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PATHOPHYSIOLOGY
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Chapter 10, Part 2: Cancer Manifestations and Treatment
Chapter 11: Cancer Epidemiology
PART 1: CHAPTER 10, Part 2
I. Clinical Manifestations of Cancer

Clinical manifestations of cancer include pain, fatigue, cachexia, anemia, leukopenia,
thrombocytopenia, and infection.
A. Pain

Little or no pain is associated with early stages of malignancy. Most occurs in late stages.

Influenced by fear, anxiety, sleep loss, fatigue, and overall physical deterioration.

It occurs as a result of the interaction among psychogenic, cultural, and physiologic components.

Mechanisms:
o
Pressure, obstruction, invasion of sensitive structures like bone, stretching of visceral
surfaces, tissue destruction, and inflammation with associated pain-inducing chemicals.

Adequate pain control is an important therapeutic goal; based on continual evaluation of pain as
reported by the individual.

Treatments include anti-inflammatory drugs, local anesthesia, and opiods (like morphine).
B. Fatigue

Fatigue is the most frequently reported symptom of cancer and cancer treatment.
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Subjective clinical manifestations, including:
o
Tiredness, weakness, lack of energy, exhaustion, lethargy, inability to concentrate, impaired
intellectual performance, depression, mood swings, sleepiness, boredom, and lack of motivation.

May be caused by a variety of mechanisms:
o
Disease processes – metabolic disturbances, neuromuscular dysfunction from circulating
cytokines (TNF-alpha and interleukin-1), and side effects of treatment.
o
Secondary effects - sleep disturbance, chronic stress, age, psychosocial factors, level of
activity, nutritional status, and environmental factors.
C. Cachexia

Most severe form of malnutrition.

Present in 80% of cancer patients at death.

Includes:
o
Anorexia, loss of appetite, early satiety (feeling of fullness), weakness, inability to maintain
weight, anemia, taste alterations, and altered protein, lipid, and carbohydrate metabolism.

Leads to protein-calorie malnutrition and progressive wasting, similar to Kwashiorkor syndrome.

Altered carbohydrate metabolism causes a syndrome resembling diabetes mellitus.
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
Basal metabolic rate increases in some cancers, which accelerates weight loss.

This increase is caused by cytokines such as TNF-alpha (also called cachectin), IL-1, IL-6, and
interferons.
D. Anemia
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Anemia is a decrease of hemoglobin in the blood.

Mechanisms:
o
Malnutrition, chronic bleeding and resultant iron deficiency, decreased secretion of
erythropoietin, chemotherapy, and malignancies in the blood-forming organs.

Synthetic erythropoietin (Procrit) can increase hematocrit in cancer patients.
E. Leukopenia and Thrombocytopenia
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Leukopenia – decreased leukocyte count; increases infection risk.
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Thrombocytopenia – decreased platelet count; increases risk of hemorrhage.
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Both caused by direct tumor invasion to the bone marrow.

Also triggered by chemotherapy, which is toxic to bone marrow, or radiation, which kills
circulating leukocytes.
F. Infection

Most significant cause of complications and death in persons with malignant disease.

Infection may be caused by leukopenia, immunosuppression, or debility from advanced disease.

Risk increases when the absolute neutrophil and lymphocyte counts fall.
G. Paraneoplastic syndromes

Symptom complexes that are not caused by the direct local effects of the tumor mass.
o
Most commonly caused by biologic substances released by the tumor, like hormones, or by
an immune response triggered by the tumor.

Paraneoplastic syndromes are rare but significant because they:
o
May be the earliest symptom of an unknown cancer.
o
May represent serious and life-threatening problems.
o
May mimic progression and therefore interfere with appropriate treatment.
II. Cancer Treatment

Cancer is treated with surgery, radiotherapy, chemotherapy, immunotherapy, and combinations of
these modalities.
A. Chemotherapy

Use of nonselective cytotoxic drugs that target vital cellular machinery or metabolic pathways
critical to both malignant and normal cell growth and replication.

Targets any rapidly dividing cell.
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
Goal – eliminate enough tumor cells so the body’s defenses can eradicate any remaining cells.
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Single-agent chemotherapy – significant early response rates, but duration is short lived because
malignant cells develop resistance.

Combination chemotherapy – synergistic use of several agents, each of which individually has an
effect against a certain cancer process.

o
Primary rationale to this approach is to avoid single-agent drug resistance.
o
Allows use of lower doses of each drug so the harmful effects to normal cells may be reduced.
Principle of dose intensity – direct correlation between dose of a chemotherapeutic agent and killing
of tumor cells (killing increases with increased dose). However, toxicity also increases.

