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Question 1

examples of familial cancers

Answer 1

A germline deletion of one allele of a gene and subsequent mutation of the remaining allele leads to carcinogenesis.
Examples include neurofibromatosis, adenomatous polyposis coli, familial breast cancer (e.g. mutations in the tumour suppressor genes breast cancer susceptibility gene 1 (BRCA1) and BRCA2), and von-Hippel Lindau syndrome.

Question 2

Examples of carcinogenic chemicals and which cancers they are associated with

Answer 2

Many chemicals act as carcinogens by damaging cellular DNA and inducing mutations in oncogenes and tumour suppressor genes. Carcinogenic chemicals include:
* Cigarette smoke - carcinogens present in cigarette smoke cause specific mutations in the p53 tumour suppressor gene.
* Aromatic amines - associated with bladder cancer
* Benzene - leukaemia
* Wood dust - nasal adenocarcinoma
* Vinyl chloride - angiosarcomas

Question 3

Physical carcinogenic agents .the risk of tumour development depends of which factors

Answer 3

Radiation increases the risk of cancer by increasing DNA damage leading to the accumulation of mutations in tumour-suppressor genes and oncogenes. The risk of tumour development is associated with:
* Radiation source – for example, damage to DNA by UV light is thought to be pathogenic in skin cancers, including malignant melanoma.
* Level of exposure - The dose received is critical to the incidence of tumour development.
* Accumulation of a radioactive isotope in a particular tissue may lead to tumour formation, for example thyroid cancer and radioactive iodine.

Question 4

What type of diets can increase the risk of cancer?

Answer 4

Many differing food substances have been implicated as causative agents through demographic studies e.g. association of colorectal carcinomas with low fibre diets in the West, and gastric carcinomas with smoked food in Japan. Many of the carcinogens are breakdown products of food (for example nitrosamines). Low fibre diets lead to an increased transit time through the bowel - thereby increasing exposure to carcinogenic substances.

Question 5

Which type of drugs can cause cancer and how? Mainly which type of cancer?

Answer 5

Cytotoxic drugs induce DNA damage and are associated with an increased risk of malignancy.

The effect is dose dependent and therefore of considerable importance in high-dose regimes.

Characteristic translocations may be induced by the topoisomerase inhibitors and lead to an acute leukaemia.

Question 6

Infective agents which are associated with cancer include:

Answer 6

Question 7

Link of Immune deficiencies and cancer

Answer 7

There is increasing evidence that the immune system is involved in tumour surveillance. Drugs causing immunodeficiency are associated with a higher risk of malignancy, as are infections that damage the immune system (for example HIV). Congenital abnormalities of the immune system, particularly T cell deficiencies, are also associated with an increased risk of tumours.

Question 8

list of aetiological agents in cancer

Answer 8

• familial genes and mutations
• carcinogenic chemicals
• physical agents/radiation
• diet
• cytoxic drugs
• infective agents
• immune deficiencies

Question 9

The majority of cancer patients present with one of a relatively small number of key presenting symptoms. These are:

Answer 9

Question 10

In deciding whether the possibility of cancer needs to be considered in the diagnostic approach a range of other patient related factors and circumstances have to be considered:

Answer 10

Question 11

• In TNM staging what does T stand for?

Answer 11

T: Primary Tumour
Tx Primary tumour cannot be assessed
T0 No evidence of primary tumour
Tis Carcinoma in situ

T1, T2, T3, T4 Increasing size and/or local extent of the primary tumour

Question 12

In TNM staging what does N means?

Answer 12

N: Regional Lymph Nodes
* Nx Regional lymph nodes cannot be assessed
* N0 No regional lymph node metastasis
* N1, N2, N3 Increasing involvement of regional lymph nodes

Question 13

In TNM staging what does M stand for?

