Week 13 Lecture Notes - Cellular Regulation: Concept overview PDF

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Goes over the concept and gives a brief overview of exemplars, risk factors, nursing interventions and possible treatment...

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CELLULAR REGULATION: CONCEPT OVERVIEW Terminology • Cellular regulation refers to all functions carried out within a cell to maintain homeostasis. This encompasses: ◦ Responses to extracellular signals (e.g., hormones, cytokines, and neurotransmitters) ◦ The intracellular response to extracellular signals ◦ Replication and growth • Terminology: ◦ Proliferation ◦ Differentiation ◦ Neoplasia ‣ Neoplasm • Benign vs. Malignant ‣ Genetics • Protooncogenes and oncogenes ◦ Carcinogens • Tumor-suppressor genes Cancer Pathophysiology • Cellular replication ◦ Cell death ◦ Physiological need ◦ Contact inhibition ◦ "Go" and "Stop" signals • Cellular differentiation ◦ Change to cell's shape and size based on how it responds to extracellular signaling • Surveillance of cellular regulation and growth ◦ Mechanisms exist to detect and correct errors ‣ Apoptosis ◦ Cellular mutations that can lead to neoplasia occurs when mistakes (e.g. incorrect genetic expression) are undetected or uncorrected • Benign Neoplasms ◦ Are able to replicate but don't metastasize ◦ Can mechanically obstruct/press down on other body structures ‣ Pain, physiologic dysfunction, death • Malignant Neoplasms (cancer) ◦ Abnormal growth patterns, multiple abnormal functions, and the ability to metastasize

• Development of cancer ◦ Initiation ‣ Mutation of cell's genetic structure ◦ Promotion ‣ Characterized by reversible proliferation of altered cells

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‣ Latent period • Based on mitotic rate of tissues and environmental factors • 1-40 years to reach critical mass ◦ Pregression ‣ Increased growth rate of tumor ‣ Invasiveness ‣ Metastasis Metastasis process begins with rapid growth of primary tumor Tumor angiogenesis Tumor cells can detach and invade surrounding tissues ◦ Transport occurs via lymphatic and vascular systems ‣ Sentinel lymph node ‣ Skip metastasis Surviving tumor cells must create and environment conducive to growth and development

• Certain cancers seem to have an affinity for a particular tissue or organ as a site of metastasis ◦ Colon cancer often spreads to the liver • Other cancers (e.g., melanoma) are unpredictable in their pattern of metastasis • The most frequent sites of metastasis are lungs, liver, bone, brain, and adrenal glands • Immune System Response ◦ May reject or destroy cancer cells ‣ Response may be inadequate ◦ Some cancer cells have changes on their surface antigens ‣ Tumor-associated antigens (TAAs) ‣ Immunologic surveillance ‣ Immunologic escape ◦ Oncofetal antigens ◦ Tumor markers • Consequences of metastasis ◦ Robs normal body tissues of nutrients and oxygen ◦ Destroys invaded tissues ◦ Leads to fatigue, weight loss, pain, organ failure, and eventual death

Classification of Cancer • Classifications of cancer ◦ Tumors can be classified by ‣ Anatomic site ‣ Histology • Grading severity ‣ Extent of disease • Staging ◦ Classification systems provide a standardized way to ‣ Communicate with health care team ‣ Prepare and evaluate treatment plan ‣ Determine prognosis ‣ Compare groups statistically • Anatomic site classification ◦ Identified by tissue of origin

• Histologic classification ◦ Appearance of cells and degree of differentiation are evaluated to determine how closely cells resemble tissue of origin ◦ Poorly differentiated tumors have a poorer prognosis than those closer in appearance to normal cells ◦ Grade I: Cells differ slightly from normal cells (mild dysplasia) and are well differentiated (low grade) ◦ Grade II: Cells are more abnormal (moderate dysplasia) and moderately differentiated (Intermediate grade) ◦ Grade III: Cells are very abnormal (severe dysplasia) and poorly differentiated (high grade) ◦ Grade IV: Cells are immature and primitive (anaplasia) and undifferentiated; cells of origin is difficult to determine (high grade) ◦ Grade X: Grade cannot be assessed • Clinical staging classifications ◦ o: Cancer in situ ◦ I: Tumor limited to tissue of origin; localized tumor growth ◦ II: limited local spread ◦ III: Extensive local and regional spread ◦ IV: Metastasis • Staging ◦ Performed initially and at several evaluation points ‣ Clinical staging • US, CT, MRI, PET scan ‣ Surgical staging • Excision, biopsy