Therapeutic index – the relative effective dose needed to kill cancer cells as compared to the dose that
would be harmful to normal cells; generally quite low; limiting factor in use of chemotherapy.
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Adjuvant chemotherapy – used after local treatment or removal of the primary tumor. Useful in
individuals who are at high risk for metastasis. Prevents the growth of micrometastatic
deposits that are not clinically detectable at diagnosis.
B. Radiation Therapy
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Goals:
o
Eradicate cancer without excessive toxicity
o
Avoid damage to normal structures

Ionizing radiation damages the cancer cell’s DNA.

May be used in conjunction with chemotherapy.
C. Surgery
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Surgical therapy is used for nonmetastatic disease, for which cure is possible by removing the
tumor, and as a palliative measure to alleviate symptoms caused by malignant tumor masses.
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Biopsy and lymph node sampling – often begins the treatment process, aids in staging the disease.
o
Sentinel nodes - lymph nodes that are the first to receive drainage from any given location;
sampling these allows less invasive tumor staging.

Debulking surgery – majority of the tumor is removed, thereby allowing for increased success of
adjuvant chemotherapy or irradiation. Used when tumor cannot be completely removed.

Palliative surgery – used to relieve current symptoms or prevent or delay anticipated symptoms
as the tumor grows.
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Benign or premalignant growths – are surgically removed to prevent damage due to growth of
tumor or progression to malignancy.
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ACTIVITY 1: Match each treatment with its description or characteristic.
1. Radiation
a. kills cancer cells left after surgery
2. Palliative surgery
b. avoids development of drug resistance
3. Combination chemotherapy
c. used to relieve symptoms of a tumor.
4. Adjuvant chemotherapy
d. facilitates adjuvant chemotherapy or radiation
5. Debulking surgery
e. direct application of ionizing energy
PART 2: CHAPTER 11
I. Gene-Environment Interaction and Risk Factors

Cancer occurs in genes, but two-thirds of all cancers are caused by environmental/lifestyle factors
interacting with genes.
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Carcinogens - environmental agents that can cause cancer.
A. Epigenetics and Genetics
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Epigenetics—change in genetic expression (phenotype) without DNA mutation (e.g., DNA
methylation).
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Usually involves factors that silence genes that should be active or activate genes that should be
silent.

Genetics, epigenetics, and environmental factors interact to cause cancer.

Epigenetic processes can be influenced by environmental/lifestyle including in utero.
B. Environmental Risk Factors
1. Tobacco Use
o
Cigarette smoke - most important cause of cancer.
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Responsible for 30% of all cancer deaths in developed countries.
o
Associated primarily with squamous and small cell carcinomas of the lung and pulmonary
adenocarcinomas.
o
Also linked to cancers of the lower urinary tract, upper respiratory and upper digestive tract,
liver, kidney, pancreas, cervix, and myeloid leukemia.
o
Environmental tobacco smoke (ETS) or secondhand smoke has also been linked to lung cancer.
2. Diet
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May account for 30% of the overall risk factors for cancer.
o
Xenobiotics - toxic, mutagenic, and carcinogenic chemicals in food.
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Examples:
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Compounds produced in the cooking of fat, meat, or proteins (nitrosamines).
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Alkaloids or mold by-products (including aflatoxin).
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May influence epigenetics.
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Research ongoing regarding vitamin influence.
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o
Foods that decrease cancer risk:
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Fruits/vegetables; fiber; foods containing vitamins A, B6, C, D, E, and folate; whole
grains; lycopene; legumes/nuts.
o
Foods that increase cancer risk:

Fat (especially large amounts of omega-6 fatty acids); high-glycemic-index
carbohydrates; refined grain products; foods with high amounts of preservatives; alcohol;
grilled, blackened foods; fried foods; high levels of calcium (≥2000 mg).
3. Obesity
o
Correlates with high body mass index (BMI).
o
High BMI is associated with higher rates of death from esophageal, stomach, colorectal, liver,
breast, gallbladder, pancreatic, prostate, kidney, and cervical cancers; non-Hodgkin
lymphoma; multiple myeloma; and leukemia.
o
Proposed mechanisms:

Adipose tissue is an active endocrine and metabolic tissue.

In response to endocrine and metabolic signaling, adipose tissue releases free fatty acids.
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Increased release of free fatty acids, resistin, TNF-α, and reduced release of adiponectin
give rise to insulin resistance and causes chronic hyperinsulinemia.

High insulin levels promote the activity of insulin-like growth factor–1 (IGF-1), which
regulates cell proliferation and inhibits apoptosis.
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Insulin promotes the synthesis and biologic availability of female and male sex hormones.

