Cancer Flashcards
What is a tumor?
- An abnormal mass of tissue
~ Either benign or malignant - Uncontrollable/autonomous growth
~ Persists even after cessation of the stimuli that initiated it
What are the general characteristics of benign tumors?
- Typical of tissue of origin
- Well-differentiated
- Few mitosis and normal
- Strictly local, often encapsulated with no metastasis
~ Capsule and basement membrane not breached - Slow growth rate
- Rare tumor necrosis
- Rare recurrence after treatment
- Good prognosis
What are the general characteristics of malignant tumors?
- Anaplastic
~ With abnormal cell size and shape
~ Not well-differentiated - Many mitoses
- Rapid growth rate and may be abnormal
- Infiltrative/frequent metastases
~ Capsule and basement membrane breached - Tumor necrosis common
- Recurrence common after treatment
- Poor prognosis
What are the main phases of tumor development and growth?
1) Transformation
- Benign cells
~ Mostly well-differentiated
~ Resemble the cell from which they originated
- Malignant
~ Transforms into anaplasia (final stage)
~ Nuclear and cellular pleomorphism (size and shape)
~ Abnormal nuclear morphology
~ Loss of polarity
~ Abundant mitoses
2) Rate of growth of transformed cells
- How differentiated the cells are
~ Well-differentiated: Resembles mature cells of tissue of origin
~ Poorly-differentiated: Primitive cells
~ Undifferentiated: Anaplastic
- Less differentiated = faster growth
3) Invasion of tumor cells to surrounding tissues
- Benign cells
~ Cohesive with a rim of condensed connective tissue/capsule
- Malignant
~ Local invasion (Detachment, attachment, degradation & migration)
4) Metastasis of tumor cells to distant sites
- Lymphatic, hematogenous and seeds into body cavities
- Intravasation, embolisation, adhesion, extravasation, metastatic growth
What are the different ways that cells can transform in cancer?
HHN DMA (HHN Done More Amazing)
1) Hypoplasia
- Fewer cells than normal
~ Usually benign
- eg postpubertal female breast underdevelopment /micromastia
2) Hyperplasia
- More cells than normal
- Controlled by normal proliferation mechanisms
- Due to external stimuli
~ eg callus exposed to pressure
3) Neoplasia
- ^ cell number
- Abnormal multiplication
~ Loss of normal proliferation regulation
~ Absence of stimuli
4) Dysplasia
- Change in normal shape, size and organisation
- Usually in response to chronic irritation
- Reversible changes if stimulus is removed
~ If not, cells become metaplastic
5) Metaplasia
- Change in cell type
- After prolonged irritation
- Reversible changes if stimulus is removed
~ If not, cells become anaplastic
6) Anaplasia
- Reversal in differentiation OR
- Loss of structural and functional differentiation of normal cells
- Not reversible in nature
- Characteristic of cancerous tumors
What are some abnormal nuclear morphology?
- Hyperchromasia
- High nuclear cytoplasmic ratio
- Chromatin clumping
- Prominent nucleoli
What are the steps in local invasion of cancer cells?
1) Detachment of tumor cells from each other
2) Attachment of tumor cell to matrix components
3) Degradation of matrix components
- To allow slow invasion through
- eg using collagenase
4) Migration of tumor cells
What are the steps in metastasis?
Clonal expansion, growth, diversification, angiogenesis into metastatic subclone -> Adhesion to and invasion of basement membrane -> Passage through extracellular matrix -> (1)
1) Intravasation
- Passage of cancer cells into blood vessels
2) Embolization
- Interaction with host lymphoid cells forms a tumor cell embolus/clump which travels along the BV
3) Adhesion
- Embolus adhesion to the basement membrane
4) Extravasation
- Passage of cancer cells out of blood vessels into distant tissues
- Metastatic deposit
- Angiogenesis and growth
5) Metastatic growth
What is the significance of nodal metastasis?