Cancer Diagnosis • Consequences of cancer ◦ Cancer diagnosis ‣ Psychosocial • Denial vs. proactiveness ‣ Strained family dynamics • Especially when child is diagnosed • Financial challenges ‣ Reduced self-esteem and self-image • Depression • Anxiety ◦ Remission and recurrence • Tips for nurses ◦ Actively listen to patient's concerns ◦ Manage your own discomfort ◦ Give clear explanations; repeat if necessary ◦ Give written information for reinforcement ◦ Refer to oncology team when possible • Steps to diagnosis ◦ Health history ‣ History of present illness ◦ Identification of risk factors ◦ Physical examination ◦ Specific diagnostic studies ‣ Cytology studies (biopsy) ‣ Chest x-ray ‣ CBC ‣ BMP/CMP • Liver function studies ‣ Endoscopic examinations ‣ Radiographic studies ‣ Radioisotope scans ‣ PET scan ‣ Tumor markers ‣ Genetic markers ‣ Molecular receptor status ‣ Bone marrow examination • What is a biopsy? ◦ A histologic examination by a pathologist of a piece of tissue ◦ Tissue may be obtained by ‣ Needle or aspiration • Fine-needle aspiration • Large core biopsy

‣ Incision procedure ‣ Excisional procedure • Diagnostic and therapeutic removal of an entire lesion ◦ Often radiograph guided ◦ Risks ◦ Pathologic evaluation of a tissue sample is only definitive means to diagnose cancer ‣ Benign or malignant ‣ Histology ‣ Histologic grade Patient Education • Risk factors ◦ Sex ‣ For men the three most common new cancer diagnoses are: • Prostate • Lung/bronchus • Colon/rectum ‣ For women, the three most common sites are: • Breast • Lung/bronchus • Colon/rectum ◦ Age ‣ Cancer is uncommon in children • Leukemia • Nervous tissue cancers ‣ 78% of new cancer diagnoses occur among those ages 55 years or older ‣ If previously cancer free by the age of 70, the probability of being diagnosed with cancer increases to 30% for men and 25% for women ◦ Smoking/tobacco ‣ Implicated in 30% of all cancer related deaths ◦ Infections ‣ Hepatitis B&C: liver cancer ‣ HPV: cervical and anal cancer ◦ Gene mutation ‣ BRCA-1 mutation • 70% risk of developing breast or ovarian cancer ◦ Radiation ‣ Ionized: x-ray, CT scans ‣ Ultraviolet: sun exposure ◦ Carcinogens ‣ Environmental exposure to asbestos, dioxins, arsenic ◦ Poor nutrition and sedentary lifestyle • Nurses play an important role in education efforts toward the prevention of cancer (primary prevention) • Prevention efforts ◦ Reduce/avoid exposure to carcinogens ◦ Eat a balanced diet that: ‣ Includes vegetables and fresh fruits, whole grains, and adequate amounts of fiber. ‣ Reduces dietary fat and preservatives, including smoked and salt-cured meats containing high nitrite concentrations ◦ Limit alcohol intake ◦ Participate in regular exercise (i.e., 30 minutes or more of moderate physical activity five times weekly). ◦ Maintain a healthy weight ◦ Obtain adequate, consistent periods of rest ◦ Eliminate, reduce, or change the perception of stressors ‣ Develop coping mechanisms ◦ Have regular physical examination that includes a health history ‣ Be familiar with your own family history and your risk factors for cancer ◦ Learn and follow the American Cancer Society's recommended cancer screening guidelines for breast, colon, cervical, and prostate cancer ◦ Learn and practice self-examination (e.g., breast or testicular self-examination)

