Transcript The body`s response to cancer

Human Disease Processes 1:
The body’s response to cancer
This lesson aims to:
 Discuss the risk factors involved in cancer formation
 Describe the local and systemic effects of cancer
 Discuss mechanisms that the immune system uses to
clear tumour cells and the difficulties involved
 Discuss common treatment of cancer
 Discuss the prognosis of cancers and the principles of
palliative care
© Krejany and Morrison 2003
HDP1 The body’s response to cancer
Lesson 11 - Overhead 1
The Growth of Cancer
“Cancers grow by progressive
infiltration, invasion, destruction and
penetration of the surrounding
tissue”
- Kumar, Cotran, Robbins
Basic Pathology, 7th Ed, 2003
© Krejany and Morrison 2003
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Pathophysiology of Cancer
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A tumour manifests as an enlarging spaceoccupying mass
Expansion compresses the local area and local
structures including blood vessels
Lack of blood flow leads to necrosis and therefore
inflammation around the tumour site
Malignant cells can break free from the tumour
and infiltrate local tissue, blood vessels and
lymphatics (metastasis)
Some neoplasms develop in this way very quickly
whereas others take a lot longer and offer better
diagnostic and treatment potential
© Krejany and Morrison 2003
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Growth
As the mass enlarges the innermost cells
are frequently deprived of nutrients and
die
 Many tumour cells trap nutrients depriving
normal cells and therefore preventing
tissue regeneration
 Inflammation and the loss of normal cells
leads to a progressive loss in organ
function
 For the tumour to be able to grow beyond
1-2 mm in diameter it must be
vascularised
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Angiogenesis
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Branches extend from pre-existing capillaries to
generate new blood vessels (neovascularisation)
This is a normal process which is important in
tissue healing and regeneration; developing
alternate routes of microcirculation at sites of
ischemia
This process can be induced and when this occurs
facilitates tumour growth by allowing nutrient
supply to growing tumour cells
Tumours are capable of synthesising additional
growth factors which promote angiogenesis to
supply the tumour with nutrients
© Krejany and Morrison 2003
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Angiogenesis
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Effects of Tumours on the Host
 Benign
are less serious than
malignant
 Both can cause problems through
compression or obstruction,
alteration of hormone synthesis,
bleeding and infections
 Malignant tumours cause additional
problems
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Local Effects of Tumours
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Pain
– Absence of pain in early formation, presence in
advanced stages
– Severity of pain depends on tumour location
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Potential causes of pain
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Direct pressure on nerves
Stretching of a visceral capsule
Infection
Ischemia
Bleeding
Irritation of nerve endings by chemical
mediators
© Krejany and Morrison 2003
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Local Effects of Tumours
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Obstruction
– compression of duct or passageway
– Blood supply or lymphatic flow leading to
ulceration or oedema
– Air flow
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Tissue necrosis and ulceration
– Lack of blood supply
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Infection
– Opportunistic
– As a result of ulceration and cell death
© Krejany and Morrison 2003
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© Krejany and Morrison 2003
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Systemic Effects of Tumours
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Cachexia
– Contributed by anorexia, fatigue, stress, increased
demand on the body as a result of tumour cell growth
– Altered carbohydrate and protein metabolism
– Cachexic factors produced by macrophages in response
to the tumour
– This leads to added fatigue, weakness and tissue
breakdown
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Anaemia
– Decreased haemoglobin as a result of anorexia
– Bleeding and blood loss
– Depression of bone marrow
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Infections
– increase as general immunity declines
– Frequent infections such as pneumonia are common
© Krejany and Morrison 2003
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Systemic Effects of Tumours
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Bleeding
– tumour cells may erode blood vessels or cause
tissue ulceration
– Chronic blood loss leads to iron deficiency
anaemia
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Paraneoplastic syndromes
– Additional problems associated with certain
tumours
– Substances that are released from the tumour
can have other effects such as:
 Affect
neurological function
 Blood clotting
 Hormone secretion
© Krejany and Morrison 2003
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Staging of Cancer
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Applied at the time of diagnosis
Describes the extent of the disease the
corresponding potential for treatment and
prognosis
Staging systems are based on the:
– Size of the tumour
– Extent of involvement of regional lymph nodes
© Krejany and Morrison 2003
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Example of Staging: Breast Cancer
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Stage I- tumour 2 cm or less in diameter; no
lymph nodes involved, no metastasis
Stage II- tumour less than 5 cm in diameter,
minimal involvement of local nodes, no
metastasis
Stage III- tumour larger than 5 cm in diameter,
more involvement of local nodes, tumour may be
fixed (invasive), no metastasis
Stage IV- tumour of any size but fixed to chest
wall or skin, spread of tumours to other nodes,
metastasis present
© Krejany and Morrison 2003
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Immune Evasion and Host Defence
The body tries to eradicate tumour
cells :
 Immunosurveillance
– not very successful as the tumour arises
from within the body and expresses self
antigens
 Cytotoxic
T cells and NK cells can kill
some tumour cells by lysing the cell
if they can be identified
© Krejany and Morrison 2003
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Immune Evasion and Host Defence
Problems with tumour cell eradication include:
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Poor immunogenicity:
– some tumours do not express novel proteins or peptides that the
immune system can recognise as immune cells see the tumour as a
normal part of the body.
