Neuroblastoma - Cancer of the muscles

Cancer of the muscles
Also known as rhabdomyosarcoma

Cancers of genito-urinary system

Cancer of the uterine cervix
Cancer of the uterus
Cancer of the ovary
Chloriocarcinoma
Cancer of the testes
Cancer of the prostate
Cancer of the penis
Cancer of the urinary bladder
Cancer of the kidney
- Hyperneproma
- Wilm’s tumor

Cancer of the lung

Cancer of the breast
The genes BRCA1 and BRCA2 are linked to breast and ovarian cancer, whereas the MLH1 gene on human chromosome 3 is associated with colon cancer and MMAC1 gene mutates to generate a protein responsible for brain and prostate cancer

Cancer of thyroid

Cancers of gastro-intestinal tract


Cancer of the mouth
Cancer of the oesophagus
Cancer of the stomach
Cancer of the colon and rectum
Cancer of the liver
Cancer of the gall-bladder
Cancer of the pancreas

Cancer of the brain

Glioma
medullobastoma

Mix of cancers

The cases become extremely complex when one type of cancer pretends to be another or when a mix of cancers accidentally is identified as cancer of only one type
Some particular subtypes of acute leukemia have been found to be associated with specific chromosomal translocation
The samples for testing cancer or leukemia comprises of bone marrow and peripheral blood samples and thereafter RNA prepared from bone marrow or blood cells would be hybridized

ALL/AML

AML affects various white blood cells including granulocytes, monocytes and platelets
Leukemic cells accumulate in the bone marrow, replace normal blood cells and spread to the liver, spleen, lymph nodes, central nervous system, kidneys and gonads
ALL is a cancer of immature lymphocytes, called lymphoblasts (sometimes called as blast cells). Normally, white blood cells repair and reproduce themselves in an orderly and controlled manner but in leukemia the process gets out of control and the cells continue to divide, but do not mature
ALL is further divided into two subcategories viz., T-lineage ALL and B-lineage ALL

Leukemias and lymphomas

Leukemias
Acute leukemia
Chronic leukemia
Lymphoma
Hodgkin’s lymphoma
Non-Hodgkin’s lymphoma

Types of cancers known

lung
breast
thyroid
nerve system
muscles
genito-urinary system
leukemia
lymphoma
skin
brain
bone
gastrointestinal tract

Detailed Look into Cancers - Broad groups of cancers

Carcinoma – any cancer that arises in epithelium, tissue that lines the skin and internal organs of the body
Sarcoma – any cancer of connective tissue. These tumors may occur in any part of the body, as they arise in the tissues that make up an organ rather than being restricted to a particular organ. They can arise in fibrous tissue, muscle, fat, bone, cartilage, blood and lymphatic vessel, etc.
Leukemia – it is a cancer of the blood in which the bone marrow and other blood forming organs over-produce immature or abnormal white cells
Lymphoma – any malignant tumor of lymph nodes or lymph gland

Indian scenario

The figures given by Indian Cancer Society state that about 1.5 million people suffer from cancer at any given point of time in India
Oral cancer and cervix cancer account for the major causes of cancer in this country

Cancer situation in India

Approx. 500,000 new cases of cancer occur every year in India
As the human life span is increasing in India, more cases of cancer are observed here also
Cancer is thus regarded as an emerging health problem in India
According to Dr. D J Jussawalla, Indian Cancer Society, “Cancer is one of the 10 leading causes of death today in India, and is advancing in rank year by year”

Cancer situation in the World

Cancer is the second common cause of death in the developed countries next to cardiovascular (heart and blood vessel) disease
In Europe and North America, approx. 1-5 die of cancer
According to WHO, out of an estimated total of 50 million are attributed cancer, and the number of deaths from cancer throughout the world is increasing

Cancer in older people

Small microscopic cancers of the prostate were very common in males
Lung and stomach cancer were seen in many cases both in males and females
Lung cancer of the type of adenocarcinoma, was found often and was commoner in females than males
Multiple cancers arising in different organs at the same time was not an uncommon feature
Lesions regarded as precursors to cancers were often observed in stomach, colon and lungs
The rate of growth of cancers in general was slow

Cancer on older people

Cancer occurs more often in people after 50 or 60 years of age
In still older people, i.e. 80 years or above, some characteristics of cancer have been noted during life and in post-mortem studies of people who have died of causes other than cancers.