• Detection of cancer ◦ Seven Warning Signs of Cancer ◦ Change in bowel or bladder habits ◦ A sore that does not heal ◦ Unusual bleeding or discharge from any body orifice ◦ Thickening or a lump in the breast or elsewhere ◦ Indigestion or difficulty in swallowing ◦ Obvious change in a wart or mole ◦ Nagging cough or hoarseness ◦ Note: these symptoms might indicate advanced disease Interprofessional Care • Interprofessional Care ◦ Goals ‣ Cure ‣ Control ‣ Palliation ◦ Treatment Modalities ‣ Targeted therapy ‣ Surgery ‣ Chemotherapy ‣ Immunotherapy ‣ Hormone therapy ‣ Radiation therapy • Curative Therapy ◦ Local and/or systemic therapy ◦ Timeframe to "cure" may differ according to the tumor and its characteristics • Control treatment ◦ Initial course and maintenance therapy • Palliation goal ◦ Relief or control of symptoms ◦ Maintain quality of life ◦ Palliative care and treatment are not mutually exclusive and can occur concurrently Personalized Medicine • Personalized/Precision medicine ◦ Genetic information is used to customize decisions about ‣ Prevention ‣ Diagnosis ‣ Treatment ◦ Targeted therapy ‣ Looks at a cancer's specific genes or proteins that contribute to cancer growth and survival ◦ Pharmacogenetics ◦ Drawbacks Surgery • Surgery ◦ Meets a variety of goals ◦ Prevention ‣ Eliminates/reduces risk of cancer in at-risk patients ‣ Prophylactic removal of non-vital organs and sites of regional spread may be removed ◦ Cure and control ‣ Remove only as much tissue as necessary and spare normal tissue ‣ Debulking • May be preceded and/or followed by chemotherapy or radiation therapy ◦ Supportive and palliative care

‣ Cure or control not possible ‣ Supportive care includes • Insertion of gastric feeding tube • Placement of central venous access device • Prophylactic surgical fixation of bones at risk for pathologic fracture

Chemotherapy • Chemotherapy ◦ Chemicals used for systemic therapy ◦ Goal: prevent cancer cells from multiplying, invading, and metastasizing to distant sites ◦ Drugs are classified by the phase(s) of the cell cycle that they target ◦ Mainstay for most solid tumors and hematologic cancers ◦ Can offer cure, control, or palliative care ◦ Effective against dividing cells ‣ Ineffective when cancer cells are in G phase (resting phase) ‣ Problem is compounded as tumors grow in size ◦ Drugs classified by molecular structure and mechanism of action ‣ Cell cycle phase non-specific drugs • Alkylating agents ◦ Damage DNA by causing breaks in the doublestranded helix ◦ Example: cyclophosphamide, melphalan • Nitrosureas ◦ Also break DNA helix, can cross blood-brain barrier ◦ Example: carmustine • Platinum drugs ◦ Impairs transcription of DNA within cell ◦ Example: Cisplatin – nephrotoxic • Anti-tumor antibiotics ◦ Inhibits synthesis of DNA and impairs transcription of RNA ◦ Example: Doxorubicin – nicknamed "Red Devil" causes severe nausea/vomiting, darkening of skin/ nails, cardiovascular side-effects (e.g. ECG changes, LV dysfunction, heart failure) ‣ Cell cycle phase specific drugs • Antimetabolites ◦ Mimic naturally occurring substances, thus interfering with enzyme function or DNA synthesis ◦ Examples: ‣ Cytarabine – may cause cerebellar toxicity (ataxia) ‣ 5-fluorouracil – comes in IV and topical preparations; can cause bloody diarrhea ‣ Methotrexate – hepatotoxic ‣ Hydroxyurea – bloody urine/stool, melon, blackening of fingernails • Mitotic inhibitors ◦ Interfere with mitosis ◦ Examples: ‣ Paclitaxel – causes peripheral neuropathy, myalgia ‣ Vincristine – causes peripheral neuropathy, diplopia, peripheral edema

