© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 1 Human Disease Processes 1: The body’s response to cancer This lesson

© Krejany and Morrison 2003© Krejany and Morrison 2003HDP1 The body’s response to cancer HDP1 The body’s response to cancer

Lesson 11 - Overhead Lesson 11 - Overhead 11

Human Disease Processes 1:Human Disease Processes 1:The body’s response to cancerThe body’s response to cancer

This lesson aims to:This lesson aims to: Discuss the risk factors involved in cancer Discuss the risk factors involved in cancer

formationformation Describe the local and systemic effects of cancerDescribe the local and systemic effects of cancer Discuss mechanisms that the immune system Discuss mechanisms that the immune system

uses to clear tumour cells and the difficulties uses to clear tumour cells and the difficulties involvedinvolved

Discuss common treatment of cancerDiscuss common treatment of cancer Discuss the prognosis of cancers and the Discuss the prognosis of cancers and the

principles of palliative careprinciples of palliative care



The Growth of CancerThe Growth of Cancer

““Cancers grow by progressive Cancers grow by progressive infiltration, invasion, destruction and infiltration, invasion, destruction and penetration of the surrounding penetration of the surrounding tissue”tissue”

- - Kumar, Cotran, RobbinsKumar, Cotran, Robbins

Basic Pathology, 7Basic Pathology, 7thth Ed, 2003 Ed, 2003



Pathophysiology of CancerPathophysiology of Cancer

A tumour manifests as an enlarging space-A tumour manifests as an enlarging space-occupying massoccupying mass

Expansion compresses the local area and local Expansion compresses the local area and local structures including blood vesselsstructures including blood vessels

Lack of blood flow leads to necrosis and therefore Lack of blood flow leads to necrosis and therefore inflammation around the tumour siteinflammation around the tumour site

Malignant cells can break free from the tumour Malignant cells can break free from the tumour and infiltrate local tissue, blood vessels and and infiltrate local tissue, blood vessels and lymphatics (metastasis)lymphatics (metastasis)

Some neoplasms develop in this way very quickly Some neoplasms develop in this way very quickly whereas others take a lot longer and offer better whereas others take a lot longer and offer better diagnostic and treatment potentialdiagnostic and treatment potential



GrowthGrowth

As the mass enlarges the innermost cells As the mass enlarges the innermost cells are frequently deprived of nutrients and are frequently deprived of nutrients and diedie

Many tumour cells trap nutrients depriving Many tumour cells trap nutrients depriving normal cells and therefore preventing normal cells and therefore preventing tissue regenerationtissue regeneration

Inflammation and the loss of normal cells Inflammation and the loss of normal cells leads to a progressive loss in organ leads to a progressive loss in organ functionfunction

For the tumour to be able to grow beyond For the tumour to be able to grow beyond 1-2 mm in diameter it must be 1-2 mm in diameter it must be vascularisedvascularised



AngiogenesisAngiogenesis

Branches extend from pre-existing capillaries to Branches extend from pre-existing capillaries to generate new blood vessels (neovascularisation)generate new blood vessels (neovascularisation)

This is a normal process which is important in This is a normal process which is important in tissue healing and regeneration; developing tissue healing and regeneration; developing alternate routes of microcirculation at sites of alternate routes of microcirculation at sites of ischemiaischemia

This process can be induced and when this occurs This process can be induced and when this occurs facilitates tumour growth by allowing nutrient facilitates tumour growth by allowing nutrient supply to growing tumour cellssupply to growing tumour cells

Tumours are capable of synthesising additional Tumours are capable of synthesising additional growth factors which promote angiogenesis to growth factors which promote angiogenesis to supply the tumour with nutrientssupply the tumour with nutrients



AngiogenesisAngiogenesis



Effects of Tumours on the HostEffects of Tumours on the Host

Benign are less serious than Benign are less serious than malignantmalignant

Both can cause problems through Both can cause problems through compression or obstruction, compression or obstruction, alteration of hormone synthesis, alteration of hormone synthesis, bleeding and infectionsbleeding and infections

Malignant tumours cause additional Malignant tumours cause additional problemsproblems



Local Effects of TumoursLocal Effects of Tumours

PainPain– Absence of pain in early formation, presence in Absence of pain in early formation, presence in

advanced stagesadvanced stages– Severity of pain depends on tumour locationSeverity of pain depends on tumour location

