Introduction to Cancer

Biomedical Science and Nursing 2 Week 12

10 facts about Cancer (WHO, 2006)

1. There are more than 100 types of cancers; any part of the body can be affected. In 2005, 7.6 million people died of cancer - 13% of the 58 million deaths worldwide. More than 70% of all cancer deaths occur in low and middle income countries. Worldwide, the 5 most common types of cancer that kill men are (in order of frequency): lung, stomach, liver, colorectal and oesophagus. Worldwide, the 5 most common types of cancer that kill women are (in the order of frequency): breast, lung, stomach, colorectal and cervical.

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10 facts about Cancer (WHO, 2006)

6. Tobacco use is the single largest preventable cause of cancer in the world. 7. One fifth of all cancers worldwide are caused by a chronic infection, for example human papillomavirus (HPV) causes cervical cancer and hepatitis B virus (HBV) causes liver cancer. 8. A third of cancers could be cured if detected early and treated adequately. 9. All patients in need of pain relief could be helped if current knowledge about pain control and palliative care were applied. 10.40% of cancer could be prevented, mainly by not using tobacco, having a healthy diet, being physically active and preventing infections that may cause cancer.

What is Cancer?
A definition Cancer is " a general term for a large group of diseases which all display uncontrolled growth and spread of abnormal cells. The process of cell division, by which tissues normally grow and renew themselves, gets out of control. These cancer cells multiply in an uncoordinated way, usually to form a tumour. Cells from the original, or primary, cancer site may infiltrate surrounding tissue to cause damage. They may also travel by means of the bloodstream or lymph system to form secondary cancers elsewhere in the body. (The Cancer Word Book, C.C.V., 2001)

Cancer is defined as the loss of cell division control

US Mortality, 2003
No. of deaths % of all deaths

Rank

Cause of Death

1. 2. 3. 4.

Heart Diseases Cancer Cerebrovascular diseases Chronic lower respiratory diseases

685,089 28.0 556,902 22.7 157,689 126,382 6.4 5.2

5.
6. 7.

Accidents (Unintentional injuries)

Diabetes mellitus Influenza and pneumonia

109,277
74,219 65,163

4.5
3.0 2.7

8.
9.

Alzheimer disease
Nephritis

63,457
42,453 34,069

2.6
1.7 1.4

10. Septicemia

Source: US Mortality Public Use Data Tape 2003, National Center for Health Statistics, Centers for Disease Control and Prevention, 2006.

Trends in the Number of Cancer Deaths Among Men and Women, US, 1930-2003
300,000
Men
290,000

Men
285,000

250,000
Number of Cancer Deaths Women

280,000

275,000

200,000
270,000

Women
2001 2002 2003

150,000

265,000 2000

100,000

50,000

0 1930

1940

1950

1960

1970

1980

1990

2000

Source: US Mortality Public Use Data Tape, 2003, National Center for Health Statistics, Centers for Disease Control and Prevention, 2006.

Normal Cell Biology

The basic unit of structure & function in all living things is the cell. Most cells have the ability to reproduce Control mechanisms govern cell replication The normal healthy cell perfectly copies itself over and over.

Cell Biology
Conditional Renewal Cells which have the ability to regenerate or reproduce but only do so under special circumstances Eg. Osteocytes of bone, parenchymal cells of the liver Continuous Renewal Cells which regenerate frequently & have a life span measured in hours or days Eg. White blood cells, epithelial cells Essentially non- renewing Cells which live for the entire life of the organism Eg. Nerve cell bodies, myocardial muscle cells

Cancer Cell Biology

If something goes wrong and the usual restrictions placed by the host on cell replication do not occur, abnormal cellular growth results Hyperplasia increase in number of cells Metaplasia transformation of a cell Dysplasia abnormal tissue development Anaplasia loss of differentiation Neoplasia the process resulting in the formation or growth of a neoplasm (abnormal tissue, faster growth)

Cancer Cell Biology

Tumor - abnormal swelling may be malignant or benign Neoplasm - new growth of cells and often refers to a tumor or a cancerous growth Benign neoplasm - is a growth which is not malignant slow growing encapsulated and looks like cell of origin Malignant neoplasm - immature cells grows rapidly invades and spreads does not look like cell of origin

Classification
Benign & malignant tumours are named according to tissue of origin Tumours are classified according to their behaviour & their cell type Malignant tumours are divided into 3 subgroups: Carcinomas Sarcomas Leukaemias & lymphomas

Examples of Malignant Neoplasms

Carcinoma - cancer arising from epithelial tissue e.g. skin - squamous cell carcinoma or from a solid/hollow organ e.g. rectum/liver Sarcoma - cancer arising from connective tissue e.g. bone osteosarcoma Glioma - cancer arising from connective tissue in the CNS Lymphoma - cancer arising from the lymph-reticular system Myeloma - cancer arising from myeloid cells or cell forming tissue

