Oncology

1. Historical background
- ONCOLOGY science that deals
with the study of tumors
- Greek words
o ONKOS tumor, mass
o LOGOS - study
- Study of cells with changed
proliferative behavior due to basic
reasons still unknown
o Cells that have lost their
response to the influence of the
normal control mechanism of the
surrounding tissues
- 18th century
o Knowledge of neoplastic disease
is limited to observation alone
because of lack of technology
o Hallmark: discovery of scrotal
skin cancer among chimney
sweeps Sir Percival Pott
- 19th century
o Discovery of the microscope
world of cells
o 1838, Johannes Muller
cellular morphology
o 1847, Rudolf Virchow theory
of local irritation
o 1882, Halsted 1st radical
mastectomy
o 1887, Julius Cohnheim theory
of embryonal rest
- 20th Century
o Further discoveries in the fields
of biochem, patho, physio
o 1915-1918, Yamagiwa and
Ichikawa hydrocarbons as
carcinogens
o 1924-1932, Kennaway and Cook
3,4 benzopyrene as chemical
carcinogen

o Viruses were linked to CA, such

as virus causing sarcoma in
chicken
o John Hunter and Berthold
action of endocrines in prostate
glands
o 1940, Higgins and Clasrk
demonstrated that prostate
tumors are androgen dependent
and estrogen controlled
o Beatson and Schinzinger
related breast CA and ovaries
o En bloc resection of the organ
together with its draining lymph
nodes
o 1950s organ transplantation
2. Divisions of Oncology
a. Research
- Laboratory methods
- Clinical procedures
- Epidemiology
b. Clinical
- Medical oncology
- Surgical oncology
- Radiologic oncology
- Immunotherapy
c. Social
- Education and training
- Rehabilitation
- Prevention
3. Surgical oncology
- Deals with surgical principles
applied in the treatment of
malignant diseasses
- Surgeon is often responsible do r
the initial diagnosis and
management of solid tumors
- Modern cancer therapy :
multidisciplinary
o Surgeons + medical oncologist +
radiation oncologist +
reconstructive surgeons +
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pathologists + radiologists +
primary care physicians
Primary )definitive) surgical
therapy : en bloc resection +
adequate margins of resection +
regional LN dissection if
necessary
Adjuvant therapy: Chemo, RT,
Hormonal, immunotherapy,
biologic therapy
Locoregional control: surgery or
RT
Systemic control: chemo, HRT,
immunotherapy

4. Epidemiology
a. Global statistics
- 2002: 10.9M new cancer cases
estimated worldwide
- Lung CA most common
o 1.35M new cases
o 1.15M deaths/yr
- Breast CA- 2nd most common
o 1.15M cases/yr
o 5th most common cause of death
- Leading causes of death from
cancer:
o Lung
o Gastric
o Liver
o Colorectal
o Breast
b. Stomach Cancer
- Incidence varies among different
regions of the world:
o Japan: 62.1/100000 men;
26.1/100000 women
o North America: 7.4/100000 men;
3.4/100000 women
o Africa: 3.4-4.4/100000 men; 2.53.6/100000 women
- Varied incidence attributed to:
o Dietary Habits

High consumption of preserved

salted foods )meat, pickles)
increases risk
Consumption of fruits and
vegetables decrease risk
o Prevalence of Helicobacter
Pylori infection
c. Breast Cancer
- High incidence in developed
countries (USA, Canada,
Australia, Northern and Western
Europe) 82.5-99.4/100000
women annually
- Low incidence in most of Africa
and Asia: <30/100000 women
- Lowest in Central Africa:
16.5/100000 women
- Geographic variation attributed to
difference in reproductive factors,
diet alcohol, obesity, physical
activity, environmental differences
and not to gene mutation (which
accounts for 5-10% of breast CA)
d. Colorectal Cancer
- Higher incidence in developed
countries
o Highest rates in N. America,
Australia, New Zealand, Western
Europe, Japanese men
o Low rates in North Africa, South
America,, most of Asia
- Differences in rates attributed to:
o Environmental exposures
o Dietary difference in
consumption of fat, meat, fiber
e. Liver cancer
- 82% occur in developing
countries
o High in China: 37.9/100000 men
o Low in America, Europe: 2.66.2/100000 men
- Major risk factors
o Hepatitis B and C infection

