patho: week 14 - cellular mutations

neoplastic cell growth: normal + abnormal - regulation, apoptosis & features

• neoplasm: new growth - potential to be normal/abnormal

  • Normal cell: growth/division control by checkpoints in cell cycle - correct mutations before continuing the replication process 

    • Apoptosis: triggered if mutation is uncorrectable /cell is not needed 

    • Features: uniform, organized, differentiated (job), rate of growth=rate of death, exchange info with neighbor cells for apoptosis- controlled

  • Abnormal cell: escape checkpoints/ ignore apoptosis signals/grow uncontrolled

    • Cancer: abnormal group of cells, do not function normally - purpose to survive/replicate

      • Compete with normal cells for space, blood supply, oxygen, nutrients

    • Features: disorganized, los differentiation, rate of growth > rate of death (spreads quickly), misshapen nonuniform, ignore apoptosis mechanisms

      • Release lots of waste when die: inflammation

metastasis & patterns of spread

• Metastasis: malignant cancer destroy tissue/penetrate basement membranes - migrate from primary site → distant site via seeding, lymph, or blood

  • Common metastatic patterns: 

    • Lung → bone/brain

    • colon → liver

    • breast → bone/brain/liver/lung

    • prostate → vertebrae

    • melanoma → brain/CNS

angiogenesis

• tumor cells dvelop BV/connect to the pre-existing blood supply: secrete vascular endothelial growth factor (VEGF) 

  • Surgical removal of tumor: difficult/high risk if too “vascular” 

    • Risk for excessive blood loss may be contraindication

  • Make pre-existing vessel fragile: ruptured vessel → hemorrhage

cancer cellular characteristics

• multiple limitlessly/grow uncontrollably

• increase blood vessel formation/nutrients/oxygen towards tumor

• evade immune system: escape cell death

• accumulate changes in genetic material

• spread to other parts of the body 

cancer: types - 2

• Solid tissue: tumor - lung, breast, skin

  • Carinoma: epithelium 

  • Sarcoma: connective tissue, muscle

• Hematologic: blood

  • Leukemia: blood cells - stem cells transforming

  • Lymphoma: lymphatic system 

  • myeloma

cancer: causes & risk factors - virus, rad, toxin, immunity, diet

• Viruses: HPV, HBV-hep b, HCV-hep c, HIV, EBV

• Radiation exposure: sun UV rays, tanning beds

• Environmental toxins: tobacco, asbestos, nitrates, pesticides, herbicides

• Comprom immunity: immunosuppressant Rx, AIDS - bone marrow stem cells → blood cancers

• Diet: high fat, high protein, low fiber, ETOH

cancer: modifiable risk

• smoking

• body weight

• alcohol

• UV radiation

• diet

• pathogenic infection: vaccinations

• physical activity

cancer: causes - genes

•  Caused by malfunction of genes that control abnormal cell growth/division 

  • Overactive proto-oncogenes: increased promotion of abnormal cell growth 

  • Underactive tumor suppressor genes: decreased inhibition of abnormal cell growth

• 5-10% of cancers directly linked to inherited faulty gene - just because you have the gene doesn't mean you will have the cancer

cancer: statistics

• Worldwide 40% of all cancers are essentially preventable 

  • Second leading cause of death behind heart disease 

  • ⅔ of all cancers occur in those older than 65 

  • More common in males: African American men have highest incidence and mortality 

• Decreased mortality: hodgkin lymphoma, myeloma, lung/bronchus, - improved mortality → screening/catching earlier 

  • Statistics: most common in US

    • Breast (16%), prostate (15%), lung & bronchus (11%), colo-rectal (8%) 

    • 50%: melanoma, bladder, non-hodgkin lymphom, kidney, renal/pelvis, uterine , leukemia

  • Statistics: mortality rates - survival rates are increasing

    • Lung/bronchus (20%), colo-rectal (9%), pancreas (8%), breast (7%) 

    • 56%: prostate, ovarian, leukemia, liver, non -hodgkin lymphoma, uterine

• Decreases in mortality: lung cancer -reduced tobacco use: smoking accounts for more than 25% of cancer deaths in the US

• Increasing rates of cancer in other areas: liver, thyroid, myeloma, leukemia

• Increasing death rates for endometrial, pancreatic, liver cancers: rising obesity/inactivity rates in the U.S., hepatitis C infection among Baby Boomers

cancer: screening - CAUTION

• C: changes in bowel or bladder habits 

• A: lesion that does not heal 

• U: unusual bleeding/discharge 

• T: thickening/lump in breast, testicle, or elsewhere 

• I: indigestion/difficulty swallowing - GERD → esophageal cancer 

• O: obvious change in wart or mole 

• N: nagging chronic cough/hoarseness

cancer: diagnostic tools

• Self exam: breast or scrotum - multiple positions 

• Radiographic imaging: XR, US, CT, MRI, mammogram, bone scan, PET scan 

• Blood/CSF/urine test: tumor markers

• Endoscopy 

• Tissue sample for pathology: fine needle aspiration (FNA), punch biopsy, bone marrow biopsy