T1N0M0:
- Small
- No spread to regional lymph nodes
- No metastasis
- Considered stage 1
T4N1M1:
- Large
- Spread to regional lymph nodes and other organs
- Considered stage 4
What is the nomenclature for cancers?
Benign:
- Suffix of -oma
- eg osteoma, lipoma, papilloma
Malignant:
- -carcinoma
~ If originated from epithelial cells
~ eg squamous cell carcinoma, adenocarcinoma
- -sarcoma
~ If originated from mesenchymal cells
~ eg fibrosarcoma, osteosarcoma, angiosarcoma
What are the predisposing factors for cancer?
- Age
- Childhood cancers
- Obesity
- Chronic inflammation
- Precancerous conditions
~ Chronic ulcerative colitis
~ Atrophic gastritis of pernicious anemia
~ Leukoplakia of mucous membranes - Genetic factors
~ Point mutation
~ Translocation
~ Amplification
~ Familial cancer symptoms - Environmental factors
What are the environmental factors that increases the risk of cancer?
- Chemicals
~ Hormones, grilled meats, asbestos - UV light/ionizing radiation
~ Usually causes basal cell carcinoma, squamous cell carcinoma, melanoma - Viral infx
~ HPV (squamous cell carc)
~ EBV (Burkitt lymphoma, NPGL carc)
~ HBV (hepatocellular carc) - Vices
What is the molecular basis of malignancy?
Failure of DNA repair or cell mutations ->
- Activation of growth-promoting hormones + Inactivation of tumor suppressor genes
~ Unregulated cell proliferation
- Alterations in genes that regulate apoptosis
~ Decreases apoptosis - Clone expansion + Angiogenesis + Additional mutations + immunity escape
~ Tumor progression and malignant neoplasm
What are the regulatory genes targeted in carcinogenesis?
- Proto-oncogenes
~ Normal genes that promote cell proliferation
~ Only switched “on” for short periods by growth-promotion factors
~ Mutates into oncogenes when damaged by carcinogens
~ Oncogenes are dominant and function autonomously
~ RAS genes, MYC genes, ABL genes - Tumor suppressor genes
~ Inhibits cellular proliferation
~ Stimulates apoptosis
~ BRCA1/2 genes, p53 genes, RB genes - Genes regulating apoptosis
- Genes revolved in DNA repair
What is the ABL gene?
- ^ tyrosine kinase activity to ^ RBC division
- Forms Philadelphia chromosome when ABL gene on chromosome 9 translocates to chromosome 22
~ Allows unregulated tyrosine kinase activity for ^ cell division/unregulated growth
What are the RB genes, BRCA1/2 genes and p53 genes?
RB
- Associated with retinoblastoma
- On chromosome 13
- Inactivated in HPV infx
- Implicated in almost all cancers
BRCA
- 1 on chromosome 17, 2 on chromosome 13
- Usually repairs damaged DNA and destroys unrepairable cells
- Most common in breast cancer, but also in colon and prostate cancer
p53
- on chromosome 17
- linked to apoptosis
- Activated when the cell is stressed or injured
~ Prevents cell division, repairs DNA and triggers apoptosis
- When gene is damaged, tumor suppression decreases
How to stage neoplasms?
Tis: in situ, non-invasive
T1: Small, minimally invasive
T2: Larger but still within primary organ site
T3: Larger and invasive beyond margins of the primary organ site
T4: Very large and invasive, with spread to adjacent organs
N0: No lymph node involvement
N1: Nearby LN
N2: Regional LN
N3: More distant LN involvement
M0: No distant metastasis
M1: Distant metastases
How to grade neoplasms?
I: Well differentiated
- Easiest to control
II: Moderately differentiated
III: Poorly differentiated
IV: Nearly anaplastic
- Poorest prognosis
What are the diagnostic methods for neoplasia?
- Hx and PExam
- Radiography (presence and location of mass lesions)
- Lab analyses and tumor markers
~ Prostate specific antigen (PSA)
~ CEA, AFP, HCG - Genetic testing
- Cytology
~ Pap smear
~ Fine needle aspiration - Tissue biopsy
- Autopsy
What are the effects of tumors on the host?
