Transcript of "Medicine 5th year, 1st & 2nd/part one lectures (Dr. Abdulla Sharief)"
Oncology Dr.Abdulla Sharief.
Oncology <ul><li>from the Greek onkos ,mass, tumour , describes the study of malignant disease. </li></ul><ul><li>There are a number of common synonyms for malignant disease such as cancer, but this term technically only applies to tumours of epithelial origin </li></ul><ul><li>The oldest treatment for malignancy is surgery, but there is now an increasing range of non-surgical treatments, encompassing both radiotherapy (clinical oncology) & drug treatments (medical oncology) . </li></ul>
SYNONYMS FOR MALIGNANT DISEASE Definition Synonym New growth: includes benign disease Neoplasia Swelling: includes benign/inflammatory disease Tumour Malignancy of epithelial cell origin Cancer, carcinoma Malignancy of mesothelial cell origin Sarcoma Malignancy of lymphoid organs (usually glands ) Lymphoma Malignancy of white blood cells Leukaemia
Prevalence: <ul><li>Malignancy is common, developing at some time in the life of more than one-third of the population </li></ul><ul><li>It is the second most common cause of death in the Western world, after cardiovascular disease. </li></ul><ul><li>There is significant variation with age, sex and geography in the incidence of the various malignancies&resources available for detection and treatment. </li></ul><ul><li>Amongst the more common solid tumours such as lung and breast cancer, the incidence is often higher in developed countries. </li></ul><ul><li>The incidence of lung cancer is four times higher in the UK than in India, although it is becoming increasingly common throughout the world. </li></ul><ul><li>Breast cancer accounts for around 20-25% of all female cancers in both India and the UK, but the incidence in the UK per 100 000 women is three times higher than in Mumbai. </li></ul><ul><li>Carcinoma of the cervix is the second most common cause of cancer death in women in the Caribbean, with an incidence almost four times higher than in the UK . </li></ul>
EPIDEMIOLOGICAL CAUSES OF CANCER Drugs -> Leukaemia • Cytotoxics <ul><li>Infection </li></ul><ul><li>Schistosomiasis ->Squamous bladder cancer </li></ul><ul><li>Human papillomavirus 16 and 18 ->Cervical cancer </li></ul>
Genetics <ul><li>Breast cancer gene ½: -> Breast and ovarian cancer </li></ul><ul><li>Hereditary non-polyposis colorectal cancer gene: Colon and endometrial cancer </li></ul><ul><li>Adenopolyposis coli gene: Colorectal cancer </li></ul>
Lifestyle <ul><li>Western (specific cause still unclear) :Breast and colorectal cancer </li></ul><ul><li>Tobacco:Lung, bladder, head and neck cancer </li></ul><ul><li>Alcohol :Oesophageal cancer </li></ul><ul><li>Aflatoxin: Liver cancer </li></ul>
Epidemiology <ul><li>For many solid cancers such as breast and colorectal, there is evidence of a multi-factorial pathogenesis, even when there is a principal environmental cause ( </li></ul><ul><li>Smoking is now established beyond all doubt as a major cause of lung cancer, but there must be additional modifying influences since not all smokers develop cancer; these may be based in the individual's genotype. </li></ul><ul><li>Similarly, most carcinomas of the cervix are related to infection with particular strains of the human papillomavirus (HPV 16 and 18), although other factors such as early age at first sexual intercourse contribute. </li></ul><ul><li>For carcinomas of the bowel or breast, the strongest aetiological factors appear to be environmental and genetic. For example, the risk of breast cancer in women of Far Eastern origin remains relatively low when they first migrate to a country with a Western lifestyle, but rises in subsequent generations to approach that of the resident population of the host country. </li></ul>
Epidemiology <ul><li>A small number of genes have been identified that significantly increase the risk of developing breast cancer ( BRCA1 , BRCA2 , AT ( ataxia telangiectasia)). </li></ul><ul><li>None of these has 100% penetrance so that there must be additional modulating factors, as yet undefined. </li></ul><ul><li>For most patients, the precise cause of a cancer is less important than the diagnosis itself, although some may be concerned that there is an increased risk for their offspring, which means that exploration of a possible genetic contribution is a key part of management. </li></ul>