Any manifestation may be cancer…

A lump or hard area in the breast
A change in a wart or mole
A persistent change in digestive and bowel habits, e.g. constipation
A persistent cough or hoarseness in a smoker
Bleeding of vagina at times other than the menstrual
Non-injury bleeding from the surface of skin, mouth of any other bodily orifice
Any ulcer that does not get well
Unexplained loss of weight
Unexplained diminished or lost appetite
Unexplained low-grade fever

Signs and symptoms

Cancers of various types and at various sites manifest themselves in a variety of ways
On external surface, any thickening of the tissues, formation of nodule or tumor, persisting sores and ulcers, can be feature of cancer
Internal cancers may grow for some time before they cause any symptom. But weight loss, anaemia and low-grade fever in older people even without any other symptom, should arouse suspicion

Support sciences

It was found that genes useful for cancer class prediction may also provide insights into cancer pathogenesis and pharmacology
The National Cancer Institute in USA maintains a project called Human Tumor Gene Index. More than 50,000 genes active in one or more cancers have been identified; with over 6,000 genes active in breast cancer cells, 277 that are not active in other tissues

Support sciences

Interpretation of tumor data would involve an experienced hematophothologist for tumor morphology, histochemistry and immunophenotyping analysis
Histopathology is the science that studies pathologic tissues. Just as in the case of all other branches of biological sciences, bioinformatics is poised to bring monumental changes to this branch as well. It is expected that it would also greatly influence the cancer pathogenesis and pharmacology

Fighting cancer

Fighting cancer is not just hoping to discover a “magic bullet” to annihilate it
It is much broader a problem
Early detection
Curative measures
Rehabilitation of the patients
Psychological problems faced by the patient and relatives

Cancer cure is expanding…

In the 1950s, only 30 percent cancers were curable
By 1977, that percentage had risen to 41
By 1980, 45 percent of all serious cancers were curable
This percentage is increasing fast

Is cancer inherited?

There are cases of some families, several members of which have suffered from cancer
Scientists have propagated some strains or breed of mice in which a large number of males developed lung cancer and over 90 percent of females breast cancer
A careful analysis of data shows that certain types of cancer are hereditary and there is a likelihood of cancer of a particular tissue or organ developing in the descendants of persons who have suffered from cancer

How does cancer spread?

Cancer spread occurs through any or all of the three routes
Local spread: cancer infiltrates the adjoining parts, organs, tissues, etc.
Lymphatic spread: the lymph glands or nodes trap the cancer cells present in the lymph fluid and cancer grows within them. Progressive spread along lymph vessels and glands may occur and in the process quite distant glands may become involved

Bloodstream spread: if cancer invades blood vessels then the cancer cells may break into the bloodstream and be carried to other parts of the body and settle over there, producing secondary cancers. The major site of spread in cases of bowel cancer is liver. The lungs are the commonest site of metastasis from other cancer sites. The spread to many other organs is also common

Tumor

Growth of cancer cells leads generally to formation of a nodule or tumor; hence cancer is also called a tumor
If it is superficial, it is firm to touch, gets fixed to surrounding tissues and is not freely moveable
However, every nodule is not cancer
Some like warts, cysts, or adenomas are benign and are easily treated
But in order to be sure whether a nodule is cancerous, a bit of the nodule is taken and examined under the microscope, which generally gives a correct diagnosis

Fast and slow-growing cancers

A cancer may be slow- or fast-growing
The rate of growth depends on the tissue in which it occurs and also on the inherent character of the type of cancer
Rapidly growing cancers are those which send metastasis in other organs, are much more dangerous
Sometimes the primary cancer in the first stage of development grows slowly, as for example, that of the stomach and remains unnoticed, while the secondaries spread rapidly in the liver, abdominal lymph glands, etc. These secondary cancers are first noticed

Cancer cells vs. normal cells

Cancer cells are different from normal cells in some aspects
They do not remain confined to one part of the body
They penetrate and infiltrate into the adjoining tissues and dislocate their function
Some of the cancer cells get detached from the main mass or site of origin and travel by blood cell and lymph channels to sites distant from the original tumor and form fresh colonies, called metastasis or secondary growths, in other organs where they grow at the cost of the normal cells
This is how they destroy the well-regulated functioning of the body and bring about its end