Potential causes of painPotential causes of pain– Direct pressure on nervesDirect pressure on nerves– Stretching of a visceral capsuleStretching of a visceral capsule– InfectionInfection– IschemiaIschemia– BleedingBleeding– Irritation of nerve endings by chemical Irritation of nerve endings by chemical

mediatorsmediators



Local Effects of TumoursLocal Effects of Tumours

Obstruction Obstruction – compression of duct or passagewaycompression of duct or passageway– Blood supply or lymphatic flow leading to Blood supply or lymphatic flow leading to

ulceration or oedemaulceration or oedema– Air flowAir flow

Tissue necrosis and ulcerationTissue necrosis and ulceration– Lack of blood supplyLack of blood supply

InfectionInfection– OpportunisticOpportunistic– As a result of ulceration and cell deathAs a result of ulceration and cell death





Systemic Effects of TumoursSystemic Effects of Tumours

CachexiaCachexia– Contributed by anorexia, fatigue, stress, increased Contributed by anorexia, fatigue, stress, increased

demand on the body as a result of tumour cell growthdemand on the body as a result of tumour cell growth– Altered carbohydrate and protein metabolismAltered carbohydrate and protein metabolism– Cachexic factors produced by macrophages in response Cachexic factors produced by macrophages in response

to the tumourto the tumour– This leads to added fatigue, weakness and tissue This leads to added fatigue, weakness and tissue

breakdownbreakdown AnaemiaAnaemia

– Decreased haemoglobin as a result of anorexiaDecreased haemoglobin as a result of anorexia– Bleeding and blood lossBleeding and blood loss– Depression of bone marrowDepression of bone marrow

InfectionsInfections– increase as general immunity declinesincrease as general immunity declines– Frequent infections such as pneumonia are commonFrequent infections such as pneumonia are common



Systemic Effects of TumoursSystemic Effects of Tumours

BleedingBleeding– tumour cells may erode blood vessels or cause tumour cells may erode blood vessels or cause

tissue ulcerationtissue ulceration– Chronic blood loss leads to iron deficiency Chronic blood loss leads to iron deficiency

anaemiaanaemia Paraneoplastic syndromesParaneoplastic syndromes

– Additional problems associated with certain Additional problems associated with certain tumourstumours

– Substances that are released from the tumour Substances that are released from the tumour can have other effects such as:can have other effects such as:

Affect neurological functionAffect neurological function Blood clottingBlood clotting Hormone secretionHormone secretion



Staging of CancerStaging of Cancer

Applied at the time of diagnosisApplied at the time of diagnosis Describes the extent of the disease the Describes the extent of the disease the

corresponding potential for treatment and corresponding potential for treatment and prognosisprognosis

Staging systems are based on the:Staging systems are based on the:– Size of the tumourSize of the tumour– Extent of involvement of regional lymph nodesExtent of involvement of regional lymph nodes



Example of Staging: Breast Example of Staging: Breast CancerCancer

Stage I- tumour 2 cm or less in diameter; no Stage I- tumour 2 cm or less in diameter; no lymph nodes involved, no metastasislymph nodes involved, no metastasis

Stage II- tumour less than 5 cm in diameter, Stage II- tumour less than 5 cm in diameter, minimal involvement of local nodes, no minimal involvement of local nodes, no metastasismetastasis

Stage III- tumour larger than 5 cm in diameter, Stage III- tumour larger than 5 cm in diameter, more involvement of local nodes, tumour may be more involvement of local nodes, tumour may be fixed (invasive), no metastasisfixed (invasive), no metastasis

Stage IV- tumour of any size but fixed to chest Stage IV- tumour of any size but fixed to chest wall or skin, spread of tumours to other nodes, wall or skin, spread of tumours to other nodes, metastasis presentmetastasis present



Immune Evasion and Host Immune Evasion and Host DefenceDefence

The body tries to eradicate tumour The body tries to eradicate tumour cells :cells :

Immunosurveillance Immunosurveillance – not very successful as the tumour arises not very successful as the tumour arises

from within the body and expresses self from within the body and expresses self antigensantigens

Cytotoxic T cells and NK cells can kill Cytotoxic T cells and NK cells can kill some tumour cells by lysing the cell some tumour cells by lysing the cell if they can be identified if they can be identified



Immune Evasion and Host Immune Evasion and Host DefenceDefence

Problems with tumour cell eradication include:Problems with tumour cell eradication include:

Poor immunogenicity: Poor immunogenicity: – some tumours do not express novel proteins or peptides that the immune 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 system can recognise as immune cells see the tumour as a normal part of the body. the body.

