal) then BSE
should be done on the same day every month.
o In standing position, note specifically for symmetry of the breast while standing in front of a
mirror.
o In lying position, elevate shoulders of the side being examined, with pillow support.
o Palpate the breast by quadrants, or from the periphery to the center in circular motion.
o Note for the following:
 Firm, non-tender, non-mobile mass.
 Solitary, irregularly shaped mass.
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Adherence to muscle or skin, causing the “dimpling” effect.
Involvement of the upper outer quadrant of the breast, or central areolar portion of breast.
Asymmetry of the breasts.
“Orange peel” skin.
Retraction of the nipple.
Abnormal discharge of the nipple.
Testicular Self-Examination
 This should be done monthly starting age 18 among men.
 Best performed after a warm bath or shower.
o Stand in front of a mirror.
o Check for any swelling on the scrotal skin.
o Examine each testicle with both hands.
o Place the index and middle fingers under the testicle with the thumbs placed on top.
o Roll the testicle gently between the thumbs and fingers.
o Find the epididymis and differentiate it from cancerous lumps which are usually found on the
sides or front of the testicle.
Papanicolaou Smear
 This is the initial diagnostic test for cervical cancer.
 A woman should have a Pap smear if she:
o Has reached the age of 18 years;
o Is sexually active;
o Has been sexually active.
 Conflicting evidence on the utility of Pap smear if the woman has:
o Reached the age of 65 years; or
o Had normal test results for three years in a row.
WARNING SIGNS OF CANCER
C – hange in bowel or bladder habits (urinary bladder and colorectal)
A – sore that does not heal on the skin or in the mouth (skin or oral)
U – nusual bleeding or discharge (colorectal, protate, urinary bladder or cervical)
T – hickening of the breast tissue or a new lump (breast or testicular)
I – ndigestion or trouble swallowing (mouth, throat, esophagus or stomach)
O – bvious changes in moles or warts (skin)
N – agging cough or hoarseness (lung or throat)
U – nexplained anemia (hematologic)
S – udden weight loss (systemic manifestation associated with malignancies
DIAGNOSIS OF CANCER
 Complete history and physical examination.
 Determine the presence of tumor and its extent.
 Identify possible spread (metastasis) of disease, or invasion of other body tissues.
 Evaluate the function of organs involved and identify the uninvolved body systems and organs.
 Obtain tissues and cells for analysis for tumor grading or staging.
Laboratory Evaluation
 Tumor marker identification
o Alpha-feto protein (hepatocellular carcinoma)
o Human chorionic gonadotrpin or HCG (chorionic carcinoma, gynecologic malignancies)
o Prostatic acid phosphatase (prostatic carcinoma)
o Prostatic specific antigen or PSA (prostatic carcinoma)
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o Carcinoembryonic antigen (gastrointestinal malignancies)
o CA-125 (ovarian carcinoma)
Imaging (MRI, CT scan, fluoroscopy, ultrasonography, endoscopy, nuclear medicine imaging, PET scan
and PET fusion scan, radioimmunoconjugates)
Histopathologic diagnosis
Staging and Grading of Neoplasis
 Determining the extent of a confirmed neoplastic disease.
 TNM system (Tumor, Nodal involvement, Metastasis)
CANCER PREVENTION
Skin – avoid overexposure to sunlight.
Oral – annual oral examination
Breast – monthly BSE from age 20.
Lungs – avoid cigarette smoking; annual chest x-ray.
Colon – digital rectal examination for persons over age 40; rectal biopsy; proctoscopic examination; guaiac stool
examination for persons age 50 and above.
Prostate – annual digital rectal examination for men above the age of 40.
Uterus - annual Pap’s smear from age 35.
Basic – annual physical examination and blood examination
DIETARY RECOMMENDATIONS AGAINST CANCER
1. Avoid obesity
2. Cut down on total fat intake.
3. Eat more high-fiber foods like raw fruit and vegetables, whole grain cereals.
4. Include foods rich in vitamin A and C in daily diet.
5. Include cruciferous vegetables in the diet like broccoli, cabbage, cauliflower and brussel sprouts.
6. Be moderate in the consumption of alcoholic beverages.
7. Be moderate in the consumption of salt – cured and smoked foods.
DIFFERENT THERAPEUTIC MODALITIES FOR CANCER
 Surgical interventions
o Preventive surgery – removal of precancerous lesions or benign tumors
o Diagnostic surgery – biopsy
o Curative surgery – removal of an entire tumor (en bloc resection)
o Reconstructive surgery – improvement of structure and function of an organ
o Palliative surgery – relief of distressing signs and symptoms; retardation of metastasis.
 Chemotherapy
o Objectives
 To destroy all malignant tumor cells without excessive destruction of normal cells.
 To control tumor growth if cure is no longer possible.
 Use as adjuvant therapy.
o Contraindications
 Infection – anti-tumor drugs are immunosuppressives
 Recent surgery – drugs retard healing process
 Impaired renal or hepatic function.
 Recent radiation therapy
 Pregnancy
 Bone marrow depression
 Radiation therapy
o Primary curative role / adjunct to other therapy / palliation
o Sources of radiation
 External radiation therapy
 Internal radiation therapy
o Types
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Sealed source (brachytherapy)
Unsealed source (oral, intravenous)
Prepared by:
ARNI A. MAGDAMO, MD, MHA, FPCP
University of the Philippines
College of Medicine