Adipose tissue cells produce steroid-hormone-metabolizing enzymes and are an
important source of estrogens in postmenopausal women.
4. Alcohol consumption
o
Chronic alcoholism is a strong risk factor for oral cavity, pharynx, hypopharynx, larynx,
esophagus, and liver cancers.
o
It is less strongly related to breast cancer and colorectal cancer; however, breast
carcinogenesis can be enhanced with relatively low daily amounts.
o
Cigarette/alcohol combination increases a person’s risk for smoking-related cancers.
5. Ionizing radiation
o
Health risks from ionizing radiation involve cancer, birth defects and eye maladies.
o
The most common cancers from ionizing radiation are acute leukemias (adults and children);
thyroid and breast carcinomas.
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Due to emissions from x-rays, radioisotopes, and other radioactive sources.
o
Exposure causes cell death, gene mutations, and chromosome aberrations.
o
Mutations in germ cells are heritable.
o
Increased use of diagnostic testing of concern.

CT scans provide 50 times more radiation to stomach than an x-ray.
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o
Bystander effects - chromosome aberrations and mutations may occur not only in the
descendants of irradiated cells but in other cells not directly irradiated.
o
Low levels of radiation can induce bystander effects and genomic instability. Both findings
appear to be associated with oxidative stress and cell-to-cell intercellular communication.
6. Ultraviolet radiation
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Causes basal cell carcinoma, squamous cell carcinoma, and melanoma.
o
Principal source is sunlight; also results from overuse of tanning beds.
o
Number 1 solar risk factor is sporadic exposure, resulting in burns.
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Promotes skin inflammation and release of free radicals and TNF-alpha.
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Skin carcinogenesis from UV light involves reactive oxygen species (ROS) (oxidative stress).
o
UV radiation is now known to cause specific gene mutations.
7. Sexual and reproductive behavior
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Sexually transmitted infection with high-risk types of HPV is required for the development of
virtually all cervical cancers (99.7%).
o
Vaccines against the high-risk types of HPV prevent infection and subsequent cancer.
8. Physical activity
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Reduces the risk of breast and colon cancers and may reduce the risk of other cancers.
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Decreases insulin and insulin-like growth factors
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Decreases obesity
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Decreases inflammatory mediators and free radicals
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Increases gut motility
9. Chemicals and occupational hazards
o
A substantial percentage of cancers of the upper respiratory passages, lung, bladder, and
peritoneum are attributed to occupational factors.
o
Occupational carcinogenic agents include:

Dyes, rubber, paint, explosives, rubber cement, heavy metals, air pollution.

Asbestos – increases risk of mesothelioma and lung cancer.
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Arsenic – found in drinking water in some areas. Increases risk of skin, lung, and bladder
cancers.

o
Radon – natural radioactive gas; primarily increases risk of bronchogenic lung cancer.
Air pollution is a concern in regard to cancer because of inhalation of emissions, including
arsenicals, benzene, chloroform, vinyl chloride, and acrylonitrile.
o
Indoor pollution is considered worse than outdoor pollution because of cigarette smoke,
cooking fumes and radon gas.
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ACTIVITY 2: Match each risk factor on the right with its characteristic.
1. Includes air pollution exposure.
a. Tobacco use
2. Causes alteration of hormones like insulin.
b. Ionizing radiation
3. Harms cells directly and thru bystander effects.
c. UV radiation
4. Factor responsible for most cancer deaths.
d. Diet
5. Risk is due to transmission of viruses.
e. Obesity
6. Risk is associated with xenobiotic intake.
f. Alcohol
7. Causes formation of reactive oxygen species.
g. Sexual behavior
8. Associated with throat and liver cancers.
h. Physical activity
9. An increase in this lessens cancer risk.
i. Occupational hazards
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ANSWER KEY TO ACTIVITIES
ACTIVITY 1: Match each treatment with its description or characteristic.
E
1. Radiation
a. kills cancer cells left after surgery
C
2. Palliative surgery
b. avoids development of drug resistance
B
3. Combination chemotherapy
c. used to relieve symptoms of a tumor.
A
4. Adjuvant chemotherapy
d. facilitates adjuvant chemotherapy or radiation
D
5. Debulking surgery
e. direct application of ionizing energy
ACTIVITY 2: Match each risk factor on the right with its characteristic.
I
1. Includes air pollution exposure.
a. Tobacco use
E
2. Causes alteration of hormones like insulin.
b. Ionizing radiation
B
3. Harms cells directly and thru bystander effects.
c. UV radiation
A
4. Factor responsible for most cancer deaths.
d. Diet
G
5. Risk is due to transmission of viruses.
e. Obesity
D
6. Risk is associated with xenobiotic intake.
f. Alcohol
C
7. Causes formation of reactive oxygen species.
g. Sexual behavior
F
8. Associated with throat and liver cancers.
h. Physical activity
H
9. An increase in this lessens cancer risk.
i. Occupational hazards