Characteristic
Encapsulated
Rarely

Malignant
Poorly
Frequently present Frequent Moderate to marked Infiltrative & expansive

Benign
Usually

Differentiated
Metastases Recurrence Vascularity Mode of growth

Partially
Rarely Rare Slight Expansive

Cell characteristics

Cells abnormal & become more unlike parent cells

Fairly normal; similar to parent cells

Cancer Cell Properties

Immortal Limited contact inhibition Diminished growth requirements Grow without anchorage support Loss of restriction point in cell cycle Disorderly and multi-layered patterns of growth

Carcinogenesis
Process in which cancer develops Transformation of normal cells to cancer cells involves the steps of: Initiation Promotion Progression Carcinogens

Cancer - A Disease of the Genes

Carcinogens - agents that have the capacity to permanently alter the molecular structure of the genetic component of a cell (DNA) elimination of 1 of the components of the DNA chain errors in DNA repair This is different to a hereditary cancer where the mutated gene is passed down to children

Protoncogenes
Normal cell gene Function to tightly regulate & control normal cell proliferation & differentiation Can be damaged by a virus, mutation/ carcinogen etc to become an oncogene

Oncogenes
Genes that may cause cancer if mutated/ regulatory mechanism damaged Mutated forms of protoncogenes (normal genes) Regulation of these genes usually well controlled by the body

Tumor suppressor genes normal - inhibit cell proliferation and growth therefore, if inactivated, cancer may develop

Risk factors
Chemical Carcinogens Polycyclic aromatic hydrocarbons (smoke, exhaust fumes, products of combustion) Aromatic amines & azo dyes (coal tar, insecticides, food dyes) Alkylating agents (mustard gas, cyclophosphamide) Nitrosamines (nicotine, food additives) Industrial compounds, asbestos Radiation Carcinogens Ionizing radiation Atomic bomb detonation Ultraviolet radiation

Risk factors
Viruses Herpes Simplex type II Epstein Barr Human Papilloma Virus Genetic Factors Downs Syndrome Familial Cancers Genetic Factors Deficient immune system (HIV, organ transplant)

Risk Factors for Developing Cancer

Risk Factor - element of personal behaviour or genetic makeup, or exposure to a known cancer causing agent that increases a persons chance of developing a particular form of cancer Non controllable Hereditary, age, gender, socio-economic status, genetic predisposition Controllable Stress, diet, occupation, tobacco, alcohol, obesity, sun exposure, geographical location, environmental factors, sexual practices

Risk Factors for Selected Cancers

CANCER SITE Lung HIGH RISK FACTORS Heavy smoking over age 50 Asbestos exposure

Breast

Family history Diet high in fat Nulliparous

Obesity Increasing age Familial adeno-polyposis Excessive exposure to UV radiation Fair skin Family history

Colo-rectal Skin

SEVEN WARNING SIGNS OF CANCER CAUTION

Perubahan pd kebiasan BAB & BAK Adanya luka yg sulit sembuh Perdarahan/sekresi yg tak biasa Benjolan pd dada atau bagian tubuh lain G3 mencerna makanan atau sulit menelan Perubahan pada tahi lalat Batuk atau suara serak yg tidak mau hilang C Change in bowel & bladder habits AA sore that doesnt heal UUnusual bleeding or discharge TThickening or a lump in the breast or elsewhere IIndigestion or difficulty in swelling OObvious charge in a wart NNagging cough or hoarseness

Metastases
Invasion/ direct spread Lymphatic dissemination Gravitational dissemination Blood stream dissemination Vascularisation Cell detachment Aggregation Arrest Establishment Proliferation

Diagrams of vertebral venous system in thoracic inlet

Anterior view: Az = azygos vein, EDV = epidural venous plexus, DCV = deep cervical vein, IVV = intervertebral vein, LBCV = left brachiocephalic vein, LPV = longitudinal prevertebral vein, RSICV = right superior intercostal vein, VV = vertebral vein, ICV = intercostal vein. Asterisk indicates esophageal veins, dotted line indicates peripheral branches of deep cervical vein in back neck.
Ibukuro, K. et al. Am. J. Roentgenol. 2001;176:1059-1065

Copyright 2006 by the American Roentgen Ray Society

Metastatic spread
Is not just a random process Main sites of metastases are to: liver lung bone lymph nodes Undifferentiated tumors more likely to metastasize than well differentiated tumor

Characteristics of malignant tumours

Progressive, uncontrolled growth at secondary site Metastatic cells more poorly differentiated than the primary tumour - can make them more difficult to treat Able to penetrate basement membrane Anchorage-independent growth Secondary tumours can develop and maintain their own blood supply

