BMD 420: Chapter 20 - Neoplasms and Cancer

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Differentiation
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Terms in this set (57)
Differentiation
- Each cell types differentiates and carries out particular functions.
- The structure reflects the function of the tissue.
Mitosis
- Part of the cell cycle
- Requires genetic control—DNA and RNA
-Regulator genes
-- Growth factors - signal proliferation - cytokines
-- Inhibitors - prevent excessive growth
Mutation
If DNA in parent cell is altered and passed on, offspring cells will carry the mutation
Apoptosis
- Programmed cell death
- Programmed number of reproductive cycles available for a specific cell type
- Effects of wear and tear causing cell damage
- Controlled by genetic elements
Neoplasms
Tumor with cellular growth that no longer responds to normal genetic controls
- Cell continues to reproduce, without need for them to reproduce
- Excessive growth deprives other cells of nutrition
- Neoplasms may consist of atypical or immature cells - unable to function as normal tissue cells
- Characteristics of each tumor depend on:
-- Type of cell from which the tumor arises
-- Unique structure and growth pattern
- Expanding mass creates pressure on surrounding structures
Nomenclature of Tumors
1) Root word indicates cell of origin (ex: chondro - cartilage)
2) Benign tumors have tissue name plus the suffix -oma (e.g., adenoma)
3) Malignant tumors (cancers) of epithelium - suffix -carcinoma (e.g., adenocarcinoma)
- Metastasize through lymph
4) Tumors of connective tissue are usually termed sarcomas and are often malignant.
- Metastasize via blood
5) Several malignant tumors have unique names:
- Hodgkin's disease
- Wilms' tumor
- Leukemia
Benign Tumor Characteristics
- Usually differentiated cells that reproduce at a higher rate than normal
- Encapsulated
- Expands but does not spread
- Freely movable on palpation
- Tissue damage
-- This is a result of compression of adjacent structures.
- Not life threatening unless in area like brain where pressure effects can become critical
Malignant Tumor Characteristics
- Undifferentiated, nonfunctional cells - not organized
- Rapid reproduction—abnormal mitotic figures
- Lost cellular connections with each other
- Reproduction not inhibited by presence of similar cells
- Infiltrate or spread into surrounding tissue
- Spread to distant sites
Malignant Tumors: Cancer
- Composed of primitive of dysplastic cells
- Lack control of mitosis and do not undergo apoptosis
- No normal organization or differentiation
- No contact inhibition
- Abnormal cell membranes
- Altered surface antigens
- Do not adhere to each other
-- Often break loose from mass
-- Invade other tissues and may spread to distant sites
- Mass compresses blood vessels.
-- Leads to necrosis and inflammation around tumor
-Tumor cells may secrete enzymes or hormones.
-- Ex: collagenase
-- Break down of proteins and cells
-- Systemic effects, such as altered calcium levels
- Inflammation and loss of normal cells
-- As mass enlarges, inner cells deprived of blood and nutrients and die
-- Lead to progressive reduction in organ integrity and function
- Angiogenesis
--Some tumor cells secrete growth factors.
