© 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 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 2 The Growth of Cancer “Cancers grow by progressive infiltration, invasion, destruction and penetration of the surrounding tissue” - Kumar, Cotran, Robbins Basic Pathology, 7 th Ed, 2003

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 3 Pathophysiology of Cancer  A tumour manifests as an enlarging space- occupying 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 HDP1 The body’s response to cancer Lesson 11 - Overhead 4 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

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 5 Angiogenesis  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 HDP1 The body’s response to cancer Lesson 11 - Overhead 6 Angiogenesis

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 7 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

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 8 Local Effects of Tumours  Pain –Absence of pain in early formation, presence in advanced stages –Severity of pain depends on tumour location  Potential causes of pain –Direct pressure on nerves –Stretching of a visceral capsule –Infection –Ischemia –Bleeding –Irritation of nerve endings by chemical mediators

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 9 Local Effects of Tumours  Obstruction –compression of duct or passageway –Blood supply or lymphatic flow leading to ulceration or oedema –Air flow  Tissue necrosis and ulceration –Lack of blood supply  Infection –Opportunistic –As a result of ulceration and cell death

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 10

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 11 Systemic Effects of Tumours  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  Anaemia –Decreased haemoglobin as a result of anorexia –Bleeding and blood loss –Depression of bone marrow  Infections – increase as general immunity declines –Frequent infections such as pneumonia are common

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 12 Systemic Effects of Tumours  Bleeding –tumour cells may erode blood vessels or cause tissue ulceration –Chronic blood loss leads to iron deficiency anaemia  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 HDP1 The body’s response to cancer Lesson 11 - Overhead 13 Staging of Cancer  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 HDP1 The body’s response to cancer Lesson 11 - Overhead 14 Example of Staging: Breast Cancer  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 HDP1 The body’s response to cancer Lesson 11 - Overhead 15 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 HDP1 The body’s response to cancer Lesson 11 - Overhead 16 Immune Evasion and Host Defence Problems with tumour cell eradication include:  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.  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.  Immunosuppression: –some tumours produce cytokines that suppress immune function  Availability: –Solid tumours- difficult for the immune cells to reach all the cells of a solid tumour

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 17 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

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 18 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%

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 19 Occupational Risks for Cancers AGENTCANCEROCCURRENCE Arseniclung, skinmetal smelting alloys, electrical devices Asbestoslung, brake linings (mesothelioma) heat resistant materials (mesothelioma) heat resistant materials BenzeneLeukemialight oil, solvents Hodgkin lymphomadry cleaning CadmiumProstatesolders, batteries Vinyl chlorideliverrefrigerant, plastics

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 20 Australian Statistics

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 21

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 22 Incidence of Cancer by Gender

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 23 Incidence of Cancer by Gender

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 24 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

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 25 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

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 26 Treatment  Basic treatment measures are –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 HDP1 The body’s response to cancer Lesson 11 - Overhead 27

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 28 Surgery  Used for the removal of solid tumours  Aimed at the removal of the tumour and the surrounding lymph nodes  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 HDP1 The body’s response to cancer Lesson 11 - Overhead 29 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

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 30 Chemotherapy

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 31 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

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 32 Side Effects of Radiotherapy  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 HDP1 The body’s response to cancer Lesson 11 - Overhead 33 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

© Krejany and Morrison 2003 HDP1 The body’s response to cancer Lesson 11 - Overhead 34 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 HDP1 The body’s response to cancer Lesson 11 - Overhead 35 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