1

CANCER
Week 3: Ch. 12-14
Objectives:

Define cancer and discuss methods for naming and classifying tumors

Describe characteristics of the cancer cell and the mechanism involved in metastasis

Discuss diagnosis, staging, and treatment of cancer

List 10 oncologic emergencies in the cancer patient

Compare childhood and adult cancers

CANCER
Derived from Greek word for crab, karkinoma

Cancer refers to a
BENIGN
benign)

Cancer is not one disease

GROW SLOWLY

Many cancers can be

WELL-DEFINED CAPSULE
and treatment
CLASSIFICATION AND
Tumors named (initially)
which they arise

GROW RAPIDLY
NOT ENCAPSULATED

NOT INVASIVE

INVASIVE

WELL DIFFERENTIATED

POORLY DIFFERENTIATED

LOW MITOTIC INDEX

HIGH MITOTIC INDEX

Benign tumors
DO NOT METASTASIZE
CAN SPREAD DISTANTLY
o Include the suffix
(METASTASIS)
o Can be life
cause bleeding, erodes through vessel)
o Can progress to cancer
o Examples:

Hemangioma benign tumor of blood vessels

Meningioma benign tumor of the meninges

malignant tumor (vs

many different types
cured with early detection
NOMENCLATURE
according to tissues from

oma
threatening (grow too big,

Malignant tumors
o Carcinomas arise from epithelial tissue
o Adenocarcinomas arise from glandular or ductal epithelium

Ex: malignant tumor from breast glandular tissue (mammary adenocarcinoma)

o Sarcoma arise from connective tissue
o Lymphoma arise from lymphatic tissue
o

MALIGNANT

Leukemia arise from blood-forming cells

Carcinoma in situ (CIS)

o Pre-invasive epithelial malignant tumor of glandular or squamous cell origin
o LOCALIZED to epithelium only
o Has not broken thru basement membrane or invaded the surrounding stroma (an early-stage cancer)
o *Common locations:

Stomach, endometrium, breast, large bowel

Cervix, skin, mouth, esophagus, bronchus

CHARACTERISTICS OF CANCER CELLS How they proliferate/survive; behave differently from normal cells

Transformation Normal cell becomes cancer cell

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Autonomy Cancer cells gain independence from normal cellular controls (part of transformation process)

Anaplasia (hallmark of cancer cells via microscope)

o Abnormal cell structure Loss of cellular differentiation/organization, marked inc in nuclear size, loss of
normal tissue structure, and evidence of ongoing proliferation
Anchorage independent Will divide even outside the human body
Immortal Unlimited lifespan!

HeLa cells
CANCER STEM CELLS

Exist in hematologic and solid tumors

Share characteristics with normal stem cells

o Self replicate Cell division creates new stem cells
o Differentiation Multiple different cell types
Critical to cancers ability to recur and metastasize
TUMOR MARKERS

Biological markers

Produced by cancer cells

Can be found in CSF, blood, urine or in tumor cells

o Examples:

PSA blood assay for prostate CA

Carcinoembryonic antigen (CEA)

Blood assay for pancreatic, GI, lung, breast CA

Detection in other body fluids related to metastasis

*Tumor markers are used to:

Screen and identify individuals at high risk for certain types of cancer

Diagnose specific types of tumors

Observe clinical course of cancer (Ex: would expect dec CEA levels after tx of colon CA)
ETIOLOGY

Carcinogens
o Injury to cell with exposure
o Latent period
Chemical
o Asbestos
o Cigarettes
Radiation
o X-rays
o UV light
o Nuclear radiation
Infection
o Chronic inflammation
o Chronic suppression/stimulation of immune system

Ex. Papillomavirus (HPV causes cervical CA), HIV, Heliobacter pylori

Irritants
o Pipe smoking
o
GENETICS
o Cancer cells develop because of gene mutations

Changes in DNA mutations, DNA/histone chemical modification, micro-RNA expression

o Two types of genetic mutation:

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Germ-line
Acquired

o
CA is disease of aging
o Genetic mutations occur over time
o 4 to 7 mutations lead to CA
o

GENES LINKED TO CA mutations in these genes leads to cancer

o Oncogenes (accelerate proliferation)
o Tumor-suppressor genes (antioncogenes) (put the brakes on)

BRCA1 & BRCA2 (breast and ovarian)

o METASTASIS defining characteristic of cancer

Spread of cancer from a primary site of origin to a distant site

o Inefficient process
o Most cancer cells cannot metastasize

Contributes to pain and suffering of cancer pt

Major cause of death

Occurs via lymph, blood, seeding, and transplantation

o

Overview:
o Detachment and invasion
o Survival and spread in circulation
o Selective adherence
o Escape from circulation
o