  • DIAGNOSIS HAS TO BE AT A CELLULAR LEVEL

cancer treatments

• surgery

• radiography (interrupt rep)

• cytotoxic chemotherapy (interrupt cell rep -not specific, all cells)

• molecular targeted therapy

• immunotherapy

types of cancers:

• solid tissue cancers:

  • lung & bronchus

  • breast

  • melanoma/skin

• hematologic cancers:

  • leukemia

  • lymphoma

  • multiple myeloma

solid tissue cancer: lung & bronchus - stats, classes, cause, s/s, diagnosis

• Largely preventable: 3rd most common type of cancer in U.S., #1 worldwide 

  • Highest mortality rate of all cancer types 

• Two major classes:

  • Small cell (20% of cases) 

  • Non-small cell (most common – 80% of cases): adenocarcinoma, squamous cell, large cell

• Cause: repeated tissue trauma from inhaled irritants/carcinogens- protective epithelial lining of lungs/bronchus replaces itself when damaged → cellular dysplasia

  • Dysplastic cells become neoplastic carcinoma: invade deeper tissues - spread

• s/s: chronic cough, pleural effusion, hemoptysis (bv), wheezing (inflam), chest pain 

• Dx testing: chest XRay, CT scan, sputum analysis, bronchoscopy, biopsy

solid tissue cancer: breast - stats, class, breast self-exams

• Most common cancer in women worldwide: may also occur in males

  • 70% of cases occur in women > 50y: can occur at any age 

    • Presence of inherited defective tumor suppressor genes BRCA1 & BRCA2 associated 50% chance of developing condition and with earlier age of onset 

• Two classifications: 

  • Invasive (penetrating) vs non-invasive (in-situ/localized) 

  • Tissue of origin and location of primary lesion: ductal, lobular

• Proper breast self-exam: when, what to look for - upper outer quadrant, also include axillary area

solid tissue cancer: breast - risk factors, s/s, diagnosis

• Risk factors: 

  • Early onset of menses, late onset menopause 

  • Obesity (increased estrogen in fat deposits) 

  • Hormone replacement therapy: hormone replacement therapy 

  • No pregnancies, late childbirth (> age 30) 

  • Family Hx of breast or ovarian CA

• s/s: 

  • Presence of single, non-tender, firm mass with irregular borders

  • Swelling in breast, nipple/skin retraction, nipple discharge - unilateral

  • Paeu d’orange: thickening of skin - resembles orange peel (inflam)

• Disease testing: mammogram, ultrasound, biopsy (need cellular)

solid tissue cancer: skin - types, risk factors, s/s

• Types: basal cell (most common-begnin), squamous cell, melanoma (most lethal) 

  • Usually form on the head, face, neck, back, hands, legs, or arms: 90% occur on sun -exposed areas of the body 

  • Melanocytes are also found in GI tract, lymph nodes, and respiratory tract

• Risk factors: 

  • Light skin color, family/personal history of skin cancer, sun exposure - work/play, history of sunburns (early in life), indoor tanning, skin that burns, freckles, reddens easily, or becomes painful in the sun, blue or green eyes, blond or red hair, certain types of moles

    • SPF: 30-50 - types chem/mineral based → 70% absorbed, to use want mineral based, absorb chem

• s/s:

  • basal cell carcinoma: waxy/pearly, white/light pink, flesh colored/ brown 

  • malignant melanoma:

    • A: asymmetrical shape

    • B: border is irregular, notched

    • C: color varies

    • D:diameter > 6mm

    • E: elevated/enlarged

solid tissue cancer: treatment

• surgery

• radiation

• chemotherapy

• immunotherapy

solid tissue cancer: treatment - surgery

• solid tumor resection

  • curative if cancer localized

  • minimal damage to other cells/tissues

  • high risk dep on tumor location/degree of vascularity 

solid tissue cancer: treatment - radiation

• goal: kill unresectable/undetected tumor cells 

  • Promotes apoptosis: causes DNA damage at specific timing in cell cycle

• Palliative reduction of large tumors 

  • Targeted rad: multiple small doses to target area 

• Side effects: fatigue most common

  • Others related to collateral injury near target area of tx 

solid tissue cancer: treatment - chemotherapy

• Admin systemically via PO/ IV for disseminated cancers 

  • Particularly lethal to rapidly dividing cells: interrupt cell cycle 

• Side effects: on-selective cell destruction → normal cells likely damaged by chemo include: 