--- Stimulate the development of new capillaries in the tumor
- Tumor cells can trap nutrients and deprive normal cells and prevent tissue regeneration
- Some neoplasms develop rapidly, other remain in situ for a long time (preinvasive stage)
Grading of Tumors
- Based on degree of differentiation of malignant cells
- Grade I - well differentiated cells similar to original cells
- Grade IV - undifferentiated with cells varying in size and shape (anaplasia)
Local Effects of Tumors1) Pain - May be absent until very late stages - Occurs when tumor is well advanced - Severity depends on the type of tumor - Can be caused by direct pressure of mass on sensor nerves - Dull, aching - stretching of a visceral capsule - Inflammation contributes to pain - Secondary causes: infection, ischemia, bleeding 2) Obstruction - Occurs when tumor compresses a duct or passageway - Blood supply or lymphatic flow may be restricted - lead to ulceration and edema - Digestive tract - Airflow in bronchi or nerve conductions may be blocked 3) Tissue necrosis and ulceration - May lead to bleeding or infection around the tumorSystemic Effects of Malignant Tumors1) Weight loss and cachexia (severe tissue wasting) 2) Anemia 3) Severe fatigue 4) Effusions 5) Infections 6) Bleeding 7) Paraneoplastic SyndromeWeight Loss and Cachexia - Systemic Effect of Malignant Tumors- Caused by Anorexia, fatigue, pain, stress - Increased demands on the body from tumor cells - Altered carb and protein metabolism - Cachectic factors produced by macrophages in response to tumorAnemia - Systemic Effect of Malignant Tumors- Caused by Anorexia and decreased food intake, chronic bleeding with iron loss, bone marrow depression - Caused by blood loss at tumor site - Nutritional deficits may reduce hemoglobin synthesis. - Decreases oxygen available to cells - fatigue and poor tissue regenerationSevere Fatigue - Systemic Effect of Malignant Tumors- Caused by inflammatory changes, cachexia, anemia - Stress of treatment schedule - Psychological factorsEffusions - Systemic Effect of Malignant TumorsInflammation causes fluid buildup in body cavities.Infections - Systemic Effect of Malignant Tumors- Occur frequently as resistance declines - Tissue breakdown develops, immune system less effectiveBleeding - Systemic Effect of Malignant Tumors- Tumor cells may erode the blood vessels or cause tissue ulceration - Bone marrow depression or hypoproteinemia may contribute to poor clotting - Chronic bleeding common in digestive tract - Chronic blood loss leads to iron deficiency anemiaParaneoplastic Syndrome - Systemic Effect of Malignant Tumors- Associated with certain tumor types - bronchogenic carcinoma *Tumor cells release substances that affect neurological function and may have hormonal effects.* - Ex: can secrete ACTH, leading to manifestations of Cushing syndromeDiagnostic Tests1) *Routine screening* - essential for early detection; following treatment to detect any further tumors 2) *Self-examination* - early detection if done consistently - Breast, testicular, and skin examinations 3) *Blood tests* - Measure blood cell levels during treatment - May detect tumor markers (e.g., PSA test) - Hg and erythrocyte low - cancer 4) *Tumor Markers* - Enzymes, antigens, hormones produced by some neoplastic cells - Can be used to screen high risk individuals, confirm diagnosis, monitor clinical course of malignancy - Chromosome markers useful as well - Specific genes linked to certain cancers 5) *Radiographic, ultrasound, MRI, CT* - Examine tissue changes or organs - Radioisotopes may be used to trace metabolic pathways 6) *Cytological tests require biopsy or cell sample * - Histological and cytological examinations to determine degree of differentiation and tumor type - Evaluate biopsies of masses and check sloughed cells in specific tissues - May be tested for growth promoter sensitivities, (e.g., estrogen-dependent tumors) - Most dependable confirmation of malignancy 7) *Genomic tumor assessment * - Identifies genetic mutations that are independent of heredity but only occur with the disease itselfSpread of Malignant Tumors- Produce secondary tumors with cells identical to the primary tumor - 3 mechanisms for the spread: 1. Invasion 2. Metastasis 3. SeedingInvasion*Local spread* *Tumor cells grow into adjacent tissues and destroy normal cells * - Tumor cells loosely attached to other cells and secrete lytic enzymes that break down tissue - Example: Uterine carcinoma invades the vagina.Metastasis*Spread to distant sites via blood or lymph or other body fluids* - Lodge in hospitable env to reproduce and create one or more secondary tumors - Only a few survive, but only