Answer 13

M: Distant/Organ Metastasis
Mx Presence of distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis

Question 14

TNM staging example for colorectal cancer

Answer 14

Question 15

How does staging of a cancer relate to TNM: e.g. Stage 1 equates to which TNM classification?

Answer 15

Question 16

What is cancer grading and what are the different components of the grading?

Answer 16

Question 17

Purpose of staging and grading in cancer

Answer 17

The purpose of staging is to indicate prognosis and the appropriate choice of treatment:
* The higher the stage and grade the poorer the prognosis. This may need to be communicated to the patient. In addition, these assessments will determine the treatment choice.
* The more advanced the disease becomes then the greater is the need for treatment which encompasses the risk of metastases.
* In general, the higher the stage the more extensive the treatment has to be.
* In particular, the presence of lymph node metastases is not only directly a problem in that these nodes need to be either removed or treated by radiotherapy or chemotherapy but is also a powerful indicator of probable systemic blood-borne metastases.

Question 18

• Uses of imaging in cancer medicine

Answer 18

• diagnosis
• staging
• response assessement
• follow up
• screening

Question 19

Imaging used in diagnosis of cancer

Answer 19

CT or US are commonly used by radiologists to guide biopsies, under local anaesthesia, to provide an adequate specimen for histological or cytological diagnosis and may obviate the need for more invasive interventions.

Question 20

Imaging used in staging of cancer

Answer 20

• CT is the standard imaging tool for the evaluation of chest and abdominal malignancies, although increasingly this is supplemented by PET-CT imaging to detect areas of intense metabolic activity (which can then detect areas of tumour spread that would be missed by CT alone). This is used routinely now in many types of cancer such as lung and oesophagus.
• MRI is important in some areas, including bone and soft tissue lesions, and regions where bone causes artefact in the CT appearances such as the pelvis or the posterior fossa of the brain.

Question 21

How is imaging used to assess response in cancer treatments? Which system is used to grade response?

Answer 21

Question 22

Role of imaging in cancer follow up

Answer 22

When detection of asymptomatic relapse has been shown to affect clinical outcome, (e.g. testicular tumours), further use of radiology for surveillance is justified. However, in most cancers, routine follow-up imaging is of no proven benefit.

Question 23

Role of imaging in screening

Answer 23

The use of screening mammography to detect breast cancer is now well established in the UK but the use of other radiological screening examinations has not proved effective (e.g. CXR to assess people at high risk of lung cancers, transvaginal ultrasound for ovarian cancer).

Question 24

Uses of MRI

Answer 24

The principle of nuclear magnetic resonance (MR) has been exploited to develop a clinical imaging tool that produces images of high soft tissue contrast in any cross-¬sectional plane. These advantages mean that MRI is now the gold standard for imaging: neurospinal, rectal, prostate and musculoskeletal tumours, and is used for staging some subtypes of head and neck cancer.

Images can also be reconstructed to examine a particular organ system, such as MR angiography of the cardiac vessels, or MR cholangiopancreatograms.

Real-time MR, using the changes in MR appearances over time or after contrast agents, is of increasing use in diagnostic work such as the assessment of breast masses.

Question 25

which patients cannot use MRI?

Answer 25

• metallic foreign objects: foreign bodies in the eye or brain (typically vascular clips, surgical staples, metallic shards following trauma) are an absolute exclusion, whereas prosthetic joints are sufficiently fixed in place so as not to be a problem
• pacemakers

Question 26

Warnings regarding CT scans

Answer 26

• Always consider pregnancy before requesting scans or X-rays for women of child-bearing age.
• Standard contrast agents can be nephrotoxic and should be used with caution in patients known to have renal impairment.
• The radiation exposure associated with a CT scan is low but there is nevertheless thought to be a risk of inducing malignancies

Question 27

Advantages of US

Answer 27

The reflection of high-frequency sound waves at soft tissue interfaces generates the ultrasound image. Ultrasound, requiring no ionising radiation, is safe, widely available and inexpensive

Question 28

US uses in cancer and its disadvantanges

Answer 28

Apart from detecting metastases in solid ‘visceral’ abdominal organs, specialist applications such as duplex and doppler ultrasound are used to assess tumour blood flow.
This can contribute to the characterisation of some neoplastic masses.
Ultrasound is also used for real-time guidance of biopsy and therapeutic interventional procedures.