PREVENTION AND SCREENING <ul><li>Smoking is the cause of most lung cancer in the world, prevention has proved much more difficult. </li></ul><ul><li>Modification of a population's lifestyle involves not only education but also political change. </li></ul><ul><li>It is clear from many studies that the risk of breast cancer is related to a woman's lifetime oestrogen exposure, and this has given some possibilities for therapeutic intervention. Premature menopause, iatrogenic or otherwise, reduces the risk of developing breast cancer but is associated with a number of other unwanted consequences such as osteoporosis. Therapeutic intervention using, for example, tamoxifen has been shown to reduce the incidence of breast cancer but not mortality, and is not without toxicity. An alternative is prophylactic surgery, such as mastectomy or colectomy, in those at high risk of developing cancers in these tissues, but this is clearly not an option for a whole population . </li></ul>
PREVENTION AND SCREENING <ul><li>Earlier diagnosis creates the potential to cure more patients. </li></ul><ul><li>When patients are diagnosed with a cancer on the basis of symptoms, the cancer may have already spread in a significant proportion, so that loco-regional treatment (usually surgical) may be insufficient for a cure. </li></ul><ul><li>Earlier identification of a cancer in an asymptomatic population could therefore 'catch' more cancers before they spread, rendering more patients curable by loco-regional treatment alone. </li></ul><ul><li>This is the concept behind screening for malignancy, which has now been successfully applied to two major cancers in many developed countries </li></ul><ul><li>Population-based mammographic screening for women between 50 and 65 years old has been shown, with some controversy, to reduce the mortality from breast cancer. </li></ul><ul><li>Patients cannot be 'forced' to be screened, so the screening method has to be acceptable to a high enough proportion of the candidate population to be effective. </li></ul>
CANCERS WITH POTENTIAL FOR SCREENING Benefits Method of screening Ca Reduced mortality Mammography BC ?Reduced mortality (indirectly inferred) Cervical smear cytology Cervical Ca Possible reduced mortality Serum prostate-specific antigen(PSA) level PC Possible reduced mortality Single flexible sigmoidoscopy Faecal occult blood test CRC
ONCOLOGY IN OLD AGE <ul><li>Incidence : around 50% of cancers occur in the 15% of thepopulation aged over 65 years . </li></ul><ul><li>Screening : women aged over 65 in the UK are not invited to breast cancer screening but can request it. Uptake is low despite increasing incidence with age . </li></ul><ul><li>Presentation : may be later for some cancers. When symptoms are non-specific, patients (and their doctors) may initially attribute them to age alone . </li></ul><ul><li>Life expectancy : an 80-year-old woman can expect to live 8 years, so cancer may still shorten life and an active approach remains appropriate . </li></ul><ul><li>Prognosis : histology, stage at presentation and observation for a brief period are better guides to outcome than age alone . </li></ul><ul><li>Rate of progression : malignancy may have a more indolent course. This is poorly understood but may be due to reduced effectiveness of angiogenesis with age, inhibiting the development of metastases . </li></ul><ul><li>Response to treatment : equivalent to that in younger people. This is well documented for a range of cancers and for surgery, radiotherapy, chemotherapy and hormonal therapy . </li></ul><ul><li>Treatment selection : chronological age is of minor importance compared to comorbid illness and patient choice. Although older patients can be treated effectively and safely, aggressive intervention is not appropriate for all individuals. Symptom control may be all that is possible or desired by the patient </li></ul>