takes a few to start a new tumor - First metastasis appears in regional lymph nodes -- Removed in surgery to eradicate micrometastases that may be missed - Lung and liver are common secondary sites - Example: Carcinoma of the colon spreads to the liver.Seeding*Spread of cancer cells in body fluids or along membranes, usually in body cavities * - Travel easily with movement of fluid and tissue - Ex: ovarian cancer - peritoneal membrane encourages dispersion of tumor cells - Malignant cells may be dislodged from tumor if excessive handling occurs during diagnostic procedures - further spreadStaging Cancer- Essential to standardize comparative studies of treatments and outcomes - Used to estimate prognosis - Most common system used is the TMN system: 1. Size of primary tumor (T) 2. Involvement of regional lymph nodes (N) 3. Spread (metastasis) of tumor (M) - Other systems may be used for specific cancers, but all are based on same principles. - Stage I - small and well localized, easy to treat, good prognosis - Stage IV - well advanced, difficult to treat at multiple sites, poorer prognosisCarcinogenesis*Process whereby normal cells are transformed into cancer cells* - Process varies greatly with respect to time - sequence of changes over long period - Cancer is thought to be a multifactorial disease because of: -- Environmental effects -- Change in gene expression (heredity) - Infection in some cases (e.g., cervical and hepatic cancers) - oncogenic viruses - Some cancers have well-established risk factorsStages in Carcinogenesis1) *Initiating factors* - *Procarcinogens* cause the first irreversible change in cellular DNA. - Genetic changes or exposure to env risk cause this first mutation - Do not create an active neoplasm 2) *Exposure to promoters* - Includes hormones and environmental chemicals - Cause further changes in DNA - Less differentiation and increased rate of mitosis and/or lack of apoptosis - Dysplasia or anaplasia may be evident. - Process leads to tumor development 3) *Continued exposure and changes in DNA * - Result in malignant tumor - Capable of growth and invasion of local tissue 4) *Changes in regulation of growth* - Cells capable of detaching form tumor and spreading to distant sites - metastasisRisk Factors of Cancer1) Genetic factors - Oncogenes that regulate all growth 2) Viruses - Oncoviruses alter host cell's DNA. 3) Radiation - Ultraviolet rays - X-rays and gamma rays - Radioactive isotopes - Risk is increased with higher cumulative dosage. - Cause cumulative chromosomal damage 4) Chemicals (check health and safety information) - Organic solvents - Asbestos - Heavy metals - Formaldehyde - Chemotherapy agents 5) Biological factors - Chronic irritation and inflammation with increased mitosis - Age - Diet - HormonesRisk Reduction of Cancer1) Limit UV exposure from sun or tanning booths. 2) Regular medical and dental examinations 3) Self-examination 4) Diet - Increased fiber content - Reduced fats - Five to ten servings of fresh fruits and vegetable daily. These foods contain antioxidants, which reduce changes in DNA - protect against free radicalsHost Defenses of Cancer- Cancer Suppressor Genes - inhibit neoplastic growth - Cell mediated and humoral immunity -- TC, NK cells, macrophagesImmunity and Cancer Risk- Cell-mediated immunity recognizes some tumor cells and destroys them. - Immunization for cervical cancer and hepatitis is recommended to reduce cancer risk from infection.Treatment of cancer1) Depends on specific cancer - Surgery, chemotherapy, immunotherapy, radiation - Combination of the above 2) The effectiveness of treatment will depend on the stage of the cancer, type and health of the client. 3) Not all cancers sensitive to radiation or chemo 4) Chemo - if cancer cells dispersed in blood 5) Surgery - solid tumor - Can be followed by chemo 6) Many treatments will result in long term remission and some in cure. 7) Curative - if tumor is small and localized 8) Palliative treatment - to reduce pain in late stage cancers is commonly done. - Reduce manifestations and complication 9) Adjuvant therapy - Prophylactic treatment used in cancers that are known to metastasize early and produce micrometastases 10) Chemo and radiation in repeated doses at intervals - maximize tumor cell death and minimize effects on local tissues 11) Any infections, dental problems, other complications treated before therapy - Major procedures while receiving therapy - tendency toward hemorrhage and severe infection 12) Other treatment - nutritional therapy, physiotherapy, OT, assistance with other specific problems (speech therapy)* Removal of tumor and surrounding tissue* - May remove nearby lymph nodes if req 1) May be done with laparoscope and several small incisions - Minimizes tissue damage - Improves recovery time 2) Removal of adequate surrounding tissue may result in changes in function. 