As ultrasound is operator dependent it can be less reliable for the serial measurement of lesions for response.

Question 29

Nuclear medicine use In cancer

Answer 29

Question 30

Uses and advantages of PET scan

Answer 30

• PET produces functional images and has the potential to differentiate malignant from benign pathologies, but its availability remains limited.
• PET is usually merged with standard CT taken at the same time in order to map functional images to detailed anatomy.
• The isotopes used have a short half-life in order to minimize radiation exposure to patients
• FDG-18, like unlabelled glucose is rapidly taken up in very metabolically active cells such as malignant cells or neurons.
• FDG-18 PET-CT can identify otherwise occult metastases from some cancers.
• It is used in situations where radical treatment appears possible but has high mortality and/or morbidity.

For example, in non-small cell lung cancer FDG-18 PET-CT may characterize lymph nodes that are involved with metastatic cancer but were not detected by size criteria alone on conventional CT - these patients might otherwise have undergone complex, morbid but ultimately futile thoracic surgery.

Question 31

Definition of a tumour marker

Answer 31

Tumour markers are substances produced either by, or in response to, tumour, and are present in blood or other tissue fluids and can be quantified.

A tumour marker should be both highly sensitive so that few people with the disease are missed and highly specific so that few people are falsely labeled as having the disease.

Question 32

Difference between sensitivity and specificity

Answer 32

• Sensitivity: The sensitivity of a marker describes its ability to detect those with a certain disease. If 100 people have the disease and the marker is elevated in only 95, its sensitivity is 0.95.
• Specificity: The specificity of a marker describes its ability to accurately define those who are disease free. If in 100 disease-free people the marker is negative in only 90 (i.e. there are 10 false positives) the specificity of the test is 0.90.

Question 33

Classes of tumour markers

Answer 33

Question 34

Uses of tumour markers

Answer 34

• screening
• diagnosis
• prognosis
• response
• relapse

Question 35

role of tumour markers in screening

Answer 35

The use of existing tumour markers to screen the general population is not appropriate.
Their use has not been shown to alter clinical outcome in randomised controlled trials.
However certain high-risk groups have been identified in whom screening can be justified (e.g. the use of αFP to detect the development of hepatocellular carcinoma in patients with cirrhosis caused by chronic viral hepatitis).

Question 36

Tumour marker use in diagnosis

Answer 36

• Most tumour markers are elevated in a broad spectrum of malignancies (e.g. CEA, initially thought to be specific for colorectal carcinoma, is elevated in a proportion of patients with pancreatic, gastric, breast and lung malignancies, and by smoking).
• Many are also elevated in benign conditions; CA125 for example is elevated in endometriosis, menstruation and pregnancy. A proportion of normal individuals have what has been classified as an abnormal level, 1% of normal women have a CA125 level greater than 35 U/ml.
• Despite those limitations tumour markers can be helpful in some diagnostic situations. For example prostate-specific antigen (PSA) is highly tissue specific and a marked elevation in a man with disseminated bone metastases is usually diagnostic of prostate cancer.
• Young male patients who present with widespread metastases should have serum LDH, αFP, and βHCG (pregnancy test) to diagnose chemo sensitive and potentially curable germ cell tumours.
• Very high levels of some tumour markers are more likely to be due to a particular malignancy, just as the specificity of any test can increase if the cutoff value is moved. For example, αFP levels greater than 500 ng/ml are rarely seen except in patients with hepatocellular carcinoma or germ cell tumours of ovary or testis.