– Also there is a lack of adhesion molecules and co-stimulatory molecules Also there is a lack of adhesion molecules and co-stimulatory molecules which are required to activate the cytotoxic cells to kill.which are required to activate the cytotoxic cells to kill.

Antigen variation:Antigen variation:– Changing cell surface expression: many tumours change what is Changing cell surface expression: many tumours change what is

expressed on the cell surface and/ or down-regulate MHC molecules to expressed on the cell surface and/ or down-regulate MHC molecules to evade detection.evade detection.

Immunosuppression: Immunosuppression: – some tumours produce cytokines that suppress immune functionsome tumours produce cytokines that suppress immune function

Availability:Availability:– Solid tumours- difficult for the immune cells to reach all the cells of a Solid tumours- difficult for the immune cells to reach all the cells of a

solid tumour solid tumour



EpidemiologyEpidemiology

Cancer epidemiology can contribute Cancer epidemiology can contribute important information about the origin of important information about the origin of the cancerthe cancer

The association of smoking with lung The association of smoking with lung cancer was derived from epidemiological cancer was derived from epidemiological studiesstudies

The recognition of the relationship of The recognition of the relationship of dietary fat and fibre content of foods and dietary fat and fibre content of foods and its association with colon cancer has also its association with colon cancer has also been discovered through epidemiologybeen discovered through epidemiology



Cancer IncidenceCancer Incidence

1.3 million new cancer cases estimated for 1.3 million new cancer cases estimated for 2002 in the US2002 in the US

555,500 people will die of cancer in the US555,500 people will die of cancer in the US Environmental factors are the most Environmental factors are the most

important determinant of cancer risk for important determinant of cancer risk for the most common cancersthe most common cancers

One large study found that the risk of One large study found that the risk of cancer from environmental factor was cancer from environmental factor was 65% whereas the contribution of genetic 65% whereas the contribution of genetic factors was between 26%- 42%factors was between 26%- 42%



Occupational Risks for CancersOccupational Risks for Cancers

AGENTAGENT CANCERCANCER OCCURRENCEOCCURRENCEArsenicArsenic lung, skinlung, skin metal smeltingmetal smelting

alloys, electrical alloys, electrical devicesdevices

AsbestosAsbestos lung, lung, brake liningsbrake linings (mesothelioma) (mesothelioma) heat resistant heat resistant

materialsmaterialsBenzeneBenzene LeukemiaLeukemia light oil, solventslight oil, solvents

Hodgkin lymphomaHodgkin lymphoma dry cleaningdry cleaningCadmiumCadmium ProstateProstate solders, batteriessolders, batteries

Vinyl chlorideVinyl chloride liverliver refrigerant, refrigerant, plasticsplastics



Australian StatisticsAustralian Statistics





Incidence of Cancer by GenderIncidence of Cancer by Gender



Incidence of Cancer by GenderIncidence of Cancer by Gender



Cancer Risk FactorsCancer Risk Factors

Genetic factors- oncogenes that regulate Genetic factors- oncogenes that regulate cell growthcell growth

Virus exposureVirus exposure Radiation-UV, sun, x-ray, gamma ray, Radiation-UV, sun, x-ray, gamma ray,

radioactive chemicalsradioactive chemicals Chemicals-natural and synthetic products Chemicals-natural and synthetic products

ie asbestos, solvents (benzene)ie asbestos, solvents (benzene) Biological factors- chronic irritation and Biological factors- chronic irritation and

inflammation, age, hormonesinflammation, age, hormones Diet- additives, processing methodsDiet- additives, processing methods Immunodeficiency Immunodeficiency



Prevention of CancerPrevention of Cancer

Limit sun exposureLimit sun exposure Reducing fat intake especially heated Reducing fat intake especially heated

saturated fats (trans FA)saturated fats (trans FA) Increase anti-oxidant levels- protect Increase anti-oxidant levels- protect

against free radicalsagainst free radicals Avoid carcinogensAvoid carcinogens Practice preventative health Practice preventative health



TreatmentTreatment

Basic treatment measures areBasic treatment measures are– surgery surgery – chemotherapychemotherapy– radiationradiation– combination therapycombination therapy

Treatment may aim at being either: Treatment may aim at being either: – Curative (if the tumour is small and localised)Curative (if the tumour is small and localised)– Palliative (aimed at symptom control and pain Palliative (aimed at symptom control and pain

management)management)