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• Topoisomerase inhibitors ◦ Inhibit topoisomerase (normal enzyme) that function to make reversible breaks and repairs in DNA that allow for flexibility of DNA in replication ◦ Examples: etoposide, irinotecan The following medications may be administered before giving chemotherapy agents: ◦ Ondansetron ◦ Diphenhydramine ◦ Famotidine ◦ Dexamethasone ◦ IV Fluids Safe handling of chemotherapy agents ◦ Drugs may pose an occupational hazard ◦ Drugs may be absorbed through ‣ Skin • Use chemo-safe disposable gloves ‣ Inhalation during preparation, transportation, and administration ◦ Only properly trained personnel should handle cancer drugs ‣ ONS certification ◦ Use care in handling bodily fluids and excretions for up to 48 hours after last chemo dose ‣ Cover toilet bowl with chux pad before flushing Methods of administration ◦ Oral ‣ More available options today ‣ Teach patients about proper storage and side effects ◦ IM ◦ IV (most common) ‣ Central venous access device (CVAD) • Used for frequent, continuous, or intermittent administration of chemo • Preferred devices ◦ Tunneled catheter ◦ Implanted port ‣ Huber needle to access ◦ Regional administration of chemo ‣ Delivery of drug directly into tumor site ‣ Higher concetrations of drug can be delivered with less systemic toxicity ‣ Common routes • Intraarterial • Intraperitoneal ◦ Medication "dwells" for 1-2 hours and fluid is then drained • Intravesical bladder ◦ Given through Foley catheter • Intrathecal or intraventricular ◦ LP and insertion into subarachnoid space Do not use peripheral IVs for chemotherapy ◦ Many chemotherapy drugs may be either irritants or vesicants ‣ Irritants will damage the intimate of the vein, causing phlebitis and sclerosis and limiting future peripheral venous access, but will not cause tissue damage if infiltrated ‣ Vesicants can cause tissue necrosis ‣ Extravasation (infiltration of drugs into tissues surrounding the infusion site), causing local tissue damage ◦ Monitor for and promptly recognize symptoms associated with extravasation of a vesicant and to take immediate action if it occurs ‣ Elevation ‣ Heat or cold, depending on the agent ‣ Medications • Dimethyl sulfoxide Chemotherapy effects on normal tissues ◦ Chemotherapy agents cannot distinguish between normal and cancer cells ◦ Side effects are result of destruction of normal cells

◦ General and drug-specific adverse effects are classified ‣ Acute ‣ Delayed • Nadir/Neutropenia discussed later ‣ Chronic • Chemotherapy agents are often given in combination ◦ Dosages are carefully calculated according to body surface area ◦ Regimens involve drugs with different mechanisms of action and varying toxicity profiles ‣ Multiple drugs that work at different places in cell cycle can more effectively kill cancer cells ‣ Mutation of cancer cells can result in resistance to chemotherapy ◦ Success is based on ‣ Low tumors burden ‣ Uninterrupted therapy ‣ Receiving the prescribed dose of medication ◦ Nurses must monitor for tolerable vs. toxic side effects of agents Radiation • Radiation is emission of energy from a source and travels through space or some material ◦ Low emission beams (skin) ◦ High emission beams (deeper organs, spared skin) • Different types of ionizing radiation are used to treat cancer ◦ Electromagnetic ◦ Particulate • Technologic advances (e.g. linear accelerator) ◦ Goal is to offer the most accurate and least invasive delivery of radiation ‣ Maximal tolerated dose • Typically delivered once a day for 5 days a week for 2 to 8 weeks • Certain tumors are more susceptible to the effects of radiation than others • Simulation ◦ A process by which radiation treatment fields are defined, filmed, and marked out on skin ◦ Target tumor defined using ‣ Variety of imaging techniques ‣ Physical examination and surgical reports ◦ Marks placed on skin to outline treatment field • Radiation is used to treat a carefully defined are of the body ◦ Not a primary treatment for systemic disease ◦ May be used by itself or with chemotherapy or surgery ‣ To treat primary tumors ‣ For palliation of metastatic lesions • External radiation (tele therapy) ◦ Most common radiation treatment ◦ Patient exposed to radiation from a megavolt machine ‣ Gamma knife technology – Cobalt ‣ Cyclotron – Neutrons or protons ‣ Linear accelerator – Ionizing radiation • Internal radiation (brachytherapy) ◦ Implantation or insertion of radioactive materials into or close to tumor ◦ Minimal exposure to healthy tissue ◦ Commonly used in combination with external radiation ◦ Patient is emitting radioactivity ◦ Limit amount of time near patients being treated ‣ Organize care ‣ Use shielding ‣ Wear film badge to monitor exposure Nursing Management after Chemo & Radiation • Common Side effects ◦ Bone marrow suppression ‣ Myelosupression: most common side effect of chemotherapy • Within 1-3 weeks, depending on the cell type ‣ Treatment-indiced reductions in RBCs and WBCs can result in • Infection (Neutropenia)