Question 37

Tumour marker use in prognosis

Answer 37

Some tumour markers can be used to give an indication of prognosis. In testicular teratoma, concentrations of HCG or αFP are powerful determinants of outcome. The rate of decline of a tumour marker following surgery or other treatments has been shown to relate to prognosis and may influence subsequent management.

Question 38

Tumour marker use in repsonse

Answer 38

One of the most clinically useful features of tumour markers is their ability to indicate response to treatment. In a patient with an elevated tumour marker, a reduction in the level of that marker whilst receiving treatment is highly suggestive of a response. The speed of reduction in βHCG and αFP following chemotherapy for germ cell tumours has been demonstrated to relate directly to survival.

Question 39

Use of tumour markers in relapse

Answer 39

In a patient who has previously been demonstrated to be have high levels of markers when disease is active (‘marker positive’), subsequent increase in the level is highly suggestive of tumour relapse. However some cancers will not show a rise in marker levels at the point of relapse and therefore over-reliance on a persistently normal level is not advisable.

Question 40

CEA indicates what type of cancer?

Answer 40

• A cell surface antigen also expressed in a variety of normal tissues.
• It is elevated in a wide variety of tumours but its common clinical use is in the setting of colorectal carcinoma
• The occurrence and degree of elevation is related to the clinical stage (4% in Dukes’ stage A, 65% with Dukes’ stage D).
• 98% of normal non-smokers have levels less than 5ng/ml.
• Elevated levels are also more common in people who smoke, or have inflammatory bowel disease, hepatitis, pancreatitis or gastritis.

Question 41

CA125 indicates which type of cancer? Specificity and sensitivity

Answer 41

Used as a marker in ovarian carcinoma, and is an antigen that is expressed on the surface of ovarian cells.

It is not perfect in sensitivity and specificity:
* An elevated serum level has been found in 1% of normal women, 6% with benign conditions (pregnancy, endometriosis and pelvic inflammatory disease) and 82% of women with ovarian carcinoma.
* A level greater than 200 U /ml was not found in normal women or those with benign conditions. As with most markers its elevation is not specific for one tumour.
* Serum levels are also elevated in pancreatic (59%), lung (32%), colorectal (21%) and breast cancer (12%), usually where these are disseminated to the abdominal cavity.

Question 42

aFP indicates which type of cancer? It is elevated in which other conditions?

Answer 42

• A glycoprotein produced by the normal foetal yolk sac, liver and intestines.
• It is undetectable in normal individuals after the first year of life.
• Its level is moderately elevated in hepatitis but high levels are also produced by hepatocellular carcinoma and cancers containing yolk sac elements (e.g. teratoma).
• High levels of αFP predict a poor prognosis in malignancy.

Question 43

HCG is raised in which cancer and which other conditions?

Answer 43

• A glycoprotein consisting of two subunits.
• HCG is elevated in patients with gestational trophoblastic disease (hydatiform mole, choriocarcinoma).
• There is also a specific elevation of the β-subunit in patients with non-seminomatous testicular cancers and some with seminoma.
• It is also raised in pregnancy!

Question 44

PSA is raised in which cancer and condition? what else is PSA used for?

Answer 44

• prostate cancer
• BPH
• prostatis
• after rectal examination
• UTI
• ejaculation

PSA lacks sufficient sensitivity and specificity to act as an accurate screening test alone

It is used in monitoring response to hormonal and cytotoxic treatments, and in surveillance after radical treatment.

Question 45

Immunoglobulins can indicate which cancers? How can they be detected?

Answer 45

Can be a measure of the paraproteinaemias (e.g. myeloma and Waldenstrom’s macroglobulinaemia) and occasionally non-Hodgkin’s lymphoma

They can be measured in the blood or their excretion can be measured as light chains in the urine (Bence-Jones protein), which occurs in 40-50% of all cases of myeloma.