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o Consumption of food
contaminated with Aflatoxin
f. Observations
- The mortality rates for different
cancers vary among countries
o Variations in incidence
o Variations in survival after
diagnosis. Dependent on:
Treatment patterns
Variations in cancer screening
practices, vis a vis, early
diagnosis and treatment
- The incidence rates also vary
widely by geography
o Due to genetic, ethnic and racial
differences
o Due to differences in
environmental and dietary
exposures
5. The Cancer Problem
a. Most common CA PCS-DOH cancer
registry (1997)
Males
Females
Both
Lung
Breast
Breast
Liver
Cervix uteri Lung
Prostate
Lung
Liver
Leukemia Ovary
Cervix
Colon
Colon
Colon
b. Poor survival attributed to:
- Advance stage
- Incomplete treatment
- Inadequate supportive care
(economic constraints)
c. Determinants for late diagnosis
- Economic factors
- Lack of cancer awareness
- Fear of CA
6. Etiology
a. Causes:
- Genetic
- Chemical
- Physical and environmental

- Viral
b. Cancer Genetics
- Genetic disease that arise from
accumulation of mutations that
leads to the selection of cells with
increasingly aggressive behavior
- Gene mutations lead to gain of
function of oncogenes or loss of
function by tumor suppressor
genes
- The individual carries a particular
germline mutation in every cell
- Investigate the genetic
background
o Crucial in planning surgical
treatment, counselling,
screening and prevention
- Factors suggestive of a
hereditary cancer
o Much younger age than usual
o Presence of bilateral disease
o Presence of multiple primary
malignancies
o Presence of a cancer in the less
affected gender
o Clustering of the same cancer
types in relatives
o Occurrence of cancer in
association with other conditions
such as mental retardation or
pathognomonic skin lesions
** Table of genes and
corresponding syndrome at the
back
c. Chemical Carcinogens
- 60-90% of CA secondary to
environmental factors/
carcinogens (chemical, physical,
viral)
- Early evidences of carcinogen =
carcinoma relation
o 1761, John Hill: excessive use of
tobacco snuff = nasal CA

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o 18th century, Percival Pott:

chimney sweeps = scrotal CA
- Groups:
o Genotoxins: cause CA by
causing mutations
o Cocarcinogens: cannot cause
CA alone by themselves, but
enhance potency of genotoxins
o Tumor promoters: enhance
tumor formation when given after
exposure to genotoxins
Carcinogen
aflatoxin
Arsenic
benzene
benzidine
beryllium
cadmium
Salted fish
chlorambucil
chromium
Coal tar/
benzpyrine
Food additives/
nitro as amine
cyclophosphamid
e
diethylstilbesterol
Ethylene oxide
ERT (estrogen)

Site
Liver CA
skin
Leukemia
bladder
Lung
Lung
N-P CA
Leukemia
Lung
Skin
GI CA
Bladder,
leukemia
Vaginal, cervical
Leukemia,
lymphoma
Endometrial,
breast
Lung, nasal
Endometrial
HCC, brain, lung
Oral

nickel
tamoxifen
Vinyl chloride
Smokeless
tobacco
tobacco
Lung, oral, etc
d. Physical Carcinogens
- Carcinogenesis through:
o Induction of chronic inflammation
and cell proliferation
Nonhealing wounds, burns,
IBD, H. pylori infection

o Exposure to physical agents that

induce DNA damage
Foreign bodies (asbestos,
silica)
Radiation (skin cancer among
Nagasaki & Hiroshima Victims)
damage to the nucleotide
bases, cross-linking and DNA
single-and double-strand
breaks
e. Viral Carcinogens
- 15% of all tumors are caused by
viruses
- Cause CA by:
o Direct transformation
o Expression of oncogenes that
interfere with cell-cycle
checkpoint or DNA repair
o Expression of cytokines or other
growth factors
o Alteration of the immune system
- ONCOGENIC VIRUSES:
o RNA
o DNA
**Table of Virus and
corresponding tumor at the back
7. Cancer Biology
a. Hallmarks of cancer:
- Physiological alterations of
malignant cells:
o Self-sufficiency of growth signals
o Insensitivity to growth inhibitory
signals
Normal cells: strict control of
cell growth and proliferation
Cancer cells: unresponsive to
normal growth controls, which
leads to uncontrolled growth
and proliferation.
o Evasion of apoptosis
(programmed cell death)
The growth of a tumor mass is
dependent on proliferation of
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tumor cells and decrease in its

apoptotic rate
o Potential for limitless
Cancer cells show alterations in
signal transduction pathways
that lead to proliferation in
response to external signals
o Angiogenesis/neovascularization
essential for growth and
metastasis
Tumors develop an angiogenic
phenotype as a result of
accumulated alterations in
response to changes such as
hypoxia
Genes that promote
angiogenesis: ras, HER2, p53
o Invasion
The ability to invade involves
changes in cell to cell
adhesion,, initiation of motility,
proteolysis of the extracellular
matrix (ECM)
o Metastasis
Hematogenous, lymphatics,
contiguous
b. Cancer initiation: steps in
tumorigenesis.
- Initiation/initiating events
o Gain of function of genes
(oncogenes)
o Loss of function of genes (tumor
suppressor genes)
- Promotion
o Accumulation of additional
deleterious mutations in clone
- Progression
o More accumulated mutations,
more aggressive behavior
o Benign in situ tumors
invasive tumors
8. Understanding oncogenes