• Hemorrhage • Overwhelming fatigue ◦ Fatigue ‣ Encourage conservation strategies • Rest before activity • Get assistance with activity • Remain active during periods of time patients feel better ‣ Maintain nutritional and hydration status ‣ Assess for reversible causes of fatigue (monitor labs) ◦ GI Disturbances ‣ Nausea (may be anticipatory or delayed), vomiting, diarrhea, mucositis, and anorexia • Use antiemetics, antidiarrheals and Magic Mouthwash prn • Promote nonirritating, low-fiber, high-calorie, high-protein diet ◦ Pulmonary effects ‣ May be progressive and irreversible ‣ Cough, dyspnea, pneumonitis, pulmonary edema ‣ Treatment • Bronchodilators • Expectorants/cough suppressants • Bed rest • Oxygen ◦ Cardiovascular effects ‣ Patients with preexisting coronary artery disease are more vulnerable ‣ Baseline and periodic echocardiograms are often done ◦ Cognitive effects ‣ "Chemo" brain • Often described as mental cloudiness or fog ‣ Can last for a short time or for years ‣ Can be severe (affect school, job, etc) ◦ Reproductive effects ‣ Inform patient of expected sexual side effects ‣ Use appropriate shielding • Radiation to testes ‣ Encourage discussion of issues related to reproduction and sexuality • Fertility preservation ‣ Refer to counseling if needed ◦ Skin reactions ‣ Occur in radiation treatment field ‣ Acute or chronic • Develop 1 to 24 hours after treatment • Generally progressive as treatment dose accumulates ‣ Erythema -> dry desquamation • Pruritus • Lubricate the dry skin with aloe vera ‣ Wet desquamation • Dermis exposed • Weeping serous fluid • Painful ‣ Prevent infection • Facilitate wound healing ‣ Protect irritated skin temperature extremes ‣ Avoid constricting garments, harsh chemicals, and deodorants ‣ Help patients deal with hair loss (alopecia) Neutropenia • Neutropenia is a reduction in neutrophils based on the absolute neutrophil count (ANC) ◦ Neutropenia is defined as ANC less than 1000 cells/µL (1x10^9/L) ‣ Decreased "segs" and increased "bands" ◦ Severe neutropenia is defined as an ANC less than 500 cells/µL • Usually seen within 1-2 weeks of last chemotherapy dose • Systemic infections caused by bacterial, fungal, and viral organisms are common • Can lead to life-threatening infection, sepsis/septic shock, and death ◦ Complicated by co-morbidities such as age, DM, hospital stay

• Classic signs of infection (e.g. fever, pain, redness, swelling, pus) may not be present ◦ Neutropenic fever (≥100.4º F [38ºC] and a neutrophil count 14.5 million in the United States • Be aware of late and long-term effects of cancer ◦ Secondary cancer ◦ Cognitive changes ◦ Cardiovascular/sexual dysfunction ◦ Psychosocial effects Related Concepts

CELLULAR REGULATION: BREAST CANCER Breast Cancer • Irregular, disorganized mass of uncontrolled cell proliferation that arises from breast tissues • Cancers of the breast are classified as non-invasive (in situ) or invasive ◦ Ductal (most are invasive) or lobular ◦ Hormone receptor or genetic status Breast Cancer Statistics • U.S. has more than 255,180 new cases of invasive breast cancers, 60,000 in situ breast cancer are diagnosed annually • Over 2,400 cases are men • Over 41,000 deaths annually • Incidence declining due to: ◦ Decreased use of hormone therapy post menopause ◦ Early detection and advances in treatment Risk Factors for Women • Genetics • Gender • Age • Hormone use

• Smoking • Obesity • Environmental • Early menses and late menopause Risk Factors for Men • Hyperestrogenism • Family history • Radiation expose • Men in BRCA positive families should consider genetic testing • Conduct self breast exam Genetics • Genetic risks ◦ 10% of breast cancers are hereditary ◦ BRCA-1 mutations ◦ BRCA-2 mutations • Prophylactic Surgery ◦ Oophorectomy ‣ BRCA mutations ◦ Mastectomy ‣ BRCA mutations Pathophysiology • Breast cancer arises from epithelia ling of ducts (ductal carcinoma) or epithelium of lobules (lobular carcinoma) • Most breast cancers are adenocarcinomas and arise in terminal section of breast ductal tissues Distribution o...