Other causes of cancer

Genetic and personal factors – age, sex, race, marital status, heredity, socio-economic status
Immune deficiency
Environmental
Virus, e.g., polyoma virus causes leukemia

Physico-chemical causes of cancer

Benza pyrene (found in coal, tar, etc.)
Asbestos causes mesothelioma, cancer of the pleura
Dyes, synthetic colors
Aromatic amines, polycyclic aromatic hydrocarbons
Urethane
Metals like nickel, chromium, arsenic, beryllium
Harmones
Aflatoxin, pesticides, insecticides
Diethy stilbesterol (medicinal compound/female sex harmone)

Cancer cause

Cancer arises from the abnormal and uncontrolled division of cells, known as cancer cells, that then invade and destroy the surrounding tissues
Cancer cells, in other words, refuse to stop multiplying and continue to increase in number
It is the failure to stop multiplying which is the hallmark of cancer
This they do even at the cost of other normal cells of body which are starved to death for lack of nutrition

Cancer treatment

Cancer being more common in older people, increasing life span of man is providing more and more candidates for getting the disease
Surgery to treat it has been used since centuries ago
Radiation was used to treat breast cancer within one year of Roentgen’s discovery
World War II provided the first drug in the form of nitrogen mustard to kill cancer cells

Cancer

It has existed all along with man
Twenty-five centuries ago, Hippocrates, called it karkinois because the swollen blood vessels going and coming from the tumor mass, gave the appearance of the claws of a crab
Susruta described cancer as a tumor which would ulcerate and would not cure, and “sow its seeds in other parts of the body”

Life style drugs

Toe nail fungus
Obesity
Baldness
Face wrinkle
Erectile dysfunction
Separation anxiety of dogs, etc.

Main targets for drug design as per WHO report Jan 2002

AIDS
Tuberculosis
Malaria

Third world diseases

Asthma
Cystic fibrosis
Huntington’s disease
Sickle cell anemia
Malaria
Tuberculosis
Typhoid
HIV/AIDS
SARS

The HP virus

After breast cancer, cervical cancer kills more women each year than any other cancer
It is particularly so in developing countries, where screening is not widespread
Lasting infection from certain strains of a common sexually transmitted virus – human papilloma virus (HPV) – causes almost all cervical cancers
HPV was first linked to cervical cancer in 1983
Infection most in women of age group 16-23 years

AIDS tests have a flaw?…

The ELISA and Western Blot tests look for
the antibodies to HIV in blood
samples
But these antibodies are also found in samples
of patients whose immune systems have been
activated by several other conditions – like
tuberculosis, multiple sclerosis and even
warts
These two tests actually look for the p24 protein
which is found in healthy persons
also

Canadian team sequencing SARS virus

Scientists from the Genome Science Centre
at the British Columbia Cancer Agency are
sequencing the Severe Acute Respiratory Syndrome
(SARS) virus
30 genome researchers from 11 countries are involved
in the project
Early identification using electron microscopy,
PCR and viral microarray have identified the SARS
virus as a corona virus

DNA repair

Using yeast genome, scientists discovered the fundamental mechanism cells use to control how and when they divide
This has enlightened everyone about cell division and DNA repair, processes that are important in cancer diagnosis and control
One of the findings is that the common chemotherapeutic drug ‘cisplatin’ is particularly effective in killing cancer cells that have s specific defect in their ability to repair their DNA

The p53 protein

One of the fly genes with a human counter part is p53,
a so-called tumor suppressor gene that when mutated allows
cells to become cancerous
The p53 gene is part of a molecular pathway that
causes cells that have suffered irreparable genetic damage
to commit suicide
It was identified that just as in human cells, fly cells
in which the p53 protein is rendered inactive, lose the ability
to self-destruct after they sustain genetic damage and instead
grow uncontrollably

Some noted works

Golub, Slonim et al (1999) published a paper on
molecular classification of cancer.
This relates to their study of class discovery
and class prediction by gene expression monitoring

Slonim, Tamayo et al (2000) subsequently studied
class prediction and discovery using gene expression
data

Ramaswamy et al (2001) brought out multiclass
cancer diagnosis using tumor gene expression
signature

smaller sets are preferred for processing…

Large samples of over 200 genes are not helpful
since if all of them are correlated with a particular
class, it is unlikely that they all represent
different biological mechanisms and hence are
unlikely to add information not already provided
by others
Though excellent research work has been carried out
in last three decades, there are no general approach
for identifying new cancer classes (class discovery)
or for assigning tumors to known classes
(class prediction)

