Pathophysiology Ch. 4
Side effects of Chemotherapy
-Anemia -Infection due to reduced ability of bone marrow to produce white blood cells (infections) -Loss of appetite (anorexia) -Mouth, gum, and throat sores (entire GI tract) -Nausea and vomiting -Diarrhea -Hair loss
Survival Rates in Cancer
-Cancer second to heart disease as most common cause of death in the US -1 in every 4 people will eventually develop cancer -Prostate cancer: most common cancer affecting males -Breast cancer: most common cancer affecting females -Early diagnosis and treatment may enhance survival -Chances for survival significantly reduced once tumor has metastasized to the regional lymph nodes or to distant sites
Noninfiltrating carcinoma
-Carcinomas arising from the surface epithelium remain localized within the epithelium for many years -At this stage it is called carcinoma in situ -Can occur in many locations of the body: Cervix Breast Urinary tract Colon Skin -Can be completely cured -Surgical excision -Treatment that eradicates abnormal epithelium
Benign Tumors
-Growth is relatively slow and orderly -Grows by expansion -Compresses and pushes aside surrounding tissue, but does not invade it -Remains localized -Can usually be completely removed surgically -Often are encapsulated -Cells are well-differentiated -Cells appear mature and closely resemble normal cells from which the tumor was derived
Malignant Tumors
-More rapid, disorderly growth -Infiltrates (invades) surrounding tissues -Tumor spreads from primary site to distant sites of the body by a process called metastasis -When the tumor invades blood or lymphatic vessels pieces can break off and travel to distant sites -Cells are less well-differentiated -Cells appear poorly differentiated and immature
Combination Therapy
-Most widely used -Hope is that tumor destruction can be maximized by attacking tumor on multiple fronts -Side effects are kept to a minimum because doses of each agent can be reduced while maintaining or improving effect on tumor *What we usually use...surgery, then radiation, maybe hormone therapy (lower side effects due to smaller doses, but the combination works together to help fight it
Proto-oncogenes
-Normal "growth genes" in the human chromosomes that promote some aspects of cell growth, differentiation, or mitotic activity -Becomes an oncogene if mutation occurs or genes are translocated to another chromosome
Tumor Suppressor Genes
-Normally suppress cell proliferation -Loss of function by mutation may lead to unrestrained cell growth -Exist in pairs on corresponding chromosomes -Both suppressor genes must cease to function before cell malfunctions (both copies have to be bad in order to cause negative effects- recessive genes) -Genes that slow cell division
DNA Repair Genes
-Regulate processes that monitor and repair any errors in DNA duplication during cell division; DNA damage from radiation, chemicals, or other environmental agents -Failure in function of DNA repair genes increase the likelihood of DNA mutations within the cell -More likely to develop oncogenes or experience failures of tumor suppressor genes
Neoplasia
-Second leading cause of death in North America -30% of population will suffer some form of the disease -25% of adults die of cancer -Kills more people under the age of 15 than any other disease
Hormone Therapy
-Some tumors require hormones for growth (hormone responsive) -Undergo temporary regression if deprived of required hormone -Can be controlled by blocking hormones Not curative but helps other treatments (breast, uterine, testicular) -not enough individually
Malignant tumors
-Start from a single cell that has sustained damage to its genome, causing it to proliferate abnormally -Clone of identical cells is formed; if unchecked, eventually develops into a distinct tumor -Exhibit behavior different from that of normal cells -Do not respond to normal growth regulatory signals -Proliferate unnecessarily -May secrete growth factors to stimulate their own growth, allowing tumors to flourish at the expense of surrounding normal cells -Secrete enzymes that break down normal cell and tissue barriers, allowing them to -Infiltrate into adjacent tissues -Invade lymphatic channels and blood vessels -Spread throughout the body -Tumor cells do not normally "wear out" as normal cells, but become "immortal" and can proliferate indefinitely
Gene and Chromosomal abnormalities