a. Oncogenes normal cellular genes

that contribute to cancer when
abnormal
- Proto-oncogene normal
counterpart of oncogenes
- More than 100 have already been
identified
- May be:
o Growth factors (platelet derived
growth factor)
o Growth factor receptors (HER2)
o Intracellular signal transduction
molecules (ras)
o Nuclear transcription factors (cmyc)
b. Designated by 3-letter abbreviations
(myc,ras)
c. Designated by prefixes based on the
origin: v virus, ccell/chromosome
9. Cancer Risk Assessment
a. Important in the evaluation of a patient
- Determinant of screening
recommendations
- Diagnostic modalities
- Treatment planning
b. Evaluation of patients
- Complete history
o Environmental exposures
o Family history
Syndromes
Thus, risk of breast cancer3x
if mother has breast CA, 6X if
both parents have breast CA
c. Basis for genetic counseling/testing
10. Cancer screening
a. Early detection is the key to successful
cancer treatment
b. Screening modalities/schedules
- Breast (women 20 years and
above)
o Breast self examination q month
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o Clinical breast examination q 3

years (20-30yo), annually (40
yo)
o Mammogram (40 yo)
- Colorectal (50 yo and above)
o Fecal occult blood (annual)
o Flexible sigmoidoscopy or BE (q
5years)
o Colonoscopy (q 10years)
- Prostate (men 50 years and
above)
o DRE/PSA annually
- Cervical (women more than 18)
o Paps (q 2-3years)
11. Clinical manifestations
a. Can either be due to local or systemic
effects:
- Rapid enlargement tumor
outgrows blood supply
necrosis, ulceration, hemorrhage
- Infection of necrotic tissues
foul smelling discharge
- Bleeding anemia
- Tissue destruction fever
- Pancreatic CA invading celiac
plexus epigastric pain
- Lung CA invade rib cage
pain
- GI CA obstruct, bleed,
perforate
- Bone marrow anemia
- Metastasis to endocrine glands
hypo/hypersecretion
- Nodal enlargement
o Virchows node GI CA
o Axillary node breast CA
o Inguinal nodes - lymphoma
b. Causes for alarm:
- Unexplained weight loss
- Hoarseness
- Anorexia
- Unremitting epigastric pain
- Rectal bleeding
c. Danger signs

Change in bowel or bladder

habits
Sore that does not heal
Unusual bleeding or discharge
Lump in breast
Indigestion or difficult swallowing
Obvious change in wart or mole
Nagging cough or harshness in
throat
Unexplained sudden weight loss
Unexplained anemia

12. Cancer diagnosis

a. Good history
b. Complete PE
- Age should not be a barrier to dx
- Skin exams for pigmented
lesions, ulcerations, nodules
- Rectal exams, especially in
bleeding
- IE and pelvic exam
- LN exams
- Breast exams
- Scrotal palpations
c. Labs/ancillary procedures
- CBC
- F/A
- U/A
- UTZ
- Enzyme determination
- Mammography
- CT
- MRI
d. Definitive diagnosis tissue biopsy
- Obtained by:
o Endoscopic washings, smears of
secretions
o Excisional biopsy
o Incisional biopsy
o NAB, FNAB
- Requisites for a good diagnosis
o Good biopsy
o Properly selected specimen
o Adequate tissue for diagnosis
o Good pathologist
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Tumors in body cavities may not

be accessible to direct bx
laparoscopy
e. In doubt?...newer procedures
- Nuclear med studies: radioactive
isotopes thyroid and liver
scans
- Vascular studies arteriography
- CAT scan
- PET scan
- Flexible endoscopy
- Laparoscopy
f. Tumor markers
- CEA : colorectal, pancreas,
breast, lung, stomach
- AFP: liver, testes

PSA: prostate
TPA (total polypeptide antigen)
breast , gyne
CA 15-3: breast
CA 19-9, 50, 242: colorectal,
pancreas, gastric
CA125: ovarian, gyne
CYFRA 21-1: nonsmall cell lung
CA
Neuron specific enolase (NSE):
neuroendocrine
PAP (prostatic acid
phosphatase): prostate
B HCG: testicular, trophoblastic,
gestational
Erb 2: breast, ovary, stomach

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