1) Direct invasion of contiguous organs Known as local spread

2) Metastases to distant organs via lymphatics and blood (direct/continuous spread)

3) Metastases by way of implantation

o
O DIAGNOSIS

Detection through screening, physical exam, and symptoms

Comprehensive medical history and physical exam

Diagnostics to further evaluate:

o Ex: CXR, CT, MRI, U/S
Definitive diagnosis through tissue pathology BIOPSY
o Is it malignant or benign? If malignant, what cell type? (i.e. squamous, epithelial, small cell)
o
O STAGING
o Involves the size of the tumor, degree to which it has invaded, and extent of spread

Stage 1 Cancer is confined to its organ of origin

Stage 2 Locally invasive

Stage 3 Regional structures (lymph nodes)

Stage 4 Distant sites

o
o
o TNM System (know how to stage)

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o
o
o
o
O
PAIN
o
o
o

CLINICAL MANIFESTATIONS OF CANCER

Little or no pain is associated with early stages of malignancy
Influenced by fear, anxiety, sleep loss, fatigue, and overall physical deterioration
Mechanisms:

Pressure, obstruction, invasion of sensitive structures, stretching of visceral surfaces, tissue

destruction, and inflammation

o
FATIGUE
o Subjective clinical manifestation
o Tiredness, weakness, lack of energy, exhaustion, lethargy, inability to concentrate, depression, sleepiness,
boredom, and lack of motivation
o Suggested causes:

Sleep disturbance, biochemical changes from circulating cytokines, secondary to disease and
treatment, psychosocial factors, level of activity, nutritional status, and environmental factors
o
CACHEXIA
o Most severe form of malnutrition
o Present in 80% of cancer patients at death
o Includes:

Anorexia

Early satiety

Weight loss

Anemia

Asthenia

Taste alterations

Altered protein, lipid, and carbohydrate metabolism

o
ANEMIA
o A decrease of hemoglobin in the blood
o Mechanisms:

Chronic bleeding resulting in iron deficiency, severe malnutrition, medical therapies, or malignancy
in blood forming organs

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LEUKOPENIA & THROMBOCYTOPENIA (dec WBCs, dec platelets)

o Direct tumor invasion to the bone marrow causes leukopenia and thrombocytopenia
o Chemotherapy drugs are toxic to bone marrow
o
INFECTION
o Risk increases when the absolute neutrophil and lymphocyte counts fall (inverse relationship)
o
PARANEOPLASTIC SYNDROMES
o Symptom complexes that cannot be explained by the local or distant spread of the tumor or by the effects of
hormones released by the tissue from which the tumor arose
o

O TREATMENT CHEMOTHERAPY
Began with mustard gas in WWII
Now extensive cancer chemo cocktails
Targets vulnerability of cancer cells
Usually given in combinations
Toxic to normal AND abnormal cells

o
O
O
O
O
O
O
O
O
O
O CHEMOTHERAPY
O
O
CLASSIFICATION: (based on what it does)
Cell cycle-phase specific
o Antimetabolites
o Plant Alkaloids
o
Cell cycle nonspecific
o Alkylating Agents
o Antitumor antibiotics
o
Hormones
o
O
TYPES:
Induction chemotherapy
o 1st chemotherapy agent given
o Accepted as best treatment
o Often given in toxic doses
Neoadjuvant
o Given PRIOR to other treatments
o Ex To shrink tumor prior to surgery
Adjuvant
o Given AFTER primary treatment (i.e. surgery) of cancer
o Lowers risk of recurrence

Salvage
o Trying to buy the pt some time; no cure
o
o

CHOP = Chemotherapy Regime for Lymphoma

C: Cytoxan (cyclophosphamide)

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H: Adriamycin (hydroxy doxorubicin)

O: vincristine (Oncovin)
P: Prednisone
o
o Given in 21 day cycles, usually 6-8 cycles

Day 1: C, H, O given IV; P given PO

Days 2-5: P given PO

Days 6 21: rest

o
O TREATMENT RADIATION
Ionizing radiation
o Damages cells by imparting enough ionizing radiation to cause molecular damage, esp to DNA-killing
cancerous cells
o Causes irreversible damage to normal cells

Lifetime radiation dosage (can only have a certain amt)

Brachytherapy
o Seed implants (prostate CA)
O
O TREATMENT SURGERY

Surgery
o Biopsy and lymph node sampling

Sentinel nodes
o Debulking surgery (part but not all)
o Palliative surgery (buying time)
o