SurgerySurgery

Used for the removal of solid tumoursUsed for the removal of solid tumours

Aimed at the removal of the tumour and the Aimed at the removal of the tumour and the surrounding lymph nodessurrounding lymph nodes

Aims to remove the boundaries and margins of Aims to remove the boundaries and margins of the tumour to ensure that all of the tumour is the tumour to ensure that all of the tumour is removedremoved

Sometimes the complete removal of the tumour Sometimes the complete removal of the tumour is impossible but reduction in size of the growth is impossible but reduction in size of the growth may be necessary to reduce compression or may be necessary to reduce compression or symptomssymptoms

Often combined with chemotherapy and/or Often combined with chemotherapy and/or radiotherapyradiotherapy



Chemotherapy and RadiotherapyChemotherapy and Radiotherapy

Administered repeatedly at intervals that Administered repeatedly at intervals that maximise tumour killing and minimise maximise tumour killing and minimise damage to normal cellsdamage to normal cells

Not all cancer cells are destroyed in one Not all cancer cells are destroyed in one treatmenttreatment

Not all cancer types are susceptible to this Not all cancer types are susceptible to this type of treatmenttype of treatment

Treatment is usually long term whether Treatment is usually long term whether curative or palliativecurative or palliative

Serious side effects are commonSerious side effects are common



ChemotherapyChemotherapy



Side Effects of ChemotherapySide Effects of Chemotherapy

Depression of bone marrow and Depression of bone marrow and dangerously low blood counts may require dangerously low blood counts may require transfusiontransfusion

Thrombocytopenia- haemorrhageThrombocytopenia- haemorrhage Leukopenia- severe infection potentialLeukopenia- severe infection potential Vomiting – effect of the drug, damage to Vomiting – effect of the drug, damage to

the GITthe GIT Hair lossHair loss Individual drug related pathologies Individual drug related pathologies



Side Effects of RadiotherapySide Effects of Radiotherapy

Depression of bone marrow therefore decreased Depression of bone marrow therefore decreased leukocytesleukocytes

Infection risk is greatly increasedInfection risk is greatly increased Bleeding from decreased plateletsBleeding from decreased platelets Burns to the skinBurns to the skin AlopeciaAlopecia Damage to digestive tract involving nausea and Damage to digestive tract involving nausea and

vomiting, diarrhoea, malnutrition, inflammation and vomiting, diarrhoea, malnutrition, inflammation and ulceration, bleeding. Ulceration to oral mucosa can ulceration, bleeding. Ulceration to oral mucosa can occur with head and neck radiationoccur with head and neck radiation

Sterility if radiation to abdomenSterility if radiation to abdomen Fatigue and lethargyFatigue and lethargy Inflammation, necrosis and scar tissue formation along Inflammation, necrosis and scar tissue formation along

the path of radiation and at the tumour sitethe path of radiation and at the tumour site



PrognosisPrognosis

Cure- defined as 5 year survival with no Cure- defined as 5 year survival with no return of symptomsreturn of symptoms

Remission and exacerbations are commonRemission and exacerbations are common Early diagnosis and treatment often limit Early diagnosis and treatment often limit

the extent of the illnessthe extent of the illness Can get remissions just prior to the Can get remissions just prior to the

disease becoming terminaldisease becoming terminal Death rates for different cancers vary Death rates for different cancers vary

greatly greatly



Palliative Care IssuesPalliative Care Issues

Important aspects and principles of Important aspects and principles of palliative care including:palliative care including:

Pain managementPain management Psychological supportPsychological support Spiritual counsellingSpiritual counselling Management of symptomsManagement of symptoms Nutrition Nutrition



Human Disease Processes 1:Human Disease Processes 1:The body’s response to cancerThe body’s response to cancer

By the end of this lesson students should be able to:By the end of this lesson students should be able to: Understand the risk factors involved in cancer Understand the risk factors involved in cancer

formationformation Understand the general clinical features of cancerUnderstand the general clinical features of cancer Understand how the immune system clears tumour Understand how the immune system clears tumour

cellscells Understand the difficulties involved in eradicating Understand the difficulties involved in eradicating

cancerscancers Understand common treatment alternatives for Understand common treatment alternatives for

cancercancer Understand the prognosis of cancers and the Understand the prognosis of cancers and the

principles of palliative careprinciples of palliative care

Documents

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 1 Human Disease Processes 1: The body’s response to cancer This lesson