-Three large groups of genes play an important role in regulating cell functions -Mutations in these genes are associated with tumor formation 1) Proto-oncogenes 2) Tumor-suppressor genes 3) DNA repair genes (subset of tumor suppressor genes)
Chemotherapy
-Toxic chemical substance are used to destroy the tumor -Work best on cells that divide frequently -Drawbacks -Not able to selectively damage only tumor cells -Chemotherapeutic agents induce a tolerance *targets METABOLIC functions of cancerous cells (and other rapidly dividing cells in the mouth, hair, bone marrow, digestive tract)
Immunotherapy
-Treatment of tumors by stimulating body's immune system -Nonspecific -Initially attempted by stimulating generalized immune response -Specific -Newer attempts try to stimulate specific cells of the immune system or act against tumor cells
Tumor Blood supply and necrosis
-Tumors derive blood supply from tissues they invade -Malignant tumors frequently induce new blood vessels to proliferate in adjacent normal tissues to supply the demands of the growing tumor (angiogenesis factor) -Malignant tumor may outgrow its blood supply; that part of the tumor with the poorest blood supply undergoes necrosis (grow so quickly, they outgrow their blood supply) -At the center of deeply placed tumors -On the surface of tumors growing from an epithelial surface -Often, small blood vessels are exposed in the ulcerated base of a tumor may ooze blood continuously leading to anemia from chronic blood loss
High grade tumor
-fast-growing tumor -aggressive tendencies to invade and metastasis -has poorer prognosis
Precancerous conditions
-nonmalignant condition with a tendency to become malignant -precancerous conditions should always be treated appropriately to prevent malignant change
Low grade tumor
-slow-growing tumor -limited tendencies to invade and metastasis -has better prognosis -more normal looking tissue
Failure of Immunologic Defenses
Cancers usually arise from multiple genetic "insults" to the genome rather than single gene mutations -Characterized by activation of oncogenes and loss of function of tumor suppressor genes *it takes multiple "insults" of these genes to cause cancer -Mutant cell produces cell proteins not present in a normal cell; these proteins are recognized as abnormal by the immune system and are destroyed -surface markers on cells, as mutations pop up surface markers become more abnormal, if immune system catches it, cancer won't develop **MUST OVERWHELM THE IMMUNE SYSTEM -Immune system destroys abnormal cells
Laboratory Procedures
Cytologic diagnosis: -from smears of body fluids or secretions (tumors shed from abnormal cells from their surfaces) -Fine needle aspiration (biopsy)-- cells obtained by aspirating material from organs or tissue Frozen section: -means of rapid evaluation of abnormal tissue obtained at surgery -permits immediate decision about proper course of treatment
Tumor Grading
Following a biopsy, various histological characteristics of the tumor are assessed and the tumor is assigned a grade Based on: -degree of differentiation -frequency of mitosis means of judging degree of malignancy (usually done by pathologist)
Nonspecific Immunotherapy
Interferon: -Regulates cell growth and immune system functions -Antiviral activity Interleukin-2: -Stimulates production of natural killer cells and cytotoxic T cells
Tumor Staging
Means of classifying malignant tumors -used for selecting treatment -an indication of prognosis System of categorizing malignant tumors in terms of their potential for invasion and metastasis
Naming of Tumors
Named and classified according to their cells and tissues of origin -not completely uniform, but certain generalizations are possible
Benign Tumor naming
Named by adding suffix -oma to the name Adenoma- glandular epithelium Angioma- blood vessels Chondroma- cartilage
Radiation therapy
Seeks to deliver a destructive dose of ionizing radiation to the tumor -Rapidly dividing cells are most sensitive to radiation damage -May be used in conjunction with surgery -Useful for pain relief -Drawbacks -Heat can cause skin burns -Also effects skin, hair, GI mucosa, bone marrow Can't selectively pick which cells to destruct so it can cause effects to skin, hair, GI, bone marrow
TNM Staging system
T-extent of tumor N- extend of spread to lymph nodes M- presence of metastasis -higher numbers associated with larger tumors and more extensive spread -internationally recognized -one of the most commonly used staging systems Each cancer has its own classification system, so letters and numbers don't always mean the same things for every kind of cancer, once these letters are determined they are then "staged" I, II, III, IV