Foundations - Bioinformatics and disease link

Gene expression data analysis could give important
clues for reasons behind cause of various diseases,
especially about the behaviour and growth of disease
causing germs

Communicable diseases – malaria,
typhoid, cholera

HIV/AIDS

Cancer

Dengue

Medical informatics

Part 1 – Foundations
Part 2 – Cancer
Part 3 – Detailed Look into Cancers
Part 4 – Response of Cancers to Chemotherapy

Definition of Risk Assessment

at the margin of our understanding of
the health effects of chemicals and
other substances

best defined as the determination of
pathology caused by human
production and activity, with the
understanding that "pathology" is a
change in some aspect of human
anatomical structure or function

Definition of Risk Assessment

Risk Assessment, or risk evaluation,
is a scientific/ mathematical discipline
which is

a substantive, changing and
controversial field

Risk Analysis

This is the overall term for all of
Risk Science

It has four elements:

- Risk Assessment (Risk Evaluation)

- Risk Communication

- Risk Perception

- Risk Management (Risk Characterization (EPA))

Buzzword Alert!

There are a number of technical
terms in this lecture

Yes, you have to know them!

These terms have precise
meaning, even though you will
often see them MIS-used.

Since risk assessment is (or aims
to be) a scientific activity we must
agree on terminology

Risk Assessment

Definitions: Risk Analysis, Risk Assessment
(Evaluation) and their components

A detailed look at HAZARD EVALUATION

Risk Perception, Risk Communication, Risk
Management

An example of risk assessment: Mesothelioma
among Quebec asbestos mining area women.

Risk and the precautionary principle

Malignant Mesothelioma - Conclusion

The increasing incidence worldwide of
malignant mesothelioma has created
an awareness of the need for new
ways to treat this disease.

In the meantime, we should continue
to provide extremes psychosocial
support as well as palliative care for
our patients with MM.

Malignant Mesothelioma - Treatment

Surgery:
most useful for palliation – for local
control of recurrent effusions. This can be either
radical resection (extrapleural pneumonectomy) or
debulking surgery vs VATS.

Chemotherapy:
poor response rates (15-20%) in
most cases. Pemetrexed and cisplatin, Gemcitabine
with cisplatin are common chemo-regimen used
currently.

Radiotherapy:
MM is resistant to traditional
radiotherapy. Local radiation to surgical sites
prevent seeding of tumor, and can provide
palliative relief of somatic chest-wall pain.

Immunotherapy:
studies in animal and clinical
trials have shown some tumor response to trials of
IFN-alpha, intrapleural IL-2, GM-CSF

Malignant Mesothelioma - Prognostic Factors

Median survival of patients with MM from time of
diagnosis is approx 12 months.

Worse prognosis in the following pts:

1. Male
2. Those with extensive diseases
3. Poor performance status
4. Elevated white-cell counts, Anemia,
Thrombocytosis
5. Sarcomatoid histologic findings
6. Expresssion of certain biochemical
markers(VEGF), evidence of SV40 virus in the
tumor

Histopathology

Since cytologic findings may be inconclusive at
times, tumor biopsy is often needed.

Cytokeratin staining helps to confirm invasion and
to distinguish MM from sarcoma or melanoma.

MM is characterized by the presence of staining for
EMA, calretinin, WT1, mesothelin, and the absence
of staining for antigens such as CEA, tumor
glycoproteins B72, MOC-31.

Electron microscopy also helps to distinguish MM
from adenocarcinoma or to differentiate
desmoplastic or sarcomatoid mesothelioma from
fibrous pleuritis.

Malignant Mesothelioma - Cytology

Cytologic evidence of MM in the pleural or ascitic
fluid is found in 33-84% of cases.

A group of immunohistochemical markers is
important in the diagnosis of MM.

Initially, one has to differentiate if the tissue is
mesothelial in origin by checking for the presence
of markers such as calretinin, WT 1 antigen.

Secondly, one has to determine if the cells are
malignant by testing for the marker known as
epithelial membrane antigen (EMA, aka CA 15-3
and mucin-1)

Cytologic analysis is sufficient to make a diagnosis
with a high level of confidence in about 80% of the
cases, if done by an experienced pathologist.