Screening pitfalls <ul><li>Only a tiny minority of most populations will have the disease, and screening requires considerable organisation, resources, and diagnosticians able to identify the occasional abnormal sample or X-ray amongst hundreds of normal ones, as missing these would invalidate the whole process. </li></ul><ul><li>A positive result must have a reasonably high chance of indicating malignancy to avoid generating unnecessary anxiety and further investigation. </li></ul><ul><li>It must be clear that the earlier diagnosis of a cancer improves the cure rate, as otherwise the individual is simply subjected to more years as a 'cancer patient'. </li></ul><ul><li>If it is not possible to cure more patients it may be better to delay diagnosis until there are symptoms, rather than screening the population . </li></ul>
CLINICAL ASSESSMENT <ul><li>In order to plan the management of a patient with malignancy, the following information is required : </li></ul><ul><li>The nature of the primary malignancy (site, type, pathology) </li></ul><ul><li>The extent of the disease (stage) </li></ul><ul><li>the patient's general condition and comorbidity </li></ul><ul><li>the available treatment options . </li></ul><ul><li>The presentation of a malignancy can involve both local & systemic features ( </li></ul><ul><li>The local signs or symptoms are usually due to mass effect or invasion of local tissues. </li></ul><ul><li>Systemic features may be the result of metastases or the non-metastatic manifestations of malignant disease . </li></ul>
Evaluation: <ul><li>From the history, details of the tumour-related problem should be established along with potential risk factors. </li></ul><ul><li>In breast cancer, family history, early menarche, late menopause and benign breast disease are associated with increased risk, while early full-term pregnancy reduces risk. </li></ul><ul><li>An impression of the rate of development of the disease may help determine prognosis and treatment. </li></ul><ul><li>A thorough clinical examination is essential to identify sites of metastases, and to identify any other conditions that may have a bearing on the management plan . </li></ul><ul><li>The overall fitness of a patient can be evaluated using a variety of scales,most common is the Eastern Cooperative Oncology Group (ECOG) performance scale </li></ul><ul><li>The outcome for patients with a performance status of 3 or 4 is worse in almost all malignancies than for those with a status of 0 to 2. </li></ul><ul><li>Treatment decisions must take such assessments into account . </li></ul>
NON-METASTATIC MANIFESTATIONS OF Ca Gastrointestinal tumours Weight loss and anorexia Any Fatigue Myeloma, breast, renal tumours Hypercalcaemia Pancreas and other gastrointestinal tumours Prothrombotic tendency Hormonal effects Small-cell lung cancer (SIADH) Ectopic adrenocorticotrophic hormone (ACTH) Neuropathies and myopathies Small-cell lung cancer Eaton-Lambert myasthenia-like syndrome Subacute cerebellar degeneration Skin abnormalities Gastro-oesophageal tumours Acanthosis nigricans Gastric, lung tumours Dermatomyositis/polymyositis
INVESTIGATIONS <ul><li>Tumour imaging and sampling are required. </li></ul><ul><li>Sampling may be achieved under direct vision as at endoscopy, bronchoscopy or colonoscopy, or with ultrasound or computed tomography (CT) guidance. </li></ul><ul><li>Superficial masses or lesions may be biopsied or fine needle aspirates may be taken. </li></ul><ul><li>In cases where treatment is initially or largely non-surgical, precise measurement of initial tumour size helps to assess subsequent response to therapy . </li></ul><ul><li>Special investigations such as serum tumour marker tests and a series of standard radiological tests to 'stage' the disease may follow (see below). </li></ul>
PATHOLOGY <ul><li>The pathologist studies the tissue sample for evidence of cellular abnormalities which reflect mutations : </li></ul><ul><li>Greater numbers of cells than in normal tissue </li></ul><ul><li>Increased size </li></ul><ul><li>A higher nuclear to cytoplasmic ratio </li></ul><ul><li>A higher proliferation rate (evidenced by visible mitotic figures </li></ul><ul><li>In addition, the cells may be in an abnormal location; they may have penetrated (invaded) the basement membrane or moved (metastasised) from their tissue of origin, e.g. to lymph nodes/liver. There is, however, a continuum from benign to malignant </li></ul><ul><li>Immunohistochemistry :Highly specific monoclonal antibodies, associated with a coloured stain, are used to detect various intracellular and cell-surface proteins to achieve a specific diagnosis ,can be used to determine the tissue of origin of a very undifferentiated tumour, identify important subtypes of common cancers (small-cell, neuro-endocrine) which have different prognoses or require different therapies </li></ul>