3) Complete removal ay not be feasible - reduce size to alleviate symptoms 4) *Radiofrequency ablation (RFA)* - Use CT scans and ultrasound to guide needs and electrodes to tumor - heat supplied in form of radio waves - destroy malignant cells and tissue immediately surrounding tumor - Alternative surgery for small single tumors in solid or fluid-filled organs, but not the lungs - Less invasive, easier for patient to tolerate, does not require loss of an entire lobe of organSurgeryRadiation Therapy- May be used alone or combined with other therapies - Causes mutations or alterations in target DNA - prevent mitosis or cause immediate cell death -Damages blood vessels - cut off blood supply to tumor cells and starve them - Most effective in rapidly dividing cells - Some types of cancers are radioresistant. - May be used as an adjuvant therapy prior to surgery to shrink tumor - Ionizing radiation - electromagnetic waves (x rays or gamma rays) or high energy penetrating particles (electrons or protons)Methods of Administration of Radiation Therapy1) External sources—cobalt machine - Radiation for a short time to specific site in the body - Requires multiple treatments - daily for 6 weeks - No radiation remains after treatment 2) Internal Insertion of radioactive material at the tumor site - Treat specific cancers (e.g., cervical or oral tumors). - Seal radioisotope in a seed or needle and implanting device at site 3) Brachytherapy - Treat breast cancer in early stages - Radioactive material implanted in surrounding tissue after removal of tumor - May replace daily administration req now for this cancer 4) Instill radioisotope in a solution into a body cavity. - Control excessive inflammatory exudate or blood from tumor - Monitor to ensure that there is no leakage - Radioisotopes may be given by injection for specific tumorsPrecautions with Radiation- Req when clients have internal sources of radiation -- Limit radiation exposure to other persons - Half life is short; cumulative time of exposure short as possible - Shielding materials block penetration by radiation1) *Bone marrow depression* - Decreased leukocytes—increase risk of infection - Decreased erythrocytes—fatigue, tissue breakdown - Decreased platelets—excessive bleeding - If decreased to critical level, treatment postponed or blood transfusions necessary - Pneumonia and septicemia are common life threatening complications 2) *Epithelial cell damage* - Damage to blood vessels and skin, hair loss - Mucosa of GI damaged - nausea, vomiting, diarrhea, risk of malnutrition and dehydration -- Bleeding - melena or hematemesis - Oral mucosa may be ulcerated - Xerostomia (dry mouth) 3) *Infertility * - Caused by abdominal radiation - Damage to ovaries or testes - Sperm banking or egg retrieval and storage before treatment 4) *Nonspecific fatigue and lethargy* - Can lead to mental depression 5) *Long term effects * - Inflammation, necrosis, scar tissue along pathway of radiation and at tumor site - Scar tissue may cause adhesions and obstructionAdverse Effects of RadiationChemotherapy- Antineoplastic drugs - Can be used alone or in combination with surgery or radiation - Drugs most effective on rapidly reproducing cells and on small tumor masses - Usually combination of two to four drugs - Given at periodic intervals - Classifications include: 1. Antimitotics 2. Antimetabolites 3. Alkylating agents 4. Antibiotics - Drugs interfere with protein synthesis and/or DNA replication - destroy cells - Choice of drugs and timing sequence depend on cell cycle of the particular tumor cell - When each drug acts on different point of cell cycle, max number of malignant cells destroyed - High doses to maximize damage to tumor with rest period for normal tissue recoveryAdriamycinantitumor antibiotic that binds DNA and inhibits synthesis of nucleic acids - act on S phaseBleomycinantitumor antibiotic that inhibits DNA synthesisVinlastinecell cycle specific antimitotic drug - acts on M stage; blocks mitosisDacarbazinealkylating agent - nonspecific drug act on several points in cycleABVD Treatment- treat Hodgkin lymphoma - IV on day 1 and 15; repeated every 4 weeksAdverse Effects of Chemo- Normal cells are also damaged 1) Bone marrow depression - Limiting factor with chemotherapy - Blood test taken before each treatment - Nadir is point of lowest cell count—different points in cycle - Count is too low - treatment may be postponed, antibiotics of hospitalization