Malignant Mesothelioma - Diagnostic Imaging

CXR: shows pleural effusion, and
occasionally may show a pleural-based
mass.

CT chest: often show pleural effusion alone
(74%) or pleural-based masses (92%) +/-
thickening of the interlobular septa (86%).

MRI: is useful in determining the extent of
the disease. To see if there is invasion of
local structures such as ribs, diaphragm, etc

PET scan: helps to distinguish benign from
malignant pleural masses. It is also useful
for detecting extrathoracic disease,
especially, if there is lymph-node
involvement.

Malignant Mesothelioma - Clinical Features

Unexplained pleural effusions with
dyspnea, as well as chest wall pain

About 80% of patients with pleural
malignant mesothelioma are male.

Cancer Syndrome: wt loss, fever, night
sweats, cachexia, fatigue,
thrombocytosis, high ESR, low
albumin, and anemia. Are usually
manifested in the later stages.

Asbestosis: The Ancient Curse - Pathogenesis

There are 4 principal processes by which asbestos
affects the pleura

The fibers irritate the pleura, thereby inducing
scarring or a more malignant process

The fibers may pierce the mitotic spindle of cells,
thereby disrupting mitosis leading to
chromosomal damage

They also induce the generation of iron-related
reactive oxygen species (ROS) causing DNA
damage

Asbestos also induces phosphorylation of the
mitogen-activated protein (MAP) kinases which
increases the expression of early-response proto-
oncogenes

Asbestosis: The Ancient Curse

Epidemiology

Incidence of malignant mesothelioma is
rising worldwide due to exposure to
asbestos especially in developing countries

In the 1960s, the first evidence of a link
btw MM and both occupational as well as
incidental asbestos exposure was reported
in S. Africa

It may have reached its peak in the U.S
since people are now more aware of the
dangerous effects of asbestos.

Asbestos Exposures, Inhalation of Asbestos, Diagnosis, Management

Asbestos exposures peaked in the United
States in 1940-1980, but continue to occur
today

Inhalation of asbestos can lead to

- parenchymal asbestosis,
- pleural abnormalities,
- lung carcinoma, and
- mesothelioma

Diagnosis involves

- exposure and medical history,
- physical examination,
- chest radiography,
- pulmonary function tests, and
- other tests as needed

Management focuses on:

- Preventing further exposures
- Smoking cessation
- Monitoring to aid early detection
- Patient education

Communication with the Patient

Obtain patient’s employer contact
information to facilitate occupational
exposure prevention (OSHA mandates 
PPE and medical surveillance)

Counsel patient regarding smoking
cessation

Have patient consult you for health changes

Provide and review patient education and
instruction sheet with patient

Lung Cancer and Mesothelioma - Disease Management

Treatment Strategy

- Early diagnosis

- Surgery

- Chemotherapy

- Radiation

Disease Management

Asbestos-associated
Disease

Parenchymal
Asbestosis and
Asbestos-Related
Pleural Abnormalities

Treatment Strategy

Stopping additional exposure

Careful monitoring to facilitate early diagnosis

Smoking cessation

Regular influenza and pneumococcal vaccines

Pulmonary rehabilitation as needed

Disability assessment

Aggressive treatment of respiratory infections

Other Tests

CT and HRCT

BAL and lung biopsy

ABGs and pulse oximetry

Colon cancer screening

Chest Radiograph Findings: Mesothelioma

Pleural effusions

Pleural mass

Diffuse pleural
thickening

Chest Radiograph Findings: Asbestos-Related Pleural Abnormalities

Pleural plaques

Areas of pleural thickening

Sometimes with calcification

Pleural effusions

Diffuse pleural thickening

Lobulated prominence of 
pleura adjacent to thoracic margin
(over ¼ of chest wall)
Interlobar tissue thickening

Rounded atelectasis

Rounded pleural mass

Bands of lung tissue radiating outwards

Chest Radiograph Findings: Parenchymal Asbestosis

Small, irregular oval
opacities

Interstitial fibrosis

“Shaggy heart sign”

Pulmonary Function Tests

Disease

Parenchymal Asbestosis

Pulmonary Function Test Findings

Reduction in FVC; normal FEV1/FVC Ratio

Reduction in FEF (25%-75%)

Restrictive pattern with decreased DLCO

Or, mixed obstructive/restrictive pattern
(reduced FEV1/FVC associated with
reduced FVC)