IMMUNOHISTOCHEMISTRY MARKERS Tumour type Routine use? Oncogene? Name Neural crest origin (e.g. melanoma) Yes No S-100 Small-cell cancer (e.g. lung) Yes No Cam 5.2 Colon and other gastrointestinal tumours Yes No Carcinoembryonic antigen (CEA) Ovary Yes No CA-125 Breast cancer (present in other tumours, e.g. ovary) Yes No Oestrogen receptor (ER) Breast cancer (present in other tumours, e.g. lung, ovary, gastric) No Yes Her-2
BIOCHEMISTRY AND TUMOUR MARKERS <ul><li>Many tumours are asssociated with abnormalities in peripheral blood. </li></ul><ul><li>This may be due to the tumour secreting proteins into the circulation, which are detectable on routine testing ,many of these so-called tumour markers can be used for diagnosis, and in some types of cancer levels reflect the extent (stage) of the disease. </li></ul><ul><li>Commonly, markers are antigens that are usually only expressed in the fetus, but they may be produced by a tumour in an adult, causing levels that are much higher than normal. </li></ul><ul><li>Hormone levels can also be used as tumour markers-for example, oestrogen may be produced by ovarian granulosa cell tumours, and human chorionic gonadotrophin (HCG) by choriocarcinomas and teratomas. </li></ul><ul><li>Few markers are uniquely associated with the tumour, so that the currently available serum tumour markers are not completely specific. </li></ul><ul><li>Their main use is to assess a cancer's response to treatment and to monitor for recurrence rather than as a diagnostic test . </li></ul>
Blood tumor markers: Tumours Normally detected? Fetal antigen? Name Gastrointestinal tract, lung, breast Yes Yes Carcinoembryonic antigen (CEA) Ovary Yes Yes CA-125 Hepatocellular carcinoma and malignant teratoma Yes (very low) Yes β-Fetoprotein (AFP) Most, reflecting tumour burden or necrosis Yes No Lactate dehydrogenase (LDH) Prostate, some breast cancers Yes No Prostate-specific antigen (PSA) Malignant teratoma, seminoma, choriocarcinoma, gastrointestinal tumours Only in pregnancy No Human chorionic gonadotrophin (HCG)
Staging <ul><li>Is the determination of the extent of the malignancy. </li></ul><ul><li>It entails clinical examination and imaging to establish possible sites or extent of disease involvement </li></ul><ul><li>The tests used depend on the likely patterns of spread. </li></ul><ul><li>The outcome is recorded using a standard staging system to enable comparison between different groups of patients. </li></ul><ul><li>Therapeutic decisions and prognostic predictions can then be made using the evidence base for the disease. </li></ul><ul><li>One of the most commonly used systems is the T (tumour), N (regional lymph nodes)& M (metastatic sites) approach of the Union Internationale contre le Cancer (UICC) </li></ul><ul><li>For some tumours the most widely used system is not the TNM of UICC; colorectal cancer, for example, is often staged using the Dukes system </li></ul>
PRESENTING PROBLEMS IN ONCOLOGY <ul><li>With the advent of screening and public awareness campaigns, the vast majority of patients with cancer in developed countries present with local symptoms to organ-based specialties. </li></ul><ul><li>A small number of patients present as an emergency. </li></ul><ul><li>Most cancer treatments used are given close to their tolerance, which may result in complications that can be life-threatening and require urgent intervention . </li></ul>
STAGING TESTS Less common/geographical variation Common Primary Bone marrow, CT of abdomen/thorax Chest X-ray, bone scan Breast Bone scan CT abdomen and thorax, bone marrow Lymphoma Bone scan, CT pelvis Prostate Ultrasound, CT liver Colon Chest X-ray, CT chest and upper abdomen Lung
TNM CLASSIFICATION Extent of primary tumour T * Extent of regional lymph node involvement N * Presence or absence of metastases M Extent of disease Excised tumour T0 Increases in primary tumour size T1 T2 T3 Increased involvement of nodes Increases in involvement N1 N2 N3 Presence of metastases Not present M0 Present M1
A particular slide catching your eye?
Clipping is a handy way to collect important slides you want to go back to later.