Careful! To achieve a cure

o Must achieve adequate surgical margins (get it all)
o Must place needle tracks and biopsy incision scars (that may be contaminated with cancer cells) carefully so
they can be removed in subsequent incisions
o Must avoid the spread of cancer cells during surgical procedures
o Must obtain adequate tissue specimens to confirm the diagnosis
o
O TREATMENT IMMUNOTHERAPY

Theoretically, antitumor responses can selectively eliminate cancer cells while sparing normal cells

Immune memory is long lived

Numerous immunologic mechanisms are capable of rejecting different types of cancer

Biologic response modifiers (BRMs)
o

Other forms of immunotherapy:

o Interferon administration
o Antigens
o Effector cell lymphokines
o Monoclonal antibodies
o

O SIDE EFFECTS OF CANCER TREATMENT

Gastrointestinal tract N/V
Bone marrow suppression Decreased platelets and WBCs
Hair and skin
o Hair loss (chemo agents target rapidly growing cells in general)
o Skin dryness, breakdown
Reproductive tract
o Decreased fertility
o Gonadal failure
o Early menopause

O
Pain

DISEASE AND TREATMENT COMPLICATIONS

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Fatigue
Cachexia
Anemia
Leukopenia and thrombocytopenia
Infection

o
O ONCOLOGIC EMERGENCIES (LIFE-THREATENING)
Metabolic
o Disseminated Intravascular Coagulation (DIC)
o Thrombocytopenia
o Sepsis/Septic Shock (d/t immunosuppression)
o Tumor Lysis Syndrome
o Hypercalcemia
o Syndrome of Inappropriate Antidiuretic Hormone (SIADH) (hypoNa+)
o Anaphylaxis
o
Structural
o Increased ICP
o Spinal Cord Compression (paralysis symptoms)
o Superior Vena Cava Compression
o Cardiac Tamponade
o Malignant Pleural Effusions
o
O CHILDHOOD CANCERS

Most common childhood cancers are leukemias, sarcomas, and embryonic tumors
o Embryonic tumors:

Originate during uterine life

Usually diagnosed before age 5

Immature embryonic tissue unable to mature or differentiate into fully developed cells

Commonly named with the term blast (i.e. an immature cell)

+ Blast BAD on CBC! (means leukemia of some type)

o

Most originate from the mesodermal germ layer

o The mesodermal layer gives rise to connective tissue, bone, cartilage, muscle, blood, blood vessels,
gonads, kidneys, and the lymphatic system
o

O CANCER ADOLESCENTS AND YOUNG ADULTS

2% of all invasive cancers
Malignancy rate in 15- to 29-y.o. is 3xs higher than that in children <15 years
Most common cancers among 15- to 19-y.o. population in U.S.
o Hodgkin lymphoma, non-Hodgkin lymphoma, germ cell tumors, central nervous system (CNS) tumors (Solid
Tumor), thyroid cancer, malignant melanoma, and acute lymphocytic leukemia (ALL 75% of pediatric
cancers)
Many of the common malignancies in children <5 y.o. are virtually absent in 15- to 19-y.o.
o Leukemia most common
Kids gen leukemias, brain tumors, and sarcomas

o
CHILDHOOD VS ADULT CANCERS

O
o

CHILDHOOD

ADULT

<1% of cancers

>99% of cancers

Involves tissue

Involves organs

Nonepithelial and
mesenchimal

Carcinomas

Short latency

Long latency periods

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Ecogenetic involvement

Environmental and lifestyle

influence

Few prevention strategies

80% preventable

Detection usually
accidental

Screenings for early

detection

80% metastasized at
diagnosis (Fast growing!)

Local or regional at
diagnosis

Responsive to treatment

Less responsive to
treatment

Long term consequences

with treatment

Fewer long term

consequences

>70% cure rate

<60% cure rate

o
o ETIOLOGY (pediatric cancers)

Multifactorial
o Genetic
o Environmental
o Prenatal exposures
o Childhood exposures
o
Genetic factors
o Oncogenes

Found in pediatric leukemias, lymphomas, and solid tumors

O Tumor suppressor genes

Found in pediatric osteosarcoma, retinoblastoma, leukemia, rhabdomyosarcoma, Wilms tumors

o Chromosome abnormalities

Aneuploidy, amplifications, deletions, translocations, and fragility

o High recurrence risk
o
Environmental factors
o Prenatal exposure Drugs, medications, and ionizing radiation
o Increased parental age
o Childhood exposure Drugs, medications, ionizing radiation, or viruses (HIV!)

Ex: Anabolic androgenic steroids, cytotoxic agents, immunosuppressive agents, Epstein-Barr virus
o
O PROGNOSIS GOOD!!

78% of children with cancer are now cured

Children more responsive and better able to tolerate treatments

More likely to be enrolled in clinical trials

Long-term effects of treatment worse on kids

Psychologic ramifications