Disease

Asbestos-Related Pleural Abnormalities

Pulmonary Function Test Findings

Often normal

Reduced FVC can be associated with
diffuse pleural thickening

Physical Examination

Focus on lungs, heart, digits, and
extremities

Pulmonary auscultation to detect
bibasilar inspiratory rales (not always present)

Observation of other signs, such as
clubbing of the fingers and cyanosis

Patient History

Exposure History :

Work history

Source, intensity, duration, and 
frequency of exposure

Time elapsed since first exposure

Workplace dust measurements or description of
exposure scenario

Use of personal protective equipment

Paraoccupational exposures

Sources of environmental exposure

Medical History :

History of smoking

History of other conditions

Mesothelioma - Signs and Symptoms

Disease

Mesothelioma

Signs and Symptoms

Usually: None (until later stages)
Sometimes: Dyspnea, chest pain, and fatigue

Lung Cancer - Signs and Symptoms

Disease

Lung Cancer

Signs and Symptoms

Usually: None (until later stages)
Sometimes: Fatigue, weight loss, or chest pain

Clinical Presentation

Disease

Asbestos-Related

Pleural Abnormalities

Signs and Symptoms

Usually: None

Sometimes: Progressive dyspnea and intermittent
chest pain (depending on the type of pleural
abnormality)

Clinical Presentation

Disease

Parenchymal Asbestosis


Signs and Symptoms

Insidious onset of dyspnea on exertion
Fatigue

Diagnosis

Medical evaluation of all patients should
include:

- Assessment of clinical presentation

- Exposure history

- Medical history

- Physical examination

- Chest radiograph and pulmonary function
tests

Radiologic and laboratory testing can include:

- CT or HRCT

- BAL

- Lung biopsy (rarely needed)

Risk Factors

Nature and extent of exposure:

Concentration of asbestos fibers

Duration of exposure

Frequency of exposure

Cigarette smoking

Other Extrathoracic Cancers

Colon cancer

Possibly cancer of larynx, stomach,
kidney, esophagus

Association with asbestos exposure
remains controversial

Regular colon cancer screening for
people over age 50 years

Screening for other extrathoracic 
cancers not recommended

Malignant Peritoneal Mesothelioma

“Doughy” feeling on abdominal
palpation

Male:female incidence is 1.5:1
(compared to 5:1 with pleural tumor)

Rapidly invasive and rapidly fatal

Often associated with high-dose
asbestos exposures

Rare

Malignant Pleural Mesothelioma

Tumor arises from the thin serosal
membrane surrounding the lungs

Rapidly invasive

Rare, although incidences are
increasing

Long latency period: Usually 30-40 years

Lung Carcinoma

Risk depends on:

Level, frequency, and duration of exposure

Time elapsed since exposure

Age at time of exposure

Smoking history (synergistic)

Individual susceptibility factors (under
investigation)

Latency period: 20-30 years

Asbestos-Related Pleural Abnormalities

Four types of abnormalities:

- Pleural plaques

- Benign asbestos pleural effusions

- Diffuse pleural thickening

- Rounded atelectasis

Mostly asymptomatic, though some
can cause dyspnea or cough

Latency periods: 10-30 years 
(shorter latency is for pleural effusion)

Parenchymal Asbestosis

Diffuse interstitial fibrosis with:

- Restrictive pattern of disease on pulmonary
function testing (but can see mixed pattern)

- Impaired gas exchange

- Progressive exertional dyspnea

Radiographic changes: >10 years

Latency period: 20-40 years

Asbestos-Associated Diseases

Respiratory diseases:

Parenchymal asbestosis

- Asbestos-related pleural abnormalities

- Lung carcinoma

- Pleural mesothelioma

Nonrespiratory diseases:

- Peritoneal mesothelioma

- Possibly, other extrathoracic cancers

- Rarely, cor pulmonale or constrictive pericarditis

Pathogenesis

Asbestos fibers induce pathogenic
changes via:

- Direct interaction with cellular macromolecules

- Generation of reactive oxygen species (ROS)

- Other cell-mediated mechanisms

These changes can lead to cell injury,
fibrosis, and possibly cancer

Asbestos is genotoxic and carcinogenic

Biologic Fate

Asbestos bodies

Lower airways and alveoli

Pleural or peritoneal spaces or the
mesothelium


Asbestos bodies

Asbestos Exposure Pathways

Most common exposure pathway:

- Inhalation of fibers

Minor pathways:

- Ingestion

- Dermal contact

Populations At Risk - Asbestos - Current Exposures

Construction workers, mechanics
(brake pads)

People in homes with friable
asbestos materials

People in areas where asbestos
-bearing rock is disturbed

Populations At Risk - Asbestos - Past Exposures

Mechanics, construction workers,
shipyard workers, and military
personnel

Secondary exposure in the
workplace

Household contacts of workers

Asbestos: Types

Serpentine
(93% of commercial use)



Chrysotile
(7% of commercial use)

Actinolite, Amosite,
Anthophyllite, Crocidolite,
Richterite, Tremolite

Asbestos: Occurrence in the United States

Until 1975: Automobile, building
construction and shipbuilding
industries

Until 1990: Contaminant in vermiculite

Today: Exists in older homes and
commercial buildings

- problematic when loose, crumbling, or disturbed

Today: Still used in brake pads, clutches,
roofing material, vinyl tiles, and some 
cement pipes

Naturally occurring asbestos is found in
parts of the U.S. areas in asbestos bearing
rocks. It is released:

- when disturbed
- as rocks weather

Asbestos: Description

Asbestos is a generic term for a group
of six mineral silicates

- Asbestos fibers are:

- Very strong

- Highly flexible

- Resistant to breakdown by acid, alkali, 
water, heat, and flame

- Non-biodegradable

- Environmentally persistent

Asbestos - Learning Objectives

What is asbestos?

Most important route of exposure

Populations most heavily exposed

Diseases associated with asbestos
exposure

Common findings on medical evaluation

Chest radiograph findings

Pulmonary function test findings

Other tests that can assist with
diagnosis

Primary treatment strategies

Instructions for patients

Prognosis

Mesothelioma patients prognosis in
large part depends on which type of
mesthelioma they have.
With the new drug Alimta and
chemotherapy, as well as surgery
mesothelioma patients are beginning to
live longer than they could have hoped
for in the past.

Surgery

Surgical removal is possible in some

cases but in many cases removal of the

tumor alone is not enough.

There are also many cases in which

surgery is not an option.

Side Effects

Alimta has also improved lung function

in many patients.

Side effect include low white blood cell

counts, vomiting, nausea, fatigue,

diarrhea, and rash.

However, taking folic acid and the

vitamin B12 helps reduce the intensity

of side effects.

Alimta

In a clinical study of 448 patients Alimta

was successful in increasing survival

time of patients by approximately 30%.

Alimta is administered in one ten

minute infusion every three weeks.

It has also shown great results in

conjunction with cisplatin, a standard

chemotherapy drug.

Treatments

Treatment options for all three types of

mesothelioma are the same.

Until recently there was no effective

treatment for mesothelioma.

A new drug, Alimta, was recently

approved by the FDA.

Mesothelioma Diagnosis

Since symptoms of mesothelioma,

which can include pain in the lower

back and shortness of breath, are often

mistaken for other problems,

mesothelioma is most frequently not

diagnosed until it is in an advanced

stage.

Types of Mesothelioma

Mesothelioma can be divided into three
different types.

Epithelioid- which has the best
prognosis out of the three types.

Sarcomatoid- which has about a 7 –
20% survival rate.

Mixed/biphasic- which has about a 20 –
35% survival rate.

Malignant Mesothelioma

Tumors found in the mesothelioma can
be both benign or malignant.
Malignant tumors are often called
malignant mesothelioma or just mesothelioma.

About the cancer

Mesothelioma is most often a cancer

associated with large amounts of

exposure to asbestos.

This cancer affects about 2,000 to

3,000 Americans every year.

Mesothelioma

Mesothelioma is a rare lung cancer that

begins in the mesothelium.

The mesothelium is made up of mesothelial

cells which line the chest and abdominal

cavities as well as the cavity around the

heart.

The mesotheiom also produces a lubricating

fluid that allows the organs to move easily.

Major Route To Exposure To Asbestos

The major route of exposure to asbestos is
inhalation

There is no known “safe” level of exposure
Tightly bound asbestos poses no immediate
hazard

Asbestos becomes a health hazard when fibres
become airborne

Exposure should be minimised by sensible
precautions

What is a safe level of exposure to asbestos?

The level of exposure that may cause health
effects is not known.

It is therefore important to keep exposure to
asbestos fibres as low as possible and
precautions must always be taken.