required 2) Vomitting - Direct chemical stimulation by drug of emetic or vomiting center of brain 3) Nausea - May occur prior to, during, or shortly after treatment - Antiemetic drugs helpful for decreasing nausea 4) Epithelial cell damage - Occurs easily bc ongoing mitosis - Hair loss (alopecia) - Breakdown of skin and mucosa 5) Damage to specific areas - With some antineoplastic drugs - Fibrosis in the lungs - Damage to myocardial cells - Kidney damageHormone Treatment- Glucocorticoid (prednisone) - decrease mitosis and inc erythrocyte counts - Sex hormones - tumor growth dependent on such hormones (estrogens may slow growth of prostate cancer)Blocking Agents- Act to block receptors for growth promoters on cancer cells - Reduce tumors and prevent recurrences - Ex: Tamoxifen - estrogen blocking agentBiological Response Modifiers (BRMs)- Augment the natural immune response - Improve surveillance and removal of abnormal cells - Natural product of human cells, interferon, and bacillus Calmette Guerin (BCG) vaccine -- BCG vaccine injected near tumor or instilled in cavity where cancer is present -- Stimulates movement of macrophages and T cellsAngiogeneisis Inhibitors- Inhibit the stimulus for growth of blood vessels - Reduce blood flow and starve the tumor - Issue bc reducing blood flow reduces delivery of chemo to the tumorAnalgesics- Prescribed to alleviate pain - May be used in high dosages - Start with low dose of mild drug and slowly increase - Side effects of narcotics: nausea, constipation, drowsiness, resp depressionGene Therapy- Replace mutated genes with healthy copy - Inactivate mutated gene - Introduce new gene - ExperimentalNutrition - Therapy for Cancer1) Patients with advanced cancer are often malnourished. 2) Contributing factors - Change in taste sensation - Anorexia - Vomiting and/or diarrhea from treatments - Sore mouth or loss of teeth - Pain and fatigue - Malabsorption caused by inflammation in the digestive tract - Altered metabolism - Nutrient trapping by tumor 3) Ice and mouth rinses to reduce discomfort from ulcers and inflammation 4) Frequent small amounts of non irritating and favorite foods 5) Total parenteral nutrition - administration of nutrient mix into peripheral veinComplementary Therapies- Massage - Meditation - Counseling - Exercise - Therapeutic touch - Research-based evidence has not been published for: -- Raw food macrobiotic diet -- Use of insulin and glucose with chemotherapy - Health care workers need to be aware of these different types of therapies to advise patients.Prognosis*Cancer-free state generally defined as 5-year survival without recurrence* - Some cancers such as childhood leukemias can be considered cured after a 10-year, cancer-free period. - Remission—no clinical signs of cancer -- Client may experience several remissions -- Disease may become terminal - Life expectancy and death rates for specific cancers vary.Skin cancer- Visible, easily diagnosed and treated (by surgery) - Develops slowly - Excellent prognosis, with exception of malignant melanoma - Highest rate of recurrence - Arise on head and neck or back - exposed to sun and irritation - Occur more freq in individuals with fair skin over 40 and live in southern climates - Basal cell carcinoma - most common - Pearly paule - develops central ulceration (rodent ulcer) - Lack of pain or pruritus (itching) and persistenceOvarian cancer- Poor prognosis because of hidden nature of cancer - High mortality rates - Hidden in peritoneal cavity - silent tumor - Hormonal and genetic factors - Presenting signs - appear after tumor is well advanced and causing pressure on adjacent structures or when inflammatory exudate forms in abdominal cavity - First indications: altered bowel or bladder function or inc abdominal girth - Tumor markers for early diagnosis (false negs do occur) -- CA125 elevated (in other conditions too) - Tumor spreads easily by lymph vessels and seeding -- Travel to liver and other organs - Invades uterus and pelvis - Treatment: surgery, radiation, chemoBrain Tumors- Both benign or malignant tumors are life-threatening because of compression of brain tissue. - Can cause death if located in brain stem or cerebellum - interefere with vital functions -Vary histologically - originating form neurons, neuroglial cells, blood vessels, or CT - Early indications - seizures, signs of pressure (headache, drowsiness, vomiting, visual problems, - Primary tumor usually fatal; thus, no metastasis - Other tumors can metastasize to brainCancer Incidence1) Most common in men - Prostate cancer - Lung cancer - Colorectal cancer 2) Most common in women - Breast cancer - Lung cancer - Colorectal cancer