  • Blood-forming cells in the bone marrow

  • hair follicles

  • epithelial cells: mouth, digestive tract, reproductive system

• General changes: fatigue, hair loss, easy bruising and bleeding, infectio, anemia (low red blood cell counts) 

• Weight changes: nausea, vomiting, appetite changes, constipation, diarrhea 

• Systemic changes:

  • mouth, tongue, and throat problems such as sores and pain with swallowing

  • nerve and muscle problems such as numbness, tingling, and pain

  • skin and nail changes such as dry skin and color change

  • urine and bladder changes and kidney problems 

• Chemo brain, can affect concentration and focus: mood, libido, fertility

solid tissue cancer: treatment - immunotherapy

• Immune cell boosters (interleukins): stimulate T cell/NK cell proliferation

• High toxicity & frequent allergic reactions: foreign source - monitored

• Programmed monoclonal antibodies: kill specific targeted tumor protein cells 

• Rapidly growing field in development

cancer: solid tissue treatment - tumor lysis syndrome

• Complication of rapid destruction of cancer cells: cancer cell waste →  release potassium/phosphate/uric acid into systemic circulation → kidneys

  • Overburden: acute tubular necrosis/renal failure 

    • Severe electrolyte derangements → cardiac and neuro changes 

    • Fluid overload → respiratory compromise

  • Considered an emergency: may require dialysis

• Nursing considerations: 

  • TLS prophylaxis: 

    • IV hydration (2.5 – 3L per day) 

    • Reduce uric acid production with rasburicase or allopurinol 

    • Frequent lab monitoring

• Monitor for s/s of TLS: oliguria/anuria, peripheral edema, muscle weakness and/or spasms, cardiac arrhythmias, AMS (lethargy, hallucinations, seizure), dyspnea, increasing O2 requirement, electrolyte abnormalities

hematologic cancers: hematology

• Hematology: mutations occur in the differentiation process - either sides

  • Stems cells have the potential to turn into any kind of cell 

  • Blood stem cells originate mainly in bone marrow/ become myeloid or lymphoid 

    • Myeloid: RBC, PLT, some WBC types 

    • Lymphoid: plasma, lymphoblast - B cells (plasma), T cells, NK cells 

hematological cancers: leukemia - def

• myeloid stem cells & lymphoid stem cell - either side (WBC come from both)

• Malignant disorders characterized by abnormal proliferation/maturation of WBC 

  • WBC abnormal: not able to fight infection 

  • Impair ability of the bone marrow to produce RBC/PLT: lots of WBC that are dysfunctional - overuse of resources → congestion

hematological cancers: leukemia - types

• Acute Lymphocytic Leukemia (ALL): 

  • Highest remission rate w/ treatment, most common type in children (80%)

• Chronic Lymphocytic Leukemia (CLL): 

  • Most benign type, slow progression (5yrs), more common in elderly 

• Acute Myeloid Leukemia (AML): no red, no PLS disfunction WBC

  • Most lethal type, rapid progression (<1yr), most common type in adults

• Chronic Myeloid Leukemia (CML):

  •  2 nd most lethal, phased progression (2 - 5 yrs), more common in middle age

hematological cancers: leukemia - risk factors

• Gender: men more likely to develop CML, CLL, AML than women 

• Age: risk of most leukemias, exception of ALL, typically increases with age 

• Genetics: some genetic abnormalities (Down syndrome or autoimmune conditions)

• Radiation: high-energy radiation (atomic bomb explosions), low-energy radiation from electromagnetic fields (power lines) 

• Chemicals: long-term exposure to herbicides/pesticides, industrial chemicals, or immunosuppressant Rx 

• CA treat: certain types of chemotherapy/radiation therapy for other cancers

hematological cancers: leukemia - s/s

• Low WBC: immunocompromised - unexplained fevers, night sweats, body aches, infections, mouth inflammation, pain or sores 

• Low RBCs: anemic - SOB, pale skin, fatigue, weakness, lack of energy or sleepiness 

• Low PLTs: thrombocytopenic- bleeding from gums, red spots on palate or ankles, easy bruising or prolonged bleeding from cuts, frequent or severe nosebleeds 

• General S/S: loss of appetite, unexplained weight loss, pain/aches in bones or joints , swollen abdomen/lymph nodes in neck, underarm, groin or stomach, HA, dizziness, vomiting

hematological cancers: leukemia - testing & treatment

• testing:

  • Blood testing → CBC reveals extreme derangements in WBCs, RBCs, & PLTs 

  • Bone Marrow/lymph node biopsy 

• treatment:

  • Chemotherapy 

  • Bone marrow stem cell transplant: harvest stem cells, lab, clean, program to function, multiply 