Oncogene
abnormally functioning gene that stimulates excessive cell growth, leading to unrestricted cell proliferation (even if we have one good copy and one bad copy, bad copy dominates)
Neoplasm
an overgrowth of cells that serves no useful purpose (tumor) -cells do not respond to control mechanisms that normally regulate cell growth and differentiation -unrestrained growth and spread -irreversible
Sarcoma
arising from any tissue other than epithelium or blood (derived from mesoderm) -Specific terminology makes reference to the particular tissue -Chondrosarcoma - cartilage -Liposarcoma - adipose -Less common, but spreads more rapidly -Anaplastic (lacks form) - Shows little differentiation -Very immature appearing cells
Polyps/papilloma
benign tumor on stalk arising from an epithelial surface
Viruses
cause some cancers in humans -Some strains of the papilloma virus predisposes to cervical carcinoma -Chronic viral hepatitis predisposes to liver cancer
Leukoplakia
from exposure to tobacco--> squamous cell cancers of the mouth
Cancer
general term referring to any type of malignant growth
Carcinoma
involves epithelial tissue (most common because it is most exposed) 85% of all tumors found in skin, LI, glands, stomach, prostate Subtypes: classified further by designating the type of epithelium from which it arose -Adenocarcinoma (internal organ or gland) -Squamous cell carcinoma (skin)
Leukemia
neoplasm of blood cells (spills over into bloodstream, doesn't form a solid tumor) -Usually do not form solid tumors -Instead, proliferates diffusely within bone marrow, overgrow and crowd out normal blood-forming cells -Neoplastic cells "spill over" into the bloodstream and large number of abnormal cells circulate in the peripheral blood
Prostate specific antigen
normally produced by prostate epithelial cells, may be elevated in prostate cancer (secretes higher levels of this antigen in blood)
Carcinoembrionic antigen
presents in amounts related to the size and distribution of tumor -produced by most malignant tumors of the GI tract, pancreas, breast
Diagnosis of Tumors
recognize early warning signs and symptoms 1) change in bowel/bladder habits 2) sore that doesn't heal 3) unusual bleeding or discharge 4) thickening or lump in breast or elsewhere 5) indigestion/difficulty swallowing 6) obvious change in wart/mole 7) nagging cough or hoarseness 8) unexplained weight loss
5 year survival rate
refers to the percentage of patients who are alive 5 years after the diagnosis -does not mean the cancer is cured (may have died from some other disease) -Tumor may have already spread by time of diagnosis and initial treatment, but metastatic deposits held in check by immune defense mechanisms -Recurrence: failure of body's defenses, reactivation of tumor; -some malignant tumors recur and prove fatal many years after initial treatment Breast cancer and malignant melanoma prone to late recurrences
Surgery
seeks to physically remove the tumor -can be curative if tumor has not metastasized Drawbacks: -edge of malignant tumor is not well define, must remove some adjacent tissue -if tumor has spread to lymph nodes, they must be removed -surgery may produce emboli that can lead to metastasis
Tumor associated antigen tests
some cancers secrete substances that can be detected in the blood by lab tests (large tumor= large levels in blood, small tumor= small levels in blood) -may be used for screening and to monitor response to treatment -CEA (carcinoembrionic antigen) -PSA (prostate specific antigen)
Specific Immunotherapy
targets patients own tumors for attack Tumor-infiltrating lymphocyte therapy: -Lymphocytes obtained from patient's own tumor are grown in laboratory with interleukin-2 -Cytotoxic cells and macrophages trying to fight the cancer -Infused back into patient to attack and destroy the tumor Tumor vaccines: -Prepared from patient's own tumor -Used to immunize the patient against the tumor to prevent recurrence or metastasis -Breast cancer vaccine in the works (immunize with your own tumor cells) Tumor antibody therapy: -Antibodies prepared against tumor antigens and coupled with antitumor drug or toxin -Infused back into patient to seek out and destroy tumor cells without damaging normal cells -Chemotherapy drug that affects only the cancer cells (not other cells)