1) Anatomic encroachment
- eg SVC syndrome
2) Hormone production
- eg prolactinoma
3) Bleeding, inf
4) Cachexia (fat + muscle loss)
- Reduced diet
~ Fat loss > muscle loss
- TNF alpha, IL-1, Proteolysis Inducing Factor (PIF)
5) Para-neoplastic syndromes
- Not directly related to the tumor spread
- Mediated by humoral factors (eg hormones or cytokines) excreted by tumor cells
- eg Acanthosis nigricans in gastric/lung cancers, clubbing in lung cancer, Trousseau / migratory thrombophlebitis in pancreatic cancer
6) Acute symptoms
- eg rupture, infarction
What are the common complications of cancer treatment or at stage 4 cancer?
- Superior vena cava syndrome (SVCS)
- Hypercalcemia
- Spinal cord compression
- Tumor lysis syndrome
What are some s/s of SVCS?
- Non-productive cough
- Fatigue
- Worsening dyspnea
~ on exertion and when lying down - Hoarseness
- Progressively enlarging veins on the chest to neck
- Increasing neck and face swelling
- Sensation of blacking out
What are the mechanism of SVCS?
1) Extrinsic compression
- eg by tumor
- Pressure exerted externally reduces venous return
~ Blood backs up into the veins of the upper body
~ Venous congestion and elevated pressure lead to swelling/edema of the face, neck, and upper extremities
2) Intravascular thrombosis
- Clot impedes venous blood flow
~ Stagnation and congestion in the upstream venous system
- Inflammatory processes around the thrombus can further exacerbate the obstruction
What are the investigations for SVCS?
- CXR, CT contrasted
- Tumor markers (AFP< HCG)
- FBC
- PT/PTT/aPTT
- Biopsy, histology
What are the complications of SVCS?
If px collapses during procedure:
- CTVS team, CTICU and HD team
If SVC collapses:
- Urgent stenting
- Removal of external compression
If tumor breaks down spontaneously:
- Management of tumor lysis syndrome
IMPT:
What is the management of SVCS?
- Treat the cause and complications of mediastinal mass
- Look out for complications of treatment
~ eg chemotherapy toxicity (neutropenic fever, N/V, central line sepsis, renal impairment)
~ fluid overload - Do not increases SVC return
~ No IV plugs and BP taking on upper limbs
~ Head of bed at 30 degrees
~ Advocate for central line insertion give treatment lately - Fall precaution or neurological changes
- Strict I/O
- Daily weight if needed
What are the s/s of hypercalcemia?
- Bone pain
- Fractures
- Renal stones/calculi
- Anorexia
- N/V
- Constipation
- Abdominal pain
- Pancreatitis
- Fatigue
- Confusion/acute delirium
- Depression
What are the causes of hypercalcemia?
- Hyperparathyroidism
- Hyperthyroidism
- Cancer
- Vitamin D intoxication
- Excessive Vitamin A
- ^ Calcitriol
- Thiazide diuretics
- Acromegaly
What is the grading of hypercalcemia?
Mild: <3mmol/L
Moderate: 3-3.5mmol/L
Severe: >3.5mmol/L
What is the management of hypercalcemia?
- NS 3L/day x3/7, 1.5L/day x2/7
- IV Pamidronate 60mg in 500 ml over 6hrs
- Treat cancer w chemo/radiotherapy
- Treat symptoms of s/s of hypercalcemia
- Look out for complications of treatments
~ Hyperhydration - fluid overload
~ Biphosphonate & denosumab - hypocalcemia and osteonecrosis of jaw - Strict I/O
- Daily wights
- Give furosemide PRN based on dr’s orders
- Pain charts
What is the treatment for hypercalcemia?