– Also there is a lack of adhesion molecules and co-stimulatory
molecules which are required to activate the cytotoxic cells to kill.
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Antigen variation:
– Changing cell surface expression: many tumours change what is
expressed on the cell surface and/ or down-regulate MHC molecules to
evade detection.
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Immunosuppression:
– some tumours produce cytokines that suppress immune function
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Availability:
– Solid tumours- difficult for the immune cells to reach all the cells of a
solid tumour
© Krejany and Morrison 2003
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Epidemiology
Cancer epidemiology can contribute
important information about the origin of
the cancer
 The association of smoking with lung
cancer was derived from epidemiological
studies
 The recognition of the relationship of
dietary fat and fibre content of foods and
its association with colon cancer has also
been discovered through epidemiology
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© Krejany and Morrison 2003
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Cancer Incidence
1.3 million new cancer cases estimated for
2002 in the US
 555,500 people will die of cancer in the US
 Environmental factors are the most
important determinant of cancer risk for
the most common cancers
 One large study found that the risk of
cancer from environmental factor was
65% whereas the contribution of genetic
factors was between 26%- 42%
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© Krejany and Morrison 2003
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Occupational Risks for Cancers
AGENT
CANCER
OCCURRENCE
Arsenic
lung, skin
Asbestos
lung,
(mesothelioma)
Benzene
Cadmium
Leukemia
Hodgkin lymphoma
Prostate
metal smelting
alloys, electrical
devices
brake linings
heat resistant
materials
light oil, solvents
dry cleaning
solders, batteries
Vinyl chloride
liver
refrigerant, plastics
© Krejany and Morrison 2003
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Australian Statistics
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© Krejany and Morrison 2003
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Incidence of Cancer by Gender
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Incidence of Cancer by Gender
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Cancer Risk Factors
Genetic factors- oncogenes that regulate
cell growth
 Virus exposure
 Radiation-UV, sun, x-ray, gamma ray,
radioactive chemicals
 Chemicals-natural and synthetic products
ie asbestos, solvents (benzene)
 Biological factors- chronic irritation and
inflammation, age, hormones
 Diet- additives, processing methods
 Immunodeficiency
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© Krejany and Morrison 2003
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Prevention of Cancer
 Limit
sun exposure
 Reducing fat intake especially heated
saturated fats (trans FA)
 Increase anti-oxidant levels- protect
against free radicals
 Avoid carcinogens
 Practice preventative health
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Treatment
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Basic treatment measures are
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surgery
chemotherapy
radiation
combination therapy
Treatment may aim at being either:
– Curative (if the tumour is small and localised)
– Palliative (aimed at symptom control and pain
management)
© Krejany and Morrison 2003
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© Krejany and Morrison 2003
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Surgery
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Used for the removal of solid tumours
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Aimed at the removal of the tumour and the
surrounding lymph nodes
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Aims to remove the boundaries and margins of
the tumour to ensure that all of the tumour is
removed
Sometimes the complete removal of the tumour
is impossible but reduction in size of the growth
may be necessary to reduce compression or
symptoms
Often combined with chemotherapy and/or
radiotherapy
© Krejany and Morrison 2003
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Chemotherapy and Radiotherapy
Administered repeatedly at intervals that
maximise tumour killing and minimise
damage to normal cells
 Not all cancer cells are destroyed in one
treatment
 Not all cancer types are susceptible to this
type of treatment
 Treatment is usually long term whether
curative or palliative
 Serious side effects are common
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© Krejany and Morrison 2003
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Chemotherapy
© Krejany and Morrison 2003
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Side Effects of Chemotherapy
Depression of bone marrow and
dangerously low blood counts may require
transfusion
 Thrombocytopenia- haemorrhage
 Leukopenia- severe infection potential
 Vomiting – effect of the drug, damage to
the GIT
 Hair loss
 Individual drug related pathologies
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© Krejany and Morrison 2003
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Side Effects of Radiotherapy
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Depression of bone marrow therefore decreased
leukocytes
Infection risk is greatly increased
Bleeding from decreased platelets
Burns to the skin
Alopecia
Damage to digestive tract involving nausea and
vomiting, diarrhoea, malnutrition, inflammation and
ulceration, bleeding. Ulceration to oral mucosa can
occur with head and neck radiation
Sterility if radiation to abdomen
Fatigue and lethargy
Inflammation, necrosis and scar tissue formation
along the path of radiation and at the tumour site
© Krejany and Morrison 2003
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Prognosis
Cure- defined as 5 year survival with no
return of symptoms
 Remission and exacerbations are common
 Early diagnosis and treatment often limit
the extent of the illness
 Can get remissions just prior to the
disease becoming terminal
 Death rates for different cancers vary
greatly
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© Krejany and Morrison 2003
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Palliative Care Issues
Important aspects and principles of
palliative care including:
 Pain management
 Psychological support
 Spiritual counselling
 Management of symptoms
 Nutrition
© Krejany and Morrison 2003
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Human Disease Processes 1:
The body’s response to cancer
By the end of this lesson students should be able to:
 Understand the risk factors involved in cancer formation
 Understand the general clinical features of cancer
 Understand how the immune system clears tumour cells
 Understand the difficulties involved in eradicating
cancers
 Understand common treatment alternatives for cancer
 Understand the prognosis of cancers and the principles
of palliative care
© Krejany and Morrison 2003
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Lesson 11 - Overhead 35