Usual sites of Metastasis

Breast Cancer Colo-rectal Cancer Lymph nodes, Bone marrow, lung, liver, brain Lymph nodes, liver, bone marrow

Lung Cancer
Prostate Cancer Leukemia

Liver, brain, adjacent structures

Bone, Pelvic structures CNS, Visceral organs

Cervical Cancer

Adjacent pelvic structures, lymph nodes

Manifestations of Cancer
Tumour involvement Invasion Infiltration Compression Metastases Systemic effects Associated with treatment Related to chronic / debilitating disease

Principles of Treatment
The goals in the treatment of cancer are: Cure Control Palliation

Treatment decision
Age Size and site of tumour Staging Aggressiveness of the cancer Prognosis Quality of life Predictability of spread Expected cure rate Risks associated with treatment Host resistance Patients wishes

Surgery
Oldest form of cancer treatment Diagnosis & staging Cure Palliation Reconstruction Prevention

Surgery & Nursing Implications

Pre operative care Education Post operative care Assessment Preventing post operative complications Rehabilitation

Chemotherapy
Use of chemicals to treat cancer Target rapidly dividing cells Over 50 chemotherapeutic agents in use Cure Control Palliation

Chemotherapy & Nursing Implications

Assessment Education Cytotoxic precautions Management of side effects of therapy

Radiotherapy
Use of high energy x-rays to treat cancer 60% of cancer patients will receive radiotherapy Alters the biological material in the atom of the cell Cure Control Palliation

Biotherapy
Use of agents from biological sources to affect the bodys biological responses Manipulate the immune system Cytokines Interferon Antibodies Growth factors

5 year survival by cancer type

60% ALL CANCERS 91% MELANOMA 12% LUNG 85% PROSTATE 84% BREAST 58% BOWEL

Colorectal cancer an overview

Highest incidence of all cancers 2nd leading cause of cancer related death Risk increases from age 40 & onwards Risk factors are:

Familial adeno polyposis (FAP) Hereditary nonpolyposis colorectal cancer (HNPCC)

Diet Inflammatory bowel disease

Risk Factors
Familial adeno polyposis (FAP) genetic disorder causing cancer in 100% pts by age 50 Accounts for 1 % of colorectal cancer Hereditary nonpolyposis colorectal cancer genetic disorder causing cancer in 70% pts by age 65 accounts for 4% of colorectal cancer Inflammatory bowel disease ulcerative colitis Diet

FAMILIAL ADENOPOLYPOSIS
an inherited disorder characterized by the development of myriad polyps in the colon, beginning in late adolescence or early adulthood. Untreated, the condition nearly always leads to colon cancer

Risk factors
Diet- attributed to 50% of colorectal cancer Strong correlation between diet and colorectal cancer Incidence greatest in industrialised western countries diet high in refined carbohydates diet high in saturated fats diet high in animal fats - red meat diet low in fibre diet low in vegetables esp green leafy vegetables diet high in alcohol/low in folate

What causes colorectal cancer?

Diet 50% Genetics 15% Unknown Factors 22% Inactivity 13%

Clinical course
Most colorectal cancers develop from a benign precursor lesion or adenoma (polyp) Dysplastic changes occur in the original lesion/polyp - becomes malignant, grow and invade into surrounding tissue Eventual penetration through the bowel wall & local spread into surrounding tissues/organs/lymph nodes Spread widely through the lymphatic system and blood stream Most common sites of spread are to the liver followed by peritoneal cavity, lung, adrenals, ovaries & bone

Screening for Colorectal Cancer

Screening is usually done for people who have a strong family history of colorectal cancer recommended for people over 50 For those people with a genetic predisposition/risk factors - screening needs to be done on a more frequent basis Screening involves the following: early FOB to check for bleeding/PR examination Sigmoidoscopy/colonoscopy every 3 to 5 years

Treatment for colorectal cancer

Surgery Curative palliative Chemotherapy Used post operatively for patients with stage II/III disease Advanced disease Radiotherapy Pre & Post operatively Used for patients with high risk of local recurrence Positive lymph nodes Painful metastases

Lung cancer an overview

Is the 4th site of new cancers Leading cause of cancer deaths Incidence & mortality rates are declining in males but increasing in females Risk Factors are: Smoking Active & passive Exposure to asbestos Malignant Mesothelioma ? Exposure to radiation & other chemicals Heavy metals

Types of lung cancer

Non Small Cell Lung cancer (NSCLC) (approx 80%) Squamous cell (approx 30%) Adenocarcinoma (approx 30-50%) Large cell (approx 10-15%) Small Cell Lung Cancer (approx 20%)

SQUAMOUS CELL LUNG CANCER

Cancer that begins in squamous cells, which are thin, flat cells that look like fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma.