    • Chemotherapy: prep pt by ensuring pt own stem cells eradicate innate stem cell process, then reintroduce stem cells 

  • Monoclonal antibodies

hematological cancer: lymphoma - def

• lymphoblasts mutate → all else below dysfunctional 

• Cancerous lymphocytes (B/T/NK cells): 

  • Mutant cells multiple and collect in lymph nodes/tissues

  • Cancerous cells impair immune system

  • Most common type of cancer in US

hematological cancer: lymphoma - types

• Hodgkin’s lymphoma (HL): more common in ages < 20y and > 50, most curable type

• Non-Hodgkin’s lymphoma (NHL): most common (>80%), 90+ subtypes of NHL, more common in ages >60, most lethal type

hematological cancer: lymphoma - risk factors

• Age: > 60y 

• Infection: HIV, EBV (prev link), H. pylori, Hep C Virus 

• Immune system: immunosuppressive treatment, autoimmune disease 

• Toxins: pesticides, herbicides, benzine, hair dyes (prior to 1980) 

• Genetics: family history of lymphoma

hematological cancer: lymphoma - s/s

• Swollen lymph nodes (often painless)

• swelling of a limb (lymphedema): pain, numbness, or tingling

• Loss of appetite

• Night sweats, fevers, chills

• Lack of energy/ fatigue

• Unexplained weight loss

• Consistent itching

hematological cancer: lymphoma - treatment

• Chemotherapy 

• Bone Marrow transplant, radiation, immunotherapies, monoclonal antibodies 

• CAR T-cells: adoptive cell immunotherapy- genetically reprogram patients’ own immune cells to find and attack cancer cells throughout the body

hematological cancer: lymphoma - CAR T cells timeline & complications

• Timeline: native immune cell programmed to target cancer cells

  • Specific CA antigen markers identified

  • Patient’s T cells removed via phlebotomy

  • Lab: T cells genetically “programmed” via viral vector encoded with CA specific antibody info 

  • Programmed CAR T-cells propagated in vitro 

  • Patient receives chemo to reduce number of CA cells

  • CAR T-cells are infused into pt

  • CA cells with specific antigen are attacked and eradicated

• Complication: can go away on own, may cause death

  • Neurologic problems: expressive aphasia, dysarthria, decreased LOC, delirium, hallucinations, seizures, coma 

    • Airway compromise risk 

  • Cytotoxin release syndrome: inflam response cytokine mediators releases → fever, low BP, dyspnea, organ failure

    • May require ICU: ventilator/drugs to maintain BP, anti seizure meds

hematologic cancer: multiple myeloma - def

• B cells dysfunctional/destructive 

• Malignant disorder of mature antibody-secreting B lymphocytes: malignant plasma cells invade bone, form multiple tumor sites 

  • May also target other tissues: lymph nodes, liver, spleen, kidney

hematologic cancer: multiple myeloma - risk factors

• Age: occurs exclusively in adults, usually >40 yrs old

• Gender: men > women

• Genetic/geographic location: African American (2x), middle East, north Africa, med

• Toxins: radiation, asbestos, pesticides

• Occupation: rubber manufacturing, carpenters, furniture/paper makers, firefighters

hematologic cancer: multiple myeloma - s/s

• R/T: bone &/or renal damage, anemia, & deficient immune response 

• Bence Jones protein: malignant B cells cells produce antibody fragments -accumulate in blood/urine - helps confirm diagnosis, can accumulate in kidneys/damage them 

• Malignant plasma cells tend to accumulate in bone 

  • Bone pain common in back, hips, skull 

  • Pathologic fractures common 

  • Bone destruction releases calcium into bloodstream → hypercalcemia

hematologic cancer: multiple myeloma - treatment

• Bone Marrow transplant

• chemotherapy

• bisphosphonates: reduce bone damage

• CAR T-cell Tx trials

cancer: remission & relapse

• Remission: partial or complete

  • Complete remission: all s/s of cancer have disappeared

    • Complete remission lasts for 5 + yrs: some providers may say the cancer is cured 

  • Cancer cells remain in the body for many years after treatment: may cause cancer relapse 

    • Most relapse: within the first 5 years after treatment 

    • Always a chance that cancer will come back later: monitored for many years, monitor for signs of late side effects related to cancer treatments

oncology nursing considerations

• Patient assessment: monitor for progression of disease, changing psychosocial needs, assess for treatment complications

• Patient education: reinforce information on treatment plan, strategies for reduction of side effects 

• Coordination of care: cluster activities to conserve energy, maximize quality time with family & friends

• Proactive symptom management: pain control is essential, GI comfort measures, treat anxiety 

• Supportive care: facilitate normal life routines whenever possible, foster ongoing dialogue about goals of care