What is the risk from a one off exposure?

The risk has not been quantified, but except for
intense exposures, the risk caused by brief
exposure is likely to be undetectably low..

Exposure to asbestos fibres in air

Small quantities are present in air breathed by
most people without developing asbestos-
related disease

People who have developed disease from
asbestos were exposed to workplace air levels
around 5 fibres/ml

Measured E in public buildings, schools

0.0001- 0.0005 fibres/ml.

Life-time E at this level < 1 in 100,000 life-
time cancer risk.

Mesothelioma

Pleural Mesothelioma

Malignant mesothelioma

Rapidly fatal : 75% dead 1 year after
diagnosis

Smoking has no apparent effect on risk

Symptoms: short of breath, chest pain,
weight loss

Has occurred in people without direct
occupational exposure but exposed to large
quantities of dust

Malignant mesothelioma

Rapidly fatal : 75% dead 1 year after
diagnosis

Smoking has no apparent effect on risk

Symptoms: short of breath, chest pain,
weight loss

Has occurred in people without direct
occupational exposure but exposed to large
quantities of dust

Malignant mesothelioma

a cancer of the lining of the lung and chest
cavity (pleural mesothelioma) (2/3)

or the lining of abdominal cavity (peritoneal
mesothelioma)

can take 30 to 50 years to develop

particularly associated with crocidolite

Australia has world’s highest incidence

Lung Cancer Image

Cancer site, lymph glands

Lung cancer And Asbestos

usually takes 10 to 20 years to develop after
asbestos exposure.

asbestos in non-smokers: 5x background
rate

asbestos in smokers: 50x background rate

Symptoms: persistent cough, weight loss, cough up blood

Asbestosis Diseased Person

Asbestosis

A chronic and progressive lung disease
caused by inhaling asbestos fibres over a long
period of time.

5- 20 years to develop

inflammation from fibres causes scarring
(fibrosis) and stiffening of the lung. This
causes less oxygen exchange

Symptoms – short of breath, cough, chest tightness

Pleural plaques Image

Pleural plaques

Pleura: 2 layers of membrane line the chest
wall & cover the lungs

asbestos may produce thickened patches

is not cancerous but can affect lung function

generally no symptoms

indicates significant previous exposure

Common in occupational E & sometimes
where high environmental levels

Cancer

Lung Cancer

Asbestos related diseases

All forms of asbestos can potentially cause:
Non cancer
pleural plaques
asbestosis
Cancer
lung cancer
malignant mesothelioma

Asbestos

Exposure to Asbestos

What are the health effects of exposure to asbestos?

Asbestos becomes a health hazard when
fibres become airborne and are inhaled.

Effects depend on length, diameter and
composition of fibre

Disease is usually associated with long-term
exposure in occupational or para-occupational
setting (immediate family or live near asbestos
mine or factory)

Risk depends on how much and how long

Asbestos

Non friable (bound) asbestos

AC sheeting (fibro)
flexible building boards
flue & water pipes
Vinyl floor tiles
Ceiling insulation

Friable asbestos material unlikely to be found in homes in Victoria

a dry material which can be reduced to powder by hand pressure.
a health risk as it becomes airborne and more likely to be inhaled.
eg: insulation inside stoves & heaters
industrial grade insulation in commercial
buildings

Different forms of asbestos material have different levels of risk

Friable (nonbound) vs bound asbestos

Where asbestos fibres are stable and bonded in good condition, little risk

However when broken, damaged or mishandled, fibres become loose and airborne, creating hazard

Where do you find Asbestos?

Over 3,000 uses of asbestos known
in majority of homes built before 1990
asbestos-cement products
electrical, thermal & acoustic insulation
fire resistant insulation

Why was it used?

Asbestos was commonly used 1940 - 1980s for
Durability
Fire resistance
Excellent insulating properties

Blue asbestos, White asbestos, Brown asbestos

Most common types of asbestos used in Australia

Serpentine
Chrysotile (white asbestos)
Amphibole
Amosite (brown asbestos)
Crocidolite (blue asbestos)

What is asbestos?

A group of naturally occurring minerals whose characteristic feature is that they occur as fibres
Masses of tiny fibres form dust if disturbed

The health effects of asbestos exposure

Dr Marion Carey
Senior Medical Adviser
Social and Environmental Health
Dept of Human Services