Mild/moderate/asymptomatic:
- Does not require immediate treatment
- Remove factors that aggravate hypercalcemia
- Ensure adequate hydration
Severe/symptomatic:
- Immediate, aggressive treatment
- Aggressive hydrations (200-300l/hr)
~ In case of CCF or CKD, use CALCITONIN instead (rapid response within 12-24 hrs) but can cause rebound hypercalcemia or tachyphylaxis)
- Furosemide
- Biphosphonates
~ ZOLENDRONIC ACID/PAMINDRONATE
- RANKL inhibitor
~ DENOSUMAB
What are the s/s of spinal cord compression?
- Back pain
- Motor findings
~ eg mechanical instability of the spina
~ difficulty in moving - Sensory findings
- Bladder and bowel dysfunction
- Ataxia
- Cauda equina syndrome
~ Medical emergency from when nerves at the end of the spinal cord get compressed
What are the investigations for spinal cord compression?
- Spine MRI
- CT (but not ideal)
- PET-CT
~ If primary site of disease is not known / newly diagnosed - Biopsy, histology
- Labs PT, aPTT, FBC
- Tumor markers
What is the epidural spinal cord compression grading scale?
Grade 0: Tumor confined to bone
Grade 1a/b: No contact with spinal cord
Grade 2: Tumor that displaces or compresses spinal cord
Grade 3: Tumor with circumferential epidural extension that causes severe spinal cord compression with obliteration of the CSF space
What is the medical management of SCC?
If spine unstable:
- Surgical fixation
~ eg pedicle screws, percutaneous cement injection
If pain:
- Glucocorticoids
~ High dose dexamethasone
- RT
- Chemo-sensitivity
- Opioids
Prophylaxis:
- Venous thromboembolism prophylaxis
~ Especially for advanced cancers
~ Prophylactic low molecular weight heparin, CLEXANE
What is the management for SCC?
- Log rolling
~ for unstable spine - Assessment of neurological involvement and spinal stability
~ Using SINS scoring tool - Management of urinary retention and constipation
~ IDC
~ Laxatives
~ I/O chart - VTE prophylaxis
~ Calf compressors
~ Bed exercises - Fall precaution
What is tumor lysis syndrome?
- Oncologic emergency caused by massive tumor cell lysis
- Releases large amounts of potassium, phosphate and nucleic acids into blood
~ Results in hyperkalemia, hyperphosphatemia, secondary hypocalcemia, hyperuricemia and AKI - Potassium and Breakdown of nucleic acids
~ Highly insoluble products
~ Forms crystals in the renal distal tubules (crystal deposition leads to AKI) - Phosphate (conc. is x4 higher in cancer cells)
~ Calcium binds to phosphate -> precipitation -> hypocalcemia -> AKI and cardiac arrhythmias
What are the types of tumor lysis syndrome?
- Spontaneous
~ Often without hyperphosphatemia - Treatment-induced
What are the risk factors for tumor lysis syndrome?
Px factors:
- Pre-existing hyperuricemia or renal disease
- Oliguria or acidic urea
- Dehydration especially during treatment
Tumor specific:
- Large tumor burden (large, ^ WBC count, bone marrow involvement, LDH >x2 normal)
~ Easily lysed by treatment
- Blood cancer
- Chemo/radiosensitivity
What is the management for tumor lysis syndrome?
1) Treat electrolyte abnormalities
- Hyperkalemia
~ Serum potassium levels
~ Continuous cardiac monitoring
~ Oral potassium-lowering agents (SODIUM POLYSTYRENE SULFONATE)
- Hyperphosphatemia
~ Aggressive hydration with concurrent use of diuretics
~ Phosphate binder therapy (CALCIUM CARBONATE) - Hypocalcemia
~ If calcium phosphate product is >60mg/dL, no calcium should be given until hyperphosphatemia is treated
~ Calcium replacement given at lowest dose to relieve symptoms
2) Target hyperhydration
- Strict I/O
- Daily weight
- Renal dialysis management for px with severe AKI
- Furosemide
What is the preventive management for TLS?
- IV hydration
- Hypouricemic agents
~ ALLOPURINOL
~ RASBURICASE (for high risk px but need to do G6PD check before giving)