Question 46

Surgery often plays a key role in the management of cancer patients. It is used in:

Answer 46

1.Diagnosis and staging
2. Treatment of cancer
3. Prevention of cancer

Question 47

Biopsy techniques include:

Answer 47

Biopsy techniques include:
* Fine needle aspiration cytology
* Tru-cut needle biopsy – a piece of the tumour is sampled under local anaesthetic
* Incisional biopsy- a piece of the tumour is sampled at surgery
* Excisional biopsy- the whole of a mass is removed

Question 48

role of surgery in diagnosis and staging of cancer

Answer 48

• An accurate histological diagnosis is required in virtually all patients and is obtained by direct biopsy
• Radical surgery may require excision of the biopsy track, therefore a poorly chosen biopsy route can necessitate a more extensive and disabling operation to achieve cure (this is particularly an issue with soft tissue sarcomas).

Surgery still plays an important role in some cancer types for accurate staging. For example, surgical axillary lymph node assessment allows an accurate assessment of lymph node involvement in breast cancer. This in turn allows a more accurate assessment of risk of future relapse and so the need for adjuvant treatment.

Question 49

Role of surgery in the treatment of cancer

Answer 49

• Surgical resection of the primary tumour with curative intent:
• Surgery to reduce bulk of residual disease
• Curative surgery for metastases
• Palliative surgery
• Prevention of cancer

Question 50

approximately …% of patients with cancer are curable by surgical resection

Answer 50

approximately 30% of patients with cancer are curable by surgical resection

Question 51

what are the requirements for carrying out curative surgery of cancer? How can you reduce the risk of local recurrence?

Answer 51

• This requires that the cancer is localised.
• Adequate margins of clearance are required to minimise the risk of local tumour recurrence
• In several tumour types, use of post-operative adjuvant radiotherapy or chemotherapy can reduce the risk of local recurrence and, in some cases, allow the use of less radical surgery.

Question 52

In which cancer is surgery to reduce bulk of residual disease carried out?

Answer 52

• in ovarian cancer effective debulking surgery in addition to chemotherapy significantly improves survival.
• Cytoreductive surgery is only likely to be of benefit if there is effective therapy for the residual tumour.

Question 53

In which occasions is curative surgery for metastases carried out?

Answer 53

• In most cancers the detection of some distant metastases indicates numerous other undetectable (‘occult’) metastases will be present and therefore curative surgical resection is not indicated and may expose the patient to an unnecessary operation and delay effective treatment.
• There are however some situations where surgical cure of distant metastases is possible e.g. solitary lung metastases from sarcomas or localized liver metastases from colon cancer. In this situation, as in debulking surgery (above), effective systemic therapy is almost always required in addition to the resection

Question 54

when is palliative surgery indicated?

Answer 54

Palliative surgery is indicated in patients when an improvement in quality of life is considered likely and the risk of harm / likely length of hospital stay are considered acceptable

Question 55

“Palliative” surgery covers a very wide range of procedures. Examples include:

Answer 55

• Intestinal obstruction from intra-abdominal tumour can often be effectively treated with a bypass procedure, relieving distressing symptoms and improving quality of life.
• Orthopaedic pinning of pathological fractures of bones can be a useful procedure in some patients; surgical results and risks are improved if bones at high risk of fracture can be identified and prophylactic intervention arranged.
  However increasing radiological expertise can remove the need for anaesthesia and prolonged periods of in-patient care when life is likely to be short. For example:
• Rather than choledochojejunostomy, biliary obstruction is often effectively treated with a biliary stent.
• Symptomatic pleural effusions or ascites can be drained for effective symptom control and in some situations in-dwelling shunts are appropriate. When recurrence occurs surgical pleurodesis may be considered in patients with reasonable life expectancy.

Question 56

role of surgery in prevention of cancer

Answer 56

In certain people with very high risk of cancer, surgical intervention can prevent cancer e.g. colectomy in patients with familial adenomatous polyposis coli or bilateral mastectomy as in the recent high profile case of Angelina Jolie.