ADENOCARCINOMA
"Adeno-" is a prefix that means "gland" Carcinoma is a malignant tumor that starts in epithelial tissue. "adenocarcinoma," which means a malignant tumor in epithelial tissue, specifically in a gland. Cancer that begins in the cells that line the alveoli and make substances such as mucus.

LARGE CELL CARCINOMA

Cancer that may begin in several types of large cells Lung cancer in which the cells are large and look abnormal when viewed under a microscope.

SMALL CELL LUNG CANCER

An aggressive (fast-growing) cancer that forms in tissues of the lung and can spread to other parts of the body. The cancer cells look small and oval-shaped when looked at under a microscope It is sometimes called "oat cell carcinoma" due to the flat cell shape and scanty cytoplasm. This type of cancer is usually always caused by smoking.

Staging & prognostic indicators

Non Small Cell Lung Cancer TNM system Stage of disease ECOG (performance) status Weight loss Small Cell Cancer Limited disease Extensive disease ECOG status Site of metastatic spread

ECOG PERFORMANCE STATUS* Grade 0 1 ECOG Fully active, able to carry on all pre-disease performance without restriction Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours Capable of only limited self-care, confined to bed or chair more than 50% of waking hours Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair Dead

2 3 4 5

* As published in Am. J. Clin. Oncol.:

Staging (TNM)
Tumour size (T): Tx: Primary tumour not able to be assessed T0: No evidence of primary tumour, ie. cancer cells seen on sputum sampling or bronchial washing only Tis: Carcinoma in situ T1: Tumour 3 cm or less, surrounded by pleura, without evidence of invasion more proximal than the lobar bronchus. T2: Tumour with any of the following features: >3cm in greatest dimension Invades visceral pleura Associated with atelectasis or obstructive pneumonitis, extending to the hilar region but not involving the entire lung.

Staging (TNM)
Tumour size (T): T3: Tumour of any size, directly invading the chest wall, diaphragm, mediastinal pleura or parietal pericardium; or tumour in the main bronchus; or in the main bronchus, less than 2cm distal to the carina, but without involvement of the carina; or with associated atelectasis or obstructive pneumonitis of the entire lung T4: Tumour of any size, invading the mediastinum, heart, great vessels, trachea, oesophagus, vertebral body, carina; or with separate tumour nodules in one lobe, or with malignant pleural effusion

Staging (TNM)
Regional lymph nodes (N): NX: Regional lymph nodes not able to be assessed N0: No regional lymph node metastasis N1: Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension N2: Metastasis in ipsilateral mediastinal and/or subcarinal lymph nodes N3: Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph nodes

Staging (TNM)
Distant Metastasis (M) MX: Distant metastasis not able to be assessed M0: No distant metastasis M1: Distant metastasis, including separate tumour nodule(s) in a different lobe (ipsi- or contralateral).

Staging
Non-small cell lung cancers are grouped into stages as follows: Stage 0: TIS N0 M0 Stage Ia: T1 N0 M0 Stage Ib: T2 N0 M0 Stage IIa: T1 N1 M0 Stage IIb: T2 N1 M0, T3 N0 M0 Stage IIIa: T1 N2 M0, T2 N2 M0, T3 N1 M0, T3 N2 M0 Stage IIIb: any T N3 MO, T4 any N M0 Stage IV: any T any N M1

Clinical course
NSCLC Usually arise in the periphery of the lung Often remain localised or have minimal spread to surrounding lymph nodes Spread via blood stream to the brain, bone, liver & kidney Spread directly to chest wall SCLC Usually arise in the central region of the lung Very aggressive & patients often have widespread disease at diagnosis often bilateral chest wall involvement Spread via blood stream & lymphatics to lymph nodes, liver, adrenal glands, bones & CNS

Clinical manifestations
Specific: Cough Shortness of breath Haemoptysis Recurrent pneumonia Non specific: Anorexia Malaise Weight loss Metastatic Symptoms Spinal Cord Compression Cerebral symptoms Bone pain SVC obstruction

Treatment of lung cancer

NSCLC Stage I/II surgery or radiotherapy/chemotherapy if unfit for surgery Stage III surgery (if fit) chemotherapy & radiotherapy Stage IV palliative treatment with chemo/radiotherapy SCLC Chemotherapy for limited & extensive disease + thoracic radiotherapy Prophylactic radiotherapy to the brain

Survival rates (nsclc)

For each stage, the prognoses, or estimated 5-year survival rates, in Europe are as follows: Stage IA - 60% Stage IB - 38% Stage IIA - 34% Stage IIB - 24% Stage IIIA - 13% (Stage IIIA lesions have a poor prognosis, but they are technically resectable) Stage IIIB - 5% (Stage IIIB lesions are non resectable) Stage IV - Less than 1%